Review Special Issues

D-pinitol, a highly valuable product from carob pods: Health-promoting effects and metabolic pathways of this natural super-food ingredient and its derivatives

  • Correction on: AIMS Agriculture and Food 6: 752-753
  • D-pinitol is a natural compound related to the important family of inositols. It can be found and isolated from many plants, being the active component of ayurvedic remedies such as Talisa patra (Abies webbiana, A. pindrow) or antidiabetic as Bougainvillea (Bougainvillea spectabilis). Although many synthetic and semi-synthetic methods have been reported for D-pinitol and its derivatives, through chemical and biochemical transformations, Ceratonia siliqua L. (Carob), a Mediterranean tree now in decline, known because of its environmental advantages, is the only raw material from which D-pinitol can be isolated in quantities enough for a viable commercial exploitation. Fortunately, the pharmacological interest in this compound has risen enormously in the last years owing to their established multifunctional properties through a variety of signalling pathways: ⅰ) anti-cancer, through inhibition of TNF-ᾳ and suppression of NF-ⱪB pathway; ⅱ) insulinomimetic and metabolic regulator in type 2 diabetes mellitus, via a post-receptor pathway of insulin action; ⅲ) antioxidant; ⅳ) hepatoprotective; ⅴ) immuno-modulator, balancing Th1/Th2 cytokines; ⅵ) osteoporosis preventive, through p38/JNK and NF-ⱪB pathways; ⅶ) anti-aging, via reduction of the insulin/IGF-1 signaling (IIS) pathway; ⅷ) improver of creatine retention; ⅸ) preventive and ameliorative of Alzheimer's disease through selective g-secretase modulation.

    Thus, the present review compress the literature reported to date in relation to the health-promoting effects and metabolic pathways of this naturally occurring super-food ingredient and its derivatives, providing an extensive guide for a future utilization of all of its potentialities, aiming a positive impact in the promotion and recovery of carob crops.

    Citation: JoséIgnacio López-Sánchez, Diego A. Moreno, Cristina García-Viguer. D-pinitol, a highly valuable product from carob pods: Health-promoting effects and metabolic pathways of this natural super-food ingredient and its derivatives[J]. AIMS Agriculture and Food, 2018, 3(1): 41-63. doi: 10.3934/agrfood.2018.1.41

    Related Papers:

    [1] José Ignacio López-Sánchez, Diego A. Moreno, Cristina García-Viguera . Correction: D-pinitol, a highly valuable product from carob pods: Health-promoting effects and metabolic pathways of this natural super-food ingredient and its derivatives. AIMS Agriculture and Food, 2021, 6(2): 752-753. doi: 10.3934/agrfood.2021044
    [2] Alexandros Tsoupras, Eirini A. Panagopoulou, George Z. Kyzas . Anti-inflammatory, antithrombotic and anti-oxidant bioactives of beer and brewery by-products, as ingredients of bio-functional foods, nutraceuticals, cosmetics, cosmeceuticals and pharmaceuticals with health promoting properties. AIMS Agriculture and Food, 2024, 9(2): 568-606. doi: 10.3934/agrfood.2024032
    [3] Anna Chizhayeva, Yelena Oleinikova, Margarita Saubenova, Amankeldy Sadanov, Alma Amangeldi, Aida Aitzhanova, Aigul Alybaeva, Makpal Yelubaeva . Impact of probiotics and their metabolites in enhancement the functional properties of whey-based beverages. AIMS Agriculture and Food, 2020, 5(3): 521-542. doi: 10.3934/agrfood.2020.3.521
    [4] Asma Hussain Alkatheri, Mahra Saleh Alkatheeri, Wan-Hee Cheng, Warren Thomas, Kok-Song Lai, Swee-Hua Erin Lim . Innovations in extractable compounds from date seeds: Farms to future. AIMS Agriculture and Food, 2024, 9(1): 256-281. doi: 10.3934/agrfood.2024016
    [5] Alexandros Tsoupras, Eirini Panagopoulou, George Z. Kyzas . Olive pomace bioactives for functional foods and cosmetics. AIMS Agriculture and Food, 2024, 9(3): 743-766. doi: 10.3934/agrfood.2024040
    [6] Andrea Ertani, Ornella Francioso, Serenella Nardi . Mini review: fruit residues as plant biostimulants for bio-based product recovery. AIMS Agriculture and Food, 2017, 2(3): 251-257. doi: 10.3934/agrfood.2017.3.251
    [7] Anthony Temitope Idowu, Oluwakemi Osarumwense Igiehon, Ademola Ezekiel Adekoya, Solomon Idowu . Dates palm fruits: A review of their nutritional components, bioactivities and functional food applications. AIMS Agriculture and Food, 2020, 5(4): 734-755. doi: 10.3934/agrfood.2020.4.734
    [8] Seyyed Abbas Hashemi, Sayeh Ghorbanoghli, Ali Asghar Manouchehri, Mahdi Babaei Hatkehlouei . Pharmacological effect of Allium sativum on coagulation, blood pressure, diabetic nephropathy, neurological disorders, spermatogenesis, antibacterial effects. AIMS Agriculture and Food, 2019, 4(2): 386-398. doi: 10.3934/agrfood.2019.2.386
    [9] Thi Thuy Le, Trung Kien Nguyen, Nu Minh Nguyet Ton, Thi Thu Tra Tran, Van Viet Man Le . Quality of cookies supplemented with various levels of turmeric by-product powder. AIMS Agriculture and Food, 2024, 9(1): 209-219. doi: 10.3934/agrfood.2024012
    [10] Orbe Chamorro Mayra, Luis- Armando Manosalvas-Quiroz, Nicolás Pinto Mosquera, Iván Samaniego . Effect of fermentation parameters on the antioxidant activity of Ecuadorian cocoa (Theobroma cacao L.). AIMS Agriculture and Food, 2024, 9(3): 872-886. doi: 10.3934/agrfood.2024047
  • D-pinitol is a natural compound related to the important family of inositols. It can be found and isolated from many plants, being the active component of ayurvedic remedies such as Talisa patra (Abies webbiana, A. pindrow) or antidiabetic as Bougainvillea (Bougainvillea spectabilis). Although many synthetic and semi-synthetic methods have been reported for D-pinitol and its derivatives, through chemical and biochemical transformations, Ceratonia siliqua L. (Carob), a Mediterranean tree now in decline, known because of its environmental advantages, is the only raw material from which D-pinitol can be isolated in quantities enough for a viable commercial exploitation. Fortunately, the pharmacological interest in this compound has risen enormously in the last years owing to their established multifunctional properties through a variety of signalling pathways: ⅰ) anti-cancer, through inhibition of TNF-ᾳ and suppression of NF-ⱪB pathway; ⅱ) insulinomimetic and metabolic regulator in type 2 diabetes mellitus, via a post-receptor pathway of insulin action; ⅲ) antioxidant; ⅳ) hepatoprotective; ⅴ) immuno-modulator, balancing Th1/Th2 cytokines; ⅵ) osteoporosis preventive, through p38/JNK and NF-ⱪB pathways; ⅶ) anti-aging, via reduction of the insulin/IGF-1 signaling (IIS) pathway; ⅷ) improver of creatine retention; ⅸ) preventive and ameliorative of Alzheimer's disease through selective g-secretase modulation.

    Thus, the present review compress the literature reported to date in relation to the health-promoting effects and metabolic pathways of this naturally occurring super-food ingredient and its derivatives, providing an extensive guide for a future utilization of all of its potentialities, aiming a positive impact in the promotion and recovery of carob crops.



    1. Introduction

    At the Paris climate conference (COP21) in December 2015, 195 countries adopted the first-ever universal, legally binding global climate deal. Governments agreed to a long-term goal of "holding the increase in the global average temperature to well below 2 °C above pre-industrial levels and to pursue efforts to limit the temperature increase to 1.5 °C above pre-industrial levels, recognizing that this would significantly reduce the risks and impacts of climate change". To attain this goal, Parties to the United Nations Framework Convention on Climate Change (UNFCC) committed "to achieve a balance between anthropogenic emissions by sources and removals by sinks of greenhouse gases in the second half of this century" [1].

    Human activities have increased levels of carbon dioxide in the atmosphere from 280 parts per million before the industrial revolution to 400 ppm today. As a result, in 2015 meteorological stations around the world recorded a 1 °C rise in global temperatures above pre-industrial times. The Fifth Assessment Report (AR5) by the UN Intergovernmental Panel on Climate Change (IPCC) considered 116 scenarios consistent with a > 66% probability of limiting the increase in global average temperature to less than 2 °C relative to the pre-industrial era. From these 116 scenarios, 101 required negative emission technologies that result in the removal of greenhouse gases from the atmosphere (NETs) to be applied in the second half of the century [2].

    Smith et al. [3] argues that the most cost-effective NET would be bio-energy with carbon capture and storage (BECCS). These solutions aim to remove diffuse CO2 from the air with plants, burn them, and then bury the carbon in concentrated form underground. Yet a major issue with BECCS is the availability of land and water. The study estimates that deploying BECCS at scale to stabilize the climate < 2 °C would require about 25 to 46% of total arable land and permanent crop areas. BECCS solutions raise the problem of trade-offs with food security [4,5], in the context of a fast-growing world population [6]. Article 2 of the Paris Agreement recognizes this risk and urges "increasing the ability to adapt to the adverse impacts of climate change and foster climate resilience and low greenhouse gas emissions development, in a manner that does not threaten food production". In line with Article 2 of the Paris Agreement [1], accelerating the adoption of climate-smart agriculture is critical to simultaneously enhance food security, promote economic growth, strengthen resilience to increased climate variability and minimize potential trade-offs with carbon management efforts such as BECCS.

    A broad consensus exists among practitioners that building the climate-smart agricultural systems of tomorrow requires enabling farmers to deal with the farming constraints of today [7]. The most pervasive of these constraints is arguably the gender gap in access to land and productive resources—information, technology, labor, finance and markets. This gender gap is believed to translate into a significant productivity gap. A growing literature on the impact of the gender gap on agricultural productivity [8,9,10,11,12,13] estimates it to vary from 4 to 40% with the majority clustering around 20 to 30% [14]. The methodologies employed to assess the gender gap from a productivity perspective are still under dispute, especially when both men and women work crops or livestock [15,16], and authors warned against conceptualizing women as a homogenously vulnerable group in agriculture [17,18].

    However, the literature strongly suggests that the gender gap in agriculture is material and diminishes substantially when women's access to productive assets is equal to men's [9]. In turn, this suggests that closing the gender gap in agriculture could achieve a "triple dividend" of gender equality, food security and climate management. Closing the gender gap should minimize potential trade-offs between food security and carbon management by increasing overall agricultural productivity, as well as leveraging women's agricultural knowledge and broader perception of food security [19]. Improving women farmers' access to productive resources could also enable them to meet the increased upfront capital, labour and information requirements of many climate-smart agriculture practices and adopt them at the same rate as men [18].

