The reversal effect of Ginsenoside Rh2 on drug resistance in human colorectal carcinoma cells and its mechanism

Liu, Guiwei; Liu, Yanhua; Jiang, Guosheng; Ren, Weidan

doi:10.1007/s13577-017-0189-3

Cited by 42 publications

(22 citation statements)

References 34 publications

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“…For example, emodin from Rheum palmatum L. has been proven to possess hepatoprotective, anti-inflammatory, antioxidant, anticoagulant, and anti-microbial activities (Nemmar et al, 2015;Dong et al, 2016). Ginsenoside rh2 from Panax ginseng C.A.Mey exhibits antimicrobial resistance and cure for pneumonia (Hsieh et al, 2018;Liu et al, 2018). Benzoylmesaconine from Aconitum carmichaeli Debeaux has antiviral and anti-nociceptive activities (Suzuki et al, 1994;Kobayashi et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Systems Pharmacology and Verification of ShenFuHuang Formula in Zebrafish Model Reveal Multi-Scale Treatment Strategy for Septic Syndrome in COVID-19

et al. 2020

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The outbreak of coronavirus disease 2019 (COVID-19) has affected millions of people worldwide. Critically ill COVID-19 patients develop viral septic syndrome, including inflammatory damage, immune dysfunction, and coagulation disorder. In this study, we investigated ShenFuHuang formula (SFH), a traditional Chinese medicine, which has been widely used as complementary therapy for clinical treatment of COVID-19 in Wuhan, to understand its pharmacological properties. Results of systems pharmacology identified 49 active compounds of SFH and their 69 potential targets, including GSK3b, ESR1, PPARG, PTGS2, AKR1B10, and MAPK14. Network analysis illustrated that the targets of SFH may be involved in viral disease, bacterial infection/mycosis, and metabolic disease. Moreover, signaling pathway analysis showed that Toll-like receptors, MAPK, PPAR, VEGF, NOD-like receptor, and NF-kappa B signaling pathways are highly connected with the potential targets of SFH. We further employed multiple zebrafish models to confirm the pharmacological effects of SFH. Results showed that SFH treatment significantly inhibited the inflammatory damage by reducing the generation of neutrophils in Poly (I:C)-induced viral infection model. Moreover, SFH treatment could improve the phagocytosis of macrophages and enhance the expression of immune genes in an immune deficiency model. Furthermore, SFH treatment exhibited promising anti-thrombosis effect in a thrombus model. This study provided additional evidence of SFH formula for treating COVID-19 patients with septic syndrome using multiple-scale estimation.

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Section: Discussionmentioning

confidence: 99%

Systems Pharmacology and Verification of ShenFuHuang Formula in Zebrafish Model Reveal Multi-Scale Treatment Strategy for Septic Syndrome in COVID-19

et al. 2020

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“…G-Rh2, one of the main components of ginseng, has numerous biological activities, and there are no reported side effects in normal cells. A previous study reported that G-Rh2 reduced cell proliferation and sensitized CRC cells to 5-fluorouracil chemotherapy (19). In addition, there is evidence that G-Rh2 may be associated with drug resistance in cancer treatment (20).…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of P-gp can reverse the multidrug resistance induced by chemotherapeutic agents (22). Previous studies have reported that G-Rh2 can reverse multidrug resistance in adriamycin-resistant human breast cancer MCF-7 cells (20) and reverse drug resistance in 5-fuorouracil-resistant LoVo and HCT-8 human CRC cells (19). In a previous study, 20 (S)-Rh2 was shown to inhibit P-gp in multidrug-resistant cancer cells (21).…”

Section: Discussionmentioning

confidence: 99%

Reversal effect of ginsenoside Rh2 on oxaliplatin‑resistant colon cancer cells and its mechanism

