OBJECTIVE: The present study aims to investigate the effects of a standardized raw extract of C. asiatica (RECA) on hydrogen peroxide (H2O2)-induced oxidative stress and apoptotic death in neural-like cells derived from mouse embryonic stem (ES) cell line.

METHODS: A transgenic mouse ES cell (46C) was differentiated into neural-like cells using 4-/4+ protocol with addition of all-trans retinoic acid. These cells were then exposed to H2O2 for 24 h. The effects of RECA on H2O2-induced neural-like cells were assessed through cell viability, apoptosis, and reactive oxygen species (ROS) assays, as well as neurite length measurement. The gene expression levels of neuronal-specific and antioxidant markers were assessed by RT-qPCR analysis.

RESULTS: Pre-treatment with H2O2 for 24 hours, in a dose-dependent manner, damaged neural-like cells as marked by a decrease in cell viability, substantial increase in intracellular ROS accumulation, and increase in apoptotic rate compared to untreated cells. These cells were used to treat with RECA. Treatment with RECA for 48 h remarkably restored cell survival and promoted neurite outgrowth in the H2O2- damaged neurons by increasing cell viability and decreasing ROS activity. RT-qPCR analysis revealed that RECA upregulated the level of antioxidant genes such as thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO-1) of treated cells, as well as the expression level of neuronal-specific markers such as Tuj1 and MAP2 genes, suggesting their contribution in neuritogenic effect.

METHODS: F. deltoidea and vitexin was administrated orally to six-weeks STZ-induced diabetic rats over 8 weeks period. The glucose and insulin tolerances were assessed by intraperitoneal glucose (2 g/kg) tolerance test (IPGTT) and intraperitoneal insulin (0.65 U/kg) tolerance test (IPITT), respectively. Subsequently, insulin resistance was assessed by homeostasis assessment model of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and the insulin/triglyceride-derived McAuley index. The histological changes in the pancreas were then observed by hematoxylin-eosin (H&E) staining. Further, the pattern of fatty acid composition and infrared (IR) spectra of the serum and pancreas were monitored by gas chromatography (GC) method and Fourier Transform Infrared (FT-IR) spectroscopy.

RESULTS: F. deltoidea and vitexin increased pancreatic antioxidant enzymes and promoted islet regeneration. However, a significant increase in insulin secretion was observed only in rats treated with F. deltoidea. More importantly, reduction of fasting blood glucose is consistent with reduced FT-IR peaks at 1200-1000 cm-1.

METHODOLOGY/PRINCIPAL FINDINGS: The hexane extract of C. cassia demonstrated high anti-proliferative activity against MCF-7 and MDA-MB-231 cells (IC50, 34 ± 3.52 and 32.42 ± 0.37 μg/ml, respectively). Oxidative stress due to disruption of antioxidant enzyme (SOD, GPx and CAT) activity is suggested as the probable cause for apoptosis initiation. Though the main apoptosis pathway in both cell lines was found to be through caspase-8 activation, caspase-9 was also activated in MDA-MB-231 cells but suppressed in MCF-7 cells. Gene expression studies revealed that AKT1, the caspase-9 suppressor, was up-regulated in MCF-7 cells while down-regulated in MDA-MB-231 cells. Although, AKT1 protein expression in both cell lines was down-regulated, a steady increase in MCF-7 cells was observed after a sharp decrease of suppression of AKT1. Trans-cinnamaldehyde and coumarin were isolated and identified and found to be mainly responsible for the observed anti-proliferative activity of CE (Cinnamomum cassia).

RESULTS: Fermented mung bean was recorded to have the highest level of free amino acids, soluble phenolic acids (especially protocatechuic acid) and antioxidant activities among all the tested products. Both fermented mung bean and soybean possessed cytotoxicity activities against breast cancer MCF-7 cells by arresting the G0/G1 phase followed by apoptosis. Moreover, fermented mung bean and soybean also induced splenocyte proliferation and enhanced the levels of serum interleukin-2 and interferon-γ.

RESULTS: Pineapple juice vinegar, which had the highest total phenolic acid content, also exhibited the greatest in vitro antioxidant capacity compared to coconut juice and nipah juice vinegars. Following acute and sub-chronic in vivo toxicity evaluation, no toxicity and mortality were evident and there were no significant differences in the serum biochemical profiles between mice administered the vinegars versus the control group. In the sub-chronic toxicity evaluation, the highest liver antioxidant levels were found in mice fed with pineapple juice vinegar, followed by coconut juice and nipah juice vinegars. However, compared to the pineapple juice and nipah juice vinegars, the mice fed with coconut juice vinegar, exhibited a higher population of CD4+ and CD8+ T-lymphocytes in the spleen, which was associated with greater levels of serum interleukin-2 and interferon-γ cytokines.

METHODS: Thirty-five male rabbits of New Zealand strain were randomly assigned to seven groups. For 12 weeks, group CH was fed 1% cholesterol diet only; group C1 was fed 1% cholesterol diet and 0.50 ml/kg/day B. angulata WF juice; group C2 was fed 1% cholesterol diet and 1.00 ml/kg/day B. angulata WF juice; group C3 was fed 1% cholesterol diet and 1.50 ml/kg/day B. angulata WF juice; group N was fed standard pellet only; group N1 was fed standard pellet and 0.50 ml/kg/day B. angulata WF juice; and group N2 was fed standard pellet and 1.00 ml/kg/day B. angulata WF juice.

RESULTS: The three doses reduced the formation of MDA and enhanced the expression of endogenous antioxidant enzymes. The highest dose used (1.50 ml/kg/day) was, however, seen as the most potent.