Unveiling the dark side of Moringa: High doses of Moringa oleifera Lam. Leaf extract increase the risk of adenocarcinoma in obesity-induced prostate hyperplasia through hyperhomocysteinemia/miR-155/STAT3 cascade

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Shaker S.E.; Aziz W.M.; Hammam O.A.; Ibrahim N.E.; Shawky H.

Journal: Journal of Ethnopharmacology

Publisher: Elsevier Ireland Ltd

Publication Date: September 2025

Volume / Issue: Volume 353

Article No.: 120373

ISSN: 3788741

DOI: 10.1016/j.jep.2025.120373

Scopus: View on Scopus

PubMed: 40774579

Document Type: Article

Authors and Affiliations

Shaker S.E., Therapeutic Chemistry Department, Pharmaceutical Industries and Drug Research Institute, National Research Centre, Cairo, Dokki, 12622, Egypt; Aziz W.M., Therapeutic Chemistry Department, Pharmaceutical Industries and Drug Research Institute, National Research Centre, Cairo, Dokki, 12622, Egypt; Hammam O.A., Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt; Ibrahim N.E., Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre, Cairo, Dokki, 12622, Egypt; Shawky H., Therapeutic Chemistry Department, Pharmaceutical Industries and Drug Research Institute, National Research Centre, Cairo, Dokki, 12622, Egypt

Abstract

Ethnopharmacological relevance: Moringa oleifera Lam., known as the “miracle tree”, has been applauded as a complementary medicine, owing to its broad-spectrum health benefits. Aim: This study provides novel insights into the unrecognized risk associated with the use of high-dose M. oleifera Lam. leaf extract (MLE) in an obesity-induced prostate hyperplasia (BPH) rat model. Methods: Dry M. oleifera leaves were water-extracted, and the phytocomposition was determined using HPLC and GC-MS. Obesity-related BPH symptoms were induced in male Sprague Dawley rats receiving a high-fat diet (HFD) for 12 weeks, plus testosterone propionate injected subcutaneously (10 mg/kg/day in corn oil) for 4 weeks. BPH animals received different MLE doses, a reference drug (Prostride), and a combination of MLE + Prostride for 30 days. The therapeutic efficacy of different treatments was assessed in terms of their modulatory effect on obesity-related markers, including body weight, lipid profile, plasma homocysteine (Hcy), and BPH-related markers, including prostate index, androgenic hormones, and prostatic transcriptome of inflammatory/oncogenic/apoptotic mediators. Results: the MLE treatment presented a dose-dependent effect in BPH animals, where the low and medium doses alleviated the BPH symptoms, as indicated by the restoration of redox homeostasis and nearly normalizing the inflammatory, oncogenic, and apoptotic transcriptome in treated prostates, reflected by the reversal of histopathological alterations. Conversely, the high-dose MLE aggravated BPH symptoms and further promoted a protumorigenic milieu through elevating plasma Hcy, which simultaneously upregulated a miR-155/STAT3-mediated oncogenic cascade. Conclusion: These findings emphasize the need for cautious dose optimization in future translational applications of MLE and reinforce the importance of context-specific phytotherapy. © 2025 Elsevier B.V.

Keywords

Chlorogenic acid; Hyperhomocysteinemia; microRNAs; Moringa oleifera; Prostate hyperplasia; Adenocarcinoma; Animals; Diet, High-Fat; Male; Obesity; Plant Extracts; Plant Leaves; Prostatic Hyperplasia; Prostatic Neoplasms; Rats; Rats, Sprague-Dawley; STAT3 Transcription Factor; 2 azido 2,4,4,6,6 pentamethylheptane; androgen; ascorbic acid; caffeic acid; catechin; cinnamic acid; coumaric acid; daidzein; dimethyl(4 phenylphenoxy)octadecyloxy silane; ellagic acid; ferulic acid; finasteride; gallic acid; gallic acid methyl ester; hesperetin; homocysteine; kaempferol; linolenic acid; malic acid; microRNA 155; Moringa oleifera extract; naringenin; palmitic acid; para coumaric acid; pentakis(trimethylsilyl)ether tagatofuranose; prostride; quercetin; rosmarinic acid; rutoside; STAT3 protein; syringic acid; testosterone propionate; transcriptome; trolox C; unclassified drug; vanillin; water; microRNA; plant extract; Stat3 protein, rat; amino acid blood level; animal experiment; animal model; animal tissue; antioxidant activity; apoptosis; Article; body weight; cancer risk; carcinogenesis; chemical composition; controlled study; dose response; drug dose comparison; drug efficacy; drug isolation; drug megadose; high performance liquid chromatography; histopathology; lipid diet; lipid fingerprinting; low drug dose; mass fragmentography; nonhuman; plant leaf; prostate hypertrophy; rat; upregulation; animal; chemistry; complication; drug therapy; etiology; genetics; metabolism; pathology; prostate tumor; Sprague Dawley rat

Citation Information

Scopus Citations: 1

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