Page 65 - IMO-2-3

Innovative Medicines & Omics

PERSPECTIVE ARTICLE
Exploring Peganum harmala as a natural

alternative to semaglutide: A novel approach to
glucagon-like peptide-1 stimulation and insulin

sensitization

1
Maher Monir. Akl * and Amr Ahmed 2
1 Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt
2 Department of Public Health, Riyadh First Health Cluster, Ministry of Health, Saudi Arabia
(This article belongs to the Special Issue: Medicinal and Pharmaceutical Chemistry)

Abstract

Glucagon-like peptide-1 (GLP-1) is a crucial incretin hormone that regulates glucose
homeostasis by enhancing insulin secretion, suppressing glucagon release, and
*Corresponding author: delaying gastric emptying. While synthetic GLP-1 receptor agonists such as semaglutide
Maher Monir. Akl have demonstrated efficacy in managing type 2 diabetes mellitus and obesity, their
(maherakl555@gmail.com) high cost, limited accessibility, and adverse effects have limited their applicability,
Citation: Akl MM, Ahmed A. necessitating the search for alternative therapeutic strategies. Peganum harmala
Exploring Peganum harmala as a (harmal), a traditional medicinal plant, has gained attention for its bioactive alkaloids,
natural alternative to semaglutide:
A novel approach to glucagon-like harmine, and harmaline, which have been shown to modulate key molecular pathways
peptide-1 stimulation and insulin involved in GLP-1 secretion and insulin sensitization. These alkaloids enhance Akt
sensitization. Innov Med Omics. phosphorylation (pS473-Akt), facilitating glucose transporter type 4 translocation and
2025;2(3):59-67.
doi: 10.36922/IMO025060009 glucose uptake, while concurrently activating the nuclear factor erythroid 2-related
factor 2 pathway, leading to increased antioxidant defenses and reduced oxidative
Received: February 5, 2025 stress in pancreatic β-cells and enteroendocrine L-cells. Furthermore, P. harmala
1st revised: February 11, 2025 alleviates insulin resistance by suppressing IRS-1 serine phosphorylation (pS307-
2nd revised: February 21, 2025 IRS-1) and improving phosphoinositide 3-kinase/Akt signaling, thereby optimizing
insulin receptor sensitivity and metabolic homeostasis. Despite these promising
3rd revised: February 24, 2025 pharmacological properties, the poor solubility and rapid metabolism of harmine and
4th revised: March 6, 2025 harmaline pose challenges to their clinical application. Nanotechnology-based drug
Accepted: March 6, 2025 delivery systems, including liposomal encapsulation and polymeric nanoparticles,
offer a potential solution to enhance bioavailability, prolong systemic circulation,
Published online: March 19, 2025 and enable targeted delivery to GLP-1-secreting cells. This paper delves into the
Copyright: © 2025 Author(s). molecular mechanisms by which P. harmala stimulates GLP-1 secretion and improves
This is an Open-Access article insulin sensitivity, compares its effects with semaglutide, and highlights the potential
distributed under the terms of the
Creative Commons Attribution role of nanotechnology in optimizing its therapeutic applications. By integrating
License, permitting distribution, traditional medicine with modern pharmaceutical advancements, P. harmala
and reproduction in any medium, represents a promising, cost-effective, and sustainable approach to metabolic disorder
provided the original work is
properly cited. management, warranting further investigation through pre-clinical and clinical studies.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Peganum harmala; Glucagon-like peptide-1; Semaglutide; Insulin sensitivity;
regard to jurisdictional claims in
published maps and institutional Nanotechnology
affiliations.

Volume 2 Issue 3 (2025) 59 doi: 10.36922/IMO025060009