    Despite this potential "triple dividend", most climate policies ignore the gender gap in agriculture [20]. Only 39% of the Intended Nationally Determined Contributions submitted by Parties to the UNFCCC as of 11/18/15 explicitly mention "gender" and/or "women" in the context of their national priorities and ambitions for reducing emissions [21]. This can be partly attributed to the fact that policy-makers, development practitioners and the private sector generally lack necessary information about the situation, role and contribution of women in agriculture and their rural environments in order to take decisions or measures to improve agricultural productivity and climate resilience in a gender-responsive manner. As highlighted by Doss [16], the assertion that closing the gender gap in access to productive assets leads to increased agricultural productivity depends upon a complex causal chain which does not in itself determine the agricultural interventions required to address the gap.

    In response, this paper presents a three-step methodology to assist policy-makers in developing countries in disentangling opportunities and trade-offs associated with different portfolio of policies and interventions to close the gender gap for CSA: (i) develop a gender-neutral barrier and risk table for CSA investments; (ii) overlay a gender analysis onto this table; and (iii) map the full spectrum of gender-differentiated risks against potentially remedial public instruments.

    Part Ⅰ introduces the root causes of the gender gap in agriculture. Part Ⅱ presents a gender-differentiated barrier and risk table for CSA investments and Part Ⅲ matches the identified gender-differentiated risks with possible policy solutions. This methodology is based on primary and secondary research. A review of the scientific and professional peer-reviewed literature was carried out to gather and synthetize existing research on the gender gap in agriculture and map investment risks and public policy instruments. The methodology is substantiated by empirical evidence collected through the formulation of three UN Women projects in Senegal, the Democratic Republic of Congo, and Malawi from September 2015 to June 2016.


    2. The gender gap in the agricultural sector

    Agriculture remains one of the most important areas of women's work globally with more than a third of employed women in the agricultural sector. Overall, in developing countries, women comprise 43% of the agricultural workforce, and play a critical role in supporting household and community food security, often in contexts of severe rural poverty and precarious livelihoods [9]. In sub-Saharan Africa, this proportion increases to 59% of employed women being in informal agricultural employment, mostly as small-scale farmers [22].

    Yet women farmers have significantly less access to land, information, finance, agricultural inputs and higher added-value markets than men. This well-documented gender gap results from discriminatory laws, policies, and social and cultural norms. For example, a recent report on Women, Business and the Law [23] identifies 155 countries out of 173 that have at least one law impeding women's economic opportunities and 18 economies where husbands can prevent their wives from working.

    Even the most well-intentioned public policies and programmes can inadvertently discriminate against women when gender-differentiated barriers are overlooked. Most agricultural policies and investments fail to consider differences in the resources available to men and women, their roles, labor burdens, and the constraints they face, and how these gender differences might be relevant to those proposed interventions [18,24,25,26,27]. It is often assumed that interventions to facilitate access to finance, technology or markets will have the same impacts on men and women; however, a growing body of evidence indicates that they regularly do not. This section presents the key gender gaps and structural barriers faced by women farmers.

    Structural barriers to land tenure security constitute a first stumbling block for many women farmers [28]. An international comparison of agricultural census data by the Food and Agriculture Organization [9] shows that less than 20% of landholders worldwide are women. According to the OECD's Social Institutions and Gender Index [29], based on data for 161 countries, in only 37% of those countries do women and men have equal land rights to own, use and control land. In 4% of those countries, women explicitly have no legal right to own, use and control land, and in 59% of those countries customary, traditional and religious practices discriminate against women and undermine the full implementation of national legal codes.

    Women's lack of land tenure security is historically related to inadequate or discriminatory legal and policy frameworks and social and cultural norms, such as male preference in inheritance, male privilege in marriage and so-called secondary land rights (meaning women farmers hold these rights through male family members). When the law guarantees women and men the same rights to own, use and control land, customary, traditional and religious practices often discriminate against women and undermine the full implementation of national legal codes. In sub-Saharan Africa, SIGI [29] data indicates that high to very high discrimination against women exists in practice in 29 of 43 countries. Women, especially widows, can also be the main victims of agricultural related property-grabbing including land, farm implements and inputs [11].

    In addition, women farmers have little access to agricultural extension services. On average, women farmers benefit from only 5% of agricultural extension services today [9]. They are rarely among the large-scale commodity producers usually targeted by agricultural extension programs. The limited number of female extension workers may also constraint the system's ability to meet and respond to women farmers' needs in some socio-economic contexts [30]. For example, only 12% of agriculture extension agents were female in Ethiopia, a county where traditional customs prevent male extension agents from working with women farmers [31].

    Furthermore, time constraints arising from the unequal sharing of the burden of unpaid domestic (for example, fetching water and fuelwood) and care work (for example, caring for children, the elderly or the sick) can severely restrict women farmers' capacity to access and act upon new information to improve their farming practices [24]. Around the world, women spend two to ten times more time on unpaid care work than men [32]. This is particularly pronounced in rural areas.

    Women also face the risk of violence, which restricts their personal movement and occupational choices. This limited mobility affects their capacity to learn from neighboring villages experiencing similar agricultural challenges [18]. When risks of violence are such that women cannot leave their homes without safe male company, they impede access to most sources of information (agricultural extension meetings, training and skills development, etc.), other productive assets, financing or markets. When violence happens at home, women's paid work environments outside the home are affected as well, and include lost time at work and reduced attention and incentives for long-term investment [33].

    Access to long-term affordable financing is another key barrier for women farmers, both in terms of their ability to invest in agricultural inputs and technologies to increase productivity and to participate in higher added-value chains and markets. Women farmers' access to financial services is constrained by a number of factors, including lack of land tenure security and lower financial literacy. Even when their land rights are secured and they have the financial literacy and agricultural information to develop a bankable project, women's plots tend to be insufficient in size and quality to qualify as collateral for a loan or credit. In addition, discriminatory legislation, social norms and lack of appropriate financial products might constrain their ability to access financing. Only 22% of women in low-income countries hold bank accounts in rural areas and commercial banks tend to work only with large farmers who are already well positioned in global value chains [34].

    Women farmers' access to finance is also constrained by the fact that they are mostly unorganized. Participation in rural organizations such as peasants' associations, agricultural labour unions, cooperatives and project beneficiary committees reduce risks and transaction costs for funders [35]. It also increases rural men's and women's access to productive resources, information and training and may provide them with a way to sell their produce. Membership in these organizations also allows farmers to represent their interests to government authorities and policy makers, as policies reflect the interests of those who develop them [36,37].

    However, rural women's membership in these organizations is often limited. In countries like India, Nepal, Bangladesh, Sri Lanka and Pakistan, women comprise just 7.5% of the total membership of agricultural cooperatives, as compared with 92.5% for men [38]. Similarly in Ethiopia, just 10 to 20% of cooperative members are women and only 3% of women hold leadership positions compared to 15% of men, and in Uganda only 5% of women hold leadership positions in their cooperatives [39]. While discrimination based in law may not prohibit women from becoming members or leaders, women are generally excluded because membership is based on land ownership and/or a head-of-household criterion [40].

    Smallholder farmers usually earn incomes from a range of sources [41]. The structural barriers faced by women as farmers can also affect them as seasonal employees and small entrepreneurs and reduce their overall capacity to save and reinvest across their range of activities. Worldwide, women entrepreneurs have lower access to finance than male entrepreneurs [42]. Women-owned formal SMEs have 260 to 320$ billion in unmet financing needs worldwide. The IFC [43] found that women-owned businesses make up between 32 and 39% of micro and small enterprises, compared with 17 to 21% of medium-sized companies. They have also lower access to justice to seek recourse against discrimination, default or poor workmanship [44].

    Climate change is expected to severely affect agricultural production and food security both globally and locally. Climate change will increase the frequency and impact of extreme hydro-meteorological events as well as weather variability, reduce the economic lifespan of infrastructure, compound existing conflicts over natural resources, worsen the vulnerability of ecosystems, and lead to the emergence of new global health challenges [2]. Climate change risks and challenges are projected to disproportionality affect women and children because of the pre-existing gender gap in land tenure, information, mobility, security, voice and agency, labour, financial and market access. It could also increase the likelihood of negative coping strategies and compound the present differential survival between the sexes in disasters, particularly where food shortage is involved [45,46].

    Small farmers can adapt to climate change by adjusting existing farming practices, such as changing varieties, tillage techniques and planting schedules; investing in new production infrastructure, such as irrigation powered by renewable energy technologies; or diversifying economic activities, including greater focus on higher-value agricultural processing and partially or fully moving out of agriculture into other, less vulnerable sectors. The scope for adjustment of existing farming practices is lower in the tropics, where planting schedules are typically dictated by rainfall and crops are already grown at their optimal temperature range [47]. Thus the adaption of smallholder farming in developing countries to climate change will depend in large part upon access to new markets, new farming inputs and new knowledge.

    However, a wide spectrum of barriers hinder this critical transformation of smallholder farming in developing countries. Given the pre-existing gender gap in agriculture, these market transformation barriers are likely to be more severe for women farmers. Notably, empirical evidence suggests that women are constrained in their capacity to adapt to climate change by the very same gender gap in agriculture that increases their vulnerability to it [18,20,48,49,50]. Thus, this paper hypothesizes that market transformation efforts intended to accelerate the adoption of climate-smart agriculture are unlikely to benefit men and women farmers equally if they do not address both generic and gender-differentiated barriers and risks. To further explore how existing structural barriers affect women farmers' investment incentives, the next section proposes a model to identify gender-differentiated risks in climate smart agriculture.


    3. Gender differentiated investment risks in climate-smart agriculture

    Numerous beneficial CSA solutions exist, ranging from improved land and water management to innovative post-harvest practices [26,51,52,53,54,55,56,57,58,59,60]. The presence of commercially attractive solutions should theoretically facilitate the development and scaling up of public and private investment for climate smart agriculture. However, investment in seemingly commercially viable climate-smart opportunities faces a range of informational, technical, institutional and financial barriers [61,62,63,64,65]. These barriers translate into significant investment risks.

    Smallholder farmers are entrepreneurs with a high discount rate. They operate in a high-risk environment with small margins, and seek to be profitable in the very near-term. Farmers are unlikely to invest or borrow at scale for CSA initiatives without a deliberate effort to reduce these barriers. Similarly, financiers are unlikely to lend for capital-intensive investments with uncertain pay-offs. When it is available, finance will come with short tenors and high interest rates, affecting the commercial attractiveness of all but the most profitable CSA investments.

    Thus it is necessary to establish a policy environment that reduces CSA investment risks. Accurately assessing the investment barriers and risks in agriculture requires a clear conceptual understanding of their interrelationships. Barrier and risk analyses are increasingly used to identify public instruments that can catalyze climate smart investments [64,65,66]. Barriers can be understood as the drivers, or the root causes, of risks. Barriers translate into risks that deter investment. Once identified, investment risks can be mapped against a set of possible public instruments and incorporated into market transformation efforts to improve the risk-reward profile of a given set of investments.

