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Results in Journal Journal of Ginseng Research: 1,126

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Tae Kyung Lee, Ji Yun Lee, Yeon-Jin Cho, Jong-Eun Kim, Seo Yeong Kim, Jung Han Yoon Park, ,
Published: 25 November 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.10.006

Abstract:
Short-term hydroponic-cultured ginseng (sHCG), which is 1-year-old ginseng seedlings cultivated for 4 weeks in a hydroponic system, is a functional food item with several biological effects. However, the optimal extraction conditions for sHCG, and the bioactivity of its extracts, have not been evaluated.
Published: 19 November 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.11.007

Abstract:
Ginsenoside Rb2 is an active protopanaxadiol-type saponin, widely existing in the stem and leave of ginseng. Rb2 has recently been the focus of studies for pharmaceutical properties. This paper provides an overview of the preclinical and clinical pharmacokinetics for Rb2, which exhibit poor absorption, rapid tissue distribution and slow excretion through urine. Pharmacological studies indicate a beneficial role of Rb2 in the prevention and treatment of diabetes, obesity, tumor, photoaging, virus infection and cardiovascular problems. The underlying mechanism is involved in an inhibition of oxidative stress, ROS generation, inflammation and apoptosis via regulation of various cellular signaling pathways and molecules, including AKT/SHP, MAPK, EGFR/SOX2, TGF-β1/Smad, SIRT1, GPR120/AMPK/HO-1 and NF-κB. This work would provide a new insight into the understanding and application of Rb2. However, its therapeutic effects have not been clinically evaluated. Further studies should be aimed at the clinical treatment of Rb2.
JiHee Hong, Dasom Gwon,
Published: 14 November 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.11.004

Abstract:
Although the tumor-suppressive effects of ginsenosides in cell cycle have been well established, their pharmacological properties in mitosis have not been clarified yet. The chromosomal instability resulting from dysregulated mitotic processes is usually increased in cancer. In this study, we aimed to investigate the anticancer effects of ginsenoside Rg1 on mitotic progression in cancer.
Jeong Yoon Lee, Sohyuk Kim, Seokho Kim, Jonghan Kim, Bong Seok Bae, Gi-Bang Koo, Seung-Ho So, Jeongmin Lee,
Published: 13 November 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.11.005

Abstract:
Benign prostatic hyperplasia (BPH) is a disease characterized by abnormal proliferation of the prostate, which occurs frequently in middle-aged men. In this study, we report the effect of red ginseng oil (KGC11o) on BPH.
Boseong Kwon, , , Dongwhane Lee, Sang-Hun Lee, C.H.O. Young-Keol, Jong S. Kim,
Published: 11 November 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.11.002

Abstract:
Korean red ginseng (KRG) extract has been shown to have beneficial effects in patients with atherosclerosis, suggesting that KRG extract may be effective in preventing subsequent ischemic stroke in patients with severe atherosclerosis.
Mijung Lee, So-Hee Lee, Min-Soo Kim, Kwang-Sung Ahn,
Published: 11 November 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.11.001

Abstract:
Gut microbiota influence the central nervous system through gut-brain-axis. They also affect the neurological disorders. Gut microbiota differs in patients with Alzheimer's disease (AD), as a potential factor that leads to progression of AD. Oral intake of Korean Red Ginseng (KRG) improves the cognitive functions. Therefore, it can be proposed that KRG affect the microbiota on the gut-brain-axis to the brain.
Kuo-Feng Hua, A-Ching Chao, Ting-Yu Lin, Wan-Tze Chen, Yu-Chieh Lee, Wan-Han Hsu, Sheau-Long Lee, Hsin-Min Wang, Ding-I. Yang,
Published: 11 November 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.11.003

Abstract:
Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation.
Yaru Li, Shuchen Zhang, Ziwei Zhu, Ruonan Zhou, Pingyuan Xu, Lingyan Zhou, Yue Kan, Jiao Li, Juan Zhao, Penghua Fang, et al.
Published: 3 November 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.10.005

Abstract:
Ginsenoside Rb1 (GRb1) is capable of regulating lipid and glucose metabolism through its action on adipocytes. However, the beneficial role of GRb1-induced up-regulation of adiponectin in liver steatosis remains unelucidated. Thus, we tested whether GRb1 ameliorates liver steatosis and insulin resistance by promoting the expression of adiponectin.
Sun-Hye Choi, Ra Mi Lee, Han-Sung Cho, Sung Hee Hwang, , Hyewhon Rhim, Hyoung-Chun Kim, Do-Geun Kim, Ik-Hyun Cho,
Published: 15 October 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.10.004

Abstract:
Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin exerts its neuronal and non-neuronal in vitro and in vivo effects through LPA receptor subtypes. However, it is unknown whether gintonin can bind to the plasma membrane of cells and can transactivate the epidermal growth factor (EGF) receptor. In the present study, we examined whether gintonin-biotin conjugates directly bound to LPA receptors and transactivated the EGF receptor.
Chang Xu, Liangchang Li, Chongyang Wang, Jingzhi Jiang, Li Li, Lianhua Zhu, Shan Jin, Zhehu Jin, Jung Joon Lee, , et al.
Published: 13 October 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.10.001

Abstract:
The effect of ginsenoside Rh2 (G-Rh2) on mast cell-mediated anaphylaxis remains unclear. Herein, we investigated the effects of G-Rh2 on OVA-induced asthmatic mice and on mast cell-mediated anaphylaxis.
Soo Hyun Park, Sangwon Chung, Min-Yu Chung, Hyo-Kyoung Choi, Jin-Taek Hwang,
Published: 13 October 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.10.002

Abstract:
Panax ginseng is a medicinal plant is a material with various pharmacological activities and research suggests that it is particularly effective in representative metabolic diseases such as hyperglycemia, hypertension, and hyperlipidemia. Therefore, in this study, systematic review and meta-analysis were performed to investigate the comprehensive effect of P. ginseng on metabolic parameters representing these metabolic diseases. A total of 23 papers were collected for inclusion in the study, from which 27 datasets were collected. The investigational products included P. ginseng and Korean Red ginseng. Across the included studies, the dose ranged from 200 mg to 8 g and the supplementation period lasted from four to 24 weeks. The study subjects varied from healthy adults to those with diabetes, hypertension, obesity, and/or hyperlipidemia. As a result of the analysis, the levels of glucose and insulin area under the curves, % body fat, systolic and diastolic blood pressures, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were significantly reduced in the P. ginseng group as compared with in the placebo group. In conclusion, P. ginseng supplementation may act as an adjuvant to prevent the development of metabolic diseases by improving markers related to blood glucose, blood pressure, and blood lipids.
Heegu Jin, Hyun-Ji Oh, Seung-Yeol Nah,
Published: 13 October 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.10.003

