Celecoxib exhibits therapeutic potential in experimental model of hyperlipidaemia.

Hyperlipidaemia is a major risk factor for cardiovascular diseases, the leading cause of death globally. Celecoxib attenuated hypercholesterolaemia associated with CCl4-induced hepatic injury in rats without improving liver function in our previous study. This present study investigated the lipid lowering potential of celecoxib in normal rats fed with coconut oil subjected to five deep-frying episodes. Male Sprague Dawley rats were randomly assigned to groups (n = 6 rats/group) which received physiological saline (10 mL/kg), unheated coconut oil (UO, 10 mL/kg) or heated coconut oil (HO, 10 ml/kg) for 60 days. Groups that received HO were subsequently treated with either physiological saline, atorvastatin (25 mg/kg), celecoxib (5 mg/kg) or celecoxib (10 mg/kg) in the last fifteen days of the experiment. Rats were sacrificed 24 hours after last treatment and blood and tissue samples collected for analysis. HO consumption produced significant hyperlipidaemia and elevation in marker enzymes of hepatic function. Celecoxib ameliorated the hyperlipidaemia as shown by the significantly (P<0.05) lower total cholesterol, triglycerides, low and very low density lipoprotein in the celecoxib-treated rats when compared with HO-fed rats that received saline. Celecoxib also reduced (P<0.05) alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and liver weight of hyperlipidaemic rats. Similarly, hepatocellular damage with the hyperlipidaemia was significantly reversed by celecoxib. However, serum TNF-α and IL-6 did not change significantly between the various groups. Taken together, data from this study suggest that celecoxib may exert therapeutic benefit in hyperlipidaemia and its attendant consequences.

Leaf and root bark extracts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) ameliorate hepatic, renal and splenic injuries induced by phenylhydrazine in rats.

Objectives Ziziphus abyssinica (ZA) is employed in managing several ailments in Traditional African Medicine. Scientific evaluations are necessary to ascertain the medicinal potential of ZA as a source of new drug molecules. This study investigated the possible therapeutic benefit of ZA leaf (ZAL) and root bark (ZARB) extracts in an experimental model of multi-organ injuries induced by phenylhydrazine (PHZ). Methods Hyperbilirubinaemia, hepatotoxicity, nephrotoxicity and splenic injuries were induced by pretreating albino rats with PHZ (40 mg/kg, p.o.) for two alternate days. Afterward, six out of the eight groups of rats (n = 5) used were treated with either ZAL or ZARB (30, 100 and 300 mg/kg/day, p.o.) for seven days. Naïve control rats received saline without PHZ whereas negative control group received saline after PHZ. After one week of treatment, rats were sacrificed and blood collected for assessment of haematological and biochemical parameters. Liver, kidney and spleen sections were processed for histology and examined under light microscope. Results Data indicate that PHZ significantly (p < 0.05) increased total bilirubin, serum alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen (BUN), creatinine and BUN/creatinine ratio whereas red blood cell count was significantly reduced. These anomalies were significantly reversed in rats treated with ZAL or ZARB. The therapeutic effect of the extracts was supported by photomicrographs of the liver, kidney, and spleen of rats which revealed recovery from PHZ-mediated pyknosis, glomerular degeneration and multiple splenic necrosis respectively. Conclusions Overall, data from this study suggest that ZA may be useful in multiple organ injuries associated with PHZ-like xenobiotic toxicity.

Sub-chronic toxicity evaluation of top three commercial herbal antimalarial preparations in the Kumasi metropolis, Ghana.

PURPOSE: Safety data on commonly used herbal medicinal (HM) products (HMPs) and marketed in Ghana are scarce. We assessed the sub-chronic toxicity of three most-patronised commercial antimalarial HMPs in Kumasi, Ghana. METHOD: Top three HMPs (designated as herbal products 'A' (HPA), 'B' (HPB) and 'C' (HPC)) were selected after a mini-survey and sub-chronic toxicity evaluation conducted in accordance with Organisation for Economic Co-operation and Development (OECD) 407 guidelines. Control rats received clean water while test groups received daily adult human dose (DAHD), 5× DAHD or 10× DAHD of either HPA, HPB or HPC for 30 days. Rats were killed on day 31 to obtain biochemical, haematology and histology samples for analysis. Data were analysed by one-way analysis of variance (ANOVA) and post hoc Tukey's test. RESULTS: The three HMPs produced alterations in liver morphology predominantly characterised by prominent foci of fatty change with scattered hepatocytes containing intracytoplasmic fat globules and congested central veins and sinusoids. The lungs showed alveolar with evidence of inflammation and foci of epithelial sloughing. Alveolar spaces were also obscured by debris and inflammatory cells. HPA and HPC produced scattered intensely congested heart vessels while HPB(10) produced haemorrhage and amorphous exudates within the heart. All HMPs produced neither treatment-related deaths nor significant change in haematological and biochemical parameters, except for HPA and HPB which decreased (P<0.05) aspartate aminotransferase (AST) and HPB, which elevated (P<0.05) fasting blood glucose (FBG). CONCLUSION: Data from the present study suggest the potential of the herbal products (HPs), HPA, HPB and HPC, to cause major organ-system dysfunction or damage. We advise cautious use of these products and recommend further safety evaluation in chronic toxicity models.

Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei.

BACKGROUND: Increasing resistance to current anti-malarial therapies requires a renewed effort in searching for alternative therapies to combat this challenge, and combination therapy is the preferred approach to address this. The present study confirms the anti-plasmodial effects of two compounds, cryptolepine and xylopic acid and the relationship that exists in their combined administration determined. METHODS: Anti-plasmodial effect of cryptolepine (CYP) (3, 10, 30 mg kg-1) and xylopic acid (XA) (3, 10, 30 mg kg-1) was evaluated in Plasmodium berghei-infected male mice after a 6-day drug treatment. The respective doses which produced 50% chemosuppression (ED50) was determined by iterative fitting of the log-dose responses of both drugs. CYP and XA were then co-administered in a fixed dose combination of their ED50s (1:1) as well as different fractions of these combinations (1/2, 1/4, 1/8, 1/16 and 1/32) to find the experimental ED50 (Zexp). The nature of interaction between cryptolepine and xylopic acid was determined by constructing an isobologram to compare the Zexp with the theoretical ED50 (Zadd). Additionally, the effect of cryptolepine/xylopic acid co-administration on vital organs associated with malarial parasiticidal action was assessed. RESULTS: The Zadd and Zexp were determined to be 12.75 ± 0.33 and 2.60 ± 0.41, respectively, with an interaction index of 0.2041. The Zexp was significantly (P < 0.001) below the additive isobole indicating that co-administration of cryptolepine and xylopic acid yielded a synergistic anti-plasmodial effect. This observed synergistic antiplasmodial effect did not have any significant deleterious effect on the kidney, liver and spleen. However, the testis were affected at high doses. CONCLUSION: The co-administration of cryptolepine and xylopic acid produces synergistic anti-malarial effect with minimal toxicity.