Vitex negundo L.: A comprehensive exploration of its phytochemistry, pharmacological attributes and molecular docking insights

• V. negundo possess diverse phytochemicals with numerous medicinal properties. • Possesses antioxidant, antitumor, antimicrobial, neuro and cardio protective properties. • In-silico studies elucidated interaction with MAPK, ERK 1/2, JNK, and mTOR pathways. Vitex negundo L. is a widely distributed medicinal plant especially in many Asian countries like India (Nirgundi) and China (Chinese Pinyin). In the ethno-botanical realm, it offers an expansive array of medicinal attributes. The literature search was conducted using key words ‘ Vitex negundo ’ or ‘Chaste tree’, ‘phytochemicals’, ‘pharmacology’ or ‘biological activities’, ‘molecular docking’, ‘traditional medicine’, ‘inflammation’, ‘clinical trials’ and ‘drug discovery’ from 1969 to November 2025 on various databases like Google Scholar, Science Direct, ResearchGate and Pub Med. By summarizing and analyzing a wide range of fundamental and clinical studies on V. negundo, it was observed that V. negundo derived phytochemicals and botanical extracts exhibit dose-dependent antioxidant, anti-androgenic, thrombolytic, anti-cholinesterase, α-glucosidase, and cyclooxygenase inhibitory activities. They influence various cellular processes, including programmed cell death, mitogenic signaling, and immune modulation through various signaling networks such as AMPK/PI3K/Akt/p38-NF-B, MAPKs/NF-κB, and TGF/Smad/Bcl2/caspase/LC3. It also affects various oncogenic signaling routes, including COX-1, MAPK, Akt, mTOR, PI3K/AKt, and Akt/FOXO3a. Notably, vitexin, an active ingredient, reduces leukocyte migration and inhibits the release of pro-inflammatory cytokines such as TNF-α, IL-1β, and NO via inactivation of p38, MAPK, ERK1/2, and JNK signaling pathways. Another phytoconstituent, vitedoin-A, inhibits osteoclast development by blocking the ERK/NFATc1 signaling network. Molecular docking simulations revealed strong binding affinities of phyto ligands like negundoside, luteolin, 5,7-dihydroxy-6,40-dimethoxy flavonone, and 9-[4,5-dihydroxy-6-(hydroxymethyl) oxan-2-yl]−1H-purin-6-one against specific key target proteins such as COX, HER2 (3RCD), PAK1, and Wnt, validating their anti-inflammatory and antitumor efficacy. Clinical studies revealed remarkable improvement in arthritis, cataract, respiratory diseases, and insomnia among selected individuals. Further studies on the pharmacokinetics are required to establish its therapeutic efficacy, safety, and bridge traditional knowledge with modern drug development.