The Efficacy of Ginsenoside Rg3 Combined with First-line Chemotherapy in the Treatment of Advanced Non-Small Cell Lung Cancer in China: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Peng, Zhi; Wu, Wen Wen; Yi, Ping

doi:10.3389/fphar.2020.630825

Cited by 30 publications

(22 citation statements)

References 53 publications

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“…Administration of GRg3 tablet (20 mg twice daily for 30 days) combined with gemcitabine and cisplatin in patients with advanced esophageal cancer increased the one-year survival rate and reduced drug-associated adverse events [ 15 , 17 ]. Meta-analysis of 20 clinical studies involving GRg3 (20 mg twice daily 6–24 weeks) combined with non-small cell lung cancer therapeutics indicated that Rg3 enhances short-term efficacy, prolongs overall survival rate, and reduces treatment-related toxicity [ 14 , 18 , 19 , 20 ]. Plasma exposure of GRg3 was increased 7.3-fold over the 6-fold dose range (10–60 mg, intramuscular injection) without a significant change in clearance and volume of distribution in Chinese healthy volunteers [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice

et al. 2021

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This study aims to investigate the effect of lactic acid bacteria (LAB) on in vitro and in vivo metabolism and the pharmacokinetics of ginsenosides in mice. When the in vitro fermentation test of RGE with LAB was carried out, protopanaxadiol (PPD) and protopanaxadiol (PPD), which are final metabolites of ginsenosides but not contained in RGE, were greatly increased. Compound K (CK), ginsenoside Rh1 (GRh1), and GRg3 also increased by about 30%. Other ginsenosides with a sugar number of more than 2 showed a gradual decrease by fermentation with LAB for 7 days, suggesting the involvement of LAB in the deglycosylation of ginsenosides. Incubation of single ginsenoside with LAB produced GRg3, CK, and PPD with the highest formation rate and GRd, GRh2, and GF with the lower rate among PPD-type ginsenosides. Among PPT-type ginsenosides, GRh1 and PPT had the highest formation rate. The amoxicillin pretreatment (20 mg/kg/day, twice a day for 3 days) resulted in a significant decrease in the fecal recovery of CK, PPD, and PPT through the blockade of deglycosylation of ginsenosides after single oral administrations of RGE (2 g/kg) in mice. The plasma concentrations of CK, PPD, and PPT were not detectable without change in GRb1, GRb2, and GRc in this group. LAB supplementation (1 billion CFU/2 g/kg/day for 1 week) after the amoxicillin treatment in mice restored the ginsenoside metabolism and the plasma concentrations of ginsenosides to the control level. In conclusion, the alterations in the gut microbiota environment could change the ginsenoside metabolism and plasma concentrations of ginsenosides. Therefore, the supplementation of LAB with oral administrations of RGE would help increase plasma concentrations of deglycosylated ginsenosides such as CK, PPD, and PPT.

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Section: Introductionmentioning

confidence: 99%

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice

et al. 2021

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“…Liu et al (2018) suggested that curcumin enhanced the activity of PTEN by down-regulating miR-21 and prevented the activity of the PI3K/AKT signaling which in turn inhibited the biological activity of GC cells. Ginsenoside Rg3, a steroidal saponin derived from Panax Ginseng in traditional Chinese medicine, has been found to have anti-tumor activity including promoting cytotoxicity of chemotherapy in various types of human cancers ( Tian et al, 2016 ; Yuan et al, 2017 ; Peng et al, 2020 ). Ginsenoside Rg3 can enhance the sensitivity to chemotherapy when used in combination with cisplatin ( Lee et al, 2014 ) or docetaxel ( Kim et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg3 Alleviates Cisplatin Resistance of Gastric Cancer Cells Through Inhibiting SOX2 and the PI3K/Akt/mTOR Signaling Axis by Up-Regulating miR-429

Wang

Geng

et al. 2022

Front. Genet.

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Platinum-based cytotoxic chemotherapy is considered the standard treatment for advanced gastric cancer (GC). However, cisplatin chemoresistance often occurs with the mechanisms being not well clarified, which results in the cancer recurrence and poor survival. Ginsenoside Rg3, isolated from the Chinese Herb Panax Ginseng, is recognized as an anti-cancer agent. Herein, we aimed to reveal whether Ginsenoside Rg3 alleviates cisplatin resistance and sensitizes GC cells to cisplatin-induced apoptosis, and draw out the underlying molecular mechanism in cisplatin-resistant GC cells. The lower expression of miR-429 was found in AGSR-CDDP cells; it was also in association with cisplatin-resistance in GC cells and expression of which was restored following Ginsenoside Rg3 treatment. We also demonstrated that miR-429 made a contribution toward chemosensitivity in GC cells partly through SOX2 regulation. SOX2 was found to contribute to developing platinum resistance and was an authentic target for miR-429 in AGSR-CDDP cells. Importantly, enforced expression of SOX2 with a pcDNA3-SOX2 construct lacking the 3′-UTR miRNA binding site diminished the cytotoxic effects of miR-429 in AGSR-CDDP cells. We demonstrated that Ginsenoside Rg3 enhanced chemosensitivity in AGSR-CDDP GC cells, at least in part, through up-regulating miR-429, thereby targeting SOX2 and modulating downstream PI3K/AKT/mTOR signaling. Ginsenoside Rg3 was also found to regulate apoptosis-related genes via miR-429 in cisplatin-resistant GC cells. Ginsenoside Rg3 treatment significantly suppressed the migration rate of AGSR-CDDP GC cells, while following transfection with anti-miR-429, the anti-migratory effects of Ginsenoside Rg3 was partially abolished. This data suggested that Ginsenoside Rg3 may impede the chemoresistance and migration of GC cells mainly mediated through miR-429. We concluded that miR-429-regulated SOX2 expression was one of the main mechanisms by which Ginsenoside Rg3 dramatically promoted its anticancer effects on cisplatin-resistant GC cells. We also underscored a supporting model in which miR-429 adjusted PI3K/AKT/mTOR signaling by regulating SOX2 in cisplatin-resistant GC cells.

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“…As early as 1996, some researchers conducted toxicological tests on Rg3, and the results showed that continuous administration of Rg3 had no obvious embryonic toxicity and teratogenicity, no obvious toxic reaction and no mutagenicity in rats. Relevant studies have reported that Rg3 combined with first-line chemotherapy improved efficacy of chemotherapy and reduced toxicity of chemotherapy drugs [21].…”

Section: Discussionmentioning

confidence: 99%

Untitled

2021

BJSTR

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Lung cancer is one of the representative causes of death globally. Ginsenosides, as a class of natural sterol compounds, attract considerable attention due to their pharmacological effects. To better evaluate the anti-lung cancer efficacy of ginsenosides, we here conducted the systematic review and summarized some of the most recent findings which regard the possible molecular mechanisms. With extensive research on anti-tumor action mechanisms, ginsenosides will be a widely applied natural medicine against lung cancer.

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The Efficacy of Ginsenoside Rg3 Combined with First-line Chemotherapy in the Treatment of Advanced Non-Small Cell Lung Cancer in China: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Cited by 30 publications

References 53 publications

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice

Ginsenoside Rg3 Alleviates Cisplatin Resistance of Gastric Cancer Cells Through Inhibiting SOX2 and the PI3K/Akt/mTOR Signaling Axis by Up-Regulating miR-429

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