PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 7
·3799-3811
·
IF 5.882
Min Wen,Yubei Liu,Ruiying Chen,Ping He,Feihua Wu,Rui Li,Yining Lin
Sclerosing cholangitis, characterized by biliary inflammation, fibrosis, and stricturing, remains one of the most challenging conditions of clinical hepatology. Geniposide (GE) has anti-inflammatory, hepatoprotective, and cholagogic effects. Whether GE provides inhibition on the development of sclerosing cholangitis is unknown. Here, we investigated the role of GE in a mouse model in which mice were fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 4 weeks to induce sclerosing cholangitis. The results demonstrated that the increased hepatic gene expressions of pro-inflammatory (IL-6, VCAM-1, MCP-1, and F4/80) and profibrogenic markers (Col1α1, Col1α2, TGF-β, and α-SMA) in DDC feeding mice were reversed after treatment with GE. GE also suppressed expressions of CK19 and Ki67 in DDC-fed mice, suggesting that GE could ameliorate DDC-induced hepatocytes and cholangiocytes proliferation. In addition, GE significantly increased bile acids (BAs) secretion in bile, which correlated with induced expressions of hepatic FXR, BAs secretion transporters (BSEP, MRP2, MDR1, and MDR2), and reduced CYP7A1 mRNA expression. Furthermore, higher expressions of ileal FXR-FGF15 signaling and reduced ASBT were also observed after GE treatment. Taken together, these data showed that GE could modulate inflammation, fibrosis, and BAs homeostasis in DDC-fed mice, which lead to efficiently delay the progression of sclerosing cholangitis.
研究领域:
肝病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Lin Li,Shuai Xu,Wenyu Wang,Xia Li,Haotian Wang,Qi Yang,Changyuan Wang,Jiangning Gu,Haifeng Luo,Qiang Meng
Background Alcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic steatosis accompanied by inflammation is an initial and inevitable stage in the complex progression of simple alcoholic liver injury to more severe liver diseases such as hepatitis, liver fibrosis, cirrhosis and liver cancer. Purpose We aimed to identify the therapeutic role of Bruceine A (BA) in ALD whilst attempting to explore whether its protective effects depend specifically on the farnesoid X receptor (FXR). Methods Autodock was applied to detect the affinity between BA and FXR. Lieber-DeCarli liquid diet with 5% ethanol (v/v) was adopted to establish the mouse ALD model. The lentivirus mediating FXR (LV-FXR) was injected into mice via the tail vein to establish FXR-overexpressed mice. FXR silencing or overexpression plasmids were transfected into AML-12 cells prior to ethanol stimulation. Quantitative real-time PCR, Western blotting and immunofluorescence assays were employed to determine the expression of related genes. We subjected liver sections to H&E and Oil Red O staining to evaluate the liver histological injury and the deposition of lipid droplets. Results BA significantly reduced body weight and liver-to-body weight ratios as well as biochemical indexes in mice. Ethanol-induced liver damage and lipid accumulation could be alleviated by BA treatment. BA bound to FXR by two hydrogen bonds. There was a positive correlation between BA administration and FXR expression. BA inhibited the expression of lipid synthesis genes and enhanced the expression of lipid metabolism genes by activating FXR, thus alleviating steatosis in ALD. Moreover, BA exerted an ameliorative effect against inflammation by inhibiting the activation of absent in melanoma 2 (AIM2) inflammasome by activating FXR. FXR overexpression possessed the ability to counter the accumulation of lipid and the activation of AIM2 inflammasome caused by ethanol. FXR deficiency exacerbated ethanol-induced liver steatosis and inflammation. The hepatoprotective effect of BA could be disrupted by FXR antagonist guggulsterone (GS) in vivo and FXR siRNA in vitro . Conclusion BA alleviated alcoholic liver disease by inhibiting AIM2 inflammasome activation through an FXR-dependent mechanism. This study may potentially represent a new therapeutic approach for ALD.
