R&D Centre in Pharmaceutical Sciences and Applied Chemistry, Bharati Vidyapeeth Deemed University, Pune, Maharashtra 411 038, India.
Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra 411 038, India.
Int Immunopharmacol. 2017 Nov;52:110-118. doi: 10.1016/j.intimp.2017.09.001. Epub 2017 Sep 8.
Inflammation activated by oxidative stress can cause various diseases, such as asthma, rheumatoid arthritis, cancer, diabetes, etc. Plant constituents with sesquiterpene lactones possess antioxidant and anti-inflammatory properties.
To determine the antioxidant and anti-inflammatory potential of isolated phytoconstituent from Cyathocline purpurea Buch-Ham ex D (CP). Don in laboratory animals. Furthermore, to understand the interactions involved in the binding of this compound to cyclooxygenase-2 (COX-2) via computational docking.
Phytoconstituent was isolated, purified and well characterized (using IR, NMR, and MS) from ethyl acetate fraction of CP methanolic extract. It was then evaluated for its in-vitro antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (HO) and hydroxyl (OH) radical assays as well as in-vivo anti-inflammatory potential against carrageenan-induced paw edema model in rats. The molecular docking study was performed against the crystal structure of COX-2 to evaluate the binding potential of phytoconstituent towards this enzyme.
The isolated compound 6α-hydroxy-4 [14], 10 [15]-guainadien-8α, 12-olide (HGN) showed significant (p<0.001) antioxidant activity with IC values of 76μg/mL. Administration of HGN (10 and 20mg/kg) significantly (p<0.001) reduced the increased paw volume after subplantar administration of carrageenan. It also exhibits good binding affinity towards with COX-2 with a docking score of -8.98 and Glide binding energy of -36.488kcal/mol shedding light on the potential mechanism of anti-inflammatory action.
The presence of hydroxyl group in HGN provides a credential to its in-vivo anti-inflammatory and in-vitro antioxidant activities. Furthermore, the good binding affinity of HGN for the active site of COX-2 may open novel vistas in therapeutic option with natural antioxidants like Cyathocline purpurea to treat various inflammatory disorders.
氧化应激引起的炎症会导致各种疾病，如哮喘、类风湿性关节炎、癌症、糖尿病等。具有倍半萜内酯的植物成分具有抗氧化和抗炎特性。
确定从 Cyathocline purpurea Buch-Ham ex D（CP）的乙酸乙酯部分分离的植物成分（CP）的抗氧化和抗炎潜力。在实验动物中。此外，通过计算对接来了解该化合物与环氧化酶-2（COX-2）结合的相互作用。
从 CP 甲醇提取物的乙酸乙酯部分中分离、纯化并充分表征（使用 IR、NMR 和 MS）植物成分。然后，通过 1,1-二苯基-2-苦基肼（DPPH）、过氧化氢（HO）和羟基（OH）自由基测定法评估其体外抗氧化活性，以及通过角叉菜胶诱导的大鼠爪肿胀模型评估其体内抗炎潜力。进行分子对接研究以评估植物成分与该酶的结合潜力。
分离的化合物 6α-羟基-4 [14]，10 [15]-桂二烯-8α，12-内酯（HGN）显示出显著的（p<0.001）抗氧化活性，IC 值为 76μg/mL。HGN（10 和 20mg/kg）给药可显著（p<0.001）降低角叉菜胶皮下给药后增加的爪体积。它还对 COX-2 具有良好的结合亲和力，对接评分为-8.98，Glide 结合能为-36.488kcal/mol，为抗炎作用的潜在机制提供了依据。
HGN 中羟基的存在为其体内抗炎和体外抗氧化活性提供了依据。此外，HGN 对 COX-2 活性位点的良好结合亲和力可能为使用天然抗氧化剂如 Cyathocline purpurea 治疗各种炎症性疾病提供新的治疗选择。
