Methylophiopogonanone A (MOA), an abundantly bioactive homoisoflavonoid isolated from the herbal medicine Ophiopogonis Radix, has been considered as the key chemical index for the quality control of Ophiopogonis Radix related herbal formulations [1]. Methylophiopogonanone A inhibited hUGTs effect of 4-HN-335 O-glucuronidation with IC50 values ranged from 1.23 ± 0.09 μμ (for UGT1A1) to 8.30 ± 0.72 μμ (for UGT2B7) [2].
Modern pharmacological studies have demonstrated that Methylophiopogonanone A held a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, anti-tumour, anti-hyperlipidemia effects and the potentials for attenuating myocardial apoptosis and improving cerebral ischemia/reperfusion injury [3,4,5,6].
Methylophiopogonanone A dose-dependently inhibited hUGT1A1-catalysed NHPN-O-glucuronidation in HeLa-UGT1A1 cells, with the apparent IC50 value of 1.54 ± 0.17 μM [2]. Methylophiopogonanone A (2.5-10 μM) treatment significantly reversed the decreased TER values when compared with the model group, which indicated that Methylophiopogonanone A had a protective effect on hypoxic BBB damage [5]. In H9C2 cells subjected to H/R, pretreatment with Methylophiopogonanone A (10 μmol/L) significantly decreased apoptosis and cleaved caspase-3 expression, elevated the Bcl-2/Bax ratio and restored NO production [6].
Pretreatment with Methylophiopogonanone A (10 mg.kg-1.d-1, po.) significantly reduced the infarct size (by 60.7%) and myocardial apoptosis (by 56.8%), and improved cardiac function, in I/R mice [6]. Cerebral water contents were less in the Methylophiopogonanone A (2.5 mg/kg and 5.0 mg/kg) treatment groups than those in the model group in MCAO rats [5].
References:
[1]. Zheng Y, Fan C, Liu M, Chen Y, Lu Z, Xu N, Huang H, Zeng H, Liu S, Cao H, Liu J. Overall quality control of the chemical and bioactive consistency of ShengMai Formula. Journal of pharmaceutical and biomedical analysis. 2020 Sep 10;189:113411.
[2]. Zhou Q H, Zhu G H, Song Y Q, et al. Methylophiopogonanone A is a naturally occurring broad‐spectrum inhibitor against human UDP‐glucuronosyltransferases: Inhibition behaviours and implication in herb‐drug interactions[J]. Basic & Clinical Pharmacology & Toxicology, 2021, 129(6): 437-449.
[3]. Li, Z., Wu, Y. Y., & Yu, B. X. (2020). Methylophiopogonanone A, an Ophiopogon homoisoflavonoid, alleviates high-fat diet-induced hyperlipidemia: assessment of its potential mechanism. Brazilian Journal of Medical and Biological Research, 53.
[4]. Dang, N. H., Chung, N. D., Tuan, H. M., Hiep, N. T., & Dat, N. T. (2017). Cytotoxic homoisoflavonoids from Ophiopogon japonicus tubers. Chemical and Pharmaceutical Bulletin, 65(2), 204-207.
[5]. Lin, M., Sun, W., Gong, W., Zhou, Z., Ding, Y., & Hou, Q. (2015). Methylophiopogonanone a protects against cerebral ischemia/reperfusion injury and attenuates blood-brain barrier disruption in vitro. PLoS One, 10(4), e0124558.
[6]. He, F., Xu, B. L., Chen, C., Jia, H. J., Wu, J. X., Wang, X. C., ... & Cheng, J. (2016). Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway. Acta Pharmacologica Sinica, 37(6), 763-771.
甲基麦冬酮 A (MOA) 是一种从草药麦冬中分离出来的具有丰富生物活性的同型异黄酮，被认为是麦冬相关草药制剂质量控制的关键化学指标[1]。甲基麦冬酮 A 抑制 4-HN-335 O-葡萄糖醛酸化的 hUGTs 效应，IC50 值范围为 1.23 ± 0.09 μμ（对于 UGT1A1）至 8.30 ± 0.72 μμ（对于 UGT2B7）[2]。
现代药理研究表明，甲基麦冬酮A具有多种药理作用，包括抗氧化、抗炎、抗肿瘤、抗高血脂等作用，具有减轻心肌细胞凋亡、改善脑缺血/再灌注损伤的潜力 < sup>[3,4,5,6].
甲基麦冬酮 A 剂量依赖性地抑制 HeLa-UGT1A1 细胞中 hUGT1A1 催化的 NHPN-O-葡萄糖醛酸化，表观 IC50 值为 1.54 ± 0.17 μM [2]。与模型组相比，甲基麦冬酮 A (2.5-10 μM) 处理显着逆转了降低的 TER 值，这表明甲基麦冬酮 A 对缺氧性 BBB 损伤具有保护作用[5]。在经过 H/R 处理的 H9C2 细胞中，用 Methylophiopogonanone A (10 μmol/L) 预处理可显着降低细胞凋亡和裂解的 caspase-3 表达，提高 Bcl-2/Bax 比率并恢复 NO 产生[6].
使用甲基麦冬花酮 A（10 mg.kg-1.d-1，口服）预处理可显着减少 I/R 患者的梗塞面积（减少 60.7%）和心肌细胞凋亡（减少 56.8%），并改善心脏功能小鼠[6]。甲基麦冬酮A（2.5 mg/kg和5.0 mg/kg）治疗组MCAO大鼠脑水含量低于模型组[5]。