Korean Ginseng Pharmacology and Clinical Uses by Jeffrey Dach MD
In a 1979 report, Dr Hiai studied the effect of Korean Ginseng on the HPA axis. After intraperitonesal injection in experimental mice, both serum ACTH and Cortsol increased. The effect was suppressed by Dexamethasone. Dr Hiai concluded that ginseng acts on the hypothalamus and/or hypophysis primarily, and stimulats ACTH production resulting in increased synthesis of cortisol by the adrenal cortex.(1)
In a 2004 report, Dr Tachikawa found that Ginseg reduced adrenal medullary production of catecholamines, the stress hormones, adrenaline, epinephrine and norpinepheine.(2)
korean ginseng
1979 HPA stimulation
1) http://www.ncbi.nlm.nih.gov/
Endocrinol Jpn. 1979 Dec;26(6):661-5.
Stimulation of pituitary-adrenocortical system by ginseng saponin. Hiai S, Yokoyama H, Oura H, Yano S.
Effects of preparations of saponin mixture and isolated ginsenosides, extracted from the root of Panax ginseng, on plasma corticotropin (ACTH) and corticosterone concentrations in rats were determined by the radioimmunoassay and competitive protein binding method. When ginseng saponin mixture was administered to rats intraperitoneally, plasma ACTH and corticosterone increased significantly 30, 60 and 90 min after the treatment. The kinetic pattern of the increase in plasma ACTH was almost parallel to that in plasma corticosterone. Isolated ginsenoside, protopanaxadiol or protopanaxatriol glycoside, also increased plasma corticosterone. The ginseng-induced increase in plasma corticosterone was suppressed by pretreatment with dexamethasone. Thus the ginseng saponin was found to act on the hypothalamus and/or hypophysis primarily, and stimulated ACTH secretion which resulted in increased synthesis of corticosterone in the adrenal cortex.
Reduces catecholamine secretion by adrenal medulla
2) http://www.ncbi.nlm.nih.gov/
J Pharmacol Sci. 2004 Jun;95(2):140-4.
Proof of the mysterious efficacy of ginseng: basic and clinical trials: suppression of adrenal medullary function in vitro by ginseng. Tachikawa E, Kudo K.Source Department of Pharmacology, School of Medicine, Iwate Medical University.
Abstract The root of Panax ginseng C.A. MEYER has been reported to have an anti-stress action. Therefore, the effects of ginseng components on functions of adrenal medulla, which is one of the most important organs responsive to stress, were investigated in vitro. First, the components of ginseng were mainly divided into two fractions, that is, the saponin-rich and non-saponin fractions.
The saponin-rich fraction greatly reduced the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh), whereas the non-saponin fraction did not affect it at all. The protopanaxatriol-type saponins inhibited the ACh-evoked secretion much more strongly than the protopanaxadiol-type. On the other hand, the oleanane-type saponin, ginsenoside-Ro, had no such effect. Recent reports have demonstrated that the saponins in ginseng are metabolized and absorbed in digestive tracts following oral administration of ginseng. All of the saponin metabolites greatly reduced the ACh-evoked secretion. M4 was the most effective inhibitor among the metabolites. M4 blocked ACh-induced Na(+) influx and ion inward current into the chromaffin cells and into the Xenopus oocytes expressing human alpha3beta4 nicotinic ACh receptors, respectively, suggesting that the saponin metabolites modulate nicotinic ACh receptors followed by the reduction of catecholamine secretion. It is highly possible that these effects of ginsenosides and their metabolites are associated with the anti-stress action of ginseng.
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Chong, S. K., & Oberholzer, V. G. (1988). Ginseng–is there a use in clinical medicine?. Postgraduate Medical Journal, 64(757), 841.
1996 Male Fertility
http://www.ncbi.nlm.nih.gov/
Panminerva Med. 1996 Dec;38(4):249-54.
Effects of Panax Ginseng C.A. Meyer saponins on male fertility.
Salvati G, Genovesi G, Marcellini L, Paolini P, De Nuccio I, Pepe M, Re M. Source V Clinica Medica, University of Rome La Sapienza, Italy.
Sixty-six patients have been treated with Panax Ginseng C.A. Meyer extract, of whom 30 oligoastenospermic sine causa (group A), 16 oligoastenospermic with idiopathic varicocele (group B). Twenty age-matched volunteers were used as controls (group C). Use of Panax Ginseng extract showed an increase in spermatozoa number/ml and progressive oscillating motility, an increase in plasma total and free testosterone, DHT, FSH and LH levels, but a decrease in mean PRL. It is suggested that ginsenosides may have an effect at different levels of the hypothalamus-pituitary-testis axis.
2008 review
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Acta Pharmacol Sin. 2008 Sep;29(9):1109-18.
Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer.
Choi KT. Korean Society of Ginseng, Seocho-Ku, Seoul 137-862, and Techno-Doctor, KOITA, Seoul, Republic of Korea.
2009 Review
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Curr Med Chem. 2009;16(19):2475-84.
