Safety of Oral Carica papaya L. Leaf 10% Ethanolic Extract for Acute and Chronic Toxicity Tests in Sprague Dawley Rats.

Carica papaya L. leaves, traditionally utilized in dietary supplements and pharmaceuticals, exhibit a broad spectrum of potentially therapeutic properties, including anti-inflammatory, antimalarial, and wound healing properties. This study examined the acute and chronic toxicity of 10% ethanolic-extracted C. papaya leaf in Sprague Dawley rats. The acute toxicity assessment was a single oral dose of 5000 mg/kg body weight, while the chronic toxicity assessment included daily oral doses of 100, 400, 1000, and 5000 mg/kg over 180 days. Systematic monitoring covered a range of physiological and behavioral parameters, including body and organ weights. End-point evaluations encompassed hematological and biochemical analyses, along with gross and histopathological examinations of internal organs. Findings revealed no acute toxicity in the C. papaya leaf extract group, although a significant decrease in uterine weight was observed without accompanying histopathology abnormalities. In the chronic toxicity assessment, no statistically significant differences between the control and the C. papaya leaf extract groups were detected across multiple measures, including behavioral, physiological, and hematological indices. Importantly, histopathological examination corroborated the absence of any tissue abnormalities. The study results indicate that C. papaya leaf extract exhibited no adverse effects on the rats during the 180-day oral administration period, affirming its potential safety for prolonged usage.

In-vitro antimalarial activity of methanolic leaf- and stem-derived extracts from four Annonaceae plants.

OBJECTIVE: Plants in the Annonaceae family are known for having abundant biologically active secondary metabolites. They have been used in alternative drugs for various diseases in several countries, for instance, the bark of Cananga odorata (Lam.) Hook and Thomson is used for Ophthalmic inflammation and wound healing in Malaysia. Extracts from the leaves and stems of four Annonaceae plants, namely Uvaria longipes (Craib) L.L.Zhou, Y.C.F.Su & R.M.K.Saunders, Dasymaschalon sp., Artabotrys burmanicus A.DC, and Marsypopetalum modestum (Pierre) B.Xue & R.M.K.Saunders were investigated for growth inhibitory activity against blood-stage Plasmodium falciparum growth in vitro and for non-specific cytotoxicity against normal peripheral blood mononuclear cells (PBMCs). Antimalarial activity was assessed by invasion inhibition assay and the percentage of infected red blood cells on blood smears were determined. Cytotoxicity was tested by culturing PBMCs with the extracts, and viabilities were determined by Annexin V/propidium iodide staining. RESULTS: A. burmanicus stem extract and M. modestum leaf extract were capable of inhibiting growth of P. falciparum when used at 200 µg/mL compared to chloroquine. The extracts at effective concentrations, did not affect the viability of PBMCs. These results support further need for characterization of active compounds from specific Annonaceae plants in order to exploit their components for potential malaria treatment.

Cytotoxic and cytostatic effects of four Annonaceae plants on human cancer cell lines.

Several species of the Annonaceae plants have been used as complementary medicine for cancer-associated illnesses in some ethnic groups of northern Thailand. This study investigated the cytotoxic and cytostatic activity of methanolic extracts derived from the stems of these plants, including Uvaria longipes (Craib) L.L.Zhou, Y.C.F.Su & R.M.K.Saunders, Artabotrys burmanicus A.DC, Marsypopetalum modestum (Pierre) B.Xue & R.M.K.Saunders, and Dasymaschalon sp. Cell death induction of seven human cancer cell lines and cell cycle analyses were assessed by Annexin V and/or propidium iodide (PI) staining and analyzed by flow cytometry. Treatment of cancer cell lines with the extract of four Annonaceae plants resulted in various cytotoxic activities depending on cell type. The extract of U. longipes exhibited the highest cytotoxic activity capable of inducing cell death of several cancer cell lines, particularly against hepatocellular carcinoma cell lines (HepG2 and Hep3B). This extract was capable of inducing cell cycle arrest at the SubG1 phase. Phytochemical screening of all the extracts revealed the presence of alkaloids, sterols, tannins, anthraquinone glycoside, coumarin, and flavonoids. Determination of active compounds by high-performance liquid chromatography standards revealed bullatacin and asiminecin in all the extracts. The extract of Annonaceae stem or its compounds may provide an opportunity for the development of new therapies against cancer.

Cell cycle arrest and apoptosis induction by methanolic leaves extracts of four Annonaceae plants.

BACKGROUND: Uvaria longipes (Craib) L.L.Zhou, Y.C.F.Su & R.M.K.Saunders, Artabotrys burmanicus A.DC, Marsypopetalum modestum (Pierre) B.Xue & R.M.K.Saunders and Dasymaschalon sp. have been used for traditional medicine to treat cancer-like symptoms in some ethnic groups of Thailand and Laos. METHODS: We evaluated the anti-cancer activity of these Annonaceae plants against several human cancer cell lines. The apoptosis induction was detected by Annexin/propidium iodide (PI) staining. Phytochemical screening was tested by standard protocols and bioactive compounds were determined by HPLC. RESULTS: The crude extracts from leaves of U. longipes, Dasymaschalon sp., A. burmanicus, and M. modestum showed particular effects that were found to vary depending on the cancer cell line, suggesting that the effect was in a cell-type specific manner. Interestingly, the induction of apoptotic cell death was prominent by the leaves-derived crude extract of M. modestum. This crude was, therefore, subjected to cell cycle analysis by PI staining. Results showed that this crude extract arrested cell cycle and increased the percentage of cells in the SubG1 phase in some cancer cell lines. The phytochemical screening tests indicated that all crude extracts contained tannins and flavonoids. HPLC of flavonoids using standards identified rutin as an active compound in U. longipes and Dasymaschalon sp., whereas quercetin was found in U. longipes and M. modestum. CONCLUSIONS: These crude extracts provide a new source for rutin and quercetin, which might be capable of inducing cancer cell apoptotic death in a cell-type specific manner. This suggests, by analyzing the major bioactive compounds, the potential use of these crudes for chemotherapy in the future.