Parvez Mohammad K, Al-Dosari Mohammed S, Tabish Rehman Md, Alajmi Mohammed F, Alqahtani Ali S, AlSaid Mansour S
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Saudi Pharm J. 2021 Oct;29(10):1102-1111. doi: 10.1016/j.jsps.2021.08.007. Epub 2021 Aug 9.
Elevation in hyperglycemia-associated methylglyoxal level can trigger vascular endothelial cells oxidative stress and apoptosis. The present work assesses the cell proliferative, anti-oxidative and anti-apoptotic potential of derived four new terpenes: a norsesquaterpenol (normonisesquaterpenol), a monocyclic triterpenoid (suaedanortriterpene dione), an aromatic monoterpenic ester and a labdane-type norditerpenic xyloside as well as two new phenols: an alkylated β-naphthol and a β-methoxy naphthalene in cultured human umbilical vein endothelial cells (HUVEC). Of these, suaedanortriterpenedione (53.7%), normonisesquaterpenol (51.4%) and norditerpenic xyloside (48%) showed the most promising cell proliferative activities compared to others. Moreover, normonisesquaterpenol, norditerpenic xyloside and suaedanortriterpenedione efficiently reversed the oxidative and apoptotic cell damage via downregulation of capase-3/7 by 44.3%, 42.2% and 39.4%, respectively against dichlorofluorescin, whereas by 46.2%, 43.5% and 42.5%, respectively against methylglyoxal. Aminoguanidine, the reference drug inhibited caspase-3/7 activity by 56.2% and 54.7% through attenuation of dichlorofluorescin and methylglyoxal, respectively. Further molecular docking analysis revealed formation of stable complexes between the tested compounds and caspase-3/7. Conclusively, we for the first time demonstrate the growth stimulatory, anti-oxidative and anti-apoptotic salutations of derived novel compounds in human endothelial cells. This warrants their further assessment as vascular cell protective and rejuvenating therapeutics, especially in hyperglycemic conditions.
与高血糖相关的甲基乙二醛水平升高会引发血管内皮细胞氧化应激和凋亡。本研究评估了四种新的萜类化合物：一种降倍半萜醇（降倍半萜烯醇）、一种单环三萜类化合物（碱蓬降三萜二酮）、一种芳香单萜酯和一种半日花烷型降二萜木糖苷，以及两种新的酚类化合物：一种烷基化β-萘酚和一种β-甲氧基萘在培养的人脐静脉内皮细胞（HUVEC）中的细胞增殖、抗氧化和抗凋亡潜力。其中，与其他化合物相比，碱蓬降三萜二酮（53.7%）、降倍半萜烯醇（51.4%）和降二萜木糖苷（48%）表现出最有前景的细胞增殖活性。此外，降倍半萜烯醇、降二萜木糖苷和碱蓬降三萜二酮通过分别下调半胱天冬酶-3/7的表达，有效逆转了氧化和凋亡性细胞损伤，对二氯荧光素的下调率分别为44.3%、42.2%和39.４%，而对甲基乙二醛的下调率分别为46.2%、43.5%和42.5%。参考药物氨基胍通过分别减弱二氯荧光素和甲基乙二醛的作用，抑制半胱天冬酶-3/7活性的比例分别为56.2%和54.7%。进一步的分子对接分析表明，测试化合物与半胱天冬酶-3/7之间形成了稳定的复合物。总之，我们首次证明了所衍生的新型化合物在人内皮细胞中的生长刺激、抗氧化和抗凋亡作用。这使得它们有必要作为血管细胞保护和恢复活力的治疗剂进行进一步评估，尤其是在高血糖条件下。
