The role of frataxin in doxorubicin-mediated cardiac hypertrophy.

Doxorubicin (DOX) is a highly effective anti-neoplastic agent; however, its cumulative dosing schedules are clinically limited by the development of cardiotoxicity. Previous studies have attributed the cause of DOX-mediated cardiotoxicity to mitochondrial iron accumulation and the ensuing reactive oxygen species (ROS) formation. The present study investigates the role of frataxin (FXN), a mitochondrial iron-sulfur biogenesis protein, and its role in development of DOX-mediated mitochondrial dysfunction. Athymic mice treated with DOX (5 mg/kg, 1 dose/wk with treatments, followed by 2-wk recovery) displayed left ventricular hypertrophy, as observed by impaired cardiac hemodynamic performance parameters. Furthermore, we also observed significant reduction in FXN expression in DOX-treated animals and H9C2 cardiomyoblast cell lines, resulting in increased mitochondrial iron accumulation and the ensuing ROS formation. This observation was paralleled in DOX-treated H9C2 cells by a significant reduction in the mitochondrial bioenergetics, as observed by the reduction of myocardial energy regulation. Surprisingly, similar results were observed in our FXN knockdown stable cell lines constructed by lentiviral technology using short hairpin RNA. To better understand the cardioprotective role of FXN against DOX, we constructed FXN overexpressing cardiomyoblasts, which displayed cardioprotection against mitochondrial iron accumulation, ROS formation, and reduction of mitochondrial bioenergetics. Lastly, our FXN overexpressing cardiomyoblasts were protected from DOX-mediated cardiac hypertrophy. Together, our findings reveal novel insights into the development of DOX-mediated cardiomyopathy.

Immunomodulatory actions of a Polynesian herb Noni (Morinda citrifolia) and its clinical applications.

Morinda citrifolia (Noni) is a popular traditional medicinal plant consumed in various forms in several countries around the world as a complementary and alternative treatment due to its established health benefits. Noni is rich in bioactive substances and has significantly exhibited pro-oxidant and immunomodulatory effects. In this review, we highlight the pharmacological basis related to the phytochemicals and polysaccharides present in Noni and its potential therapeutic effects. We screened electronic databases such as PubMed, Google Scholar, Scopus for scientific literature. Our results indicate that Noni is beneficial for various diseases with its crude extracts showing therapeutic benefit for a wide range of pathological diseases. We believe that further pharmacological and toxicological studies in addition to well-designed controlled clinical trials can validate Noni to be an effective and novel natural product for prophylactic and therapeutic use of several diseases.

Anti-oxidative and DNA protecting effects of flavonoids-rich Scutellaria lateriflora.

Scutellaria lateriflora (American skullcap), a native plant of North America, has been used by Americans and Europeans as a nerve tonic for more than 200 years. In vivo studies have shown anxiolytic activity ofS. lateriflora in animals and humans. However, the neuroprotective mechanisms ofS. lateriflora are not fully understood. Oxidative stress plays a vital role in the neurodegenerative and neuropsychiatric diseases such as anxiety, Alzheimer's disease, depression, and Parkinson's disease. Bioactive compounds present in various medicinal plants neutralize or scavenge toxic free radicals and thus suppress oxidative stress. Therefore, the objective of this study was to investigate the antioxidant effects of S. lateriflora. The antioxidant potential of aqueous or ethanolic extracts of S. lateriflora was determined in mouse brain tissue using various biochemical assays. Protective effects of S. lateriflora against oxidative stress induced DNA fragmentation was determined using plasmid DNA. The ethanolic and aqueous extracts scavenged the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. The ethanolic extract reduced tert-butyl peroxide-induced reactive oxygen species (ROS) and lipid peroxides in the mouse brain homogenates. Furthermore, the ethanolic extract of S. lateriflora protected hydrogen peroxide-UV induced cleavage of supercoiled plasmid DNA. In conclusion, S. lateriflora exhibited significant antioxidant effects. The current findings posit S. lateriflora as one of the potential experimental herbal drugs that should be screened for its therapeutic potential against various oxidative stress associated mental disorders.