Gao

et al. 2019

Exp Ther Med

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Chemotherapy is an important treatment modality for colon cancer, however, drug resistance is the main factor leading to treatment failure. Ginsenoside Rh2 (G-Rh2), the main bioactive metabolite of ginseng, is known to possess the ability to potently induce cell apoptosis, inhibit cell proliferation and reverse multidrug resistance in a variety of cancer cells. The present study examined the effect of G-Rh2 on oxaliplatin (L-OHP)-resistant colon cancer cells and its potential mechanism. L-OHP-resistant colon cancer cells (LoVo/L-OHP) and LoVo cells were used in the present study. The effect of G-Rh2 on LoVo/L-OHP and LoVo cell proliferation was measured using a 3-(4,5 dimethylthiazol-z-yl)-3,5-diphenyltetrazolium bromide assay. The effects of G-Rh2 on LoVo/L-OHP and LoVo cell apoptosis were detected by flow cytometry. The mRNA and protein expression of apoptosis-related genes Bax, Bcl-2 and caspase-3, drug resistance-related genes P-glycoprotein (P-gp) and Smad4, were determined in LoVo/L-OHP and LoVo cells treated with G-Rh2 by reverse transcription-quantitative polymerase chain reaction and western blot analyses. G-Rh2 treatment significantly inhibited the proliferation and induced the apoptosis of LoVo/L-OHP and LoVo cells. In addition, G-Rh2 treatment resulted in a significant increase in pro-apoptotic factors, Bax and caspase-3, and decrease in anti-apoptotic factor Bcl-2 in the LoVo/L-OHP and LoVo cells. Furthermore, G-Rh2 treatment significantly decreased the levels of P-gp and increased the levels of Smad4 in the LoVo/L-OHP and LoVo cells. It was found that L-OHP had no significant effects on LoVo/L-OHP cell proliferation or apoptosis, whereas G-Rh2 + L-OHP treatment significantly inhibited LoVo/L-OHP cell proliferation and induced apoptosis. L-OHP had no significant effects on the expression of P-gp, Smad4, Bcl-2, Bax or caspase-3 in LoVo/L-OHP cells. Treatment with G-Rh2 + L-OHP significantly reduced the expression of P-gp and Bcl-2, and enhanced the expression levels of Smad4, Bax and caspase-3. These findings demonstrated that G-Rh2 reversed the drug resistance of LoVo/L-OHP cells to L-OHP, and this may be mediated by inhibiting cell proliferation and promoting apoptosis and regulating the expression of drug resistance genes. These results suggest that G-Rh2 may function as a potent anticancer drug for drug resistance in colon cancer treatment.

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“…Ginsenoside Rh2 (Figure 1) belongs to the family of Protopanaxadiol saponins and is an anticancer molecular entity extracted from ginseng, the dried root of Panax ginseng C. A. Meyer. 1,2 Preclinical studies showed that Rh2 could inhibit the growth of various types of cancer cells, including lung cancer, 3,4 colorectal carcinoma, [5][6][7] prostate cancer, [8][9][10] glioma, 11,12 and hepatocellular carcinoma. [13][14][15] The antineoplastic mechanism is not entirely clear.…”

mentioning

confidence: 99%

“…Yet, it has been found that Rh2 could inhibit cell metabolism, regulate protein signaling, change telomerase activity, or induce cell apoptosis. [3][4][5][6][7][8][9][10][11][12][13][14][15] Rh2 is characterized by low toxicity and low molecular weight with good solubility in lipids. 16 Increasing studies have demonstrated that Rh2 has obvious synergistic effects to some chemotherapeutic agents, even at a noneffect dosage.…”

mentioning

confidence: 99%

Pharmacokinetics of Ginsenoside Rh2, the Major Anticancer Ingredient of Ginsenoside H Dripping Pills, in Healthy Subjects

Wang

Liu

Chen

et al. 2020

Clinical Pharm in Drug Dev

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Ginsenoside H dripping pill (GH) is a novel clinical-stage adjuvant for the treatment of non-small cell lung cancer. In this study, the pharmacokinetics of ginsenoside Rh2, the major anticancer ingredient of GH, was investigated in healthy volunteers. Enrolled volunteers were assigned to 3 cohorts-7.8, 15.6, and 31.2 mg-and received single and/or multiple GH orally. Blood samples were assayed by a validated bioanalytical method, and drug concentrations were analyzed using a noncompartmental methodology. The results showed that ginsenoside Rh2 was absorbed with medium speed and reached C max a median of 3 hours after administration. The exposure of ginsenoside Rh2 was approximately dosedependent in terms of AUC and C max . The plasma concentration of ginsenoside Rh2 reached steady state after oral administration of GH twice daily for 5 days. There was no obvious accumulation in exposure parameters in the multipledose study.

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The reversal effect of Ginsenoside Rh2 on drug resistance in human colorectal carcinoma cells and its mechanism

Cited by 42 publications

References 34 publications

Systems Pharmacology and Verification of ShenFuHuang Formula in Zebrafish Model Reveal Multi-Scale Treatment Strategy for Septic Syndrome in COVID-19

Systems Pharmacology and Verification of ShenFuHuang Formula in Zebrafish Model Reveal Multi-Scale Treatment Strategy for Septic Syndrome in COVID-19

Reversal effect of ginsenoside Rh2 on oxaliplatin‑resistant colon cancer cells and its mechanism

Pharmacokinetics of Ginsenoside Rh2, the Major Anticancer Ingredient of Ginsenoside H Dripping Pills, in Healthy Subjects

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