Anti-apoptotic and antioxidant mechanisms may underlie the abrogative potential of Ocimum gratissimum Linn. Leaf extract and fractions against trastuzumab-induced cardiotoxicity in Wistar rats.

Clinical use of trastuzumab (TZM), has been widely associated with increased incidence of cardiotoxicity. Ocimum gratissimum Linn. is a household medicinal plant popularly used for treating inflammatory conditions. In this study, we investigated the abrogative potential of 100 mg/kg/day of the ethanol leaf extract of Ocimum gratissimum Linn. (OG) and its petroleum ether (PEOG), ethyl acetate (EAOG) and ethanol (EOG) fractions in TZM intoxicated Wistar rats for 7 days using anthropometric, biochemical, histopathological and immunohistochemical endpoints. In addition, secondary metabolite constituents in OG and its fractions were determined through Gas Chromatography-Mass Spectrometry (GC-MS). The study results showed that oral pretreatments with OG and OG fractions as well as the fixed dose valsartan-lisinopril (VAL-LSP) combination effectively ameliorated and restore nearly normal levels the TZM-altered plasma cardiac troponin I and antioxidant profile which were corroborated by histopathological and immunohistochemical findings as indicated by the inhibition of TZM-induced activation of caspases-3 and - 9 and profound upregulation of BCL-2 expression. Phytoscan of OG and its fractions showed the presence of thymol and in high amount. Overall, our findings revealed the cardioprotective potentials of OG, OG fractions and fixed dose VAL-LSP combination against TZM-induced cardiotoxicity which probably was mediated via abrogation of cardiomyocyte apoptosis and antioxidant mechanisms.

Oxidized dietary lipids induce vascular inflammation and atherogenesis in post-menopausal rats: estradiol and selected antihyperlipidemic drugs restore vascular health in vivo.

BACKGROUND: Thermoxidation of edible oil through deep fat frying results in the generation of several oxidized products that promote lipid peroxidation and ROS production when eaten. Consumption of thermoxidized oil in post-menopausal conditions where the estrogen level is low contributes to cardiovascular disease. This study evaluates the role of estradiol and antihyperlipidemic agents (AHD) in restoring the vascular health of ovariectomized (OVX) rats fed with thermoxidized palm oil (TPO) and thermoxidized soya oil (TSO) diets. METHOD: A total of 10 groups of rats (n = 6) were set up for the experiment. Group I (normal control) rats were sham handled while other groups were OVX to bring about estrogen deficient post-menopausal state. Group II (OVX only) was not treated and received normal rat chow. Groups III-X were fed with either TPO or TSO diet for 12 weeks and treated with estradiol (ETD) 0.2 mg/kg/day, atorvastatin (ATV) 10 mg/kg/day, and a fixed-dose combination of ezetimibe and ATV (EZE 3 mg/kg/day + ATV 10 mg/kg/day). RESULTS: Pro-atherogenic lipids levels were significantly elevated in untreated TSO and TPO groups compared to OVX and sham, resulting in increased atherogenic and Coronary-risk indices. Treatment with Estradiol and AHDs significantly reduced the total cholesterol, triglycerides, low-density lipoprotein cholesterol as well as AI and CRI compared to untreated TSO and TPO groups, whereas TSO and TPO groups showed significant elevation in these parameters compared to Group I values. Moreover, aortic TNF-α levels were extremely elevated in the untreated TSO and TPO compared to Group I. TNF-α levels were significantly reduced in rats treated with AHDs and ETD. Localized oxidative stress was indicated in the aortic tissues of TSO and TPO-fed OVX rats by increased malondialdehyde and decreased glutathione, catalase, and superoxide dismutase levels. This contributed to a depletion in aortic nitric oxide. AHDs and ETD replenished the nitric oxide levels significantly. Histological evaluation of the aorta of TSO and TPO rats revealed increased peri-adventitia fat, aortic medial hypertrophy, and aortic recanalization. These pathologic changes were less seen in AHDs and ETD rats. CONCLUSION: This study suggests that ETD and AHDs profoundly attenuate oxidized lipid-induced vascular inflammation and atherogenesis through oxidative-stress reduction and inhibition of TNF-α signaling.

African Vegetables (Clerodendrum volibile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab-Induced Cardiotoxicity in Wistar Rats.

