Ziziphus abyssinica root bark extract ameliorates paracetamol-induced liver toxicity in rats possibly via the attenuation of oxidative stress.

Ziziphus abyssinica root bark is widely used in folk medicine to manage liver diseases, particularly, jaundice but its effect on paracetamol-induced liver toxicity (PILT) has not yet been validated. This study explored the ameliorative effect of ethanolic root bark extract of Ziziphus abyssinica (ZAE) against PILT in rats. The flavonoid and phenolic content of ZAE was evaluated using Folin-Ciocalteau and aluminium trichloride colorimetric methods, respectively. Antioxidant activity of ZAE was determined in vitro by evaluating its ferrous reducing antioxidant capacity (FRAC) as well as DPPH and nitic oxide (NO) radicals scavenging activities. Sprague-Dawley rats were assigned to six groups (n = 6) and administered with normal saline (10 mL/kg, p.o.), N-acetylcysteine (50 mg/kg, i.p.) and ZAE (30, 100, and 300 mg/kg, p.o.) respectively for seven days after which they received paracetamol (PCM, 3000 mg/kg, p.o.). Animals were sacrificed 48 h after paracetamol administration under light anaesthesia and assessed for liver toxicity and oxidative stress. Total flavonoid and phenolic contents of ZAE were 1313.425 µg/mL quercetin equivalence and 268.31 µg/mL gallic acid equivalence respectively. ZAE exhibited marked FRAC as well as DPPH and NO radical scavenging activities with IC50s of 80.41 ± 1.56, 67.56 ± 1.11 and 7.11 ± 1.48 µg/mL respectively. ZAE and N-acetylcysteine significantly (p < 0.05) reduced the paracetamol-mediated elevation of serum total bilirubin, proteins and activity of liver enzymes (AST, ALP, and ALT). Similarly, ZAE increased hepatic glutathione, total thiols and catalase activity of the paracetamol intoxicated rats. Morphological changes associated with the paracetamol hepatotoxicity were also ameliorated by ZAE. Overall, the hepatoprotective effect of ZAE may be related to its antioxidant property.

Protective Effect of Bergapten against Human Erythrocyte Hemolysis and Protein Denaturation In Vitro.

Bergapten, a furocoumarin found in many medicinal plants, is used for the management of various conditions. The present in vitro study evaluated the ability of bergapten to prevent human erythrocyte hemolysis and protein denaturation. Bergapten administered at 10, 30, and 100 µg/ml exhibited a significant concentration-dependent protection on the erythrocyte membrane exposed to hypotonicity and heat-induced hemolysis. The concentration at which bergapten inhibited 50% of the cells from hemolysis (IC50) was determined on a dose-response curve, plotted as logarithmic (concentration) against percentage inhibition, keeping the hemolysis produced within the control group at 100%. Bergapten treatment produced an IC50 value of 7.71 ± 0.27 µg/ml and 4.23 ± 0.42 µg/ml for hypotonicity and heat-induced hemolysis, respectively. Diclofenac sodium at similar concentrations produced an IC50 value of 12.22 ± 0.30 µg/ml and 9.44 ± 0.23 µg/ml in the hypotonicity and heat-induced hemolysis, respectively. The ability of bergapten to inhibit protein denaturation was studied as part of an investigation on its mechanism of action. The results showed a significant concentration-dependent reduction in protein denaturation. When administered at 10, 30, and 100 µg/ml, bergapten produced a concentration-dependent reduction in albumin denaturation. Bergapten inhibited protein denaturation with IC50 values of 5.34 ± 0.30 µg/ml and 12.18 ± 0.20 µg/ml in the heat-treated egg albumin and bovine serum albumin denaturation experiments, respectively. Diclofenac sodium (10, 30, and 100 µg/ml) exhibited a similar protection against heat-treated egg albumin and bovine serum albumin denaturation experiments with IC50 values of 8.93 ± 0.17 µg/ml and 12.72 ± 0.11 µg/ml, respectively. Taken together, data from this study show that the pharmacological properties of bergapten may in part be related to its membrane-stabilizing and antidenaturation properties.

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.

Turning Up the Volume for Precision Herbal Medicine in Africa in an Era of COVID-19 and Planetary Biodiversity Loss.

