The role of Kolaviron, a bioflavonoid from Garcinia kola, in the management of cardiovascular diseases: A systematic review.

While the cardiovascular effects of Kolaviron (KV) and Garcinia kola (GK) are documented in the literature, a thorough search through literature revealed a fragmentation of information on the effect of KV and GK on cardiovascular diseases (CVDs). This systematic review aims to evaluate and summarize preclinical or clinical evidence on the effect of KV and GK on CVDs. Using the PRISMA guidelines, a systematic literature search was conducted in five medical databases (PubMed, Cochrane, EMBASE, CINAHL, and Web of Science). Inclusion criteria included both in vivo and in vitro studies related to CVDs. Eligible studies included those in which specific clinical parameters, CVD biomarkers, or voltage-gated channel effects were reported. The quality of the included studies was assessed using a modified Collaborative Approach to Meta-Analysis and Review of Animal Data from the Experimental Studies (CAMARADE) checklist. A total of 22 studies were included in this systematic review. The median and mean values of the included studies' quality scores were 6 and 5.864 ± 0.296, respectively. The results from the quality assessment of included studies validate their suitability, usefulness, and fit. Based on this systematic review, the effect of KV and GK on CVDs can be divided into eight emerging trends: (1) Anti-hypertensive/Blood pressure lowering effect; (2) Lipid profile improvement effect (3) Anti-atherosclerotic effect; (4) Anti-thrombotic effect; (5) Cardioprotection; (6) Vasodilatory effect; (7) Antioxidant effects; and (8) Genetic expression and therapeutic target for cardiovascular dysfunction. From this systematic review, it can be concluded that KV is helpful in managing CVD risk factors such as hypertension and high lipids/cholesterol. Several included studies in this review demonstrated the antihypertensive, lipid improvement, antioxidant, and signaling pathway modulation effects of KV. This potentially makes KV a good therapeutic target for the management of CVDs.

Ninety-day oral toxicological profiling of Kolaviron (an extract of Garcinia kola) in male and female rats.

There remains an insufficiency of data on the long-term toxicological profile of Garcinia kola Heckel and its extract, Kolaviron (KV), despite several studies on its pharmacological effects. This research was designed to investigate the long-term histopathological, hematological, biochemical, hormonal, reproductive, and oxidative effects of 90 days administration of KV to male and female rats, as well as additional 30 days reversibility study to assess the potential for reversal of induced effects. Fifty-six male and female Wistar rats divided into four groups were treated orally with distilled water/propylene glycol, 20 mg/kg KV, 100 mg/kg KV, and 500 mg/kg KV for 90 days. At the end of 90 days and 30 additional days of reversibility study, 5 ml blood was collected from animals for relevant analyses. Vital organs were harvested for histopathological assessments. In this study, KV did not elicit any adverse effect on histopathological presentations of vital organs which were generally non-abnormal. There was significant increase (p < 0.05) in LEU, MON, EOS%, BAS%, HCT (male animals) and LYM%, EOS%, BAS%, RBC, hemoglobin and MCH (female animals). There was significant diminution (p < 0.05) in cholesterol, triglycerides, LDL, and VLDL levels, with significant increase (p < 0.05) in HDL level in both male and female animals. KV elicited a non-significant increase in sperm count accompanied by a significant increase (p < 0.05) in levels of Follicle stimulating hormone (FSH) and testosterone in male rats. Furthermore, KV elicited significant (p < 0.001-0.05) elevation in the levels of GSH, SOD and CAT, and diminution in the level of MDA. The findings in this study suggest that long-term administration of KV is considerably safe with some variations in response between male and female animals. The possible sustenance of observed effects after cessation of KV administration, lipid lowering, erythropoiesis inducing, and immune system boosting activities of KV were confirmed in this study.

Ameliorative effect of Kolaviron, an extract of Garcinia kola seeds, on induced hypertension.