Trastuzumab (TZM) is a humanized monoclonal antibody that has been approved for the clinical management of HER2-positive metastatic breast and gastric cancers but its use is limited by its cumulative dose and off-target cardiotoxicity. Unfortunately, till date, there is no approved antidote to this off-target toxicity. Therefore, an acute study was designed at investigating the protective potential and mechanism(s) of CVE and IGE in TZM-induced cardiotoxicity utilizing cardiac enzyme and oxidative stress markers and histopathological endpoints. 400 mg/kg/day CVE and IGE dissolved in 5% DMSO in sterile water were investigated in Wistar rats injected with 2.25 mg/kg/day/i.p. route of TZM for 7 days, using serum cTnI and LDH, complete lipid profile, cardiac tissue oxidative stress markers assays, and histopathological examination of TZM-intoxicated heart tissue. Results showed that 400 mg/kg/day CVE and IGE profoundly attenuated increases in the serum cTnI and LDH levels but caused no significant alterations in the serum lipids and weight gain pattern in the treated rats. CVE and IGE profoundly attenuated alterations in the cardiac tissue oxidative stress markers' activities while improving TZM-associated cardiac histological lesions. These results suggest that CVE and IGE could be mediating its cardioprotection via antioxidant, free radical scavenging, and antithrombotic mechanisms, thus, highlighting the therapeutic potentials of CVE and IGE in the management of TZM-mediated cardiotoxicity.

Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats.

Cardiotoxicity as an off-target effect of doxorubicin therapy is a major limiting factor for its clinical use as a choice cytotoxic agent. Seeds of Irvingia gabonensis have been reported to possess both nutritional and medicinal values which include antidiabetic, weight losing, antihyperlipidemic, and antioxidative effects. Protective effects of Irvingia gabonensis ethanol seed extract (IGESE) was investigated in doxorubicin (DOX)-mediated cardiotoxicity induced with single intraperitoneal injection of 15 mg/kg of DOX following the oral pretreatments of Wistar rats with 100-400 mg/kg/day of IGESE for 10 days, using serum cardiac enzyme markers (cardiac troponin I (cTI) and lactate dehydrogenase (LDH)), cardiac tissue oxidative stress markers (catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH)), and cardiac histopathology endpoints. In addition, both qualitative and quantitative analyses to determine IGESE's secondary metabolites profile and its in vitro antioxidant activities were also conducted. Results revealed that serum cTnI and LDH were significantly elevated by the DOX treatment. Similarly, activities of tissue SOD, CAT, GST, and GSH levels were profoundly reduced, while GPx activity and MDA levels were profoundly increased by DOX treatment. These biochemical changes were associated with microthrombi formation in the DOX-treated cardiac tissues on histological examination. However, oral pretreatments with 100-400 mg/kg/day of IGESE dissolved in 5% DMSO in distilled water significantly attenuated increases in the serum cTnI and LDH, prevented significant alterations in the serum lipid profile and the tissue activities and levels of oxidative stress markers while improving cardiovascular disease risk indices and DOX-induced histopathological lesions. The in vitro antioxidant studies showed IGESE to have good antioxidant profile and contained 56 major secondary metabolites prominent among which are γ-sitosterol, Phytol, neophytadiene, stigmasterol, vitamin E, hexadecanoic acid and its ethyl ester, Phytyl palmitate, campesterol, lupeol, and squalene. Overall, both the in vitro and in vivo findings indicate that IGESE may be a promising prophylactic cardioprotective agent against DOX-induced cardiotoxicity, at least in part mediated via IGESE's antioxidant and free radical scavenging and antithrombotic mechanisms.

Clerodendrum volubile Ethanol Leaf Extract: A Potential Antidote to Doxorubicin-Induced Cardiotoxicity in Rats.

Doxorubicin is widely applied in hematological and solid tumor treatment but limited by its off-target cardiotoxicity. Thus, cardioprotective potential and mechanism(s) of CVE in DOX-induced cardiotoxicity were investigated using cardiac and oxidative stress markers and histopathological endpoints. 50-400 mg/kg/day CVE in 5% DMSO in distilled water were investigated in Wistar rats intraperitoneally injected with 2.5 mg/kg DOX on alternate days for 14 days, using serum troponin I and LDH, complete lipid profile, cardiac tissue oxidative stress marker assays, and histopathological examination of DOX-treated cardiac tissue. Preliminary qualitative and quantitative assays of CVE's secondary metabolites were also conducted. Phytochemical analyses revealed the presence of flavonoids (34.79 ± 0.37 mg/100 mg dry extract), alkaloids (36.73 ± 0.27 mg/100 mg dry extract), reducing sugars (07.78 ± 0.09 mg/100 mg dry extract), and cardiac glycosides (24.55 ± 0.12 mg/100 mg dry extract). 50-400 mg/kg/day CVE significantly attenuated increases in the serum LDH and troponin I levels. Similarly, the CVE dose unrelatedly decreased serum TG and VLDL-c levels without significant alterations in the serum TC, HDL-c, and LDL-c levels. Also, CVE profoundly attenuated alterations in the cardiac tissue oxidative stress markers' activities while improving DOX-associated cardiac histological lesions that were possibly mediated via free radical scavenging and/or antioxidant mechanisms. Overall, CVE may play a significant therapeutic role in the management of DOX-induced cardiotoxicity in humans.