Current evaluation of the millennium phytomedicine–ginseng (I): etymology, pharmacognosy, phytochemistry, market and regulations. Jia L, Zhao Y. Developmental Therapeutics Program, National Cancer Institute/NIH,
Abstract The dawning of this millennium broke new ground in life science and technology, presented us genomic and proteomic revolution, nanotechnology innovation, and high performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) used for separating and identifying new chemical entities at pico-, or even femto-concentrations. Applications of these high technologies to the traditional Chinese medicine (TCM) opened a new chapter in the ancient medicine, and prompted us to re-evaluate the thousand-year-old phytomedicine- ginseng from current perspectives. We, therefore, collected the latest information (mostly within 10 years) on ginseng, and condensed the information into two parts of this review serial. The present part covers etymology of ginseng, its pharmacognosy (natural origin, physical appearance, chemical properties, and specie identification), its cultivation and processing-related metabolic changes in active ingredients, standardized analytical methods used for quality control of various ginseng products, modern analytical methods used to identify and classify more than 100 chemical entities (many were recently unfolded) derived from ginseng species and their metabolites. The global markets and production of ginseng and relevant government regulations are herein updated to exchange information and understandings about current people’s uses and cultivation of ginseng. The second part of the review serial will classify all these 100 chemical entities separated from various ginseng species into different groups based on their structural similarities, and summarize bioactivities of these entities. The second part of the review serial will also focus on recent findings of ginseng pharmacology and its clinical trials for various diseases, and brief side effects of ginseng.
2oo9 review free full text
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Ginseng Compounds: An Update on Their Molecular Mechanisms and Medical Applications Current vascular pharmacology
Curr Vasc Pharmacol. 2009 July; 7(3): 293–302. Jian-Ming Lü, Qizhi Yao, and Changyi Chen.
Korean Panax ginseng C A Meyer is mainly used to maintain the homeostasis of the body, and the pharmacological efficacy of Korean ginseng identified by modern science includes improved brain function, pain-relieving effects, preventive effects against tumors as well as anti-tumor activity, enhanced immune system function, anti-diabetic effects, enhanced liver function, adjusted blood pressure, anti-fatigue and anti-stress effects, improved climacteric disorder and sexual functions, as well as anti-oxidative and anti-aging effects. Further clinical studies of these pharmacological efficacies will continue to be carried out. Korean ginseng is found to have such main properties as ginsenoside, ployacetylene, acid polysaccharide, anti-oxidative aromatic compound, and insulin-like acid peptides. The number of ginsenoside types contained in Korean ginseng (38 ginsenosides) is substantially more than that of ginsenoside types contained in American ginseng (19 ginsenosides). Furthermore, Korean ginseng has been identified to contain more main non-saponin compounds, phenol compounds, acid polysaccharides and polyethylene compounds than American ginseng and Sanchi ginseng.
2013 Effect on CNS
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J Ginseng Res. 2013 Mar;37(1):8-29.
A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system.
Kim HJ, Kim P, Shin CY. Department of Pharmacology, School of Medicine and Advanced Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Korea.
Addictions
http://journals.prous.com/
Methods Find Exp Clin Pharmacol 1998, 20(1): 77
Pharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants Takahashi, M., Tokuyama, S.
Analgesic effects of opioids, such as morphine and U-50,488H, were blocked by ginseng in a nonopioid dependent manner. Furthermore, ginseng inhibited the tolerance to and dependence on morphine, and eliminated the suppressive effect of the development of morphine tolerance by coexposure to footshock stress, but not psychological stress. On the other hand, behavioral sensitization (reverse tolerance to their ambulation-accelerating effect) to morphine, methamphetamine and cocaine was also inhibited by ginseng. Interestingly, ginseng also inhibited the appearance of the recurrent phenomenon (reappearance of the sensitized state was observed at the time of readministration of methamphetamine and cocaine even after a 30-day discontinuation of drug administration) of the effect of methamphetamine and cocaine. The conditioned place preference of methamphetamine and cocaine was completely blocked by ginseng. These findings provide evidence that ginseng may be useful clinically for the prevention of abuse and dependence of opioids and psychostimulants.
http://www.ncbi.nlm.nih.gov/
Fitoterapia. 2000 Aug;71 Suppl 1:S1-5.
The aphrodisiac and adaptogenic properties of ginseng. Nocerino E, Amato M, Izzo AA. Source Department of Experimental Pharmacology, University of Naples Federico II, via D. Montesano 49, Naples, Italy.
Abstract Ginseng is the root of the perennial herbs of Panax quinquefolium and Panax ginseng which contain a series of tetracyclic triterpenoid saponins (ginsenosides) as active ingredients. It is considered a tonic or adaptogenic that enhances physical performance (including sexual), promotes vitality and increases resistance to stress and ageing. The adaptogenic properties of ginseng are believed to be due to its effects on hypothalamic-pituitary-adrenal axis, resulting in elevated plasma corticotropin and corticosteroids levels. When used appropriately, ginseng appears to be safe. Nevertheless, documented side effects include hypertension, diarrhoea, restlessness, mastalgia and vaginal bleeding.
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Nocerino, Emilia, Marianna Amato, and Angelo A. Izzo. “The aphrodisiac and adaptogenic properties of ginseng.” Fitoterapia 71 (2000): S1-S5.
