Methylophiopogonanone A

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.