    Building on this market transformation methodology and drawing on primary and secondary research, Table 1 clusters generic barriers to CSA into nine independent risk categories. To assess whether the gender gap translates into gender-differentiated risks which deter investment in CSA—and would thus explain the perceived slower adoption rate of CSA by women farmers in the literature—we then overlay a gender analysis onto this gender-neutral investment barrier and risk analysis. For each gender-neutral risk listed in Table 1, we assess its gender-differentiated probability of occurrence and potential severity. We also list additional gender-specific barriers. The full gender-differentiated risk analysis is given in Supplementary Annex 1.

    Table 1. A gender differentiated barrier and risk analysis for climate smart agriculture.
    Risk category Description Underlying barriers Increased probability of occurrence and severity of impact of risks for women Additional gender-specific barriers
    1. Production risk Risks associated with adoption of new farming practices in a changing socio-economic and physical environment -Limited awareness of the impact of climate change and knowledge of CSA practices
    -Limited access to climate-resilient farm inputs and new and/or improved technologies such as solar-powered irrigation pumps
    -Limited agricultural extension services
    -Limited capacity to interpret and apply climate and weather information to adjust farming practices
    -Limited saving rates and safety net to experiment with non-traditional agricultural practices and meet higher upfront costs of climate smart inputs and technologies
    -Uncertainty on market demand or/and lack of access to markets for new farming products
    -Land regime uncertainties discourage long-term investment
    -Lower access to climate and weather information
    -Lower membership in farmer associations to access inputs
    -Lower access to agricultural extension services
    -Gender gap in access to finance
    -Gender gap in access to land
    -Limited access to labour and tools that are usually part of men's domain
    -Gender segregated labour and tools
    -Lower participation in market institutions
    2. Technology, input and farming practice risk Risk arising from limitations in the quality and availability of climate smart farm inputs and technologies, as well as its treatment by customs -Lack of technical standards and quality assurance mechanisms for new CSA technologies
    -Poor quality and availability of farm inputs (climate resilient seeds, fertilizers, etc.) and technology
    -Limited capacity to provide after-sale services to farmers
    -Gender gap in access to technical information and skills
    -Lower access to recourse against poor quality
    -Social norms can limit women access to technology providers
    3. Labour inputs risk Risks arising from the lack of skilled and qualified potential employees to develop and promote climate smart inputs, technologies and practices -High illiteracy rates in rural areas
    -Lack of a competitive labour market
    -Labour shortage during key agricultural period (soil preparation, etc.)
    -Limited capacity to prepare bankable project proposals
    -Higher female illiteracy rate in rural areas
    -Gender disaggregated occupation limiting women choices due to discriminatory social norms and stereotypes.
    -Increase workload because of gender differentiated tasks (weeding, biomass collection, etc.)
    -Negative impact on women health through exposure to chemicals, physically stressing gender differentiated tasks and heavier equipment.
    -Women's disproportionate responsibility for domestic work and unpaid care limit their capacity to acquire and apply new skills required for climate smart agriculture and agri-business
    -Risk of harassment and violence limit women's mobility and access to information
    4. Financing risk Risks arising from scarcity of domestic investor capital (debt and equity) for climate-smart agriculture, and domestic investors' lack of familiarity with climate-smart agriculture and appropriate financing structures -Capital scarcity—liquidity constraints in domestic banking
    -Capital scarcity—underdeveloped domestic financial sector
    -Capital scarcity—competing incentives
    -Lack of track record and poor risk assessment capacity for climate resilient technologies and practices
    -Lack of appropriate collateral of farmers for a bank loans and difficulty in assessing farmers' creditworthiness due to their lack of credit histories
    -Lack of tailored financial products and limited in-house expertise in climate-resilient farming High transaction costs to provide small loans to remote farmers -Lack of risk management services.
    -Lack of rural banks more likely to affect women farmers due to lack of mobility
    -Lower level of collateral and uncertain property rights reduce the credit worthiness of women farmers
    -Harmful social norms on women access to finance and aptitude as investors
    5. Regulatory risk Risks arising from lack of or counterproductive regulatory and public policies to support CSA -Lack or inadequate climate change strategies and policies
    -Limited understanding of the role and importance of public policies to support CSA
    -Limited capacity to identify barriers to CSA and implement policies to remove them
    -Budget constrains to design and implement policies to catalyze CSA investment
    -Lack of cross-sectoral and inter-departmental coordination to promote integrated policies
    -Complex, inconsistent or opaque licensing processes for new CSA technologies
    -Lack of long-term macro-economic signals affect CSA markets
    -Negative distortions that reduce incentives to investment in climate-resilient infrastructure and practices (agricultural and fossil fuels subsidies, etc.)
    -Undervalued natural capital: Life support services provided by not accounted by public and private sectors, leading to unsustainable natural resource uses and underinvestment in ecosystem services conservation.
    -Uncertainty or impediments due to government policy or political instability.
    -Lack of trust among economic actors, which hinders the effectiveness of public-private partnerships (Brickell and Elias, 2013)
    -Limited capacity to identify gender specific barriers and risks to CSA and implement policies to remove them
    -Lesser voice and agency of women farmers to influence economic policies
    -Lack of cross-sectoral coordination affects the capacity to link CSA policies with other sectoral policies (education, health, etc.) critical to address structural gender barriers
    -Women are softer targets for corruption
    -Gender differentiated risks not taken into consideration in -CSA strategies and policies, which unintentionally result in discriminatory practices
    6. Market risk Risks arising from limitations and uncertainty in the agricultural market regarding market outlook, access, price and competition for climate smart farm products, technologies and practices -Limited awareness of opportunities and risk associated with climate change, compounded by lack of data and technical skills
    -Lack of market governance institutions to break smallholder isolation and generate economies of scale (farmer associations, intermediary institutions, commodity exchanges, investment promotion agencies, etc.)
    -Lack of logistical infrastructure to limit post-harvest losses and secure market for CSA products
    -High transaction costs for small-scale opportunities in remote areas
    -Difficulty in converting social benefits into private profits
    -Limited access to affordable, long-term finance to meet higher upfront costs of climate-resilient product development and marketing
    -Reluctance of private sector to participate in programmes requiring various degrees of government support due to fear of policy reversal
    -Lack of proven technologies and practices to address specific adaptation challenges; uncertainty on future pay-off in the absence of proven business models
    -Subsidies and practices that encourage inefficient uses of natural resources
    -Lower membership in market governance institutions
    -Lesser voice to influence infrastructure investment
    -Limited mobility because of risks of violence impedes access to markets
    7. Social acceptance risk Risks arising from lack of awareness and resistance to climate smart inputs, technologies, practices and farm products in communities -Resistance by consumers to new farm products
    -Lack of public support for phase out of Subsidies and practices that discourage CSA.
    -Changes in control over resources (ex: crops traditionally controlled by women shift to men as a result of inter-cropping)
    8. Currency risk Risks arising from currency mismatch between hard currency debt/equity and domestic currency revenues. -Uncertainty due to volatile local currency
    9. Sovereign risk Risk arising from a mix of cross-cutting political, economic, institutional and social characteristics in the particular country which are not specific to CSA -Conflict, political instability, economic performance, weather events/natural disaster, legal governance, ease of doing business, crime and law enforcement, land tenure and infrastructure
     | Show Table
    DownLoad: CSV

    The gender-differentiated barrier and risk analysis suggests that about half of the CSA investment risks have a higher probability of occurrence and/or severity for women farmers than for men farmers. Furthermore, women farmers might face additional gender-specific barriers, mostly linked to their disproportionate responsibility for unpaid domestic and care work, the risk of violence and unequal power relations with men.

    For example, the lack of land tenure security increases the risk for women farmers to invest in long-term sustainable land management practices—even fairly straightforward CSA practices, such as agroforestry or planting native tree species mean a 5-7 yearsinvestment. In addition, climate-smart agricultural approaches tend to require greater upfront capital for investments in climate resilient infrastructure, such as irrigation systems. Lack of land tenure security also reduces women farmers' capacity to leverage land as collateral to access long-term affordable finance. Women farmers already without access to short-term finance to purchase fertilizers and other agricultural inputs, due to the absence of collateral and prevailing discriminatory social norms, will be even harder pressed to obtain the long-term affordable finance required for climate resilient agriculture.

    Similarly, climate-smart agriculture is increasingly knowledge-based. As discussed in section I, women often have less access to agricultural information and extension services. As such, women farmers are likely to have the least access to additional climate and weather information that could help them anticipate variations in temperature and rainfalls, choose appropriate seeds, and make informed decisions about when and what to plant in a changing climate. They will have also the least access to extension services to enable them to adopt new farming practices and seize new market opportunities.

    Climate change could also exacerbate the time poverty and unpaid domestic and care work burdens of women farmers in numerous locations as they need to walk longer distances to fetch water and fuel, and to dedicate more time to care for the sick and the vulnerable [67]. Several studies [24,27,68] have shown that women's labour burden can increase with new technologies and practices, for instance more weeding as a result of non-tillage, and limit the capacity of women to adopt climate-smart practices.

    Furthermore, they may face increased labour shortages during the growing cycle as a result of changes in weather patterns. For example, ploughing is often considered a male occupation. Climate change may reduce the optimal window for soil preparation, forcing women to wait for men farmers to complete the preparation of their own plots before they can turn their attention to women's plots.

    In addition, climate could disproportionally affect the heath of women through the growing risk of gender-based violence under stress conditions, lower physical resistance levels under food and water scarcity (e.g. eating less and last because of harmful social norms), greater exposure to toxic chemicals, use of heavier equipment, and longer distances to fetch and carry fuel and water.


    4. Mapping CSA risks against remedial public instruments

    The urgency of climate change means that it is vital to accelerate the adoption of climate-smart agriculture while preventing trade-offs between food security and climate action. However, the gender differentiated barrier-risk analysis suggests that climate change is likely to exacerbate the existing structural barriers and risks faced by women farmers, while at the same time creating new ones. This is likely to slow down their adoption of CSA practices, potentially generating a downward spiral.

    Whether these gender-differentiated investment barriers and risks to CSA are present will be highly context-specific. Women, and no less women farmers, are not a homogenously vulnerable group [18]. Women in rural areas vary widely by location, age, ethnicity, culture and social class, health, religion, work status as do their agricultural contexts in a rapidly changing climate [18,24,26,29]. For example, major progress has been made in terms of gender parity in primary and secondary education [69].

    Despite overall positive trends, considerable variation exists across countries and socio-economic segments in terms of gender parity in primary education access, which is key for the adoption of CSA practices. Notably, conflict-affected areas are sites of extreme disadvantage in education. In Afghanistan, 70 girls per 100 boys are in school, while in neighboring India, nearly 90 boys for 100 girls are enrolled [69]. Similarly, the poorest girls remain the most likely to never set foot in a classroom. In sub-Saharan Africa, gender parity in completion of primary education exists among the richest 20% but among the poorest 20%, 83 females completed primary education for 100 boys [69].