Review
The aphrodisiac and adaptogenic properties of ginseng
Emilia Nocerino, Marianna Amato, Angelo A. IzzoU Department of Experimental Pharmacology, Uni¨ersity of Naples
Abstract
Ginseng is the root of the perennial herbs of Panax quinquefolium and Panax ginseng which contain a series of tetracyclic triterpenoid saponins ginsenosides. as active ingredi-ents. It is considered a tonic or adaptogenic that enhances physical performance including sexual., promotes vitality and increases resistance to stress and ageing. The adaptogenic properties of ginseng are believed to be due to its effects on hypothalamic]pituitary]adrenal axis, resulting in elevated plasma corticotropin and corticosteroids levels. When used appropriately, ginseng appears to be safe. Nevertheless, documented side effects include hypertension, diarrhoea, restlessness, mastalgia and vaginal bleeding.
http://www.aafp.org/afp/2003/
Panax Ginseng DAVID KIEFER, M.D., TRACI PANTUSO, B.S., University of Arizona College of Medicine, Tucson, Arizona
Am Fam Physician. 2003 Oct 15;68(8):1539-1542.
Alternative Medicine Review Volume 14, Number 2 2009
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Panax ginseng
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2011 Allergic rhinitis
http://www.ncbi.nlm.nih.gov/
Allergy Asthma Immunol Res. 2011 Apr;3(2):103-10. doi: 10.4168/aair.2011.3.2.103. Epub 2011 Feb 14.
Therapeutic effects of fermented red ginseng in allergic rhinitis: a randomized, double-blind, placebo-controlled study.
Jung JW, Kang HR, Ji GE, Park MS, Song WJ, Kim MH, Kwon JW, Kim TW, Park HW, Cho SH, Min KU.
Source Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Allergic rhinitis is clinically defined as a disorder of the nose induced by IgE mediated inflammation after allergen exposure of the nasal mucosa. Many reports have stated that Panax ginseng and fermented red ginseng have anti-inflammatory effects, especially against Th2-type inflammation. This study was conducted to evaluate the therapeutic effects of fermented red ginseng in allergic rhinitis.
METHODS: In this 4-week, double-blind, placebo-controlled study, 59 patients with persistent perennial allergic rhinitis were randomly divided into two groups: those receiving fermented red ginseng tablets (experimental group) and those receiving placebo (control group). The primary efficacy variable was the total nasal symptom score (TNSS; rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy variables were the Rhinitis Quality of Life (RQoL) score and skin reactivity to inhalant allergens, as determined by the skin prick test.
RESULTS: There was no significant difference in the TNSS score and TNSS duration score between the experimental and placebo groups in weeks 1, 2, 3, or 4. For nasal congestion, fermented red ginseng was significantly effective (P<0.005), while placebo caused no change. The activity and emotion of RQoL improved markedly secondary to treatment with fermented red ginseng (P<0.05), while placebo caused no change. Additionally, fermented red ginseng reduced skin reactivity to sensitized perennial allergens (P<0.05). Fermented red ginseng was well tolerated.
CONCLUSIONS: Fermented red ginseng improved nasal congestion symptoms and RQoL in patients with perennial allergic rhinitis.
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Addiction 1998
http://www.ncbi.nlm.nih.gov/
Methods Find Exp Clin Pharmacol. 1998 Jan-Feb;20(1):77-84.
Pharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants.
Takahashi M, Tokuyama S. Department of Pharmacoinformatics, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Abstract
Pharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants are summarized. Analgesic effects of opioids, such as morphine and U-50, 488H, were blocked by ginseng in a nonopioid dependent manner. Furthermore, ginseng inhibited the tolerance to and dependence on morphine, and eliminated the suppressive effect of the development of morphine tolerance by coexposure to footshock stress, but not psychological stress. On the other hand, behavior sensitization (reverse tolerance to their ambulation-accelerating effect) to morphine, methamphetamine and cocaine was also inhibited by ginseng. Interestingly, ginseng also inhibited the appearance of the recurrent phenomenon (reappearance of the sensitized state was observed at the time of readministration of methamphetamine and cocaine even after a 30-day discontinuation of drug administration) of the effect of methamphetamine and cocaine. The conditioned place preference of methamphetamine and cocaine was completely blocked by ginseng. These findings provide evidence that ginseng may be useful clinically for the prevention of abuse and dependence of opioids and psychostimulants.
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Cancer
http://www.ncbi.nlm.nih.gov/
Novel Ginsenosides 25-OH-PPD and 25-OCH3-PPD as Experimental Therapy for Pancreatic Cancer: Anticancer Activity and Mechanisms of Action Wei Wang, Elizabeth R. Rayburn, […], and Ruiwen Zhang
In conclusion, both of the ginsenosides, 25-OH-PPD and 25-OCH3-PPD, might represent novel therapeutic agents for pancreatic cancer. Both compounds exerted potent in vitro and in vivo anti-cancer activities, and led to down-regulation of important oncogenic and pro-growth/pro-proliferation proteins. A dose of 10 mg/kg of either compound inhibited the growth of Panc-1 xenograft tumors by more than 50%, with no appreciable toxicity to the mice. This indicates that not only might the ginseng and notoginseng
compounds represent potential therapeutic agents, but that they may also be safe enough to be used to prevent primary or metastatic tumors. Our present data provide support for the further development of the compounds for pancreatic cancer
Breast Cancer Model
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http://www.ncbi.nlm.nih.gov/
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PLoS One. 2012;7(7):e41586. doi: 10.1371/journal.pone.0041586. Epub 2012 Jul 23.
