Rajarathinam Geethalakshmi, Dronamraju Sarada V L
Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, 603203, India.
Mol Biol Rep. 2018 Aug;45(4):547-561. doi: 10.1007/s11033-018-4193-9. Epub 2018 May 24.
Dimethyl octenol from chloroform extract and oleanene tetrol from water extract of Trianthema decandra (TD) were isolated and characterized by using HPLC, UV, FT-IR, NMR, LC-MS and CHNS, their structure were elucidated from their respective spectral data. The anti-inflammatory activity of chloroform extract, water extract, dimethyl octenol and oleanene tetrol of T. decandra were studied and underlying cellular and molecular mechanisms of action were investigated in vitro and in vivo using macrophage-like cell line (RAW264.7 cells) and type II collagen induced arthritis mice models. Nitric oxide production was inhibited and TNF-α secretion was supressed in stimulated RAW cells treated with the chloroform extract and dimethyl octenol of T. decandra. Further, the chloroform and water extract, dimethyl octenol and oleanene tetrol inhibited protein denaturation and stabilized HRBC membranes in vitro. Reduction in inflammation as a measure of paw diameter was recorded in all the treated animals when compared to control animals. Catalase, peroxidase and glutathione peroxidase levels significantly increased in the joint tissue of treated groups. The possible mechanism of action of these compounds was studied using in silico molecular docking methods with phospholipase A (PLA), cycloxygenase-1 (COX-1) and cycloxygenase-2 (COX-2) as targets. Among the three target proteins, the inhibition of the inflammatory protein PLA and COX-2 towards dimethyl octenol and oleanene tetrol respectively. Our results contribute towards confirmation of the traditional use of TD and its compounds for the therapy of rheumatoid arthritis and other inflammatory joint disorders.
从露花(TD)的氯仿提取物中分离出二甲基辛烯醇,并从其水提取物中分离出齐墩果烷四醇,通过高效液相色谱(HPLC)、紫外光谱(UV)、傅里叶变换红外光谱(FT-IR)、核磁共振(NMR)、液相色谱-质谱联用(LC-MS)和元素分析(CHNS)对其进行表征,并根据各自的光谱数据阐明其结构。研究了露花氯仿提取物、水提取物、二甲基辛烯醇和齐墩果烷四醇的抗炎活性,并使用巨噬细胞样细胞系(RAW264.7细胞)和II型胶原诱导的关节炎小鼠模型在体外和体内研究了其潜在的细胞和分子作用机制。用露花氯仿提取物和二甲基辛烯醇处理刺激后的RAW细胞,可抑制一氧化氮的产生并抑制肿瘤坏死因子-α(TNF-α)的分泌。此外,氯仿提取物、水提取物、二甲基辛烯醇和齐墩果烷四醇在体外可抑制蛋白质变性并稳定人红细胞(HRBC)膜。与对照动物相比,所有处理动物的爪直径减小,炎症减轻。处理组关节组织中的过氧化氢酶、过氧化物酶和谷胱甘肽过氧化物酶水平显著升高。以磷脂酶A(PLA)、环氧化酶-1(COX-1)和环氧化酶-2(COX-2)为靶点,采用计算机辅助分子对接方法研究了这些化合物可能的作用机制。在这三种靶蛋白中,炎症蛋白PLA和COX-2分别对二甲基辛烯醇和齐墩果烷四醇有抑制作用。我们的研究结果有助于证实露花及其化合物在治疗类风湿性关节炎和其他炎症性关节疾病方面的传统用途。