OBJECTIVES: Early diagnosis and management of known cardiovascular disease risk attributes such as hypertension lessens morbidity and mortality as well as increase quality of life of patients. This present study was modelled to investigate the ameliorative effect of Kolaviron, an extract of Garcinia kola Heckel seeds, in ethanol- and sucrose-induced hypertension. METHODS: Test animals were divided into six groups of six animals each for each hypertensive model. Animals were treated daily with distilled water (10 ml/kg); 35% ethanol (3 g/kg) or sucrose (5-7%); Kolaviron (50, 100 and 200 mg/kg) separately plus ethanol or sucrose and Amlodipine (0.14 mg/kg) separately plus ethanol or sucrose for 8 weeks. Systolic, diastolic and mean arterial pressures were determined using non-invasive BP system after 8 weeks. Blood was obtained for the assessment of biochemical parameters, lipid profile and antioxidant indices. Vital organs were collected for approximation of tissue antioxidant levels. RESULTS: Results show that Kolaviron at various doses and Amlodipine significantly reduced (p<0.05-0.001) the elevated systolic, diastolic, and mean arterial pressures produced by ethanol and sucrose administration. Additionally, Kolaviron and Amlodipine significantly overturned (p<0.05-0.001) the reduction in GSH, SOD and CAT, and elevation in MDA levels elicited by ethanol and sucrose. Furthermore, Kolaviron and Amlodipine produced significant reduction (p<0.001) in levels of cholesterol, triglycerides and low-density lipoproteins, as well as significant increase (p<0.01-0.001) in levels of high-density lipoproteins. CONCLUSIONS: Results from this study demonstrate that Kolaviron possibly possesses significant antihypertensive effect which may possibly be attributed to its antioxidant effects and relative improvement of lipid profile.

COVID-19 Pandemic: A Case for Phytomedicines.

Coronavirus disease 2019 (COVID-19) is an infection caused by a newly discovered coronavirus which was identified in Wuhan, China. The race is on globally to repurpose drugs for COVID-19 and develop a safe and effective vaccine against the disease. There is an urgent need to search for effective remedies against COVID-19 from the rich and extensive flora of Africa and the world. A literature search was conducted to obtain information on drugs with the potential for effectiveness in the treatment of COVID-19 based mostly on outcomes of preclinical studies and a few clinical investigations. This was considered important to this perspective as some of the identified mechanisms of action may be related to potential anti-COVID-19 actions of phytomedicines. The findings from the literature search were also used to establish the need for exploration of phytomedicines in the fight against COVID-19. This perspective identifies the need to preserve the rich tradition of herbal medicine in Africa, repositioning it by inculcating all aspects of discovery, development, and chemical evaluation of pharmaceuticals from medicinal plants for effective management of prevalent diseases. The identified mechanisms of action of current drugs under consideration for the treatment of COVID-19 include preventing fusion of SARS-CoV-2 with human cells; decrease acidity in endosomes, cell membrane-derived vesicles for transportation of the virus within the host cell and within which the virus can replicate; and blockade of the production of proinflammatory cytokines. Phytomedicines may possibly elicit either one or a combination of these effects. The case for the exploration of phytomedicines against COVID-19 is strengthened by the emergence of a number of conventional drugs from medicinal plants and the emergence of botanicals with proven efficacy for some medical conditions. Caution against indiscriminate use of medicinal plants in the guise of treating COVID-19 has been highlighted and the need for reliable preclinical and clinical studies.

Anxiolytic- and antidepressant-like activities of hydroethanol leaf extract of Newbouldia laevis (P.Beauv.) Seem. (Bignoniaceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Newbouldia laevis (Bignoniaceae) is a woody tropical plant commonly found in southwest Nigeria. Ethnobotanical survey and literature revealed its application in the management of CNS disorders e.g. psychosis, insomnia, convulsions and associated anxiety and depression. This study evaluated the anxiolytic and antidepressant activities of the hydroethanol leaf extract of N. laevis in mice. MATERIALS AND METHODS: The hole-board (HBT), elevated plus maze (EPMT), light/dark exploration (LDET), open field (OFT), social interaction (SIT) (anxiolytic activity), forced swim (FST) and tail suspension (TST) (antidepressant property) tests were employed in this investigation. Mice randomly allotted to different groups were treated orally with distilled water (10 ml/kg), diazepam (1 and 3 mg/kg), imipramine (20 mg/kg) and N. laevis (25-200 mg/kg). The mice were subjected to the various tests 60 min post-treatment. RESULTS: In the HBT, N. laevis (25 and 100 mg/kg) increased the number of sectional crossings significantly (p < 0.05). In the OFT, N. laevis (25-200 mg/kg) increased the number of general square crossings, centre square crossings, rearings and assisted rearings (p < 0.05). In the EPMT, the extract (25 and 50 mg/kg) increased the open arms time spent, number of head dips and entry (p < 0.05). In the LDET, N. laevis increased the number of transitions at 100 and 200 mg/kg (p < 0.05). For the SIT, N. laevis (25 and 200 mg/kg) increased the frequency and duration of interaction respectively (p < 0.05). In the FST and TST, N. laevis (25-200 mg/kg) increased the latency and reduced the total duration of immobility (p < 0.05). The effect of the extract on duration of immobility was significantly reversed by sulpiride (Dopamine D2 receptor antagonist). CONCLUSION: The hydroethanol leaf extract of N. laevis possesses anxiolytic- and antidepressant-like activities, the later possibly mediated by dopaminergic enhancement(s).

