Ethnopharmacology-aided antiplasmodial evaluation of six selected plants used for malaria treatment in Nigeria.

ETHNOPHARMACOLOGICAL RELEVANCE: Sub - Saharan Africa has a high malaria burden and Nigeria accounts for majority of malaria cases worldwide. The aim of this study was to evaluate selected plants extracts used against malaria in Nigeria for antiplasmodial activity. MATERIALS AND METHODS: An ethnomedicinal based - approach by literature survey was used to identify plants used in the study. The parts of the plant used were collected and extracted with 70% v/v ethanol; a portion of each extract was used to prepare successive solvent and residual fractions. Chloroquine-sensitive (3D7) P. falciparum strain and human embryonic kidney cells (HEK293) were used for antiplasmodial and cytotoxicity screening respectively. Hemolysis assay was also carried out on red blood cells (RBCs). Test for in vivo efficacy of an active extract was conducted in a mouse model of established P. berghei ANKA-infection. RESULTS: A total of six plants; Andropogon schirensis, Celtis durandii, Chasmanthera dependens, Daniellia ogea, Icacina trichantha and Triumfetta cordifolia were selected and screened. Triumfetta cordifolia leaf extract was observed to display moderate in vitro antiplasmodial activity (IC50 = 48.09 µg/ml) and was non-toxic to HEK293 cells and erythrocytes. At a dose of 400 mg/kg, T. cordifolia significantly (p<0.001) suppressed parasitemia, significantly (p<0.001) inhibited RBC depletion and prolonged survival in infected mice. CONCLUSIONS: T. cordifolia ethanol extract possesses antiplasmodial efficacy and this is the first report of its kind on the plant. It is a potential candidate for further studies to identify its mechanism of action.

Alpha lipoic acid supplementation ameliorates the wrath of simulated tropical heat and humidity stress in male Murrah buffaloes.

A supplement which ameliorates temperature-humidity menace in food producing livestock is a prerequisite to develop climate smart agricultural packages. A study was conducted to investigate the heat stress ameliorative efficacy of alpha lipoic acid (ALA) in male Murrah water buffaloes (Bubalus bubalis). Eighteen animals (293.61 ± 4.66Kg Bwt) were randomly allocated into three groups (n = 6); NHSC (non-heat-stressed control), HS (heat-stressed) and HSLA (heat-stressed-supplemented with ALA@32 mg/kg Bwt orally) based on the temperature humidity index (THI) and ALA supplementation. HS and HSLA were exposed to simulated heat challenge in a climatically controlled chamber (40 °C) for 21 consecutive days, 6 h daily. Physiological responses viz. Respiration rate (RR), Pulse rate (PR) and Rectal temperature (RT) were recorded daily before and after heat exposure. Blood samples were collected at the end of heat exposure on days 1, 6, 11, 16, and 21 and on day 28 (7th day post exposure which is considered as recovery) for peripheral blood mononuclear cells (PBMCs) separation, followed by RNA and Protein extraction for Real time quantitative PCR and Western blot analysis respectively, of heat shock proteins (HSPs). Two-way repeated measure ANOVA was performed between groups at different experimental periods. RR (post exposure) in HS and HSLA was significantly higher (P < 0.05) than NHSC from day 1 onwards but HSLA varied significantly from the HS 8th day onwards. Post exposure RT and PR in both HS and HSLA varied (P < 0.05) from NHSC throughout the study; but between HS and HSLA, RT significantly varied on initial 2 days and last 6 days (from days 16 to 21). HSP70 mRNA expression significantly up regulated in high THI groups with respect to the low THI group throughout the experimental period. During chronic stress (days 16 and 21) HSP70 significantly (P < 0.05) increased in HS but not in HSLA (P > 0.05) with respect to NHSC. ALA supplementation up-regulates and sustains (P < 0.05) the expression of HSP90 in HSLA in comparison to the HS and NHSC. HSP105 expression was significantly up-regulated (P < 0.05) in HS on days 16 and 21 (during long-term exposure) but only on day 21 (P < 0.05) in HSLA. HSP70, HSP90, and HSP105 protein expression dynamics were akin to the mRNA transcript data between the study groups. In conclusion, supplementing ALA ameliorates the deleterious effect of heat stress as reflected by improved physiological and cellular responses. ALA supplementation improved cellular antioxidant status and sustained otherwise easily decaying heat shock responses which concertedly hasten the baton change from a limited window of thermo tolerance to long run acclimatization.

Protective effects of ethanolic extract of Nigella sativa seed in paracetamol induced acute hepatotoxicity in vivo.

Paracetamol overdose causes serious liver necrosis. Hepatoprotective activity of ethanolic extract of Nigella sativa in Paracetamol induced acute hepatotoxicity was investigated in rats. Fasted male Wistar rats were orally treated with Nigella sativa extract in graded doses for 5 days followed by Nigella sativa extract and paracetamol 3 g kg(-1) on 6 and 7th day. Circulatory liver markers and reduced glutathione (GSH) levels were estimated and histopathological study of liver performed. Paracetamol caused a significant increase in serum alkaline phosphatase, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and total Bilirubin and a significant decrease in GSH compared to control. Nigella sativa pretreatment significantly prevented the increase in liver enzymes and total bilirubin and decrease in GSH level as compared to paracetamol group. Liver histopathology showed marked reduction in sinusoidal dilatation, midzonal necrosis, portal triaditis and occasional apoptosis in Nigella sativa extract treated groups as compared to group receiving only paracetamol. Nigella sativa extract possesses hepatoprotective action against paracetamol induced acute hepatoxicity. Further research is needed to advocate its prophylactic use for drug induced hepatotoxicity.

