Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia.
Faculty of Pharmacy, MAHSA University, Bandar Saujana Putra, 42610, Jenjarom, Selangor, Malaysia.
Inflammopharmacology. 2021 Jun;29(3):841-854. doi: 10.1007/s10787-021-00807-w. Epub 2021 Apr 17.
In our previous laboratory findings, Cyathocalyx pruniferus extracts exhibited platelet-activating factor inhibition, suggesting their anti-inflammatory potential. Hence, this study was designed with the aim to isolate phyto-constituents from C. pruniferus with potent anti-inflammatory activities. Column and volume liquid chromatography were used for isolation of phyto-constituents. The structure elucidation was carried out using spectroscopic analysis (HRESI-MS, H and C-NMR) and compared with published literature. For cytotoxicity analysis, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay was performed on peripheral blood mononuclear cells. Anti-inflammatory activities were evaluated against the levels of inflammatory cytokines (IL-1β and IL-6), prostaglandin-E (PGE) and cyclooxegenase-2 (COX-2), in lipopolysaccharide (LPS)-induced human plasma using ELISA and radioimmunoassay (RIA). The chromatographic purification of methanol leaves extract afforded 13 (1-13) secondary metabolites. Additionally, cytotoxicity analysis suggested that isolates were non-cytotoxic at 100 μM. In anti-inflammatory evaluation, 2-octaprenyl-1, 4-benzoquinone (5) produced strong (≥ 70%) inhibition of PGE, COX-2, IL-1β and IL-6 at 50 µM. Moreover, 2-octaprenyl-1,4-benzoquinone (5) exhibited concentration-dependent inhibition with IC values (µM) of 11.21, 6.61, 2.20 and 3.56 as compared to controls; indomethacin for PGE (11.84) and dexamethasone in COX-2 (5.19), IL-1β (1.83) and IL-6 (3.76) analysis, respectively. In conclusion, two new compounds including 2-octaprenyl-1, 4-benzoquinone (5) and 14-methyloctadec-1-ene (6) are reported for the first time from plant species. Additionally, 2-octaprenyl-1, 4-benzoquinone (5) dose-dependently suppressed the production of pro-inflammatory mediators involved in acute and chronic inflammation at non-cytotoxic concentrations.
在我们之前的实验室研究中,皱边石仙桃提取物表现出对血小板激活因子的抑制作用,提示其具有抗炎潜力。因此,本研究旨在从皱边石仙桃中分离具有强大抗炎活性的植物成分。使用柱和体积液相色谱法进行植物成分的分离。通过光谱分析(HRESI-MS、H 和 C-NMR)进行结构解析,并与已发表的文献进行比较。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法检测外周血单个核细胞的细胞毒性。采用 ELISA 和放射免疫法(RIA)检测脂多糖(LPS)诱导的人血浆中炎症细胞因子(IL-1β 和 IL-6)、前列腺素 E(PGE)和环氧化酶-2(COX-2)的水平,评估抗炎活性。甲醇叶提取物的色谱纯化得到 13(1-13)种次生代谢物。此外,细胞毒性分析表明,在 100μM 时,分离物无细胞毒性。在抗炎评估中,2-辛基-1,4-苯醌(5)在 50µM 时对 PGE、COX-2、IL-1β 和 IL-6 的抑制作用强(≥70%)。此外,2-辛基-1,4-苯醌(5)表现出浓度依赖性抑制,IC 值(µM)分别为 11.21、6.61、2.20 和 3.56,与对照物相比;PGE 的吲哚美辛(11.84)和 COX-2 的地塞米松(5.19)、IL-1β(1.83)和 IL-6(3.76)分析。总之,从植物物种中首次报道了两种新化合物,包括 2-辛基-1,4-苯醌(5)和 14-甲基十八-1-烯(6)。此外,2-辛基-1,4-苯醌(5)以剂量依赖的方式抑制了非细胞毒性浓度下急性和慢性炎症中涉及的促炎介质的产生。