Assessing the Acute Toxicological Effects of Annona muricata Leaf Ethanol Extract on Rats: Biochemical, Histopathological, and Metabolomics Analyses.

Annona muricata is a common plant used in Africa and South America to manage various types of disease. However, there is insufficient toxicological information or published standard available regarding repeated dose animal toxicity data. As part of the safety assessment, we exposed Sprague Dawley rats to an acute oral toxicity of A. muricata. The intent of the current study was to use advanced proton nuclear magnetic resonance (1H NMR) in serum and urinary metabolomics evaluation techniques to provide the in vivo acute toxicological profile of A. muricata leaf ethanol extract in accordance with the Organization for Economic Co-operation and Development's (OECD) 423 guidelines. A single 2000 mg/kg dose of A. muricata leaf ethanol extract was administered to Sprague Dawley rats over an observational period of 14 days. The toxicity evaluation (physical and behavior observation, body weight, renal function test, liver function test and 1H NMR analysis) showed no abnormal toxicity. Histopathological analysis manifested mild changes, i.e., the treated kidney manifested mild hypercellularity of mesangial cells and mild red blood cell congestion. In addition, there was mild hemorrhage into tissue with scattered inflammatory cells and mild dilated central vein with fibrosis in the liver. However, the changes were very mild and not significant which correlate with other analyses conducted in this study (biochemical test and 1H NMR metabolomic analysis). On the other hand, urinary 1H NMR analysis collected on day 15 revealed high similarity on the metabolite variations for both untreated and treated groups. Importantly, the outcomes suggest that A. muricata leaf ethanol extract can be safely consumed at a dose of 2000 mg/kg and the LD50 must be more than 2000 mg/kg.

Urinary Metabolomics and Biochemical Analysis of Antihyperglycemic Effect of Ficus deltoidea Jack Varieties in Streptozotocin-Nicotinamide-Induced Diabetic Rats.

Patients are turning into herbs for the management of diabetes, which cause increasing in the demand of plant-based alternative medicines. Ficus deltoidea or locally known as "Mas Cotek" in Malaysia is a famous herbal plant. However, many varieties of F. deltoidea existed with varied antidiabetic activities inspire us to evaluate in vivo antidiabetic activity of the most available varieties of F. deltoidea. Therefore, antihyperglycemic effect of different varieties of F. deltoidea at dose 250 mg/kg was evaluated on streptozotocin-nicotinamide-induced diabetic rats and further assessed their urinary metabolites using proton nuclear magnetic resonance (1H-NMR). The hyperglycemic blood level improved towards normoglycemic state after 30 days of treatment with standardized extracts of F. deltoidea var. trengganuensis, var. kunstleri, and var. intermedia. The extracts also significantly managed the biochemical parameters in diabetic rats. Metabolomics results showed these varieties were able to manage the altered metabolites of diabetic rats by shifting some of the metabolites back to their normal state. This knowledge might be very important in suggesting the use of these herbs in long-term treatment for diabetes. The most potential variety can be recommended, which may be useful for further pharmacological studies and herbal authentication processes.

Standardized ethanol-water extract of Ficus deltoidea Angustifolia reduces blood pressure in spontaneously hypertensive rats.

Ficus deltoidea is used in Malay traditional medicine for the treatment of a number of disorders, including hypertension. There is, however, no scientific evidence on its anti-hypertensive effects. This study, therefore, investigated the effects of a standardized ethanolic-water extract of Ficus deltoidea Angustifolia (FD-A) on blood pressure (BP) in spontaneously hypertensive rats (SHR). Male SHR with systolic BP of >150 were divided into 4 groups (n = 8) and given either FD-A (800 or 1000 mg kg-1 day-1) or losartan (10 mg kg-1 day-1) or 0.5 ml of distilled water (control) daily for 28 days. BP, body weight, food and water intake, serum and urinary electrolytes, endothelin-1 (ET-1), total antioxidant capacity (TAC) and components of the renin-angiotensin-aldosterone system were measured. Data were analyzed using ANOVA with statistical significance set at p < 0.05. Following treatment, BP, heart rate, and heart weight in FD-A and losartan-treated rats were significantly lower than those in the controls. Serum TAC and urinary calcium excretion were significantly higher, whereas serum ET-1 concentration was significantly lower in FD-A treated rats when compared to those in controls. No significant differences were found in the components of the renin-angiotensin-aldosterone system between controls and FD-A treated rats. In conclusion, FD-A when given daily at doses of either 800 or 1000 mg kg-1 day-1 body weight reduces BP in SHR. This effect does not seem to involve the renin-angiotensin-aldosterone-system but might involve some other mechanisms. Abbreviations: FD-A: Ficus deltoidea Angustifolia; ACE: Angiotensin-converting enzyme; SHR: Spontaneously hypertensive rats; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; AUC: Area under curve; RAAS: Renin Angiotensin Aldosterone System.