Researchers from Osaka University in Japan, have recently discovered that quercetin, a component of the traditional Chinese herbal medicine tartary buckwheat extract, can induce autophagy and aggrephagy in skin and liver cells. These findings may have implications for the treatment of diseases associated with protein aggregation, such as alcoholic liver disease and Alzheimer’s.
Oddly enough, quercetin, is also a part of Dr. Zilenko’s recommended regiment. Seeds like quinoa, amaranth, and buckwheat that have been used for centuries in traditional cuisine are having a trendy moment in culinary circles as alternatives to wheat and other grains.
In a study published last month in Antioxidants, researchers from Osaka University revealed that an ingredient in Chinese buckwheat liquor, which contains various herbal medicine extracts, can induce autophagy, a process that cells use to clean up proteins that are damaged or no longer needed.
TBE induces autophagy progression. (A) Tf-LC3-expressing HeLa cells were treated with or without Torin-1 or TBE for 6 h under nutrient-rich conditions. Bar:10 µm. (B) The graph shows the signal intensity ratio of GFP/RFP in each field of view after 6 h. Median: line; upper and lower quartiles: boxes; 1.5 interquartile range: whiskers. * denotes p < 0.05 by unpaired two-tailed Student’s t-test 
TBE induces autophagy flux under nutrient-rich conditions. (A) GFP-LC3-expressing HeLa cells were treated with Torin-1 or TBE for 6 h under nutrient-rich conditions. The number of GFP punctae per cell was counted, with over 20 cells in each sample. Median: line; upper and lower quartiles: boxes; 1.5 interquartile range: whiskers. Bar: 10 µm (B) HeLa cells were treated with Torin-1 or TBE with or without bafilomycin A1 for 6 h. The lysates were assessed by Western blotting with anti-LC3 antibody. The graph shows the average and standard deviation of the ratio of the LC3 signal to the tubulin signal from three independent experiments. * denotes p < 0.05 by unpaired two-tailed Student’s t-test. 
TBE enhances dephosphorylation of mTORC1 substrates. (A) GFP-TFEB-expressing HeLa cells were treated with or without Torin-1 or TBE for 4 h and observed under a confocal microscope. Bar: 25 µm. (B) The graph shows the ratio of GFP intensity in a 7 µm2 of the cytosol to the sum of GFP intensities in certain areas of the cytoplasm and nucleus. Median: line; upper and lower quartiles: boxes; 1.5 interquartile range: whiskers. * denotes p < 0.05 by unpaired two-tailed Student’s t-test. (C) HeLa cells were treated with or without Torin-1 or TBE for 4 h and subjected to Western blotting using anti-phospho-ULK1 (Ser757), anti-ULK, anti-TFEB, anti-phospho-S6K, anti-p70 kinase, anti-4E-BP1, and anti-tubulin antibodies. The graph shows the quantification of each band intensity 
Quercetin enhances autophagy. (A) GFP-LC3-expressing HeLa cells were treated with or without Torin-1, TBE, or quercetin for 4 h under nutrient-rich conditions. The graph shows the number of GFP-LC3 punctae over 1.3 µm in diameter per cell. (B) GFP-TFEB-expressing HeLa cells were treated with or without Torin-1, TBE, or quercetin for 4 h under nutrient-rich conditions. The graph shows the ratio of GFP intensity in a certain area of the cytosol to the sum of GFP intensities in certain areas of the cytoplasm and nucleus. (C) Huh7 cells were treated with puromycin for 4 h, and further cultured with or without Torin-1, TBE, or quercetin for 1 h after washing out puromycin. Intracellular p62 was detected by immunostaining. The graph shows the number of p62 dots over 2.5 µm in diameter per cell. Median: line; upper and lower quartiles: boxes; 1.5 interquartile range: whiskers. Bar: 10 µm for (A,B); 25 µm for (C). * denotes p < 0.05 by unpaired two-tailed Student’s t-test. 
TBE and quercetin enhance the induction of aggrephagy. HeLa cells were treated with puromycin for 4 h, Figure 1. Bafilomycin A1, TBE, quercetin, or rutin at the indicated concentrations for 1 h. p62 was detected by immunostaining. The graph shows the number of p62 dots over 1.4 µm in diameter per HeLa cell. Bar: 25 µm. Median: line; upper and lower quartiles: boxes; 1.5 interquartile range: whiskers. * denotes p < 0.05 by unpaired two-tailed Student’s t-test. 
TBE induces autophagosome formation. HeLa cells expressing GFP-Atg5 (A), ULK1-EGFP (B), or GFP-WIPI1 (C) were treated with Torin-1 or TBE for 4 h. The cells were observed under a confocal microscope. The number of GFP punctae over 0.56 µm in diameter was counted per cell, with over 20 cells in each sample. Median: line; upper and lower quartiles: boxes; 1.5 interquartile range: whiskers. Bar: 10 µm. * denotes p < 0.05 by unpaired two-tailed Student’s t-test. 
Autophagy plays an important role in diseases such as cancer and Alzheimer’s disease, so finding a way to encourage this process is a topic of considerable interest. Herbal substances are an intriguing potential source of compounds that could be used in this type of treatment.
“We already knew that tartary buckwheat liquor, which is used in traditional Chinese medicine, can decrease antioxidants in mice, and that it has some antibacterial effects,” explains lead author of the study Sumiko Ikari. “What we wanted to find out in this study is whether it also affects autophagy.” To explore this possibility, the researchers treated epithelial (skin) cells and liver cells with tartary buckwheat extract and looked at how different fluorescent markers of autophagy responded.
“The results clearly showed that tartary buckwheat induces autophagy in epithelial cells,” states Takeshi Noda, senior author. “We found that treating cells with the extract stimulated the formation of autophagasomes, specialized cellular structures that carry out autophagy, and altered the location of proteins involved in regulating autophagy.”
Upon examining specific components of tartary buckwheat extract, the researchers found that one component, quercetin, had the same effects as the extract. What’s more, both tartary buckwheat extract and quercetin prompted liver cells to clean up protein aggregates through a process known as aggrephagy.
“Our findings suggest that tartary buckwheat extract and quercetin induce not only autophagy, but also aggrephagy,” says Ikari. Given that protein aggregates in liver cells are closely linked to alcoholic liver disease, these findings suggest that quercetin could be a useful treatment for patients with this condition. It may also hold promise for treatment of other diseases associated with protein aggregation, such as Alzheimer’s and Covid-19.
Natural sources of quercetin include:
Quercetin is also present in herbal remedies, such as ginkgo biloba and St John’s wort and is available in powder and pill supplement form.
New World Journal 
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