Evidence-based Complementary and Alternative Medicine
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2018
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IF 2.064
Renjie Xu,Yichu Yuan,Jia Qi,Jia Zhou,Xiaowen Guo,Jian Zhang,Ruanjuan Zhan
Loganin, iridoid glycosides, is the main bioactive ingredients in the plant Strychnos nux-vomica L. and demonstrates various pharmacological effects, though poor oral bioavailability in rats. In this study, the intestinal absorption mechanism of loganin was investigated using the human intestinal Caco-2 cell monolayer model in both the apical-to-basolateral (A-B) and the basolateral-to-apical (B-A) direction; additionally, transport characteristics were systematically investigated at different concentrations, pHs, temperatures, and potential transporters. The absorption permeability (AB) of loganin, which ranged from 12.17 to 14.78 × 10−6cm/s, was high at four tested concentrations (5, 20, 40, and 80μM), while the major permeation mechanism of loganin was found to be passive diffusion with active efflux mediated by multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP). In addition, it was found that loganin was not the substrate of efflux transporter P-glycoprotein (P-gp) since the selective inhibitor (verapamil) of the efflux transporter exhibited little effects on the transport of loganin in the human intestinal Caco-2 cells. Meanwhile, transport from the apical to the basolateral side increased 2.09-fold after addition of a MRP inhibitor and 2.32-fold after addition of a BCRP inhibitor. In summary, our results clearly demonstrate, for the first time, a good permeability of loganin in the human intestinal Caco-2 cell model and elucidate, in detail, the intestinal absorption mechanism and the effects of transporters on iridoid glycosides compounds.
研究领域:
药理学
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生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
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2026
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IF 4.9
Xinwen Li,Huiling Zhang,Chao Zhang,Xiaomin Zhang,Jiefeng He
Liver cirrhosis represents the irreversible end‐stage of various chronic liver diseases, whereas hepatic fibrosis, characterized by hepatic stellate cell (HSC) activation, constitutes the critical pathological intermediate in this progression. In this study, we investigated the antifibrotic effects of loganin, a natural iridoid glycoside, and elucidated its underlying mechanisms in bile duct ligation (BDL)–induced cholestatic liver injury and hepatic fibrosis and in TGF‐β1–stimulated HSCs. Sprague–Dawley rats subjected to BDL surgery received loganin for 14 days, resulting in marked amelioration of hepatomegaly, inflammatory infiltration, hepatocyte necrosis, and collagen deposition, alongside restoration of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (T‐BIL) levels and suppression of fibrogenic gene expression (collagen type I alpha 1 chain [COL1α1], alpha‐smooth muscle actin [α‐SMA], and fibronectin). Moreover, loganin attenuated hepatic autophagy, as evidenced by reduced Beclin‐1 expression and LC3B‐II/I ratio, with decreased colocalization of α‐SMA and LC3B. Bioinformatics analysis and molecular docking indicated that epidermal growth factor receptor (EGFR) may be the target protein through which loganin exerts its antifibrotic effect. Experimental validation demonstrated that loganin suppressed BDL‐induced EGFR phosphorylation in vivo. In TGF‐β1–activated HSC‐T6 cells, loganin inhibited cell activation, downregulated fibrosis markers, impaired autophagic flux, and suppressed TGF‐β1–induced upregulation of Beclin‐1 and LC3B‐II/I. Critically, cotreatment with the EGFR agonist EGF reversed the autophagy‐inhibitory and antifibrotic effects of loganin, whereas the EGFR inhibitor AG‐1478 mimicked loganin’s actions, confirming EGFR signaling as the functional mediator. Overall, these results indicated that loganin could alleviate liver injury and hepatic fibrosis in BDL rats by inhibiting autophagy and activation of HSCs, and this protective effect is mediated by the EGFR pathway.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2021
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IF 4.932
Jin Zhang,Changsong Wang,Hongliang Wang,Xueting Li,Jingjing Xu,Kaijiang Yu
Sepsis is a systemic inflammatory response syndrome resulted from severe infection. Excessive inflammation response plays an important role in sepsis-induced acute lung injury (ALI). Loganin is an iridoid glycoside isolated from Corni fructus and exerts an anti-inflammatory effect in multiple inflammatory diseases; however, the role of loganin in sepsis-induced ALI remains unknown. In the current study, the cecal ligation and puncture (CLP)-induced murine sepsis model was constructed to investigate the anti-inflammatory property of loganin in sepsis-induced ALI. Lipopolysaccharide (LPS)-treated Raw 264.7 cells and primary murine peritoneal macrophages were established to further explore underlying mechanism of loganin. Results showed that intragastrical administration of loganin significantly increased murine survival, reduced the alveolar structure damage and inflammatory cell infiltration. Loganin suppressed the release of the M1 macrophage-associated pro-inflammatory cytokines and induced the activation of M2-type anti-inflammatory cytokines. Besides, loganin dramatically inhibited NLRP3 inflammasome-mediated caspase-1 activation and subsequent IL-1β secretion. Further in vitro studies confirmed that loganin efficiently inhibited M1 macrophage polarization and NLRP3 inflammasome activation by blocking the extra-cellular signal-regulated kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways. Taken together, the anti-inflammatory effect of loganin in sepsis-induced ALI was associated with the ERK and NF-κB pathway-mediated macrophage polarization and NLRP3 inflammasome activation. Our study offers a favorable mechanistic basis to support the therapeutic potential of loganin in anti-inflammatory diseases, such as sepsis-induced ALI.
研究领域:
药理学
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免疫学
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传染病学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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