Evaluation of conditions for the intestinal probiotic-mediated biotransformation of Sennosides into Physcion in <i>Cassia occidentalis</i> extracts

Sheng-Yuan Yang; Shih-Lun Liu; Chung-Ju Chen; Chia-Sen Juo; Shuo-Wen Tsai; Yuh-Shuen Chen; Sheng-Yuan Yang; Shih-Lun Liu; Chung-Ju Chen; Chia-Sen Juo; Shuo-Wen Tsai; Yuh-Shuen Chen

doi:10.3934/agrfood.2026019

AIMS Agriculture and Food

2026, Volume 11, Issue 2: 357-379. doi: 10.3934/agrfood.2026019

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Research article

Evaluation of conditions for the intestinal probiotic-mediated biotransformation of Sennosides into Physcion in Cassia occidentalis extracts

1.
Department of Food Science and Biotechnology, National Chung Hsing University, South District, Taichung, Taiwan
2.
Department of Food Nutrition and Health Biotechnology, Asia University, Wufeng District, Taichung, Taiwan
3.
Department of Chemical Engineering, National Taiwan University, Da'an District, Taipei, Taiwan
4.
JiaLian Bio-medical Tech Co., Ltd, Xitun District, Taichung, Taiwan
5.
Department of Food Science and Technology, HungKuang University, Shalu District, Taichung, Taiwan
‡ Sheng-Yuan Yang, Shih-Lun Liu, and Chung-Ju Chen contributed equally to this work and should be considered as co-first authors.

Received: 06 February 2026 Revised: 06 May 2026 Accepted: 19 May 2026 Published: 08 June 2026

Anthraquinone compounds (AQCs) are functional constituents of various medicinal and edible plants belonging to families such as Fabaceae, Polygonaceae, and Liliaceae. They include sennosides, emodin, rhein, aloe-emodin, chrysophanol, and physcion, which show physiological activities, such as bowel movement promotion, hepatoprotection, anti-inflammatory effects, and antioxidation, as well as antimicrobial properties. The seeds of Cassia occidentalis L. (Fabaceae), an annual herb widely distributed in tropical and subtropical regions, are abundant in anthraquinone compounds, of which sennosides account for approximately 80% of the total anthrone-related constituents, and have traditionally been used as stimulant laxatives. However, sennosides are inactive forms and do not exert physiological effects until they reach the colon, where they are biotransformed by intestinal microbiota into downstream metabolites with biological activity. The major bioactive sennoside metabolites are rhein anthrone and rhein, which can be detected in the mouse colon within 2–3 h after oral administration of sennosides, confirming the crucial role of gut microbiota, particularly the intestinal probiotics Bifidobacterium and Lactobacillus, in sennoside conversion. This study aimed to investigate whether commercially available common gut probiotics possess the ability to hydrolyze sennosides in C. occidentalis extracts, to determine the suitable conditions for such hydrolysis, and to further evaluate the efficiency of sennoside conversion into physcion and rhein. Of the 20 commonly used intestinal probiotic strains tested in this study, Lactobacillus delbrueckii subsp. lactis (BCRC 14069) and Lactobacillus helveticus (BCRC 14092) were the most efficient at sennoside hydrolysis. Under suitable conversion conditions, the hydrolysis rate reached over 95%, reducing the residual sennoside content to 6–7 mg/g while significantly enhancing the production efficiency of the downstream metabolites, physcion and rhein. Furthermore, even when administered at relatively high doses according to different application needs, the hydrolyzed products remained compliant with both Taiwan Food and Drug Administration (TFDA) (12 mg/day) and European Food Safety Authority (EFSA) (10 mg/day) regulatory limits. These findings provide scientific support for microbial biotransformation and the potential use of anthraquinone compounds, and a way to mitigate the adverse effects (such as intestinal dependence and electrolyte imbalance) of traditional sennoside-based products. This work facilitated the development of C. occidentalis or sennoside-based products for use in functional foods and nutraceuticals and promotes their modernization in herbal applications.
- Cassia occidentalis L.,
- sennosides,
- biotransformation,
- physcion,
- intestinal probiotics,
- Anthraquinone compounds
Citation: Sheng-Yuan Yang, Shih-Lun Liu, Chung-Ju Chen, Chia-Sen Juo, Shuo-Wen Tsai, Yuh-Shuen Chen. Evaluation of conditions for the intestinal probiotic-mediated biotransformation of Sennosides into Physcion in Cassia occidentalis extracts[J]. AIMS Agriculture and Food, 2026, 11(2): 357-379. doi: 10.3934/agrfood.2026019