研究领域:
药理学
·
肝病学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 7
Hongyu Jiang,Wenyan Xiong,Yingna Feng,Xingjie Li,Jinzhuo Tan,Zongde Zhang
IntroductionFast-growing solid tumors exhibit aerobic glycolysis to meet metabolic demands and evade immune surveillance. While the tumor microenvironment (TME) plays a crucial role in supporting this glycolytic phenotype, the contribution of host metabolites remains incompletely understood.MethodsThe role of bile acids (BAs) in tumor progression was evaluated using multiple mouse models, including C57BL/6J mice injected with B16 melanoma cells, BALB/c mice inoculated with 4T1 breast cancer cells, and MMTV-PyMT mice with spontaneous tumor development. To assess the impact of BA depletion, subjects were fed a 2% cholestyramine diet compared to a regular diet. The study employed various analytical techniques, including UPLC-MS to evaluate BA profiles, flow cytometry for immune cell analysis, and Seahorse extracellular flux analyzers to measure oxygen consumption and extracellular acidification rates.ResultsHere, we demonstrate that multiple bile acids (BAs) are significantly enriched in the TMEs of melanoma and breast cancer. Mechanistically, this BA enrichment drives tumor aerobic glycolysis and promotes immune evasion by modulating the interaction between the farnesoid X receptor (FXR) and retinoic acid receptor alpha (RARa). Depletion of BAs in vivo suppressed tumor progression, enhanced T cell infiltration, and alleviated T cell exhaustion, accompanied by transcriptome-wide shifts towardincreased expression of genes involved in oxidative phosphorylation. Furtherinvestigations revealed that BAs activate and stabilize the FXR-RARa complex,thereby upregulating glycolytic pathways and impairing anti-tumor immunity. Conversely, BA depletion reduced FXR/RARa protein levels and disrupted tumorimmune barrier function.DiscussionThese findings unveil a mechanism by which bile acids promote tumor progression by modulating tumor metabolism and the immune microenvironment through FXR-RARa signaling. Targeting the BA-FXR-RARa axiscould offer promising strategies for cancer therapy and diagnosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Lin Jing,Yixuan Liao,Honghong Zhan,Qianyu Chen,Xiaodong Wei,Yinda Qiu,Fancheng Meng,Zhihua Liao,Min Chen
Ethnopharmacology relevance Herpetrione, an active lignan isolated from Herpetospermum pedunculosum , a traditional Tibetan medicinal plant renowned for its use in hepatobiliary diseases, has been long applied in the treatment of jaundice, hepatitis, hepatic fibrosis and other conditions, demonstrating remarkable hepatoprotective efficacy. Aim of the study Based on the traditional efficacy of Herpetospermum pedunculosum as well as the hepatoprotective activity of herpetrione, we aim to investigate the therapeutic effects and molecular mechanisms of herpetrione against α-naphthylisothiocyanate (ANIT)-induced cholestasis in mice. Materials and methods Therapeutic effects of herpetrione were evaluated in ANIT-induced cholestatic mice and Fxr knockout mice. Molecular interactions with FXR were validated using CETSA, SIP, ITC, and SPR assays, with binding sites confirmed via molecular docking and amino acid mutation analyses. FXR-regulated signaling was explored in HepG2 cells treated with guggulsterone/lithocholic acid, using Co-IP, yeast one-hybrid, and dual-luciferase assays to clarify mechanisms. Results Herpetrione significantly alleviated ANIT-induced cholestatic liver injury, evidenced by reduced serum biomarkers of bile acid accumulation and liver damage, improved hepatobiliary pathology, and decreased hepatic inflammatory infiltration. Mechanistically, it directly bound the ligand-binding domain (Glu467/Ile317/Leu464) of FXR, then ligand-bound FXR recruit coactivator SRC-1 to trigger transcriptional upregulation of BSEP/MRP2/SHP to enhance bile acid excretion while inhibiting synthesis, thereby restoring hepatic and bile acid homeostasis. Notably, herpetrione-activated FXR directly binds the promoter region of NFKB1 to inactivate NF-κB signaling and suppress inflammation. Importantly, the therapeutic effects of herpetrione were abrogated in Fxr knockout mice. Conclusion This dual regulation of bile acid homeostasis and inflammatory signaling through targeting the FXR highlights the therapeutic potential of herpetrione in cholestatic injury.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Yuanyuan Zhang,Mingyang Liu,Yifan Zhang,Fengxia Qin,Yuan Tian,Fengguo Xu,Yuxin Zhang,Pei Zhang