    Yet, the large number of possible additional or more severe barriers increases the likelihood that some gender-differentiated risks will be present in most locations and communities. This will translate into higher investment, transaction and opportunity costs. When available, finance is likely to come at a premium to compensate investors for perceived or actual technical, market, regulatory, institutional and political risks, adversely affecting the commercial viability of CSA investments by women farmers.

    Targeted interventions will be required to address gender differentiated risks that will hamper the adoption of CSA by women farmers. Similarly to the identification of risks and underlying barriers, the selection of an optimal portfolio of public policy instruments will depend on the specific challenges and opportunities present in each location. A practice that is climate smart in one location might be inappropriate in another [68,70].

    Furthermore, barriers and risks need to be assessed for each group of stakeholders involved in the CSA supply chain to women farmers. CSA investment will typically involve five common stakeholder groups: producers, end-consumers, policymakers, financiers and the supply chain firms. Each stakeholder will have different incentives, which are also gendered. Most of the barriers affecting women farmers as producers discussed in Part I can also touch women in other stakeholder groups (i.e., discriminatory social norms/stereotypes, inheritance and marriage laws, threat of violence, etc.).

    Understanding the incentives and roles of the different stakeholders across geographies is critical to assess the viability of, and catalyze investment in, climate-smart agriculture. Several barriers can combine to prevent a given stakeholder group from using or investing in a climate-smart technology or management practice. For example, an agribusiness considering a crop diversification investment may face barriers such as market distortions from agricultural subsidies, limited local supply of skills, import/export barriers, limited access to credit, poor logistical infrastructure or domestic political instability, among others. Similarly, a given barrier can affect several stakeholder groups. As an illustration, lack of access to long-term affordable finance to meet the higher upfront costs of CSA technologies and the lack of risk management instruments will simultaneously affect farmers, investors and supply chain firms.

    This means that addressing the barriers related to one stakeholder group in isolation cannot transform a market. Likewise, removing only some of the barriers affecting a given group of stakeholders will not be enough to enable them to fully adopt CSA technologies and practices. An analytical framework is required to support the systemic identification, discussion and prioritization of targeted interventions to remove generic and gendered risks and barriers. The gender-informed investment barrier and risk analysis can be broadened to provide such a framework.

    Public policy instruments can transform markets and catalyze investment to accelerate the adoption of beneficial technologies and practices through reducing, transferring and/or compensating for risks. They can broadly be divided into three groups [66]:

    · Policy de-risking instruments: These seek to remove the underlying barriers that are the root causes of risks. As the name implies, these instruments utilize policy interventions to mitigate risk and include, for instance, local skills development; regulatory and legal development; strengthened market governance institutions; and long-term, stable, coherent and transparent national policies. These instruments provide a foundation for investment.

    · Risk transfer instruments: Some investment risks such as small market size, limited infrastructure or political instability can only be partially addressed through policy measures. Risk sharing instruments do not seek to directly address the underlying barriers, but instead transfer some of the risks that private investors face to public actors. These instruments can include, for example, loan guarantees, political risk insurance and public co-investments.

    · Financial compensation instruments: Recognizing that all risks cannot be eliminated through policy de-risking or risk transfer instruments, efforts to reduce risks can be complemented by additional financial incentives to compensate for any residual above-average risks and costs.

    The last step of the proposed methodology to address gender-differentiated CSA investment risks is to match each generic and gendered investment barrier and risk identified in Table 1 against a possible portfolio of remedial policy de-risking, risk transfer or compensation instruments. For example, Table 1 identifies "limited awareness of the impact of climate change and knowledge of CSA practices" as a key production barrier. Small and poor farmers are the key affected stakeholder group. The probability of occurrence and severity of this risk will be higher for women smallholders given the gender gap in access to information. In addition to generic awareness-raising campaigns about climate-induced risks (policy de-risking instrument), gender differentiated preferences in accessing climate information should be identified and the media mix configured to optimally reach out to both women and men farmers (gender differentiated policy de-risking instrument). Complementary gendered solutions such as a challenge grant for climate and weather information providers to develop appropriate information services for women farmers (financial compensation instrument) could be considered.

    A key benefit of adopting the barrier-risk-instrument model as the conceptual framework to identify public policy responses is that it involves a transparent, structured process whereby assumptions are made explicit, and can be checked, debated and enriched to strengthen the design of CSA market transformation initiatives. A further benefit is to enable an analysis of potential synergies, overlaps and trade-offs across public policy instruments. For example, efforts to raise awareness and increase access to applied climate information should be designed so that they build on and/or complement interventions to engender extension services to reduce other gendered production risks. Increase awareness of the impact of climate change should also facilitate the adoption of risk transfer instruments such as weather-indexes.

    Based on the literature review [26,53,54,55,56,57,58,59,60,71,72,73] and empirical evidence derived from the formulation of three UN Women CSA projects in sub-Saharan Africa, we have identified a number of possible public instruments to address each of the generic and gender-specific risks and barriers analyzed in Table 1. In the selection of the instruments, a strong attention is paid to information and communication technologies as well as innovative financing instruments to break the isolation of women farmers, create economies of scale and bring them into local, national and global supply value chains [74,75,76,77,78,79,80,81]. The full mapping of possible public policy instruments is presented in Annex I. This list of instruments is indicative and, as such, subjective. For example, some stakeholders might choose to place a lower or stronger premium on innovative financing instruments. Furthermore, it will need to be localized and further expanded to meet the unique barriers and requirements of each geography. A number of tools for data collection and analysis exist to conduct such a localization exercise [72,82,83].

    Public policy instruments to catalyze investments come at a cost. Irrespective of the instrument portfolio that is selected, there will be a cost to the supply chain, consumers and/or taxpayers. Numerical methodologies have been developed to assess the cost-effectiveness of different mixes of public instruments to transform renewable energy markets [65]. These methodologies rely on the professional judgment of industry analysts, entrepreneurs and investors. For smallholder CSA, it will also be critical to rely on the best judgment of concerned entrepreneurs and investors—women farmers and other supply chain stakeholders—and invite them to localize and apply these analytical tools.

    The differential in financial literacy does not lessen the need to engage stakeholders to determine how to best address their unique requirements, and include their voices and decisions in the design of solutions. Participatory approaches for CSA can substitute to numerical models developed for renewable energy. As for any market transformation effort, a robust monitoring and evaluation framework should be established to lay the foundation for a mutual learning system as well as the quantification of the impact of different portfolio of policy instruments.

    The barrier-risk-instrument table provides a breadth of information. Such a systemic analysis is critical to ensure that all local barriers and resulting risks are discussed and removed in a cost-effective manner. However, its breath of information can prove overwhelming and reduce its usefulness for agricultural and climate policy makers and practitioners. To facilitate the application and localization of the proposed methodology, Annex Ⅱ embeds possible interventions identified in the generic barrier-risk-instrument table into an overall theory of change. Specifically, the theory of change clusters interventions to address key gender gaps in: (i) CSA policies; (ii) access to finance and technologies; (iii) access to information; and (iv) access to markets. It also provides a visual representation of the derived logical framework.

    The localization of the illustrative theory of change can serve as a starting point for a policy dialogue on gender differentiated investment risks to CSA. Then, it can lay the foundation for the development of a full barrier-risk-instrument table to integrate gender into overall CSA market transformation efforts. The UN Women project documents in Malawi, Senegal and DRC illustrate how this illustrative theory of change and logical framework can be localized to meet the unique requirement of each geography and concerned communities in a gender-responsive manner [48,49,50].


    5. Conclusion

    This paper argues that addressing gender-differentiated investment risks for climate-smart agriculture offers a potential, but currently unrealized, triple dividend. It can simultaneously advance gender equality, food security and cost-effective climate management, all of which lie at the heart of the new Sustainable Development Goals. It should be, therefore, an investment priority for policy makers.

    However, the gender differentiated barrier and risk model developed in this paper suggests that for women farmers, existing structural barriers to gender equality—notably in access to land, productive assets and markets—are likely to translate into additional risks for investment in climate smart agriculture, greater likelihood that risks will translate into negative impacts, and greater severity of these impacts. This will limit the capacity of women farmers, who account for the majority of farmers in some locations, to invest in CSA and act as change agents to address climate change at scale. Ultimately, it could compound the gender gap and increase the vulnerability of communities and societies to climate change and significantly affect their food security.

    Accordingly, on-going efforts to promote climate-smart agriculture must be engendered to benefit equally women and men farmers and entrepreneurs, and to increase the efficiency of climate change action. However, there is limited guidance and information on the type of public interventions needed to reduce CSA risks for both men and women, the ways to best combine and sequence them, and the respective cost-effectiveness of different potential portfolios of such measures.

    The proposed methodology can facilitate efforts to design and implement gender-responsive CSA policies in a transparent and systemic manner. The adoption of such an analytical framework can also facilitate the feedback loop needed to refine the proposed approach based on emerging findings from its application. Such feedback is critical to assess the cost effectiveness of agricultural interventions targeting the gender gap and to build the evidence-based required to catalyze public and private climate action at scale


    Conflict of Interest

    I confirm that I do not have any conflict of interest in connection to the paper.


