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Cisplatin is widely used as one of the most effective anticancer agents in the treatment of some neoplasms. Reproductive toxicity is the most common outcome associated with cisplatin testicular damage. Alternative natural medicines for treating male testicular disorders and infertility have received extensive attention in research. Natural products, medicinal herbs, and their secondary metabolites have been shown as promising agents in the management of testicular damage induced by chemotherapy drugs. This study aimed to review the research related to natural substances that are promising in mitigation of the cisplatin-induced toxicity in the reproductive system. PubMed and Scopus were searched for studies on various natural products for their potential protective property against reproductive toxicity induced by cisplatin from 2000 to 2020. Eligibility was checked based on selection criteria. Fifty-nine articles were included in this review. Mainly in animal studies, several natural agents have positively affected cisplatin-reproductive-toxicity factors, including reactive oxygen species, inflammatory mediators, DNA damage, and activation of the mitochondrial apoptotic pathway. Most of the natural agents were investigated in short-term duration and high doses of cisplatin exposure, considering their antioxidant activity against oxidative stress. Considering antioxidant properties, various natural products might be effective for the management of cisplatin reproductive toxicity. However, long-term recovery of spermatogenesis and management of low-dose-cisplatin toxicity should be considered as well as the bioavailability of these agents before and after treatment with cisplatin without affecting its anticancer activity.

Various plant species have been shown to be effective in the prevention or adjuvant therapy of cancer. Alpinia officinarum and its main phytochemicals have also been the subject of several studies for their anticancer properties.The objective of this study is to analyze the extracts of A. officinarum to quantify flavonoids and to evaluate the growth inhibitory effects of the extracts on MCF-7 and LNCaP cells.A. officinarum aqueous and hydroalcoholic extracts were analyzed by using High-Performance Liquid Chromatography (HPLC) for the quantification of three flavonoid compounds. Then, MCF-7, LNCaP, and fibroblast cells were treated with several concentrations (25, 50, 100, 200, and 400 μg/mL) of extracts (24, 48 and 72h). Cell viability was assessed using an MTT assay. Flow cytometry was conducted to evaluate apoptosis.Galangin and kaempferol (3.85 and 1.57 mg/g dry extract) were quantified, respectively, in hydroalcoholic and aqueous extracts using a validated method. The hydroalcoholic extract significantly decreased the viability of MCF-7 (IC50: 43.45μg/mL for 48h) and LNCaP cells (IC50: 168 μg/mL for 48h). The aqueous extract reduced cancer cell viability by more than 50% only at 200 and 400 μg/mL (72 h). Treatment of primary fibroblasts with both extracts showed no significant decrease in cell viability (25-100 μg/mL; 24 and 48h). The hydroalcoholic extract induced a significant increase in apoptotic cells in both MCF-7 and LNCaP cells.Obtained results demonstrated the cytotoxicity of A. officinarum through apoptosis induction in two cancer cell lines. Further investigations are required to determine the underlying apoptotic cell death mechanisms induced by A. officinarum in cancerous cells.