Abstract:
Gintonin-enriched fraction (GEF), a non-saponin fraction of ginseng, is a novel glycolipoprotein rich in hydrophobic amino acids. GEF has recently been shown to regulate lipid metabolism and browning in adipocytes; however, the mechanisms underlying its effects on energy metabolism and whether it affects sarcopenic obesity are unclear. We aimed to evaluate the effects of GEF on skeletal muscle atrophy in high-fat diet (HFD)-induced obese mice.
Seoung Rak Lee, Bum Soo Lee, Jae Sik Yu, Heesun Kang, Min Jeong Yoo, Sang Ah Yi, Jeung-Whan Han, Sil Kim, , Jin-Chul Kim, et al.
Published: 6 October 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.09.004

Abstract:
Withania somnifera (Solanaceae), generally known as Indian ginseng, is a medicinal plant that is used in Ayurvedic practice for promoting health and longevity. This study aims to identify the bioactive metabolites from Indian ginseng and elucidate their structures.
, Sung Dae Kim, Seung-Chun Park,
Published: 5 October 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.09.003

Abstract:
Ginseng has been widely studied due to its various therapeutic properties on various diseases such as cardiovascular disease (CVD). Cardiovascular disease has been canonically known to be caused by high levels of low-density lipoproteins (LDL) in the bloodstream, in addition to the impaired vasodilatory effects of cholesterol. However, current research on CVD has revealed a cascade of mechanisms involving a series of events that contribute to the progression of CVD. Although this has been elucidated and summarized in previous studies the detailed correlation between platelet aggregation and innate immunity that plays an important role in CVD progression has not been thoroughly summarized. Furthermore, immune cell subtypes also contribute to the progression of plaque formation in the subendothelial layer. Thrombus formation and the coagulation cascade also have a vital role in the progression of atherosclerosis. Hence, in this mini review we aim to elucidate, summarize, and propose the potent therapeutic effect of ginseng on CVD, mainly on platelet aggregation, plaque formation, and thrombus formation.
, Hong Wang, Ming Zhang, Mengxue Shi, Cailing Yang, Qiang Ni, Qi Wang, Jing Li, Xuemei Wang, Chen Zhang, et al.
Published: 11 September 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.09.001

Abstract:
In physical activity or labor, the human body is in a state of high intensity stress, and all parts or physiological functions of the body respond positively to maintain or balance the need for movement. The human body has many physiological changes in the process of movement, and fatigue is the external manifestation of various complex changes inside the human body. Fatigue is also a physiological mechanism of self-protection after the body reaches a certain level of activity, which can prevent the occurrence of life-threatening excessive functional failure. The generation of fatigue is a very complex process, and its mechanism has not been concluded yet. Therefore, it is an important work to search and screen the effective components of natural plants that have anti-fatigue effect and to explore their mechanism.
Tae Jin Kim, Do Hyeon Pyun, Myeong Jun Kim, Ji Hoon Jeong, A.M. Abd El-Aty,
Published: 10 September 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.09.002

Abstract:
Compound K (CK) is among the protopanaxadiol (PPD)-type ginsenoside group, which produces multiple pharmacological effects. Herein, we examined the effects of CK on muscle atrophy under hyperlipidemic conditions along with its pro-myogenic effects. Further, the molecular pathways underlying the effects of CK on skeletal muscle have been justified.
Haixia Pan, Linhan Yang, Hansong Bai, ,
Published: 30 August 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.08.004

Abstract:
Ginsenoside Rg3 and gemcitabine have mutual enhancing antitumor effects. However, the underlying mechanisms are not clear. This study explored the influence of ginsenoside Rg3 on Zinc finger protein 91 homolog (ZFP91) expression in pancreatic adenocarcinoma (PAAD) and their regulatory mechanisms on gemcitabine sensitivity.
Jae Eun Park, Hyeon Woo Kim, Sung Hwan Yun,
Published: 27 August 2021
Journal of Ginseng Research, Volume 45, pp 754-762; https://doi.org/10.1016/j.jgr.2021.08.006

Abstract:
Ginsenoside Rh2, a major saponin derivative in ginseng extract, is recognized for its anticancer activities. Compared to coding genes, studies on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) that are regulated by Rh2 in cancer cells, especially on competitive endogenous RNA (ceRNA) are sparse.
Published: 21 August 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.08.003

Abstract:
In aged skin, reactive oxygen species (ROS) induces degradation of the extracellular matrix (ECM), leading to visible aging signs. Collagens in the ECM are cleaved by matrix metalloproteinases (MMPs). Syringaresinol (SYR), isolated from Panax ginseng berry, has various physiological activities, including anti-inflammatory action. However, the anti-aging effects of SYR via antioxidant and autophagy regulation have not been elucidated. The preventive effect of SYR on skin aging was investigated in human HaCaT keratinocytes in the presence of H2O2, and the keratinocyte cells were treated with SYR (0–200 μg/mL). mRNA and protein levels of MMP-2 and -9 were determined by real-time PCR and Western blotting, respectively. Radical scavenging activity was researched by 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. LC3B level was assessed by Western blotting and confocal microscopy. SYR significantly reduced gene expression and protein levels of MMP-9 and -2 in both H2O2-treated and untreated HaCaT cells. SYR did not show cytotoxicity to HaCaT cells. SYR exhibited DPPH and ABTS radical scavenging activities with an EC50 value of 10.77 and 10.35 μg/mL, respectively. SYR elevated total levels of endogenous and exogenous LC3B in H2O2-stimulated HaCaT cells. 3-Methyladenine (3-MA), an autophagy inhibitor, counteracted the inhibitory effect of SYR on MMP-2 expression. SYR showed antioxidant activity and up-regulated autophagy activity in H2O2-stimulated HaCaT cells, lowering the expression of MMP-2 and MMP-9 associated with skin aging. Our results suggest that SYR has potential value as a cosmetic additive for prevention of skin aging.
Tianyi Wu, Wenxiao Qi, Haojie Shan, Bin Tu, Shilin Jiang, Ye Lu,
Published: 21 August 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.08.005

Abstract:
During the pathogenesis of tendinopathy, the chronic inflammation caused by the injury and apoptosis leads to the generation of scars. Ginsenoside Rg1 (Rg1) is extracted from ginseng and has anti-inflammatory effects. Rg1 is a unique phytoestrogen that can activate the estrogen response element. This research aimed to explore whether Rg1 can function in the process of tendon repair through the estrogen receptor. In this research, the effects of Rg1 were evaluated in tenocytes and in a rat model of Achilles tendinitis (AT). Protein levels were shown by western blotting. qRT-PCR was employed for evaluating mRNA levels. Cell proliferation was evaluated through EdU assay and cell migration was evaluated by transwell assay and scratch test assay. Rg1 up-regulated the expression of matrix-related factors and function of tendon in AT rat model. Rg1 reduced early inflammatory response and apoptosis in the tendon tissue of AT rat model. Rg1 promoted tenocyte migration and proliferation. The effects of Rg1 on tenocytes were inhibited by ICI182780. Rg1 activates the insulin-like growth factor-I receptor (IGF1R) and MAPK signaling pathway. Rg1 promotes injured tendon healing in AT rat model through IGF1R and MAPK signaling pathway activation.
, Bongjun Sur,
Published: 10 August 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.08.002

