In silico to In vivo development of a polyherbal against Haemonchus contortus.

Haemonchus contortus is a major constraint in the development of small ruminant subsector due to significant production losses incurred by it. The present study explores the antiparasitic potential of three anthelmintic plants (Butea monosperma, Vitex negundo and Catharanthus roseus (L.) G.Don) against H. contortus taking albendazole as the standard. In silico molecular docking and pharmacokinetic prediction studies were conducted with known bioactive molecules of these plants (palasonin, vinblastine, vincristine, betulinic acid and ursolic acid) against Glutamate Dehydrogenase (GDH) and tubulin molecules of the parasite. Methanolic extracts of these herbs were fractionated (hexane, ethyl acetate, chloroform and methanol) and used in in vitro larvicidal studies. Based on the in vitro data, two herbal prototypes were developed and clinically tested. All the 5 ligand molecules showed better binding affnity for GDH and tubulin protein as compared with albendazole and shared similar binding site in the core of the GDH hexamer with slight variations. Albendazole approximately stacked against GLY190A residue, showing hydrophobic interactions with PRO157A and a Pi-cation electrostatic interaction with ARG390 along with four hydrogen bonds. Vincristine formed 2 pi-anionic electrostatic bonds with ASP158 of B and C subunits alongwith hydrogen bonding and hydrophobic interaction and an additional pi-anion electrostatic interaction at ASP158A for vinblastine. Albendazole bound to α-tubulin next to colchicine site whereas vinblastine is bound at the nearby laulimalide/peloruside site of the dimer. Betulinic acid showed lateral interaction between the H2-H3 loop of one alpha subunit and H10 of the adjacent alpha subunit of two tubulin dimers. Ursolic acid and palasonin bound at the intradimer N site of microtubulin involving the H1-H7 and H1-H2 zone, respectively. The in vitro studies demonstrated good dose dependent anthelmintic potential. Both the prototypes were quite efficacious in clearing the infection, keeping it to a minimal for more than 5 months, probably, through direct anthelmintic effect through GDH, tubulin depolymerization and uncoupling as well as indirectly through immunomodulation along with antioxidant and anti-inflammatory properties.

Vitex negundo protects against cerebral ischemia-reperfusion injury in mouse via attenuating behavioral deficits and oxidative damage.

Global cerebral ischemia/reperfusion (I-R) injury often results in an irreparable brain damage like behavioral impairment and neuronal death. This neurological complication involves diverse intricate pathological mechanisms like oxidative stress, inflammation, and apoptosis. Recently, the therapeutic value of plant-based polyphenols has gained researcher's attention. The present study focused on the putative neuroprotective role of negundoside on behavioral and oxidative stress status in an experimental model of global cerebral ischemia and reperfusion-induced brain injury. Negundoside was isolated from the leaves of Vitex negundo Linn. by chromatography for investigating its possible neurobehavioral and neuropharmacological implications. Healthy Balb/C mice of either sex were subjected to 10 min of global cerebral ischemia (GCI) followed by 24-h reperfusion. Mice were pre-treated intraperitoneally with negundoside at varying doses (1, 3, 5, 10, and 15 mg/kg) 60 min before the induction of GCI. Mice were later subjected to a battery of behavioral tests for evaluating memory-related and motor abilities. Elevated plus maze (EPM) was used to determine the anxiety levels and short-term memory whereas motor abilities were evaluated by inclined beam-walking test, rotarod, and lateral push test. TBARS and reduced glutathione (GSH) content in brains were analyzed spectrophotometrically as oxidative stress markers. Behavioral study revealed enhanced anxiety-related responses and motor deficits in I-R injured mice. Additionally, GSH and TBARS levels were found to be altered following I-R-induced neuronal injury. Contrastingly, negundoside administration was able to alleviate the behavioral and biochemical alterations to the normal levels. Together, our findings provide preliminary evidence of neuroprotective role of negundoside against global cerebral ischemia and reperfusion-induced behavioral dysfunction and oxidative damage in mice brain.

Phenols from Vitex negundo / 中成药

AIM To study the phenols from Vitex negundo Linn..METHODS The ethyl acetate fraction of 70％ ethanol extract from V.negundo was isolated and purified by silica,Sephadex LH-20 and ODS column,then the structures of obtained compounds were identified by spectral data.RESULTS Seven compounds were isolated and identified as luteolin-4'-O-β-D-glucopyranoside (1),isoorientin 6-O-caffeate (2),3,4,5-tricaffeoyl quinic acid (3),(+)-pinoresinol-4-O-β-D-glucoside (4),methyl isoferuloyl-7-(3,4-dihydroxyphenyl) lactate (5),benzyl 7-O-β-D-glucoside (6) and oresbiusin A (7).CONCLUSION All the compounds are isolated from this plant for the first time,and compounds 1,3,5-7 are first isolated from genus Vitex.

Anti-nephrotoxic activity of some medicinal plants from tribal rich pockets of Odisha.

BACKGROUND: Gentamicin, a strong cationic drug accumulated at biological membranes causes net increase in oxidative stress and lipid peroxidation leading to necrotic changes in renal tubles and consequently precipitates acute nephrotoxicity. Several phytoconstituents and plants extracts demonstrated significant anti-oxidant and cyto-protective activities. Vitex negundo Linn. (VN), Oroxylum indicum Vent. (OI) and Barringtonia acutangula Linn. (BA) are widely found throughout the Asian sub-continent including India, used extensively in different forms of Indian traditional medicine like Ayurveda and Unani. OBJECTIVE: Nephroprotective activity of extracts of VN roots, OI whole plant and BA leaves were investigated against experimentally induced acute nephrotoxicity [Gentamicin (i.p; 80mg/kg for 7 days)] in Wistar rats as test animals. MATERIALS AND METHODS: The rats were treated with Cystone (5 mL/kg; p.o) taken as positive control and methanol-dichloromethane (1:1) extracts of VN, OI and BA (200 mg/kg; p.o) as test drugs for 7 days. Following the said treatments, biochemical parameters of urine (volume, creatinine and lactate dehydrogenase (LDH)) and serum (urea, creatinine, albumin and total protein) were estimated. Renal anti-oxidant markers viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lipid peroxidation (LPO) in renal tissue were assayed. Tissue sections of kidneys from different groups were made and histopathological features were observed. RESULT: The extracts of VN, OI and BA significantly attenuated the nephrotoxicity by elevation of body weight, CAT, GPx and SOD or lowering urine LDH and creatinine, serum urea; serum creatinine and LPO respectively. Histopathological score of VN, OI and BA treated groups were 1+, 2+ and 2+ respectively against 4+ of the toxic group. CONCLUSION: The findings suggested the significant nephroprotection of VN roots followed by OI whole plant and BA leaves.