Research progress on the metabolic transformation of Shenling Baizhu San under the influence of the gut microbiota

Jinlan Di , Xiaochun Zhang

Adv. Chi. Med ›› 2025, Vol. 2 ›› Issue (3) : 103 -119.

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Adv. Chi. Med ›› 2025, Vol. 2 ›› Issue (3) :103 -119. DOI: 10.1002/acm4.70001
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Research progress on the metabolic transformation of Shenling Baizhu San under the influence of the gut microbiota

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Abstract

The gut microbiota plays a pivotal role in maintaining host metabolic homeostasis and overall physiological functions. Shenling Baizhu San (SLBZS), a time-honored classical prescription for tonifying Qi, strengthening the spleen, removing dampness, and arresting diarrhea, has shown broad clinical efficacy in digestive disorders. Emerging evidence indicates that the metabolic fate, pharmacokinetics, and bioavailability of SLBZS's complex herbal constituents are profoundly influenced by interactions with specific intestinal microorganisms and their enzymatic repertoire. This review systematically summarizes advances in five key areas:(1) the major bioactive components of SLBZS and their modern therapeutic applications; (2) characterization of gut microbial communities and their relevant degradative enzymes; (3) in vitro and in vivo studies elucidating microbe-mediated biotransformation of SLBZS constituents; (4) modulation of host signaling pathways—such as NF-κB, peroxisome proliferator-activated receptor, and AMPK—by SLBZS metabolites; and (5) the pharmacological implications of these microbial conversions for enhancing compound bioactivity and therapeutic outcomes. By integrating phytochemical analyses, microbial genomics, and metabolomics data, researchers have begun to identify the specific microbial taxa responsible for key hydrolysis, reduction, and deglycosylation reactions. Understanding these host-microbe-herb interactions not only sheds light on the mechanistic basis of SLBZS's efficacy, but also informs strategies to optimize its formulation and dosing. Such insights will facilitate the modernization and precision application of traditional Chinese medicine, ultimately improving patient prognosis in gastrointestinal and systemic diseases.

Keywords

degradative enzymes / gut microbiota / metabolic transformation / Shenling Baizhu San / signaling pathways

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Jinlan Di, Xiaochun Zhang. Research progress on the metabolic transformation of Shenling Baizhu San under the influence of the gut microbiota. Adv. Chi. Med, 2025, 2(3): 103-119 DOI:10.1002/acm4.70001

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References

[1]

Fan CL , Zhang R , Wang HP , et al. Effects of Shenling Baizhu San on LPS-induced inflammation in GES-1 cells via the TLR4/NF-κB/Nrf2 pathway and autophagy. Mod Drugs Clin Remedies. 2024; 39 (9): 2193- 2203 (in Chinese).

[2]

Tian X , Zhong CL , Xi XJ , et al. Exploration of medication patterns of traditional Chinese medicine for ulcerative colitis during remission based on data mining. J Guangzhou Univ Tradit Chin Med. 2024; 41 (9): 2483- 2490 (in Chinese).

[3]

Liang JL , Yang QH , Liang S , et al. Study on therapeutic principles of Shenling Baizhu San in the treatment of chronic diarrhea. J Univ Tradit Chin Med. 2018; 20 (3): 72- 75 (in Chinese).

[4]

Hu YR , Wu CQ , Chen CP , Wang YB , Liu YJ . Clinical observation of 30 cases of radiation enteritis treated by modified Shenling Baizhu San. Chin J Integrated Tradit West Med. 2004 (11): 1055 (in Chinese).

[5]

Luo AH , Zhang GF . Clinical significance of Shenling Baizhu San in combination with platinum-based chemotherapy for locally advanced cervical cancer treated with radical radiotherapy. China J Mod Med. 2016; 26 (17): 125- 129 (in Chinese).

[6]

Jiang JH , Liu L , Yi SP . Clinical observation of modified Shenling Baizhu San combined with Erchen Decoction in the treatment of chronic bronchitis with phlegm-dampness obstructing the lung syndrome. Heilongjiang Med J. 2023; 36 (5): 1034- 1037 (in Chinese).

[7]

Li A , Jiang T , Zhan M , et al. Network pharmacology and molecular docking analysis of Shenling Baizhu San in the treatment of knee osteoarthritis. Chinese J Tissue Eng Res. 2022; 26 (2): 197- 204 (in Chinese).

[8]

Xie T , Yuan J , Mei L , Li P , Pan R . Luteolin suppresses TNF-α- induced inflammatory injury and senescence of nucleus pulposus cells via the Sirt6/NF-κB pathway. Exp Ther Med. 2022; 24 (1): 469.