Natural product ginsenoside 25-OCH3-PPD inhibits breast cancer growth and metastasis through down-regulating MDM2.
Wang W, Zhang X, Qin JJ, Voruganti S, Nag SA, Wang MH, Wang H, Zhang R. Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas, United States of America.
Although ginseng and related herbs have a long history of utility for various health benefits, their application in cancer therapy and underlying mechanisms of action are not fully understood. Our recent work has shown that 20(S)-25-methoxyl-dammarane-
In this study, we have demonstrated several important points: 1) 25-OCH3-PPD suppresses the growth of breast cancer in vivo; 2) 25-OCH3-PPD inhibits MDM2 expression at both transcriptional and post-translational levels; 3) the inhibition of MDM2 by 25-OCH3-PPD is essential for its anti-tumor activities; and 4) 25-OCH3-PPD inhibits breast cancer cell migration in vitro and metastasis in vivo. Our previous studies have demonstrated that 25-OCH3-PPD decreases cell viability, inhibits proliferation, induces apoptosis, and arrests cells in the G1 phase in other type of cancer cells [7]–[9]. 25-OCH3-PPD modulates the levels of several proteins related to apoptosis and cell proliferation, including cleaved
caspases-3, −8, and −9 and, cleaved PARP, Bax, p21, and p27 [7]–[9]. The treatment of 25-OCH3-PPD results in a decrease in Bcl-2, cyclin D1, cdks 2, 4 and 6, E2F1 and MDM2 [7]–[9].
Considering that MDM2 is linked to several of these findings [10]–[16], we decided to focus on the mechanism of MDM2 inhibition in this study. MDM2 plays an essential role in cancer development and progression [12]. MDM2 overexpression has been correlated with poor prognosis, increased metastasis and increased aggressiveness of human cancers [10]. MDM2 is suggested to be a potential target for human cancer therapy [15]. The expression of MDM2 is induced by p53 [23] and MDM2 binds to p53 with high affinity and inhibits its transcriptional activity [24], indicating that MDM2 functions as a negative feedback
In summary, our preclinical data indicate that 25-OCH3-PPD, a novel MDM2 inhibitor, is a potential therapeutic and anti-metastatic agent for human breast cancer. Evidences supporting the notion include the efficacy of 25-OCH3-PPD in breast cancer models (regardless of p53 status), favorable safety profiles at effective doses, and significant anti-metastasis effects. Further pre-clinical and clinical studies are warranted to provide a rationale for the development of 25-OCH3-PPD as a novel chemotherapy for breast cancer.
Zhang R.
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Front Pharmacol. 2012;3:25. doi: 10.3389/fphar.2012.00025. Epub 2012 Feb 28.
Ginsenosides as Anticancer Agents: In vitro and in vivo Activities, Structure-Activity Relationships, and Molecular Mechanisms of Action.
Nag SA, Qin JJ, Wang W, Wang MH, Wang H, Zhang R.
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center Amarillo, TX, USA.
Conventional chemotherapeutic agents are often toxic not only to tumor cells but also to normal cells, limiting their therapeutic use in the clinic. Novel natural product anticancer compounds present an attractive alternative to synthetic compounds, based on their favorable safety and efficacy profiles. Several pre-clinical and clinical studies have demonstrated the anticancer potential of Panax ginseng, a widely used traditional Chinese medicine. The anti-tumor efficacy of ginseng is attributed mainly to the presence of saponins, known as ginsenosides. In this review, we focus on how ginsenosides exert their anticancer effects by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (c-myc, EGFR, and vascular endothelial growth factor), tumor suppressors (p53 and p21), oncogenes (MDM2), cell death mediators (Bcl-2, Bcl-xL, XIAP, caspases, and death receptors), inflammatory response molecules (NF-κB and COX-2), and protein kinases (JNK, Akt, and AMP-activated protein kinase). We also discuss the structure-activity relationship of various ginsenosides and their potentials in the treatment of various human cancers. In summary, recent advances in the discovery and evaluation of ginsenosides as cancer therapeutic agents support further pre-clinical and clinical development of these agents for the treatment of primary and metastatic tumors.
A brief history of ginseng and ginseng products
Panax ginseng was discovered over 5000 years ago on the hills of Manchuria in China and since then held its place as a highly venerated medicinal plant in Traditional Chinese Medicine (Hemmerly, 1977). The ancient Chinese used it for various health benefits, ranging from overcoming fatigue to treating severe cardiac problems; ancient texts showed that ginseng was valued more than gold and was often reserved for treatment of royalty. The “Shennong Bencao Jing” written around 100 A.D. attributed longevity boosting properties to ginseng and stated that it was good for “enlightening the mind and increasing the wisdom” (Dharmananda, 2002).