Abstract:
Post-traumatic stress disorder (PTSD) is a psychiatric disease that develops following exposure to a traumatic event and is a stress-associated mental disorder characterized by an imbalance of neuroinflammation. Korean red ginseng (KRG) is the herbal supplement that is known to be involved in a variety of pharmacological activities. We aimed to investigate the effects of KRG on neuroinflammation as a potential mechanism involved in single prolonged stress (SPS) that negatively influences memory formation and consolidation and leads to cognitive and spatial impairment by regulating BDNF signaling, synaptic proteins, and the activation of NF-kB. We analyzed the cognitive and spatial memory, and inflammatory cytokine levels during the SPS procedure. SPS model rats were injected intraperitoneally with 20, 50, or 100 mg/kg/day KRG for 14 days. KRG administration significantly attenuated the cognitive and spatial memory deficits, as well as the inflammatory reaction in the hippocampus associated with activation of NF-κB in the hippocampus induced by SPS. Moreover, the effects of KRG were equivalent to those exerted by paroxetine. In addition, KRG improved the expression of BDNF mRNA and the synaptic protein PSD-95 in the hippocampus. Taken together, these findings demonstrate that KRG exerts memory-improving actions by regulating anti-inflammatory activities and the NF-κB and neurotrophic pathway. Our findings suggest that KRG is a potential functional ingredient for protecting against memory deficits in mental diseases, such as PTSD.
Yuli Han, Xuewang Li, Liu Yang, Duoduo Zhang, Lan Li, Xianan Dong, Yan Li, ,
Published: 10 August 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.08.001

Abstract:
The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca2+]i. The open-field test and pole-climbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca2+]i. Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.
Zuan Lin, Rongfang Xie, Chenhui Zhong, Jianyong Huang, ,
Published: 30 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.07.008

Abstract:
Ginsenoside Rb1 (Rb1), one of the most important ingredients in Panax ginseng Meyer, has been confirmed to have favorable activities, including reducing antioxidative stress, inhibiting inflammation, regulating cell autophagy and apoptosis, affecting sugar and lipid metabolism, and regulating various cytokines. This study reviewed the recent progress on the pharmacological effects and mechanisms of Rb1 against cardiovascular and nervous system diseases, diabetes, and their complications, especially those related to neurodegenerative diseases, myocardial ischemia, hypoxia injury, and traumatic brain injury. This review retrieved articles from PubMed and Web of Science that were published from 2015 to 2020. The molecular targets or pathways of the effects of Rb1 on these diseases are referring to HMGB1, GLUT4, 11β-HSD1, ERK, Akt, Notch, NF-κB, MAPK, PPAR-γ, TGF-β1/Smad pathway, PI3K/mTOR pathway, Nrf2/HO-1 pathway, Nrf2/ARE pathway, and MAPK/NF-κB pathway. The potential effects of Rb1 and its possible mechanisms against diseases were further predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and disease ontology semantic and enrichment (DOSE) analyses with the reported targets. This study provides insights into the therapeutic effects of Rb1 and its mechanisms against diseases, which is expected to help in promoting the drug development of Rb1 and its clinical applications.
Sun Hee Hyun, Kiran D. Bhilare, Gyo In, ,
Published: 26 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.07.007

Abstract:
Traditionally, Asian ginseng or Korean ginseng, Panax ginseng has long been used in Korea and China to treat various diseases. The main active components of Panax ginseng is ginsenoside, which is known to have various pharmacological treatment effects such as antioxidant, vascular easing, anti-allergic, anti-inflammatory, anti-diabetes, and anticancer. Most reactive oxygen species (ROS) cause chronic diseases such as myocardial symptoms and cause fatal oxidative damage to cell membrane lipids and proteins. Therefore, many studies that inhibit the production of oxidative stress have been conducted in various fields of physiology, pathophysiology, medicine and health, and disease. Recently, ginseng or ginsenosides have been known to act as antioxidants in vitro and in vivo results, which have a beneficial effect on preventing cardiovascular disease. The current review aims to provide mechanisms and inform precious information on the effects of ginseng and ginsenosides on the prevention of oxidative stress and cardiovascular disease in animals and clinical trials.
Published: 23 July 2021
Journal of Ginseng Research, Volume 45, pp 744-753; https://doi.org/10.1016/j.jgr.2021.07.006

Abstract:
Gintonin-enriched fraction (GEF) is a new non-saponin component glycolipoprotein isolated from ginseng root. This study examined the effect of GEF on age-related sarcopenia in old C57BL/6J mice.
Ying-Jie Chen, Jia-Ying Wu, Yu-Yi Deng, Ying Wu, Xiao-Qi Wang, Amy Sze-Man Li, Lut Yi Wong, , ,
Published: 14 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.07.002

Abstract:
Sorafenib is effective in treating hepatoma, but most patients develop resistance to it. STAT3 signaling has been implicated in sorafenib resistance. Artesunate (ART) and 20(R)-ginsenoside Rg3 (Rg3) have anti-hepatoma effects and can inhibit STAT3 signaling in cancer cells. This study aimed to evaluate the effects of Rg3 in combination with ART (Rg3-plus-ART) in overcoming sorafenib resistance, and to examine the involvement of STAT3 signaling in these effects. Sorafenib-resistant HepG2 cells (HepG2-SR) were used to evaluate the in vitro anti-hepatoma effects of Rg3-plus-ART. A HepG2-SR hepatoma-bearing BALB/c-nu/nu mouse model was used to assess the in vivo anti-hepatoma effects of Rg3-plus-ART. CCK-8 assays and Annexin V-FITC/PI double staining were used to examine cell proliferation and apoptosis, respectively. Immunoblotting was employed to examine protein levels. ROS generation was examined by measuring DCF-DA fluorescence. Rg3-plus-ART synergistically reduced viability of, and evoked apoptosis in HepG2-SR cells, and suppressed HepG2-SR tumor growth in mice. Mechanistic studies revealed that Rg3-plus-ART inhibited activation/phosphorylation of Src and STAT3 in HepG2-SR cultures and tumors. The combination also decreased the STAT3 nuclear level and induced ROS production in HepG2-SR cultures. Furthermore, over-activation of STAT3 or removal of ROS diminished the anti-proliferative effects of Rg3-plus-ART, and removal of ROS diminished Rg3-plus-ART's inhibitory effects on STAT3 activation in HepG2-SR cells. Rg3-plus-ART overcomes sorafenib resistance in experimental models, and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling contribute to the underlying mechanisms. This study provides a pharmacological basis for developing Rg3-plus-ART into a novel modality for treating sorafenib-resistant hepatoma.
Genmeng Yang, Juan Li, Yanxia Peng, Baoyu Shen, Yuanyuan Li, Liu Liu, Chan Wang, Yue Xu, Shucheng Lin, Shuwei Zhang, et al.
Published: 14 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.07.005

