AUTHOR=Liu Wen-Ya , Xu Di , Hu Zi-Yun , Meng Hui-Hui , Zheng Qi , Wu Feng-Ye , Feng Xin , Wang Jun-Song 

TITLE=Total cucurbitacins from Herpetospermum pedunculosum pericarp do better than Hu-lu-su-pian (HLSP) in its safety and hepatoprotective efficacy

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1344983

DOI=10.3389/fphar.2024.1344983

ISSN=1663-9812

ABSTRACT=<p>The pericarp of <italic>Herpetospermum pedunculosum</italic> (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl<sub>4</sub>-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD<sub>50</sub> and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD<sub>50</sub>) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD<sub>50</sub> of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.</p>