[9]

Jiang Z , Deng L , Li M , Alonge E , Wang Y , Wang Y . Ginsenoside Rg1 modulates the PI3K/AKT pathway for enhanced osteogenesis via GPER. Phytomedicine. 2024; 124: 155284.

[10]

Lou C , Lin C , Wang W , et al. Extracts of Oldenlandia diffusa protect chondrocytes by inhibiting apoptosis and the associated inflammatory response in osteoarthritis. J Ethnopharmacol. 2023; 316: 116744.

[11]

Ma Q , Ouyang Y , Meng F , et al. A review of pharmacological and clinical studies on the application of Shenling Baizhu San in the treatment of ulcerative colitis. J Ethnopharmacol. 2019; 244: 112105.

[12]

Sheahan ML , Flores K , Coyne MJ , et al. A ubiquitous mobile genetic element changes the antagonistic weaponry of a human gut symbiont. Science. 2024; 386 (6720): 414- 420.

[13]

Zhu B , Wang X , Li L . Human gut microbiome:the second genome of the human body. Protein Cell. 2010; 1 (8): 718- 725.

[14]

Zou Y , Wang S , Zhang H , et al. The triangular relationship between traditional Chinese medicines, intestinal flora, and colorectal cancer. Med Res Rev. 2024; 44 (2): 539- 567.

[15]

Cheng H , Yang W , Xu H , et al. Microbiota metabolites affect sleep as drivers of brain-gut communication. Int J Mol Med. 2025; 56 (3): 1- 14.

[16]

Huang Y , Zhou Y , Li H , et al. The effects of a partially hydrolyzed formula with low lactose and probiotics on mild gastrointestinal disorders of infants:a single-armed clinical trial. Nutrients. 2021; 13 (10): 3469.

[17]

Han M , Yin J , Wang X , et al. Pentachlorophenol increases diabetes risk by damaging beta-cell secretion and disrupting gut microbial-related amino acids and fatty acids biosynthesis. J Hazard Mater. 2024; 480: 136103.

[18]

Li J , Ghosh TS , Arendt E , Shanahan F , O'Toole PW . Cross- cohort gut microbiome signatures of irritable bowel syndrome presentation and treatment. Adv Sci. 2024; 11 (41): e2308313.

[19]

Foster JA , Trivedi MH . The gut-brain axis in depression:are multi-omics showing the way? Cell Rep Med. 2024; 5 (9): 101741.

[20]

Lam KC , Araya RE , Huang A , et al. Microbiota triggers STING- type I IFN-dependent monocyte reprogramming of the tumor microenvironment. Cell. 2021; 184 (21): 5338- 5356.

[21]

Luo XJ , Yang JH , Hu JP . Cistanche polysaccharides improve diabetic nephropathy in mice by modulating gut microbiota and suppressing TLR4/NF-κB signaling. Food Sci. 2024; 45 (21): 185- 193 (in Chinese).

[22]

Levin BJ , Balskus EP . Discovering radical-dependent enzymes in the human gut microbiota. Curr Opin Chem Biol. 2018; 47: 86- 93.

[23]

Kastner K , Bitter J , Pfeiffer M , et al. Enzyme machinery for bacterial glucoside metabolism through a conserved non- hydrolytic pathway. Angew Chem Int Ed. 2024; 63 (43): e202410681.

[24]

Bojarova P , Kren V . Glycosidases:a key to tailored carbohydrates. Trends Biotechnol. 2009; 27 (4): 199- 209.

[25]

Shin KC , Oh DK . Classification of glycosidases that hydrolyze specific positions and types of sugar moieties in ginsenosides. Crit Rev Biotechnol. 2016; 36 (6): 1036- 1049.

[26]

Ketudat CJ , Esen A . β-Glucosidases. Cell Mol Life Sci. 2010; 67 (20): 3389- 3405.

[27]

Liu P , Chen Y , Ma C , Ouyang J , Zheng Z . β-Galactosidase:a traditional enzyme given multiple roles through protein engineering. Crit Rev Food Sci Nutr. 2023; 65 (7): 1- 20.

[28]

Ju L , Pan Z , Zhang H , et al. New insights into the origin and evolution of alpha-amylase genes in green plants. Sci Rep. 2019; 9 (1): 4929.

[29]

Ichinose H , Fujimoto Z , Kaneko S . Characterization of an alpha-L-rhamnosidase from Streptomyces avermitilis. Biosci Biotechnol Biochem. 2013; 77 (1): 213- 216.

[30]

Ruigrok R , Weersma RK , Vich VA . The emerging role of the small intestinal microbiota in human health and disease. Gut Microbes. 2023; 15 (1): 2201155.

[31]

Rosen CE , Palm NW . Functional classification of the gut microbiota:the key to cracking the microbiota composition code. Bioessays. 2017; 39 (12): 1700032.

