4.6 Review

Preparation and bioactivity of the rare ginsenosides Rg3 and Rh2: An updated review

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Specific and efficient hydrolysis of all outer glucosyls in protopanaxadiol type and protopanaxatriol type ginsenosides by a β-glucosidase from Thermoclostridium stercorarium

Cheng Zeng et al.

Summary: A new method for enzymatic preparation of minor ginsenosides was developed using T. stercorarium beta-glucosidase (Tsbgl). Tsbgl demonstrated efficient deglycosylation activity towards natural ginsenosides, providing a specific and efficient way to produce minor ginsenosides.

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Enhanced biotransformation of the minor ginsenosides in red ginseng extract by Penicillium decumbens β-glucosidase

So-Yeon Kim et al.

Summary: This study successfully converted ginsenoside Rb1 to Compound K (C-K) using a beta-glucosidase from Penicillium decumbens, increasing the content of C-K and Rh2 in ginseng extracts. By a simple biotransformation process, enhancing the health benefits of ginseng extracts.

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Ginsenoside Rg3 protects glucocorticoid-induced muscle atrophy in vitro through improving mitochondrial biogenesis and myotube growth

Ryuni Kim et al.

Summary: Rg3 has been found to prevent dexamethasone-induced myotube atrophy by activating specific signaling pathways and promoting muscle-specific gene expression, while also protecting against mitochondrial dysfunction. These findings suggest that Rg3 may have therapeutic potential for muscle aging and diseases such as cancer cachexia.

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Identification of β-Glucosidase Activity of Lentilactobacillus buchneri URN103L and Its Potential to Convert Ginsenoside Rb1 from Panax ginseng

Gereltuya Renchinkhand et al.

Summary: Lentilactobacillus buchneri isolated from Korean fermented plant foods can effectively hydrolyze ginsenoside Rb1 into Rd and Rg3. The strain also exhibits higher enzymatic activities compared to other strains, which makes it suitable for the production of functional foods, beverages, cosmetics, and health products.
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Ginsenoside Rh2 mitigates doxorubicin-induced cardiotoxicity by inhibiting apoptotic and inflammatory damage and weakening pathological remodelling in breast cancer-bearing mice

Jingang Hou et al.

Summary: The study found that ginsenoside Rh2 can reduce the cardiotoxicity caused by doxorubicin (Dox) by inhibiting cardiac histopathological changes, apoptosis, necrosis, and inflammation. Rh2 also attenuates pathological remodeling by reducing fibroblast to myofibroblast transition (FMT) and endothelial-mesenchymal transition (EndMT). RNA-sequencing analysis showed that Dox treatment predominantly targets cell cycle and microtubule attachment, while Rh2 regulates these effects. Interestingly, Rh2 also attenuates fibrosis by promoting senescence in myofibroblasts and reversing established myofibroblast differentiation in EndMT.

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The involvement of Parkin-dependent mitophagy in the anti-cancer activity of Ginsenoside

Xin Sun et al.

Summary: Rg3 induces mitophagy in human colon cancer cells and exerts anticancer effect by regulating the activity of GAPDH.

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Ginsenoside Rh2 administration produces crucial antidepressant-like effects in a CUMS-induced mice model of depression

Lin-Sheng Shi et al.

Summary: This study investigated the antidepressant effects and mechanisms of action of Ginsenoside Rh2 in a depression animal model. The results showed that Rh2 reduced depressive-like symptoms and promoted the activation of the BDNF signaling pathway.

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Ginsenoside Rh2 Inhibits NLRP3 Inflammasome Activation and Improves Exosomes to Alleviate Hypoxia-Induced Myocardial Injury

Zhongwen Qi et al.

Summary: The study found that Ginsenoside Rh2 could improve the inflammatory microenvironment after acute myocardial infarction and enhance the protective effect of exosomes against myocardial injury, providing new insights into the modification of exosomes in MI treatment.

FRONTIERS IN IMMUNOLOGY (2022)

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Ginsenoside Rg3 induces apoptosis and inhibits proliferation by down-regulating TIGAR in rats with gastric precancerous lesions

Shangbin Lv et al.

Summary: The study demonstrates that GRg3 has therapeutic effects on MNNG-induced GPL rats by down-regulating the expression levels of TIGAR and production levels of GSH, NADP, and G6PD and up-regulating the concentration of ROS, inducing apoptosis and inhibiting cell proliferation.

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Protective effect of ginsenoside Rh2 on scopolamine-induced memory deficits through regulation of cholinergic transmission, oxidative stress and theERK-CREB-BDNFsignaling pathway

Jingwei Lv et al.