The discovery of an American counterpart for this “miracle” plant happened in 1714, due to the efforts of Father Lafitau, a Jesuit priest, working with the Iroquois in Canada. Based on the theory that ginseng might grow wild in the Americas, due to a similarity in climactic conditions with China, Father Lafitau undertook a laborious search for the plant and eventually discovered that it was used as a medicinal herb
Conclusion Pre-clinical and clinical studies indicate that ginsenosides can be effective and safe anticancer agents. Ginsenoside saponins exhibit diverse molecular mechanisms of action, regulating most known modulators of carcinogenesis. Because of various mechanisms of cell death employed by ginsenosides, it may be difficult for cells to develop resistance to ginsenoside-induced cell death. Furthermore, the ability to kill tumor cells and relative non-toxicity to normal cells make ginsenosides attractive candidates for drug development.
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Gensing Targets are nuclear hormone receptors
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Chin Med. 2007 May 15;2:6.
Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides.
Yue PY, Mak NK, Cheng YK, Leung KW, Ng TB, Fan DT, Yeung HW, Wong RN.Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.
In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions. Angiogenesis in the human body is regulated by two sets of counteracting factors, angiogenic stimulators and inhibitors. The ‘Yin and Yang’ action of ginseng on angiomodulation was paralleled by the experimental data showing angiogenesis was indeed related to the compositional ratio between ginsenosides Rg1 and Rb1. Rg1 was later found to stimulate angiogenesis through augmenting the production of nitric oxide (NO) and vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such responses were mediated through the PI3K–>Akt pathway. act in a hierarchical cascade pattern to modulate cell architecturBy means of DNA microarray, a group of genes related to cell adhesion, migration and cytoskeleton were found to be up-regulated in endothelial cells. These gene products may interal dynamics which is concomitant to the observed phenomena in angiogenesis. By contrast, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg3 and Rh2) have been demonstrated in various models of tumor and endothelial cells, indicating that ginsenosides with opposing activities are present in ginseng. Ginsenosides and Panax ginseng extracts have been shown to exert protective effects on vascular dysfunctions, such as hypertension, atherosclerotic disorders and ischemic injury. Recent work has demonstrates the target molecules of ginsenosides to be a group of nuclear steroid hormone receptors. These lines of evidence support that the interaction between ginsenosides and various nuclear steroid hormone receptors may explain the diverse pharmacological activities of ginseng. These findings may also lead to development of more efficacious ginseng-derived therapeutics for angiogenesis-related diseases.
The pharmacological and therapeutic effects of ginseng have been demonstrated to affect the central nervous system (CNS), cardiovascular system, endocrine secretion, immune function, metabolism, biomodulating action, anti-stress, and anti-aging
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At present, ginseng is not only used as a therapeutic by traditional medical practitioners but is also as health supplements readily available in the commercial market. The diversity of highly desirable physiological effects of ginseng has intrigued scientists for years. In general, most of its pharmacological actions have been attributed to a group of triterpenoid saponins called ginsenosides. Although the modulatory effects of ginseng or probably ginsenosides have been extensively investigated, the actual molecular mechanisms remain largely unknown. Recently, it has been found that ginsenosides can act as functional ligands to activate different steroid hormone receptors. Through such mechanisms, ginseng can exert its effects on the human body by acting in a similar way as the steroid hormones. The interaction between ginsenosides and various nuclear steroid hormone receptors may explain the diverse activities of
ginseng, which may eventually lead to further development of ginseng-derived therapeutics for angiogenesis-related diseases
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menopause
http://www.ncbi.nlm.nih.gov/
Int J Gynaecol Obstet. 1999 Dec;67(3):169-74.
Effect of Korean red ginseng on psychological functions in patients with severe climacteric syndromes.Tode T, Kikuchi Y, Hirata J, Kita T, Nakata H, Nagata I.S Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama, Japan.
To evaluate the degree of psychological dysfunction and levels of stress hormones in postmenopausal women with climacteric syndromes and effect of Korean red ginseng (RG) on them.
METHODS:
ACTH, cortisol and DHEA-S in peripheral blood from 12 postmenopausal women with climacteric syndromes or 8 postmenopausal women without any climacteric syndrome were measured before and 30 days after treatment with daily oral administration of 6 g RG. Blood samples were collected in the early morning on the bed-rest. In postmenopausal women with climacteric syndromes such as fatigue, insomnia and depression, psychological tests using the Cornell Medical Index (CMI) and the State-Trait Anxiety Inventory (STAI) were performed before and 30 days after treatment with RG.
RESULTS:
CMI score as well as anxiety (A)-state in STAI score in postmenopausal women with climacteric syndromes was significantly higher than that without climacteric syndrome, while DHEA-S levels in postmenopausal women with climacteric syndromes were about a half of those without climacteric syndrome.
Consequently, cortisol/DHEA-S (C/D) ratio was significantly higher in postmenopausal women with climacteric syndromes than in those without climacteric syndrome. When postmenopausal women with climacteric syndromes were treated with daily oral administration of 6 g RG for 30 days, CMI and STAI A-state scores decreased within normal range. Although the decreased DHEA-S levels were not restored to the levels in postmenopausal women without climacteric syndrome, the C/D ratio decreased significantly after treatment with RG.
CONCLUSIONS:
Improvement of CMI and STAI scores in postmenopausal women suffering climacteric syndromes, particularly fatigue, insomnia and depression, by RG seemed to be brought about in part by effects of RG on stress-related hormones as shown by a decrease in C/D ratio.
CAncer
http://www.ncbi.nlm.nih.gov/
Int J Epidemiol. 1998 Jun;27(3):359-64.