[32]

Li P , Callery PS , Gan LS , Balani SK . Esterase inhibition by grapefruit juice flavonoids leading to a new drug interaction. Drug Metabol Dispos. 2007; 35 (7): 1203- 1208.

[33]

Rha CS , Seong H , Jung YS , et al. Stability and fermentability of green tea flavonols in in-vitro-simulated gastrointestinal digestion and human fecal fermentation. Int J Mol Sci. 2019; 20 (23): 5890.

[34]

Matern U . Acylhydrolases from parsley (Petroselinum hortense):relative distribution and properties of four esterases hydrolyzing malonic acid hemiesters of flavonoid glucosides. Arch Biochem Biophys. 1983; 224 (1): 261- 271.

[35]

Franco RR , Mota AV , Ribeiro ZL , Silva LR , Lopes LG . Antidiabetic potential of Bauhinia forficata Link leaves:a non- cytotoxic source of lipase and glycoside hydrolase inhibitors with antioxidant and antiglycation properties. Biomed Pharmacother. 2020; 123: 109798.

[36]

Kim DY , Yuan HD , Chung IK , Kim YC . Compound K, intestinal metabolite of ginsenoside, attenuates hepatic lipid accumulation via AMPK activation in human hepatoma cells. J Agric Food Chem. 2009; 57 (4): 1532- 1537.

[37]

Garcia-Villalba R , Beltrán D , Frutos MD , Tomás-Barberán FA , Espín JC , Tomás-Barberán FA . Metabolism of different dietary phenolic compounds by the urolithin-producing human-gut bacteria Gordonibacter urolithinfaciens and Ellagibacter isourolithinifaciens. Food Funct. 2020; 11 (8): 7012- 7022.

[38]

Rechner AR , Smith MA , Kuhnle G , Gibson GR , Debnam ES , Rice-Evans CA . Colonic metabolism of dietary polyphenols:influence of structure on microbial fermentation products. Free Radic Biol Med. 2004; 36 (2): 212- 225.

[39]

Ning L , Hong J . Gut microbial β-glucuronidase:a key regulator of endobiotic homeostasis. Cell Host Microbe. 2024; 32 (6): 783- 785.

[40]

Candelieri F , Raimondi S , Ranieri R , Amaretti A , Rossi M , Rossi M . β-Glucuronidase pattern predicted from gut metagenomes indicates potentially diversified pharmacomicrobiomics. Front Microbiol. 2022; 13: 826994.

[41]

Edwinson AL , Yang L , Peters S , et al. Gut microbial β-glucuronidases regulate host luminal proteases and are depleted in irritable bowel syndrome. Nat Microbiol. 2022; 7 (5): 680- 694.

[42]

Paley EL , Merkulova-Rainon T , Faynboym A , Shestopalov VI , Aksenoff I . Geographical distribution and diversity of gut microbial NADH:ubiquinone oxidoreductase sequence associated with Alzheimer's disease. J Alzheim Dis. 2018; 61 (4): 1531- 1540.

[43]

Kim HS , Lee S , Lee DY . Aurozyme:a revolutionary nanozyme in colitis, switching peroxidase-like to catalase-like activity. Small. 2023; 19 (41): e2302331.

[44]

Grondin JM , Dejean G , Van Petegem F , Brumer H . Cell surface xyloglucan recognition and hydrolysis by the human gut commensal Bacteroides uniformis. Appl Environ Microbiol. 2022; 88 (1): e0156621.

[45]

Selma MV , Espin JC , Tomas-Barberan FA . Interaction between phenolics and gut microbiota:role in human health. J Agric Food Chem. 2009; 57 (15): 6485- 6501.

[46]

Wang WT , Xue YJ , Zhou JK , et al. Exploring the antimicrobial activity of rare ginsenosides and the progress of their related pharmacological effects. Phytomedicine. 2024; 133: 155904.

[47]

Christensen LP . Ginsenosides:chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res. 2009; 55: 1- 99.

[48]

Kim DH . Gut microbiota-mediated pharmacokinetics of ginseng saponins. J Ginseng Res. 2018; 42 (3): 255- 263.

[49]

Wang YS , Zhu H , Li H , Li Y , Zhao B , Jin YH . Ginsenoside compound K inhibits nuclear factor-kappa B by targeting Annexin A2. J Ginseng Res. 2019; 43 (3): 452- 459.

[50]

Lee HY , Cho DY , Kim DH , et al. Examining the alterations in metabolite constituents and antioxidant properties in mountain-cultivated ginseng (Panax ginseng C.A. Meyer) organs during a two-month maturation period. Antioxidants. 2024; 13 (5): 612.

[51]

Sharma A , Lee HJ . Ginsenoside compound K:insights into recent studies on pharmacokinetics and health-promoting activities. Biomolecules. 2020; 10 (7): 1028.

