New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy

Law, Betty Yuen Kwan; Mok, Simon Wing Fai; Wu, An Guo; Lam, Christopher Wai Kei; Yu, Margaret Xin Yi; Wong, Vincent Kam Wai

doi:10.3390/molecules21030359

Cited by 53 publications

(45 citation statements)

References 409 publications

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“…PAH acts as an autophagy inducer in MFCs. Consistent with our results, several papers have shown that some natural products isolated from traditional Chinese medicine are effective to control autophagy …”

Section: Discussionsupporting

confidence: 93%

Perilaldehyde activates AMP‐activated protein kinase to suppress the growth of gastric cancer via induction of autophagy

Zhang

Liu

Qin

et al. 2018

J of Cellular Biochemistry

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Background and Aim: Perillaldehyde (PAH), one of the major oil components in Perilla frutescens, is very critical to health maintenance, for a wide range of human chronic diseases, including cancers. AMP‐activated protein kinase (AMPK) has been implicated in the activation of autophagy in distinct tissues. This study was designed to explore whether PAH prevents gastric cancer growth and to investigate the molecular mechanism. Methods and Results: In cultured mouse gastric cancer cell line MFCs and human gastric cancer cell lines GC9811‐P, PAH activated AMPK by increasing the Thr172 phosphorylation and activity in a time‐/concentration‐dependent manner. Furthermore, incubation of MFCs with PAH also increased autophagy as determined by monodansylcadaverine (MDC) staining, which was reversed by AMPK inhibitor compound C. PAH further decreased MFCs cell survival, which was abolished by compound C or autophagy inhibitor 3‐Methyladenine (3‐MA). In vivo studies indicated that 4‐week administration of PAH (100 mg/kg/day) suppressed the growth of gastric cancer and increased the levels of autophagy‐related proteins, including beclin‐1, LC3‐II, cathepsin, caspase‐3, p53, and cathepsin in tumors isolated from the xenograft model of gastric cancer in mice. Moreover, these anticancer effects produced by PAH were abolished by coadministration of compound C or 3‐MA in vivo. Conclusions: PAH increases AMPK phosphorylation and activity to induce gastric cancer cell autophagy to inhibit the growth of gastric cancer. In perspective, therapy of PAH should be applied to treat patients with gastric cancer.

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Section: Discussionsupporting

confidence: 93%

Perilaldehyde activates AMP‐activated protein kinase to suppress the growth of gastric cancer via induction of autophagy

Zhang

Liu

Qin

et al. 2018

J of Cellular Biochemistry

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“…Autophagy is a catabolic cellular process in which the dysfunctional cytoplasmic constituents are removed to maintain metabolic balance. It occurs not only in normal cells but also in cancer cells . It is widely accepted that autophagy plays a complex role in oncogenesis: it represses tumor growth in the early stages on the one hand but is required for progression to advanced or invasive tumors on the other hand .…”

Section: Discussionmentioning

confidence: 99%

“…It occurs not only in normal cells but also in cancer cells. 30 It is widely accepted that autophagy plays a complex role in oncogenesis: it represses tumor growth in the early stages on the one hand but is required for progression to advanced or invasive tumors on the other hand. 24 During the past 5 years, autophagy induced by plantderived drugs has been widely studied in various tumors.…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway

et al. 2018

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Thymoquinone (TQ, 2‐methyl‐5‐isopropyl‐1,4‐benzoquinone), a bioactive constituent extracted from the seeds of Nigella sativa, has been proved to exert anti‐tumor efficiency in various cancers. Autophagy is a self‐digestion phenomenon, and its role in tumor formation and progression remains controversial. In the present study, we investigated the effects of TQ on renal cell cancer (RCC) cell lines (786‐O and ACHN) using wound healing assay, transwell assay and western blot analysis. We found that TQ effectively inhibited the metastatic capacity of RCC cells in vitro, which was also verified in a xenograft model. Meanwhile, we observed LC3 puncta and detected the expression of LC3 in TQ‐treated RCC cells, and then found that autophagy was induced by TQ in 786‐O and ACHN cell lines. In addition, TQ inhibited the migration and invasion as well as the EMT in RCC cells in an autophagy‐dependent manner. To further explore the underlying mechanism, we detected the AMPK/mTOR signaling pathway. The results indicated that TQ inhibited the metastasis of RCC cells by inducing autophagy via AMPK/mTOR signaling pathway. In conclusion, our findings provide a novel therapeutic strategy that aims at TQ‐induced autophagy in RCC treatment.

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“…27) AMP activated protein kinase (AMPK) could stimulate the autophagy in skeletal muscle cells via its effect on the transcriptional function of FoxO and participate in autophagosome formation. 28) Therefore, the mTOR, AMPK, FoxO singling pathway was related to exhaustive exercise-induced skeletal muscle injury.…”

Section: Resultsmentioning

confidence: 99%

To Elucidate the Inhibition of Excessive Autophagy of <i>Rhodiola crenulata</i> on Exhaustive Exercise-Induced Skeletal Muscle Injury by Combined Network Pharmacology and Molecular Docking

Hou

Wang

et al. 2020

Biological & Pharmaceutical Bulletin

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Autophagy can remodel skeletal muscle in response to exercise. However, excessive autophagy can have adverse effects on skeletal muscle. Although Rhodiola crenulata (R. crenulata) is thought to regulate autophagy, its active ingredients and mechanisms of action remain unclear. In this study, molecular docking and network pharmacology were used to screen for autophagy-related targets of R. crenulata. Subsequently, protein-protein interaction (PPI) analysis was used to find the relationships between the inverse docking targets and autophagy-related targets and therefore highlight the key targets. And then the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database was recruited to explain the functions and enrichment pathways of the target proteins. Finally, the potential targets were validated by immunohistochemistry of a mouse model of exhaustive exercise-induced skeletal muscle injury. We found a network of 15 major constituents of R. crenulata with 30 autophagy-related and 105 inverse-docking targets by molecular docking and network pharmacology. The results of PPI analysis indicated that 16 inverse-docking targets interacted 8 autophagy-related proteins. Further pathway analysis showed that R. crenulata could regulate exerciseinduced skeletal muscle autophagy through mammalian target of rapamycin (mTOR), AMP activated protein kinase (AMPK) and Forkhead box protein O (FoxO). The results of our animal experiments indicated that R. crenulata could suppress the expression of Ubiquitin-like protein ATG12 (ATG12), Beclin-1 (BECN1), and Serine/threonine-protein kinase ULK1 (ULK1), while increasing the expression of MTOR, NAD-dependent protein deacetylase sirtuin-1 (SIRT1), and Microtubule-associated protein tau (MAPT). In conclusion, this study demonstrated that R. crenulata may protect skeletal muscle injury induced by exhaustive exercise via regulating the mTOR, AMPK, and FoxO singling pathway.

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New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy

Cited by 53 publications

References 409 publications

Perilaldehyde activates AMP‐activated protein kinase to suppress the growth of gastric cancer via induction of autophagy

Perilaldehyde activates AMP‐activated protein kinase to suppress the growth of gastric cancer via induction of autophagy

Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway

To Elucidate the Inhibition of Excessive Autophagy of <i>Rhodiola crenulata</i> on Exhaustive Exercise-Induced Skeletal Muscle Injury by Combined Network Pharmacology and Molecular Docking

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