Non-organ specific cancer prevention of ginseng: a prospective study in Korea. Yun TK, Choi SY.Laboratory of Experimental Pathology, Korea Cancer Center Hospital, Seoul.
A number of studies have reported that increased consumption of natural products reduced the risk of cancer. Our previous case-control studies have shown a significant reduction in the risk of cancer development among those who regularly consumed ginseng. We conducted a prospective cohort study to evaluate the preventive effect of ginseng against cancer on a population residing in a ginseng cultivation area on the basis of the result of case-control studies.
METHODS: This study was conducted in Kangwha-eup from August 1987 to December 1992. We studied 4634 people over 40 years old who completed a questionnaire on ginseng intake. In an attempt to obtain detailed information about ginseng intake, we asked them to specify their age at initial intake, their frequency and duration of ginseng intake, the kind of ginseng, etc. Multiple logistic regression was used to estimate relative risks (RR) when controlling simultaneously for covariates.
RESULTS: Ginseng consumers had a decreased risk (RR = 0.40, 95% confidence interval [CI] : 0.28-0.56) compared with non-consumers. On the type of ginseng, the RR was 0.31 (95% CI: 0.13-0.74) for fresh ginseng extract consumers and 0.34 (95% CI: 0.20-0.53) for consumers of multiple combinations. There was no cancer death among 24 red ginseng consumers. There was a decreased risk with a rise in the frequency of ginseng intake, showing a dose-response relationship. The RR of ginseng consumers were 0.33 (95% CI: 0.18-0.57) in gastric cancer and 0.30 (95% CI : 0.14-0.65) in lung cancer. Among ginseng preparations, fresh ginseng extract consumers were significantly associated with a decreased risk of gastric cancer (RR = 0.33, 95% CI: 0.12-0.88).
CONCLUSIONS: These results strongly suggest that Panax ginseng C.A. Meyer has non-organ specific preventive effect against cancer, providing support for the previous case-control studies.
2003
http://www.ncbi.nlm.nih.gov/
Mutat Res. 2003 Feb-Mar;523-524:63-74.
Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds.Yun TK.Laboratory of Experimental Pathology, Korea Cancer Center Hospital, 215-4 Gongneung Dong, Nowon Ku, Seoul 139-706, South Korea.
Abstract Panax ginseng C.A. Meyer has been the most highly recognized medicinal herb in the Orient. The prolonged administration of red ginseng extract significantly inhibits the incidence of hepatoma and also proliferation of pulmonary tumors induced by aflatoxin B(1) and urethane. Statistically significant anticarcinogenic effects were in aged or heat treated extracts of ginseng and red ginseng made by steaming in a 9 weeks medium-term anticarcinogenicity test using benzo[a]pyrene. In case-control studies, odds ratios (OR) of the cancer of lip, oral cavity and pharynx, larynx, lung, esophagus, stomach, liver, pancreas, ovary, and colorectum were significantly reduced. As to the type of ginseng, the ORs for cancer were reduced in user of fresh ginseng extract intakers, white ginseng extract, white ginseng powder, and red ginseng. In a cohort study with 5 years follow-up conducted in a ginseng cultivation area, ginseng users had a decreased relative risk (RR) compared with non-users. The relative risks (RRs) of ginseng users were decreased in gastric cancer and lung cancer. These findings strongly suggest that Panax ginseng C.A. Meyer cultivated in Korea has non-organ specific cancer preventive effects against various cancers. To investigate the active components for cancer prevention, several fractions of fresh and red ginseng and four semi-synthetic ginsenoside Rh(1), Rh(2), Rg(3) and Rg(5), the major saponin components in red ginseng, were prepared among the ginsenosides. By using Yun’s model, Rg(3) and Rg(5) showed statistically significant reduction of lung tumor incidence and Rh(2) had a tendency to decrease the incidence. In conclusion, these results strongly suggested that Panax ginseng C.A. Meyer cultivated in Korea is a non-organ specific cancer preventive against human cancers and also indicated that the anticarcinogenicity or human cancer preventive effect of Panax ginseng is due to ginsenoside Rg(3), Rg(5) and Rh(2).
colon cancer 2012
http://www.ncbi.nlm.nih.gov/
http://www.ncbi.nlm.nih.gov/
Int J Oncol. 2012 Jun;40(6):1970-6. doi: 10.3892/ijo.2012.1399. Epub 2012 Mar 12.
Ginsenoside compound K, not Rb1, possesses potential chemopreventive activities in human colorectal cancer.
Wang CZ, Du GJ, Zhang Z, Wen XD, Calway T, Zhen Z, Musch MW, Bissonnette M, Chang EB, Yuan CS.
Source Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA.
