Saikosaponins and the deglycosylated metabolites exert liver meridian guiding effect through PXR/CYP3A4 inhibition

Liu, Qiwei; Xue, Yunwen; Liu, Jingjing; Ren, Siqi; Xu, Jie; Yang, Jinni; Xing, Yuanyue; Zhang, Zunjian; Song, Rui

doi:10.1016/j.jep.2021.114344

Cited by 9 publications

(4 citation statements)

References 35 publications

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“…As one of the main sites of drug metabolism, the intestine has important effects on drug absorption, metabolism, bioactivity, and toxicity [ 40 ]. It has been reported in the literature that saikosaponins are mainly transformed into the corresponding saikogenins by intestinal microflora with glycosidase activity [ 24 , 25 ]. Moreover, the quantitative analysis of saikosaponins and saikogenins in colon contents revealed that the main site of RPA-promoted conversion of saikosaponins to saikogenins occurs in the intestine ( Figs.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, it is speculated that intestinal microflora has a certain influence on RB-induced hepatotoxicity, suggesting that the difference in gut microbiota composition may be the potential reason for different people to have different tolerance to RB-induced hepatotoxicity. In addition, some scholars speculated that saikosaponins were converted into saikogenins by intestinal microflora before absorption and then exerted pharmacological effects [ [24] , [25] , [26] ]. Our previous studies showed that the combined use of RB and RPA could promote the conversion of saikosaponins to saikogenins in serum compared with RB alone [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase

Chen

Gong

Tian

et al. 2023

Journal of Pharmaceutical Analysis

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase

Chen

Gong

Tian

et al. 2023

Journal of Pharmaceutical Analysis

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“… Orchestrating drug metabolism: since most TCM formulas have multiple herbs functioning in a synergistic or counteracting mode to achieve homeostasis, drug interaction is a major challenge for drug efficacy and safety. As seen in our metabolomics analysis, cytochrome P450 (CYPs), enzymes with catalytic activities regulating drug metabolism and drug-drug interactions [ 106 ], was inhibited by the JW treatment, suggesting that the JW treatment facilitates the bioavailability of active components, which might be attributable to PP [ 107 ], BD [ 89 , 108 ], and LC [ 109 , 110 ]. Altogether, maintaining the balance between drug metabolism and bioavailability is the key of this formula to enhance efficacy and reduce toxicity.…”

Section: Discussionmentioning

confidence: 99%

Validation of the Anticolitis Efficacy of the Jian-Wei-Yu-Yang Formula

Yan

Tang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Inflammatory bowel disease (IBD) is a major cause of morbidity and mortality due to its repetitive remission and relapse. The Jian-Wei-Yu-Yang (JW) formula has a historical application in the clinic to combat gastrointestinal disorders. The investigation aimed to explore the molecular and cellular mechanisms of JW. Methods. 2% dextran sodium sulfate (DSS) was diluted in drinking water and given to mice for 5 days to establish murine models of experimental colitis, and different doses of JW solution were administered for 14 days. Network pharmacology analysis and weighted gene co-expression network analysis (WGCNA) were utilized to predict the therapeutic role of JW against experimental colitis and colitis-associated colorectal cancer (CAC). 16S rRNA sequencing and untargeted metabolomics were conducted using murine feces. Western blotting, immunocytochemistry, and wound healing experiments were performed to confirm the molecular mechanisms. Results. (1) Liquid chromatography with mass spectrometry was utilized to confirm the validity of the JW formula. The high dose of JW treatment markedly attenuated DSS-induced experimental colitis progression, and the targets were enriched in inflammation, infection, and tumorigenesis. (2) The JW targets were related to the survival probability in patients with colorectal cancer, underlying a potential therapeutic value in CRC intervention. (3) Moreover, the JW therapy successfully rescued the decreased richness and diversity of microbiota, suppressed the potentially pathogenic phenotype of the gut microorganisms, and increased cytochrome P450 activity in murine colitis models. (4) Our in vitro experiments confirmed that the JW treatment suppressed caspase3-dependent pyroptosis, hypoxia-inducible factor 1α (HIF1α), and interleukin-1b (IL-1b) in the colon; facilitated the alternative activation of macrophages (Mφs); and inhibited tumor necrosis factor-α (TNFα)-induced reactive oxygen species (ROS) level in intestinal organoids (IOs). Conclusion. The JW capsule attenuated the progression of murine colitis by a prompt resolution of inflammation and bloody stool and by re-establishing a microbiome profile that favors re-epithelization and prevents carcinogenesis.

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“…Saikosaponin c and saikosaponin d inhibited MRP2 activity in HEK293 cells and BRL-3A cell with high MRP2 expression 160 . Saikosaponins and their metabolites also showed a liver meridian guiding effect by inhibiting PXR/CYP3A4 161 . Furthermore, saikosaponin a, saikosaponin c, and saikosaponin d were absorbed rapidly in rats 155 .…”

Section: Tcms For the Treatment Of Covid-19 Infectionsmentioning

confidence: 99%

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

Ye¹,

Fan²,

Zhao³

et al. 2023

Acta Pharmaceutica Sinica B

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Saikosaponins and the deglycosylated metabolites exert liver meridian guiding effect through PXR/CYP3A4 inhibition

Cited by 9 publications

References 35 publications

Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase

Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase

Validation of the Anticolitis Efficacy of the Jian-Wei-Yu-Yang Formula

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

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