Page 71 - IMO-2-3

Innovative Medicines & Omics Peganum harmala and GLP-1: A natural approach

These alkaloids exhibit poor water solubility and rapid establish its clinical viability. Moreover, exploring its synergy
hepatic metabolism, limiting their systemic efficacy. with existing GLP-1RAs and its broader implications in
Nanotechnology-based drug delivery systems offer a neurodegenerative and cardiovascular diseases could unlock
viable solution by encapsulating harmine and harmaline additional therapeutic opportunities.
in liposomes, polymeric nanoparticles, or lipid-based By integrating traditional medicine with modern
carriers, improving their stability and controlled release, biomedical innovations, P. harmala holds the promise
enhancing intestinal permeability, ensuring targeted of transforming metabolic disorder management. Its
delivery to enteroendocrine L-cells for GLP-1 stimulation affordability, accessibility, and natural origin make it
and pancreatic β-cells for insulin secretion, and reducing a valuable candidate for global healthcare strategies,
systemic toxicity, a key consideration given the dose- particularly in regions where conventional GLP-1RAs
dependent effects of P. harmala alkaloids. By leveraging remain financially and logistically restrictive. Moving
nanotechnological advancements, the therapeutic forward, interdisciplinary collaborations between
potential of P. harmala can be optimized, allowing for oral pharmacologists, endocrinologists, and nanotechnology
administration with enhanced bioavailability and a more experts will be crucial in realizing the full therapeutic
sustained pharmacokinetic profile. While pre-clinical data potential of P. harmala, paving the way for its integration
suggest that P. harmala possesses significant metabolic into evidence-based clinical practice.
benefits, several challenges must be addressed before its
clinical application. One key issue is the standardization of Acknowledgments
alkaloid content, as variations in harmine and harmaline
concentrations across plant extracts necessitate rigorous The first author, Maher Monir Akl, in full agreement
protocols to ensure consistent therapeutic effects. In with the second author, Amr Ahmed, extends heartfelt
addition, long-term safety and toxicity studies are crucial. appreciation to the individuals and institutions that have
Despite its historical use in traditional medicine, P. harmala directly or indirectly contributed to this work. Special
exhibits dose-dependent neurotoxic and hepatotoxic gratitude goes to patients, researchers, and healthcare
risks, requiring comprehensive evaluations. Furthermore, professionals whose dedication inspires ongoing scientific
comparative efficacy studies with GLP-1RAs are essential. efforts to improve health outcomes.
Direct clinical trials comparing P. harmala to semaglutide A personal acknowledgment is extended to my mother
and other GLP-1 analogs are needed to establish its for her unwavering support and encouragement, as well as
relative efficacy and pharmacodynamic properties. With to my life partner, whose belief in my potential has been
ongoing advancements in phytochemical standardization, a source of strength and motivation. Their support has
nanotechnology-based delivery systems, and metabolic fueled my relentless pursuit of knowledge, with the hope
disease modeling, P. harmala represents a compelling that this research will contribute meaningfully to scientific
natural candidate for the future of incretin-based and advancement and human well-being.
insulin-sensitizing therapies .41
Funding
8. Conclusion
None.
P. harmala presents a compelling natural alternative for
enhancing GLP-1 secretion, improving insulin sensitivity, Conflict of interest
and mitigating oxidative stress, offering a novel therapeutic The authors declare that there are no conflicts of interest.
avenue for metabolic disorders. Across its bioactive
alkaloids, particularly harmine and harmaline, P. harmala Author contributions
exerts multifaceted pharmacological effects, modulating
key molecular pathways involved in glucose metabolism, Conceptualization: All authors
pancreatic β-cell protection, and systemic insulin regulation. Writing – original draft: All authors
Furthermore, advancements in nanotechnology provide a Writing – review & editing: All authors
promising strategy to overcome bioavailability limitations,
ensuring its therapeutic efficacy. While the potential of Ethics approval and consent to participate
P. harmala as a metabolic therapeutic is evident, further
research is required to bridge the gap between pre-clinical Not applicable.
findings and clinical application. Rigorous investigations, Consent for publication
including randomized controlled trials, standardized dosing
studies, and long-term safety assessments, are imperative to Not applicable.

Volume 2 Issue 3 (2025) 65 doi: 10.36922/IMO025060009