    [1] Nasar-Abbas SM, E-Huma Z, Vu T, et al. (2016) Carob Kibble: A Bioactive-Rich Food Ingredient. Compr Rev Food Sci Food Saf 15: 63-72. doi: 10.1111/1541-4337.12177
    [2] Bhat KA, Shah BA, Gupta KK, et al. (2009) Semi-synthetic analogs of pinitol as potential inhibitors of TNF-alpha cytokine expression in human neutrophils. Bioorg Med Chem Lett 19: 1939-1943. doi: 10.1016/j.bmcl.2009.02.050
    [3] Anderson AB, MacDonald DL, Fischer HOL (1952) The structure of pinitol. J Am Chem Soc 74: 1479-1480. doi: 10.1021/ja01126a036
    [4] Posternak T (1936) Recherches dans la série des cyclites Ⅲ. Sur la configuration des inosites actives. Helv Chim Acta 19: 1007-1010. doi: 10.1002/hlca.193601901132
    [5] Catelani G, D'Andrea F, Griselli A, et al. (2008) A new stereoselective approach to a selectively protected derivative of D-pinitol and its evaluation as alpha-L-rhamnopyranose mimetic. Tetrahedron Lett 49: 4534-4536. doi: 10.1016/j.tetlet.2008.05.040
    [6] Dowd M, Stevens E (2002) The crystal structures of D-Pinitol and 1-Quebrachitol by low-temperature X-ray diffraction. J Carbohydr Chem 21: 373-383. doi: 10.1081/CAR-120014901
    [7] Dowd MK, Stevens ED, Experimental Crystal Structure Determination. CCDC 172582,2014. Available from: https://dx.doi.org/10.5517/cc5sl5p.
    [8] Raya-Gonzalez D, Pamatz-Bolanos T, Rio-Torres R, et al. (2008) D-(+)-Pinitol, a component of the heartwood of Enterolobium cyclocarpum (Jacq.) Griseb. Z Naturforsch C: J Biosci 63: 922-924. doi: 10.1515/znc-2008-11-1225
    [9] Anderson I, (1972) The cyclitols, In: Pigman W, Horton D. Eds. The Carbohydrates, 2nd ed., New York and London: Academic Press, Inc., Vol. 1A Chemistry and Biochemisty.
    [10] Calle J, Rivera A, Josephnathan P (1987) Pinitol from leaves of Gliricidia sepium. Planta Med 53: 303. doi: 10.1055/s-2006-962717
    [11] Poongothai G, Sripathi SK (2013) A review on insulinomimetic pinitol from plants. Int J Pharm Bio Sci 4: 992-1009.
    [12] Al-Suod H, Lior M, Ratiu IA, et al. (2016) A window on cyclitols: Characterization and analytics of inositols. Phytochem Lett 20: 507-519. doi: 10.1016/j.phytol.2016.12.009
    [13] Labed A, Ferhat M, Labed-Zouad I, et al. (2016) Compounds from the pods of Astragalus armatus with antioxidant, anticholinesterase, antibacterial and phagocytic activities. Pharm Biol 54: 3026-3032. doi: 10.1080/13880209.2016.1200632
    [14] Lahuta LB, Ciak M, Rybinski W, et al. (2017) Diversity of the composition and content of soluble carbohydrates in seeds of the genus Vicia (Leguminosae). Genet Resour Crop Evol 2017: 1-14.
    [15] Phillips DV, Dougherty DE, Smith AE (1982) Cyclitols in soybean. J Agric Food Chem 30: 456-458. doi: 10.1021/jf00111a011
    [16] Adinarayana D, Ramachandraiah P (1985) C-Glycosylphenolics from Rhynchosia suaveolens. J Nat Prod 48: 156-157. doi: 10.1021/np50037a042
    [17] Tetik N, Turhan I, Oziyci HR, et al. (2011) Determination of D-pinitol in carob syrup. Int J Food Sci Nutr 62: 672-676. doi: 10.3109/09637486.2011.560564
    [18] Sharma N, Verma MK, Gupta DK, et al. (2016) Isolation and quantification of pinitol in Argyrolobium roseum plant, by 1H-NMR. J Saudi Chem Soc 20: 81-87. doi: 10.1016/j.jscs.2014.07.002
    [19] Pérez-Pastor A, Soares-Neto JP, de la Rosa JM, et al. (2016) Carbon footprint assessment in carob tree plantations. Vida Rural April: 52-60.
    [20] Baumgartner S, Gennerritzmann R, Haas J, et al. (1986) Isolation and identification of cyclitols in carob pods (Ceratonia siliqua L.). J Agric Food Chem 34: 827-829. doi: 10.1021/jf00071a015
    [21] Oziyci HR, Turhan I, Tetik N (2015) Concentration of D-pinitol in carob extract by using multi-stage enrichment processes. GIDA 40: 125-131.
    [22] Turhan I (2011) Optimization of extraction of D-pinitol and phenolics from cultivated and wild types of carob pods using response surface methodology. Int J Food Eng 7: 639-646.
    [23] Turhan I (2014) Relationship between sugar profile and D-pinitol content of pods of wild and cultivated types of carob bean (Ceratonia siiqua L.). Int J Food Prop 17: 363-370. doi: 10.1080/10942912.2011.631255
    [24] Lin TH, Tan TW, Tsai TH, et al. (2013) D-pinitol inhibits prostate cancer metastasis through inhibition of aVb3 integrin by modulating FAK, c-Src and NF-kB pathways. Int J Mol Sci 14: 9790-9802. doi: 10.3390/ijms14059790
    [25] Streeter JG (1980) Carbohydrates in soybean nodules: Ⅱ. Distribution of compounds in seedlings during the onset of nitrogen fixation. Plant Physiol 66: 471-476. doi: 10.1104/pp.66.3.471
    [26] Hudlicky T, Price JD, Rulin F, et al. (1990) Efficient and enantiodivergent synthesis of (+)-and (-)-pinitol. J Am Chem Soc 112: 9439-9440. doi: 10.1021/ja00181a081
    [27] Hudlicky T, Rulin F, Tsunoda T, et al. (1991) Biocatalysis as a rational approach to enantiodivergent synthesis of highly oxygenated compounds: (+)-and (-)-Pinitol and Other Cyclitols. Isr J Chem 31: 229-238. doi: 10.1002/ijch.199100027
    [28] Hudlicky T, Mandel M, Rouden J, et al. (1994) Microbial Oxidation of Aromatics in Enantiocontrolled Synthesis. Part 1. Expedient and General Asymmetric Synthesis of lnositols and Carbohydrates via an Unusual Oxidation of a Polarized Diene with Potassium Permanganate. J Chem Soc Perkin Trans 1 1: 1553-1567. doi: 10.1039/p19940001553
    [29] Ley SV, Sternfeld F (1989) Microbial oxidation in synthesis: Preparation of (+)-and (-)-pinitol from benzene. Tetrahedron 45: 3463-3476. doi: 10.1016/S0040-4020(01)81025-5
    [30] Ley SV, Sternfeld F, Taylor S (1987) Microbial oxidation in synthesis: A six step preparation of (+)-Pinitol from benzene. Tetrahedron Lett 28: 225-226. doi: 10.1016/S0040-4039(00)95692-2
    [31] Aceña JL, Arjona O, Plumet J (1996) Total synthesis of (+)-pinitol. Tetrahedron: Asymmetry 7: 3535-3544. doi: 10.1016/S0957-4166(96)00461-2
    [32] Sethi G, Ahn KS, Sung B, et al. (2008) Pinitol targets nuclear factor-kB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis. Mol Cancer Ther 7: 1604-1614. doi: 10.1158/1535-7163.MCT-07-2424
    [33] Gao Y, Zhang M, Wu T, et al. (2015) Effects of D-pinitol on insulin resistance through the PI3K/Akt signaling pathway in type 2 diabetes mellitus rats. J Agric Food Chem 63: 6019-6026. doi: 10.1021/acs.jafc.5b01238
    [34] Liu SC, Chuang SM, Tang CH (2012) D-pinitol inhibits RANKL-induced osteoclasteogenesis. Int Immunopharmacol 12: 494-500. doi: 10.1016/j.intimp.2012.01.002
    [35] Zhou Y, Park CM, Cho CW, et al. (2008) Protective effect of pinitol against D-galactosamine-induced hepatotoxicity in rats fed on a high-fat diet. Biosci Biotechnol Biochem 72: 1657-1666. doi: 10.1271/bbb.70473
    [36] Shin YC, Jeon JY (2004) The physiological activities of pinitol isolated from soybean. Food Ind Nutr 30: 2680-2688.
    [37] Choi MS, Lee MK, Jung UJ, et al. (2009) Metabolic response of soy pinitol on lipid-lowering, antioxidant and hepatoprotective action in hamsters fed-high fat and high cholesterol diet. Mol Nutr Food Res 53: 751-759. doi: 10.1002/mnfr.200800241
    [38] Rengarajan T, Nandakumar N, Rajendran P, et al. (2014) D-pinitol promotes apoptosis in MCF-7 cells via induction of p53 and Bax and inhibition of Bcl-2 and NF-kB. Asian Pac J Cancer Prev 15: 1757-1762. doi: 10.7314/APJCP.2014.15.4.1757
    [39] Rengarajan T, Nandakumar N, Rajendran P, et al. (2015) D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-kB. J Physiol Biochem 71: 191-204. doi: 10.1007/s13105-015-0397-9
    [40] Fentiman IS (2001) Fixed and modifiable risk factors for breast cancer. Int J Clin Pract 55: 527-530.
    [41] Parkin DM, Bray F, Ferlay J, et al. (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94: 153-156. doi: 10.1002/ijc.1440
    [42] Mundy GR (2002) Metastasis: Metastasis to bone: Causes, consequences and therapeutic opportunities. Nat Rev Cancer 2: 584-593. doi: 10.1038/nrc867
    [43] Bryant RJ, Hamdy FC (2008) Screening for prostate cancer: An update. Eur Urol 53: 37-44. doi: 10.1016/j.eururo.2007.08.034
    [44] Ernst DS, Hanson J, Venner PM (1991) Analysis of prognostic factors in men with metastatic prostate cancer. Uro-Oncology Group of Northern Alberta. J Urol 146: 372-376. doi: 10.1016/S0022-5347(17)37797-2
    [45] Jayasooriya R, Kang CK, Park SR, et al. (2015) Pinitol suppresses tumor necrosis factor-a-induced invasion of prostate cancer LNCaP cells by inhibiting nuclear factor-kB-Mediated matrix metalloproteinase-9 expression. Trop J Pharm Res 14: 1357-1364. doi: 10.4314/tjpr.v14i8.6
    [46] Ayala GE, Dai H, Ittmann M, et al. (2004) Growth and survival mechanisms associated with perineural invasion in prostate cancer. Cancer Res 64: 6082-6090. doi: 10.1158/0008-5472.CAN-04-0838
    [47] Nakamachi H, Suzuki H, Akakura K, et al. (2002) Clinical significance of pulmonary metastases in stage D2 prostate cancer patients. Prostate Cancer Prostatic Dis 5: 159-163. doi: 10.1038/sj.pcan.4500573
    [48] Pezzuto JM (1997) Plant-derived anticancer agents. Biochem Pharmacol 53: 121-133. doi: 10.1016/S0006-2952(96)00654-5
    [49] Conney AH, Lou YR, Xie JG, et al. (1997) Some perspectives on dietary inhibition of carcinogenesis: Studies with curcumin and tea. Proc Soc Exp Biol Med 216: 243-245. doi: 10.3181/00379727-216-44173
    [50] Park EJ, Pezzuto JM (2002) Botanicals in cancer chemoprevention. Cancer Metastasis Rev 21: 231-255. doi: 10.1023/A:1021254725842
    [51] Available from: a) https://www.cancer.gov/about-cancer/treatment/cam/patient/suns-soup-pdq. b) https://www.cancer.gov/about-cancer/treatment/cam/patient/prostate-supplements-pdq#section/_95.
    [52] Rengarajan T, Nandakumar N, Balasubramanian MP (2013) D-pinitol prevents rat breast carcinogenesis induced by 7, 12-dimethylbenz (a) anthracene through inhibition of Bcl-2 and induction of p53, caspase-3 proteins and modulation of hepatic biotransformation enzymes and antioxidants. Biomed Prev Nutr 3: 31-41. doi: 10.1016/j.bionut.2012.07.001
    [53] Kim YS, Park JS, Kim MJ, et al. (2014) Inhibitory effect of D-pinitol on both growth and recurrence of breast tumor from MDA-MB-231 Cancer Cells. Korean J Pharmacogn 45: 174-180.