Therapeutic Potentials of Selected Antihypertensive Agents and Their Fixed-Dose Combinations Against Trastuzumab-Mediated Cardiotoxicity.

Trastuzumab (TZM) is useful in the clinical management of HER2-positive metastatic breast, gastric, and colorectal carcinoma but has been limited by its off-target cardiotoxicity. This study investigates the therapeutic potentials of 0.25 mg/kg/day amlodipine, 0.035 mg/kg/day lisinopril, 5 mg/kg/day valsartan, and their fixed-dose combinations in TZM-intoxicated Wistar rats that were randomly allotted into 10 groups of 6 rats for each group. Group I rats were treated with 10 ml/kg/day sterile water orally and 1 ml/kg/day sterile water intraperitoneally; Groups II, III, and IV rats were orally gavaged with 5 mg/kg/day valsartan and 1 ml/kg/day sterile water intraperitoneally, 0.25 mg/kg/day amlodipine and 1 ml/kg/day sterile water via the intraperitoneal route, 0.035 mg/kg/day lisinopril and 1 ml/kg/day sterile water administered intraperitoneally, respectively. Group V rats were orally treated with 10 ml/kg/day of sterile water prior to intraperitoneal administration of 2.25 mg/kg/day of TZM. Groups VI-VIII rats were equally pretreated with 5 mg/kg/day valsartan, 0.25 mg/kg/day amlodipine, and 0.035 mg/kg/day lisinopril before intraperitoneal 2.25 mg/kg/day TZM treatment, respectively; Groups IX and X rats were orally pretreated with the fixed-dose combinations of 0.25 mg/kg/day amlodipine +0.035 mg/kg/day lisinopril and 5 mg/kg/day valsartan +0.035 mg/kg/day lisinopril, respectively, before TZM treatment. Cardiac injury and tissue oxidative stress markers, complete lipids profile, histopathological, and immunohistochemical assays were the evaluating endpoints. Results showed that repeated TZM treatments caused profound increases in the serum TG and VLDL-c levels, serum cTnI and LDH levels, and cardiac tissue caspase-3 and -9 levels but decreased BCL-2 expression. TZM also profoundly attenuated CAT, SOD, GST and GPx activities, and increased MDA levels in the treated tissues. In addition, TZM cardiotoxicity was characterized by marked vascular and cardiomyocyte congestion and coronary artery microthrombi formation. However, the altered biochemical, histopathological, and immunohistochemical changes were reversed with amlodipine, lisinopril, valsartan, and fixed-dose combinations, although fixed-dose valsartan/lisinopril combination was further associated with hyperlipidemia and increased AI and CRI values and coronary artery cartilaginous metaplasia. Thus, the promising therapeutic potentials of amlodipine, lisinopril, valsartan and their fixed-dose combinations in the management of TZM cardiotoxicity, majorly mediated via antiapoptotic and oxidative stress inhibition mechanisms were unveiled through this study.

Evaluation of Male Fertility-Enhancing Activities of Water Seed Extract of Hunteria umbellata in Wistar Rats.

