Experimental Study of Antiatherosclerosis Effects with Hederagenin in Rats

Lu, Su-hong; Guan, Jianhua; Huang, Yanli; Pan, Yuwei; Yang, Wei; Lan, Hai; Huang, Si; Hu, Jing; Zhao, Guoping

doi:10.1155/2015/456354

Cited by 32 publications

(32 citation statements)

References 28 publications

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“…Hederagenin ( He , 3b,23-dihydroxyurs-12-ene-28-oic acid; Figure 1 ) is a member of the pentacyclic triterpenoid family, which is extracted mainly from the medicinal plant ivy ( Hedera helix L.) and Dipsacus asper [ 12 , 13 ]. A variety of pharmacological activities were ascribed to He , such as anticancer [ 14 ], anti-inflammatory [ 15 ], neuroprotective [ 16 ], and antiatherosclerosis effects [ 17 ]. Notably, He exhibits potential antitumor activity in several cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin–Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis

Fang

Zhang

Han

et al. 2018

IJMS

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Hederagenin (He) is a novel triterpene template for the development of new antitumor compounds. In this study, 26 new He–pyrazine derivatives were synthetized in an attempt to develop potent antitumor agents; they were screened for in vitro cytotoxicity against tumor and non-tumor cell lines. The majority of these derivatives showed much stronger cytotoxic activity than He. Remarkably, the most potent was compound 9 (half maximal inhibitory concentration (IC50) was 3.45 ± 0.59 μM), which exhibited similar antitumor activities against A549 (human non-small-cell lung cancer) as the positive drug cisplatin (DDP; IC50 was 3.85 ± 0.63 μM), while it showed lower cytotoxicity on H9c2 (murine heart myoblast; IC50 was 16.69 ± 0.12 μM) cell lines. Compound 9 could induce the early apoptosis and evoke cell-cycle arrest at the synthesis (S) phase of A549 cells. Impressively, we innovatively introduced the method of cluster analysis modeled as partial least squares discriminant analysis (PLS-DA) into the structure–activity relationship (SAR) evaluation, and SAR confirmed that pyrazine had a profound effect on the antitumor activity of He. The present studies highlight the importance of pyrazine derivatives of He in the discovery and development of novel antitumor agents.

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Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin–Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis

Fang

Zhang

Han

et al. 2018

IJMS

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“…Hederagenin is a triterpenoid isolated from the plant Hedera Helix (also known as the common Ivy). Recently, hederagenin was reported to exert anti-cancer 12 , antiinflammatory 13 , anti-atherosclerosis 14 , and anti-depression 15 activities in vitro and in vivo. In the present study, the effects of hederagenin on autophagy was investigated in the lung cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Hederagenin potentiated cisplatin- and paclitaxel-mediated cytotoxicity by impairing autophagy in lung cancer cells

Wang

Liu

et al. 2020

Cell Death Dis

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Autophagy inhibition has been demonstrated to increase the efficacy of conventional chemotherapy. In this study, we identified hederagenin, a triterpenoid derived from Hedera helix, as a potent inhibitor of autophagy and then hypothesized that hederagenin might synergize with chemotherapeutic drugs (e.g., cisplatin and paclitaxel) to kill lung cancer cells. Firstly, we observed that hederagenin induced the increased autophagosomes in lung cancer cells concomitantly with the upregulation of LC3-II and p62, which indicated the impairment of autophagic flux. The colocalization assay indicated hederagenin could not block the fusion of lysosomes and autophagosomes, whereas the lysosomal acidification might be inhibited by hederagenin as revealed by the reduced staining of acidity-sensitive reagents (i.e., Lysotracker and acridine orange). The aberrant acidic environment then impaired the function of lysosome, which was evidenced by the decrease of mature cathepsin B and cathepsin D. Lastly, hederagenin, in agree with our hypothesis, promoted pro-apoptotic effect of cisplatin and paclitaxel with the accumulation of reactive oxygen species (ROS); while the synergistic effect could be abolished by the ROS scavenger, N-acetyl-L-cysteine. These data summarily demonstrated hederagenin-induced accumulation of ROS by blocking autophagic flux potentiated the cytotoxicity of cisplatin and paclitaxel in lung cancer cells.

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“…Hederagenin (HE), a triterpenoid which is the aglycone part of numerous saponins isolated from ivy ( Hedera helix Linné ) leaves, has been reported to have anti-tumour, anti-apoptosis, and anti-inflammatory effects ( Zhang et al, 2012 ; Lu et al, 2015 ). Apoptosis and inflammation are both key molecular pathways involved in cerebral ischaemia/reperfusion (CI/R) injury.…”

Section: Introductionmentioning

confidence: 99%

Hederagenin Attenuates Cerebral Ischaemia/Reperfusion Injury by Regulating MLK3 Signalling

Song

Cao

et al. 2020

Front. Pharmacol.

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Cerebral ischaemia/reperfusion (CI/R) injury is a major challenge due to the lack of effective neuroprotective drugs. Hederagenin (HE) is the aglycone part of saponins extracted from Hedera helix Linné that has exhibited anti-apoptotic and anti-inflammatory effects; however, the role of HE in CI/R has not been elucidated. In this study, mice were intraperitoneally (i.p.) injected with HE (26.5, 53, or 106 μmol/kg body weight) for 3 days after middle cerebral artery occlusion (MCAO). Neural function and brain infarct volume were evaluated. HE treatment attenuated CI/R-induced apoptosis and inflammatory cytokine expression within the infarcted areas. HE treatment also decreased the activation of the MLK3 signalling pathway, which potentiates CI/R damage via the MAPK and NFκB pathways. Due to HE’s safety profile, it has potential to be used for the clinical treatment of ischaemic stroke.

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Experimental Study of Antiatherosclerosis Effects with Hederagenin in Rats

Cited by 32 publications

References 28 publications

Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin–Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis

Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin–Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis

Hederagenin potentiated cisplatin- and paclitaxel-mediated cytotoxicity by impairing autophagy in lung cancer cells

Hederagenin Attenuates Cerebral Ischaemia/Reperfusion Injury by Regulating MLK3 Signalling

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