Abstract:
This study investigates the effects of ginsenoside Rb1 (GsRb1) on methamphetamine (METH)-induced toxicity in SH-SY5Y neuroblastoma cells and METH-induced conditioned place preference (CPP) in adult Sprague-Dawley rats. It also examines whether GsRb1 can regulate these effects through the NR2B/ERK/CREB/BDNF signaling pathways. SH-SY5Y cells were pretreated with GsRb1 (20 μM and 40 μM) for 1 h, followed by METH treatment (2 mM) for 24 h. Rats were treated with METH (2 mg/kg) or saline on alternating days for 10 days to allow CPP to be examined. GsRb1 (5, 10, and 20 mg/kg) was injected intraperitoneally 1 h before METH or saline. Western blot was used to examine the protein expression of NR2B, ERK, P-ERK, CREB, P-CREB, and BDNF in the SH-SY5Y cells and the rats' hippocampus, nucleus accumbens (NAc), and prefrontal cortex (PFC). METH dose-dependently reduced the viability of SH-SY5Y cells. Pretreatment of cells with 40 μM of GsRb1 increased cell viability and reduced the expression of METH-induced NR2B, p-ERK, p-CREB and BDNF. GsRb1 also attenuated the expression of METH CPP in a dose-dependent manner in rats. Further, GsRb1 dose-dependently reduced the expression of METH-induced NR2B, p-ERK, p-CREB, and BDNF in the PFC, hippocampus, and NAc of rats. GsRb1 regulated METH-induced neurotoxicity in vitro and METH-induced CPP through the NR2B/ERK/CREB/BDNF regulatory pathway. GsRb1 could be a therapeutic target for treating METH-induced neurotoxicity or METH addiction.
Haibo Zhang, Jun-Koo Yi, Hai Huang, , Wookbong Kwon, Eungyung Kim, Soyoung Jang, Si-Yong Kim, Seong-Kyoon Choi, Duhak Yoon, et al.
Published: 12 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.07.004

Abstract:
Colorectal cancer (CRC) has a high morbidity and mortality worldwide. 20 (S)-ginsenoside Rh2 (G-Rh2) is a natural compound extracted from ginseng, which exhibits anticancer effects in many cancer types. In this study, we demonstrated the effect and underlying molecular mechanism of G-Rh2 in CRC cells in vitro and in vivo. Cell proliferation, migration, invasion, apoptosis, cell cycle, and western blot assays were performed to evaluate the effect of G-Rh2 on CRC cells. In vitro pull-down assay was used to verify the interaction between G-Rh2 and Axl. Transfection and infection experiments were used to explore the function of Axl in CRC cells. CRC xenograft models were used to further investigate the effect of Axl knockdown and G-Rh2 on tumor growth in vivo. G-Rh2 significantly inhibited proliferation, migration, and invasion, and induced apoptosis and G0/G1 phase cell cycle arrest in CRC cell lines. G-Rh2 directly binds to Axl and inhibits the Axl signaling pathway in CRC cells. Knockdown of Axl suppressed the growth, migration and invasion ability of CRC cells in vitro and xenograft tumor growth in vivo, whereas overexpression of Axl promoted the growth, migration, and invasion ability of CRC cells. Moreover, G-Rh2 significantly suppressed CRC xenograft tumor growth by inhibiting Axl signaling with no obvious toxicity to nude mice. Our results indicate that G-Rh2 exerts anticancer activity in vitro and in vivo by suppressing the Axl signaling pathway. G-Rh2 is a promising candidate for CRC prevention and treatment.
Jinhong Park, Minjae Lee, Minsu Kim, Sunhong Moon, Seunghee Kim, Sueun Kim, Seong-Ho Koh, Young-Myeong Kim,
Published: 12 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.07.003

Abstract:
Korean red ginseng extract (KRGE) has been used as a health supplement and herbal medicine. Astrocytes are one of the key cells in the central nervous system (CNS) and have bioenergetic potential as they stimulate mitochondrial biogenesis. They play a critical role in connecting the brain vasculature and nerves in the CNS. Brain samples from KRGE-administered mice were tested using immunohistochemistry. Treatment of human brain astrocytes with KRGE was subjected to assays such as proliferation, cytotoxicity, Mitotracker, ATP production, and O2 consumption rate as well as western blotting to demonstrate the expression of proteins related to mitochondria functions. The expression of hypoxia-inducible factor-1α (HIF-1α) was diminished utilizing siRNA transfection. Brain samples from KRGE-administered mice harbored an increased number of GFAP-expressing astrocytes. KRGE triggered the proliferation of astrocytes in vitro. Enhanced mitochondrial biogenesis induced by KRGE was detected using Mitotracker staining, ATP production, and O2 consumption rate assays. The expression of proteins related to mitochondrial electron transport was increased in KRGE-treated astrocytes. These effects were blocked by HIF-1α knockdown. The factors secreted from KRGE-treated astrocytes were determined, revealing the expression of various cytokines and growth factors, especially those related to angiogenesis and neurogenesis. KRGE-treated astrocyte conditioned media enhanced the differentiation of adult neural stem cells into mature neurons, increasing the migration of endothelial cells, and these effects were reduced in the background of HIF-1α knockdown. Our findings suggest that KRGE exhibits prophylactic potential by stimulating astrocyte mitochondrial biogenesis through HIF-1α, resulting in improved neurovascular function.
Xin Sun, Yeting Hong, Yuhan Shu, Caixia Wu, Guiqin Ye, Hanxiao Chen, Hongying Zhou, ,
Published: 8 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.009

