JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Sumin Ge,Sihua Wu,Qin Yin,Meng Tan,Sichuan Wang,Yonghao Yang,Zixuan Chen,Lei Xu,Hui Zhang,Chuang Meng,Yufei Xia,Naoki Asakawa,Wenping Wei,Kaizheng Gong,Xin Pan
Ethnopharmacological relevance Eclipta prostrata (Linn.) is a traditional medicinal Chinese herb that displays multiple biological activities, such as encompassing immunomodulatory, anti-inflammatory, anti-tumor, liver-protective, antioxidant, and lipid-lowering effects. Ecliptasaponin A (ESA), a pentacyclic triterpenoid saponin isolated from Eclipta prostrata (Linn.), has been demonstrated to exert superior anti-inflammatory activity against many inflammatory disorders. Aim of the study Inflammation plays a critical role in acute myocardial infarction (AMI). This study aims to explore the treatment effects of ESA in AMI, as well as the underlying mechanism. Methods An AMI mouse model was established in mice via left anterior descending coronary artery (LAD) ligation. After surgery, ESA was injected at doses of 0.5, 1.25, and 2.5 mg/kg, respectively. Myocardial infarction size, cardiomyocyte apoptosis and cardiac echocardiography were studied. The potential mechanism of action of ESA was investigated by RNA-seq, Western blot, surface plasmon resonance (SPR), molecular docking, and immunofluorescence staining. Results ESA treatment not only significantly reduced myocardial infarct size, decreased myocardial cell apoptosis, and inhibited inflammatory cell infiltration, but also facilitated to improve cardiac function. RNA-seq and Western blot analysis proved that ESA treatment-induced differential expression genes mainly enriched in HMGB1/TLR4/NF-κB pathway. Consistently, ESA treatment resulted into the down-regulation of IL-1β, IL-6, and TNF-α levels after AMI. Furthermore, SPR and molecular docking results showed that ESA could bind directly to HMGB1, thereby impeding the activation of the downstream TLR4/NF-κB pathway. The immunofluorescence staining and Western blot results at the cellular level also demonstrated that ESA inhibited the activation of the HMGB1/TLR4/NF-κB pathway in H9C2 cells. Conclusion Our study was the first to demonstrate a cardiac protective role of ESA in AMI. Mechanism study indicated that the treatment effects of ESA are mainly attributed to its anti-inflammatory activity that was mediated by the HMGB1/TLR4/NF-κB pathway.
研究领域:
药理学
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心脏病学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION
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2024
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IF 2.2
Wenyue Qiu,Wenxin Jiang,Yiman Su,Hui Huang,Jiali Ye,Rongmei Wang,Zhaoxin Tang,Rongsheng Su
Lipopolysaccharides (LPS) is the major compoent of Gram-negative bacteria and an important factor in inducing inflammation, which usually leads to multiple organ failure in broilers, seriously affecting the growth performance of broilers and hindering the development of poultry farming. Under the policy of prohibiting antibiotics in feed, it has become more urgent to find natural drugs to prevent liver damage caused by LPS in broilers. Asiatic acid (AA) is a pentacyclic triterpene that has been proven to have anti-inflammatory and antioxidant effects. However, the protective effects of AA in LPS-induced liver damage in broilers still need to be clarified. This study aims to explore the complete mechanism of AA against LPS-induced acute liver injury (ALI) in broilers. A total of 60 broilers (1 day old) were randomly divided into the control group, LPS group, LPS+AA (15, 30 and 60 mg/kg) group and control+AA (60 mg/kg) group. At 16, 18 and 20 days of age, the broilers were attacked with LPS (0.5 mg/kg) to construct liver injury model. H&E staining assessed liver pathological changes. The mRNA and protein expression levels related to the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis in the liver tissue were detected. Our results founded that intraperitoneal injection of LPS in broilers increased the activities of AST and ALT, as well as raising the related gene and protein expression of the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis. Interestingly, AA improved LPS-induced liver damage and decreased the activities of AST and ALT in broilers. Additionally, AA mitigated LPS-induced ALI by reducing the mRNA levels and protein expressions of the HMGB1/TLR4/NF-κB pathway, pyroptosis and ERS-mediated apoptosis. In conclusion, the present study investigated that AA mitigated LPS-induced ALI in broilers by reducing pyroptosis and ERS-mediated apoptosis via inhibition of the HMGB1/TLR4/NF-κB pathway. Therefore, AA may serve as a potential feed additive for the prevention of LPS-induced ALI in broilers.
研究领域:
兽医学
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药理学
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免疫学
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动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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