PHYTOCHEMISTRY
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2023
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IF 3.8
Qi Hong,Miao-Miao Guo,Jin Yang,Xing Wei,Li Liao,Xiu-Juan Xin,Di Zhang,Fa-Liang An
Four previously undescribed diketopiperazine-type alkaloids including one oxepin-containing diketopiperazine-type alkaloid, oxepinamide L (1), three 4-quinazolinone alkaloids, puniceloids E-G (10–12), together with 12 known analogues, protuboxepin D (2), oxepinamides D-G, J-K and I (3–9), puniceloids B-D (13–15) and protubonine B (16), were isolated from the culture of the marine-derived fungus Aspergillus puniceus FAHY0085. The structures of the previously undescribed compounds were comprehensively elucidated by detailed interpretation of their NMR and HRESIMS data. Their absolute configurations were unambiguously determined by ROESY experiments, Marfey's method, calculated ECD experiments and single-crystal X-ray diffraction analysis. Compounds (3–4, 6–8, 14–15) were evaluated for their cytotoxic activity against HepG2, MCF-7, SW1116 and HeLa cells and compound 6 and 14 showed moderate cytotoxic activity against HeLa cells with IC 50 49.61 ± 2.91 and 28.38 ± 1.57 μM, respectively. Compounds (1–8, 11–15) were screened for their transcriptional activation of liver X receptor α and compound 11 with known compounds 13–15 showed significant transcriptional activation of liver X receptor α with EC 50 values in the range 2–50 μM.
研究领域:
化学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2017
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IF 2.896
Meijing Liu,Changhui Liu,Hao Chen,Xiaotao Huang,Xiaohui Zeng,Juncheng Zhou,Suiqing Mi
Schaftoside (SS) is a bioactive compound present in the Herba Desmodii Styracifolii (DS), a herb that has been used to treat cholelithiasis and urolithiasis in Chinese medicine. Whether SS inhibits cholesterol (Ch) gallstone formation has not been investigated. This study examined the effects of oral intake of SS on Ch gallstone formation in C57BL/6 mice fed a lithogenic diet. The rate of gallstone formation was recorded. Levels of Ch, triglycerides (TG) and bile salts (BS) were measured in the bile and serum. Liver histopathology was examined microscopically, and mRNA expression levels of key genes involved in cholesterol and bile metabolism were determined by qPCR . Mice fed SS were protected against gallstone formation, had increased biliary levels of BS, and reduced biliary Ch levels, resulting in a lower Ch saturation index (CSI). In addition, mice fed SS had lower serum TG and Ch levels, increased mRNA expression of liver X receptor α , ATP binding cassette transporter 5/8 (ABCG5/8), and ileal bile acid binding protein (IBABP) in the ileum, and of farnesoid X receptor and bile salt export protein (BSEP) in the liver and ileum. SS also protected against histologically determined liver damage. Overall, these data indicate that SS protects against Ch gallstone formation in mice, and that the effect is mediated by activation of ileal liver X receptor α and hepatic farnesoid X receptor.
研究领域:
药理学
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胃肠病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
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IF 3.322
Hengte Xing,Chuancai Liang,Chenyu Wang,Xiongfeng Xu,Yong Hu,Bo Qiu
In this study, we aim to investigate the effect of metformin on cholesterol synthesis and efflux-related genes in chondrocytes during osteoarthritis (OA) and explore the underlying mechanisms. Primary chondrocytes were harvested from Wistar rat cartilage and divided into control and treatment groups. Chondrocytes in the treatment group were treated with interleukin-1β (IL-1β) mimicking the inflammatory environment of osteoarthritis. Subsequently, RT-qPCR, Western blotting, immunofluorescence staining, and Cell Counting Kit-8 (CCK-8) were conducted. Significant reductions in phosphorylated AMP-activated protein kinase (p-AMPK) and silent information regulator 1 (SIRT1) protein expression were observed in both human OA chondrocytes and cultured primary murine chondrocytes treated with IL-1β, while AMP-activated protein kinase (AMPK) was not inhibited. Moreover, in the presence of IL-1β, metformin significantly increased the expression of p-AMPK and SIRT1 at the protein and mRNA level. Meanwhile, metformin could reverse IL-1β-induced cartilage extracellular matrix degradation in chondrocytes from the rat model of OA (treated by IL-β) by activating the AMPK/SIRT1 pathway. Moreover, metformin activated AMPK and SIRT1, mediated by the activation of SREBP-2 and HMGCR in OA chondrocytes. Inhibiting AMPK/SIRT1 activity by its specific inhibitor could suppress IL-1β-induced expression of LXRα, ABCA1 and ApoA1 and cholesterol efflux. Thus, metformin inhibits cholesterol synthesis and promotes cholesterol efflux by activating the AMPK/SIRT1 pathway in OA chondrocytes. This study improves our understanding of the effect of metformin on cholesterol accumulation in OA chondrocytes.
研究领域:
药理学
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风湿病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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