Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
Drug Des Devel Ther. 2022 Sep 28;16:3327-3342. doi: 10.2147/DDDT.S380324. eCollection 2022.
Liver regulates metabolism of biomolecules and injury of liver causes distortion of metabolic functions. This injury may be oxidative or inflammatory induced by numerous factors including alcohol, pathogens and xenobiotics. This scientific study was planned to investigate the anti-inflammatory and anti-oxidant potential of p-coumaric acid (p-CA) on Lipopolysaccharide/D-Galactosamine (LPS/D-GalN) induced liver injury.
DPPH analysis, reducing power assay and HPLC analysis were performed during in-vitro studies of p-CA. Similarly, in-vivo experiments were performed using Wistar Albino rats. Normal control and intoxicated group received (5mL/kg normal saline p.o), standard treatment groups received ascorbic acid (100mg/kg p.o) and silymarin (25mg/kg p.o), while p-CA treatment groups received (100mg/kg p.o) for 28-days. After completion of 28-days, LPS/D-GalN injection (300 mg D-GalN/kg and 10 µg LPS/kg i.p.) was given at 6th, 12th and 24-hours to all groups except normal control group. Animals were sacrificed; serum and liver samples were harvested and subjected to biochemical and histological examinations, respectively.
The results revealed that p-CA possess strong antioxidant activity. Increased levels of leukocyte infiltration (TLC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), lipid panel (eg TG, TC, LDL-C, VLDL-C), whereas decreased HDL-C levels noticed in LPS/D-GalN groups as compared to normal control groups. Pro-Inflammatory markers (eg TNF-α, IL-6, IL-1β) and lipid peroxidation marker, eg malondialdehyde (MDA) increased while superoxide dismutase (SOD) and reduced glutathione (GSH) levels were decreased significantly in groups treated with LPS/D-GalN. ANOVA with Bonferroni post hoc analysis was used for statistical analysis of. H&E staining was done to assess architectural abnormalities among liver cells.
In conclusion, p-CA could ameliorate LPS/D-GalN induced hepatic injury via regulation of immune responses, liver function enzymes, lipid profile, oxidative stress and pro-inflammatory markers.
肝脏调节生物分子的代谢,肝脏损伤会导致代谢功能紊乱。这种损伤可能是由酒精、病原体和外源性物质等多种因素引起的氧化或炎症。本研究旨在探讨对香豆酸(p-CA)对脂多糖/半乳糖胺(LPS/D-GalN)诱导的肝损伤的抗炎和抗氧化作用。
在 p-CA 的体外研究中进行了 DPPH 分析、还原力测定和 HPLC 分析。同样,在 Wistar 白化大鼠中进行了体内实验。正常对照组和中毒组给予(5mL/kg 生理盐水灌胃),标准治疗组给予抗坏血酸(100mg/kg 灌胃)和水飞蓟素(25mg/kg 灌胃),p-CA 治疗组给予(100mg/kg 灌胃)28 天。28 天后,除正常对照组外,所有组均在第 6、12 和 24 小时给予 LPS/D-GalN 注射(300mg D-GalN/kg 和 10μg LPS/kg 腹腔注射)。动物被处死;采集血清和肝脏样本,分别进行生化和组织学检查。
结果表明,p-CA 具有很强的抗氧化活性。与正常对照组相比,LPS/D-GalN 组白细胞浸润(TLC)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、总胆红素(TBIL)、脂质谱(如 TG、TC、LDL-C、VLDL-C)水平升高,而高密度脂蛋白胆固醇(HDL-C)水平降低。LPS/D-GalN 组促炎标志物(如 TNF-α、IL-6、IL-1β)和脂质过氧化标志物,如丙二醛(MDA)升高,而超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)水平显著降低。方差分析和 Bonferroni 事后检验用于统计分析。进行 H&E 染色以评估肝细胞的结构异常。
总之,p-CA 可以通过调节免疫反应、肝功能酶、脂质谱、氧化应激和促炎标志物来改善 LPS/D-GalN 诱导的肝损伤。