Department of Zoology, Animal Physiology and Biochemistry Laboratory, Gauhati University, Guwahati, 781014, Assam, India.
Inflammopharmacology. 2021 Jun;29(3):801-823. doi: 10.1007/s10787-021-00832-9. Epub 2021 Jun 9.
The Aquaporins (AQPs) could prove to be striking targets of inflammation. The aim of this study was to study the involvement of AQPs and explore the anti-inflammatory activity of Garcinia extract in LPS induced acute systemic inflammation in Wistar rats. Adult male Wistar rats (n = 6) were pretreated with Garcinia orally twice for 7 days, followed by a single intraperitoneal dose (5.5 mg/kgbw) of LPS. Serum ALT, AST, ALP, Creatinine, Urea and BUN, nitric oxide, prostaglandin, cytokine and chemokine levels were measured. LC-MS analysis of Garcinia was performed to identify the phytoconstituents present. The iNOS and COX enzyme activity were determined in the target tissues. qPCR analysis of inos, cox-2 and aqps was performed. Relative protein expression of AQPs was studied by Western blot analysis. Molecular docking studies were performed to study the interaction of garcinol and hydroxycitric acid, the two important phytoconstituents of Garcinia with AQP. The qPCR analysis showed tissue-specific up-regulation of aqp1, aqp3, aqp4 and aqp8 in LPS induced rats. Garcinia extract treatment effectively lowered the mRNA expression of these AQPs. Garcinia extract significantly inhibited the LPS-induced NO, prostaglandin, cytokine and chemokine production in serum and also decreased tissue-specific transcript level of inos and cox-2, thus suggesting the anti-inflammatory role of Garcinia. Also, docking studies revealed interactions of garcinol and hydroxycitric acid with AQP1, 3, 4 and 8. Therefore, the present study suggests the possible involvement of AQP1, 3, 4 and 8 in inflammation and the efficacy of Garcinia extract as an anti-inflammatory agent. Therefore, AQPs can act as prognostic markers of inflammation and can be targeted with Garcinia extract.
水通道蛋白 (AQP) 可能成为炎症的重要靶点。本研究旨在研究 AQP 的参与情况,并探索 Garcinia 提取物在 LPS 诱导的 Wistar 大鼠急性全身炎症中的抗炎活性。成年雄性 Wistar 大鼠(n=6)经口预处理 Garcinia 两次,共 7 天,随后单次腹腔内给予 LPS(5.5mg/kgbw)。测量血清 ALT、AST、ALP、肌酐、尿素和 BUN、一氧化氮、前列腺素、细胞因子和趋化因子水平。对 Garcinia 进行 LC-MS 分析以鉴定存在的植物成分。测定靶组织中 iNOS 和 COX 酶活性。进行 inos、cox-2 和 aqps 的 qPCR 分析。通过 Western blot 分析研究 AQP 的相对蛋白表达。进行分子对接研究,以研究 Garcinia 中两种重要植物成分 garcinol 和羟基柠檬酸与 AQP 的相互作用。qPCR 分析显示,LPS 诱导的大鼠组织特异性上调 aqp1、aqp3、aqp4 和 aqp8。Garcinia 提取物处理可有效降低这些 AQP 的 mRNA 表达。Garcinia 提取物可显著抑制 LPS 诱导的 NO、前列腺素、细胞因子和趋化因子在血清中的产生,还可降低组织特异性 inos 和 cox-2 的转录水平,提示 Garcinia 具有抗炎作用。此外,对接研究表明 garcinol 和羟基柠檬酸与 AQP1、3、4 和 8 之间存在相互作用。因此,本研究表明 AQP1、3、4 和 8 可能参与炎症,Garcinia 提取物作为抗炎剂具有疗效。因此,AQP 可以作为炎症的预后标志物,并可以用 Garcinia 提取物进行靶向治疗。