The molecular mechanisms underlying doxorubicin-induced cardiotoxicity are still being investigated, but are known to involve oxidative stress, mitochondrial dysfunction, and the dysregulation of autophagy. The objective of the current study was to examine the protective role of metformin and its effect on autophagy in doxorubicin-induced cardiotoxicity. Sprague–Dawley rats were divided into four groups at random. The doxorubicin-treated group received doxorubicin (3 mg/kg every second day) intraperitoneally. The metformin-treated group received 250 mg/kg/day metformin via gavage. The doxorubicin + metformin-treated group received both at the above-mentioned doses. The control group received vehicle only. Following the two-week treatment, the hearts were isolated, and cardiac functions were registered. Serum levels of lactate dehydrogenase (LDH), creatine kinase iso-enzyme MB (CK-MB) enzyme, Troponin T, and cardiac malondialdehyde (MDA) were also measured. Heart tissue samples were histopathologically examined by using Masson’s trichrome staining and Western blot analysis was conducted for evaluating the expression level of AMP-activated protein kinase (AMPK) and autophagy-associated proteins beclin-1, LC3B-II, and p62, respectively. The results revealed that treatment with metformin conferred increased cardiac protection against the development of cardiotoxicity manifested by a significant decrease in serum Troponin T and cardiac MDA levels, and remarkable improvement in heart function in connection with histopathological features. Furthermore, by focusing on the contribution of autophagic proteins, it was found that metformin normalised autophagy, which may help cardiomyocytes survive doxorubicin-induced toxicity. These results promote the use of metformin, which would be a preferable drug for patients receiving doxorubicin.

Honey is a consumer-preferred, highly esteemed natural product with a broad variety of distinct bioactive components. In recent days, the consumption of high-added-value, honey-based products are increasingly coming to the forefront of interest, and thus huge efforts are being made by researchers/developers to elaborate honey variants with fortified biological value. Relevant human clinical trials have scarcely been accomplished; thus, the biological impact of honey and its derivatives has not been thoroughly revealed. In this work, we present our experiments on the development of a novel honey-based prototype and its plausible physiological impacts certified via human clinical trials. The investigated product was a newly elaborated honeydew-based prototype fortified with pumpkin, sea buckthorn, and inulin, which was subjected to a 13-week-long, double-blind, placebo-controlled human clinical trial. The prototypes were applied to 20 adult volunteers to establish the complex impact of the newly developed product. Conclusions drawn at the end of the trial were based on results of blood tests taken at diverse phases of the study. The positive physiological effects of consumption of the investigated products are underpinned by the fact that no significant elevations have been measured in terms of the blood glucose level and parameters featuring long-term blood sugar levels. Slight decrease of both LDL and HDL cholesterol levels were also experienced.