Natural products that suppress 2-deoxy-d-glucose-induced cell death as potential drug seeds for mitochondrial diseases
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Updated: Jan 12, 2026
Experimental Protocol for Detecting Mitochondrial Function in Hepatocytes Exposed to Organochlorine Pesticides
Published on: September 16, 2020
Koyo Honda1, Yuki Hitora1, Yusaku Sadahiro1
1Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Abstract:
Mitochondrial dysfunction is not only a known cause of mitochondrial disease but has also been implicated in diabetes and neurodegenerative diseases. Therefore, modulating mitochondrial function may provide new insights into the treatment of these diseases. In this study, we used a cancer cell-based energy metabolism restriction model with a glycolytic inhibitor and screened a natural product library and a fungal extract library to identify natural products that improve mitochondrial function. Seven compounds, including quillaic acid (1) and 20-deoxyingenol (2), were identified as mitochondrial function modulators from the Selleck natural product library. Furthermore, an extract of a fungus, Trichoderma sp., from an in-house fungal extract library suppressed 2-deoxy-d-glucose-induced cell death. Bioassay-guided fractionation of the extract afforded seven known sorbicillinoids. Among them, bisvertinol (8) did not directly affect cellular energy metabolism but appeared to protect mitochondria from oxidative stress through its antioxidant properties.
Insights
Researchers screened natural products to find compounds that enhance mitochondrial function, crucial for treating diseases like diabetes and neurodegenerative conditions. They identified several compounds, including bisvertinol, which protects mitochondria from oxidative stress.
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Mitochondrial dysfunction is linked to various diseases, including diabetes and neurodegenerative disorders.
- Modulating mitochondrial function offers potential therapeutic strategies for these conditions.
Purpose of the Study:
- To identify natural products that improve mitochondrial function using a cancer cell-based energy metabolism restriction model.
- To investigate the protective effects of fungal extracts and their compounds against cellular stress.
Main Methods:
- Screening of natural product and fungal extract libraries using a glycolytic inhibitor model.
- Bioassay-guided fractionation of fungal extracts to isolate active compounds.
- Assessing compounds for their ability to modulate mitochondrial function and protect against oxidative stress.
Main Results:
- Seven compounds, including quillaic acid and 20-deoxyingenol, were identified as mitochondrial function modulators.
- An extract from Trichoderma sp. suppressed cell death induced by 2-deoxy-d-glucose.
- Bisvertinol, a sorbicillinoid, protected mitochondria from oxidative stress via antioxidant properties without directly altering cellular energy metabolism.
Conclusions:
- Natural products, particularly from fungal sources, can modulate mitochondrial function and offer protection against cellular stress.
- Bisvertinol shows promise as a mitochondrial protectant through its antioxidant activity, suggesting potential therapeutic applications.
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