Ginsenosides as anticancer agents: In vitro and in vivo activities, structure–activity relationships, and molecular mechanisms of action

Nag, Subhasree; Qin, Jiang‐Jiang; Wang, Wei; Wang, Ming-Hai; Wang, Hui; Zhang, Ruiwen

doi:10.3389/fphar.2012.00025

Cited by 283 publications

(237 citation statements)

References 149 publications

(193 reference statements)

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“…Rg1 has been indicated to have an effect on the function of human diseases via anti-inflammatory and antioxidant defense systems (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). The present study demonstrated that Rg1 increased the viability of muscle cells within a starvation model, by inhibiting protein degradation via the AKT/FoxO pathway and promoting protein synthesis by the mTOR pathway.…”

Section: Discussionsupporting

confidence: 54%

Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes

Peng

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Skeletal muscle atrophy is often caused by catabolic conditions including fasting, disuse, aging and chronic diseases, such as chronic obstructive pulmonary disease. Atrophy occurs when the protein degradation rate exceeds the rate of protein synthesis. Therefore, maintaining a balance between the synthesis and degradation of protein in muscle cells is a major way to prevent skeletal muscle atrophy. Ginsenoside Rg1 (Rg1) is a primary active ingredient in Panax ginseng, which is considered to be one of the most valuable herbs in traditional Chinese medicine. In the current study, Rg1 was observed to inhibit the expression of MuRF-1 and atrogin-1 in C2C12 muscle cells in a starvation model. Rg1 also activated the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT), and forkhead transcription factor O, subtypes 1 and 3a. This phosphorylation was inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. These data suggest that Rg1 may participate in the regulation of the balance between protein synthesis and degradation, and that the function of Rg1 is associated with the AKT/mTOR/FoxO signaling pathway. IntroductionMuscle atrophy is characterized by an increase in protein degradation and reduction in protein synthesis. It is associated with a number of human diseases and catabolic conditions, including fasting, disuse, aging, cancer, neuromuscular diseases, stroke, chronic obstructive pulmonary disease, chronic heart failure, HIV-acquired immunodeficiency syndrome and sepsis (1-5). Muscle volume shrinking and muscle weakness induced by muscular dystrophy typically disrupt and adversely affect the life of patients (3,6-8). Therefore, it is essential to understand the mechanism by which skeletal muscle atrophy is regulated.A large amount of protein hydrolysis has previously been identified to occur during muscle atrophy and the ubiquitin-proteasome system (UPS) has been demonstrated to be involved in this process (9)(10)(11)(12)(13)(14). In this system, the proteins are first conjugated into multiple molecules of ubiquitin. The 26S proteasome then recognizes and degrades the ubiquitinated proteins (15,16). Multiple enzymes regulate the protein ubiquitination; these include E1, the ubiquitin-activating enzyme, E2, the ubiquitin conjugating enzyme and E3 ubiquitin ligases (17,18). E3 ubiquitin ligases serve a major role in the specificity of protein degradation, because the specific binding between the protein substrate and E3 occurs prior to the reaction with ubiquitin (18,19).It has been demonstrated that the insulin-signaling pathway is involved in the inhibition of UPS (20). In this pathway, the phosphorylation of insulin receptor substrate is stimulated when insulin binds its receptor. Phosphatidylinositol 3-kinase (PI3K), an intracellular intermediate, is recruited to phosphorylate a serine/threonine kinase, protein kinase B (AKT) during this process. AKT then phosphorylates the forkhead box class O transcription factors, subtype 1 and 3a (FoxO1 and FoxO3a), which pre...

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Section: Discussionsupporting

confidence: 54%

Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes

Peng

et al. 2017

Experimental and Therapeutic Medicine

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“…Based on their chemical structures, ginsenosides can be classified into three principal structural types, namely, protopanaxadiol, protopanaxatriol, and oleanane. More than 40 ginsenosides have been identified and isolated so far [12,13]. Their nomenclature is based on the designation of Rx and Fx, where R and F refer to the origin of ginsenosides, namely, roots and leaves ("folia") of the species, respectively, and x (x = 0, a1, a2, b1, etc.)…”