Germination behaviour of seeds of Withania somnifera (L.) Dunal: a high value medicinal plant.

In order to evolve a quick method for smooth and optimum germination for Withania somnifera- a medicinally efficacious multipurpose plant, present investigation was carried to study the effect of physico-chemical treatments, storage, temperature, photoperiod and growth regulators (GA3, IAA, IBA, 2-4 D and BA) on germinability. The most effective treatment is GA3 at 150 µg/ml concentration at 25 °C. The optimal temperature for germination is 25 °C and continuous light favored germination showing that photoperiod has a significant role. The seedlings derived from seeds performed well when grown in a glasshouse. The data have implications for conservation and cultivation of the species studied.

An endophytic Neurospora sp. from Nothapodytes foetida producing camptothecin.

The medicinal plant, Nothapodytes foetida contains a number of important alkaloids like camptothecin (an anticancer drug molecule) but its concentration is less to meet the existing demand of this important molecule, so in an effort for accessible availability of camptothecin. An endophyte (designated ZP5SE) was isolated from the seed of Nothapodytes foetida and was examined as potential source of anticancer drug lead compound i.e. camptothecin, when grown in Sabouraud liquid culture media under shake flask conditions. The presence of anticancer compound (camptothecin) in this fungus was confirmed by chromatographic and spectroscopic methods in comparison with authentic camptothecin. Isolated endophyte (Neurospora crassa) producing camptothecin may become an easily accessible source for the production of precursor anticancer drug molecule in future at large scale.

Interaction of pentazocine with calcium channel blocking drugs during chemical and thermal pain in mice.

The present study was designed to investigate the antinociceptive interaction of a clinically used opioid, pentazocine which produces its analgesic effect mainly through kappa receptors, with some calcium channel blockers (CCBs, viz. Diltiazem, flunarizine, nimodipine and verapamil--each representing one chemical class) in formalin and tail flick tests in mice. All the CCBs, except verapamil, significantly inhibited the formalin-induced pain response in a dose-dependent manner. However, none of these drugs affected tail flick latency at any of the studied doses. Pentazocine showed a significant antinociceptive response in both pain models, although a high dose was required to increase the tail flick latency. Pretreatment with all CCBs, individually enhanced the analgesic effect of pentazocine in both formalin and tail flick tests. In the latter test of nociception, a per se ineffective dose of pentazocine, showed a significant analgesic response in presence of CCB dose which itself was not effective in the test. Chronic concomitant administration of diltiazem with pentazocine did not prevent the development of tolerance to the opioid compound. However, diltiazem when given in combination with pentazocine to pentazocine-tolerant animals, it effectively reversed the tolerance. Results of the study thus suggest that concomitant treatment with CCBs, irrespective of their chemical nature, not only potentiate the antinociceptive effect of pentazocine in opioid naive animals in both tonic and acute nociceptive tests but also reverse the pentazocine tolerance.

Enteroclysis-guided fine-needle aspiration cytology of focal small-bowel lesions.

PURPOSE: To study the role of enteroclysis-guided percutaneous fine-needle aspiration cytology (FNAC) of focal small-bowel lesions. MATERIAL AND METHODS: Twenty patients with non-palpable circumscribed small-bowel lesions found on enteroclysis underwent FNAC after confirmation of needle position under fluoroscopy. RESULTS: Positive diagnosis was obtained in 18 (90%) of the patients. Thirteen patients with positive FNAC and one with inconclusive cytology underwent surgery. In all, the cytological diagnosis was confirmed by histopathology. No complications were seen. CONCLUSION: Enteroclysis-guided FNAC of focal small-bowel lesions is a safe and accurate diagnostic method.

An evaluation of total parenteral nutrition using Vamin and Aminosyn as protein base in critically ill preterm infants.

A total of 75 preterm infants with gestation less than 32 wk received total parenteral nutrition (TPN) using Vamin and Aminosyn as protein base lasting more than 20 days. They were monitored for signs of liver dysfunction, cholestatic jaundice, and TPN-induced metabolic bone disease (osteopenia of prematurity). It was observed that severity of TPN-induced cholestasis depends on the duration of TPN and quantity of protein infused. When used as a protein base, Vamin seemed to be superior to Aminosyn. TPN-induced metabolic bone disease was strongly correlated to the duration of TPN. We suggest close monitoring of critically ill preterm infants on TPN for quantity of protein infusate, liver dysfunction, cholestatic jaundice, and TPN-induced metabolic bone disease. Intravenous protein intake should be limited to less than 2.5 g/kg/day in preterm infants with gestation less than 32 wk.