Investigation of Antidepressant, Anxiolytic and Sedative Activities of the Aqueous Leaf Extract of Musa sapientum Linn. (Banana; Musaceae).

BACKGROUND: Musa sapientum Linn. (Musaceae) is used in traditional African medicine in the management of mental disorders. This study was conducted to evaluate the central nervous system activities of the aqueous leaf extract of M. sapientum (MS). MATERIALS AND METHODS: MS (50, 100 and 200 mg/kg, p.o.) was administered to separate groups of mice 1 h before behavioural studies. The antidepressant effect was studied using the forced swimming test (FST) and tail suspension test (TST) while the elevated plus maze (EPM) and the hole-board tests were used to evaluate the anxiolytic effect. The probable mechanism of antidepressant-like effect was also investigated. RESULTS: MS (50, 100 and 200 mg/kg) produced significant (P<0.0001) reduction in the duration of immobility with peak effect at 200 mg/kg (79.6%) in FST and 66.9 % in TST respectively when compared with control. The pre-treatment of mice with prazosin (α1-adrenoceptor antagonist, 62.5 µg/kg, i.p.) and sulpiride (dopamine D2 receptor antagonist, 50 mg/kg, i.p.) significantly prevented the antidepressant effect produced by MS in FST. However, pre-treatment of mice with metergoline (5-HT2 receptor antagonist, 4 mg/kg, i.p.) and yohimbine (α2-adrenoceptor antagonist, 1 mg/kg, i.p.) did not prevent the antidepressant effect of MS. In the EPM test, MS did not significantly increase open arm exploration. It also did not significantly increase the number of head dips in the hole-board test. CONCLUSIONS: Results showed that MS had antidepressant activity possibly mediated through α1-adrenergic and D2 dopaminergic receptors, without significant anxiolytic effect.

Protective effect of carvedilol alone and coadministered with diltiazem and prednisolone on doxorubicin and 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats.

This study investigated the protective effects of carvedilol alone and coadministered with prednisolone and diltiazem on doxorubicin (DOX) and 5-fluorouracil (5-FU)-induced toxicity. Each of 2 pools of 70 female rats were randomly allotted into 10 groups of 7 animals each and treated as follows: Group 1: normal saline (10 mL/kg); Group 2: normal saline and DOX (40 mg/kg)/5-FU (20 mg/kg) alone; Group 3: gallic acid (200 mg/kg) and DOX/5-FU; Group 4: carvedilol (0.075 mg/kg) and DOX/5-FU; Group 5: carvedilol (0.15 mg/kg) and DOX/5-FU; Group 6: carvedilol (0.30 mg/kg) and DOX/5-FU; Group 7: diltiazem (3.43 mg/kg) and DOX/5-FU; Group 8: diltiazem (3.43 mg/kg), carvedilol (0.15 mg/kg), and DOX/5-FU; Group 9: prednisolone (0.57 mg/kg) and DOX/5-FU; and Group 10: prednisolone (0.57 mg/kg), carvedilol (0.15 mg/kg), and DOX/5-FU. Treatments were done p.o. for 16/14 days for the DOX/5-FU models. DOX/5-FU was administered i.p. to the rats in Groups 2-10 on day 14/10-14. On day 17/15 (DOX/5-FU), blood samples were collected, and liver and kidneys of rats were harvested for antioxidant and histopathological assessments. Carvedilol alone and coadministered with prednisolone significantly (P < .05) decreased alanine aminotransferase level compared with administration of DOX alone. Carvedilol alone and coadministered with diltiazem significantly (P < .05) decreased creatinine level compared with administration of DOX/5-FU alone. Carvedilol alone and coadministered with diltiazem and prednisolone significantly (P < .05) increased the level of hepatic superoxide dismutase and catalase, and decreased malondialdehyde compared with DOX administration alone. Histopathological observations correlated with results of biochemical and antioxidant analyses. Carvedilol administered alone and coadministered with diltiazem and prednisolone reduced the effect of DOX/5-FU-induced hepatic and renal toxicities due to enhanced in vivo antioxidant activity. The protective effect was more prominent in the doxorubicin model compared with the 5-fluorouracil test. Coadministration of carvedilol with either diltiazem or prednisolone did not show better protection relative to carvedilol alone.

