Abstract
Tartary buckwheat is used as an ingredient in flour and tea, as well as in traditional Chinese medicine for its antioxidant effects. Here, we found that an ethanol extract of tartary buckwheat (TBE) potently induced autophagy flux in HeLa cells by suppressing mTORC1 activity, as revealed by dephosphorylation of the mTORC1 substrates Ulk1, S6K, and 4EBP, as well as by the nuclear translocation of transcriptional factor EB. In addition to non-selective bulk autophagy, TBE also induced aggrephagy, which is defined as autophagy against aggregated proteins. Quercetin is a flavonol found at high levels in TBE. We showed that quercetin induced both non-selective bulk autophagy and aggrephagy. These effects were also observed in Huh-7 cells derived from hepatocytes. Thus, aggrephagy induction by TBE and quercetin may relieve alcoholic hepatitis, which is closely linked to the accumulation of protein aggregations called Mallory–Denk bodies.
Highlights
Macroautophagy is an intracellular degradation process that supports cellular homeostasis [1]
We showed that tartary buckwheat (TBE) treatment induced autophagy by suppressing mTORC1 activity, and that quercetin was the ingredient that exerted this effect
We further revealed that TBE and quercetin promoted bulk autophagy, and aggrephagy against aggregated proteins
Summary
Macroautophagy (hereafter referred to as autophagy) is an intracellular degradation process that supports cellular homeostasis [1]. As a result, increasing numbers of studies have demonstrated the vital connection between autophagy and a wide variety of human diseases, such as cancer and neurodegenerative diseases [3]. To address these autophagy-related conditions, a number of attempts by the pharmaceutical industry and academia are underway worldwide to artificially regulate autophagy activity in vivo by the use of exogenous compounds [4]. Traditional Chinese medicine has attracted wide attention as a source of potential autophagy modulators [5] This therapeutic approach has a different foundation than European medicine, and it is broadly accepted, mainly in East Asia. We recently reported that Shigyakusan, a mixture of compounds used in Kampo (Japanese-style traditional Chinese medicine) and a close relative of Shini-san in traditional
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