Pulchinenosides: Correlation of surface activity-cytotoxicity and hepatocyte apoptosis mechanism study

Bioorg Med Chem Lett. 2021 Jul 1:43:128080. doi: 10.1016/j.bmcl.2021.128080.

Dan Su ¹, Tingting Wang ¹, Chen Jin ², Yali Liu ³, Abid Naeem ², Zhou Liao ¹, Mingyue Zhou ¹, Changlian Chen ⁴, Yonggui Song ⁵, Zhifu Ai ⁶

Affiliations

1 Key Laboratory of Animal Model of TCM Syndromes of Depression, Jiangxi Administration of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330006, China; Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330006, China.
2 Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330006, China.
3 Key Laboratory of Animal Model of TCM Syndromes of Depression, Jiangxi Administration of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330006, China.
4 Affiliated Hospital of Jiangxi University of Chinese Medicine, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330006, China.
5 Key Laboratory of Animal Model of TCM Syndromes of Depression, Jiangxi Administration of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330006, China; Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330006, China. Electronic address: songyonggui1999@163.com.
6 Key Laboratory of Animal Model of TCM Syndromes of Depression, Jiangxi Administration of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330006, China; Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330006, China. Electronic address: aizhifu1668@163.com.

PMID: 33964439 DOI: 10.1016/j.bmcl.2021.128080

Abstract

Saponin is an active component of many phytomedicine, which has extensive pharmacology effects. Meanwhile, it is reported that cytotoxicity, especially hemolysis and hepatotoxicity, in pentacyclic triterpenoid saponin (PTS) hindered their further development and application. Surface activity, a unique physical property of saponins, is believed to be related to membrane toxicity. However, the correlation between the surface activity and cytotoxicity of saponins is still unexplained. In this paper, our aim was to explore the relationship between surface activity-cytotoxicity of pulchinenosides and the hepatotoxicity mechanism of PTS in vitro. The surface activity of different saponins was investigated by contact angle, surface free energy (SFE), and oil/water partition coefficient (log Papp). In the cytotoxicity study, the hemolysis and hepatotoxicity activity of different saponins was compared by HD₅₀ of erythrocyte and MTT, flow cytometry and LDH assay in LO2 cells respectively. And in the hepatotoxicity mechanism study, western blot was used for observing the expression of proteins related to Apoptosis and exploring the liver injury mechanism of PTS. The results suggested that the influences of surface activity on hepatocytes and erythrocytes were different, indicating that the correlation of surface activity-cytotoxicity could provide more information for development of PTS. And the result of hepatotoxicity mechanism study of saponins suggested that endogenous and exogenous apoptotic pathways could be the potential targets of PTS, which could not only provide basis for clinical monitoring and treatment of the toxicity in saponins, but also provide more reference for the clinical application of PTS and phytomedicine containing PTS.

Keywords

Hemolysis; Hepatotoxicity; Membrane toxicity; Pentacyclic triterpenoid saponins; Structure; Surface activity.

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