BACKGROUND: In this study, the male fertility-enhancing activity of 100, 200, and 400 mg/kg/day of Hunteria umbellata water seed extract (HU) in Wistar rats was studied for 60 days. In doing this, effect of repeated doses of HU was studied on the weight gain pattern, gonadosomatic index (GSI), serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TS), prolactin (PRL), and estradiol (ES)} as well as testicular antioxidant status of the treated rats as a way of elucidating the mechanism(s) of action of HU. METHOD: Thirty-six (36) male Wistar rats were randomly divided into six groups (I-VI) of six rats per group. Group I rats were gavaged with 10 ml/kg/day of distilled water and served as an untreated control; Group II rats were gavaged with 0.3 mg/kg/day of clomiphene in distilled water; Groups III-V rats received 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day of HU, respectively, and Group VI rats received 20 mg/kg/day of Vitamin C all in distilled water. All treatments were for 60 days after which the treated rats were humanely sacrificed. Sera of blood samples were processed for the above stated hormonal profile. Similarly, testicular tissues obtained were processed for semen analysis and complete antioxidant profile of the HU-treated testicles by assaying for superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), glutathione reductase (GSR), glutathione peroxidase (GSH-Px), and Thiobarbituric Reactive Species (TBARS). RESULTS: Prolonged treatments with 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day of HU for 60 days induced dose dependent reductions in weight gain pattern with the most significant (p<0.001) effect recorded with the highest dose of HU. Conversely, significant (p<0.001) increase was recorded for GSI at the same HU dose. Clomiphene and HU also induced significant (p<0.01, p<0.001) dose dependent increases in the total sperm count, %live sperm, but reverse effects on %dead sperm and %abnormal sperm. On the hormonal profile, oral treatment with 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day of the extract induced profound (p<0.05, p<0.01, and p<0.001) dose related increases in the sera TS, LH, and FSH while it caused reverse effect on serum PRL but caused no significant alterations in the serum ES levels. Similarly, oral treatment with vitamin C and 100-400 mg/kg/day of HU induced profound (p<0.05, p<0.01, and p<0.001) increases in the antioxidant enzyme activities. CONCLUSION: Overall, prolonged oral treatment with 100-400 mg/kg body weight of HU for 60 days significantly improved sperm function which was mediated via enhanced spermatogenesis, steroidogenesis, and antioxidant mechanisms.

Morinda lucida Aqueous Stem Bark Extract Ameliorates Hepato-Renal Dysfunctions in Experimental Diabetes Model.

Diabetes Mellitus (DM) is a leading pan-systemic endocrine disorder with attendant high morbidity and mortality owing to its deleterious effects on vital body organs caused by untreated chronic hyperglycemia, attendant oxidative stress and glycation processes. The present study is designed to investigate possible protective role and mechanism(s) of action 125-500 mg/kg/day of Morinda lucida aqueous stem bark extract (MLASE) on renal and hepatic functions in alloxan-induced hyperglycemic rats for 8 days. Forty-two alloxan-induced hyperglycemiic male Wistar rats were randomly allotted to Groups II-VI and orally treated with 10 ml/kg/day distilled water, 5 mg/kg/day glibenclamide, 125 mg/kg MLASE, 250 mg/kg MLASE, and 500 mg/kg/day MLASE, respectively. Group I normal rats served as untreated control and were orally treated with 10 ml/kg of distilled water, all under same sham-handling. Blood samples were taken for measurement of fasting blood glucose, renal and hepatic function profile. Liver and kidney tissue samples were taken for determination of the activities of oxidative stress markers such as malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GPx), catalase (CAT) and superoxidase dismutase (SOD). Results showed that intraperitoneal injection with 120 mg/kg of alloxan in cold 0.9% normal saline reliably and significantly induced a steadily sustained hyperglycemia which were ameliorated by short-term oral treatment with 125-500 mg/kg/day of MLASE, dose dependently, similar to that ameliorated by the standard antihyperglycemic drug, glibenclamide. Similarly, MLASE significantly mitigated against derangements in the measured renal and hepatic function parameters as well as oxidative stress induced by alloxan-induced hyperglycemia. In conclusion, results of this study showed the protective role of 125-500 mg/kg/day of MLASE in chronic hyperglycemia-associated renal and hepatic dysfunctions which was mediated via antioxidant and free radical scavenging activities of MLASE.

Modulatory potentials of the aqueous stem bark extract of Mangifera indica on carbon tetrachloride-induced hepatotoxicity in rats.