[52]

Liu KK , Wang QT , Yang SM , Chen Jy , Wu Hx , Wei W . Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis. Acta Pharmacol Sin. 2014; 35 (5): 599- 612.

[53]

Yang L , Zheng L , Xie X , et al. Targeting PLA2G16, a lipid metabolism gene, by ginsenoside compound K to suppress the malignant progression of colorectal cancer. J Adv Res. 2022; 36: 265- 276.

[54]

Zhou L , Tan F , Zhang X , Li Y , Yin W . Neuroprotection and mechanisms of ginsenosides in nervous system diseases:progress and perspectives. IUBMB Life. 2024; 76 (11): 862- 882.

[55]

Bae EA , Shin JE , Kim DH . Metabolism of ginsenoside Re by human intestinal microflora and its estrogenic effect. Biol Pharmaceut Bull. 2005; 28 (10): 1903- 1908.

[56]

Tournas VH , Kohn JS , Katsoudas EJ . Interactions between various microbes and ginseng botanicals. Crit Rev Microbiol. 2011; 37 (2): 113- 120.

[57]

Xue H , Liang B , Wang Y , et al. The regulatory effect of polysaccharides on the gut microbiota and their effect on human health:a review. Int J Biol Macromol. 2024; 270: 132170.

[58]

Wang Y , Zhang M , Ruan D , et al. Chemical components and molecular mass of six polysaccharides isolated from the sclerotium of Poria cocos. Carbohydr Res. 2004; 339 (2): 327- 334.

[59]

Zhang YY , Zhuang D , Wang HY , Liu Cy , Lv Gp , Meng Lj . Preparation, characterization, and bioactivity evaluation of oligosaccharides from Atractylodes lancea (Thunb.) DC. Carbohydr Polym. 2022; 277: 118854.

[60]

Hu X , Xu F , Li J , et al. Ultrasonic-assisted extraction of polysaccharides from coix seeds:optimization, purification, and in vitro digestibility. Food Chem. 2022; 374: 131636.

[61]

Chen YY , Chen SY , Chang HY , Liu YC , Chuang BF , Yen GC . Phyllanthus emblica L. polysaccharides ameliorate colitis via microbiota modulation and dual inhibition of the RAGE/NF-κB and MAPKs signaling pathways in rats. Int J Biol Macromol. 2024; 258: 129043.

[62]

Mann ER , Lam YK , Uhlig HH . Short-chain fatty acids:linking diet, the microbiome and immunity. Nat Rev Immunol. 2024; 24 (8): 577- 595.

[63]

Yu X , Ou J , Wang L , et al. Gut microbiota modulate CD8+ T cell immunity in gastric cancer through butyrate/GPR109A/HOPX. Gut Microbes. 2024; 16 (1): 2307542.

[64]

Perry RJ , Peng L , Barry NA , et al. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature. 2016; 534 (7606): 213- 217.

[65]

Li Z , Wang X , Li X , et al. Polysaccharides from Lanzhou lily attenuate induced nonalcoholic fatty liver disease by modifying the gut microbiota and metabolite profile. Chem Biodivers. 2024; 22 (1): e202401538.

[66]

Zhang C , Pi X , Li X , Huo J , Wang W . Edible herbal source- derived polysaccharides as potential prebiotics:composition, structure, gut microbiota regulation, and related health effects. Food Chem. 2024; 458: 140267.

[67]

Yue B , Zong G , Tao R , Wei Z , Lu Y . Crosstalk between traditional Chinese medicine-derived polysaccharides and the gut microbiota:a new perspective to understand traditional Chinese medicine. Phytother Res. 2022; 36 (11): 4125- 4138.

[68]

Sun J , Jiang Y , Wang B , et al. Structural characterization of polysaccharides from Atractylodes chinensis (DC.) Koidz. and protective effect against alcohol-induced intestinal injury in rats. Int J Biol Macromol. 2024; 282: 136641.

[69]

Chen L , Zhang S , Wang Y , et al. Integrative analysis of transcriptome and metabolome reveals the biosynthesis regulation of sesquiterpenoids and polyacetylenes in Atractylodes lancea (Thunb.) DC. Int J Biol Macromol. 2023; 253: 127044.

[70]

Jian T , Zhou L , Chen Y , et al. Total sesquiterpenoids of loquat leaves alleviated high-fat diet-induced obesity by targeting fecal metabolic profiling and gut microbiota composition. J Agric Food Chem. 2022; 70 (41): 13279- 13288.

[71]

Zhang XW , Wang S , Tu PF , Zeng KW . Sesquiterpene lactone from Artemisia argyi induces gastric carcinoma cell apoptosis via activating NADPH oxidase/reactive oxygen species/mitochondrial pathway. Eur J Pharmacol. 2018; 837: 164- 170.

