Amelioration of insulin resistance by Rk₁+ Rg₅complex under endoplasmic reticulum stress conditions

Abstract

Background:Diabetes mellitus is a metabolic syndrome exaggerated by stress conditions. Endoplasmic reticulum stress (ERS) impairs the insulin signaling pathway making the diabetic conditions worsen. Pharmacological agents are supplied externally to overcome this malfunction. Ginsenosides from Panax ginseng C.A Meyer possesses many pharmacological properties and are used for the treatment of diabetes.Objective:To investigate the effects of the Rk1 +Rg5 complex on the amelioration of insulin resistance in 3T3-L1 cells under endoplasmic reticulum stress conditions.Materials and Methods:Heat-processed ginseng extracts are found to contain many pharmacologically active ginsenosides. Among them Rk1 +Rg5 is found to be present in higher concentrations than the other minor ginsenosides. The Rk1 +Rg5 complex was tested for its effect in the 3T3-L1 insulin-resistant model and subjected to the MTT assay, glucose oxidase assay and gene expression studies using RT-PCR and real-time PCR under endoplasmic reticulum stress conditions.Results:Rk1 +Rg5 treatment is found to increase the glucose uptake into the cells when compared to that of a positive control (tunicamycin treatment group, TM). Further we have analyzed the role at gene expression level. The Rk1 +Rg5 complex was found to show an effect on the IGF 2R receptor, CHOP-10, and C/EBP gene at a particular treated concentration (50 μM). Moreover, stress condition (about 50% decreases) was overcome by the ginsenoside treatments at 50 μM.Conclusion:The present results showed that under endoplasmic reticulum stress conditions Rk1 +Rg5 complex exhibits a potential protective role in insulin-resistant 3T3-L1 cells.

Ginsenoside Rk1 bioactivity: a systematic review

“…Out of the 28 studies included, 21 studies were related to the effectiveness of G-Rk1 only and seven studies were reported on the combined effects of G-Rk1 and G-Rg5. The most common study design was in vitro study with 22 studies ( Ahn et al, 2016 ; Ju et al, 2012 ; Kang et al, 2007 ; Kang et al, 2006 ; Kim et al, 2012 ; Kim et al, 2009 ; Kim et al, 2008 ; Kim et al, 2013b ; Ko et al, 2009 ; Kwak & Pyo, 2016 ; Lee et al, 2009 ; Lee et al, 2010 ; Lee, 2014 ; Lim et al, 2009 ; Liu et al, 2007 ; Park et al, 2002 ; Ponnuraj et al, 2014 ; Quan et al, 2015 ; Ryu et al, 2016 ; Siddiqi et al, 2014 ; Toh et al, 2011 ; Xue et al, 2017 ), while in vivo study was less common with only two studies ( Jing et al, 2006 ; Kim et al, 2010 ). The remaining four articles were both in vitro and in vivo studies ( Bao et al, 2005 ; Hu et al, 2017 ; Maeng et al, 2013 ; Park et al, 2015 ).…”

“…Sixteen studies were categorized as high quality ( Hu et al, 2017 ; Kang et al, 2006 ; Kim et al, 2009 ; Kim et al, 2008 ; Ko et al, 2009 ; Kwak & Pyo, 2016 ; Lee et al, 2009 ; Lee, 2014 ; Lim et al, 2009 ; Liu et al, 2007 ; Maeng et al, 2013 ; Park et al, 2002 ; Quan et al, 2015 ; Ryu et al, 2016 ; Toh et al, 2011 ; Xue et al, 2017 ). Twelve studies ( Ahn et al, 2016 ; Bao et al, 2005 ; Jing et al, 2006 ; Ju et al, 2012 ; Kang et al, 2007 ; Kim et al, 2012 ; Kim et al, 2010 ; Kim et al, 2013b ; Lee et al, 2010 ; Park et al, 2015 ; Ponnuraj et al, 2014 ; Siddiqi et al, 2014 ) were categorized as moderate quality. Seven of them ( Ahn et al, 2016 ; Bao et al, 2005 ; Jing et al, 2006 ; Kim et al, 2013b ; Park et al, 2015 ; Ponnuraj et al, 2014 ; Siddiqi et al, 2014 ) focused on the effectiveness of combined (G-Rk1, G-Rg5), thus, they were downgraded in indirectness item of GRADE factors.…”

“…Twelve studies ( Ahn et al, 2016 ; Bao et al, 2005 ; Jing et al, 2006 ; Ju et al, 2012 ; Kang et al, 2007 ; Kim et al, 2012 ; Kim et al, 2010 ; Kim et al, 2013b ; Lee et al, 2010 ; Park et al, 2015 ; Ponnuraj et al, 2014 ; Siddiqi et al, 2014 ) were categorized as moderate quality. Seven of them ( Ahn et al, 2016 ; Bao et al, 2005 ; Jing et al, 2006 ; Kim et al, 2013b ; Park et al, 2015 ; Ponnuraj et al, 2014 ; Siddiqi et al, 2014 ) focused on the effectiveness of combined (G-Rk1, G-Rg5), thus, they were downgraded in indirectness item of GRADE factors. Three studies ( Kang et al, 2007 ; Kim et al, 2010 ; Lee et al, 2010 ) were not completely pertained to our main outcome since they did not concern mainly with G-Rk1.…”

“… Ponnuraj et al (2014) assessed the effect G-Rk1 on insulin resistance. 3T3-L1 cells were treated with G-Rg5/G-Rk1 complex at different concentrations where tunicamycin was used to induce stress on the endoplasmic reticulum (ER).…”

“…In this systematic review, we found that various pharmacological and therapeutic effects of G-Rk1 have been reported in the 28 included studies such as anti-cancer effects ( Kim et al, 2008 ), antiplatelet aggregation activities ( Ju et al, 2012 ; Lee et al, 2009 ), cognitive function enhancement ( Bao et al, 2005 ), anti-inflammatory effects ( Kim et al, 2010 ; Lee, 2014 ), lipid accumulation reduction ( Kim et al, 2009 ), antioxidant effects ( Ryu et al, 2016 ), anti-insulin resistance ( Ponnuraj et al, 2014 ), and protection against human arthritis and nephrotoxicity ( Kim et al, 2010 ; Park et al, 2015 ).…”