Sub-Chronic Toxicity of the Hydroethanolic Leaf Extract of Telfairia occidentalis Hook. f. (Cucurbitaceae) in Male Rats.

Background: Due to its nutritional and medicinal values, the leaf of Telfairia occidentalis Hook f. (Cucurbitaceae) is consumed in different parts of Nigeria. Acute and sub-chronic toxicity of the hydroethanolic leaf extract of Telfairiaoccidentalis were investigated in this study. Methods: Sixty-four male rats were randomized into four different groups of 16 animals each and were separately administered 80, 400 and 2000 mg/kg T. occidentalis orally (p.o.) for 60 days. Animals were sacrificed and blood samples were collected for hematological and biochemical analyses. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: A significant (p < 0.05) reduction in weight of the testes, compared to the control group, was observed in the group treated with 2000 mg/kg extract. No significant change was observed in the weight of other vital organs relative to the control group. There were significant (p < 0.01) increases in sperm motility and count in the group administered 80 mg/kg extract and significant (p < 0.001) reductions in both parameters at 2000 mg/kg. There were significant increases in the levels of hemoglobin and packed cell volume at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, significant reductions in aspartate aminotransferase and alanine aminotransferase levels at doses of 400 and 2000 mg/kg relative to control were observed. Compared to control, the extract significantly reduced (p < 0.05) the level of total cholesterol (400 mg/kg) and caused a significant increase in the level of high-density lipoprotein (80, 400 and 2000 mg/kg). Significant (p < 0.05) increase in the level of malondialdehyde, decrease in superoxide dismutase level and histopathological abnormalities were observed in the testes at 2000 mg/kg. Upon cessation of treatment with T. occidentalis for 30 days, the observed effects were reversed. Conclusions: The findings showed that the hydroethanolic leaf extract of Telfairia occidentalis is relatively non-toxic on acute and sub-chronic exposures at low to moderate doses, with the potential to elicit anti-anemic effects, reduce the risk of atherosclerosis and cardiovascular disease, and enhance antioxidant status in the brain and liver. Although possibly beneficial at low to moderate doses, the extract could be harmful to the testes with prolonged oral exposure at high dose.

Methionine and vitamin B-complex ameliorate antitubercular drugs-induced toxicity in exposed patients.

Tuberculosis therapy utilizes drugs that while effective cause treatment-related toxicity. Modulation of antitubercular drugs-induced toxicity by methionine and vitamin B-complex in patients was evaluated. 285 treatment-naïve tuberculosis patients at the Chest Clinics of Infectious Diseases Hospital, Yaba and General Hospital, Lagos in Lagos, Nigeria was prospectively recruited and allotted into test (antitubercular medicines, methionine and vitamin B-complex) and control groups (antitubercular medicines). Data on adverse drug reactions and blood samples were collected at initiation, 2 months and 6 months, and then analyzed. Red blood cells and packed cell volume were significantly higher (P < 0.05) in the test group compared to control at 6 months of therapy. At the end of 2 months, results showed a significant decrease (P < 0.001) in aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, urea, creatinine and total bilirubin in the test group compared to control. Reduced glutathione and superoxide dismutase were significantly increased (P < 0.001) and malondialdehyde significantly decreased (P < 0.001) in the test versus control groups at the end of 2 and 6 months. Adverse drug reactions were significantly lower (P < 0.001) in the test group (32.4%) compared to control group (56.2%), with 1 death. Hepatotoxicity was significantly higher (P = 0.026) in control (6.9%), compared to test group (0%). Alcohol and cigarette smoking were significantly (P = 0.019 and P = 0.027) associated with the occurrence of adverse drug reactions. Methionine and vitamin B-complex modulated hepatic, renal, hematological, antioxidant indices and adverse effects in patients administered antitubercular medicines. Such interventions can enhance compliance and better treatment outcomes in tuberculosis patients.