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Abstract

Anthraquinone compounds (AQCs) are functional constituents of various medicinal and edible plants belonging to families such as Fabaceae, Polygonaceae, and Liliaceae. They include sennosides, emodin, rhein, aloe-emodin, chrysophanol, and physcion, which show physiological activities, such as bowel movement promotion, hepatoprotection, anti-inflammatory effects, and antioxidation, as well as antimicrobial properties. The seeds of Cassia occidentalis L. (Fabaceae), an annual herb widely distributed in tropical and subtropical regions, are abundant in anthraquinone compounds, of which sennosides account for approximately 80% of the total anthrone-related constituents, and have traditionally been used as stimulant laxatives. However, sennosides are inactive forms and do not exert physiological effects until they reach the colon, where they are biotransformed by intestinal microbiota into downstream metabolites with biological activity. The major bioactive sennoside metabolites are rhein anthrone and rhein, which can be detected in the mouse colon within 2–3 h after oral administration of sennosides, confirming the crucial role of gut microbiota, particularly the intestinal probiotics Bifidobacterium and Lactobacillus, in sennoside conversion. This study aimed to investigate whether commercially available common gut probiotics possess the ability to hydrolyze sennosides in C. occidentalis extracts, to determine the suitable conditions for such hydrolysis, and to further evaluate the efficiency of sennoside conversion into physcion and rhein. Of the 20 commonly used intestinal probiotic strains tested in this study, Lactobacillus delbrueckii subsp. lactis (BCRC 14069) and Lactobacillus helveticus (BCRC 14092) were the most efficient at sennoside hydrolysis. Under suitable conversion conditions, the hydrolysis rate reached over 95%, reducing the residual sennoside content to 6–7 mg/g while significantly enhancing the production efficiency of the downstream metabolites, physcion and rhein. Furthermore, even when administered at relatively high doses according to different application needs, the hydrolyzed products remained compliant with both Taiwan Food and Drug Administration (TFDA) (12 mg/day) and European Food Safety Authority (EFSA) (10 mg/day) regulatory limits. These findings provide scientific support for microbial biotransformation and the potential use of anthraquinone compounds, and a way to mitigate the adverse effects (such as intestinal dependence and electrolyte imbalance) of traditional sennoside-based products. This work facilitated the development of C. occidentalis or sennoside-based products for use in functional foods and nutraceuticals and promotes their modernization in herbal applications.

