Moringa oleifera mitigates ethanol-induced oxidative stress, fatty degeneration and hepatic steatosis by promoting Nrf2 in mice.

BACKGROUND: Moringa oleifera (M. oleifera) is cultivated throughout the world and it is known by numerous regional names and is consumed as medication for various diseases such as hypertension, diabetes, HIV and is potential source of nutrients and natural antioxidants making it among the most useful trees. METHODS: We evaluated the therapeutic potential of M. oleifera on ethanol-induced fatty liver. The mice were treated with 30% ethanol (EtOH) alone or in combination with different concentration of M. oleifera extracts (100, 200 and 400 mg/kg). We performed biochemical estimation for the serum of important liver damage markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and triglyceride (TG). We performed histopathological analysis from the liver tissues of different mice groups. We also performed ELISA assay, western blotting analysis and SPECT imaging to obtain our results. RESULTS: The results for serum (AST, p < 0.0001), (ALT, p < 0.0006) and triglyceride (TG, p < 0.0003) were found to be significantly reduced in all doses of M. oleifera extract treatment groups in comparison with the ethanol group. H&E staining analysis and scoring revealed a significant reduction in lipid droplet accumulation and a significant reduction of liver steatosis (p < 0.0001), lobular inflammation (p < 0.0013), ballooning (p < 0.0004) and immunohistochemistry for TNF-α. M. oleifera also ameliorated ethanol-induced oxidative stress evaluated through MDA (p < 0.0001), H2DCFDA, JC-1 staining and a significant down-regulation of CYP2E1 enzyme (p < 0.0001) in the 200 and 400 mg/kg groups in comparison with EtOH groups. M. oleifera extract also boosted the antioxidant response evaluated through total GSH assay (p < 0.0001) and nuclear translocation of Nrf2. Furthermore, we performed SPECT imaging and evaluated the liver uptake value (LUV) to assess the extent of liver damage. LUV was observed to be lower in the ethanol group, whereas LUV was higher in control and M. olifera treated groups. CONCLUSION: In summary, from this experiment we conclude that M. oleifera extract has the potential to ameliorate ethanol-induced liver damage.

Phorbol 12-Myristate 13-Acetate Induced Toxicity Study and the Role of Tangeretin in Abrogating HIF-1α-NF-κB Crosstalk In Vitro and In Vivo.

Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 µg) caused chromosomal aberrations on the Allium cepa root tip and induced mitotic dysfunction. Similarly, PMA caused embryonic and larval deformities and a plummeted survivability rate on zebrafish embryo in a dose-dependent manner. Persistently, PMA treatment on immortalized human keratinocyte human keratinocyte (HaCaT) cells caused massive inflammatory rush at 4 h and a drop in cell survivability at 24 h. Concomitantly, we replicated a cutaneous inflammation similar to human psoriasis induced by PMA. Herein, we used tangeretin (TAN), as an antagonist to counteract the inflammatory response. Results from an in vivo experiment indicated that TAN (10 and 30 mg/kg) significantly inhibited PMA stimulated epidermal hyperplasia and intra-epidermal neutrophilic abscesses. In addition, its treatment effectively neutralized PMA induced elevated reactive oxygen species (ROS) generation on in vitro and in vivo systems, promoting antioxidant response. The association of hypoxia-inducible factor 1-alpha (HIF-1α)-nuclear factor kappa-light-chain-enhancer of activated b cells (NF-κB) crosstalk triggered by PMA enhanced PKCα-ERK1/2-NF-κB pathway; its activation was also significantly counteracted after TAN treatment. Conclusively, we demonstrated TAN inhibited the nuclear translocation of HIF-1α and NF-κB p65. Collectively, TAN treatment ameliorated PMA incited malignant inflammatory response by remodeling the cutaneous microenvironment.

Effect of Amino Acids on the Generation of Ginsenoside Rg3 Epimers by Heat Processing and the Anticancer Activities of Epimers in A2780 Human Ovarian Cancer Cells.

Ginsenosides are the active components of Panax ginseng. Many research studies indicate that these deglycosylated, less-polar ginsenosides have better bioactivity than the major ginsenosides. In the present study, we sought to verify the enhanced anticancer effect of P. ginseng extract after undergoing the Maillard reaction as well as elucidate the underlying mechanism of action. The effects of 9 amino acids were tested; among them, the content of 20(S)-Rg3 in the ginseng extract increased to more than 30, 20, and 20% when processed with valine, arginine, and alanine, respectively, compared with that after normal heat processing. The ginseng extract that was heat-processed with arginine exhibited the most potent inhibitory effect on A2780 ovarian cancer cell proliferation. Therefore, the generation of 20(S)-Rg3 was suggested to be involved in this effect. Moreover, the inhibitory effect of 20(S)-Rg3 on A2780 cell proliferation was significantly stronger than that of 20(R)-Rg3. Protein expression levels of cleaved caspase-3, caspase-8, caspase-9, and PARP in the A2780 ovarian cancer cells markedly increased, whereas the expression of BID decreased after 20(S)-Rg3 treatment. Therefore, we confirmed that the anticancer effects of the products of ginseng that was heat-processed with arginine are mediated mainly via the generation of the less-polar ginsenoside 20(S)-Rg3.