Ginsenoside Rd Inhibits the Metastasis of Colorectal Cancer via Epidermal Growth Factor Receptor Signaling Axis

Phi, Lan Thi; Sari, Ita Novita; Wijaya, Yoseph Toni; Kim, Kwang Seock; Park, Kichul; Cho, Art E.; Kwon, Hyog Young

doi:10.1002/iub.1984

Cited by 33 publications

(24 citation statements)

References 43 publications

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“…Intestinal enzymes can metabolize high content GSRb1 to GSRd, which can then be absorbed and used by the body. Studies have shown that GSRd has strong biological activity and shows unique protective effects on the cardiovascular system ( Zhang et al, 2019 ), immune system ( Zhu et al, 2014 ), alimentary system ( Liu et al, 2018 ; Phi et al, 2019 ), and central nervous system ( Cong and Chen, 2016 ). Several animal studies have shown that GSRd can improve motor system function, reduce striatum injury area and cerebral infarction volume, have neurotrophic and protective effects on neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, and improve neurological dysfunction caused by ischemic stroke ( Ye et al, 2009 ; Wang et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rd Ameliorates Auditory Cortex Injury Associated With Military Aviation Noise-Induced Hearing Loss by Activating SIRT1/PGC-1α Signaling Pathway

Chen

Liu

et al. 2020

Front. Physiol.

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Free radicals and oxidative stress play an important role in the pathogenesis of noiseinduced hearing loss (NIHL). Some ginseng monomers showed certain therapeutic effects in NIHL by scavenging free radicals. Therefore, we hypothesized that ginsenoside Rd (GSRd) may exert neuroprotective effects after noise-induced auditory system damage through a mechanism involving the SIRT1/PGC-1α signaling pathway. Fortyeight guinea pigs were randomly divided into four equal groups (normal control group, noise group, experimental group that received GSRd dissolved in glycerin through an intraperitoneal injection at a dose of 30 mg/kg body weight from 5 days before noise exposure until the end of the noise exposure period, and experimental control group). Hearing levels were examined by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Hematoxylin-eosin and Nissl staining were used to examine neuron morphology. RT-qPCR and western blotting analysis were used to examine SIRT1/PGC-1α signaling and apoptosis-related genes, including Bax and Bcl-2, in the auditory cortex. Bax and Bcl-2 expression was assessed via immunohistochemistry analysis. Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were determined using a commercial testing kit. Noise exposure was found to up-regulate ABR threshold and down-regulate DPOAE amplitudes, with prominent morphologic changes and apoptosis of the auditory cortex neurons (p < 0.01). GSRd treatment restored hearing loss and remarkably alleviated morphological changes or apoptosis (p < 0.01), concomitantly increasing Bcl-2 expression and decreasing Bax expression (p < 0.05). Moreover, GSRd increased SOD and GSH-Px levels and decreased MDA levels, which alleviated oxidative stress

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rd Ameliorates Auditory Cortex Injury Associated With Military Aviation Noise-Induced Hearing Loss by Activating SIRT1/PGC-1α Signaling Pathway

Chen

Liu

et al. 2020

Front. Physiol.

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“…These results were consistent with previous studies, which reported that TLR2 was a direct target of miR-144-5p and miR-144-5p down-regulated TLR2 expression. 10,11) Herein, the GS-Rd/miR-144-5p/TLR2 axis was established. Subsequently, this axis was verified by TLR2 expression, as detected by Western blotting and RT-qPCR.…”

Section: Discussionmentioning

confidence: 99%

“…The result was consistent with a previous study. 11) Effect of GS-Rd and miR-144-5p on TLR2 Expression in U251 and U87 Cells The GS-Rd/miR-144-5p/TLR2 nexus was investigated by RT-qPCR and Western blot in the following experiments. The TLR2 mRNA levels were found to be up-regulated in untreated U251 and U87 cells compared with normal human astrocytes (NHA) (Fig.…”

Section: Expression Of Mir-144-5p In Human Glioblastoma Andmentioning

confidence: 99%

“…[6][7][8][9] In previous studies, TLR2 was validated as a target of miR-144-5p, and the expression of TLR2 can be inhibited by the overexpression of miR-144-5p. 10,11) Ginsenoside Rd (GS-Rd) has shown strong anti-tumor activity through inhibiting epidermal growth factor receptor (EGFR) signaling, oxidative stress, and protein kinase B (Akt)/mammarian target of rapamycin kinase (mTOR)/ ribosomal protein S6 kinase (p70S6K) (Akt/mTOR/p70S6K) signaling in various cancers. [12][13][14][15] Wang et al first found that GS-Rd reduces breast cancer metastasis and that this mechanism of action implicates the down-regulation of SMAD family member 2 (Smad2) targeting by miR-18a.…”

