Bioactive constituents of Emblica officinalis overcome oxidative stress in mammalian cells by inhibiting hyperoxidation of peroxiredoxins.

Emblica officinalis (Amla) is a renowned fruit having nutritional and medicinal traits mostly linked to its antioxidants content. In the current study, the methanolic crude extract of amla fruit is subjected to sequential fractionation to get its partially purified fractions. The ethyl acetate (EA) and butanol (BUT) fractions of amla showed maximum antioxidant potential. The ferric reducing capability and nitric oxide scavenging activity were highest in EA fraction. One of the highlights of the study is the cellular antioxidant assay conducted in HeLa cells. Additionally, HeLa cells pre-treated with EA and BUT fractions were able to combat oxidative stress via total reduction in hyperoxidation of intracellular peroxiredoxin enzyme. Gallic acid, ascorbic acid, ellagic acid, rutin, quercetin, and catechol are the major compounds present in these fractions as identified by LC-ESI-MS followed by their quantification by HPLC. These findings indicate that components of E. officinalis can protect intracellular oxidative stress-mediated degeneration. PRACTICAL APPLICATIONS: The study highlighted that E. officinalis is a promising source of phenolics and flavonoids acting as natural antioxidants, which showed varied potential to scavenge ROS. Also, the plant fractions were able to fight intracellular oxidative stress via total reduction in hyperoxidation of the human peroxiredoxin. In conclusion, we can say that the regular intake of such food supplements that affect important antioxidant enzymes can be of special interest in the management of oxidative stress-mediated human ailments.

Deciphering the in vivo redox behavior of human peroxiredoxins I and II by expressing in budding yeast.

Peroxiredoxins (Prxs), scavenge cellular peroxides by forming recyclable disulfides but under high oxidative stress, hyperoxidation of their active-site Cys residue results in loss of their peroxidase activity. Saccharomyces cerevisiae deficient in human Prx (hPrx) orthologue TSA1 show growth defects under oxidative stress. They can be complemented with hPRXI but not by hPRXII, but it is not clear how the disulfide and hyperoxidation states of the hPrx vary in yeast under oxidative stress. To understand this, we used oxidative-stress sensitive tsa1tsa2Δ yeast strain to express hPRXI or hPRXII. We found that hPrxI in yeast exists as a mixture of disulfide-linked dimer and reduced monomer but becomes hyperoxidized upon elevated oxidative stress as analyzed under denaturing conditions (SDS-PAGE). In contrast, hPrxII was present predominantly as the disulfide in unstressed cells and readily converted to its hyperoxidized, peroxidase-inactive form even with mild oxidative stress. Interestingly, we found that plant extracts containing polyphenol antioxidants provided further protection against the growth defects of the tsa1tsa2Δ strain expressing hPrx and preserved the peroxidase-active forms of the Prxs. The extracts also helped to protect against hyperoxidation of hPrxs in HeLa cells. Based on these findings we can conclude that resistance to oxidative stress of yeast cells expressing individual hPrxs requires the hPrx to be maintained in a redox state that permits redox cycling and peroxidase activity. Peroxidase activity decreases as the hPrx becomes hyperoxidized and the limited protection by hPrxII compared with hPrxI can be explained by its greater sensitivity to hyperoxidation.

Sodium Dodecyl Sulphate-Supported Nanocomposite as Drug Carrier System for Controlled Delivery of Ondansetron.

Sodium dodecyl sulphate-supported iron silicophosphate (SDS/FeSP) nanocomposite was successfully fabricated by the co-precipitation method. The SDS/FeSP nanocomposite was investigated as a drug carrier for ondansetron. The cumulative drug release of ondansetron was observed at various pH values for different time intervals, i.e., from 20 min to 48 h. A ranking of the drug release was observed at different pHs; pH 2.2 > saline (pH 5.5) > pH 7.4 > pH 9.4 > distilled water. Maximum release of encapsulated drug was found to be about 45.38% at pH 2.2. The cell viability tests of SDS/FeSP nanocomposite concluded that SDS/FeSP nanocomposite was non-cytotoxic in nature.