Phytochemical Constituents and Pharmacological Mechanisms Underlying the Anti-inflammatory and Antipyretic Potential of Adiantum caudatum Linn.: A Comprehensive Review

Ethnopharmacological Relevance: Adiantum caudatum Linn. (Pteridaceae), popularly known as the 'walkingmaidenhair fern' or 'Mayurshikha', has been venerated across Asian, African, and European traditional medicineparadigms—including Ayurveda, Unani, Siddha, and Traditional Chinese Medicine (TCM)—for centuries. Traditionallyprescribed for mitigating pyrexia, inflammatory arthritis, respiratory disorders, cutaneous wounds, and generalized febrileconditions, the plant represents a crucial ethnomedicinal reservoir. However, until recently, a coherent mechanisticconsolidation elucidating how its chemical matrix orchestrates anti-inflammatory and antipyretic pharmacologicalcascades remained scarce. Aim of the Review: This comprehensive review systematically delineates the botanicalcharacteristics, traditional uses, phytochemical profile, safety profile, and in-depth cellular and molecular mechanismsunderlying the anti-inflammatory and antipyretic properties of Adiantum caudatum Linn., bridging classical ethnobotanicalwisdom with contemporary molecular pharmacology. Methods: An exhaustive systematic literature search was performedacross primary scientific databases (PubMed, Scopus, Web of Science, ScienceDirect, Wiley Online Library, SpringerLink,and Google Scholar) from inception up to August 2026. Explicit inclusion criteria identified peer-reviewed investigationsexamining the chemical isolation, structural elucidation, in vitro assays, in vivo preclinical models, molecular docking, andsignaling pathways modulated by A. caudatum extracts and isolated constituents. Key Findings: Phytochemicalinvestigations have established that A. caudatum synthesizes a diverse spectrum of specialized metabolites, prominentlydominated by migrated hopane and fernane triterpenoids (adiantone, isoadiantone, 21-hydroxyadiantone, fern-9(11)-en-3-one, adiantoxide), flavonoids (quercetin, rutin, isoquercitrin, kaempferol-3-O-rutinoside, luteolin, populnin),phenylpropanoid sulfate conjugates, hydroxycinnamic acids (caffeic, ferulic, p-coumaric, chlorogenic acids), tannins, andsterols. Mechanistically, A. caudatum attenuates inflammation through multimodal networks: (i) blocking NF-κB nucleartranslocation via preventing IκBα phosphorylation, (ii) suppressing MAPK cascades (ERK1/2, p38, JNK), (iii)downregulating cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) catalytic expression, (iv) curtailing excessive nitricoxide (NO) and inducible nitric oxide synthase (iNOS), (v) inhibiting pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL 17), and (vi) promoting the cytoprotective Nrf2/HO-1 antioxidant axis. Its antipyretic efficacy operates centrally viasuppressing preoptic hypothalamic PGE2 biosynthesis through dual COX-2/mPGES-1 attenuation, resetting hypothalamicthermoregulatory set-points, and restoring balance in endogenous cryogens and central neurotransmitters. Conclusions:Preclinical data substantiate the profound ethnomedicinal utility of Adiantum caudatum as a potent anti-inflammatory andantipyretic botanical therapeutic. The synergistic interaction between triterpenoid scaffolds and flavonoid glycosidesprovides multi-target pharmacodynamic action with an enviable safety margin. Future endeavors require advancedchromatographic standardization, bio-guided pharmacokinetic profiling, nanoformulation design to circumventbioavailability limits, and rigorously designed randomized clinical trials.