[72]

Zhang X , Wang LX , Hao R , et al. Sesquiterpenoids in agarwood:biosynthesis, microbial induction, and pharmacological activities. J Agric Food Chem. 2024; 72 (42): 23039- 23052.

[73]

Ren Y , Jiang W , Luo C , Zhang X , Huang M . Atractylenolide III ameliorates TNBS-induced intestinal inflammation in mice by reducing oxidative stress and regulating intestinal flora. Chem Biodivers. 2021; 18 (8): e2001001.

[74]

Abu-Izneid T , Rauf A , Shariati MA , et al. Sesquiterpenes and their derivatives-natural anticancer compounds:an update. Pharmacol Res. 2020; 161: 105165.

[75]

Cheng H , Zhang D , Wu J , et al. Atractylodes macrocephala Koidz. volatile oil relieves acute ulcerative colitis via regulating gut microbiota and its metabolism. Front Immunol. 2023; 14: 1127785.

[76]

Tang JJ , Huang LF , Deng JL , et al. Cognitive enhancement and neuroprotective effects of OABL, a sesquiterpene lactone, in 5xFAD Alzheimer's disease mice model. Redox Biol. 2022; 50: 102229.

[77]

Wang L , Yang R , Yuan B , Liu Y , Liu C . The antiviral and antimicrobial activities of licorice, a widely used Chinese herb. Acta Pharm Sin B. 2015; 5 (4): 310- 315.

[78]

Kim DH , Hong SW , Kim BT , Bae EA , Park HY , Han MJ . Biotransformation of glycyrrhizin by human intestinal bacteria and its relation to biological activities. Arch Pharm Res. 2000; 23 (2): 172- 177.

[79]

Akao T , Hattori M , Kobashi K , et al. Hydrolysis of glycyrrhizin to 18β-glycyrrhetyl monoglucuronide by lysosomal β-D-glucuronidase of animal livers. Biochem Pharmacol. 1991; 6-7: 1025- 1029.

[80]

Afkhami-Poostchi A , Mashreghi M , Iranshahi M , Matin MM . Use of a genetically engineered E. coli overexpressing β- glucuronidase accompanied by glycyrrhizic acid, a natural and anti-inflammatory agent, for targeted treatment of colon carcinoma in a mouse model. Int J Pharm. 2020; 579: 119159

[81]

Qi H , Ma QH , Feng W , et al. Glycyrrhetinic acid blocks SARS-CoV-2 infection by activating the cGAS-STING signaling pathway. Br J Pharmacol. 2024; 181 (20): 3976- 3992.

[82]

Zou B , Zhang S , Li F , et al. Gancao decoction attenuates hepatic necroptosis via activating caspase-8 in cholestatic liver injury. J Ethnopharmacol. 2024; 326: 117909.

[83]

Zhao X , Liu J , Hu Y , et al. Optimization of glycyrrhetinic acid liposome by response surface methodology and investigation of its immunological activity. Int J Biol Macromol. 2012; 51 (3): 299- 304.

[84]

Zhan M , Zhou D , Lei L , et al. Glycyrrhizic acid and glycyrrhetinic acid-loaded cyclodextrin MOFs with enhanced antibacterial and anti-inflammatory effects for accelerating diabetic wound healing. Colloids Surf B Biointerfaces. 2024; 245: 114200.

[85]

Ma C , Wang F , Zhu J , et al. 18β-Glycyrrhetinic acid attenuates H2O2-induced oxidative damage and apoptosis in intestinal epithelial cells via activating the PI3K/Akt signaling pathway. Antioxidants. 2024; 13 (4): 468.

[86]

Yuan X , Zhou Y , Sun J , et al. Preventing acute liver injury via hepatocyte-targeting nano-antioxidants. Cell Prolif. 2023; 56 (12): e13494.

[87]

Van Uum SH , Walker BR , Hermus AR , et al. Effect of glycyrrhetinic acid on 11β-hydroxysteroid dehydrogenase activity in normotensive and hypertensive subjects. Clin Sci. 2002; 102 (2): 203- 211.

[88]

Afkhami-Poostchi A , Mashreghi M , Iranshahi M , Matin MM . Use of a genetically engineered E. coli overexpressing β- glucuronidase accompanied by glycyrrhizic acid, a natural and anti-inflammatory agent, for directed treatment of colon carcinoma in a mouse model. Int J Pharm. 2020; 579: 119159

[89]

Armanini D , Calò L , Semplicini A . Pseudohyperaldosteronism: pathogenetic mechanisms. Crit Rev Clin Lab Sci. 2003; 40 (3): 295- 335.

