Hederacolchiside A1
(Synonyms: 革叶常春藤皂苷 A1) 目录号 : GC38088Hederacolchiside A1 是从白头翁中分离的,通过调节 PI3K/Akt/mTOR 信号通路诱导凋亡,从而抑制肿瘤细胞的增殖。Hederacolchiside A1 具有抗血吸虫病活性,影响体内和体外的寄生虫生存力。
Cas No.:106577-39-3
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Hederacolchiside A1, isolated from Pulsatilla chinensis, suppresses proliferation of tumor cells by inducing apoptosis through modulating PI3K/Akt/mTOR signaling pathway[1]. Hederacolchiside A1 has antischistosomal activity, affecting parasite viability both in vivo and in vitro[2].
Hederacolchiside A1 reduces the mitochondrial membrane potential and Bcl-2 protein levels, whereas cleaved caspase-3 was higher[1]. Hederacolchiside A1 effectively inhibits the phosphorylations of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) [1].
hederacolchiside A1 (3.0, 4.5, and 6.0mg/kg, ip) can significantly inhibit the weight of tumor in an H22 xenograft model[1]. Hederacolchiside A1 (3.25, 7.5, and 15.0mg/kg, ig) can significantly inhibit the weight of tumor in nude mice xenograft tumor models using human breast carcinoma MCF-7 cells[1].
[1]. Yan-Er Wang, et al. Hederacolchiside A1 suppresses proliferation of tumor cells by inducing apoptosis through modulating PI3K/Akt/mTOR signaling pathway. Chinese Herbal Medicines.Volume 10, Issue 2, April 2018, Pages 215-222 [2]. Kang N, et al. Antischistosomal Properties of Hederacolchiside A1 Isolated from Pulsatilla chinensis. Molecules. 2018 Jun 13;23(6).
Cas No. | 106577-39-3 | SDF | |
别名 | 革叶常春藤皂苷 A1 | ||
Canonical SMILES | C[C@]12[C@]3(C([C@@]4([H])[C@](C(O)=O)(CCC(C)(C)C4)CC3)=CC[C@]1([H])[C@@]5([C@@](C(C)([C@@H](O[C@@]6([H])[C@@H]([C@H]([C@@H](O[C@]7([H])O[C@@H]([C@@H](O)[C@H](O)[C@H]7O)CO)CO6)O)O[C@@]8([H])[C@@H]([C@@H]([C@@H](O)[C@H](C)O8)O)O)CC5)C)([H])CC2)C)C | ||
分子式 | C47H76O16 | 分子量 | 897.1 |
溶解度 | Soluble in DMSO | 储存条件 | 4°C, protect from light |
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Hederacolchiside A1 Suppresses Autophagy by Inhibiting Cathepsin C and Reduces the Growth of Colon Cancer
Cancers (Basel) 2023 Feb 16;15(4):1272.PMID:36831614DOI:10.3390/cancers15041272.
While autophagy degrades non-functional or unnecessary cellular components, producing materials for synthesizing cellular components, it can also provide energy for tumor development. Hederacolchiside A1 (HA1) derived from anemone raddeana has anticancer effects on several carcinomas by inducing apoptosis or exhibiting cytotoxicity, but the relationship with autophagy has not been studied. We investigated the association between HA1 and autophagy and evaluated its anticancer effect on colon cancer. HA1 induced accumulation of the autophagy-related markers LC3B and SQSTM1, with distinct vacuolar formation, unlike other autophagy inhibitors; the effects were similar to those of chloroquine. In addition, HA1 decreased the expression and proteolytic activity of lysosomal protein cathepsin C, reduced the growth of colon cancer cells in vitro, and inhibited tumor growth in vivo. It also reduced the expression of Ki-67 and cathepsin C in mouse tissues and reduced the growth of spheroids and organoids composed of cancer cells. Taken together, these results imply that HA1 regulates cell growth and autophagy and has potential as a promising therapeutic agent in colon cancer.
Antischistosomal Properties of Hederacolchiside A1 Isolated from Pulsatilla chinensis
Molecules 2018 Jun 13;23(6):1431.PMID:29899232DOI:10.3390/molecules23061431.
Background: Schistosomiasis is a major neglected disease for which the current control strategy involves mass treatment with praziquantel, the only available drug. Hence, there is an urgent need to develop new antischistosomal compounds. Methods: The antischistosomal activity of Hederacolchiside A1 (HSA) were determined by total or female worm burden reductions in mice harboring Schistosoma japonicum or S. mansoni. Pathology parameters were detected on HSA against 1-day-old S. japonicum-harboring mice. Moreover, we confirmed the antischistosomal effect of HSA on newly transformed schistosomula (NTS) of S. japonicum in vitro. Results: HSA, a natural product isolated from Pulsatilla chinensis (Bunge) Regel, was initially corroborated to possess promising antischistosomal properties. We demonstrated that HSA had high activity against S. japonicum and S. mansoni less in 11 days old parasites harbored in mice. The antischistosomal effect was even more than the currently used drugs, praziquantel, and artesunate. Furthermore, HSA could ameliorate the pathology parameters in mice harboring 1-day-old juvenile S. japonicum. We also confirmed that HSA-mediated antischistosomal activity is partly due to the morphological changes in the tegument system when NTS are exposed to HSA. Conclusions: HSA may have great potential to be an antischistosomal agent for further research.
Synthesis and biological evaluation of Hederacolchiside A1 derivatives as anticancer agents
Bioorg Med Chem Lett 2016 Oct 1;26(19):4576-4579.PMID:27592134DOI:10.1016/j.bmcl.2016.08.077.
Modification of Hederacolchiside A1 (HA1) on 28-COOH gave a series of novel triterpenoid saponin compounds containing ester or amide group. Comparing with natural product HA1, several derivatives showed decreased toxicity in the mice acute toxicity trial and increased the anticancer activity in vitro. Especially compound 1 exhibited the strongest antiproliferative activities against human cancer cell lines tested (IC50=1.1-4.6μM) and potent tumor inhibition rate in vivo (46.8%).
Synthesis of beta-hederin and Hederacolchiside A1: triterpenoid saponins bearing a unique cytotoxicity-inducing disaccharide moiety
Carbohydr Res 2006 Jan 16;341(1):60-7.PMID:16297897DOI:10.1016/j.carres.2005.10.015.
A facile synthetic approach toward oleanolic acid glycoside bearing alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl moiety, a unique oligosaccharide that strongly induces antitumor activity of oleanane-type triterpenoid saponins, was developed. Based on this approach beta-hederin (oleanolic acid 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside) was efficiently prepared from oleanolic acid through stepwise glycosylation in linear eight steps with 52% overall yield, while Hederacolchiside A1 (oleanolic acid 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranoside) in linear 13 steps with 20% overall yield.
Pores formation on cell membranes by Hederacolchiside A1 leads to a rapid release of proteins for cytosolic subproteome analysis
J Proteome Res 2008 Apr;7(4):1683-92.PMID:18338859DOI:10.1021/pr7006973.
Hederacolchiside A1 was used to progressively permeabilize the membrane of human melanoma MEL-5 cells. Holes formation was followed by Scanning Electron Microscopy and interaction of the saponin with cholesterol and phospholipids by TOF-SIMS. 2D-LC-MS/MS and 2D-SDS-PAGE show that the release of soluble proteins into serum-free culture media increases with time. This can lead to a new rapid and efficient strategy to analyze the cytosolic subproteome and it opens the door to get information from the cytosolic compartment for clinical proteomic studies.