Triple-negative breast cancer (TNBC) subtype is one of the most aggressive tumors with no definite receptor, hence has a limited number of effective chemotherapeutics. Doxorubicin (Dox) is the first-line drug for the TNBC treatment, acting as a DNA intercalator and topoisomerase II (Topo II) inhibitor; however, it has been observed to exhibit strong cardiotoxicity. Tanshinone IIA (Tan IIA) has a previously confirmed antitumor activity against breast cancer in addition to its well-known cardioprotective effect. In our study, molecular docking reveals the potential activity of Tan IIA as a DNA intercalator and Topo II inhibitor as a recommended possible mechanism of action compared to Dox as a reference drug. Moreover, we wanted to assess a new use for Tan IIA in the TNBC treatment in combination with Dox to broaden its therapeutic window and compensate for its cardiotoxic effects by the cardioprotective effects of Tan IIA. On performing the in vitro MTT assay to evaluate the cytotoxic effects of Dox, Tan IIA and their combinations at different concentrations of the MDA-MB-231 cell line revealed the potential activity of Tan IIA compared to Dox, in addition to the confirmed synergistic effects of Dox/Tan IIA combinations on TNBC cell lines. Furthermore, the analysis of the gene expression profiles of PI3K, mTOR, and AKT as anti-apoptotic genes were examined in the MDA-MB-231 cell line after the treatment with the IC50 of Dox, Tan IIA, and their combination, and compared to the control using PCR. These results confirmed the synergistic effect of the Dox/Tan IIA combination that exceeded that of Dox alone.

The increasing prevalence of obesity has become a demanding issue in both high-income and low-income countries. Treating obesity is challenging as the treatment options have many limitations. Recently, diet modification has been commonly applied to control or prevent obesity and its risks. In this study, we investigated novel therapeutic approaches using a combination of a potential probiotic source with prebiotics. Forty-eight adult male Sprague–Dawley rats were selected and divided into seven groups (eight rats per group). The first group was fed a high-fat diet, while the second group was a negative control. The other five groups were orally administered with a probiotic, Lactiplantibacillus plantarum (L. plantarum), and potential prebiotics sources (chia seeds, green tea, and chitosan) either individually or in combination for 45 days. We collected blood samples to analyze the biochemical parameters and dissected organs, including the liver, kidney, and pancreas, to evaluate obesity-related injuries. We observed a more significant decrease in the total body weight by combining these approaches than with individual agents. Moreover, treating the obese rats with this combination decreased serum catalase, superoxide dismutase, and liver malondialdehyde levels. A histopathological examination revealed a reduction in obesity-related injuries in the liver, kidney, and pancreas. Further docking studies indicated the potential role of chia seeds and green tea components in modulating obesity and its related problems. Therefore, we suggest that the daily administration of a pre- and probiotic combination may reduce obesity and its related problems.