Among Yoruba herbalists (Southwest Nigeria), hot water infusion of Mangifera indica L. ( Máng Guǒ) stem bark is reputedly used for the treatment of fever, jaundice and liver disorders. The present study, therefore, investigates the protective effects and mechanism(s) of chemopreventive and curative effects of 125-500 mg/kg/day of Mangifera indica aqueous stem bark extract (MIASE) in acute CCl4-induced liver damage in rats. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day of MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 20% CCl4, i.p.). The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), total bilirubin (TB), conjugated bilirubin (CB) and fasting blood glucose (FBG) levels were estimated. In addition, hepatic tissue reduced glutathione (GSH) and the malondialdehyde (MDA) concentrations, catalase (CAT), superoxide (SOD) activities in the hepatic homogenate, and histopathological changes in the rat liver sections were determined. Preliminary qualitative phytochemical screening for bioactive compounds in MIASE was also conducted. Results showed that oral treatment with 125-500 mg/kg/day of MIASE significantly attenuated the increase in serum ALT, AST, ALP, FBG, TB, CB and LDL-c levels in acute liver injury induced by CCl4 treatment. Findings also revealed significant elevations in the serum TC, TG, HDL-c, TP and ALB levels. There was marked architectural remodeling in the hepatic lesions of hepatocyte vacuolation and centrilobular necrosis induced by CCl4 treatment, coupled with significant weight loss. MIASE also markedly enhanced SOD and CAT activities while reducing MAD formation; and increased GSH concentration in the hepatic homogenate compared with untreated CCl4-intoxicated group, with more protection offered in the curative than the chemopreventive models of CCl4 hepatotoxicity. Thus, these results indicate that MIASE has a profound protective effect against acute CCl4-induced hepatotoxicity in rats, which may be due to its free radicals scavenging effect, inhibition of lipid peroxidation, and its ability to increase antioxidant activity.

Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats.

There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl(-), HCO3(-)), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (p<0.05) increases in serum Na+, K+, Cl(-), urea and creatinine. CCl4 also caused significant (p<0.05) decreases in renal tissue SOD, CAT and GSH and significant (p<0.05) increases in MDA. The oral MIASE treatment (125-500 mg/kg) was found to significantly (p<0.05) attenuate the increase in serum electrolytes, urea and creatinine. Similarly, MIASE significantly (p<0.05) attenuated the decrease in SOD, CAT and GSH levels and correspondingly attenuated increases in MDA. Mangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology.

Evaluation of the anti-arthritic activity of the hydroethanolic leaf extract of Alchornea cordifolia in rats.

BACKGROUND: Different decoctions of Alchornea cordifolia leaves are used by Yoruba herbalists (Southwest Nigeria) for the local treatment of ulcers, rheumatic pains, febrile convulsions, and for enhancing physical performance. MATERIALS AND METHODS: In this study, the anti-arthritic effect of 100 - 400 mg/kg/day of the hydroethanolic leaf extract of Alchornea cordifolia (HEAC) was investigated in Complete Freund's Adjuvant (CFA)-induced arthritic rats as a way of evaluating its efficacy in the local management of arthritis. In addition, the effects of HEAC on liver and renal function parameters as well as its effect on the antioxidant enzyme system were investigated. Arthritis was induced using 0.1 ml of 10 mg/ml of Complete Freund's Adjuvant (CFA) following 1 h oral pretreatment and 8(th) day post-arthritic induction with 100, 200 and 400 mg/kg/day of HEAC and 3 mg/kg/day of celecoxib as the reference drug. The anti-arthritic activity of HEAC was assessed based on the ability of HEAC to alter the paw edema diameter, body weight, full blood count, renal and liver function markers, glycoprotein, lysosomal enzymes and possible antioxidant potential in the arthritic rats. RESULTS: Oral pretreatment with 100, 200, and 400 mg/kg/day of HEAC produced significant (p<0.001, p<0.05 and p<0.01) reductions in the paw edema diameter in a non-dose dependent fashion in ACF-induced arthritic rats with the 100 mg/kg/day of HEAC producing the most significant anti-arthritic effect. Similarly, HEAC increased hepatic GSH levels, CAT and SOD activities suggesting possible antioxidant mechanism for its anti-arthritic effect. CONCLUSION: Overall, results of this study lend credence to the folkloric use of water decoction of Alchornea cordifolia leaves against rheumatoid arthritis. However, further pharmacological investigations would be required at isolating and determining the active anti-arthritic molecule(s) in HEAC in the nearest future.

Dose and time-dependent sub-chronic toxicity study of hydroethanolic leaf extract of Flabellaria paniculata Cav. (Malpighiaceae) in rodents.

