Decoding the mechanistic landscape of harpagoside: From molecular targets to translational pharmacology.
- 2025-12-12
- Fitoterapia 188
- Harpreet Kaur
- Dinesh Kumar
- Vinod Kumar Gauttam
- Ashish Suttee
- Romanpreet Kaur
- Rajni Tanwar
- Suresh Babu Kondaveeti
- Neeraj Choudhary
- PubMed: 41391813
- DOI: 10.1016/j.fitote.2025.107029
Study Design
- Type
- Review
Harpagoside, a pharmacologically active iridoid glycoside from Harpagophytum procumbens (Devil's Claw), exhibits broad therapeutic properties including anti-inflammatory, antioxidant, analgesic, anticancer, and bone-protective effects. Preclinical studies demonstrate pathway modulation at concentrations of 10-50 μM, targeting NF-κB, AP-1, Nrf2/HO-1, PI3K/Akt, and MAPKs, with in vivo evidence for bone preservation, metabolic regulation, and neuroprotection. Clinical trials using standardized extracts (50-100 mg/day harpagoside or 2.6 g/day powdered root) have reported significant improvements in osteoarthritis and chronic low back pain, with fewer gastrointestinal adverse effects compared to NSAIDs. Unlike previous reviews, this article emphasizes the multi-pathway and systems pharmacology mechanisms of harpagoside, its prodrug-like behavior through biotransformation into active metabolites, and formulation strategies, such as nanoparticles, phospholipid complexes, and semi-synthetic derivatives, to overcome poor oral bioavailability. Current challenges include variability in phytochemical content, limited pharmacokinetic and safety data, and insufficient GLP-compliant long-term toxicity studies. By integrating molecular targets, preclinical and clinical evidence, and advances in delivery technologies, this review positions harpagoside as a prototype multi-target phytochemical with significant translational promise in inflammatory, metabolic, and degenerative disorders.