References

[1]	Zhao L, Zheng L (2023) A review on bioactive Anthraquinone and derivatives as the regulators for ROS. Molecules 28: 8139. https://doi.org/10.3390/molecules28248139 doi: 10.3390/molecules28248139
[2]	Feng HY, Wang YQ, Yang J, et al. (2025) Anthraquinones from Rheum officinale Ameliorate Renal Fibrosis in Acute Kidney Injury and Chronic Kidney Disease. Drug Des Dev Ther 19: 5739–5760. https://doi.org/10.2147/DDDT.S521265 doi: 10.2147/DDDT.S521265
[3]	Zhang R, Huang C, Wu F, et al. (2023) Review on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coli. Front Pharmacol 14: 1160480. https://doi.org/10.3389/fphar.2023.1160480 doi: 10.3389/fphar.2023.1160480
[4]	Laasonen M (2003) Near infrared spectroscopy, a quality control tool for the different steps in the manufacture of herbal medicinal products: University of Helsinki.
[5]	Liu L, Zhang H, Wan B, et al. (2026) Advances and therapeutic potential of Anthraquinone compounds in neurodegenerative diseases: A comprehensive review. Drug Des Dev Ther 20: 580330. https://doi.org/10.2147/DDDT.S580330 doi: 10.2147/DDDT.S580330
[6]	Malik EM, Müller CE (2016) Anthraquinones as pharmacological tools and drugs. Med Res Rev 36: 705–748. https://doi.org/10.1002/med.21391 doi: 10.1002/med.21391
[7]	Possemiers S, Bolca S, Verstraete W, et al. (2011) The intestinal microbiome: A separate organ inside the body with the metabolic potential to influence the bioactivity of botanicals. Fitoterapia 82: 53–66. https://doi.org/10.1016/j.fitote.2010.07.012 doi: 10.1016/j.fitote.2010.07.012
[8]	Possemiers S, Vermeiren J, Marzorati M, et al. (2011) The gut microbiota as target for innovative drug development: Perspectives and a case study of inflammatory bowel diseases, Drug Development–A Case Study Based Insight into Modern Strategies. https://doi.org/10.5772/27905
[9]	Hattori M, Namba T, Akao T, et al. (1988) Metabolism of sennosides by human intestinal bacteria. Pharmacology 36: 172–179. https://doi.org/10.1159/000138437 doi: 10.1159/000138437
[10]	Akao T, Che QM, Kobashi K, et al. (1994) Isolation of a human intestinal anaerobe, Bifidobacterium sp. strain SEN, capable of hydrolyzing sennosides to sennidins. Appl Environ Microb 60: 1041–1043. https://doi.org/10.1128/aem.60.3.1041-1043.1994 doi: 10.1128/aem.60.3.1041-1043.1994
[11]	Taiwan Food and Drug Administration (2018) Restrictions on the use and labeling of the food ingredient "Sennosides". MOHW Food No 1061303321. Taipei, Taiwan: Taiwan Food and Drug Administration.
[12]	Peschlow EL (1993) Sennoside-induced secretion and its relevance for the laxative effect. Pharmacology 47: 14–21. https://doi.org/10.1159/000139838 doi: 10.1159/000139838
[13]	E. Panelo. F. Additives (2018) Safety of hydroxyanthracene derivatives for use in food, EFSA J 16: e05090. https://doi.org/10.2903/j.efsa.2018.5090 doi: 10.2903/j.efsa.2018.5090
[14]	Wang YN, Zhang ZH, Liu HJ, et al. (2023) Integrative phosphatidylcholine metabolism through phospholipase A(2) in rats with chronic kidney disease. Acta Pharmacol Sin 44: 393–405. https://doi.org/10.1038/s41401-022-00947-x doi: 10.1038/s41401-022-00947-x
[15]	Miao H, Wang KE, Li P, et al. (2025) Rhubarb: Traditional uses, phytochemistry, multiomics-based novel pharmacological and toxicological mechanisms. Drug Des Devel Ther 19: 9457–9480. https://doi.org/10.2147/DDDT.S557114 doi: 10.2147/DDDT.S557114
[16]	Zhang Y, Jiang Y, Shang K, et al. (2024) Updated pharmaceutical progress on plant antibiotic rhein and its analogs: Bioactivities, structure-activity relationships and future perspectives. Bioorgan Med Chem 113: 117895. https://doi.org/10.1016/j.bmc.2024.117895 doi: 10.1016/j.bmc.2024.117895
[17]	Fu Y, Yang L, Liu L, et al. (2024) Rhein: An updated review concerning its biological activity, pharmacokinetics, structure optimization, and future pharmaceutical applications. Pharmaceuticals 17: 1665. https://doi.org/10.3390/ph17121665 doi: 10.3390/ph17121665
[18]	Chiba T, Wang T, Kikuchi S (2024) Colonoscopic resolution of melanosis coli after cessation of Senna laxative use. Int Med Case Rep J 17: 783–787. https://doi.org/10.2147/IMCRJ.S475869 doi: 10.2147/IMCRJ.S475869