Flabellaria paniculata Cav. (Malpighiaceae) is a climbing shrub, the preparations of which are used in the treatment of wounds and ulcers in Nigeria and Ghana. This study investigated the sub-chronic toxicity profile of the hydroethanolic leaf extract of F. paniculata (HLE-FP). HLE-FP was administered p.o. (20, 100, and 500 mg/kg) for 30 and 60 days to different groups of rats. Control animals received 10 ml/kg distilled water. In the group of animals for reversibility study, HLE-FP administration ceased on the 60th day and animals were monitored for a further 15 days. Results showed that oral treatment with HLE-FP for 30 days caused significant (p < 0.05) reductions in weight gain pattern compared to control. These changes were sustained with 60 days treatment. However, no significant (p > 0.05) differences in relative organ weights between control and treatment groups were observed. HLE-FP-treated rats showed significant (p < 0.05) increases in Hb, PCV and RBC on day 30 and significant (p < 0.05) increases in MCV and MCH indices on day 60 compared to control. There were significant (p < 0.05) elevations in serum K(+), urea and creatinine compared to control. The liver function tests showed slight but non-significant alterations in relevant parameters when compared to control. Biochemical findings were supported by histopathological observations of vital organs including the kidney and liver. Toxicities observed in respect of kidney function were irreversible at 15 days of stoppage of treatment. In the acute toxicity study, HLE-FP given p.o. caused no lethality at 5000 mg/kg but behavioral manifestations like restlessness, generalized body tremor, feed, and water refusal were observed. The i.p. LD50 was estimated to be 2951.2 mg/kg. Findings in this study showed that HLE-FP is relatively non-toxic on acute exposure and generally safe on sub-chronic administration, but could be deleterious on the kidneys on prolonged oral exposure at a high dose. Thus, caution should be exercised with its long-term usage.

Evaluation of the toxicological profile of the leaves and young twigs of Caesalpinia bonduc (Linn) roxb.

Acute and sub-acute toxicological effects of ethanolic extract of the leaves and young twigs of Caesalpinia bonduc were carried out on albino rats. Single extract doses from 2000 to 5000 mg/kg body weight were administered orally and monitored for 14 days in acute study, while extract doses from 200 to 1600 mg/kg body weight were orally administered daily for 28 days in sub-acute study and recovery was assessed 14 days after dosing. Biochemical, haematological and histopathological examinations were carried out. There was no mortality in the experimental animals in all acute treatment doses. However, there were significant alterations in the biomarkers and induced cellular damage to the liver in all acute treatment doses. In the sub-acute toxicity treatment, the assessed biomarkers were unaffected at extract dose of 200 mg/kg body weight compared to control, while significant changes were observed in rats administered with extract doses of 400 mg/kg body weight and above. No significant difference was observed between the tested groups and the recovery groups in the sub-acute toxicity study. In conclusion, the ethanolic extract of C. bonduc could be toxic to selected organs of the rat body in acute and sub-acute treatments.

Antihyperglycemic profile of erinidine isolated from Hunteria umbellata seed.

Water decoction made from the seed of Hunteria umbellata is widely used in the traditional management of diabetes mellitus by Nigerian herbalists, particularly, in the southwest region of the country. Recently, a new bisindole alkaloid, erinidine, was isolated but its antihyperglycemic profile remains largely un-investigated scientifically. This forms the basis for the current study which is primarily designed at investigating the antihyperglycemic profile of erinidine and other fractions in both in vitro and in vivo models of diabetes mellitus. In the present study, erinidine was isolated and purified using the earlier described methods and its antihyperglycemic potentials tested in in vitro models such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity, aldose reductase assays and α-glucosidase inhibition assay testings. In addition, 50 mg/kg of erinidine and that of other fractions were evaluated in in vivo models of normal and chemically-induced hyperglycemic rats. Results showed that erinidine was a light yellow, amorphous solid with UV (CHCl3) λ max 256 nm, HRESIMS m/z 382.1881 [(M+H)(+)] (calculated for C22H26N4O2, 382.1876) and melting point of 230 °C. The in vitro study showed the antihyperglycemic action of erinidine to be weakly mediated via α-glucosidase inhibition mechanism as the results for other in vitro tests such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity and aldose reductase assays were all negative. However, the in vivo results showed 50 mg/kg erinidine given per os to normal and alloxan-induced hyperglycemic rats to significantly (p<0.05, p<0.001) attenuate an increase in their post-absorptive blood glucose concentrations after 3 g/kg glucose loading in the rats, suggesting its antihyperglycemic mechanism to be via α-glucosidase inhibition. This result, although, further corroborated the in vitro findings but also suggests that erinidine needs to be biotransformed in vivo for its inhibitory activity on intestinal glucose absorption to become evident. Thus, the present study suggests erinidine to be the possible antihyperglycemic agent in Hunteria umbellata seed extract mediating its antihyperglycemic action via intestinal glucose uptake inhibition.

Survey of Hypertension, Diabetes and Obesity in Three Nigerian Urban Slums.