    [54] Rengarajan T, Nandakumar N (2012) Protective efficacy of dietary D-pinitol on hepatic and renal tissues during experimental breast cancer in rats challenged with 7, 12-Dimethylbenz (a) anthracene: A biochemical approach. Biomed Aging Pathol 2: 85-93. doi: 10.1016/j.biomag.2012.07.008
    [55] Rengarajan T, Rajendran P, Nandakumar N, et al. (2014) Free radical scavenging and antioxidant activity of D-pinitol against 7, 12-Dimethylbenz (a) anthracene induced breast cancer in sprague dawley rats. Asian Pac J Trop Dis 4: 384-390. doi: 10.1016/S2222-1808(14)60592-2
    [56] Rengarajan T, Nandakumar N, Balasubramanian MP (2012) D-pinitol attenuates 7, 12-dimethylbenz (a) anthracene induced hazards through modulating protein bound carbohydrates, adenosine triphosphatases and lysosomal enzymes during experimental mammary carcinogenesis. J Exp Ther Oncol 10: 39-49.
    [57] Song SG, Park JS, Kim YS (2015) Use of pinitol and D-chiro inositol in cancer treatment and prevention of cancer relapse. Korean patent KR 20150088589 (A).
    [58] Kumar A, Takada Y, Boriek AM, et al. (2004) Nuclear factor-kB: Its role in health and disease. J Mol Med 82: 434-448. doi: 10.1007/s00109-004-0555-y
    [59] Chaturvedi MM, Sung B, Yadav VR, et al. (2011) NF-kB addiction and its role in cancer: 'One size does not fit all'. Oncogene 30: 161-1630. doi: 10.1038/onc.2010.566
    [60] Kong D, Li Y, Wang Z, et al. (2007) Inhibition of angiogenesis and invasion by 3, 3'-diindolylmethane is mediated by the nuclear factor-kB downstream target genes MMP-9 and uPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer. Cancer Res 67: 3310-3319. doi: 10.1158/0008-5472.CAN-06-4277
    [61] Lechertier T, Hodivala-Dilke K (2012) Focal adhesion kinase and tumour angiogenesis. J Pathol 226: 404-412. doi: 10.1002/path.3018
    [62] Hwangbo C, Kim J, Lee JJ, et al. (2010) Activation of the integrin effector kinase focal adhesion kinase in cancer cells is regulated by crosstalk between protein kinase Calpha and the PDZ adapter protein mda-9/Syntenin. Cancer Res 70: 1645-1655. doi: 10.1158/0008-5472.CAN-09-2447
    [63] Boukerche H, Su ZZ, Prévot C, et al. (2008) Mda-9/Syntenin promotes metastasis in human melanoma cells by activating c-Src. Proc Natl Acad Sci USA 105: 15914-15919. doi: 10.1073/pnas.0808171105
    [64] Kumar K, Sachdanandam P, Arivazhagan R (1991) Studies on the changes in plasma lipids and lipoproteins proteins in patients with benign and malignant breast cancer. Biochem Int 23: 581-589.
    [65] Damen J, Ramshorst JV, Hoeven RPV, et al. (1984) Alterations in plasma lipoprotein and heparin-releasable lipase activities in mice bearing the grsl ascites tumor. Biochim Biophys Acta 793: 287-296. doi: 10.1016/0005-2760(84)90331-X
    [66] Rengarajan T, Nandakumar N, Balasubramanian MP (2012) D-pinitol a low molecular cyclitol prevents 7, 12-dimethylbenz (a) anthracene induced experimental breast cancer through regulating anti-apoptotic protein Bcl-2, mitochondrial and carbohydrate key metabolizing enzymes. Biomed Prev Nutr 2: 25-30. doi: 10.1016/j.bionut.2011.11.001
    [67] Rawal LB, Tapp RJ, Williams ED, et al. (2012) Prevention of type 2 diabetes and its complications in developing countries: A review. Int J Behav Med 19: 121-133. doi: 10.1007/s12529-011-9162-9
    [68] Rathmann W, Giani G (2004) Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 27: 1047-1053. doi: 10.2337/diacare.27.10.2568
    [69] Zhang BB, Moller DE (2000) New approaches in the treatment of type 2 diabetes. Curr Opin Chem Biol 4: 461-467. doi: 10.1016/S1367-5931(00)00103-4
    [70] Buse JB (2011) Type 2 diabetes mellitus in 2010: Individualizing treatment targets in diabetes care. Nat Rev Endocrinol 7: 67-68. doi: 10.1038/nrendo.2010.230
    [71] Sivakumar S, Palsamy P, Subramanian SP (2010) Impact of D-pinitol on the attenuation of proinflammatory cytokines, hyperglycemia-mediated oxidative stress and protection of kidney tissue ultrastructure in streptozotocin-induced diabetic rats. Chem Biol Interact 188: 237-245. doi: 10.1016/j.cbi.2010.07.014
    [72] Geethan PK, Prince PS (2008) Antihyperlipidemic effect of D-pinitol on streptozotocin-induced diabetic Wistar rats. J Biochem Mol Toxicol 22: 220-224. doi: 10.1002/jbt.20218
    [73] WHO Expert Committee on Diabetes Mellitus: Second Report (1980) World Health Organ Tech Rep Ser 646: 1-80.
    [74] Bates SH, Jones RB, Bailey CJ (2000) Insulin like effect of pinitol. Br J Pharmacol 130: 1944-1948. doi: 10.1038/sj.bjp.0703523
    [75] Narayanan CR, Joshi DD, Mujumdar AM, et al. (1987) Pinitol, a new antidiabetic compound from the leaves of Bougainvillea pectabilis. Curr Sci 56: 139-141.
    [76] Rastegar S, Soltani S, Roohipoor A, et al. (2017) Study of plants with D-chiro-inositol and its derivatives on diabetes. Int J Pharmacogn 4: 43-53.
    [77] Nascimento N, Cortez LU, Sousa LG, et al. (2014) Pinitol ameliorates impaired pressurenatriuresis in experimental diabetes. FASEB J 28: 1063-1065. doi: 10.1096/fasebj.28.1_supplement.1063.5
    [78] Sivakumar S, Palsamy P, Subramanian SP (2010) Attenuation of oxidative stress and alteration of hepatic tissue ultrastructure by D-pinitol in streptozotocin-induced diabetic rats. Free Radic Res 44: 668-678. doi: 10.3109/10715761003733901
    [79] Sivakumar S, Subramanian SP (2009) Pancreatic tissue protective nature of D-pinitol studied in streptozotocin-mediated oxidative stress in experimental diabetic rats. Eur J Pharmacol 622: 65-70. doi: 10.1016/j.ejphar.2009.09.021
    [80] Davis A, Christiansen M, Horowitz JF, et al. (2000) Effect of pinitol treatment on insulin action in subjects with insulin resistance. Diabetes Care 23: 1000-1005. doi: 10.2337/diacare.23.7.1000
    [81] Ortmeyer HK, Huang LC, Zhang L, et al. (1993) Chiroinositol deficiency and insulin resistance. Ⅱ. Acute effects of D-chiroinositol administration in streptozotocin diabetic rats, normal rats given a glucose load, and spontaneously insulin-resistant rhesus monkeys. Endocrinology 132: 646-651. doi: 10.1210/endo.132.2.8425484
    [82] Fonteles MC, Huang LC, Larner J (1996) Infusion of pH 2.0 D-chiroinositol glycan insulin putative mediator normalizes plasma glucose in streptozotocin diabetic rats at a dose equivalent to insulin without inducing hypoglycaemia. Diabetologia 39: 731-734. doi: 10.1007/BF00418546
    [83] Fonteles MC, Almeida MQ, Larner J (2000) Antihyperglycemic effects of 3-O-methyl-D-chiro-inositol and D-chiro-inositol associated with manganese in sterptozotocin diabetic rats. Horm Metab Res 32: 129-132. doi: 10.1055/s-2007-978606
    [84] Ortmeyer HK, Larner J, Hansen BC (1995) Effects of D-chiroinositol added to a meal on plasma glucose and insulin in hyperinsulinemic rhesus monkeys. Obes Res 3: 605S-608S. doi: 10.1002/j.1550-8528.1995.tb00232.x
    [85] Kang MJ, Kim JI, Yoon SY, et al. (2006) Pinitol from soybeans reduces postprandials blood glucose in patients with type 2 diabetes mellitus. J Med Food 9: 182-186. doi: 10.1089/jmf.2006.9.182
    [86] Dang NT, Mukai R, Yoshida K, et al. (2010) D-pinitol and myo-inositol stimulate translocation of glucose transporter 4 in skeletal muscle of C57BL/6 mice. Biosci Biotechnol Biochem 74: 1062-1067. doi: 10.1271/bbb.90963
    [87] Yu J, Choi S, Park ES, et al. (2012) D-chiro-inositol negatively regulates the formation of multinucleated osteoclasts by down-regulating NFATc1. J Clin Immunol 32: 1360-1371. doi: 10.1007/s10875-012-9722-z
    [88] Kim JI, Kim JC, Kang MJ, et al. (2005) Effects of pinitol isolated from soybeans on glycemic control and cardiovascular risk factors in patients with type 2 diabetes mellitus: A randomized controlled study. Eur J Clin Nutr 59: 456-458. doi: 10.1038/sj.ejcn.1602081
    [89] Kim MJ, Yoo KH, Kim JH, et al. (2007) Effect of pinitol on glucose metabolism and adipocytokines in uncontrolled type 2 diabetes. Diabetes Res Clin Pract 77: S247-S251. doi: 10.1016/j.diabres.2007.01.066
    [90] Kim HJ, Park KS, Lee SK, et al. (2012) Effects of pinitol on glycemic control, insulin resistance and adipocytokine levels in patients with type 2 diabetes mellitus. Ann Nutr Metab 60: 1-5. doi: 10.1159/000334834
    [91] Yap A, Nishiumi S, Yoshida KI, et al. (2007) Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives. Cytotechnology 55: 103-108. doi: 10.1007/s10616-007-9107-y
    [92] Larner J (2002) D-chiro-inositol its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res 3: 47-60. doi: 10.1080/15604280212528
    [93] Yamashita Y, Yamaoka M, Hasunuma T, et al. (2013) Detection of orally administered inositol stereoisomers in mouse blood plasma and their effects on translocation of glucose trasporter 4 in skeletal muscle cells. J Agric Food Chem 61: 4850-4854. doi: 10.1021/jf305322t
    [94] Hernández-Mijares A, Bañuls C, Peris JE, et al. (2013) A single acute dose of pinitol from a naturally-occurring food ingredient decreases hyperglycaemia and circulating insulin levels in healthy subjects. Food Chem 141: 1267-1272. doi: 10.1016/j.foodchem.2013.04.042
    [95] Martin-Lomas M, Rademacher TW, Caro HN, et al. (2001) Alkylated inositolglycans and their use. Worldwide patent WO 0185747(A1).
    [96] Ostlund RE, Sherman WR (1998) Pinitol and derivatives thereof for the treatment of metabolic disorders. United States patent US 5827896(A).
    [97] Larner J, Price J, Picariello T, et al. (1997) Method of treating defective glucose metabolism using synthetic insulin substances. United States patent US 5652221(A).
    [98] Koon MH (2013) Combination of pinitol and natural product for treating diabetes mellitus. Korean patent KR 20130017864(A).
    [99] Koon MH (2013) Combination of pinitol and drug for treating diabetes mellitus. Korean patent KR 20130017859(A).
    [100] Jun JG, Jun YJ, Kim JJ, et al. (2004) Use of chiro-inositol or pinitol for prevention of oxidative damage and prophylaxis composition for diabetic complications containing the chiro-inositol or pinitol. Korean patent KR 20040051455(A).
    [101] Holman GD, Kasuga M (1997) From receptor to transporter: Insulin signalling to glucose transport. Diabetologia 40: 991-1003. doi: 10.1007/s001250050780
    [102] White MF (1997) The insulin signaling system and IRS proteins. Diabetologia 40: S2-S17. doi: 10.1007/s001250051387