Antidiarrhoeal activity of aqueous leaf extract of Caladium bicolor (Araceae) and its possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Caladium bicolor (Araceae) is a horticulture plant also used by some traditional medicine practitioners in the treatment of diarrhoea and other gastrointestinal disorders. This study was conducted to evaluate the antidiarrhoeal activity of the aqueous leaf extract of C. bicolor and its possible mechanisms of action in rodents. MATERIALS AND METHODS: Normal and castor oil-induced intestinal transit and castor oil-induced diarrhoea tests were carried out in mice while gastric emptying and enteropooling tests were conducted in rats following the administration of distilled water (10 ml/kg, p.o.), C. bicolor extract (1-50mg/kg, p.o.) and loperamide (5mg/kg, p.o.). The probable mechanisms of action of C. bicolor was investigated following pre-treatment with yohimbine (10mg/kg, s.c.; α2-adrenoceptor antagonist), pilocarpine (1mg/kg, s.c.; non-selective muscarinic receptor agonist), prazosin (1mg/kg, s.c.; α1-adrenoceptor antagonist) and propranolol (1mg/kg, i.p.; non-selective ß-adrenoceptor antagonist) 15 min prior to administration of C. bicolor extract (50mg/kg, p.o.). After 30 min of pre-treatment with these drugs, the mice were subjected to the castor oil-induced intestinal transit test. RESULTS: C. bicolor extract did not produce significant (p>0.05) effect on normal intestinal transit unlike loperamide which caused significant (p<0.001) inhibition (61.57%). The extract caused significant (p<0.001) dose-dependent inhibition of castor oil-induced intestinal transit with peak effect, 100% inhibition, elicited at the dose of 50mg/kg compared to 86.97% inhibition for loperamide. Yohimbine and pilocarpine most significantly (p<0.001) reversed this effect of the extract. In the castor oil-induced diarrhoea test, the extract (1mg/kg) and loperamide significantly (p<0.05, 0.01) delayed the onset of diarrhoea. For diarrhoea score, the extract (1 and 50mg/kg) inhibited diarrhoea development (47.53% and 43.83% inhibition, respectively) like loperamide (5mg/kg; 54.94%). The in vivo antidiarrhoeal index of the extract at 1 and 50mg/kg was 50.07% and 42.81% respectively compared to 58.15% for loperamide. CONCLUSIONS: The results obtained in this study suggest that the aqueous leaf extract of C. bicolor possess antidiarrhoeal activity due to its anti-motility effect possibly via antagonist action on intestinal muscarinic receptors and agonist action on intestinal α2-adrenoceptors. This justifies the use of the extract in traditional medicine for the treatment of diarrhoea.

Hypoglycemic, antilipidemic and antioxidant effects of valproic acid in alloxan-induced diabetic rats.

This study was designed to investigate the hypoglycemic, antilipidemic and antioxidant effects of valproic acid (VA) in alloxan-induced diabetic rats. VA (100, 300 and 600mg/kg p.o.) and insulin (17IU/kg s.c.) were administered once daily for 21 days. Fasting blood glucose level was determined at 7 days interval. On day 21, blood samples were collected for assay of serum biochemical parameters (total protein, creatinine, urea, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL), and low density lipoprotein (LDL)). Kidneys and livers were harvested for antioxidant indices and histopathological examination. In diabetic rats, VA produced a dose and day-dependent reduction in glucose level. Peak effect (52.79% reduction; P<0.001) was produced at the dose of 600mg/kg on day 21. In normoglycemic rats, VA (600mg/kg) caused significant reduction (P<0.05) in blood glucose level on days 1 and 21 with 16.38% and 15.63% reductions respectively. In diabetic rats, VA significantly reduced the level of catalase (CAT) and malondialdehyde (MDA) in the kidney, and increased the level of superoxide dismutase, CAT and glutathione peroxidase with reduction in MDA in the liver compared to diabetic control, especially at the dose of 600mg/kg. VA (600mg/kg) generally increased the level of HDL and reduced the levels of TG, LDL, TC, AST, ALT, ALP, bilirubin, creatinine and urea compared with diabetic control. The findings in this study suggest that VA possess beneficial antidiabetic effects.

