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Peer-reviewedCC BYBiomedicine & Pharmacotherapy

Signaling pathways driving multiple sclerosis: From mechanisms to natural‑product interventions

  • Ahmed M. El‐Dessouki1
  • Heba Nasr Shalaby2
  • Samar S. Khalaf3
  • Mai A. Abd‐Elmawla4
  • Heba R. Ghaiad5
  • Sherif S. Abdel Mageed6
  • Riham A. El‐Shiekh7
  • Sadek Ahmed8
  • Hazim O. Khalifa9
9 affiliations
  1. 1Pharmacology and Toxicology Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, Egypt
  2. 2Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
  3. 3Biochemistry Department Faculty of Pharmacy Heliopolis University, Cairo, Egypt
  4. 4Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt; Department of Biochemistry, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt
  5. 5Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
  6. 6Pharmacology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
  7. 7Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
  8. 8Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
  9. 9Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, United Arab Emirates; United Arab Emirates University (UAEU) Center for Public Policy and Leadership, United Arab Emirates University, Al Ain, United Arab Emirates. Electronic address: [email protected]
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Abstract

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system characterized by inflammation and progressive neurodegeneration. MS is a heterogeneous disease with varying presentations, disease courses, and prognosis. Although current disease-modifying therapies (DMTs) have been reported to reduce the frequency and severity of inflammatory demyelinating hallmarks of MS, improve relapse rate and long-term outcomes, they do not fully prevent disease progression, nor do they reverse existing neurological damage. This ongoing gap has driven growing interest in natural products as complementary or adjunctive strategies for MS management. Naturally occurring phytochemicals have been proposed as a potentially safe and effective therapeutic and complementary option for MS. Natural compounds have been reported to demonstrate anti-inflammatory, immunomodulatory, antioxidant, and neuroprotective activities in experimental models of MS. Together, these multifunctional properties target key mechanistic pathways implicated in disease pathogenesis, such as oxidative stress, mitochondrial dysfunction, and immune dysregulation. However, despite promising preclinical data, clinical translation remains limited by variability in dosing, bioavailability challenges, and insufficient large-scale trials. In this context, this review explores the scientific rationale for natural products in MS, provides an overview of disease mechanisms relevant to such interventions, and highlights future research needs to advance these compounds toward evidence-based integration.

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Cite

BibTeXRIS
BibTeX
@article{eldessouki2026signaling,
  title = {{Signaling pathways driving multiple sclerosis: From mechanisms to natural‑product interventions}},
  author = {Ahmed M. El‐Dessouki and Heba Nasr Shalaby and Samar S. Khalaf and Mai A. Abd‐Elmawla and Heba R. Ghaiad and Sherif S. Abdel Mageed and Riham A. El‐Shiekh and Sadek Ahmed and Hazim O. Khalifa},
  journal = {Biomedicine \& Pharmacotherapy},
  year = {2026},
  month = may,
  doi = {10.1016/j.biopha.2026.119543},
  url = {https://doi.org/10.1016/j.biopha.2026.119543},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Signaling pathways driving multiple sclerosis: From mechanisms to natural‑product interventions
AU  - Ahmed M. El‐Dessouki
AU  - Heba Nasr Shalaby
AU  - Samar S. Khalaf
AU  - Mai A. Abd‐Elmawla
AU  - Heba R. Ghaiad
AU  - Sherif S. Abdel Mageed
AU  - Riham A. El‐Shiekh
AU  - Sadek Ahmed
AU  - Hazim O. Khalifa
PY  - 2026
DA  - 2026/05/25
JO  - Biomedicine & Pharmacotherapy
DO  - 10.1016/j.biopha.2026.119543
UR  - https://doi.org/10.1016/j.biopha.2026.119543
AB  - Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system characterized by inflammation and progressive neurodegeneration. MS is a heterogeneous disease with varying presentations, disease courses, and prognosis. Although current disease-modifying therapies (DMTs) have been reported to reduce the frequency and severity of inflammatory demyelinating hallmarks of MS, improve relapse rate and long-term outcomes, they do not fully prevent disease progression, nor do they reverse existing neurological damage. This ongoing gap has driven growing interest in natural products as complementary or adjunctive strategies for MS management. Naturally occurring phytochemicals have been proposed as a potentially safe and effective therapeutic and complementary option for MS. Natural compounds have been reported to demonstrate anti-inflammatory, immunomodulatory, antioxidant, and neuroprotective activities in experimental models of MS. Together, these multifunctional properties target key mechanistic pathways implicated in disease pathogenesis, such as oxidative stress, mitochondrial dysfunction, and immune dysregulation. However, despite promising preclinical data, clinical translation remains limited by variability in dosing, bioavailability challenges, and insufficient large-scale trials. In this context, this review explores the scientific rationale for natural products in MS, provides an overview of disease mechanisms relevant to such interventions, and highlights future research needs to advance these compounds toward evidence-based integration.
SN  - 0753-3322
SN  - 1950-6007
ER  -