Abstract:
Colon cancer, the third most frequent occurred cancer, has high mortality and extremely poor prognosis. Ginsenoside, the active components of traditional Chinese herbal medicine Panax ginseng, exerts antitumor effect in various cancers, including colon cancer. However, the detailed molecular mechanism of Ginsenoside in the tumor suppression have not been fully elucidated. Here, we chose the representative ginsenoside Rg3 and reported for the first time that Rg3 induces mitophagy in human colon cancer cells, which is responsible for its anticancer effect. Rg3 treatment leads to mitochondria damage and the formation of mitophagosome; when autophagy is inhibited, the clearance of damaged mitochondria can be reversed. Next, our results showed that Rg3 treatment activates the PINK1-Parkin signaling pathway and recruits Parkin and ubiquitin proteins to mitochondria to induce mitophagy. GO analysis of Parkin targets showed that Parkin interacts with a large number of mitochondrial proteins and regulates the molecular function of mitochondria. The cellular energy metabolism enzyme GAPDH is validated as a novel substrate of Parkin, which is ubiquitinated by Parkin. Moreover, GAPDH participates in the Rg3-induced mitophagy and regulates the translocation of Parkin to mitochondria. Functionally, Rg3 exerts the inhibitory effect through regulating the nonglycolytic activity of GAPDH, which could be associated with the cellular oxidative stress. Thus, our results revealed GAPDH ubiquitination by Parkin as a crucial mechanism for mitophagy induction that contributes to the tumor-suppressive function of ginsenoside, which could be a novel treatment strategy for colon cancer.
MyungHo Jin, Kyung-Min Kim, Chiyeon Lim, ,
Published: 6 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.012

Abstract:
Stroke is a neurological disorder characterized by brain tissue damage following a decrease in oxygen supply to brain due to blocked blood vessels. Reportedly, 80% of all stroke cases are classified as cerebral infarction, and the incidence rate of this condition increases with age. Herein, we compared the efficacies of Korean White ginseng (WG) and Korean Red ginseng (RG) extracts (WGex and RGex, respectively) in an ischemic stroke mouse model and confirmed the underlying mechanisms of action. Mice were orally administered WGex or RGex 1 h before middle cerebral artery occlusion (MCAO), for 2 h; the size of the infarct area was measured 24 h after MCAO induction. Then, the neurological deficit score was evaluated and the efficacies of the two extracts were compared. Finally, their mechanisms of action were confirmed with tissue staining and protein quantification. In the MCAO-induced ischemic stroke mouse model, WGex and RGex showed neuroprotective effects in the cortical region, with RGex demonstrating superior efficacy than WGex. Ginsenoside Rg1, a representative indicator substance, was not involved in mediating the effects of WGex and RGex. WGex and RGex could alleviate the brain injury caused by ischemia/reperfusion, with RGex showing a more potent effect. At 1,000 mg/kg body weight, only RGex reduced cerebral infarction and edema, and both anti-inflammatory and anti-apoptotic pathways were involved in mediating these effects.
Jingui Hu, Ling Zhang, Fei Fu, Qiong Lai, Lu Zhang, Tao Liu, Boyang Yu, ,
Published: 3 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.011

Abstract:
Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.
Min Ji Han, Ji Eun Shin, Seok Jun Park,
Published: 3 July 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.010

Abstract:
Sarcopenia, defined as loss of muscle mass and strength with age, becomes a public health concern as the elderly population increases. This study aimed to determine whether the mixture of soluble whey protein hydrolysate (WPH) and Panax ginseng berry extract (GBE) has a synergetic effect on sarcopenia and, if so, to identify the relevant mechanisms and optimal mixing ratio. In the first experiment, C57BL/6 mice were hindlimb immobilized for one-week and then administered WPH 800 mg/kg, GBE 100 mg/kg, WPH 800 mg/kg+ GBE 100 mg/kg mixture, and Fructus Schisandrae extract (SFE) 200 mg/kg for two weeks. In the second experiment, experimental design was same, but mice were administered three different doses of WPH and GBE mixture (WPH 800 mg/kg+ GBE 100 mg/kg, WPH 800 mg/kg+ GBE 90 mg/kg, WPH 1000 mg/kg+ GBE 75 mg/kg). In the first experiment, we confirmed the synergetic effect of WPH and GBE on muscle mass and identified that GBE was more effective on the protein synthesis side, and WPH tended to be slightly more effective for protein degradation. In the second experiment, among three different ratios, the WPH 800 mg/kg+ GBE 100 mg/kg was most effective for muscle mass and strength. The mixtures activated muscle protein synthesis via PI3K/Akt/mTORc1 pathway and inhibited muscle protein degradation via suppressing ubiquitin-proteasome system (UPS) and autophagy-lysosome system (ALS), and these effects were more GBE dose-dependent than WPH. The WPH and GBE mixture having a synergetic effect is a potential agent to prevent sarcopenia.
Na-Ra Han, Seong-Gyu Ko, ,
Published: 24 June 2021
Journal of Ginseng Research, Volume 45, pp 610-616; https://doi.org/10.1016/j.jgr.2021.06.008

Abstract:
Thymic stromal lymphopoietin (TSLP) acts as a master switch for inflammatory responses. Ginsenoside Rg3 (Rg3) which is an active ingredient of Panax ginseng Meyer (Araliaceae) is known to possess various therapeutic effects. However, a modulatory effect of Rg3 on TSLP expression in the inflammatory responses remains poorly understood.
Na Zhang, , Yun-Long Guo, Hao Yue, Chang-Bao Chen, Shu-Ying Liu
Published: 23 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.007

Abstract:
Dried and red ginseng are well-known types of processed ginseng and are widely used as healthy food. The dried and red ginseng quality may vary with the storage period of raw ginseng. Therefore, herein, the effect of the storage period of fresh ginseng on processed ginseng quality was evaluated through multicomponent quantification with statistical analysis. A method based on ultrahigh performance liquid chromatography coupled to triple quadrupole mass spectrometry in multiple-reaction monitoring mode (UPLC-MRM-MS) was developed for quantitation of ginsenosides and oligosaccharides in dried and red ginseng. Principal component analysis and partial least squares discriminant analysis were conducted to evaluate the dynamic distributions of ginsenosides and oligosaccharides after different storage periods. Eighteen PPD, PPT and OLE ginsenosides and nine reducing and nonreducing oligosaccharides were identified and quantified. With storage period extension, the ginsenoside content in the processed ginseng increased slightly in the first 2 weeks and decreased gradually in the following 9 weeks. The content of reducing oligosaccharides decreased continuously as storage time extending, while that of the nonreducing oligosaccharides increased. Chemical conversions occurred during storage, based on which potential chemical markers for the storage period evaluation of fresh ginseng were screened. According to ginsenoside and oligosaccharide distributions, it was found that the optimal storage period was 2 weeks and that the storage period of fresh ginseng should not exceed 4 weeks at 0 °C. This study provides deep insights into the quality control of processed ginseng and comprehensive factors for storage of raw ginseng.
Kim Sia Sng, Gan Li, Long-Yun Zhou, Yong-Jia Song, Xu-Qing Chen, Yong-Jun Wang, ,
Published: 18 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.05.009