Section: Introductionmentioning

confidence: 99%

Untitled

2018

Planta Med

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Supporting information available online at http://www.thieme-connect.de/products ABSTR AC TGinsenoside Rh1 is one of major bioactive compounds extracted from red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. The objective of this study was to review the pharmacological effects of ginsenoside Rh1 in a systematic manner. We performed searches on eight electronic databases including MEDLINE (Pubmed), Scopus, Google Scholar, POPLINE, Global Health Library, Virtual Health Library, the System for Information on Grey Literature in Europe, and the New York Academy of Medicine Grey Literature Report to select the original research publications reporting the biological and pharmacological effects of ginsenoside Rh1 from in vitro and in vivo studies regardless of publication language and study design. Upon applying the inclusion and exclusion criteria, we included a total of 57 studies for our systemic review. Ginsenoside Rh1 exhibited the potent characteristics of anti-inflammatory, antioxidant, immunomodulatory effects, and positive effects on the nervous system. The cytotoxic effects of ginsenoside Rh1 were dependent on different types of cell lines. Other pharmacological effects including estrogenic, enzymatic, anti-microorganism activities, and cardiovascular effects have been mentioned, but the results were considerably diverged. A higher quality of evidence on clinical trial studies is highly recommended to confirm the consistent efficacy of ginsenoside Rh1.

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“…Ginsenoside-Rg5 obtained by the processing of ginseng has shown promising anticancer, anti-inflammatory and anti-aging properties (15)(16)(17). There are several reports which demonstrate the activity of ginsenoside-Rg5 against cancer (18,19), dermatis (20), inflammation (21) and neurotrophic disorders (22). This study was performed to investigate the effects of ginsenoside-Rg5 on destruction of cartilage through onset of cartilage matrix damage and death of chondrocytes in OA rat model.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside-Rg5 treatment inhibits apoptosis of chondrocytes and degradation of cartilage matrix in a rat model of osteoarthritis

Zhang

2017

Oncology Reports

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Abstract. This study investigated the effect of ginsenoside-Rg5 on the degradation of articular cartilage in osteoarthritis rat model and on induction of chondrocyte apoptosis. Osteoarthritis rat model was prepared by ligament transection and medial meniscus resection. The rats were then treated with different doses (1, 2, 5, 10 and 15 µM) of ginsenoside-Rg5 for 48 h. The results from histopathological analysis revealed a significant (P=0.005) prevention of cartilage degradation in OA rat model by ginsenoside-Rg5 treatment at 15 µM. Ginsenoside-Rg5 treatment prevented the disintegration of synovial membrane to a significant (P=0.005) extent. The proportion of apoptotic cells in the knee joints was reduced to 7% by ginsenoside-Rg5 treatment after one month compared to the control. Treatment of the rats with ginsenoside-Rg5 caused increase in the levels of proteoglycan, collagen and type II collagen by 5-, 3-and 4-fold compared to the control group. Immunohistochemistry revealed that the level of MMP-13 was reduced to 45% and that of TIMP-1 was increased by 67% on treatment with ginsenoside-Rg5. The levels of interleukin-1β, tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthetase were reduced by 67, 54, 32 ad 49%, respectively after one month of treatment with 15 mg/kg dose of ginsenoside-Rg5. The expression was increased to 67 and 52% for BMP-2 and TGF-β1, respectively on treatment with ginsenoside-Rg5. Thus ginsenoside-Rg5 prevents cartilage degradation in the OA rats and inhibits cartilage apoptosis, therefore it can be used for osteoarthritis treatment. IntroductionOsteoarthritis (OA) is one of the commonly observed diseases of joints caused by the disintegration of cartilage matrix and death of chondrocytes (1). There is always an equilibrium maintained by extracellular cartilage matrix between the formation and loss of chondrocytes (2,3). Loss of chondrocytes is a limiting factor for the formation of extracellular cartilage matrix which subsequently leads to the development of osteoarthritis (4). Many factors such as proteoglycan and collagen (type II) are involved in the regulation of normal functioning of chondrocytes (5). Studies have revealed that chondrocyte loss and extracellular matrix degradation involve several factors including, generation of peroxide radicals, TNF-α and interleukins (6,7). All these factors initiate inflammatory reactions leading to chondrocyte apoptosis (8). Expression of interleukin-1β is responsible for the production of inhibitors of metalloproteinase (TIMPs) leading to the inhibition of matrix metalloproteinase (MMP) generation and subsequent chondrocyte death and OA (9-11).Traditional Chinese medicine (TCM) involves the use of various herbs as well as dietary ingredients for several disorders depending upon the type of the syndrome (12). Numerous studies have been performed to demonstrate the chemotherapeutic potential of TCM against various types of cancers (13). Ginseng has a long traditional medicinal importance for the treatment of cancers, stress and...

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Ginsenosides as anticancer agents: In vitro and in vivo activities, structure–activity relationships, and molecular mechanisms of action

Cited by 283 publications

References 149 publications

Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes

Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes

Untitled

Ginsenoside-Rg5 treatment inhibits apoptosis of chondrocytes and degradation of cartilage matrix in a rat model of osteoarthritis

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