Institute of Pharmacy, Nirma University, S. G. Highway, Ahmedabad, 382481, Gujarat, India.
SSR College of Pharmacy, Sayli, Silvassa, 306230, U. T. of D&NH, India.
Biomed Pharmacother. 2018 Dec;108:374-390. doi: 10.1016/j.biopha.2018.09.011. Epub 2018 Sep 15.
Bergenia ciliata (Haw) Sternb. possess immunomodulatory, anti-inflammatory, antioxidant, anti-urolithiatic, wound healing, anti-malarial, anti-diabetic and anti-cancer properties. Moreover, the methanolic extracts of the rhizomes of the plant were found to demonstrate beneficial neuroprotective effects in the intracerebroventricular streptozotocin-induced model in rats. Thus, the present study was undertaken to further explore the neuroprotective potential of the aqueous (BA) and methanolic extracts (BM) of B. ciliata through various in-vitro and in-vivo studies. Both the extracts at all tested concentrations i.e. 50-50,000 ng/mL did not cause any significant reduction of cell viability of SH-SY5Y cells when tested for 48 h when assessed through MTT and resazurin metabolism- based cell viability assays. The pre-treatment with the extracts could confer significant (p < 0.001) and dose-dependent protective effects against NMDA induced injury in SH-SY5Y cells. BM [IC: 5.7 and 5.19 μg/mL for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) respectively] led to more potent inhibition of both the enzymes as compared to BA (IC: 227.12 and 23.25 μg/mL for AChE and BuChE respectively). BM also proved to be a 1.85-fold better scavenger of the DPPH free radicals as compared to BA. Thus, BM was taken further for the evaluation of the beneficial effects of 14-day pre-treatment in rats in the scopolamine (2 mg/kg, i.p.) induced amnesia model at 125, 250 and 500 mg/kg, p.o. BM pre-treatment at 250 and 500 mg/kg could significantly ameliorate the cognitive impairment (p < 0.001), inhibit AChE (p < 0.001) and BuChE (p < 0.05) activity, restore GSH levels (p < 0.05) in serum and brain homogenates and recover the morphology of hippocampal neurons back to normal. Moreover, the BM administration at 500 mg/kg also showed beneficial effects through the significant (p < 0.05) reduction of Aβ, phosphorylated tau (p-tau) and GSK-3β immunoreactivity in the brain homogenates of the intracerebroventricularly streptozotocin (ICV STZ) injected rats as observed from the results of the ELISA assays. The outcomes of the study unveiled that BM exerts its beneficial effects through prevention of NMDA induced excitotoxic cell death, dual cholinesterase inhibition, antioxidant activity coupled with the reduction of the immunoreactivity for the Aβ, p-tau and GSK-3β indicating its potential to be screened further for various other models to determine the exact mechanism of action.
岩白菜素（Haw）Sternb.具有免疫调节、抗炎、抗氧化、抗尿路结石、伤口愈合、抗疟疾、抗糖尿病和抗癌特性。此外，该植物根茎的甲醇提取物在大鼠侧脑室链脲佐菌素诱导模型中显示出有益的神经保护作用。因此，本研究旨在通过各种体外和体内研究进一步探索岩白菜素的水提物（BA）和甲醇提取物（BM）的神经保护潜力。在通过 MTT 和基于 Resazurin 代谢的细胞活力测定评估 48 小时时，两种提取物在所有测试浓度（即 50-50,000ng/mL）下均未导致 SH-SY5Y 细胞活力显著降低。提取物预处理可显著（p<0.001）和剂量依赖性地对抗 NMDA 诱导的 SH-SY5Y 细胞损伤。BM（乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的 IC 分别为 5.7 和 5.19μg/mL）比 BA（AChE 和 BuChE 的 IC 分别为 227.12 和 23.25μg/mL）对两种酶的抑制作用更强。BM 对 DPPH 自由基的清除能力也比 BA 强 1.85 倍。因此，进一步评估了 BM 在腹腔注射东莨菪碱（2mg/kg）诱导的记忆障碍模型中，14 天预处理对大鼠的有益作用，剂量为 125、250 和 500mg/kg，po。BM 预处理 250 和 500mg/kg 可显著改善认知障碍（p<0.001），抑制 AChE（p<0.001）和 BuChE（p<0.05）活性，恢复血清和脑匀浆中 GSH 水平（p<0.05），并使海马神经元的形态恢复正常。此外，BM 给药 500mg/kg 还通过显著降低脑匀浆中 Aβ、磷酸化 tau（p-tau）和 GSK-3β的免疫反应性，对侧脑室链脲佐菌素（ICV STZ）注射大鼠产生有益作用（通过 ELISA 测定结果观察到）。研究结果表明，BM 通过防止 NMDA 诱导的兴奋性细胞死亡、双重胆碱酯酶抑制、抗氧化活性以及降低 Aβ、p-tau 和 GSK-3β的免疫反应性发挥其有益作用，表明其具有进一步筛选各种其他模型以确定确切作用机制的潜力。
