Emerging roles of anacardic acid and its derivatives: a pharmacological overview

Anacardic acid (AA) is a bioactive phytochemical found in nutshell of Anacardium occidentale. Chemically, it is a mixture of several closely related organic compounds, each consisting of salicylic acid substituted with an alkyl chain. The traditional Ayurveda depicts nutshell oil as a medicinal remedy for alexeritic, amebicidal, gingivitis, malaria and syphilitic ulcers. However, the enduring research and emerging evidence suggests that AA could be a potent target molecule with bactericide, fungicide, insecticide, anti-termite and molluscicide properties and as a therapeutic agent in the treatment of the most serious pathophysiological disorders like cancer, oxidative damage, inflammation and obesity. Furthermore, AA was found to be a common inhibitor of several clinically targeted enzymes such as NFκB kinase, histone acetyltransferase (HATs), lipoxygenase (LOX-1), xanthine oxidase, tyrosinase and ureases. In view of this, we have made an effort to summarize the ongoing research on the therapeutical role of AA and its derivatives. The current MiniReview sheds light on the pharmacological applications, toxicity and allergic responses associated with AA and its derivatives. Although the available records are promising, much more detailed investigations into the therapeutical properties, particularly the anti-cancer and anti-inflammatory activities, are urgently needed. We hope the present MiniReview will attract and encourage further research on elucidating and appreciating the possible curative properties of AA and its derivatives in the management of multifactorial diseases

Jackfruit (Artocarpus heteophyllus) seed extract exhibits fibrino(geno)lytic activity

Objective: The current study assesses the fibrinogen and fibrin clot hydrolyzing activities of aqueous seed extract of Jackfruit (AqSEJ). Methods: The protein banding pattern of AqSEJ (100 μg) was analyzed on SDS-PAGE. The proteolytic activity of AqSEJ was confirmed by spectrophotometer and zymography experiments. Fibrinogen, fibrin and plasma protein hydrolyzing activities of AqSEJ were analyzed on SDS-PAGE under reduced conditions. Plasminogen activation and indirect hemolytic activities was analyzed using spectrophotometer. The non-toxic property of AqSEJ was tested by edema, hemorrhage in experimental mice. Results: AqSEJ exhibited proteolytic activity and the specific activity was found to be 1.04 units/mg/min. Furthermore, AqSEJ non-specifically hydrolyzed Aα, followed by Bβ and γ chains of human fibrinogen and specifically hydrolyzed α polymer and α chain of partially cross linked human fibrin clot without affecting β chain and γ-γ dimer even up to the tested dose of 30 µg for the incubation period of 8 hours. Importantly, AqSEJ did not hydrolyze other plasma proteins and devoid of plasminogen activation property. The proteolytic activity of AqSEJ was completely neutralized by PMSF and IAA, while EDTA, EGTA, 1,10-Phenanthroline did not, suggesting the presence of serine and cysteine family proteases. Moreover, AqSEJ did not cause edema and hemorrhage in experimental mice up to the tested dose of 200 µg and nontoxic to RBC cells. Conclusion: AqSEJ hydrolyzes fibrinogen and fibrin clot and non-toxic in nature. Hence, this work showcases the potential applications of Jack fruit seed proteases in the treatment of thrombotic disorder

Neutralization of haemorrhagic activity of viper venoms by 1-(3-Dimethylaminopropyl)-1-(4-Fluorophenyl)-3-Oxo-1, 3-dihydroisobenzofuran-5-carbonitrile

Viper envenomation undeniably induces brutal local manifestations such as haemorrhage, oedema and necrosis involving massive degradation of extracellular matrix at the bitten region and many a times results in dangerous systemic haemorrhage including pulmonary shock. Snake venom metalloproteases (SVMPs) are being considered to be the primary culprits for the venom-induced haemorrhage. As a consequence, the venom researchers and medical practitioners are in deliberate quest of SVMP inhibitors. In this study, we evaluated the inhibitory effect of 1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-3-oxo-1,3-dihydroisobenzofu ran-5-carbonitrile (DFD) on viper venom-induced haemorrhagic and PLA(2) activities. DFD effectively neutralized the haemorrhagic activity of the medically important viper venoms such as Echis carinatus, Echis ocelatus, Echis carinatus sochureki, Echis carinatus leakeyi and Crotalus atrox in a dose-dependent manner. The histological examinations revealed that the compound DFD effectively neutralizes the basement membrane degradation, and accumulation of inflammatory leucocytes at the site of Echis carinatus venom injection further confirms the inhibition of haemorrhagic activity. In addition, DFD dose dependently inhibited the PLA(2) activities of Crotalus atrox and E. c. leakeyi venoms. According to the docking studies, DFD binds to hydrophobic pocket of SVMP with the ki of 19.26 x 10(-9) (kcal/mol) without chelating Zn2+ in the active site. It is concluded that the clinically approved inhibitors of haemorrhagins could be used as a potent first-aid agent in snakebite management. Furthermore, a high degree of structural and functional homology between SVMPs and their relatives, the MMPs, suggests that DFD analogues may find immense value in the regulation of multifactorial pathological conditions like inflammation, cancer and wound healing