The use of irinotecan (CPT-11), a first-line chemotherapeutic agent for colorectal cancer (CRC), is limited by acquired drug resistance and severe adverse effects. It has been found that activation of farnesoid X receptor (FXR) signaling reduced the growth of CRC. Here, we investigated the combination of obeticholic acid (OCA), a well-characterized FXR agonist, with CPT-11 as a potential therapeutic combination for CRC. In vitro experiments demonstrated that the OCA-CPT-11 synergistically inhibited proliferation and migration in FXR-high HT29 and SW620 cells, but exhibited minimal synergy in FXR-low HCT116 and Caco-2 cells. Genetic knockdown of FXR in HT29 cells attenuated the synergistic effects, whereas FXR overexpression in HCT116 cells enhanced them. These findings indicate that the synergistic effect of OCA-CPT-11 depends on basal FXR expression levels, highlighting the need to identify both FXR inducers and agonists. Through literature and database screening, silibinin (SB) and nigakinone (Nig) were identified to upregulate and activate FXR. Both SB-CPT-11 and Nig-CPT-11 exhibited strong synergistic anti-CRC effects in vitro , even under low FXR conditions. Nig achieved synergy with CPT‑11 at lower effective concentrations than SB, so it was prioritized as the lead candidate for in vivo evaluation. Consistently, the Nig-CPT‑11 combination synergistically inhibited the growth of HCT116 subcutaneous xenograft tumors in vivo . Notably. In summary, combining FXR inducers and agonists with CPT-11 offers a promising strategy for the treatment of CRC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 41
·期 11
·1465-1475
·
IF 5.064
Liang Li-min,Zhou Jun-jie,Xu Feng,Liu Pei-hua,Qin Lan,Liu Li,Liu Xiao-dong
Peptide transporter 1 (PepT1), highly expressed on the apical membrane of enterocytes, is involved in energy balance and mediates intestinal absorption of peptidomimetic drugs. In this study, we investigated whether and how diabetes affected the function and expression of intestinal PepT1. Diabetes was induced in rats by combination of high-fat diet and low dose streptozocin injection. Pharmacokinetics study demonstrated that diabetes significantly decreased plasma exposures of cephalexin and acyclovir following oral administration of cephalexin and valacyclovir, respectively. Single-pass intestinal perfusion analysis showed that diabetes remarkably decreased cephalexin absorption, which was associated with decreased expression of intestinal PepT1 protein. We assessed the levels of bile acids in intestine of diabetic rats, and found that diabetic rats exhibited significantly higher levels of chenodeoxycholic acid (CDCA), cholic acid (CA) and glycocholic acid (GCA), and lower levels of lithocholic acid (LCA) and hyodeoxycholic acid (HDCA) than control rats; intestinal deoxycholic acid (DCA) levels were unaltered. In Caco-2 cells, the 6 bile acids remarkably decreased expression of PepT1 protein with CDCA causing the strongest inhibition, whereas TNF-α, LPS and insulin little affected expression of PepT1 protein; short-chain fatty acids induced rather than decreased expression of PepT1 protein. Farnesoid X receptor (FXR) inhibitor glycine-β-muricholic acid or FXR knockdown reversed the downregulation of PepT1 expression by CDCA and GW4064 (another FXR agonist). In diabetic rats, the expression of intestinal FXR protein was markedly increased. Oral administration of CDCA (90, 180 mg·kg −1 ·d −1 , for 3 weeks) dose-dependently decreased the expression and function of intestinal PepT1 in rats. In conclusion, diabetes impairs the expression and function of intestinal PepT1 partly via CDCA-mediated FXR activation.