In Vitro and In Vivo Anticancer Activity of Root Extracts of Sansevieria liberica Gerome and Labroy (Agavaceae).

Introduction. Sansevieria liberica Gerome and Labroy (Agavaceae) is a perennial plant widely distributed in tropical Africa. Preparations of the plant are commonly used across Nigeria for the treatment of inflammatory conditions. Based on the fact that herbal medicine is a strong component of integrative medicine, this study was conducted to evaluate the anticancer activity of root extracts of Sansevieria liberica. Methods. Sulforhodamine B (SRB) in vitro cytotoxicity assay, Sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used in this study. Results. SL-A002 (IC50 23 µg/mL with HeLa), SL-A003 (IC50 22 µg/mL with HCT-116), and SL-A004 (IC50 23 and 18 µg/mL with A549 and THP-1, resp.) demonstrated significant activity in the SRB cytotoxicity assay. Potency was highest with the following pairs of extract : cancer cell line: SL-A002 : HeLa (IC50 23 µg/mL), SL-A003 : HCT-116 (IC50 22 µg/mL), and SL-A004 : THP-1 (IC50 18 µg/mL). SL-A002 demonstrated significant dose-dependent antitumor activity in the Sarcoma-180 (S-180) ascites model with peak effect produced at the dose of 120 mg/kg (i.p.) with inhibition of 89.36% compared to 97.96% for 5-FU (20 mg/kg i.p.). The inhibition of tumor growth by SL-A002 in the S-180 solid tumor model was 47.40% compared to a value of 50.18% for 5-FU. SL-A002 was also significantly active in the L1210 lymphoid leukemia model with 158.33% increase in mean survival time, the same value for 5-FU. Conclusions. The hydroethanolic extract of Sansevieria liberica, SL-A002, possesses significant anticancer activity to warrant further extensive study to identify, isolate, and characterize the specific bioactive molecules responsible for the observed antitumor activity and the precise mechanism(s) of action.

90 Days toxicological assessment of hydroethanolic leaf extract of Ipomoea asarifolia (Desr.) Roem. and Schult. (Convolvulaceae) in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoea asarifolia (Convolvulacae), commonly known as "morning glory" is found across West Africa. Preparations of the plant are used traditionally for the treatment of diverse ailments including diabetes, neuralgia, arthritic pain and stomach ache. This study was designed to assess the safety profile of the hydroethanolic leaf extract of I. asarifolia through a 90-day subchronic toxicity study in rats. MATERIALS AND METHODS: I. asarifolia was administered p.o. at doses of 40, 200 and 1000mg/kg to separate groups of rats for 90 days. Distilled water was given p.o. to rats in the control group. Some set of rats in each group were left for additional 30 days without administration of the extract for reversibility study. Animals were weighed weekly and relevant parameters were assayed at the end of the main and reversibility study periods. RESULTS: There was no significant change (p>0.05) in the body weight of rats, and food and water intake in I. asarifolia treated groups compared with control. I. asarifolia (40-1000 mg/kg) significantly but reversibly reduced (p<0.05, 0.001) sperm motility and count. The extract did not generally cause significant change (p>0.05) in the weight of vital organs and haematological parameters except in the case of reversible reduction in the level of haemoglobin and red blood cell count (p<0.01; 40 mg/kg). The level of biochemical parameters and electrolytes were not significantly changed (p>0.05) except for the reversible reduction in the level of aspartate aminotransferase (AST; p<0.0001; 200 and 1000 mg/kg) and increase in the level of Na(+) (p<0.01; 200 mg/kg). The level of kidney reduced glutathione (GSH) was reversibly increased (p<0.01; 1000 mg/kg) while the level of enzymatic and non-enzymatic in vivo antioxidants was generally comparable and not significantly different (p>0.05) from control in respect of all other vital organs. Histological presentations were generally normal in respect of the liver, kidneys, brain, heart, lungs, pancreas, spleen and testes. CONCLUSIONS: The findings in this study suggest that the hydroethanolic leaf extract of I. asarifolia is relatively safe administered orally for an extended period with potential renal in vivo antioxidant activities. However, the extract may cause reversible male sterility, anaemia and hypernatraemia.

Anticancer activity of the phytomedicine DAS-77.

