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

Abstract

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.

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

“…Most recently, Rg2 was reported to exhibit neuronal and metabolic benefits through autophagy induction [36]. 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].…”

miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell lung cancer by targeting Sirt1

“…Convincing evidence showed that AMPK-mTOR pathway is important in regulating autophagy (25,47). Activation of AMPK is capable of inhibiting the phosphorylation of mTOR, and thus promotes cell autophagy (24,48). Autophagy is closely related to tumor metastasis, EMT, apoptosis and drug resistance (49–51).…”

Cellular stress response mechanisms as therapeutic targets of ginsenosides

“…Angiotensin II (Ang II), a key mediator of the renin–angiotensin system, has been demonstrated to induce abnormal autophagy in podocytes, resulting in renal injury. 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.…”

“…The ginsenosides that serve as autophagy inducer include CK, Rg3, Rh2, Rg1, Rg2, and F2 . Meanwhile, the ginsenosides that can inhibit autophagy include Ro, Rg3, Rg1, and Rb1 (Fig. ).…”

“…Thus, maintaining the homeostasis of autophagy may be a mechanism of reducing renal injury. Moreover, Rg1 was found to inhibit the abnormal autophagy induced by aldosterone in rat renal tubular NRK‐52E cells and mouse podocytes, as well as angiotensin II in mouse podocytes, which may contribute to the alleviation of renal injury.…”