Abstract:
Spinal cord injury (SCI) is defined as damage to the spinal cord that temporarily or permanently changes its function. There is no definite treatment established for neurological complete injury patients. This study investigated the effect of ginseng extract and ginsenosides on neurological recovery and antioxidant efficacies in rat models following SCI and explore the appropriate dosage. Searches were done on PubMed, Embase, and Chinese databases, and animal studies matches the inclusion criteria were selected. Pair-wise meta-analysis and subgroup analysis were performed. Ten studies were included, and the overall methodological qualities were low quality. The result showed ginseng extract and ginsenosides significantly improve neurological function, through the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale (pooled MD = 4.40; 95% CI = 3.92 to 4.88; p < 0.00001), significantly decrease malondialdehyde (MDA) (n = 290; pooled MD = −2.19; 95% CI = −3.16 to −1.22; p < 0.0001) and increase superoxide dismutase (SOD) levels (n = 290; pooled MD = 2.14; 95% CI = 1.45 to 2.83; p < 0.00001). Both low (<25 mg/kg) and high dosage (≥25 mg/kg) showed significant improvement in the motor function recovery in SCI rats. Collectively, this review suggests ginseng extract and ginsenosides has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials and applications.
Han Suk Choi, Hyo Bin Koo, Sung Won Jeon, Jung Yeon Han, Joung Sug Kim, Kyong Mi Jun,
Published: 18 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.004

Abstract:
The roots of Panax ginseng contain two types of tetracyclic triterpenoid saponins, namely, protopanaxadiol (PPD)-type saponins and protopanaxatiol (PPT)-type saponins. In P. ginseng, the protopanaxadiol 6-hydroxylase (PPT synthase) enzyme catalyses protopanaxatriol (PPT) production from protopanaxadiol (PPD). In this study, we constructed homozygous mutant lines of ginseng by CRISPR/Cas9-mediated mutagenesis of the PPT synthase gene and obtained the mutant ginseng root lines having complete depletion of the PPT-type ginsenosides. Two sgRNAs (single guide RNAs) were designed for target mutations in the exon sequences of the two PPT synthase genes (both PPTa and PPTg sequences) with the CRISPR/Cas9 system. Transgenic ginseng roots were generated through Agrobacterium-mediated transformation. The mutant lines were screened by ginsenoside analysis and DNA sequencing. Ginsenoside analysis revealed the complete depletion of PPT-type ginsenosides in three putative mutant lines (Cr4, Cr7, and Cr14). The reduction of PPT-type ginsenosides in mutant lines led to increased accumulation of PPD-type ginsenosides. The gene editing in the selected mutant lines was confirmed by targeted deep sequencing. We have established the genome editing protocol by CRISPR/Cas9 system in P. ginseng and demonstrated the mutated roots producing only PPD-type ginsenosides by depleting PPT-type ginsenosides. Because the pharmacological activity of PPD-group ginsenosides is significantly different from that of PPT-group ginsenosides, the new type of ginseng mutant producing only PPD-group ginsenosides may have new pharmacological characteristics compared to wild-type ginseng. This is the first report to generate target-induced mutations for the modification of saponin biosynthesis in Panax species using CRISPR–Cas9 system.
Yoshito Ikeda, , Yasuyuki Yamada, Mizuki Kawakami, Ikuko Amano, , Takahiro Mukai, Taiho Kambe,
Published: 15 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.006

Abstract:
Zinc homeostasis is essential for human health and is regulated by several zinc transporters including ZIP and ZnT. ZIP4 is expressed in the small intestine and is important for zinc absorption from the diet. We investigated in the present study the effects of Panax ginseng (P. ginseng) extract on modulating Zip4 expression and cellular zinc levels in mouse Hepa cells. Hepa cells were transfected with a luciferase reporter plasmid that contains metal-responsive elements, incubated with P. ginseng extract, and luciferase activity was measured. Using 65ZnCl2, zinc uptake in P. ginseng-treated cells was measured. The expression of Zip4 mRNA and protein in Hepa cells was also investigated. Finally, using a luciferase reporter assay system, the effects of several ginsenosides were monitored. The luciferase activity in cells incubated with P. ginseng extract was significantly higher than that of control cells cultured in normal medium. Hepa cells treated with P. ginseng extract exhibited higher zinc uptake. P. ginseng extract induced Zip4 mRNA expression, which resulted in an enhancement of Zip4 protein expression. Furthermore, some ginsenosides, such as ginsenoside Rc and Re, enhanced luciferase activity driven by intracellular zinc levels. P. ginseng extract induced Zip4 expression at the mRNA and protein level and resulted in higher zinc uptake in Hepa cells. Some ginsenosides facilitated zinc influx. On the basis of these results, we suggest a novel effect of P. ginseng on Zip4-mediated zinc influx, which may provide a new strategy for preventing zinc deficiency.
Jung Eun Min, , Ji Yeon Hong, Sun Jo Kim, Nguyen Hoang Anh, Daijie Wang, Xiao Wang, Jeong Hill Park, ,
Published: 15 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.005

Abstract:
Ginseng, officially known as Panax ginseng Meyer, has been traditionally used as a medicinal herb, particularly in Asia. Ginseng is propagated from seeds; however, seed germination is challenging, especially in its natural environment on farms. The seeds typically exhibit morphophysiological dormancy and require release from both morphological and physiological dormancy before germination. Although some studies have proposed methods for increasing seed germination rates, the underlying mechanisms of its dormancy release process remain unclear. Here, we investigated metabolic alterations during dehiscence in P. ginseng to determine their potential roles in dormancy release. We compared the ginseng seed metabolome before and after dehiscence and the ginsenoside and phytosterol compositions of the seeds in both periods in the presence of related enzymes. After seed dehiscence, the sugar, amino acid, and squalene concentrations were significantly altered, phytosterols associated with the stigmasterol biosynthesis pathway were increased, while ginsenoside and brassinosteroid levels were not significantly altered. In addition, squalene epoxidase, cycloartenol synthase, 24-methylenesterol C-methyltransferase, and the stigmasterol biosynthesis pathway were activated. Overall, our findings suggest that morphological activities that facilitate ginseng seed growth are the primary phenomena occurring during the dehiscence process. This study improves the understanding of P. ginseng germination processes and promotes further research of its germination and cultivation.
Muhammad Irfan, , Ki-Ja Lee, ,
Published: 11 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.05.010