[90]

Riva A , Kolimar D , Spittler A , et al. Conversion of rutin, a prevalent dietary flavonol, by the human gut microbiota. Front Microbiol. 2020; 11: 585428.

[91]

Goris T , Cuadrat R , Braune A . Flavonoid-modifying capabilities of the human gut microbiome-an in silico study. Nutrients. 2021; 13 (8): 2688.

[92]

Paraiso IL , Plagmann LS , Yang L , et al. Reductive metabolism of xanthohumol and 8-prenylnaringenin by the intestinal bacterium Eubacterium ramulus. Mol Nutr Food Res. 2019; 63 (2): e1800923.

[93]

Yang G , Hong S , Yang P , et al. Discovery of an ene-reductase for initiating flavone and flavonol catabolism in gut bacteria. Nat Commun. 2021; 12 (1): 790.

[94]

Ruan JQ , Li S , Li YP , Wu WJ , Lee SMY , Yan R . The presystemic interplay between gut microbiota and orally administered calycosin-7-O-β-D-glucoside. Drug Metabol Dispos. 2015; 43 (10): 1601- 1611.

[95]

Day AJ , Dupont MS , Ridley S , et al. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver β-glucosidase activity. FEBS Lett. 1998; 436 (1): 71- 75.

[96]

Braune A , Blaut M . Deglycosylation of puerarin and other aromatic C-glucosides by a newly isolated human intestinal bacterium. Environ Microbiol. 2011; 13 (2): 482- 494.

[97]

Cao H , Chen X , Jassbi AR , Xiao J . Microbial biotransformation of bioactive flavonoids. Biotechnol Adv. 2015; 33 (1): 214- 223.

[98]

Li M , Xu X , Jia Y , et al. Transformation of mulberry polyphenols by Lactobacillus plantarum SC-5:increasing phenolic acids and enhancement of anti-aging effect. Food Res Int. 2024; 192: 114778.

[99]

Braune A , Blaut M . Bacterial species involved in the conversion of dietary flavonoids in the human gut. Gut Microbes. 2016; 7 (3): 216- 234.

[100]

Walle T . Methylation of dietary flavones greatly improves their hepatic metabolic stability and intestinal absorption. Mol Pharm. 2007; 4 (6): 826- 832.

[101]

Ou K , Sarnoski P , Schneider KR , Song K , Khoo C , Gu L . Microbial catabolism of procyanidins by human gut microbiota. Mol Nutr Food Res. 2014; 58 (11): 2196- 2205.

[102]

Zhang HJ , Fu J , Yu H , et al. Berberine promotes the degradation of phenylacetic acid to prevent thrombosis by modulating gut microbiota. Phytomedicine. 2024; 128: 155517.

[103]

Deng Y , Hou X , Wang H , Du H , Liu Y . Influence of gut microbiota-mediated immune regulation on response to chemotherapy. Pharmaceuticals. 2024; 17 (5): 604.

[104]

Lee G , Park JS , Lee EJ , Ahn JH , Kim HS . Anti-inflammatory and antioxidant mechanisms of urolithin B in activated microglia. Phytomedicine. 2019; 55: 50- 57.

[105]

Sun Y , Li G , Li W , Zhang T , Miao M . Exploring a maize-derived dietary fiber-phenolic acid complex with prebiotic effects. Food Chem. 2024; 460: 140444.

[106]

Cao CH , Jiang GF , Xie BC , et al. A bibliometric and visual analysis of Shenling Baizhu San based on CiteSpace. J Tradit Chin Med Univ Hunan. 2023; 39 (10): 134- 140 (in Chinese).

[107]

Liu YQ , Wang YJ , Zhang L , et al. Molecular mechanisms of Shenling Baizhu San in lung cancer treatment:a network pharmacology and molecular docking study. J Liaoning Univ Tradit Chin Med. 2022; 24 (3): 53- 59 (in Chinese).

[108]

Fisch D , Zhang T , Sun H , et al. Molecular definition of the endogenous Toll-like receptor signaling pathways. Nature. 2024; 631 (8021): 635- 644.

[109]

Engelmann C , Sheikh M , Sharma S , et al. Toll-like receptor 4 is a therapeutic target for prevention and treatment of liver failure. J Hepatol. 2020; 73 (1): 102- 112.

[110]

McKeown-Longo PJ , Higgins PJ . Integration of canonical and noncanonical pathways in TLR4 signaling:complex regulation of the wound repair program. Adv Wound Care. 2017; 6 (10): 320- 329.

[111]

Lin C , Wang H , Zhang M , et al. TLR4-biased small molecule modulators. Pharmacol Therapeut. 2021; 228: 107918.

[112]

Wang RJ , Wang G , Zhang L . Role of the TLR4/MyD88/NF-κB signaling pathway in rheumatoid arthritis and advances in traditional Chinese medicine interventions. Chin J Inf Tradit Chin Med. 2023; 40 (8): 84- 89 (in Chinese).