[19]	Cheng L, Chen Q, Pi R, et al. (2021) A research update on the therapeutic potential of Rhein and its derivatives. Eur J Pharmacol 899: 173908. https://doi.org/10.1016/j.ejphar.2021.173908 doi: 10.1016/j.ejphar.2021.173908
[20]	Zhou YX, Xia W, Yue W, et al. (2015) Rhein: A review of pharmacological activities. Evid-Based Compl Alt 2015: 578107. https://doi.org/10.1155/2015/578107 doi: 10.1155/2015/578107
[21]	Liu X, Li H, Gao X (2025) Nitroreductase from Enterococcus faecalis catalyzes the metabolic activation of sennoside A in the colon via a unique CC reductive cleavage. Int J Biol Macromol 319: 145153. https://doi.org/10.1016/j.ijbiomac.2025.145153 doi: 10.1016/j.ijbiomac.2025.145153
[22]	Zhou YX, Zhang RQ, Rahman K, et al. (2019) Diverse pharmacological activities and potential medicinal benefits of Geniposide. Evid-Based Compl Alt 2019, 4925682. https://doi.org/10.1155/2019/4925682 doi: 10.1155/2019/4925682
[23]	Chen Y, Mu L, Xing L, et al. (2019) Rhein alleviates renal interstitial fibrosis by inhibiting tubular cell apoptosis in rats. Biol Res 52: 50. https://doi.org/10.1186/s40659-019-0257-0 doi: 10.1186/s40659-019-0257-0
[24]	Guillén H, Curiel JA, Landete JM, et al. (2009) Characterization of a nitroreductase with selective nitroreduction properties in the food and intestinal lactic acid bacterium Lactobacillus plantarum WCFS1. J Agric Food Chem 57: 10457–10465. https://doi.org/10.1021/jf9024135 doi: 10.1021/jf9024135
[25]	Gao X, Ren J, Wu Q, et al. (2012) Biochemical characterization and substrate profiling of a new NADH-dependent enoate reductase from Lactobacillus casei. Enzyme Microb Tech 51: 26–34. https://doi.org/10.1016/j.enzmictec.2012.03.009 doi: 10.1016/j.enzmictec.2012.03.009
[26]	Yadav JP, Arya V, Yadav S, et al. (2010) Cassia occidentalis L. : A review on its ethnobotany, phytochemical and pharmacological profile. Fitoterapia 81: 223–230. https://doi.org/10.1016/j.fitote.2009.09.008 doi: 10.1016/j.fitote.2009.09.008
[27]	Gebrezgi EM, Hiben MG, Kidanu KG, et al. (2020) Subacute hepatotoxicity of extracts of senna occidentalis seeds in Swiss albino mice. J Toxicol 2020: 8843044. https://doi.org/10.1155/2020/8843044 doi: 10.1155/2020/8843044
[28]	Dehkordi NG, Ghanadian M, Arabha S (2014) Development of a validated HPLC method for the determination of sennoside A and B, two major constituents of Cassia obovata Coll. J Herbmed Pharmacol 3: 119–124.
[29]	Lemli J, Lemmens L (1980) Metabolism of sennosides and rhein in the rat. Pharmacology 20: 50–57. https://doi.org/10.1159/000137398 doi: 10.1159/000137398
[30]	Shimada K, Fujikawa K, Yahara K, et al. (1992) Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion. J Agr Food Chem 40: 945–948. https://doi.org/10.1021/jf00018a005 doi: 10.1021/jf00018a005
[31]	Nardini M (2022) Phenolic compounds in food: Characterization and health benefits. Molecules 27. https://doi.org/10.3390/molecules27030783 doi: 10.3390/molecules27030783
[32]	Zhishen J, Mengcheng T, Jianming W (1999) The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem 64: 555–559. https://doi.org/10.1016/S0308-8146(98)00102-2 doi: 10.1016/S0308-8146(98)00102-2
[33]	Yang L, Akao T, Kobashi K, et al. (1996) Purification and characterization of a novel sennoside-hydrolyzing. BETA. -Glucosidase from Bifidobacterium Sp. strain SEN, a human intestinal anaerobe. Biol Pharm Bull 19: 705–709. https://doi.org/10.1248/bpb.19.705 doi: 10.1248/bpb.19.705
[34]	Narrowe AB, Lemons JMS, Mahalak KK, et al. (2024) Targeted remodeling of the human gut microbiome using Juemingzi (Senna seed extracts). Front Cell Infect Mi 14: 1296619. https://doi.org/10.3389/fcimb.2024.1296619 doi: 10.3389/fcimb.2024.1296619
[35]	Matsumoto M, Ishige MA, Yazawa Y, et al. (2012) Promotion of intestinal peristalsis by Bifidobacterium spp. capable of hydrolysing sennosides in mice. PLoS One 7: e31700. https://doi.org/10.1371/journal.pone.0031700 doi: 10.1371/journal.pone.0031700

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