研究领域:
药理学
·
内分泌学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Mengting Li,Danyang Chen,Yu Shao,Zimeng Wang,Yanan Peng,Qiu Zhao,Lan Liu
Sinomenine (SIN), a bioactive alkaloid with anti-inflammatory activity, has shown therapeutic potential in ulcerative colitis (UC), but its precise molecular targets remain unclear. This study investigated the key targets and mechanisms underlying SIN-mediated protection in UC. In a dextran sulfate sodium (DSS)-induced colitis mouse model, SIN dose-dependently alleviated colitis symptoms, restored colon length, improved histopathology injury, and enhanced intestinal barrier integrity by increasing ZO-1 and claudin-1 expression. Integrated bioinformatics analyses, including differential expression analysis, WGCNA, network pharmacology, and machine-learning algorithms, identified farnesoid X receptor (FXR) as a core therapeutic target of SIN. Molecular docking predicted stable SIN-FXR binding, and cellular thermal shift assay further supported engagement of SIN with FXR. FXR expression was reduced in UC tissues and DSS-induced colitis mice but was restored after SIN treatment. Functional enrichment and single-cell RNA sequencing analyses linked FXR to lipid metabolism, immune regulation, and the Th17/Treg balance. Mechanistically, SIN suppressed arachidonic acid metabolism, reduced pro-inflammatory cytokines, increased anti-inflammatory cytokines, decreased Th17 cells, and promoted Treg accumulation. Co-administration of SIN with the FXR agonist fexaramine further potentiated its protective effects, whereas the FXR antagonist glycine-β-muricholic acid markedly reversed SIN-mediated improvements in intestinal inflammation, barrier integrity, arachidonic acid metabolism, and Th17/Treg homeostasis. Collectively, these findings demonstrate that SIN ameliorates experimental colitis, at least in part, by targeting FXR to modulate lipid metabolism and restoring Th17/Treg balance. This study provides a mechanistic basis for the therapeutic application of SIN, either alone or in combination with FXR agonists, in UC treatment.
✓ 已验证
DOI
PubMed
高影响因子
Advances in Traditional Medicine
·
2026
·
IF 1.4
Wu Huan,Zhou Li,Lin Wei,Zhang Hong-xing,Zhang Zhao-qing,Wang Xiao-fei,Ju Shi-ru,Liu Zhi-gang,Hu Fei
This study aimed to explore the association between the effect of electroacupuncture (EA) in improving hyperlipidemia and changes in the intestinal flora and bile acid metabolism, and to preliminarily investigate its possible molecular basis. Wistar rats were stratified into five groups: control, model, sham EA, EA, and EA+FXR agonist. Comprehensive assessments included hepatic histopathology (H&E staining), serum lipid profiling (TC, TG, LDL-C, HDL-C), 16S rDNA sequencing of gut microbiota, targeted bile acid metabolomics, and molecular analyses (Western blot, immunohistochemistry and qRT-PCR) of FXR/FGF15 pathway components and associated enzymes (CYP7B1, CYP27A1). EA intervention significantly attenuated hyperlipidemia manifestations by reducing body weight, improving hepatic steatosis, and normalizing serum lipid parameters. Gut microbiota analysis revealed EA-enhanced microbial diversity with specific modulations: decreased Firmicutes / Bacteroidota ratio, enriched Akkermansia and Bacteroidota , and reduced Muribaculum abundance. Targeted metabolomics identified EA-mediated restoration of bile acid metabolism, particularly elevation of secondary bile acids. Molecular analyses demonstrated EA activation of the FXR/FGF15 axis with downstream regulation of hepatic CYP7B1 and CYP27A1. The effect of EA in improving hyperlipidemia is significantly associated with the changes in the structure of the intestinal microbiota and the activation of the FXR/FGF15 signaling pathway. This finding suggests that the metabolic benefits of EA may involve the molecular connection of the gut microbiota-bile acid axis.
