There are abundant sources of anticancer drugs in nature that have a broad prospect in anticancer drug discovery. Natural compounds, with biological activities extracted from plants and marine and microbial metabolites, have significant antitumor effects, but their mechanisms are various. In addition to providing energy to cells, mitochondria are involved in processes, such as cell differentiation, cell signaling, and cell apoptosis, and they have the ability to regulate cell growth and cell cycle. Summing up recent data on how natural products regulate mitochondria is valuable for the development of anticancer drugs. This review focuses on natural products that have shown antitumor effects via regulating mitochondria. The search was done in PubMed, Web of Science, and Google Scholar databases, over a 5-year period, between 2015 and 2020, with a keyword search that focused on natural products, natural compounds, phytomedicine, Chinese medicine, antitumor, and mitochondria. Many natural products have been studied to have antitumor effects on different cells and can be further processed into useful drugs to treat cancer. In the process of searching for valuable new drugs, natural products such as terpenoids, flavonoids, saponins, alkaloids, coumarins, and quinones cover the broad space.

Lung cancer is one of the most prevalent malignancies worldwide. Despite the undeniable progress in lung cancer research made over the past decade, it is still the leading cause of cancer-related deaths and continues to challenge scientists and researchers engaged in searching for therapeutics and drugs. The tumor microenvironment (TME) is recognized as one of the major hallmarks of epithelial cancers, including the majority of lung cancers, and is associated with tumorigenesis, progression, invasion, and metastasis. Targeting of the TME has received increasing attention in recent years. Natural products have historically made substantial contributions to pharmacotherapy, especially for cancer. In this review, we emphasize the role of the TME and summarize the experimental proof demonstrating the antitumor effects and underlying mechanisms of natural products that target the TME. We also review the effects of natural products used in combination with anticancer agents. Moreover, we highlight nanotechnology and other materials used to enhance the effects of natural products. Overall, our hope is that this review of these natural products will encourage more thoughts and ideas on therapeutic development to benefit lung cancer patients.

Background/Objectives: Danggui Beimu Kushen pill (DBK) is a traditional Chinese medicine renowned for its efficacy in the treatment of inflammatory conditions. It has been used in the modern clinical treatment of ulcerative colitis (UC). Further research is required to clarify its underlying mechanisms. Methods: DBK compounds were analyzed using UPLC-ESI-MS/MS. A mouse model of Dextran sulfate sodium (DSS)-induced UC was used to assess the efficacy of DBK. Network pharmacology identified DBK targets in UC, which were validated by molecular docking simulations. Cytokine levels were quantified using ELISA. Western blotting, immunofluorescence (IF), and immunohistochemistry (IHC) were employed to explore its underlying molecular mechanisms. Results: DBK treatment enhanced body weight and colon length in mice with DSS-induced colitis. Inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IL-23, and IL-17A) were notably decreased in both serum and colon tissues. Network pharmacology and molecular docking analyses identified the IL-6/IL-6R and IL-17A/IL-17RA signaling pathways as crucial for the DBK treatment of UC. Additional validation using WB, IHC, and IF analyses demonstrated that DBK alleviated UC by suppressing the IL-6/STAT3 and IL-17/TRAF6/NF-κB pathways. Conclusions: DBK mitigates intestinal injury in mice with DSS-induced colitis and exerts therapeutic effects on UC by inhibiting the IL-6/IL-6R and IL-17A/IL-17RA signaling pathways to reduce inflammation. These findings provide significant insights into the mechanism of DBK treatment for UC.

Ethyl caffeate (EC) is a phenylpropanoid compound derived from Elephantopus scaber. In our previous work, EC was investigated to have a strong synergistic antifungal effect against azole-resistant strains of Candida albicans when combined with fluconazole (FLU). However, the protective effect and mechanism of EC + FLU on oropharyngeal candidiasis (OPC) caused by drug-resistant strains of C. albicans has not been investigated. This study aimed to investigate the protective effect and mechanism of EC combined with FLU against C. albicans-resistant strains that lead to OPC. An OPC mouse model revealed that EC + FLU treatment reduced fungal load and massive hyphal invasion of tongue tissues, and ameliorated the integrity of the tongue mucosa. PAS staining results showed more structural integrity of the tongue tissues and reduced inflammatory cell infiltration after EC + FLU treatment. Phosphorylation of EGFR and other proteins in the EFGR/JNK/c-JUN signaling pathway was significantly downregulated by EC + FLU. EGFR and S100A9 mRNA expression was also reduced. The above results were verified in FaDu cells. ELISA results showed that the concentration of inflammatory factors in the cell supernatant was significantly reduced after EC combined with FLU treatment. Molecular docking revealed that EC exhibited high binding energy to EGFR. In conclusion, EC enhances the susceptibility of azole-resistant C. albicans to FLU, and the underlying mechanism is related to the inhibition of the EGFR/JNK/c-JUN signaling pathway. This result suggests that EC has potential to be developed as an antifungal sensitizer to treat OPC caused by azole-resistant C. albicans. Combination therapy can take advantage of the synergistic effect between drugs to significantly improve antifungal efficacy, overcome strain resistance and slow down the development of drug resistance.