What would it take in terms of the structural reforms in science, technology, and culture to cultivate sustainable therapeutic and preventive medicine innovations against zoonotic infections such as coronavirus disease 2019 (COVID-19) in the 21st century? In May 2019, the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services warned that "around one million animal and plant species are now threatened with extinction." Biodiversity is essential for drug discovery and development. We are currently facing a dual challenge in therapeutics innovation with COVID-19 and loss in planetary biodiversity. Hence, there is an urgent need for new ideas and strategies for drug discovery as well as repurposed drugs for the COVID-19 pandemic. To these ends, the existing scholarship in, and the field of precision herbal medicine provide an alternative source for discovery of novel therapeutics against the novel coronavirus. We propose that the application of precision herbal medicine in Africa could usefully contribute to current efforts for therapeutics innovation for the COVID-19 pandemic, and beyond. The pandemic calls for interdisciplinary dialogue and turning up the volume for precision herbal medicine in Africa, and importantly, in ways informed by robust systems science as well as broad public engagement to codesign medicines in the 21st century.

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.

Heavy metal content and health risk assessment of commonly patronized herbal medicinal preparations from the Kumasi metropolis of Ghana.

PURPOSE: To address the question of whether users of herbal products (HPs) are exposed to harmful contaminants, we evaluated six HPs mostly patronized in Kumasi for heavy metal contamination and assessed the health risk associated with their use. This study is one of the first safety evaluation studies on finished multiherbal products in the region. METHOD: Three antimalarial, two antidiabetic and one antihypertensive HPs were selected after a mini-survey and coded randomly as HP A-F. The HPs were acid digested for quantitative analysis of heavy metals using Inductively Coupled Plasma Mass Spectrometer. Hg quantification was carried out using cold vapour atomic absorption spectroscopy. RESULTS: The cancer risk estimation values for the carcinogenic metals ranged between 1.54 × 10-9 to 3.73 × 10-4 and were all within acceptable limits. The non-cancer health risk evaluation revealed that, some of the products pose health risk to consumers. The estimated daily intake (EDI) for As in HPF was 2.48 × 10-4 mg/kg/day compared to the reference limit of 1.67 × 10-4 mg/kg/day. HPF also had high hazard index (HI) of 5.70 (HI >1) in children as compared to 1.68 (HI >1) in adults showing a 3.4 folds increase in the health risk among the former. CONCLUSION: The six polyherbal products exhibited carcinogenic risk within acceptable limits. Although, the non-carcinogenic risk assessment of products HPA to HPE suggests safety, this can only be ascertained after further characterization of their health risks in detailed chronic toxicity studies. The high HI for product HPF suggests health risk for consumers of this product.

Occupational exposure to municipal solid wastes and development of toxic neuropathies: possible role of nutrient supplementation, complementary and alternative medicines in chemoprevention.

Achieving effective municipal solid waste (MSW) management remains a major challenge and waste generation and accumulation continue to constitute important environmental and public health concern, particularly in most developing countries. Although the general population is at risk of adverse health consequences and hazards associated with exposure to MSW, the waste management workers (WMWs) are the most vulnerable because of their direct involvement in the disposal of waste, with increasing evidence of work-related health and safety risks among these individuals. Among the numerous work-related health hazards prevalent in WMWs, development of toxic neuropathies following chronic occupational exposure remains poorly recognized. However, the risk or predisposition to toxic neuropathies is becoming evident considering the increasing recognition of large amount of neurotoxic heavy metals and hazardous industrial materials present in MSW in most parts of the world. The present review seeks to draw attention to the continuous vulnerability of the WMWs to developing toxic neuropathies. This is aimed at facilitating conscious efforts by relevant governmental and nongovernmental agencies towards promoting risk reduction and ensuring adequate protection against possible toxic polyneuropathies associated with occupational exposure to solid wastes. While continuous education of the WMWs on the need for adequate compliance to safety regulations and practice remains sacrosanct towards achieving significant reduction in toxic neuropathies and related adverse health consequences of waste handling, it is also our intention in this review to underscore the possible relevance of nutrient supplementation and alternative medicines in chemoprevention.

The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety.

The use of herbal medicinal products and supplements has increased tremendously over the past three decades with not less than 80% of people worldwide relying on them for some part of primary healthcare. Although therapies involving these agents have shown promising potential with the efficacy of a good number of herbal products clearly established, many of them remain untested and their use are either poorly monitored or not even monitored at all. The consequence of this is an inadequate knowledge of their mode of action, potential adverse reactions, contraindications, and interactions with existing orthodox pharmaceuticals and functional foods to promote both safe and rational use of these agents. Since safety continues to be a major issue with the use of herbal remedies, it becomes imperative, therefore, that relevant regulatory authorities put in place appropriate measures to protect public health by ensuring that all herbal medicines are safe and of suitable quality. This review discusses toxicity-related issues and major safety concerns arising from the use of herbal medicinal products and also highlights some important challenges associated with effective monitoring of their safety.