✓ 已验证
DOI
高影响因子
CURRENT ISSUES IN MOLECULAR BIOLOGY
·
2026
·Vol. 48
·期 7
·682
·
IF 4.1
Wei Zhao,Bao Yu,Chengli Li,Jingjing Li,Haijun Huang,Weiguo Cao
Cholestatic liver injury (CLI) is a complex condition for which current treatment options remain limited. Lysimachiae Herba (LH), a traditional Chinese medicine with hepatoprotective properties, has not yet been fully characterized in terms of its active constituents and underlying mechanisms in CLI. This study was designed to systematically determine the chemical composition of LH, characterize its absorbed constituents in vivo, and elucidate its therapeutic mechanisms against CLI. UPLC-Q-TOF-MS/MS was employed to analyze the chemical composition of LH and its absorbed components in rat serum. Key targets and signaling pathways were predicted using network pharmacology and molecular docking, followed by experimental validation in an ANIT-induced CLI mouse model and LCA-treated HepG2cells through biochemical assays, histological examination, transcriptomic analysis, qRT-PCR, Western blotting, and immunofluorescence analysis. A total of 129 compounds were tentatively identified in LH, among which 26 were detected in the bloodstream. Network analysis and molecular docking suggested that LH regulates bile acid homeostasis predominantly by the FXR signaling pathway. Both in vivo and in vitro experiments provided convergent evidence that LH modulates the FXR-related bile acid regulatory network, enhances bile acid efflux transporter expression, and alleviates CLI. In conclusion, this study systematically elucidates the chemical composition, absorbed constituents, and pharmacological mechanisms of LH in CLI, highlighting the involvement of FXR-related bile acid regulation as an important mechanism and providing a scientific basis for the potential development of LH for cholestatic liver injury.
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Zhang Tiantian,Zhang Feng,Zhang Yani,Li Hongxin,Zhu Guanghao,Weng Taotao,Huang Cheng,Wang Ping,He Yuqi,Hu Jing,Ge Guangbo
Introduction: Alisol B 23-acetate (AB23A), a major bioactive constituent in the Chinese herb Zexie (Rhizoma Alismatis), has been found with multiple pharmacological activities. AB23A can be readily hydrolyzed to alisol B in mammals, but the hydrolytic pathways of AB23A in humans and the key enzymes responsible for AB23A hydrolysis are still unrevealed. This study aims to reveal the metabolic organs and the crucial enzymes responsible for AB23A hydrolysis in human biological systems, as well as to decipher the impact of AB23A hydrolysis on its biological effects.Methods: The hydrolytic pathways of AB23A in human plasma and tissue preparations were carefully investigated by using Q-Exactive quadrupole-Orbitrap mass spectrometer and LC-UV, while the key enzymes responsible for AB23A hydrolysis were studied via performing a set of assays including reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses. Finally, the agonist effects of both AB23A and its hydrolytic metabolite(s) on FXR were tested at the cellular level.Results: AB23A could be readily hydrolyzed to form alisol B in human plasma, intestinal and hepatic preparations, while human butyrylcholinesterase (hBchE) and human carboxylesterases played key roles in AB23A hydrolysis in human plasma and tissue preparations, respectively. It was also found that human serum albumin (hSA) could catalyze AB23A hydrolysis, while multiple lysine residues of hSA were covalently modified by AB23A, suggesting that hSA catalyzed AB23A hydrolysis via its pseudo-esterase activity. Biological tests revealed that both AB23A and alisol B exhibited similar FXR agonist effects, indicating AB23A hydrolysis did not affect its FXR agonist effect.Discussion: This study deciphers the hydrolytic pathways of AB23A in human biological systems, which is very helpful for deep understanding of the metabolic rates of AB23A in humans, and useful for developing novel prodrugs of alisol B with desirable pharmacokinetic behaviors.