Abstract Ginsenoside compound K (C-K) is an intestinal microbiota metabolite of ginsenoside Rb1, a major constituent in American ginseng. However, previous ginseng anti-cancer observations were largely focused on ginseng parent compounds but not metabolites, and anti-colorectal cancer studies on C-K were limited. This study investigated the anti-proliferative effects of C-K when compared to those of Rb1, and the related mechanisms of action, in HCT-116 and SW-480 colorectal cancer cells. The effects of Rb1 and C-K on the proliferation of HCT-116 and SW-480 human colorectal cancer cells were compared using an MTS assay. Cell cycle and cell apoptosis were assayed using flow cytometry. Enzymatic activities of caspases were determined by colorimetric assay, and interactions of C-K and caspases were explored by docking analysis. C-K showed significant anti-proliferative effects in HCT-116 and SW-480 cells at concentrations of 30-50 µM. At the same concentrations, Rb1 did not show any effects, while C-K arrested the cells in the G1 phase, and significantly induced cell apoptosis. Compared to HCT-116 (p53 wild-type), the p53 mutant cell line SW-480 was more sensitive to C-K as assessed by cell cycle regulation and apoptosis induction. C-K activated expression of caspases 8 and 9, consistent with docking analysis. The docking data suggested that C-K forms hydrogen bonds with Lys253, Thr904 and Gly362 in caspase 8, and with Thr62, Ser63 and Arg207 in caspase 9. C-K, but not its parent ginsenoside Rb1, showed significant anti-proliferative and pro-apoptotic effects in human colorectal cancer cells. These results suggest that C-K could be a potentially effective anti-colorectal cancer agent.
http://www.ncbi.nlm.nih.gov/
Am J Chin Med. 2012;40(4):657-69. doi: 10.1142/S0192415X12500498.
Herbal medicines as adjuvants for cancer therapeutics.
Wang CZ, Calway T, Yuan CS. Tang Center for Herbal Medicine Research, Pritzker School of Medicine, University of Chicago, Illinois 60637, USA.
Abstract In the United States, many patients, including cancer patients, concurrently take prescription drugs and herbal supplements. Co-administration of prescription medicines and herbal supplements may have negative outcomes via pharmacodynamic and pharmacokinetic herb-drug interactions. However, multiple constituents in botanicals may also yield beneficial pharmacological activities. Botanicals could possess effective anticancer compounds that may be used as adjuvants to existing chemotherapy to improve efficacy and/or reduce drug-induced toxicity. Herbal medicines, such as ginseng, potentiated the effects of chemotherapeutic agents via synergistic activities, supported by cell cycle evaluations, apoptotic observations, and computer-based docking analysis. Since botanicals are nearly always administrated orally, the role of intestinal microbiota in metabolizing ginseng constituents is presented. Controlled clinical studies are warranted to verify the clinical utility of the botanicals in cancer chemoprevention.
http://www.ncbi.nlm.nih.gov/
Pan, Li, Hee-Byung Chai, and A. Douglas Kinghorn.
“Discovery of new anticancer agents from higher plants.”
Frontiers in Bioscience (Scholar Edition) 4 (2012): 142.
Discovery of new anticancer agents from higher plants Li Pan, Hee-Byung Chai, and A. Douglas Kinghorn
A mixture of protopanaxadiol (25) and protopanaxatriol (26) (Pandimex™) has been approved conditionally in mainland China for the treatment of advanced cancers of the breast, colon-rectum, lung, and pancreas, and is ongoing a Phase I clinical trial in the United States for advanced lung, gastric, breast, and pancreatic cancers in combination with paclitaxel or alone (85, 86)
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http://www.ncbi.nlm.nih.gov/
Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells
Kar Wah Leung, Fung Ping Leung, […], and Ricky NS Wong
<<<image Chemical structures of ginsenoside protopanaxadiol >>>>>>
British Journal of Pharmacology
Blackwell Publishing Ltd
Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells
Kar Wah Leung, Fung Ping Leung, […], and Ricky NS Wong
Ginsenosides are used widely for medicinal purposes, but the mechanisms of their action are still unclear, although there is some evidence that these effects are mediated by nuclear receptors. Here we examined whether two metabolites of ginsenoside, protopanaxadiol (g-PPD) and protopanaxatriol (g-PPT), could modulate endothelial cell functions through the glucocorticoid receptor (GR) and oestrogen receptor (ER).
Experiment approaches:The effects of g-PPD and g-PPT on intracellular calcium ion concentration ([Ca2+]i) and nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) were measured using Fura-2-acetoxymethyl ester, 4-amino-5-methylamino-2′,7′-
Results:Ginsenoside protopanaxadiol and g-PPT increased [Ca2+]i, eNOS phosphorylation and NO production in HUVECs, which were inhibited by the GR antagonist, RU486, the ER antagonist, ICI 182,780 and siRNA targeting GR or ERβ. The NO production was Ca2+-dependent and the [Ca2+]i elevation in HUVECs resulted from both intracellular Ca2+ release and extracellular Ca2+ influx.
Conclusions and implications:Ginsenoside protopanaxadiol and g-PPT were functional ligands for both GR and ERβ, through which these ginsenoside metabolites exerted rapid, non-genomic effects on endothelial cells.
Keywords: angiogenesis, endothelial cell, ginsenoside, intracellular calcium concentration, nitric oxide, nuclear receptor
Introduction Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is an important physiological process in development and wound healing. Dysregulation of angiogenesis that promotes neovascular growth underlies the progression of many pathologies, including ocular disease and cancer. On the other hand, a lack of appropriate neovascularization can prevent wound healing and is associated with occurrence of ulcers, coronary artery disease and strokes.
