Ginsenoside Rg1 reduces aldosterone-induced autophagy via the AMPK/mTOR pathway in NRK-52E cells

Wang, Li; Ma, Nan; Tan, Ruizhi; Wang, Hong‐Lian; Wen, Jianping; Liu, Yu-Hang; Furhad,; Fan, Junming

doi:10.3892/ijmm.2015.2242

Cited by 29 publications

(38 citation statements)

References 30 publications

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“…Interestingly, in a report it was shown that Rg1 inhibited angiotensin II-induced podocyte autophagy via the AMPK/mTOR/PI3K pathway [37]. However in another study, Rg1 was demonstrated to reduce aldosterone-induced autophagy via the AMPK/mTOR pathway in NRK-52E cells [38]. Similarly, Rb1 was reported to have positive [39] and negative [40] effects on neuronal autophagy, respectively, in two different papers.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

Huang

Wang

Yang

et al. 2017

IJMS

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Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy. In vitro, Rb2 (50 µmol/L) obviously increased autophagic flux in HepG2 cells and primary mouse hepatocytes, and consequently reduced the lipid accumulation induced by oleic acid in combination with high glucose. Western blotting analysis showed that Rb2 partly reversed the high fatty acid in combination with high glucose (OA)-induced repression of autophagic pathways including AMP-activated protein kinase (AMPK) and silent information regulator 1 (sirt1). Furthermore, pharmacological inhibition of the sirt1 or AMPK pathways attenuated these beneficial effects of Rb2 on hepatic autophagy and lipid accumulation. Taken together, these results suggested that Rb2 alleviated hepatic lipid accumulation by restoring autophagy via the induction of sirt1 and activation of AMPK, and resulted in improved nonalcoholic fatty liver disease (NAFLD) and glucose tolerance.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

Huang

Wang

Yang

et al. 2017

IJMS

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“…It has been observed that pests rarely feed on the stems and leaves of wild ginseng, which is highly associated with the content of ginsenosides . Recent studies have discovered that the total ginsenosides exhibited significant antifeeding and growth inhibition activities against Mythimna separata (Walker) larvae . Further mechanistic studies revealed that the total ginsenosides reduced the protein content and the activity of digestive enzymes, inhibited the activities of acetylcholinesterase and glutathione s‐transferase, and disturbed the original dynamic balance of protective enzymes (e.g., superoxide dismutase, chloramphenicol acetyltransferase, and peroxidases) .…”

Section: Chemical Defense Role Of Ginsenosides In Plantsmentioning

confidence: 96%

“…Recent studies have demonstrated that excessive autophagy triggered by the generation of ROS is involved in renal cell injury, particularly podocytes, induced by high levels of aldosterone and angiotensin II . Thus, maintaining the homeostasis of autophagy may be a mechanism of reducing renal injury.…”

Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 98%

“…Rg1 can both downregulate the activity of AMPK and GSK‐3β to suppress Ang II‐induced autophagy by activating mTOR signaling, as well as increase the activity of P70S6K, a downstream effector of the mTOR complex 1 (mTORC1), to block Ang II‐induced autophagy via a negative‐feedback loop by inhibiting PI3K . Similarly, Rg1 was also found to inhibit aldosterone‐induced autophagy and hypoxia/reperfusion‐induced autophagy, in which the suppression of AMPK and activation of mTOR were shown to be the primary underlying mechanisms. Rb1 inhibited the autophagic death caused by ischemic insults via activation of the PI3K/Akt pathway, which is an upstream activator of Mtor …”

Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 99%

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Cellular stress response mechanisms as therapeutic targets of ginsenosides

2017

Medicinal Research Reviews

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Ginseng, one of the most widely used traditional herbal medicines and dietary supplements, has historically been recognized as a tonic herb and adaptogen that can enhance the body's tolerance to various adversities. Ginsenosides are a diverse group of steroidal saponins that comprise the major secondary metabolites of ginseng and are responsible for its multiple pharmacological effects. Emerging evidence suggests that hormetic phytochemicals produced by environmentally stressed plants can activate the moderate cellular stress response mechanisms at a subtoxic level in humans, which may enhance tolerance against severe dysfunction or disease. In this review, we initially describe the role of ginsenosides in the chemical defense of plants from the genus Panax suffering from biotic and abiotic stress. Next, we summarize the diverse evolutionarily conserved cellular stress response pathways regulated by ginsenosides and the subsequent stress tolerance against various dysfunctions or diseases. Finally, the structure-activity relationship involved in the effect of ginsenosides is also analyzed. The evidence presented in this review implicates that ginseng as "the King of all herbs" could be regarded as a well-characterized example of the critical role of cellular stress response mechanisms in understanding the health benefits provided by herbal medicines from an evolutionary and ecological perspective.

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“…Recently, ginsenoside‐Rg1, the major active ingredient of ginseng, has attracted great attention not only in China, but also in Japan, Korea, and other western countries, due to its extensive pharmacological activities, including neuroprotective and nootropic effects, as well as anticancer, antioxidant, and anti‐inflammatory properties (Zhang et al, ; Mochizuki et al, ; Li et al, ). Interestingly, previous studies have shown that Rg1 can reduce autophagy in cardiomyocytes treated with hypoxia/reoxygenation (Zhang et al, ), and in renal tubular cells exposed to aldosterone (Wang et al, ), suggesting the anti‐autophagy property may be another pharmacological activity of Rg1, which may also inhibit ANG‐II‐induced autophagy in podocyte.…”

Section: Introductionmentioning

confidence: 97%

Ginsenoside Rg1 inhibits angiotensin II‐induced podocyte autophagy via AMPK/mTOR/PI3K pathway

Tan

Wang

et al. 2016

Cell Biology International

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Recent researches have reported the extensive pharmacological activities of Ginsenoside Rg1 including antioxidant, anti-inflammatory, and anticancer properties. Furthermore Rg1 was also shown to protect various kinds of cells from self-digestion by its anti-autophagy activity. In previous studies, angiotensin II (Ang II), a key mediator of renin-angiotensin system, has been demonstrated to contribute to the progression of renal injury including abnormal autophagy. However, whether Rg1 can relieve Ang II-induced autophagy in podocyte as well as the underlying molecular mechanism remains to be elucidated. Here, we employed Ang II-treated podocyte as a model to investigate the effect of Rg1 on autophagy and the involved signal pathways. In the present study, we found that Ang II strongly promoted autophagy in immortalized mouse podocyte cells by observing the formation of autophagosomes and detecting the expression of autophagic marker, for example, LC3-II. Notably, compared to the Ang II-treated cells, treatment with Rg1 significantly inhibited the formation of autophagosomes and expression of autophagy-related proteins in Ang II pre-treated podocyte. Meanwhile, Rg1 downregulated the activity of AMPK and GSK-3β and upregulated the activity of P70S6K in Ang II-treated podocyte. In conclusion, these findings demonstrate that Ang II promotes autophagy in podocyte, and Rg1 effectively attenuates this process through AMPK/mTOR/PI3K pathway, suggesting that Rg1 may be beneficial to alleviate podocyte injury.

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Ginsenoside Rg1 reduces aldosterone-induced autophagy via the AMPK/mTOR pathway in NRK-52E cells

Cited by 29 publications

References 30 publications

Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

Cellular stress response mechanisms as therapeutic targets of ginsenosides

Ginsenoside Rg1 inhibits angiotensin II‐induced podocyte autophagy via AMPK/mTOR/PI3K pathway

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