研究领域:
药理学
·
酶学
·
代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Jiahua Luo,Hui Xiong,Tengfei Zhao,Xinyue Hu,You Shi,Mingzhe Zhang,Weihua Zhang,Youcai Zhang
Farnesoid X receptor (FXR) is a central regulator of hepatic metabolic homeostasis, and emerging evidence implicates FXR in iron-induced liver injury. Six-transmembrane epithelial antigen of the prostate 3 (STEAP3) is a ferrireductase involved in cellular iron processing, but its upstream regulation in the liver is poorly understood. Here, we identify mouse hepatic Steap3 as a previously unrecognized direct transcriptional target of FXR. Analysis of STEAP family expression showed that STEAP3 is highly expressed in both human and mouse liver tissues. In three mouse models, hepatic Steap3 was the only STEAP family member consistently suppressed by iron overload. Notably, Fxr deficiency in mice reduced basal hepatic Steap3 expression and attenuated iron-mediated Steap3 repression, whereas FXR activation by GW4064 induced Steap3 expression and partially restored its expression under iron-overload conditions. Further ChIP-seq analyses and luciferase reporter assays demonstrated that mouse Steap3 is a direct transcriptional target gene of FXR. Human transcriptomic, ChIP-seq, and motif analyses suggested that human STEAP3 may be regulated by FXR in human liver cells, although the FXR-binding signal near the STEAP3 promoter appeared relatively weak. Together, these findings establish Steap3 as a direct FXR target gene in mouse liver and suggest that FXR-dependent regulation of hepatic ferrireductase expression may represent a previously underappreciated component of the hepatic response to iron overload.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Lan Luo,Wei Liu,Shenglan Qi,Jiamei Chen,Hua Zhang,Yongping Mu,Gaofeng Chen,Wei'an Yuan,Ping Liu,Linzhang Zhang
DDC-induced cholestatic liver injury in mice was significantly ameliorated by IAS II through the suppression of ductular reaction, hepatic fibrosis, and inflammatory responses. • Gut microbiota integrity is essential for IAS II efficacy, as its protective effects are lost upon antibiotic depletion. • IAS II activates PPAR-α and FXR signaling in a receptor-dependent manner to restore BA homeostasis, a mechanism validated by in vitro inhibitor studies. Cholestatic liver disease (CLD) is a severe hepatobiliary disorder with limited treatment options. Although the natural compound Isoastragaloside II (IAS II) has been suggested to possess general hepatoprotective properties, its therapeutic efficacy against CLD has not been reported. In this study, the therapeutic potential and underlying mechanisms of IAS II for CLD were investigated using a murine model established by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding. It was demonstrated that DDC-induced cholestatic liver injury was significantly alleviated by IAS II treatment, as indicated by the normalization of key serum biochemical parameters. An integrated analysis of histopathological, protein, and gene expression data demonstrated that IAS II treatment effectively suppressed the ductular reaction, inhibited hepatic fibrosis, and attenuated inflammation. Analysis of 16S rRNA sequencing data revealed that IAS II treatment was accompanied by alterations in gut microbiota composition, including an enrichment of Bacteroides and a reduction in Lachnospiraceae_NK4A136_group . Antibiotic depletion experiments demonstrated that the hepatoprotective effects of IAS II were abrogated by gut microbiota depletion, confirming the essential role of the gut microbiota in its pharmacological action. At the molecular level, IAS II activated both the PPAR-α pathway (as indicated by transcriptomic analysis) and the FXR pathway (as confirmed by subsequent validation), which collectively resulted in a significant reduction in the hepatic accumulation of toxic bile acids (BAs). In vitro studies in LCA-induced HepG2 cells further revealed that the restoration of PPAR-α, ACOX2, FXR, and BSEP protein expression by IAS II required receptor activation, as these effects were blocked by specific inhibitors. In summary, to our knowledge, this study provides the first demonstration that a protective effect against DDC-induced cholestatic liver injury is conferred by IAS II through coordinated regulation of PPAR-α and FXR signaling, restoration of BA homeostasis, and in a gut microbiota-dependent manner, with these effects requiring the activation of both PPAR-α and FXR pathways, thereby identifying IAS II as a novel and promising therapeutic candidate for CLD. Download: Download high-res image (191KB) Download: Download full-size image
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）