Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves

Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Penang, Malaysia.
Clinics (São Paulo, Brazil) (Impact Factor: 1.19). 06/2013; 68(6). DOI: 10.6061/clinics/2013(06)23
Source: PubMed


Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves.
Sprague Dawley rats were orally treated with five different single doses of the extract and screened for signs of toxicity for two weeks after administration. In the subchronic study, three different doses of the extract were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. Phytochemical standardization was performed using a colorimeter and high-performance liquid chromatography. Heavy metal detection was performed using an atomic absorption spectrometer.
The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the subchronic toxicity study, there were no significant adverse effects on food consumption, body weight, organ weights, mortality, clinical chemistry, hematology, gross pathology, or histopathology. However, a dose-dependent increase in the serum urea level was observed. The Ames test revealed that the extract did not have any potential to induce gene mutations in S. typhimurium, either in the presence or absence of S9 activation. Phytochemical analysis of the extract revealed high contents of phenolics, flavonoids, and tannins. High-performance liquid chromatography analysis revealed high levels of vitexin and isovitexin in the extract, and the levels of heavy metals were below the toxic levels.
The no-observed adverse effect level of F. deltoidea in rats was determined to be 2500 mg/kg.

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    • "Vegetable oils rich in bioactive compounds are receiving growing interest due to their role in disease prevention through diet improvement (Coimbra and Jorge, 2011). However, toxicological studies are required to determine the toxicity and thus establish criteria for the selection of a safe dose (Berenguer-Rivas et al., 2013; Farsi et al., 2013). The present study may represent the first study that demonstrates the absence of toxicity of the oil extracted from the pulp of A. aculeata, which can contribute to the safe use of this species. "
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    ABSTRACT: Acrocomia aculeata, popularly known as “bocaiúva”, is a species used for nutritional purposes and for the treatment of various diseases, as it has, among other things, high levels of antioxidant compounds. This study aimed to assess the toxicological profile of A. aculeata, through acute and subacute toxicity tests. Male and female rats (Wistar) received by gavage 2000 mg/kg of oil extracted from the pulp of A. aculeata (OPAC) for the acute toxicity test and 125, 250, 500 or 1000 mg/kg of OPAC for subacute toxicity test. In the acute toxicity study no mortality or behavioral changes were observed in rats treated with 2000 mg/kg, indicating that the LD50 is higher than this dose. In the subacute toxicity test, the tested doses produced no significant changes in hematological, biochemical or histopathological parameters in the animals exposed. These results demonstrate the absence of acute and subacute toxicity after oral exposure to A. aculeata oil in rats. However, further studies in animals and in humans are needed in order to have sufficient safety evidence for its use in humans.
    Food and Chemical Toxicology 10/2014; 74. DOI:10.1016/j.fct.2014.10.026 · 2.90 Impact Factor
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    • "Phytochemical such as protein, polysaccharide, glycosaponin, phenolics, flavonoids and tanins were analyzed in the F. deltoidea leaf extracts. The total contents of proteins, polysaccharides and glycosaponin in the extracts were estimated calorimetrically, according to the previous study [16]. Total phenolics were determined using the Folin-Ciocalteau reagent with gallic acid as a standard and the results were expressed as mg of gallic acid equivalents, whereas total flavonoids were determined using the AlCl3 colorimetric method with quercetin (QNT) as a standard and the results were expressed as μg of QNT equivalent. "
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    ABSTRACT: Background Recently, there has been increasing interest in Ficus deltoidea Jack. (Moraceae) due to its chemical composition and the potential health benefits. The present study was undertaken to investigate the effect of extracts of F. deltoidea leaves on diabetes. Methods The petroleum ether, chloroform and methanol extracts of F. deltoidea were prepared and subjected to standardization using preliminary phytochemical and HPLC analysis. Dose selection was made on the basis of acute oral toxicity study (50–5000 mg/kg b. w.) as per OECD guidelines. Diabetes mellitus was induced with streptozotocin and rats found diabetic were orally administered with the extract (250, 500 and 1000 mg/kg) for 14 days. Levels of blood glucose and insulin were measured in control as well as diabetic rats on 0, 7 and 14th day. In addition, glucose metabolism regulating gene expression was assessed using RT-PCR. Results HPLC analysis revealed that the methanol extract is enriched with C-glycosylflavones particularly, vitexin and isovitexin. In oral glucose tolerance test, oral administration of the methanol extract increased the glucose tolerance. The methanol extract showed significant (P < 0.01) antidiabetic activity. The extract treatment caused significant reduction (p < 0.01) in elevated fasting blood glucose level in streptozotocin-induced diabetic rats. The streptozotocin-related weight loss in rats was noticeably reversed by the extract treatment. Finally, RT-PCR analysis revealed a novel mechanisms for the anti-diabetic action of methanol extract of F. deltoidea. The extract exerted its effect via an increase of insulin secretion which impeded the hepatic glucose production, via down-regulation of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase genes expression on one hand, and up-regulation of hepatic GK and PPARγ genes expression on the other hand. The extract caused an increased expression of GLUT-4 gene expression in skeletal muscles which leads to normalize the hyperglycemia. The extract also nullified the toxic effects of streptozitocin by blocking its entry into the islet β-cells through reducing the expression of GLUT-2 gene. Conclusion It can be concluded that, F. deltoidea could potentially inhibits the streptozitocin-induced hyperglycemia in rats. Further the herb can be utilized as useful remedy for alleviation of diabetes complications.
    BMC Complementary and Alternative Medicine 07/2014; 14(1):220. DOI:10.1186/1472-6882-14-220 · 2.02 Impact Factor
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    • "Comprehensive attempts have been made on efficiency and safety studies on F. deltoidea [34–36]. A study by Shafaei et al. [35] confirmed that F. deltoidea leaves do not contain toxic elements by evaluating toxicological elements (lead, cadmium, arsenic, and mercury) using atomic absorption spectroscopy technique, standardisation parameters (moisture, volatile, total ash, and acid insoluble ash), and Microbial Limit Test (MLT) for microbial contamination. "
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    ABSTRACT: Ficus deltoidea Jack (Moraceae) has had a long history of use in traditional medicine among the Malays to alleviate and heal ailments such as sores, wounds, and rheumatism and as an after-birth tonic and an antidiabetic drug. Modern pharmacological studies demonstrated that this plant has a wide variety of beneficial attributes for human health. Despite its importance, a review of this species has not been published in the scientific literature to date. Here, we review and summarize the historic and current literature concerning the botany, traditional uses, phytochemistry, pharmacological effects, and toxicity of this wonder plant. This summary could be beneficial for future research aiming to exploit the therapeutic potential of this useful, medicinal species.
    Evidence-based Complementary and Alternative Medicine 03/2014; 2014:902734. DOI:10.1155/2014/902734 · 1.88 Impact Factor
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