This study was designed to investigate the anticancer activity of extracts of the phytomedicine DAS-77. The sulforhodamine B (SRB) in vitro cytotoxicity assay, Sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were employed. DAS-A001 (ethanol extract, IC50 12 and 13 µg/mL with HCT-116 and PC3, respectively); DAS-A002 (hydroethanol extract, IC50 <5 and 13 µg/mL with HCT-116 and PC3, respectively); DAS-A003 (aqueous extract, IC50 <5 µg/mL with THP-1); and DAS-A004 (dichloromethane:methanol extract; IC50 <5 and 17 µg/mL with HCT-116 and PC3, respectively) demonstrated significant activity in vitro. DAS-A002 and DAS-A003 (80-120 mg/kg) elicited significant (P < .05-.001) dose-dependent inhibition of tumor growth in the S-180 ascites model. Peak effects were produced at the highest dose of 120 mg/kg with inhibition values of 87.50% and 89.23% for DAS-A002 and DAS-A003, respectively, compared with a value of 97.27% for 5-FU (20 mg/kg). As regards the S-180 solid tumor model, inhibition of tumor growth was found to be 52.56% and 37.95%, respectively, for DAS-A002 and DAS-A003. The effect of DAS-A002 was comparable and not significantly different (P > .05) from that of 5-FU (20 mg/kg; 50.18% inhibition). DAS-A003 but not DAS-A002 showed significant activity in the leukemia model with 177.78% increase in mean survival time relative to 211.11% for 5-FU. Findings in this study suggest that the hydroethanol and aqueous extracts of DAS-77 possess significant anticancer activity.

Evaluation of neuropharmacological effects of aqueous leaf extract of Albizia glaberrima (Leguminosae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Albizia glaberrima is a shrub found in the deciduous forest and jungle of the coastal plain of West Africa. Preparations of the plant are used traditionally in the treatment of fever, pain and central nervous system disorders, including epilepsy. This study was conducted to investigate the neuropharmacological effects of the aqueous leaf extract of Albizia glaberrima in mice. MATERIALS AND METHODS: The hole-board, elevated plus-maze, thiopentone-induced sleep (anxiolytic/sedative-hypnotic), traction, climbing, inclined screen (muscle relaxant), strychnine-, picrotoxin- and pentylenetetrazole (PTZ)-induced convulsion (anticonvulsant) tests were employed in this study. RESULTS: Albizia glaberrima extract at 200mg/kg significantly increased the duration of head dips (p<0.05) and number of open arms entry (p<0.01) compared with control in the hole-board and elevated plus-maze tests, respectively. At 400mg/kg, Albizia glaberrima extract significantly reduced the number of sectional crossings relative to control. The extract at 400mg/kg significantly (p<0.05) increased the duration of sleep compared with control in the thiopentone-induced hypnosis test. Albizia glaberrima extract at 200mg/kg and diazepam (5mg/kg) significantly (p<0.05, 0.01) increased the post-treatment climbing time and reduced the latency to slide down in the climbing and inclined screen tests, respectively. The extract was not effective in the strychnine-induced seizure model, while in the picrotoxin test Albizia glaberrima extract at 100mg/kg significantly (p<0.05) reduced the duration of convulsion while reducing mortality at 400mg/kg, as was the case with diazepam (2mg/kg). The extract and diazepam significantly (p<0.01, 0.001) increased onset and reduced duration of convulsion, with significant level of protection against convulsion and reduction in mortality in the PTZ-induced seizure model. Preliminary phytochemical screening of the extract revealed the presence of phenols>tannins>saponins>flavonoids. The extract was found to be relatively non-toxic when administered p.o. up to 5000mg/kg and the LD50 was 398.11mg/kg when administered i.p. CONCLUSIONS: The aqueous leaf extract of Albizia glaberrima possesses dose-dependent anxiolytic/muscle relaxant (low dose) and sedative-hypnotic/anticonvulsant (high dose) activities possibly mediated via enhancement of GABAergic inhibitory actions.

Ameliorative Effect of Hydroethanolic Leaf Extract of Byrsocarpus coccineus in Alcohol- and Sucrose-Induced Hypertension in Rats.

