Itrīfal Mulayyin, a promising drug to manage Shaqīqa Muzmin (chronic migraine): A comprehensive review

Migraine is a highly disabling neurological disorder and the second leading cause of disability-adjusted life years (DALYs) among neurological conditions worldwide. Chronic migraine ( Shaqīqa Muzmin ) is associated with inadequate management of acute episodes, medication overuse, psychological stress, obesity, and systemic inflammation. Increasing evidence implicates the gut–brain axis—a bidirectional communication network involving neural, immune, and endocrine pathways—in migraine pathophysiology. Alterations in gut microbiota, pro-inflammatory cytokines, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, and neurotransmitters such as serotonin, dopamine, and calcitonin gene-related peptide (CGRP) are considered central to this mechanism. This review explores the therapeutic potential of Itrīfal Mulayyin , a classical Unani polyherbal formulation, in chronic migraine through its effects on the gut–brain axis, humoral balance, and neuroinflammatory pathways. Data were synthesized from classical Unani texts, the Unani Formulary of India, and modern biomedical literature. Pharmacological activities of the formulation’s constituents were examined in relation to migraine and gut–brain regulation. Itrīfal Mulayyin is a semisolid formulation comprising Terminalia chebula , Terminalia bellirica , Phyllanthus emblica , Rheum emodi , Convolvulus scammonia , Operculina turpethum , Foeniculum vulgare , Lavandula stoechas , Pistacia lentiscus , and sugar base ( Qiwām ). Classical literature attributes to it three core actions: (i) Munaqqi Dimāgh (brain cleanser) – detoxifying humoral imbalance; (ii) Mulayyin-i-Am‘a (laxative) – enhancing gastrointestinal motility and waste elimination; and (iii) Musakkin-i-Alam (analgesic) – alleviating pain. Modern pharmacology supports these actions, demonstrating antioxidant, anti-inflammatory, neuroprotective, and gut-modulating properties of its ingredients. Together, these mechanisms suggest a regulatory role on the gut–brain axis and a potential in reducing migraine frequency and severity. By bridging Unani theory and biomedical evidence, Itrīfal Mulayyin emerges as a promising complementary therapy for chronic migraine. Its multimodal actions warrant systematic pharmacological validation and clinical trials to establish its efficacy and safety in migraine management.