Section: Introductionmentioning

confidence: 99%

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Ginsenoside Rd Inhibits Glioblastoma Cell Proliferation by Up-Regulating the Expression of miR-144-5p

Liu

Sun

et al. 2020

Biological & Pharmaceutical Bulletin

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miR-144-5p exhibits anti-tumor activities in various cancers. Although treatment for glioblastoma has progressed rapidly, novel targets for glioblastoma are insufficient, particularly those used in precision medicine. In the current study, we found that ginsenoside Rd reduced the proliferation and migration of glioblastoma cells. Ginsenoside Rd up-regulated the tumor-suppressive miR-144-5p in glioblastoma cells. Moreover, Toll-like receptor 2, which is a target of miR-144-5p, was down-regulated. After inhibition of miR-144-5p, the effect of Ginsenoside Rd on proliferation inhibition and down-regulation of Toll-like receptor 2 was reduced. These data demonstrated the ginsenoside Rd/miR-144-5p/Toll-like receptor 2 regulatory nexus that controls the glioblastoma pathogenesis of glioblastoma. Our work provided novel targets for glioblastoma diagnosis and treatment.

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“…Mice were fed with an HFD (D12492; Research Diets, New Brunswick, New Jersey) to establish DIO models. Rd intraperitoneal injection dose usually ranges from 5 to 100 mg/kg/day in mice . Our preliminary experimental results showed that Rd could not significantly improve obesity until the injection dose was as high as 15 mg/kg/day (data not shown), and therefore we decided that the DIO mice would be administered an intraperitoneal injection of 15 mg/kg of Rd or phosphate‐buffered saline (PBS) (vehicle) daily.…”

Section: Methodsmentioning

confidence: 99%

Ginsenoside Rd Ameliorates High Fat Diet‐Induced Obesity by Enhancing Adaptive Thermogenesis in a cAMP‐Dependent Manner

Lü

Han

Zhao

et al. 2020

Obesity

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Objective With the discovery of thermogenic adipocytes in humans, it has been hypothesized that enhancing adaptive thermogenesis may improve obesity. Although many studies have found that ginseng can improve obesity, the beneficial effects of ginsenoside Rd on obesity and its mechanisms have not been studied. Methods High‐fat diet‐induced obese mice were used as the study subjects, with intraperitoneal injection of Rd daily at a dose of 15 mg/kg. Body weight and energy metabolism were observed. The effects of Rd on glucose tolerance, insulin sensitivity, and cold tolerance were tested. The expression of genes associated with thermogenesis was analyzed. Finally, the mechanisms by which Rd regulates adaptive thermogenesis were studied. Results Rd ameliorated obesity and insulin resistance. Rd increased cold tolerance through enhancing thermogenic gene expression in brown adipose tissue and increased the browning of white adipose tissue induced by cold stress. Rd increased intracellular cyclic adenosine monophosphate (cAMP) content. Decreasing intracellular cAMP levels by an inhibitor of adenylyl cyclase SQ22536 abolished the promoting effects of Rd on the expression of thermogenic genes. Conclusions Rd improves obesity and insulin resistance. The upregulation of thermogenesis by Rd is dependent on the cAMP/protein kinase A signaling pathway.

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Ginsenoside Rd Inhibits the Metastasis of Colorectal Cancer via Epidermal Growth Factor Receptor Signaling Axis

Cited by 33 publications

References 43 publications

Ginsenoside Rd Ameliorates Auditory Cortex Injury Associated With Military Aviation Noise-Induced Hearing Loss by Activating SIRT1/PGC-1α Signaling Pathway

Ginsenoside Rd Ameliorates Auditory Cortex Injury Associated With Military Aviation Noise-Induced Hearing Loss by Activating SIRT1/PGC-1α Signaling Pathway

Ginsenoside Rd Inhibits Glioblastoma Cell Proliferation by Up-Regulating the Expression of miR-144-5p

Ginsenoside Rd Ameliorates High Fat Diet‐Induced Obesity by Enhancing Adaptive Thermogenesis in a cAMP‐Dependent Manner

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