Ameliorating effect of rutin against diclofenac-induced cardiac injury in rats with underlying function of FABP3, MYL3, and ANP.

Diclofenac is a widely prescribed anti-inflammatory drug having cardiovascular complications as one of the main liabilities that restrict its therapeutic use. We aimed to investigate for any role of rutin against diclofenac-induced cardiac injury with underlying mechanisms as there is no such precedent to date. The effect of rutin (10 and 20 mg/kg) was evaluated upon concomitant oral administration for fifteen days with diclofenac (10 mg/kg). Rutin significantly attenuated diclofenac-induced alterations in the serum cardiac markers (LDH, CK-MB, and SGOT), serum cytokine levels (TNF-α and IL-6), and oxidative stress markers (MDA and GSH) in the cardiac tissue. Histopathological examination and Scanning Electron Microscopy (SEM) findings displayed a marked effect of rutin to prevent diclofenac-mediated cardiac injury. Altered protein expression of myocardial injury markers (cTnT, FABP3, and ANP) and apoptotic markers (Bcl-2 and Caspase-3) in the cardiac tissue upon diclofenac treatment was considerably shielded by rutin treatment. MYL3 was unaffected due to diclofenac or rutin treatment. Rutin also significantly improved diclofenac-induced gastrointestinal and hepatic alterations based on the observed ameliorative effects in key mediators, oxidative stress markers, histopathology examination, and SEM findings. Overall results suggest that rutin can protect the diclofenac-induced cardiac injury by lowering oxidative stress, inhibiting inflammation, and reducing apoptosis. Further research work directs toward the development of phytotherapeutics for cardioprotection.

Antimicrobial and Cytotoxic Potential of Helminthosporin from Rumex abyssiniscus Jacq. Discovered as a Novel Source of Syringic Acid and Bis(2-ethyloctyl) Phthalate.

Rumex abyssinicus Jacq. is a perennial medicinal herb widely used in traditional medicine to treat many diseases. Phytochemicals of the plant were isolated using column chromatography and thin layer chromatography techniques. Extract, fractions and pure compounds were screened for antimicrobial activity against sensitive and multi-drug resistant microbes and their cytotoxicity was performed on different cancer cell lines. The mechanism of action of purified helminthosporin as well as the potent fraction containing a mixture of two compounds was assessed. Fraction R7C3 was the most potent antibacterial with the lowest MIC value of 0.12 µg/mL. Helminthosporin was the most potent compound with the lowest MIC value of 1.95 µg/mL. The compound was more potent than the antibiotic chloramphenicol against multi-drug resistant (MDR) bacteria with MIC equal to 16 µg/mL. The fraction and helminthosporin were shown to destroy the cell wall of the yeast and bacteria, and DNA fragmentation effect on the genome of Candida albicans and Bacillus cereus. Helminthosporin was the most cytotoxic compound with IC50 ˂ 10 µM. Fraction R7C3 showed the most potent cytotoxic effects on all cancer cell lines, with IC50 ranging from ˂1 to 4.35 ng/mL. Our study is the first report on the mechanism of action of helminthosporin, a potent candidate in the development of new drugs against multi-resistant bacteria and cancer cells. In addition, this study uncovered Rumex abyssinicus as a new source of syringic acid and bis(2-ethyloctyl) phthalate.

Protective effect of Bacillus species associated with Rumex dentatus against postharvest soil borne disease in potato tubers and GC-MS metabolite profile.

Potato is constantly exposed to various kinds of phytopathogens which cause diseases during the developmental stage and post-harvest storage. This investigation was designed to assay the anti-phytopathogen activity of bacterial endophytes and their suppressive effects on rot disease in potato. The study also aimed to screen isolates for their plant growth-promoting traits and establish GC-MS-based metabolite profile of the potent isolate. Endophytes were isolated from Rumex dentatus and identified based on 16S rRNA gene. They were screened in dual culture assay against fungal phytopathogens and the potent isolate was tested for its capability to suppress Fusarium rot disease in potato tubers. The mechanism of action of endophytes on the phytopathogens was assessed using scanning electron microcopy. Isolates were also screened in vitro to assay their capability to produce phytohormones, hydrolytic enzymes, and to solubilize phosphates. Endophytic isolates produced proteases with a diameter of halo zone ranging from 7 to 32 mm. Bacillus sp. KL5 exhibited the highest production of indole acetic acid (IAA) with the amount of 104.28 µg/mL and was the most potent antagonist of Fusarium oxysporum and Verticillium dahliae with an inhibitory percentage of 61.53 and 100%, respectively. It showed a reduction of potato rot disease severity by more than 50%. GC-MS of active fractions of KL5 showed the presence of dibutylphthalate and 2,4-di-tert-butylphenol as major metabolites. From this study, it is evident that endophytic Bacillus species from R. dentatus are potent antagonists of F. oxysporum and V. dahliae. Bacillus sp. KL5 is a potent inhibitor of pathogenic F. oxysporum in potato tubers and can be developed as a biocontrol agent.

Glabridin ameliorates methotrexate-induced liver injury via attenuation of oxidative stress, inflammation, and apoptosis.

Despite unprecedented advances in modern medicine, no safe and effective drug is available to date for oral administration to combat drug-induced liver injury, which is a vital concern nowadays. The present study deals with the hepatoprotective effect of pure glabridin, a key phytoconstituent from Glycyrrhiza glabra with mechanistic investigations using an in-vivo methotrexate-induced liver injury model as there is no such precedent. The study was performed in the Swiss mice model where a single dose of methotrexate (40 mg/kg) was given on the 7th day through an intraperitoneal route to induce hepatotoxicity, and glabridin as a test compound was administered orally for eleven consecutive days at 10 to 40 mg/kg. Glabridin markedly improved serum biochemical parameters (SGPT, SGOT), proinflammatory cytokine (TNF-α) level, oxidative stress markers (MDA, GSH, SOD, CAT) as compared to methotrexate alone. Alterations in methotrexate-induced liver architecture were considerably prevented by glabridin treatment as suggested by liver histopathological examination and SEM investigation. Glabridin substantially prevented methotrexate-induced down-regulation of Nrf2, & activation of NF-κB, and caused up-regulation of BAX at different dose levels. Overall, glabridin is found to protect methotrexate-induced hepatotoxicity by improving important factors for oxidative stress, inflammation, and apoptosis.