    [103] Huang LC, Fonteles MC, Houston DB, et al. (1993) Chiroinositol deficiency and insulin resistance. Ⅲ. Acute glycogenic and hypoglycemic effects of two inositol phospsoglycan insulin mediators in normal and streptozotocin diabetic rats. Endocrinology 132: 652-657. doi: 10.1210/endo.132.2.8425485
    [104] PI3 Kinase/Akt Signaling Pathway, In: Cell Signaling Technology. Available from: https://www.cellsignal.com/contents/science-pathway-research-pi3k-akt-signaling-resources/pi3k-akt-signaling-pathway/pathways-akt-signaling.
    [105] Rahal A, Kumar A, Singh V, et al. (2014) Oxidative stress, pro-oxidants, and antioxidants: The interplay. Biomed Res Int 2014: 761264. doi: 10.1155/2014/761264
    [106] Shin YC, Jeon YJ, Kim JJ (2007) Use of pinitol or chiroinositol for protecting the liver. United States patent US 2007098826 (A1).
    [107] Magielse J, Arcoraci T, Breynaert A, et al. (2013) Antihepatotoxic activity of a quantified desmodium adscendens decoction and D-pnitol against chemically-induced liver in rats. J Ethnopharmacol 146: 250-256. doi: 10.1016/j.jep.2012.12.039
    [108] Keppler D, Lesch R, Reutter W, et al. (1968) Experimental hepatitis induced by D-galactosamine. Exp Mol Pathol 9: 279-290. doi: 10.1016/0014-4800(68)90042-7
    [109] Beck G, Habicht GS (1996) Immunity and the invertebrates. Sci Am 275: 60-66. doi: 10.1038/scientificamerican1196-60
    [110] Alexander P (1975) Tumour immunology in perspective, In: Schcultz J, Leiff RC. Eds., Critical factors in cancer immunology, New York: Academic Press, 213-222.
    [111] Katz A (1983) Immunobiologic staging of patients with carcinoma of the nad and neck. Laryngoscope 93: 445-463. doi: 10.1002/lary.1983.93.4.445
    [112] Gleich GJ, kita H (1997) Bronchial asthma: Lessons from murine models. Proc Natl Acad Sci USA 94: 2101-2102. doi: 10.1073/pnas.94.6.2101
    [113] Chauhan PS, Gupta KK, Bani S (2011) The immunosuppressive effects of Agyrolobium roseum and pinitol in experimental animals. Int Immunopharmacol 11: 286-291. doi: 10.1016/j.intimp.2010.11.028
    [114] Kim JC, Shin JY, Shin DH, et al. (2005) Synergistic anti-inflammatory effects of pinitol and glucosamine in rats. Phytother Res 19: 1048-1051. doi: 10.1002/ptr.1788
    [115] Lee JS, Lee CM, Jeong YI, et al. (2007) D-pinitol regulates Th1/Th2 balance via suppressing Th2 immune response in ovalbumin-induced asthma. FEBS Lett 581: 57-64. doi: 10.1016/j.febslet.2006.11.077
    [116] Lee JS, Jung ID, Jeong YI, et al. (2007) D-pinitol inhibits Th1 polarization via the suppression of dendritic cells. Int Immunopharmacol 7: 79-804.
    [117] Heo JC, Lee SH, Hwang YH, (2011) Extract of immuno-suppressive activities of pinitol isolated from soybean. Korean patent KR 20110116627(A).
    [118] Yun YC, Choi CM, Jeon YJ, (2007) Composition for preventing and treating inflammatory disease comprising glucosamine and Pinitol. Korean patent KR 20070002401(A).
    [119] Goltzman D (2002) Discoveries, drugs and skeletal disorders. Nat Rev Drug Discov 1: 784-796. doi: 10.1038/nrd916
    [120] Rodan GA, Martin TJ (2000) Therapeutic approaches to bone diseases. Science 289: 1508-1514. doi: 10.1126/science.289.5484.1508
    [121] Jaerang R, Hyeon-Koon M (2010) Composition for prevention or treatment of bone metabolism disorder comprising d-pinitol as an active ingredient. Chinese patent CN 101808628(A).
    [122] Kirkwood TB, Austad SN (2000) Why do we age? Nature 408: 233-238. doi: 10.1038/35041682
    [123] Hada B, Yoo MR, Seong KM, et al. (2013) D-chiro-inositol and pinitol extend the life span of Drosophila Melanogaster. J Gerontol 68: 226-234. doi: 10.1093/gerona/gls156
    [124] Fontana L, Partridge L, Longo V (2010) Science 328: 321-326.
    [125] Bartke A, Chandrashekar V, Dominici F, et al. (2003) Insulin-like growth fact 1 (IGF-1) and aging: Controversies and new insights. Biogerontology 4: 1-8. doi: 10.1023/A:1022448532248
    [126] Van-Heemst D (2010) Insulin, IGF-1 and logevity. Aging Dis 1: 147-157.
    [127] Chung HY, Kim HJ, Kim JW, et al. (2001) The inflammation hypothesis of aging: Molecular modulation by calorie restriction. Ann N Y Acad Sci 928: 327-335. doi: 10.1111/j.1749-6632.2001.tb05662.x
    [128] Ishida M, Suzuki T, Tsuji A (2015) Biological clock adjusting agent. Japanese patent JP 2015140305(A).
    [129] Choi SK, Park KD, Kim DA, et al. (2013) Preparation method for Ceratonia siliqua fruit extract and cosmetic composition for anti-aging comprising the same. Korean patent KR 101339915(B1).
    [130] Choi SK, Park KD, Kim DA, et al. (2015) Cosmetic composition for anti-aging comprising Ceratonia siliqua fruit extract. Korean patent KR 20150060004(A).
    [131] Barcelos RP, Stefanello ST, Mauriz JL, et al. (2016) Creatine and the liver: Metabolism and possible interactions. Mini Rev Med Chem 16: 12-18. doi: 10.2174/1389557515666150722102613
    [132] Cooper R, Naclerio F, Allgrove J, et al. (2012) Creatine supplementation with specific view to exercise/sports performance: An update. J Int Soc Sports Nutr 9: 1-11. doi: 10.1186/1550-2783-9-33
    [133] Greenwood M, Kreider RB, RasMussen C, et al. (2001) D-pinitol augments whole body creatine retention in man. J Exerc Physiol Online 4: 41-47.
    [134] Cooke MB, Cribb PJ (2015) Effective nutritional supplement combinations, In: Greenwood M, Cooke MC, Ziegenfuss T, Kalman DS, Jose-Antonio Eds., Nutritional Supplements in Sports and Exercise, 2nd ed., Switzerland: Springer.
    [135] Chantler S, Smit K (2015) Pinitol, In: Castell LM, Stear SJ, Burke LM Eds., Nutritional Supplements in Sport, Exercise and Health: An A-Z Guide, London and New York: Routledge-Taylor & Francis Group.
    [136] Kerksick CM, Wilborn CD, Campbell WI, et al. (2009) The effects of creatine monohydrate supplementation with and without D-pinitol on resistance training adaptations. J Strength Cond Res 23: 2673-2682. doi: 10.1519/JSC.0b013e3181b3e0de
    [137] Dykstra JC (2001) A combination of pinitol and creatine to enhance uptake and retention of creatine. Worldwide patent WO 0180853(A1).
    [138] Heuer MA, Clement K, Chaudhuri S (2008) Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle. Worldwide patent WO 2008025116(A1).
    [139] Weeks C (2003) Stimulating transport of glucose into animal administration of pinitol. United States patent US 6518318.
    [140] Ferrante RM, Cunnigham CK (2012) Performance enhancing composition and method of delivering nutrients. United States patent US 2012100247(A1).
    [141] Ferrante RM, Cunnigham CK (2012) Performance enhancing compositions and method of delivering nutrients. United States patent US 2012100120(A1).
    [142] Ferrante RM, Cunnigham CK (2015) Performance enhancing composition and method of delivering nutrients. United States patent US 2015196579(A1).
    [143] Heuer MA, Clement K, Chaudhuri S (2008) Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle. United States patent US 2008058254(A1).
    [144] Dykstra JC, Prairie E (2003) Combination of pinitol and creatine to enhance uptake and retention of creatine. United States patent US 2003212134(A1).
    [145] Heuer MA, Clement K, Chaudhuri S (2008) Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle. Canadian patent CA 2558110(A1).
    [146] Folch J, Petrov D, Ettcheto M, et al. (2016) Current research therapeutic strategies for Alzheimer's disease treatment. Neural Plast 2016: 1-15. doi: 10.1155/2016/8501693
    [147] Pitt J, Thorner M, Brautigan D, et al. (2013) Protection against the synaptic targeting and toxicity of Alzheimer's-associated Aβ oligomers by insulin mimetic chiro-inositols. FASEB J 27: 199-207. doi: 10.1096/fj.12-211896
    [148] Wischik CM, Harrington CR, Storey JMD (2014) Tau-aggregation inhibitor therapy for Alzheimer's disease. Biochem Pharmacol 88: 529-539. doi: 10.1016/j.bcp.2013.12.008
    [149] Shea TB, Remington R (2015) Nutritional supplementation for Alzheimer's disease? Curr Opin Psychiatry 28: 141-147. doi: 10.1097/YCO.0000000000000138
    [150] Amirrad F, Bousoik E, Shamloo K, et al. (2017) Alzheimer's disease: Dawm of a new era? J Pharm Pharm Sci 20: 184-225. doi: 10.18433/J3VS8P
    [151] Hung SY, Fu WM (2017) Drug candidates in clinical trials for Alzheimer's disease. J Biomed Sci 24: 1-12. doi: 10.1186/s12929-016-0310-z
    [152] Acton QA (2013) Therapies and treatments, In: Neurodegenerative diseases: New insights for the healthcare professional, Georgia: ScholarlyEditions, 203-204.
    [153] Yates P, Woodward M (2017) Drug treatments in development for Alzheimer's disease, In: Ames D, O'Brien JT, Burns A. Editors, Dementia, 5 Eds., New York: CRC Press, 559.
    [154] Pasinetti GM (2006) Compositions and methods for treating Alzheimer's disease and related disorders and promoting a healthy nervous system. United States patent US 2006/0111450A1.
    [155] Pasinetti GM (2013) Compositions and methods for treating Alzheimer's disease and related disorders and promoting a healthy nervous system. United States patent US 2013/0123370A1.
    [156] McLaurin J (2010) Methods of preventing, treating and diagnosing disorders of protein aggregation. European patent EU 2153829A1.
    [157] Available from: a) https://clinicaltrials.gov/ct2/show/NCT00470418. b) Available from: https://clinicaltrials.gov/ct2/show/NCT01928420.
    [158] Falshaw A, Hart JB, Tyler PC (2000) New synthesis of 1 d-and 1 L-1, 2-anhydro-myo-inositol and assessment of their glycosidase inhibitory activities. Carbohydr Res 329: 301-308. doi: 10.1016/S0008-6215(00)00192-0
    [159] Zhan T, Lou H (2007) Synthesis of azole nucleoside analogues of D-pinitol as potential antitumor agents. Carbohydr Res 342: 865-869. doi: 10.1016/j.carres.2007.01.004
    [160] Li M, Wu A, Zhou P (2006) A concise synthesis of (+)-pancratistatin using pinitol as a chiral building blog. Tetrahedron Lett 47: 3707-3710. doi: 10.1016/j.tetlet.2006.03.138
    [161] Tegge W, Ballou CE (1989) Chiral synthesis of D-and L-myo-inositol 1, 4, 5-triphosphate. Proc Natl Acad Sci USA 86: 94-98. doi: 10.1073/pnas.86.1.94
    [162] Ballou CE, Fischer HOL (1953) Derivatives of D-mannohexodialdose (6-aldo-D-Mannose). J Am Chem Soc 75: 3673-3675. doi: 10.1021/ja01111a020
  • This article has been cited by:

