ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Multiple Enzymes Expressed by the Gut Microbiota Can Transform Typhaneoside and Are Associated with Improving Hyperlipidemia.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Developmental Programming of Drug Response: Microbiota as a Missing Dimension in Perinatal Drug Discovery.International journal of molecular sciences · 2026Review
- Tetrahedral framework nucleic acids as a promising vehicle for small molecule drugs of traditional Chinese medicine: application to disease prevention and treatment.Journal of nanobiotechnology · 2026Review
- Inhibitory effects of the flavonoids extracted from Pollen Typhae on palmitic acid-induced NLRP3 inflammasome activation in macrophages involving AMPK-mediated lipid metabolism.BMC complementary medicine and therapies · 2025Article
- Yinchenhao Decoction Mitigates Cholestatic Liver Injury in Mice via Gut Microbiota Regulation and Activation of FXR-FGF15 Pathway.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Multiple Enzymes Expressed by the Gut Microbiota Can Transform Typhaneoside and Are Associated with Improving Hyperlipidemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Restoration of peripheral ILC3s by washed microbiota transplantation improves lipid profiles in hyperlipidemia patients.Frontiers in immunology · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
The mechanism of multiple enzymes mediated drug metabolism in gut microbiota is still unclear. This study explores multiple enzyme interaction process of typhactyloside (TYP) with gut microbiota and its lipid-lowering pharmacological activity. TYP, with bioavailability of only 2.78%, is an active component of Typha angustifolia L. and Pushen capsules which is clinically treated for hyperlipidemia. The metabolic process of TYP is identified, and key enzymes involved in TYP metabolism are validated through gene knockout and overexpression techniques. Through overexpressing α-rhamnosidase (Rha) in Escherichia coli, TYP is verified to metabolize into isorhamnetin-3-O-neohesperidin (M1) and isorhamnetin-3-O-glucoside (M2) after removing rhamnose through Rha. Besides, knockout of β-glucosidase (Glu) confirms that TYP generates M3 through Glu after removing glucose. Combined with molecular docking, M3 is transformed to generate 3,4-dihydroxyphenylacetic acid (M4), protocatechuic acid (M5), and 3-hydroxyphenylacetic acid (M6) through flavonoid reductase (Flr) and chalcone isomerase (Chi). In conclusion, multiple enzymes involved in TYP metabolism (Rha/Glu→Flr→Chi) are identified. Through in vivo experiments, combined use of M3 and M5 also shows excellent anti-hyperlipidemia efficacy. This is the first study on complex metabolism mechanism and pharmacological activity of natural flavonoids mediated by multiple enzymes, which provide insight to investigate analogous natural products.
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