BACKGROUND: Non-communicable diseases (NCDs) exist in slums as the inhabitants adopt an urbanized lifestyle which places them at a higher risk for. Lack of knowledge about the morbidity, complications and the method of control contributes to a large percentage of undetected and untreated cases. METHODS: This cross-sectional survey polled 2,434 respondents from Ijora Oloye, Ajegunle and Makoko, three urban slums in Lagos metropolis, southwestern Nigeria between June 2010 and October 2012. We investigated the prevalence of hypertension, diabetes and obesity. Respondents signed consent forms and their health conditions were documented based on self-reported history of diabetes, hypertension and family history using a semi-structured questionnaire. Diagnostic tests; weight and height for body mass index, blood glucose, and blood pressure were performed. RESULTS: More than one quarter of the participants were suffering from hypertension and only half of this were diagnosed earlier, while a further few were already on treatment. Therefore on screening, it had been possible to diagnose over three hundred more respondents, who were not previously aware of their health status. The respondents' BMI showed that more than half of them were either overweight or obese and are at risk for diabetes, while 3.3% were confirmed as being diabetic, with their sugar levels greater than the normal range. CONCLUSION: This study therefore revealed the near absence of screening programs for chronic diseases such as hypertension, diabetes and obesity in these urban slums. This was further confirmed by the detection of new and undiagnosed cases of hypertension in about one quarter of the respondents.

The leaf and seed aqueous extract of Phyllanthus amarus improves insulin resistance diabetes in experimental animal studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Amongst the Yoruba tribe (Southwest Nigeria), water decoction of the leaf and seed of Phyllanthus amarus Schum. and Thonn. is reputably used for the local management of diabetes mellitus, obesity and hyperlipidemia. AIM OF THE STUDY: The present study seeks to evaluate the effectiveness and elucidate mechanism(s) of action of the aqueous leaf and seed extract of Phyllanthus amarus (PAE) in normal and 10% sucrose-induced hyperglycemia and dyslipidemia as an experimental model of insulin resistance diabetes mellitus. MATERIALS AND METHODS: In this study, the repeated oral antihyperglycemic action of 150-600 mg/kg/day of PAE was evaluated in normal and 10% sucrose-induced insulin resistance rats using indicators such as fasting blood glucose (FBG), insulin and insulin resistance indices. The extract's weight losing, antihyperlipidemic and anti-atherogenic effects were also evaluated by measuring the effect of the extract on the body weight, plasma levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and atherogenic indices. RESULTS: In normal rats, PAE caused significant (p<0.05, p<0.01 and p<0.001) and dose related decreases in body weight, FBG, TG, TC, LDL-c, and atherogenic indices. Repeated oral treatment with 10% sucrose drink for 30 days was associated with significant (p<0.001) weight gain, hyperglycemia, insulin resistance indices, hyperlipidemia and atherogenic indices. However, pre-treatment with PAE significantly (p<0.05, p<0.01 and p<0.001) and dose-dependently attenuated increase in any of these measured parameters. CONCLUSIONS: Overall, results of this study showed PAE to effectively control insulin resistance DM which was mediated via improvement in insulin resistance, thus, validating its ethnomedical use in the local management of DM.

Analgesic activity of the aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. in rodents.

The analgesic effect and possible mechanism(s) of action of 50-200 mg/kg of the aqueous seed extract of H. umbellata (HU) were investigated in different experimental models of analgesia using the tail flick, tail immersion, acetic acid-induced writhing tests and formalin-induced algesia. Oral pre-treatment with 50-200 mg/kg of HU caused significant and dose related analgesic effect in the treated rats in all the experimental models used. This analgesia was mediated via central and peripheral mechanisms. Overall, the results showed that HU possesses analgesic effect which lends support to its folkloric use in the local management of pain.

Metformin: an effective attenuator of risperidone-induced insulin resistance hyperglycemia and dyslipidemia in rats.