Management of anxiety and sleep disorders: role of complementary and alternative medicine and challenges of integration with conventional orthodox care.

There is renewed attention and greater focus on anxiety and sleep- sleep-related disturbances because of the high prevalence, complexity, and their health related implications. The role of complementary and alternative medicine (CAM), which refers to therapeutic approaches that are "complementary to the end goals of decreasing illness and enhancing wellness, but are alternative to conventional medical treatment" is also increasingly recognized. In this review, we considered CAM approach to the management of anxiety and sleep disorders and discussed a few challenges associated with the effective integration of alternative therapy with conventional orthodox medical care.

Phenolic extract of soybean (Glycine max) attenuates cisplatin-induced nephrotoxicity in rats.

The present study investigated the modulatory role of phenolic extract of soybean (PESB) in a rat model of nephrotoxic acute renal failure induced by cisplatin. Cisplatin (2 mg/kg/day) was administered to the rats for 5 days and the animals were pretreated with PESB (250-1000 mg/kg). Blood urea nitrogen reduced by 49.8% and 59.0%, serum creatinine by 34.7% and 62.1% and urinary N-acetyl-beta-D-glucosaminidase also decreased by 37.7% and 49.2% following treatment with 250- and 500-mg/kg doses of the extract respectively in the cisplatin-treated rats. The extract also significantly increased renal myeloperoxidase activity by 26.8% and 40.6% at these doses. PESB also decreased renal xanthine oxidase activity and serum nitrate/nitrite in the cisplatin-treated rats. In addition, PESB significantly attenuated the marked renal oxidative damage that accompanied cisplatin treatment. The extract improved liver histology and significantly increased the activities of the antioxidant enzymes measured [superoxide dismutase, catalase, glutathione-S-transferase], prevented glutathione depletion and decreased malondialdehyde level following cisplatin treatment. Furthermore, cisplatin-induced decrease in the activities of glucose-6-phosphatase and 5'-nucleotidase in these rats was attenuated only at 250 mg/kg dose of the extract. We concluded therefore that PESB via antioxidant and possibly anti-inflammatory actions offered protective benefit against cisplatin-mediated acute toxic injury to the kidney.

Modulation of gentamicin-induced renal dysfunction and injury by the phenolic extract of soybean (Glycine max).

Gentamicin (GM) is one of the most important of the aminoglycoside antibiotics used widely for the treatment of serious and life-threatening infections and whose clinical use is limited by its nephrotoxicity. As the pathogenesis of GM-induced renal dysfunction and injury involves reactive oxygen species, the polyphenolic constituents of soybean with antioxidant property may protect against GM-induced renal toxicity. We therefore tested this hypothesis using phenolic extract of soybean (PESB) on GM-induced nephrotoxicity rat model. Administration of GM (80 mg/kg, s.c.) for 12 days to rats induced marked renal failure, characterized by a significantly increased plasma creatinine, urea and Na(+) ions levels, with K(+) depletion. This was also associated with decreases in the activity of the renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)] measured and depletion of both blood and renal reduced glutathione (GSH) levels. The activities of membrane-bound glucose-6-phosphatase (G6Pase) and 5(1)-nucleotidase (5(1)-NTD) enzymes as well as gamma-glutamyltransferase (gamma-GT) and aspartate aminotransferase (AST) (enzymes that are located in the proximal tubule) were decreased. Renal histology examination further confirmed the damage to the kidney as it reveals severe necrosis of the proximal renal tubules with deposition of colloid casts. These alterations were ameliorated in rats pretreated with PESB. The decrease in the activities of SOD, CAT, GST as well as GSH depletion observed in GM-treated rats was prevented in the rats pretreated with PESB. The activities of gamma-GT, AST and G6Pase were also increased in the kidney. These protective effects were dose dependent except for G6Pase activity and GSH levels that were preserved only at 500 mg/kg dose of PESB, and 5'-NTD activity that was dose dependently decreased. Furthermore, the extent of tubular damage induced by GM was reduced in rats that also received PESB. The lower dose (500 mg/kg) of the extract, however, appeared to provide better histological protection. These results suggest that the PESB has protective effects on GM-mediated nephropathy and this may be related to the action of the antioxidant polyphenolic content of the soybean.