Therapeutic Efficacy of Nyctanthes arbor-tristis Flowers to Inhibit Proliferation of Acute and Chronic Primary Human Leukemia Cells, with Adipocyte Differentiation and in Silico Analysis of Interactions between Survivin Protein and Selected Secondary Metabolites.

Although the antidiabetic efficacy of Nyctanthes arbor-tristis flowers has been reported, antiproliferative and anti-obesity activities are yet to be explored. We examined the anti-obesity and antiproliferative potentials of different fractions (hexane, chloroform, ethyl acetate, methanol) of N. abor-tristis flower extract for the first time using 3T3-L1 cells, primary peripheral blood mononuclear cells (PBMC) isolated from healthy and adult acute myeloid (AML) and chronic lymphocytic leukemia (CLL) patients, recombinant Jurkat T cells, and MCF7 cell lines. The in vitro hypoglycemic activity was evaluated using the inhibition of -amylase enzyme and glucose uptake by yeast cells. The percentage glucose uptake and -amylase inhibitory activity increased in a dose-dependent manner in the crude and the tested fractions (hexane and ethyl acetate). Inhibition of the 3T3-L1 cells' differentiation was observed in the ethyl acetate and chloroform fractions, followed by the hexane fraction. Antiproliferative analyses revealed that Nyctanthes exerted a high specific activity against anti-AML and anti-CLL PBMC cells, especially by the hexane and ethyl acetate fractions. The gas chromatography/mass spectrometry analysis indicated the presence of 1-heptacosanol (hexane fraction), 1-octadecene (hexane and chloroform fractions), and other organic compounds. Molecular docking demonstrated that phenol,2,5-bis(1,1-dimethylethyl) and 4-hydroxypyridine 1-oxide compounds showed specificity toward survivin protein, indicating the feasibility of N. abor-tristis in developing new drug leads against leukemia.

Low doses of chlorpyrifos interfere with spermatogenesis of rats through reduction of sex hormones.

Use of pesticides results in indirect effects on human health. We aimed to evaluate implications of toxicological effects of subchronic chlorpyrifos exposure on reproductive function in male rats. A total of 48 adult Wistar male rats were separated into four groups (n = 12). Animals were gavaged with 2.5 mg/kg (T1), 5 mg/kg (T2), or 10 mg/kg (T3) body weight of chlorpyrifos (CPF) or distilled water (control) daily for 30 days. Organ weights, epididymal sperm parameters, DNA integrity, sex hormonal (FHS and LH) levels, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and creatinine concentrations were determined on day 31. Another two sets of (four groups/set; n = 10) animals were orally treated with the same doses of CPF, control animal groups were treated with distilled water only for 30 days, and fertility indices and blood plasma acetylcholine esterase (AchE) were determined on day 31. Exposure to CPF resulted in a significant (p < 0.05) decrease in weights of testis and epididymis. An increase in liver weight resulted in reduced sperm counts and sperm motility and an increase in sperm abnormalities. Significant reduction in serum testosterone (p < 0.01), luteinizing hormone (p < 0.05), and follicular stimulating hormone (p < 0.05) levels was evident in animals treated with the highest dose. A significant decrease in the number of viable implantation sites and pups was observed in female rats mated with the T3 (p < 0.01) and T2 (p < 0.05) males. The ALT, AST, GGT, and creatinine contents were significantly increased (p < 0.05 and p < 0.01, respectively) on CPF exposure. A significant (p < 0.01) reduction in blood plasma AchE enzyme was observed with the highest dose. Our results demonstrated that prolonged exposure of CPF induces spermatogenesis damage, possibly through interference with sex hormones and AchE enzyme resulting in reduction of fertility. Therefore, awareness programs on handling CPF (pesticides) to enhance safety warrant minimization of its hazards.

Hypoglycemic and hypolipidemic activities of aqueous extract of flowers from Nycantus arbor-tristis L. in male mice.

BACKGROUND: Boiled aqueous extract of flowers (AEF) from Nyctanthes arbor-tristis L. are used in Sri Lankan traditional Ayruvedic Medicine to manage diabetes mellitus. AEF has widely been used as a folk medicine for the treatment of various ailments due to its therapeutic activity. However, little is known concerning therapeutic activity of the extract as well as its underline mechanisms and safety. Diabetes is known to increase low-density cholesterol and decrease high-density cholesterol thus triggering coronary diseases. Hence, the primary objective of the present study is to investigate the hypoglycemic and hypolipidemic activities of the AEF. METHODS: AEF was prepared and male mice (n = 9 group) were gavaged either with 250, 500 and 750 mg/kg of AEF or distilled water (DW). Subsequently, fasting and random blood glucose concentrations were determined. To investigate mechanisms of actions of AEF, animals were orally administered with 500 mg/kg or the vehicle (DW) and glucose tolerance was performed before and after glucose challenge. For further studies, in vitro alpha-amylase assay and glucose absorption from the gastrointestinal tract were performed using 500 mg/kg of the extract. Additionally, glycogen content in the liver and skeletal muscles, a complete lipid profile assay, and toxicological and biochemical parameters were conducted after a chronic study. RESULTS: Five hundred mg/kg and 750 mg/kg of AEF significantly (p < 0.01) reduced fasting blood glucose levels respectively by 49 and 39% at 4 h post-treatment, while 500 mg/kg of AEF also decreased the random blood glucose level significantly (p < 0.01) by 32% at 4 h post-treatment. AEF significantly inhibited glucose absorption by 85% from the intestine and increased diaphragm uptake of glucose by 64%. The extract also exhibited inhibition (16.66%) of alpha-amylase enzyme activity. It also decreased the level of total cholesterol (by 44.8%), triglyceride (by 53%) and increased (by 57%) the high-density lipoprotein cholesterol. Treatment with AEF did not induce any overt signs of toxicity or hepatotoxicity. CONCLUSION: Results the present study indicated that AEF possess hypoglycemic and hypolipdemic properties. Therefore, AEF could be used as an alternative medicine in management of diabetes mellitus.