    1. Marina Sánchez-Hidalgo, Antonio J. León-González, Marina Gálvez-Peralta, Nuria H. González-Mauraza, Carmen Martin-Cordero, d-Pinitol: a cyclitol with versatile biological and pharmacological activities, 2021, 20, 1568-7767, 211, 10.1007/s11101-020-09677-6
    2. Nurul Husna Ibrahim, Mohamad Fairuz Yahaya, Wael Mohamed, Seong Lin Teoh, Chua Kien Hui, Jaya Kumar, Pharmacotherapy of Alzheimer’s Disease: Seeking Clarity in a Time of Uncertainty, 2020, 11, 1663-9812, 10.3389/fphar.2020.00261
    3. Ana M. Zuluaga, Adal Mena-García, Ana C. Soria Monzón, Maite Rada-Mendoza, Diana M. Chito, Ana I. Ruiz-Matute, Maria L. Sanz, Microwave assisted extraction of inositols for the valorization of legume by-products, 2020, 133, 00236438, 109971, 10.1016/j.lwt.2020.109971
    4. Laura Siracusa, Cristina Occhiuto, Maria Sofia Molonia, Francesco Cimino, Marco Palumbo, Antonella Saija, Antonio Speciale, Concetta Rocco, Giuseppe Ruberto, Mariateresa Cristani, A pinitol-rich Glycyrrhiza glabra L. leaf extract as functional supplement with potential in the prevention of endothelial dysfunction through improving insulin signalling, 2020, 1381-3455, 1, 10.1080/13813455.2020.1764046
    5. Tomasz Antonowski, Adam Osowski, Lesław Lahuta, Ryszard Górecki, Andrzej Rynkiewicz, Joanna Wojtkiewicz, Health-Promoting Properties of Selected Cyclitols for Metabolic Syndrome and Diabetes, 2019, 11, 2072-6643, 2314, 10.3390/nu11102314
    6. Tadashi Yoshida, Christiaan J. Malherbe, Kazunobu Okon, Yutaka Miura, Makoto Hattori, Hiroshi Matsuda, Christo J.F. Muller, Elizabeth Joubert, Enhanced production of Th1- and Th2-type antibodies and induction of regulatory T cells in mice by oral administration of Cyclopia extracts with similar phenolic composition to honeybush herbal tea, 2020, 64, 17564646, 103704, 10.1016/j.jff.2019.103704
    7. Magdalena Ligor, Ileana-Andreea Rațiu, Hossam Al-Suod, Agnieszka Owczarczyk-Saczonek, Lesław Lahuta, Ryszard Górecki, Bogusław Buszewski, 2021, Chapter 7, 978-3-030-61878-0, 163, 10.1007/978-3-030-61879-7_7
    8. Il-Sup Kim, Cheorl-Ho Kim, Woong-Suk Yang, Physiologically Active Molecules and Functional Properties of Soybeans in Human Health—A Current Perspective, 2021, 22, 1422-0067, 4054, 10.3390/ijms22084054
    9. Özge ŞENER, Bengi HAKGÜDER TAZE, Carob As A Functional Food Ingredient: Properties and Food Applications, 2022, 2636-879X, 10.47137/usufedbid.1130043
    10. José Ignacio López-Sánchez, Diego A. Moreno, Cristina García-Viguera, Correction: D-pinitol, a highly valuable product from carob pods: Health-promoting effects and metabolic pathways of this natural super-food ingredient and its derivatives, 2021, 6, 2471-2086, 752, 10.3934/agrfood.2021044
    11. Esther García-Díez, Helena Sánchez-Ayora, María Blanch, Sonia Ramos, María Ángeles Martín, Jara Pérez-Jiménez, Exploring a cocoa–carob blend as a functional food with decreased bitterness: Characterization and sensory analysis, 2022, 165, 00236438, 113708, 10.1016/j.lwt.2022.113708
    12. Elif Yaver, Novel crackers incorporated with carob and green lentil flours: Physicochemical, textural, and sensory attributes, 2022, 46, 0145-8892, 10.1111/jfpp.16911
    13. Danko Jeremic, Lydia Jiménez-Díaz, Juan D. Navarro-López, Past, present and future of therapeutic strategies against amyloid-β peptides in Alzheimer’s disease: a systematic review, 2021, 72, 15681637, 101496, 10.1016/j.arr.2021.101496
    14. Joanna Płonka, Joanna Szablińska-Piernik, Bogusław Buszewski, Irena Baranowska, Lesław B. Lahuta, Analyses of Antioxidative Properties of Selected Cyclitols and Their Mixtures with Flavanones and Glutathione, 2021, 27, 1420-3049, 158, 10.3390/molecules27010158
    15. María Emilia Brassesco, Teresa R.S. Brandão, Cristina L.M. Silva, Manuela Pintado, Carob bean (Ceratonia siliqua L.): A new perspective for functional food, 2021, 114, 09242244, 310, 10.1016/j.tifs.2021.05.037
    16. Aristea Gioxari, Charalampia Amerikanou, Irini Nestoridi, Eleni Gourgari, Harris Pratsinis, Nick Kalogeropoulos, Nikolaos K. Andrikopoulos, Andriana C. Kaliora, Carob: A Sustainable Opportunity for Metabolic Health, 2022, 11, 2304-8158, 2154, 10.3390/foods11142154
    17. Aamir Khan, Ashif Iqubal, Mohd Wasim, Mansoor Ali Syed, Syed Ehtaishamul Haque, D‐pinitol attenuates isoproterenol‐induced myocardial infarction by alleviating cardiac inflammation, oxidative stress and ultrastructural changes in Swiss albino mice, 2022, 49, 0305-1870, 1232, 10.1111/1440-1681.13703
    18. Maria Derkaczew, Piotr Martyniuk, Adam Osowski, Joanna Wojtkiewicz, Cyclitols: From Basic Understanding to Their Association with Neurodegeneration, 2023, 15, 2072-6643, 2029, 10.3390/nu15092029
    19. Xinxin Liu, Tomoyuki Koyama, D-Pinitol Improved Glucose Metabolism and Inhibited Bone Loss in Mice with Diabetic Osteoporosis, 2023, 28, 1420-3049, 3870, 10.3390/molecules28093870
    20. Xinxin LIU, Chuan HE, Tomoyuki KOYAMA, D-Pinitol Ameliorated Osteoporosis via Elevating D-chiro-Inositol Level in Ovariectomized Mice, 2023, 69, 0301-4800, 220, 10.3177/jnsv.69.220
    21. Irit Schwartz Nadam, Aouatef Bellamine, Rafael Salom, Sonia Guilera, A. M. Inarejos‐Garcia, Giora Pillar, Effects of the active botanical blend “WKUP GT” on attention and cognitive functions after lunch in healthy volunteers, 2024, 0885-6222, 10.1002/hup.2895
    22. Nur Intan Saidaah Mohamed Yusof, Fazlin Mohd Fauzi, Nature's Toolbox for Alzheimer's Disease: A Review on the Potential of Natural Products as Alzheimer's Disease Drugs, 2024, 01970186, 105738, 10.1016/j.neuint.2024.105738
    23. Peter A. Thomas, Xavier Garcia‐Martí, Tarek A. Mukassabi, Joan Tous, International Biological Flora: Ceratonia siliqua, 2024, 0022-0477, 10.1111/1365-2745.14325
    24. Manfred Choo-Yong Ku, Shao-Quan Liu, Unveiling the cocoa-carob flavour gap in dark chocolates via instrumental and descriptive sensory analyses, 2024, 195, 09639969, 114992, 10.1016/j.foodres.2024.114992
    25. Adrienne M. Lambert, Cade M. Christensen, Megan M. McRee, Vaios Moschos, Markiesha H. James, Janica N. D. Gordon, Haley M. Royer, Marc N. Fiddler, Barbara J. Turpin, Solomon Bililign, Jason D. Surratt, Chemical Characterization of Organic Aerosol Tracers Derived from Burning Biomass Indigenous to Sub-Saharan Africa: Fresh Emissions versus Photochemical Aging, 2024, 2837-1402, 10.1021/acsestair.4c00206
    26. Nurul Husna Ibrahim, Jaya Kumar, Wael M.Y. Mohamed, 2025, 9780443157028, 437, 10.1016/B978-0-443-15702-8.00027-0
    27. Mohamad Ali El Chami, Guillermo Palacios-Rodríguez, José L. Ordóñez-Díaz, Raquel Rodríguez-Solana, Rafael M. Navarro-Cerrillo, José M. Moreno-Rojas, Proximate Analysis, Total Phenolic Content, and Antioxidant Activity of Wild Carob Pulp from Three Mediterranean Countries, 2025, 15, 2076-3417, 1340, 10.3390/app15031340
    28. Kadir Aksu, Melek Çol Ayvaz, Ömer Faruk Çelik, Goncagül Serdaroğlu, Elvan Üstün, Latif Kelebekli, Synthesis, Biological Activities, DFT Calculations, and Molecular Docking Studies of O‐Methyl‐Inositols, 2025, 1612-1872, 10.1002/cbdv.202402346
  • Reader Comments
  • © 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(13219) PDF downloads(3190) Cited by(25)

Article outline

Figures and Tables

Figures(9)  /  Tables(2)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog