Active herbal or natural compounds have high chemical diversity and specificity than synthetic drugs. Recently, we have validated the hypoglycemic salutation of Oncocalyx glabratus in rodent model, and demonstrated the activation of PPARα/γ by its newly ioslated flavan derivative Oncoglabrinol C (5,3′-Dihydroxyflavan 7-4′-O-digallate) in liver cells (HepG2). Here we evaluated the potential of Oncoglabrinol C against Dichlorofluorescin (DCFH) and Methylglyoxal (MGO) induced endothelial cells (HUVEC) oxidative and apoptotic damage, including activation of PXR-mediated hepatic CYP3A4. Our MTT assay showed protection of ~57% and ~63.5% HUVEC cells by 10 and 20 μg/ml doses of Oncoglabrinol C, respectively through attenuating DCFH triggered free-radicals. Also, the two doses effectively protected ~53% and ~65.5% cells, respectively by reversing MGO toxicity. In DCFH and MGO treated cells, Oncoglabrinol C (20 μg/ml) effectively downregulated caspase 3/7 activity by ~33% and ~43.5%, respectively. Moreover, in reporter gene (dual-luciferase) assay, Oncoglabrinol C (20 μg/ml) moderately activated hepatic CYP3A4. Molecular docking of Oncoglabrinol C indicated its strong interactions with cellular caspase 3/7, PPARα/γ and PXR proteins, which supported its anti-apoptotic (antagonistic) as well as pro-hypoglycemic and PXR/CYP activating (agonistic) activities. Taken together, our findings demonstrated the potential of Oncoglabrinol C in reversing the endothelial oxidative and apoptotic damage as well as in the activation of hepatic CYP3A4. This warrants further evaluations of Oncoglabrinol C and related compounds towards developing effective and safe drugs against diabetes associated cardiovascular disorders.

活性草药或天然化合物比合成药物具有更高的化学多样性和特异性。最近，我们已在啮齿动物模型中验证了天芥菜的降血糖作用，并证明了其新活化的黄烷衍生物Oncoglabrinol C（5,3'-Dihydroxyflavan 7-4'- O-戊二酸酯）（HepG2）。在这里，我们评估了Oncoglabrinol C对抗二氯荧光素（DCFH）和甲基乙二醛（MGO）诱导的内皮细胞（HUVEC）氧化和凋亡的潜力，包括激活PXR介导的肝CYP3A4。我们的MTT分析显示，通过减弱DCFH触发的自由基，分别以10和20μg/ ml剂量的Oncoglabrinol C可以保护〜57％和〜63.5％的HUVEC细胞。同样，这两种剂量通过逆转MGO毒性分别有效地保护了约53％和约65.5％的细胞。在DCFH和MGO处理的细胞中，Oncoglabrinol C（20μg/ ml）有效地将caspase 3/7活性分别下调了〜33％和〜43.5％。此外，在报告基因（双荧光素酶）测定中，Oncoglabrinol C（20μg/ ml）适度活化了肝CYP3A4。Oncoglabrinol C的分子对接表明它与细胞caspase 3/7，PPARα/γ和PXR蛋白有很强的相互作用，支持其抗凋亡（拮抗）以及促降血糖和PXR / CYP激活（激动）活性。综上所述，我们的发现证明了Oncoglabrinol C在逆转内皮氧化和凋亡损伤以及肝CYP3A4活化方面的潜力。这就需要对Oncoglabrinol C和相关化合物进行进一步评估，以开发出针对糖尿病相关心血管疾病的有效且安全的药物。我们的发现证明了Oncoglabrinol C在逆转内皮氧化和细胞凋亡以及肝CYP3A4活化方面的潜力。这就需要对Oncoglabrinol C和相关化合物进行进一步评估，以开发出针对糖尿病相关心血管疾病的有效且安全的药物。我们的发现证明了Oncoglabrinol C在逆转内皮细胞氧化和凋亡损伤以及肝CYP3A4活化方面的潜力。这就需要对Oncoglabrinol C和相关化合物进行进一步评估，以开发出针对糖尿病相关心血管疾病的有效且安全的药物。