Active compound from the leaves of vitex negundo L. shows anti-inflammatory activity with evidence of inhibition for secretory phospholipase A2 through molecular docking

Abstract

Novel compounds with significant medicinal properties have gained much interest in therapeutic approaches for treating various inflammatory disorders like arthritis, odema and snake bites and the post-envenom (impregnating with venom) consequences. Inflammation is caused by the increased concentration of secretory Phospholipases A2 (sPLA2s) at the site of envenom. A novel compound Tris(2,4-di-tert-butylphenyl) phosphate (TDTBPP) was isolated from the leaves of Vitex negundo and the crystal structure was reported recently. The acute anti-inflammatory activity of TDTBPP was assessed by Carrageenan-induced rat paw odema method. TDTBPP reduced the raw paw odema volume significantly at the tested doses of 50 mg/kg and 70 mg/kg body weight. Molecular docking studies were carried out with the X-ray crystal structures of Daboia russelli pulchella's (Vipera russelli, Indian Russell's viper) venom sPLA2 and Human non-pancreatic secretory PLA2 (Hnps PLA2) as targets to illustrate the antiinflammatory and antidote activities of TDTBPP. Docking results showed hydrogen bond (H-bond) interaction with Lys69 residue lying in the anti-coagulant loop of D. russelli's venom PLA2, which is essential in the catalytic activity of the enzyme and hydrophobic interactions with the residues at the binding site (His48, Asp49). Docking of TDTBPP with Hnps PLA2 structure showed coordination with calcium ion directly as well as through the catalytically important water molecule (HOH1260) located at the binding site.

Assessing Cu impacts on freshwater diatoms: biochemical and metabolomic responses of Tabellaria flocculosa (Roth) Kützing

“…Tris 2,4 di-tert-butylphenyl phosphate increased as T. flocculosa was exposed to increasing Cu concentrations. This compound was isolated from Vitex negundo leaves and was also reported to have antioxidant properties (Vinuchakkaravarthy et al, 2011).…”

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“…TDTBPP reduced the raw paw odema volume significantly at the tested doses of 50 mg/kg and 70 mg/kg body weight. 44 Another study was undertaken to assess the anti-inflammatory effect of ethanolic extract of Vitex negundo roots in rats. The anti-inflammatory action was studied by Plethysmometer method.…”

Phytochemical and Pharmacological Profile of Vitex negundo

“…Tris (2,4‐ditert‐butylphenyl) phosphate ( 117 ), a new compound isolated from VN leaves, also exhibited significant antiinflammatory activity in carrageenin‐induced paw edema test in rat at the dose of 50 and 70 mg/kg. Further docking results indicated that the possible molecular mechanism was related to the inhibition on secretory Phospholipase A 2 (Vinuchakkaravarthy et al, ). In a recent polyarthritis test in rats (Pandey et al, ), agnuside ( 98 ), a iridoid glycoside isolated from VN, significantly suppressed the expression of leukotrine B 4 and other pro‐inflammatory cytokines in a dose‐dependent manner, which exerted antiinflammatory by keeping the balance of Th1/Th2, thus without any ulcerogenic potential due to its weak inhibition on PGE 2 .…”