The use of atypical antipsychotics in the clinical management of schizophrenia and schizoaffective disorders has been associated with the development of insulin resistance. The present study evaluates the possible individual ameliorating effect of single daily oral treatments with 20 mg/kg/day of metformin and 0.1 mg/kg of glibenclamide in two groups of Wistar rats pretreated with 0.2 mg/kg of risperidone for 60 days. Two additional groups of rats were only treated with 0.2 mg/kg of risperidone and 10 mL/kg of distilled water, respectively, also for 60 days. Results showed that oral pre-treatment with metformin significantly attenuated increases in the weight gain pattern, fasting glucose, fasting plasma insulin, serum triglyceride and total cholesterol levels that were elevated by risperidone treatment. Metformin also significantly reduced glycosylated hemoglobin concentration, fasting insulin-glucose ratio and fasting insulin resistance index. Conversely, oral pre-treatment with glibenclamide for 60 days did not significantly reduce any of the measured parameters except for glycosylated hemoglobin concentrations. Thus, results of this study showed that 20 mg/kg of metformin effectively ameliorated the development of risperidone-induced insulin resistance and dyslipidemia which was mediated via improvement in insulin resistance. This study provides insight into the therapeutic potential of metformin in preventing risperidone-induced insulin resistance diabetes mellitus and dyslipidaemia.

Anti-obesity and antihyperlipidaemic effect of Hunteria umbellata seed extract in experimental hyperlipidaemia.

AIM OF THE STUDY: In Nigerian folk medicine, water infusion of the dried seeds of Hunteria umbellata (K. Schum.) Hallier f. has a reputation for the local management of obesity and hyperlipidaemia. The present study is aimed at evaluating the anti-obesity and antihyperlipidaemic activities as well as the underlying mechanisms of action of the aqueous seed extract of Hunteria umbellata (HU) in normal, triton-induced, and olive oil-induced hyperlipidaemic rats. MATERIALS AND METHODS: Normal and olive oil-induced hyperlipidaemic, and triton-induced hyperlipidaemic rats were pre-treated with single, daily oral administration of 10 ml/kg of distilled water, 20 mg/kg of simvastatin, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in 10 ml/kg of distilled water for 28 days and 24 h. The effects of these drugs on % body weight change, feeding pattern, serum lipids, coronary artery risk index (CRI) and atherogenic index (AI) and Lee's index (LI) were investigated. RESULTS: Oral pre-treatment with simvastatin and graded oral doses of HU significantly (p<0.05) reduced the weight gain pattern and caused dose related (p<0.05, p<0.01 and p<0.001) reductions in the serum lipids, CRI, AI and LI. Also, HU pre-treatment significantly improved triton-induced hepatic histological lesions. CONCLUSIONS: Results of this study showed that HU has both anti-obesity and antihyperlipidaemic effects which may partly be mediated via inhibition of intestinal lipid absorption and de novo biosynthesis of cholesterol. Thus, the results justify the ethnopharmacological use of the extract in the management of obesity and hyperlipidaemia.

Further evaluation of antihyperglycaemic activity of Hunteria umbellata (K. Schum) Hallier f. seed extract in experimental diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: In African traditional medicine, water decoction made from the dry seeds of Hunteria umbellata (K. Schum) Hallier f. is highly valued in the management of diabetes mellitus. AIM: In the present study, the antihyperglycaemic activity of the seed aqueous extract of Hunteria umbellate (K. Schum) Hallier f. (HU) was investigated in alloxan-induced, high fructose- and dexamethasone-induced hyperglycaemic rats. MATERIALS AND METHODS: Alloxan-induced, dexamethasone-induced and high fructose-induced hyperglycaemic rats were treated with single, daily oral administration of 1 mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in Groups III, IV, V and VI, for 14 days, 21 days and 8 weeks, respectively. The effects of these drugs on FBG, free plasma insulin levels, HbA(1c), serum TG and TC, and insulin resistance indices were investigated. RESULTS: Data generated in the current study showed that glibenclamide and graded oral doses of HU caused significant dose related (p < 0.05, < 0.01 and < 0.001) reductions in FBG when compared to the values obtained for the model control (Group II) rats. Similarly, daily oral administration of 66.7 g/kg fructose to rats for 8 weeks was associated with significant (p < 0.001) hyperglycaemia, elevations in plasma HbA(1c), free insulin, fasting insulin resistance indices, serum TG, and cholesterol. However, concomitant oral treatments with 1mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg, and 200 mg/kg of HU extract significantly and dose dependently (p < 0.05, < 0.01 and < 0.001) attenuated development of hyperglycaemia, decreased levels of plasma HbA(1c), free insulin, and serum triglyceride and cholesterol, in the Groups III, IV, V and VI rats, respectively, when compared to fructose-induced hyperglycaemic (Group II) rats. Similar effect was also recorded in the dexamethasone-induced hyperglycaemic rats. CONCLUSION: Results of this study suggest that the hypoglycaemic and antihyperlipidaemic effects of HU are mediated via enhanced peripheral glucose uptake and improvements in hyperinsulinaemia.