[113]

Yang J , Jia M , Zhang X , Wang P . Calycosin attenuates MPTP- induced Parkinson's disease by suppressing activation of TLR/NF-κB and MAPK pathways. Phytother Res. 2019; 33 (2): 309- 318.

[114]

Shan JL , Cheng HY , Wen L , et al. Advances in the mechanisms of TLR/MyD88/NF-κB signaling in various diseases. Chin Pharmacol Bull. 2019; 35 (4): 451- 455 (in Chinese).

[115]

Xu X , Wang WW , Tu Y , et al. Effects of Shenling Baizhu San on the gut microbiota of ulcerative colitis rats based on 16S rDNA sequencing. Chin J Integrated Tradit West Med. 2023; 43 (11): 1334- 1342 (in Chinese).

[116]

Zou J , Wang SP , Wang YT , et al. Regulation of the NLRP3 inflammasome with natural products against chemical-induced liver injury. Pharmacol Res. 2021; 164: 105388.

[117]

Hu X , Chi Q , Liu Q , Wang D , Zhang Y , Li S . Atmospheric H2S triggers immune damage by activating the TLR-7/MyD88/NF- κB pathway and NLRP3 inflammasome in broiler thymus. Chemosphere. 2019; 237: 124427.

[118]

Soraci L , Gambuzza ME , Biscetti L , et al. Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson's disease:mechanisms and therapeutic implications. J Neurol. 2023; 270 (3): 1346- 1360.

[119]

Hwang I , Yang J , Hong S , et al. Non-transcriptional regulation of NLRP3 inflammasome signaling by interleukin-4. Immunol Cell Biol. 2015; 93 (6): 591- 599.

[120]

Zhang A , Wang P , Ma X , et al. Mechanisms regulating NLRP3 inflammasome expression and activation in human dental pulp fibroblasts. Mol Immunol. 2015; 66 (2): 253- 262.

[121]

Jiang L , Zhang WT , Xiao T , et al. Materials basis, mechanisms of action, and safety evaluation of Shenling Baizhu San against ulcerative colitis. J Wuhan Univ (Nat Sci Ed). 2024; 70 (2): 236- 252 (in Chinese).

[122]

Zhang JJ , Shi JX , Huang J , et al. Effects of Shenling Baizhu San on NLRP3, NLRP6 proteins and related inflammatory factors in mice with ulcerative colitis. Chin J Exp Tradit Med Formulae. 2019; 25 (4): 36- 41 (in Chinese).

[123]

Xiang Q , Wen J , Zhou Z , et al. Effect of hydroxy-α-sanshool on lipid metabolism in liver and hepatocytes via AMPK signaling pathway. Phytomedicine. 2024; 132: 155849.

[124]

Zhang Q , He CX , Wang LY , et al. Hydroxy-α-sanshool from the fruits of Zanthoxylum bungeanum promotes browning of white fat by activating TRPV1 to induce PPAR-γ deacetylation. Phytomedicine. 2023; 121: 155113.

[125]

Xi Y , Kim S , Nguyen T , et al. 2-Geranyl-1-methoxyerythrabyssin II alleviates lipid accumulation and inflammation in hepatocytes through AMPK activation and AKT inhibition. Arch Pharm Res. 2023; 46 (9): 808- 824.

[126]

Huttasch M , Roden M , Kahl S . Obesity and MASLD:is weight loss the (only) key to treat metabolic liver disease? Metabolism. 2024; 157: 155937.

[127]

Montaigne D , Butruille L , Staels B . PPAR control of metabolism and cardiovascular functions. Nat Rev Cardiol. 2021; 18 (12): 809- 823.

[128]

Zhang SQ , Li YJ , Qin HW , et al. Mechanisms by which Shenling Baizhu San ameliorates obesity-induced type 2 diabetes in mice via AMPK signaling. Chin Tradit Herb Drugs (Zhongcaoyao). 2022; 45 (11): 2737- 2742 (in Chinese).

[129]

Zhang YP , Yang QH , Deng YJ , et al. Effects of Shenling Baizhu San on ultrastructure and AMPKα phosphorylation in the liver of rats with high-fat diet-induced non-alcoholic fatty liver disease. Chin J Pharmacol Clin Chin Materia Medica. 2016; 32 (1): 6- 10 (in Chinese).

[130]

Huang SY , Chen JB , Li JY , et al. Effects of Shenling Baizhu San on hepatic lipid metabolism in mice with metabolic associated fatty liver disease via KLF16/PPAR-α pathway. Chin Tradit Herb Drugs Clin Pharmacol (Zhongyao Xinyao yu Linchuang Yaoli). 2024; 35 (8): 1163- 1169 (in Chinese).