Hypertension remains a major health problem worldwide considering the prevalence of morbidity and mortality. Plants remain a reliable source of efficacious and better tolerated drugs and botanicals. This study was designed to investigate the effect of the chemo-profiled hydroethanolic leaf extract of Byrsocarpus coccineus in ethanol- and sucrose-induced hypertension. Groups of rats were treated orally (p.o.) with distilled water (10 ml/kg), ethanol (35%; 3 g/kg), sucrose (5-7%), and B. coccineus (100, 200, and 400 mg/kg), and nifedipine together with ethanol and sucrose separately for 8 weeks. At the end of the treatment period, blood pressure and heart rate of rats were determined. Blood was collected for serum biochemical parameters and lipid profile assessment, and the liver, aorta, kidney, and heart were harvested for estimation of in vivo antioxidants and malondialdehyde (MDA). Results obtained in this study showed that B. coccineus at the various doses administered reduced the systolic, diastolic, and arterial blood pressure elevated by ethanol and sucrose. Also, the extract reversed the reduction in catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) induced by ethanol and sucrose. The level of MDA was reduced compared to the ethanol- and sucrose-induced hypertensive group. With respect to lipid profile, administration of B. coccineus at the various doses reduced the levels of triglycerides, low-density lipoprotein (LDL), cholesterol, and atherogenic indices, compared to the ethanol and sucrose groups. In conclusion the hydroethanolic leaf extract of B. coccineus exerted significant antihypertensive effect and this is probably related to the antioxidant property and improvement of lipid profile observed in this study.

Antinociceptive and anti-inflammatory activities of ethanolic extract of Alafia barteri

This study analyzes the antinociceptive and anti-inflammatory properties of ethanolic leaf extract of Alafia barteri Oliv., Apocynaceae, based on its medicinal use in the treatment of toothaches, inflammation and fevers. The antinociceptive effect was assessed in mice using acetic acid-induced writhing, tail clip, tail immersion and formalin assays. Anti-inflammatory activity was evaluated on carrageenan-induced paw oedema in rats, and xylene-induced ear oedema in mice. In acetic acid-induced writhing test, the extract at different doses (50, 100 and 200 mg/kg, p.o.) significantly (p < 0.05) and dose-dependently reduced pain by 35.04, 56.49 and 84.25%, respectively. The extract also significantly inhibited both the early and late phases of formalin-induced nociception in mice. In the tail immersion test, the extract caused a significant inhibition of pain (34.43% inhibition, after 90 min) at a dose of 200 mg/kg, while the effect of the extract in the tail clip test was only significant at the 100 mg/kg dose. A. barteri caused a significant inhibition of paw oedema development in the carrageenan and xylene-induced oedema tests. There was no mortality recorded following treatment with the extract (5 g/kg, p.o.). The results support the traditional use of A. barteri in the treatment of various diseases associated with pain and inflammation.

Hepatoprotective and in vivo antioxidant activities of the hydroethanolic leaf extract of Mucuna pruriens (Fabaceae) in antitubercular drugs and alcohol models.

AIM: Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity assays in rats. METHOD: In each of the models used, seven groups were allotted. The different groups received normal saline (10 mL·kg(-1), p.o.); hepatotoxicant (isoniazid-rifampicin, INH-RIF, 100 mg·kg(-1), i.p. or 20% ethanol 5 g·kg(-1), p.o.) and normal saline (10 mL·kg(-1), p.o.); hepatotoxicant and extract at doses of 100, 200, and 400 mg·kg(-1) p.o.; hepatotoxicant and silymarin 50 mg·kg(-1) p.o.; and extract at 400 mg·kg(-1) p.o. On the 21(st) day of treatment, blood was collected for assessment of serum biochemical parameters and harvested liver samples were assessed for antioxidants. RESULTS: The hepatotoxicants significantly (P < 0.05-0.001) increased the levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin, and malondialdehyde (MDA); and reduced the levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione GSH compared to control. M. pruriens significantly reversed (P < 0.05-0.001) the elevation in the level of ALT, AST, ALP, and bilirubin caused by the hepatotoxicants. The extract (200 and 400 mg·kg(-1)) significantly reversed (P < 0.05) the diminution in the level of in vivo antioxidants and increased the level of MDA produced by INH-RIF. M. pruriens (100-400 mg·kg(-1)) elicited significant reduction (P < 0.001) in the level of MDA compared to the alcohol group. Silymarin also reversed the deleterious effects of the hepatotoxicants. CONCLUSION: The hydroethanolic extract of Mucuna pruriens leaves possesses hepatoprotective activity with enhancement of in vivo antioxidants as a possible mechanism of action.