Abstract:
Fermentation may alter the bioavailability of certain compounds, which may affect their efficacy and pharmacological responses. This study investigated the antiplatelet effects of red ginseng extract (RGE) and fermented red ginseng extract (FRG). A rodent model was used to evaluate the antiplatelet and antithrombotic effects of the extracts. Rats were orally fed with human equivalent doses of the extracts for 1 week and examined for various signaling pathways using standard in vivo and ex vivo techniques. Light transmission aggregometry was performed, and calcium mobilization, dense granule secretion, integrin αIIbβ3-mediated signaling molecules, cyclic nucleotide signaling events, and various protein molecules were evaluated ex vivo in collagen-stimulated washed platelets. Furthermore, antithrombotic properties were evaluated using a standard acute pulmonary thromboembolism model, and the effects on hemostasis were investigated using rat and mice models. Both RGE and FRG significantly inhibited platelet aggregation, calcium mobilization, and dense granule secretion along with integrin-mediated fibrinogen binding and fibrinogen adhesion. cAMP levels were found to be elevated in RGE-treated rat platelets. Ginseng extracts did not exert any effect on prothrombin time and activated partial thromboplastin time. RGE-treated mice showed significantly better survival under thrombosis than FRG-treated mice, with no effects on hemostasis, whereas FRG-treated mice exhibited a slight increment in bleeding time. Both extracts, especially RGE, are remarkable supplements to maintain cardiovascular health and are potential candidates for the treatment and prevention of platelet-related cardiovascular disorders.
Wenzhen Li, Yifan Wang, Xinbo Zhou, Xiaohong Pan, , Hongliu Sun, Zeping Xie, ,
Published: 10 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.002

Abstract:
20(S)-protopanaxadiol (20(S)-PPD), one of the main active metabolites of ginseng, performs a broad spectrum of anti-tumor effects. Our aims are to search out new strategies to enhance anti-tumor effects of natural products, including 20(S)-PPD. In recent years, fasting has been shown to be multi-functional on tumor progression. Here, the effects of fasting combined with 20(S)-PPD on hepatocellular carcinoma growth, apoptosis, migration, invasion and cell cycle were explored. CCK-8 assay, trypan blue dye exclusion test, imagings photographed by HoloMonitorTM M4, transwell assay and flow cytometry assay were performed for functional analyses on cell proliferation, morphology, migration, invasion, apoptosis, necrosis and cell cycle. The expressions of genes on protein levels were tested by western blot. Tumor-bearing mice were used to evaluate the effects of intermittent fasting combined with 20(S)-PPD. We firstly confirmed that fasting-mimicking increased the anti-proliferation effect of 20(S)-PPD in human HepG2 cells in vitro. In fasting-mimicking culturing medium, the apoptosis and necrosis induced by 20(S)-PPD increased and more cells were arrested at G0-G1 phase. Meanwhile, invasion and migration of cells were decreased by down-regulating the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in fasting-mimicking medium. Furthermore, the in vivo study confirmed that intermittent fasting enhanced the tumor growth inhibition of 20(S)-PPD in H22 tumor-bearing mice without obvious side effects. Fasting significantly sensitized HCC cells to 20(S)-PPD in vivo and in vitro. These data indicated that dietary restriction can be one of the potential strategies of chinese medicine or its active metabolites against hepatocellular carcinoma.
Jingyu Ni, Zhihao Liu, Miaomiao Jiang, Lan Li, Jie Deng, Xiaodan Wang, Jing Su, Yan Zhu, Feng He, Jingyuan Mao, et al.
Published: 5 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.001

Abstract:
Ginsenoside Rg3 is one of the main active ingredients in ginseng. Here, we aimed to confirm its protective effect on the heart function in transverse aortic coarctation (TAC)-induced heart failure mice and explore the potential molecular mechanisms involved. The effects of ginsenoside Rg3 on heart and mitochondrial function were investigated by treating TAC-induced heart failure in mice. The mechanism of ginsenoside Rg3 for improving heart and mitochondrial function in mice with heart failure was predicted through integrative analysis of the proteome and plasma metabolome. Glucose uptake and myocardial insulin sensitivity were evaluated using micro-positron emission tomography. The effect of ginsenoside Rg3 on myocardial insulin sensitivity was clarified by combining in vivo animal experiments and in vitro cell experiments. Treatment of TAC-induced mouse models with ginsenoside Rg3 significantly improved heart function and protected mitochondrial structure and function. Fusion of metabolomics, proteomics, and targeted metabolomics data showed that Rg3 regulated the glycolysis process, and Rg3 not only regulated glucose uptake but also improve myocardial insulin resistance. The molecular mechanism of ginsenoside Rg3 regulation of glucose metabolism was determined by exploring the interaction pathways of AMPK, insulin resistance, and glucose metabolism. The effect of ginsenoside Rg3 on the promotion of glucose uptake in IR-H9c2 cells by AMPK activation was dependent on the insulin signaling pathway. Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of the AMPK pathway.
Hong-Lin Xu, Guang-Hong Chen, Yu-Ting Wu, Ling-Peng Xie, Zhang-Bin Tan, Bin Liu, Hui-Jie Fan, Hong-Mei Chen, Gui-Qiong Huang, , et al.
Published: 5 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.05.011

Abstract:
Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms.
Yeye Hu, Yang He, Zhiqiang Niu, Ting Shen, Ji Zhang, Xinfeng Wang, ,
Published: 4 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.06.003

Abstract:
Panax polysaccharides are biopolymers that are isolated and purified from the roots, stems, leaves, flowers, and fruits of Panax L. plants, which have attracted considerable attention because of their immunomodulatory activities. In this paper, the composition and structural characteristics of purified polysaccharides are reviewed. Moreover, the immunomodulatory activities of polysaccharides are described both in vivo and in vitro. In vitro, Panax polysaccharides exert immunomodulatory functions mainly by activating macrophages, dendritic cells, and the complement system. In vivo, Panax polysaccharides can increase the immune organ indices and stimulate lymphocytes. In addition, this paper also discusses the membrane receptors and various signalling pathways of immune cells. Panax polysaccharides have many beneficial therapeutic effects, including enhancing or activating the immune response, and may be helpful in treating cancer, sepsis, osteoporosis, and other conditions. Panax polysaccharides have the potential for use in the development of novel therapeutic agents or adjuvants with beneficial immunomodulatory properties.
, , , Yoko Tomita, Timothy J. Price, Andrea Yool, Amanda R. Townsend,
Published: 3 June 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.05.008

