Extra-Oral Receptors in Bidalaka: Eyelid Delivery Mechanisms of Tikta Rasa Herbs

Abstract

Bidalaka, a classical Ayurvedic periocular therapy involving medicated paste application over closed eyelids, has been employed for centuries in managing anterior segment conditions, principally inflammation. Classical texts attribute its efficacy to Tikta rasa (bitter-tasting) herbs possessing Shothahara (anti-inflammatory) and Kandughna (anti-pruritic) properties. This review proposes a receptor-mediated pharmacological framework in which Bidalaka’s therapeutic action is, at least in part, mediated through activation of extra-oral bitter taste receptors (TAS2Rs) on periocular keratinocytes and resident immune cells via G protein-coupled receptor signaling. The eyelid’s exceptionally thin cutaneous barrier confers superior drug permeability, while keratinocyte-expressed TAS2Rs – including TAS2R38 and TAS2R14 – coupled with α-gustducin, activate phospholipase Cβ2-mediated calcium signaling, barrier reinforcement through p38 mitogen-activated protein kinase/peroxisome proliferator-activated receptor gamma pathways, and suppression of mast cell degranulation, histamine, prostaglandin D2 , tumor necrosis factor-alpha, and chemokine release upon bitter agonist stimulation. The shared microvascular and lymphatic anatomy between the eyelid and palpebral conjunctiva further facilitates transdermal-to-ocular drug translocation. This convergence of eyelid anatomy, TAS2R biology, and periocular vascular architecture provides a coherent molecular rationale for Bidalaka’s efficacy, supporting both standardization of Ayurvedic ophthalmic therapies and development of novel transdermal ophthalmic drug delivery platforms.