Ginsenoside Rg3 prevents INS-1 cell death from intermittent high glucose stress

Kim, You Jeong; Park, Su Min; Jung, Hwa Jin; Lee, Eun Ju; Kim, Tae Kyoon; Kim, Tae-Nyun; Kwon, Min Jeong; Lee, Soon Hee; Rhee, Byoung Doo; Kim, Mi-Kyung; Park, Jeong Hyun

doi:10.1080/19382014.2016.1161874

Cited by 15 publications

(14 citation statements)

References 29 publications

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“…The intramuscular injection of 20(S)-Rg3 has more effects in vivo and in vitro (animal and phase I clinical research), higher bioavailability, and good continuous dosing security. Moreover, 20(S)-Rg3 is more suitable for application in clinical medicine, such as a novel inhibitor of autophagy [15] or protecting INS-1 cell death from intermittent high glucose [16]. It also has been confirmed that 20(S)-Rg3 is a compound that has many pharmacological effects such as anticancer [17], inhibition of brain injury [18], and diabetic kidney injury resistance [19].…”

Section: Introductionmentioning

confidence: 97%

20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

Zhou

Sun

Yang

et al. 2020

Journal of Diabetes Research

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Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD.

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Section: Introductionmentioning

confidence: 97%

20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

Zhou

Sun

Yang

et al. 2020

Journal of Diabetes Research

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“…Ginsenoside Rb2 and its hydrolytic product ginsenoside Rg3 belong to the protopanaxadiol type of dammarane ginsenosides. Ginsenosides Rb2 and Rg3 have multiple functions in immune regulation, anti-oxidation, anti-inflammation, anti-aging and anti-fatigue ( Choi, 2002 ; Choi et al, 2015 ; Joo et al, 2015 ; Kim et al, 2016 ; Sun et al, 2017 ). However, their pro-angiogenic effects have not been vigorously studied, while their anti-angiogenesis along with anti-tumorigenic effects have been shown in several cancers ( Mochizuki et al, 1995 ; Joo et al, 2015 ; Sun et al, 2016 ; Sun et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, their pro-angiogenic effects have not been vigorously studied, while their anti-angiogenesis along with anti-tumorigenic effects have been shown in several cancers ( Mochizuki et al, 1995 ; Joo et al, 2015 ; Sun et al, 2016 ; Sun et al, 2017 ). As one of the few examples, related to pro-angiogenic effects, Kim et al reported that ginsenoside Rg3 at 1, 5, 10 µM was able to prevent INS-1 cell death by increasing cell proliferation ( Kim et al, 2016 ). Likewise, in our experimental conditions using HUVECs, ginsenoside Rg3 at lower concentrations (below 10 μM) markedly increased HUVEC proliferation.…”

Section: Discussionmentioning

confidence: 99%

Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways

et al. 2021

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Shexiang Baoxin Pill (SBP) is an oral formulation of Chinese materia medica for the treatment of angina pectoris. It displays pleiotropic roles in protecting the cardiovascular system. However, the mode of action of SBP in promoting angiogenesis, and in particular the synergy between its constituents is currently not fully understood. The combination of ginsenosides Rb2 and Rg3 were studied in human umbilical vein endothelial cells (HUVECs) for their proangiogenic effects. To understand the mode of action of the combination in more mechanistic detail, RNA-Seq analysis was conducted, and differentially expressed genes (DEGs), pathway analysis and Weighted Gene Correlation Network Analysis (WGCNA) were applied to further identify important genes that a play pivotal role in the combination treatment. The effects of pathway-specific inhibitors were observed to provide further support for the hypothesized mode of action of the combination. Ginsenosides Rb2 and Rg3 synergistically promoted HUVEC proliferation and tube formation under defined culture conditions. Also, the combination of Rb2/Rg3 rescued cells from homocysteine-induced damage. mRNA expression of CXCL8, CYR61, FGF16 and FGFRL1 was significantly elevated by the Rb2/Rg3 treatment, and representative signaling pathways induced by these genes were found. The increase of protein levels of phosphorylated-Akt and ERK42/44 by the Rb2/Rg3 combination supports the notion that it promotes endothelial cell proliferation via the PI3K/Akt and MAPK/ERK signaling pathways. The present study provides the hypothesis that SBP, via ginsenosides Rb2 and Rg3, involves the CXCR1/2 CXCL8 (IL8)-mediated PI3K/Akt and MAPK/ERK signaling pathways in achieving its proangiogenic effects.

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“…The cells were diluted with RPMI-1640 complete medium to approximately 2×10 5 /L, plated onto 6-well-plates, and then incubated at 37°C, 5% CO 2 , and 95% humidity for 48 h. After the culture reached 80% confluence, the medium was discarded, and cells were maintained in RPMI-1640 complete medium with different concentrations of glucose and FTZ serum. High-glucose induction of oxidative stress was conducted [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Chinese Medicine FTZ Recipe Protects against High-Glucose-Induced Beta Cell Injury through Alleviating Oxidative Stress

Bei

Wang

Chen

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Objective. To investigate the effect of FTZ on high-glucose-induced oxidative stress and underlying mechanisms. Methods. We used a β cell dysfunction and diabetes model that was induced in rats fed a high-fat high-sugar diet (HFHSD) for 6 weeks and injected once with 35 mg/kg streptozocin (STZ). Then, 3 and 6 g/kg of FTZ were administered by gavage for 8 weeks. In addition, an ex vivo model of oxidative stress was induced by stimulating INS-1 cells with 25 mmol/L glucose for 48 h. Result. The levels of fasting blood glucose (FBG) in diabetic model rats were obviously higher than those in the normal group; furthermore with reduced levels of β cells, catalase (CAT), superoxide dismutase (SOD), and Bcl-2 increased lipid peroxide malondialdehyde (MDA) and caspase-3 in the pancreatic tissue of the diabetic model rats. Afterward, the cells were incubated with FTZ-containing serum and edaravone. The 25 mmol/L glucose-induced SOD reduction increased MDA and intracellular ROS. The protein expression level of Mn-SOD and CAT in the model group decreased significantly compared with that in the control group. Conclusion. FTZ treatment significantly improved the alteration in the level of SOD, CAT, Bcl-2, caspase-3, and MDA coupled with β cell dysfunction in diabetic rats. Oxidative stress in INS-1 cells was closely associated with a higher rate of apoptosis, increased production of ROS and MDA, enhanced Bax expression, and caspase-3, -9 activities and markedly decreased protein expression of Mn-SOD and CAT. FTZ-containing serum incubation notably reversed the high-glucose-evoked increase in cell apoptosis, production of ROS and MDA, and Bax protein levels. Furthermore, FTZ stimulation upregulated the expression levels of several genes, including Mn-SOD, CAT, and Bcl-2/Bcl-xl. In addition, FTZ decreased the intracellular activity of caspase-3, -9 in INS-1 cells. FTZ protected β-cells from oxidative stress induced by high glucose in vivo and in vitro. The beneficial effect of FTZ was closely associated with a decrease in the activity of caspase-3, -9 and intracellular production of ROS, MDA, and Bax coupled with an increase in the expression of Mn-SOD, CAT, and Bcl-2/Bcl-xl.

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Ginsenoside Rg3 prevents INS-1 cell death from intermittent high glucose stress

Abstract: Ginsenoside Rg3 protected INS-1 cell death from IHG with reducing apoptosis and increasing proliferation.

Cited by 15 publications

References 29 publications

20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways

Chinese Medicine FTZ Recipe Protects against High-Glucose-Induced Beta Cell Injury through Alleviating Oxidative Stress

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