[131]

Zhu YF . Regulation and Mechanism of Shenling Baizhu San on Intestinal Barrier in Ulcerative Colitis via the miR-130a/PPARγ/Occludin Pathway. Doctoral dissertation. Shandong University of Traditional Chinese Medicine; 2022 (in Chinese).

[132]

Shackley M , Ma Y , Tate EW , Brown AJH , Frost G , Hanyaloglu AC . Short chain fatty acids enhance expression and activity of the umami taste receptor in enteroendocrine cells via a Gα(i/o) pathway. Front Nutr. 2020; 7: 568991.

[133]

Damodaran TV , Greenfield ST , Patel AG , Dressman HK , K. Lin S , Abou-Donia MB . Toxicogenomic studies of the rat brain at an early time point following acute sarin exposure. Neurochem Res. 2006; 31 (3): 367- 381.

[134]

Shan SY , Guo F , Yang H , et al. Trimethylamine N-oxide promotes atherosclerosis by inhibiting Keap1/Nrf2 signaling pathway. Hebei Med J (Hebei Yixue). 2024; 30 (6): 892- 899 (in Chinese).

[135]

Hayes JD , McMahon M , Chowdhry S , Dinkova-Kostova AT . Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathway. Antioxidants Redox Signal. 2010; 13 (11): 1713- 1748.

[136]

Wu L , Hu Z , Luo X , et al. Itaconic acid alleviates perfluorooctanoic acid-induced oxidative stress and intestinal damage by regulating the Keap1/Nrf2/HO-1 pathway and reshaping the gut microbiota. Int J Mol Sci. 2024; 25 (18): 9826.

[137]

Li YZ , Tang CJ , Tang XK , et al. Moxibustion combined with low-frequency pulsed electromagnetic field regulates ferroptosis via NRF2/GPX4 signaling to alleviate osteoarthritis. Prog Anat Sci. 2024: 1- 5 (in Chinese).

[138]

Gao Y , Wang YL , Wang SL . Effects of liraglutide on myocardial injury in diabetic rats through activation of Nrf2/HO-1 signaling pathway. Chin Pharmacol Bull. 2024: 1- 11 (in Chinese).

[139]

Zhu JX , Song N , Yang Y , et al. Ginsenoside Rb1 induces oxytosis in HepG2 hepatocellular carcinoma cells via KEAP1/PGAM5/AIFM1 pathway. Chin J Cancer Biother (Zhongguo Zhongliu Shengwu Zhiliao Zazhi). 2024; 31 (5): 445- 451 (in Chinese).

[140]

Liang L , Zhao YX , Qu NY , et al. Anti-aging antioxidant basis and mechanism of sea buckthorn based on Keap1-Nrf2 pathway and UPLC-Q-TOF-MS technology. J Liaoning Univ Tradit Chin Med (Liaoning Zhongyiyao Daxue Xuebao). 2024: 1- 13 (in Chinese).

[141]

Xie ZQ , Hu JW , Zeng JS , et al. Effects and mechanisms of the volatile oil components of Xiaoyaosan dissected formula on LPS-induced depression-like behavior in mice via PI3K/Akt/Nrf2 signaling pathway. Chin Herb Med (Zhongcaoyao). 2024; 55 (7): 2283- 2291 (in Chinese).

[142]

Mu L , Xiao M . Long-term efficacy and safety of Shenling Baizhu powder in the treatment of ulcerative colitis. Liaoning J Tradit Chin Med. 2016; 43 (2): 309- 311.

[143]

Qin L . Clinical observation of 75 cases of ulcerative colitis treated with Shenling Baizhu San. J Chin Clin Med. 2012; 4 (13): 76- 77.

[144]

Liu Y , Xie X , Wang W , et al. A randomized controlled trial protocol to evaluate the effect of modified Shenling Baizhu powder on delaying disease progression in stable-phase COPD patients (GOLD stages 1-2). Medicine (Baltim). 2020; 99 (43): e22700.

[145]

Wang Q , Zhang B , Lin P , Ren Q , Gao K , Kong C . Clinical efficacy of Shenling Baizhu San in patients with sarcopenia. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue[Chin Crit Care Emerg Med]. 2021; 33 (8): 994- 998.

[146]

Son MJ , Kim Y , Song YI , et al. Herbal medicines for treating acute otitis media:a systematic review of randomized controlled trials. Compl Ther Med. 2017; 35: 133- 139.

[147]

Ming W , Yun Z . Clinical value of modified Shenling Baizhu powder in managing targeted therapy-induced diarrhea in non-small cell lung cancer. J Tradit Chin Med. 2024; 44 (5): 1000- 1005.

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The Author(s). Advanced Chinese Medicine published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.

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