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

Abstract- Ethnopharmacological Relevance: Adiantum caudatum Linn. (Pteridaceae), popularly known as the 'walking
maidenhair fern' or 'Mayurshikha', has been venerated across Asian, African, and European traditional medicine
paradigms—including Ayurveda, Unani, Siddha, and Traditional Chinese Medicine (TCM)—for centuries. Traditionally
prescribed for mitigating pyrexia, inflammatory arthritis, respiratory disorders, cutaneous wounds, and generalized febrile
conditions, the plant represents a crucial ethnomedicinal reservoir. However, until recently, a coherent mechanistic
consolidation elucidating how its chemical matrix orchestrates anti-inflammatory and antipyretic pharmacological
cascades remained scarce. Aim of the Review: This comprehensive review systematically delineates the botanical
characteristics, traditional uses, phytochemical profile, safety profile, and in-depth cellular and molecular mechanisms
underlying the anti-inflammatory and antipyretic properties of Adiantum caudatum Linn., bridging classical ethnobotanical
wisdom with contemporary molecular pharmacology. Methods: An exhaustive systematic literature search was performed
across 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 investigations
examining the chemical isolation, structural elucidation, in vitro assays, in vivo preclinical models, molecular docking, and
signaling pathways modulated by A. caudatum extracts and isolated constituents. Key Findings: Phytochemical
investigations have established that A. caudatum synthesizes a diverse spectrum of specialized metabolites, prominently
dominated 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, and
sterols. Mechanistically, A. caudatum attenuates inflammation through multimodal networks: (i) blocking NF-κB nuclear
translocation 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 nitric
oxide (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 via
suppressing preoptic hypothalamic PGE2 biosynthesis through dual COX-2/mPGES-1 attenuation, resetting hypothalamic
thermoregulatory 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 and
antipyretic botanical therapeutic. The synergistic interaction between triterpenoid scaffolds and flavonoid glycosides
provides multi-target pharmacodynamic action with an enviable safety margin. Future endeavors require advanced
chromatographic standardization, bio-guided pharmacokinetic profiling, nanoformulation design to circumvent
bioavailability limits, and rigorously designed randomized clinical trials.