Summary: The study demonstrated that Rh2 treatment effectively improved memory deficits induced by Scop in mice by modulating the cholinergic system, inhibiting oxidative stress, and activating the ERK-CREB-BDNF signaling pathway. These findings suggest that Rh2 may be a promising candidate compound for treating Alzheimer's disease.

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Anti-Cancer Effects of an Optimised Combination of Ginsenoside Rg3 Epimers on Triple Negative Breast Cancer Models

Maryam Nakhjavani et al.

Summary: The combination of Rg3 epimers with 50μM SRg3 and 25μM RRg3 inhibited migration of TNBC cells, reduced stem cell marker, affected AKT signaling in mammospheres, and showed promising results in shrinking primary tumors and reducing metastasis load in a mouse model of metastatic TNBC.

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Alleviative effects of 20(R)-Rg3 on HFD/STZ-induced diabetic nephropathy via MAPK/NF-κB signaling pathways in C57BL/6 mice

Ying Li et al.

Summary: In this study, treatment with 20(R)-Rg3 for 8 weeks in T2D mice not only decreased FBG and AGEs levels, but also improved insulin, blood lipids, oxidative stress, and renal function by regulating MAPKs and NF kappa B signal pathways, showing significant ameliorative effects on DN mice.

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Enhancement of biotransformation of ginsenosides in white ginseng roots by aerobic co-cultivation of Bacillus subtilis and Trichoderma reesei

Guo Xie et al.

Summary: In this study, the biotransformation of ginsenosides in white ginseng roots was successfully enhanced by co-cultivating Bacillus subtilis and Trichoderma reesei aerobically. The optimal nitrogen source was found to be corn steep liquor, and the use of staged inoculation further improved the transformation efficiency.

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Ginsenoside Rg3 exerts a neuroprotective effect in rotenone-induced Parkinson's disease mice via its anti-oxidative properties

Yingjie Han et al.

Summary: The study demonstrates that ginsenoside Rg3 can significantly improve neuroprotective effects in rotenone-induced Parkinson's disease mice, manifested in enhanced motor function and regulation of oxidative stress.

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(20S) Ginsenoside Rh2 Exerts Its Anti-Tumor Effect by Disrupting the HSP90A-Cdc37 System in Human Liver Cancer Cells

Chen Chen et al.

Summary: 20S G-Rh2 inhibits the survival and proliferation of human liver cancer cells by targeting HSP90A and disturbing the HSP90A-Cdc37 chaperone system. This may make it a promising alternative drug for liver cancer therapy.

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

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Ginsenoside Rh2 stimulates the production of mitochondrial reactive oxygen species and induces apoptosis of cervical cancer cells by inhibiting mitochondrial electron transfer chain complex

Ying Liu et al.

Summary: The study demonstrated the potential anti-cervical cancer activity of G-Rh2 by inhibiting mitochondrial complex activity to induce apoptosis in cervical cancer cells.

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Ginsenoside Rh2 alleviates ulcerative colitis by regulating the STAT3/miR-214 signaling pathway

Xuanqing Chen et al.

Summary: The study found that Rh2 exhibits potential application value in the treatment of ulcerative colitis (UC), and its mechanism is related to the downregulation of STAT3/miR-214 levels.

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Rg3 promotes the SUMOylation of SERCA2a and corrects cardiac dysfunction in heart failure

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Ginsenoside Rg3 ameliorates acetaminophen-induced hepatotoxicity by suppressing inflammation and oxidative stress

Yan Gao et al.

Summary: The study demonstrated that Rg3 could alleviate APAP-induced liver damage, reduce oxidant and inflammatory response, alleviate hepatocellular damage, showing the potential of Rg3 as a potential therapeutic medicine for preventing hepatic injury.

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Ginsenoside Rg3 ameliorates allergic airway inflammation and oxidative stress in mice

Wen-Chung Huang et al.

Summary: The study showed that ginsenoside Rg3 significantly reduced airway inflammation, oxidative stress, and airway hyperresponsiveness in asthmatic mice, as well as decreased eosinophil infiltration. In tracheal epithelial cells, ginsenoside Rg3 also reduced inflammatory responses and oxidative stress.

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Ginsenoside Rg3 inhibits osteosarcoma progression by reducing circ_0003074 expression in a miR-516b-5p/KPNA4-dependent manner

Tehasi Wang et al.

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Ginsenoside 20(S)-Rg3 suppresses cell viability in esophageal squamous cell carcinoma via modulating miR-324-5p-targeted PSME3

Min Jiang et al.

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Di Yang et al.

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Ginsenoside Rg3 attenuates angiotensin II-induced myocardial hypertrophy through repressing NLRP3 inflammasome and oxidative stress via modulating SIRT1/NF-κB pathway

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