Abstract:
Epimers of ginsenoside Rg3 (Rg3) have a low bioavailability and are prone to deglycosylation, which produces epimers of ginsenoside Rh2 (S-Rh2 and R-Rh2) and protopanaxadiol (S-PPD and R-PPD). The aim of this study was to compare the efficacy and potency of these molecules as anti-cancer agents. Crystal violet staining was used to study the anti-proliferatory action of the molecules on a human epithelial breast cancer cell line, MDA-MB-231, and human umbilical vein endothelial cells (HUVEC) and compare their potency. Cell death and cell cycle were studied using flow cytometry and mode of cell death was studied using live cell imaging. Anti-angiogenic effects of the drug were studied using loop formation assay. Molecular docking showed the interaction of these molecules with vascular endothelial growth factor receptor-2 (VEGFR2) and aquaporin (AQP) water channels. VEGF bioassay was used to study the interaction of Rh2 with VEGFR2, in vitro. HUVEC was the more sensitive cell line to the anti-proliferative effects of S-Rh2, S-PPD and R-PPD. The molecules induced necroptosis/necrosis in MDA-MB-231 and apoptosis in HUVEC. S-Rh2 was the most potent inhibitor of loop formation. In silico molecular docking predicted a good binding score between Rh2 or PPD and the ATP-binding pocket of VEGFR2. VEGF bioassay showed that Rh2 was an allosteric modulator of VEGFR2. In addition, SRh2 and PPD had good binding scores with AQP1 and AQP5, both of which play roles in cell migration and proliferation. The combination of these molecules might be responsible for the anti-cancer effects observed by Rg3.
Chunmei Hu, Linhan Yang, Yi Wang, , ,
Published: 25 May 2021
Journal of Ginseng Research, Volume 45, pp 734-743; https://doi.org/10.1016/j.jgr.2021.05.004

Abstract:
The underlying mechanisms of the potential tumor-suppressive effects of ginsenoside Rh2 are complex. N6-methyladenosine (m6A) RNA methylation is usually dysregulated in cancer. This study explored the regulatory effect of ginsenoside Rh2 on m6A RNA methylation in cancer.
Daram Yang, Hyuneui Jeong, Seung-Mi Hwang, Jong-Won Kim, Hee-Won Moon, Ye-Eun Lee, Hyo-Bin Oh, ,
Published: 21 May 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.05.006

Abstract:
Nonalcoholic steatohepatitis (NASH) is one of the main chronic liver diseases. NASH is identified by lipid accumulation, inflammation, and fibrosis. Jinan Red Ginseng (JRG) and licorice have been widely used because of their anti-inflammatory and hepatoprotective effects. Hence, this study assessed JRG and licorice extract mixtures' effects on NASH progression. Palmitic acid (PA) and the western diet (WD) plus, high glucose-fructose water were used to induce in vitro and in vivo NASH. Mice were orally administered with JRG-single (JRG-S) and JRG-mixtures (JRG-M; JRG-S + licorice) at 0, 50, 100, 200 or 400 mg/kg/day once a day during the last half-period of diet feeding. JRG-S and JRG-M reduced NASH-related pathologies in WD-fed mice. JRG-S and JRG-M consistently decreased the mRNA level of genes related with inflammation, fibrosis, and lipid metabolism. The treatment of JRG-S and JRG-M also diminished the SREBP-1c protein levels and the p-AMPK/AMPK ratio. The FAS protein levels were decreased by JRG-M treatment both in vivo and in vitro but not JRG-S. JRG-M effectively reduced lipogenesis by modulating AMPK downstream signaling. Our findings suggest that this mixture can be used as a prophylactic or therapeutic alternative for the remedy of NASH.
Bo-Ram Lee, Su-Jeong Sung, Kwang-Hyun Hur, Seong-Eon Kim, Shi-Xun Ma, Yong-Hyun Ko, Young-Jung Kim, Youyoung Lee, Seok-Yong Lee,
Published: 20 May 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.05.007

Abstract:
Methamphetamine (METH) is the most widely used psychostimulant and has been known to exhibit reinforcing effects even after long abstinence. We showed the inhibitory effect of Korean Red Ginseng extract (RGE) on METH-induced addictive behaviors in animal models mimicking the human drug-use pattern. We first investigated the effect of RGE on the acquisition of METH-induced dependence using self-administration and conditioned place preference (CPP) tests. Additionally, further experiments such as METH-induced motivational behavior and seeking behavior were conducted. To study the underlying mechanism, dopamine receptor, dopamine transporter, and N-methyl-D-aspartate receptor were assessed through Western blot analysis. Treatment with RGE significantly reduced METH-induced self-administration on a fixed-ratio 1 schedule of reinforcement. It could be also decreased a progressive ratio schedule, and inhibited METH-primed reinstatement. In CPP, RGE significantly prevented the development of METH-induced CPP. Moreover, RGE not only shortened the withdrawal period clearly, but also prevented the reinstatement of CPP. RGE treatment also reversed METH-induced overexpression of dopamine transporter, dopamine 1 receptor and NMDA receptor in the nucleus accumbens. Our findings reflect that RGE has therapeutic potential to suppress METH-induced addictive behaviors by regulating dopaminergic and NMDAergic system.
Soon-Kyung Hwang, Yun-Jeong Jeong, Hyun-Ji Cho, Yoon-Yub Park, Kwon-Ho Song,
Published: 19 May 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.05.005

Abstract:
Background: Red Ginseng has been used for many years to treat diseases. Ginsenoside Rg3 has documented therapeutic effects, including anticancer and anti-inflammatory activities. However, the anticancer effect of Rg3-enriched red ginseng extract (Rg3-RGE) and its underlying mechanisms have not been fully explored. We investigated whether Rg3-RGE plays an anti-tumor role in lung cancer cells. Methods: To examine the effect of Rg3-RGE on lung cancer cells, we performed cell viability assays, flow cytometry, western blotting analysis, and immunofluorescence to monitor specific markers. Results: Rg3-RGE significantly inhibited cell proliferation and induced mitochondria-dependent apoptosis. Furthermore, Rg3-RGE also increased expression of mitophagy-related proteins such as PINK1 and Parkin. In addition, treatment with Rg3-RGE and mitophagy inhibitors stimulated cell death by inducing mitochondria dysfunction. Conclusions: Rg3-RGE could be used as a therapeutic agent against lung cancer.
Weijie Chen, Xiuzhu Li, Zhejie Chen, Wei Hao, PeiFen Yao, Meng Li, Kunmeng Liu, Hao Hu, ,
Published: 18 May 2021
Journal of Ginseng Research; https://doi.org/10.1016/j.jgr.2021.05.003

Abstract:
Ginseng is an international herb that has been used for thousands of years. Two species most commonly applied and investigated in the ginseng family are Asian ginseng and American ginseng. The number of randomized controlled clinical trials (RCTs) has conspicuously increased, driven by the rapid development of ginseng. However, the reporting of RCT items of ginseng is deficient because of different trial designs and reporting formats, which is a challenge for researchers who are looking for the data with high quality and reliability. Thus, this study focused on providing an extensive analysis of these two species and examined the quality of the RCTs, based on the Consolidated Standards of Reporting Trials (CONSORT) guideline. Ninety-one RCTs conducted from 1980 to 2019 that were related to Asian ginseng and American ginseng used singly met our inclusion criteria. We found that the reporting quality of the two species has improved during the past 40 years. Publication date and sample size were significantly associated with the reporting quality. Rigorous RCTs designed for the species of ginseng are warranted, which can shed light on product research and development of ginseng in the future.
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