Dammarane-type triterpenoids from Gynostemma longipes and their protective activities on hypoxia-induced injury in PC12 cells

IF 4 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Chinese Journal of Natural Medicines Pub Date : 2024-05-01 DOI:10.1016/S1875-5364(24)60643-6
Haizhen LIANG , Xiaojuan CHEN , Qi LI , Mengmeng ZHANG , Pengxin LU , Jie ZHANG , Juan SONG , Tao ZHANG , Baolin GUO , Baiping MA
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Abstract

Sixteen new dammarane-type triterpenoid saponins (1–16) featuring diverse structural variations in the side chain at C-17, along with twenty-one known analogues (17–37), have been isolated from the rhizomes of Gynostemma longipes C. Y. Wu, a plant renowned for its medicinal and edible properties. The structural elucidation of these compounds was accomplished through comprehensive analyses of 1D and 2D NMR and HRMS spectroscopic data, supplemented by comparison with previously reported data. Subsequent assays on the isolates for their protective effects against hypoxia-induced damage in pheochromocytoma cells (PC12 cells) revealed that nine saponins exhibited significant anti-hypoxic activities. Further investigation into the anti-hypoxia mechanisms of the representative saponins demonstrated that compounds 22 and 36 markedly reduced the levels of hypoxia-induced apoptosis. Additionally, these compounds were found to decrease the release of lactate dehydrogenase (LDH) and malondialdehyde (MDA), while increasing the activity of superoxide dismutase (SOD), thereby indicating that the saponins could mitigate hypoxia-induced injuries by ameliorating apoptosis and oxidative stress. These findings offer substantial evidence for the future utilization and development of G. longipes, identifying dammarane-type triterpenoid saponins as its active anti-hypoxic constituents.

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长叶绞股蓝中的达玛烷三萜类化合物及其对缺氧诱导的 PC12 细胞损伤的保护活性
从绞股蓝根茎中分离出了 16 种新的达玛烷型三萜皂甙(1-16),其 C-17 侧链的结构变化多样,同时还分离出了 21 种已知的类似物(17-37),绞股蓝因其药用和食用特性而闻名于世。通过对一维和二维 NMR 及 HRMS 光谱数据进行综合分析,并与之前报道的数据进行比较,这些化合物的结构得以阐明。随后对分离物进行了检测,以确定其对缺氧诱导的嗜铬细胞瘤细胞(PC12 细胞)损伤的保护作用,结果显示九种皂苷具有显著的抗缺氧活性。对代表性皂苷的抗缺氧机制的进一步研究表明,化合物 22 和 36 显著降低了缺氧诱导的细胞凋亡水平。此外,这些化合物还能减少乳酸脱氢酶(LDH)和丙二醛(MDA)的释放,同时提高超氧化物歧化酶(SOD)的活性,从而表明皂苷可以通过改善细胞凋亡和氧化应激来减轻缺氧引起的损伤。这些发现为今后利用和开发龙舌兰提供了大量证据,并确定达玛烷型三萜皂苷是其有效的抗缺氧成分。
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来源期刊
Chinese Journal of Natural Medicines
Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.50
自引率
4.30%
发文量
2235
期刊介绍: The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.
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