Author: Lv, Chaoyue ; Wu, Xue ; Jin, Lingli ; Bao, Jingxia ; Ren, Disuo ; Wu, Zhixuan ; Zhang, Shuwei ; Huang, Shaolong ; Meng, Xinyu ; Xia, Erjie ; Wang, Ouchen ; Ru, Jiatong ; Zhang, Heyu

BACKGROUNDBreast cancer ranks first in the global incidence rate of cancer among women. Triple-negative breast cancer (TNBC) is considered to be the most dangerous type because of the lack of specific therapeutic targets and rapid progression. The emergence of ferroptosis provides a new therapeutic perspective for TNBC. α-Hederin is a triterpenoid saponin derived from the traditional Chinese medicine Ivy, which has been proven to have anti-cancer effects on various cancers, but its efficacy and mechanism of inducing ferroptosis in TNBC remain to be further clarified.OBJECTTo investigate the effect and mechanism of α-Hederin induced ferroptosis in TNBC.METHODCell viability was measured by CCK-8 assay, and cell proliferation and migration were evaluated by clone assay and scratch assay. The effect of α-Hederin on TNBC cell apoptosis was assessed by flow cytometry. Transcriptomics searches for critical pathways. Intracellular and lipid reactive oxygen species and Fe²⁺and Fe were detected by DCFH-DA probe, FerroOrange fluorescent probe and C11-BODIPY fluorescent probe, and the contents of malondialdehyde and reduced glutathione were detected by MDA and GSH kits. Erastin was used as a positive control for ferroptosis and Ferrrostatin-1(Fer-1) as an inhibitor. The relationship between α-Hederin and GPX4, IRF was analyzed by western blot and si-RNA, and the association was further confirmed by molecular simulation docking, external SPR experiments, and luciferase experiments. Constructing xenograft mouse models and human derived organoid models to evaluate the anti-TNBC efficacy of α-Hederin, and verifying the efficacy and ferroptosis mechanism of the drug in vivo through HE staining and IHC.RESULTα-Hederin significantly inhibited the progression of TNBC. In vitro, α-Hederin decreased cancer cell viability through ferroptosis, increased glutathione degradation and MDA production, and promoted intracellular Fe²⁺ and ROS production, whereas Fer-1, an ferroptosis inhibitor, reversed this effect. Mechanistically, molecular docking and SPR experiments showed binding of α-Hederin to the key regulator IRF1, and knockdown/overexpression of IRF1 significantly affected the expression of GPX4, a downstream target of the ferroptosis pathway. In vivo, α-Hederin prevented tumor growth in xenograft and organoid models via the IRF1/GPX4 axis.CONCLUSIONWe proved for the first time in this research that α-Hederin exerts anti-TNBC effects through a novel IRF1/GPX4 ferroptosis pathway.

01 May 2025·International Immunopharmacology

In-depth molecular assessment of Hedera helix's L. α – Hederin & Hederacoside C as a gastroprotective & a possible safe Omeprazole phyto-alternative in ethanol-induced gastric ulcer mice model

Article

Author: Nabil, Ghazal ; Gamil, Noha M ; Shokry, Aya A ; Bashir, Dina W

Hedera helix L. is among the most popular over-the-counter formulations for effectively alleviating respiratory disorders in adults & children due to its unique active constituents such as α - Hederin & Hederacoside C. Even though its respiratory pharmacological activity is thoroughly researched, its other pharmacological activities remain relatively unexplored. Alcoholism is a Western cultural habit that is associated with various side effects, including peptic ulcer disease (PUD) & drug interaction. The PUD is commonly & recurrently presented clinically, increasing the load on healthcare systems. PUD not only negatively affects the quality of life but is also associated with serious complications such as bleeding, penetration, perforation, pyloric stenosis, & gastric cancer. Alcohol interaction with drugs could either lead to therapeutic failure, accumulation of drug-toxic metabolites, or disturbance of the alcohol detoxification pathway, putting the treatment of alcoholism-induced PUD with a drug-interacting medication such as Omeprazole under the limelight. In line with that, finding plant-derived molecules with the potency of Omeprazole but without its associated side effects & drug-interacting property is a desperate clinical need. In this regard, we aimed to investigate the gastroprotective effect, potency, & molecular mechanism of α - Hederin & Hederacoside C pretreatment against ethanol-induced gastric ulcer in mice model. These compounds were tested in two upgrading doses (50 mg/kg & 75 mg/kg) compared to negative, positive, & Omeprazole groups. Our study revealed that daily oral administration of α - Hederin or Hederacoside C protected the stomach against ethanol-induced gastric ulcers in a dose-dependent manner. The potency of high doses of both compounds was comparable to Omeprazole. Their effectiveness was related to their ability to set the activated invasive forces, including CYP1A2, neutrophils, MDA, leptin, TNF-α, IL-6, IL-12, & NF-κB-p65 & to amplify the intrinsic defensive forces, including COX-2, PGE-2, CAT, & SOD. These intertwined actions were reflected in maintaining vibrant stomach architecture, such as mucosal layer re-epithelization, gland reconstruction, & restoring tunica muscularis normal thickness. Moreover, they limited the exaggeration of the repairing system, including HSP-70, VEGF, & Annexin-1, where their forge was positively correlated with damage depth. Therefore, we compendiously deduced that herbal-based medicine could face the constraints of synthesized medicine satisfactorily without their culminating side effects.

01 Apr 2025·Chemistry & Biodiversity

Current Perspective and Mechanistic Insights on α‐Hederin for the Prevention and Treatment of Several Noncommunicable Diseases

Review

Author: Elgindy, Ali M. ; El‐Shiekh, Riham A. ; Atwa, Ahmed M. ; Ibrahim, Kawther Magdy ; Mustafa, Aya M. ; Ebid, Nouran ; Senna, Mohamed Magdy

ABSTRACTα‐Hederin, a naturally occurring compound found in various plant sources, has remarkable properties and therapeutic potential for human health. One notable attribute is its potent anti‐inflammatory activity, such as in arthritis, asthma, and inflammatory bowel disease. In addition, it exhibits notable antioxidant effects implicated in the development of chronic diseases, including cardiovascular disorders and certain types of cancer. According to research, it may limit the growth and proliferation of cancer cells, making it a possible candidate for future cancer treatments. Moreover, it is a promising neuroprotective agent and enhances cognitive function, suggesting its potential in the treatment of neurodegenerative illnesses like Alzheimer's and Parkinson's disease. The multifaceted benefits of α‐hederin make it an intriguing compound with significant therapeutic implications. As research progresses, exploring its mechanisms of action and clinical applications is warranted. Harnessing the potential of α‐hederin may pave the way for innovative treatment strategies and improved outcomes in the battle against various chronic diseases.

100 Deals associated with α-Hederin

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Hyperlipidemias	China	-	-

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Preclinical	Sri Lanka	University of Colombo	12 Apr 2024
Non-Small Cell Lung Cancer	Preclinical	China	Shanghai University of Traditional Chinese Medicine	01 Feb 2024

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