INTERNATIONAL IMMUNOPHARMACOLOGY
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2021
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IF 4.932
Hui-Jie Liu,Sheng-Tian Cao,Bao-Ying Wen,Xue Han,Yong Li,Shan Li,Jing Li,Lei Zhang
Non-alcoholic steatohepatitis (NASH) is a devastating form of non-alcoholic fatty liver disease (NAFLD) with distinguished hallmarks of steatosis and inflammation. Rotundic acid (RA) is a natural pentacyclic triterpene compound extracted from the bank of Ilex rotunda Thunb with a wide range of biological activities. The aim of the study is to evaluate the pharmacological effect and action mechanism of RA on NASH in vitro and in vivo . RA has weak lipid lowering ability in rat primary hepatocytes, significantly decreases serum LDL level, hepatic TG and TC levels and lipid droplets, reduces NAS compared with the NASH group, and alleviates hepatic inflammation. RA also enhances the recovery of intestinal bacterial community and intestinal-derived short-chain fatty acid caused by high food diet (HFD). Further investigation shows that RA protects against HFD-induced NASH via downregulating the expression of SREBP-1c/SCD1 signaling pathway and improving gut microbiota. These findings imply that RA might be helpful for the alleviation of NASH.
研究领域:
药理学
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肝病学
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胃肠病学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Haihua Shang,Yinghui Sun,Ze Wang,Ying Zhou,Huajiao Yang,Xiaoyan Ci,Tao Cui,Yuanyuan Xia,Yuan Gu,Maoliang Liao,Quansheng Li,Duanyun Si,Changxiao Liu
Ethnopharmacological relevance Ilicis Rotundae Cortex (IRC), the dried barks of Ilex rotunda Thunb. (Aquifoliaceae), has been used for the prevention or treatment of colds, tonsillitis , dysentery , and gastrointestinal diseases in folk medicine due to its antibacterial and anti-inflammatory effects. However, there is no report about the intestinal absorption of major compounds that support traditional usage. Aim of study Considering the potential of rotundic acid (RA) – major biologically active pentacyclic triterpenes found in the IRC, this study was purposed to uncover the oral absorption mechanism of RA using in situ single-pass intestinal perfusion (SPIP) model, in vitro cell models (Caco-2, MDCKII-WT, MDCKII-MDR1, MDCKII-BCRP, and HEK293-OATP2B1 cells) and in vivo pharmacokinetics studies in rats. Materials and methods The molecular properties (solubility, lipophilicity , and chemical stability) and the effects of principal parameters (time, compound concentrations, pH, paracellular pathway, and the different intestinal segments) were analyzed by liquid chromatography-tandem mass spectrometry. The susceptibility of RA to various inhibitors, such as P-gp inhibitor verapamil , BCRP inhibitor Ko143 , OATP 2B1 inhibitor rifampicin , and absorption enhancer EGTA were assessed. Results RA was a compound with low water solubility (12.89 μg/mL) and strong lipophilicity (LogP = 4.1). RA was considered stable in all media during the SPIP and transport studies. The SPIP and cell experiments showed RA was moderate absorbed in the intestines and exhibited time, concentration, pH, and segment-dependent permeability. In addition, results from the cell model, in situ SPIP model as well as the in vivo pharmacokinetics studies consistently showed that verapamil, rifampicin, and EGTA might have significant effect on the intestinal absorption of RA. Conclusion The mechanisms of intestinal absorption of RA might involve multiple transport pathways, including passive diffusion, the participation of efflux (i.e., P-gp) and influx (i.e., OATP2B1) transporters, and paracellular pathways.
研究领域:
药理学
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民族药理学
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药剂学
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生物药剂学
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药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）