Ginsenoside Rg3 inhibits angiogenesis in a rat model of endometriosis through the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway

Cao, Yang; Ye, Qing; Zhuang, Mengfei; Xie, Shuwu; Zhong, Ruihua; Cui, Jingang; Zhou, Jieyun; Zhu, Yan; Zhang, Tingting; Cao, Lin

doi:10.1371/journal.pone.0186520

Cited by 63 publications

(43 citation statements)

References 22 publications

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“…The PI3K/AKT/mTOR signaling pathway is involved in the antitumor effects of ginsenoside Rg3 in lung cancer cells ( Xie et al, 2017 ). Ginsenoside Rg3 inhibits angiogenesis in a rat model of endometriosis through the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway ( Cao et al, 2017 ). Recent studies also have revealed that activation of the PI3K/AKT pathway exhibits a protective effect in a mouse model of ALI.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway

Yang

Wang

et al. 2018

Front. Pharmacol.

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Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Ginsenoside Rg3, a type of traditional Chinese medicine extracted from ginseng, is widely used to cure many inflammation-related diseases. However, the specific molecular mechanism of the effects of ginsenoside Rg3 on inflammation has rarely been reported. Thus, we established a mouse model of lipopolysaccharide (LPS)-induced ALI to investigate the immune protective effects of ginsenoside Rg3 and explore its molecular mechanism. In wild type (WT) mice, we found that ginsenoside Rg3 treatment significantly mitigated pathological damages and reduced myeloperoxidase (MPO) activity as well as the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6); furthermore, the production of anti-inflammatory mediators interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), polarization of M2 macrophages and expression levels of the phosphorylation of phosphatidylinositol 3-hydroxy kinase (PI3K), protein kinase B (PKB, also known as AKT), mammalian target of rapamycin (mTOR) and Mer receptor tyrosine kinase (MerTK) were promoted. However, there were no significant differences with regards to the pathological damage, MPO levels, inflammatory cytokine levels, and protein expression levels of the phosphorylation of PI3K, AKT and mTOR between the LPS treatment group and ginsenoside Rg3 group in MerTK-/- mice. Taken together, the present study demonstrated that ginsenoside Rg3 could attenuate LPS-induced ALI by decreasing the levels of pro-inflammatory mediators and increasing the production of anti-inflammatory cytokines. These processes were mediated through MerTK-dependent activation of its downstream the PI3K/AKT/mTOR pathway. These findings identified a new site of the specific anti-inflammatory mechanism of ginsenoside Rg3.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway

Yang

Wang

et al. 2018

Front. Pharmacol.

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“…Neiyi Fang resisted EM through decreasing the expression of mRNA and protein of TGF‐β1 and can remarkably restrain the growth of ectopic endometrium and inhibit inflammatory response , which were all consistent with our findings. Currently, Gestrinone was the most frequently used drug for the treatment of EM, promoting apoptosis and inhibiting growth and angiogenesis of the ectopic endometrium . CNYP administration herein showed comparable benefits to Gestrinone in surgically induced EM rats in the context of USP10 expression and ERK1/2 activation.…”

Section: Discussionmentioning

confidence: 67%

Cai's Neiyi Prescription promotes apoptosis and inhibits inflammation in endometrial stromal cells with endometriosis through inhibiting USP10

Zhu

Zhang

et al. 2018

Biotech and App Biochem

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To observe the effect of Cai's Neiyi Prescription (CNYP) on the apoptosis and inflammation in endometrial stromal cells with endometriosis (EM) both in vivo and in vitro, EM model rats and endometrial stromal cells were treated with CNYP and the level of USP10, p-ERK1/2, ERK1/2, and apoptosis-related protein as well as the levels of proinflammatory factors were measured by Western blotting and ELISA, respectively. Rats with surgically induced EM showed increased USP10 expression and ERK/2 activation. Intragastric administration of CNYP granule significantly inhibited EM-induced ERK1/2 activation and expression of USP10 and Bcl-2, but increased the expression of Bax and Caspase-7 in EM-induced rats. CNYP granule administration also inhibited EM-induced inflammation in rats. Moreover, the ectopic endometrial stromal cells isolated from EM patients demonstrated decreased ERK1/2 activation and expression of USP10 and Bcl-2 and increased expression of Bax and Caspase-7 after cultured in DMEM containing CNYP-medicated rat serum, which were reversed by USP10 overexpression and were enhanced by USP10 siRNA. USP10 overexpression also inhibited while USP10 siRNA enhanced the CNYP-induced inhibition of inflammation in ectopic endometrial stromal cells. Taken together, our results suggest that CNYP granule promotes apoptosis and inhibits inflammation in endometrial stromal cells with EM through inhibiting USP10. C 2018

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“…The anti-angiogenic effect of Rg3 is mainly due to the regulation of VEGF and suppression of the interaction between endothelial cells and the extracellular matrix by reducing the microvessel density in tumor tissues [ 111 , 112 ]. Ginsenoside Rg3 has been shown to inhibit angiogenesis in endometrial lesions in a rat model by blocking VEGFR-2 and inhibiting the PI3K/Akt/mTOR signaling pathway [ 113 ]. Rg3 has been shown to effectively alter the fibrotic properties of human embryonic stem cells (HESCs) in patients with endometriosis, likely via miR-27b-3p modulation [ 114 ].…”

Section: Resultsmentioning

confidence: 99%

Anti‐Angiogenic Alternative and Complementary Medicines for the Treatment of Endometriosis: A Review of Potential Molecular Mechanisms

Zheng

Cao²,

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Endometriosis is caused by the growth or infiltration of endometrial tissues outside of the endometrium and myometrium. Symptoms include pain and infertility. Surgery and hormonal therapy are widely used in Western medicine for the treatment of endometriosis; however, the side effects associated with this practice include disease recurrence and menopause, which can severely influence quality of life. Angiogenesis is the main biological mechanism underlying the development of endometriosis. Numerous natural products and Chinese medicines with potent anti-angiogenic effects have been investigated, and the molecular basis underlying their therapeutic effects in endometriosis has been explored. This review aims to describe natural products and compounds that suppress angiogenesis associated with endometriosis and to assess their diverse molecular mechanisms of action. Furthermore, this review provides a source of information relating to alternative and complementary therapeutic products that mediate anti-angiogenesis. An extensive review of the literature and electronic databases, such as the China National Knowledge Infrastructure, PubMed, and Embase, was conducted using the keywords ‘endometriosis,' ‘traditional Chinese medicine,' ‘Chinese herbal medicine,' ‘natural compounds,' and ‘anti-angiogenic' therapy. Anti-angiogenic therapy is an emerging strategy for the treatment of endometriosis. Natural anti-angiogenic products and Chinese medicines provide several beneficial clinical effects, including pain relief. In this review, we summarize clinical trials and experimental studies of endometriosis using natural products and Chinese medicines. In particular, we focus on anti-angiogenic products and alternative and complementary medicines for the treatment of endometriosis and additionally examine their therapeutic efficacy and mechanisms of action. Anti-angiogenic natural products and/or compounds provide a new approach for the treatment of endometriosis. Future work will require randomized trials with larger numbers of subjects, as well as long-term follow-up to confirm the findings described here.

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Ginsenoside Rg3 inhibits angiogenesis in a rat model of endometriosis through the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway

Cited by 63 publications

References 22 publications

Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway

Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway

Cai's Neiyi Prescription promotes apoptosis and inhibits inflammation in endometrial stromal cells with endometriosis through inhibiting USP10

Anti‐Angiogenic Alternative and Complementary Medicines for the Treatment of Endometriosis: A Review of Potential Molecular Mechanisms

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