Anti-diabetic effect of cotreatment with resveratrol and pioglitazone in diabetic rats.

OBJECTIVE: Limitations and side effects associated with current anti-diabetic treatments have necessitated the search for new therapeutic alternatives. This study aimed to explore the combined use of resveratrol (RVT) and established anti-diabetic drug pioglitazone (PGZ) against streptozotocin (STZ)-induced diabetes mellitus (DM). MATERIALS AND METHODS: STZ was supplemented daily to Sprague-Dawley rats to induce DM. The synergistic effect of the RVT (20 mg/kg) and PGZ (0.65 mg/kg) on DM complications was evaluated after 8 weeks of treatment. Biochemical analyses were performed to evaluate the effectiveness of our treatment on glucose level, insulin sensitivity, lipid disturbances, oxidative mediators and inflammatory markers. RESULTS: STZ induced DM onset that is accompanied with elevated diabetic markers, lipid disturbances, remarkable oxidative damage and hyper-inflammation. The PGZ+RVT combination has the best effect as illustrated by significant (p < 0.05) decreases in fasting blood glucose, insulin, HbA1c and HOMA-IR levels. This combination attenuated (p < 0.05) lipid disturbances and their associated elevated atherogenic biomarkers. At the same time, treatments with PGZ+RVT exhibited an anti-inflammatory effect as it attenuated the increase in inflammatory parameters (CRP, TNF-α, IL-6). Also, it restored total antioxidant capacity and peroxisome proliferator-activated receptor (PPARg) levels that decreased by STZ-DM induction. CONCLUSIONS: This study provides PGZ+RVT as promising DM therapeutic alternative. This synergistic combination alleviates most of DM-related complications and insulin resistance.

Punicalagin and zinc (II) ions inhibit the activity of SARS-CoV-2 3CL-protease in vitro.

OBJECTIVE: Coronavirus 2019 (COVID-19) has now been declared as a worldwide pandemic. Currently, no drugs have been endorsed for its treatment; in this manner, a pressing need has been developed for any antiviral drugs that will treat COVID-19. Coronaviruses require the SARS-CoV-2 3CL-Protease (3CL-protease) for cleavage of its polyprotein to yield a single useful protein and assume a basic role in the disease progression. In this study, we demonstrated that punicalagin, the fundamental active element of pomegranate in addition to the combination of punicalagin with zinc (Zn) II, appear to show powerful inhibitory activity against SARS-CoV-2. MATERIALS AND METHODS: The 3CL protease assay kit was used to quantify 3CL protease action. The tetrazolium dye, MTS, was used to evaluate cytotoxicity. RESULTS: Punicalagin showed inhibitory action against the 3CL-protease in a dose-dependent manner, and IC50 was found to be 6.192 µg/ml for punicalagin. Punicalagin (10 µg/mL) demonstrated a significant inhibitory activity toward 3CL-protease activity (p < 0.001), yet when punicalagin is combined with zinc sulfate monohydrate (punicalagin/Zn-II) extremely strong 3CL-protease activity (p < 0.001) was obtained. The action of 3CL-protease with punicalagin/Zn-II was decreased by approximately 4.4-fold in contrast to only punicalagin (10 µg/mL). Likewise, we did not notice any significant cytotoxicity caused by punicalagin, Zn-II, or punicalagin/Zn-II. CONCLUSIONS: We suggest that these compounds could be used as potential antiviral drugs against COVID-19.