For these reasons, modulation of the process of neovessel formation is clinically relevant to a wide range of disorders. Recombinant human platelet-derived growth factor, a pro-angiogenic agent, was the first to be introduced for treating diabetic foot ulcers in 1999 (Steed, 2006), followed by clinical trials for vascular endothelial growth factor (VEGF) gene therapy in patients with cardiovascular disease (Losordo et al., 1998; Rosengart et al., 1999). This approach reduced myocardial ischemia and improved angina (Losordo et al., 1998; Rosengart et al., 1999). Several drugs have also been developed to combat excessive angiogenesis. For example, bevacizumab (Avastin) and ranibizumab are antibodies targeting VEGF, which inhibit VEGF-induced endothelial cell growth. These drugs are widely used in treatments for cancer and more recently for age-related macular degeneration and glaucoma (Andreoli and Miller, 2007; Ichhpujani et al., 2007; Khosravi Shahi and Fernández Pineda, 2008). Soluble VEGF receptor and neuropilin receptor are used clinically to suppress neovascularization (Baka et al., 2006).
Pro-angiogenic molecules, including VEGF and bFGF, promote neovascularization by increasing intracellular calcium ion concentration ([Ca2+]i) and nitric oxide (NO) levels in endothelial cells (Morbidelli et al., 1996; Babaei et al., 1998). Calcium channel blockers, like nifedipine, verapamil, amlodipine and diltiazem, are now under clinical trials as angiogenesis regulatory agents, complementing cancer therapy (Munaron, 2006). In mice deficient in endothelial NO synthase (eNOS), there is an impaired intrinsic angiogenic response to hindlimb ischemia, and a lack of responsiveness in these mice to treatment with VEGF (Murohara et al., 1998). Treatment with the NO precursor, L-arginine, potentiated post-surgical angiogenesis and accelerated wound healing in patients (Ruel et al., 2008). Thus, [Ca2+]i and NO represent key determinants of angiogenesis.
In addition to the classical pro-angiogenic agents, some steroids like the glucocorticoids and oestrogens, also play a part in modulating vascular activities. Both steroids can regulate angiogenic (Iwai et al., 2004; Kasselman et al., 2007), and cell adhesion molecules (Burke-Gaffney and Hellewell, 1996; Simoncini et al., 2000; Groten et al., 2005), as well as affecting the expression of junctional proteins (Forster et al., 2005) in endothelial cells through their respective receptors, glucocorticoid receptor (GR) and oestrogen receptor (ER) (Simoncini et al., 2000; Groten et al., 2005; Kasselman et al., 2007). Insufficient glucocorticoid or over-expression of GR in endothelial cells is associated with vascular malformation and infant hypotension (Friedman et al., 1996). Also, oestrogen and its receptors have a role in atheroprotective actions (Hodgin et al., 2001).
A recently described agent shown to have beneficial effects in the cardiovascular, endocrine, immune and central nervous systems is Panax ginseng, although the actual mechanisms of action for this drug are largely undefined. Ginsenosides are the pharmacologically active ingredients of ginseng, which appear in two major variants: 20(S)-protopanaxadiol and 20(S)-protopanaxatriol. All ginsenosides have the basic steroidal backbone (Figure 1). Upon oral consumption, the 20(S)-protopanaxadiol and 20(S)-protopanaxatriol ginsenosides transform into their respective end metabolites, protopanaxadiol (g-PPD) and protopanaxatriol (g-PPT), respectively, by acid hydrolysis and a series of deglycosylations by the intestinal microflora (Hasegawa et al., 1996; Bae et al., 2002; Chi et al., 2005). Over 80% of g-PPD and g-PPT enter the circulation (Chen and Staba, 1980; Cui et al., 1997) and both metabolites possess anti-oxidative (Wang et al., 1995; Jiang et al., 1996) and GR-dependent anti-tumour activities (Park et al., 1999; Li et al., 2006; Wang et al., 2007). Based on the structural similarity of these molecules to steroid hormones, several reports suggest that the actions of these compounds are mediated through nuclear receptors (Attele et al., 1999).
Although ginsenosides have been widely used for thousands of years and have shown strong health benefits for a wide range of physiological ailments, there is surprisingly little known about the molecular effects or biochemical mechanisms of actions for these drugs. The rapid stimulatory effects of g-PPD and g-PPT on [Ca2+]i and NO production that we have shown here on human endothelial cells suggest a potential value of ginsenosides and their metabolites as angiotherapeutic agents.
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2010
http://www.ncbi.nlm.nih.gov/
Leung, Kar W., and Alice ST Wong. “Pharmacology of ginsenosides: a literature review.” Chinese Medicine 5.1 (2010): 20.
Ginsenosides modulate expressions and functions of receptors such as receptor tyrosine kinases (RTK) [91], serotonin receptors (5-HT) [92], NMDA receptors [93] and nicotinic acetylcholine receptors (AChR) [94]. Direct interactions of ginsenosides with the receptor ligand-binding sites have only been demonstrated in steroid hormone receptors; ginsenosides Rg1 [58,95,96] and Re [97] are functional ligands of the glucocorticoid receptor (GR) while ginsenosides Rh1 and Rb1 are functional ligands of the estrogen receptor (ER), in particular, the ER beta isoform of Rb1 [59,98]. These findings provide an explanation for the aggravation of menopausal symptoms by ginsenosides [99,100] and modulation of the endocrine system in the case of chronic consumption of ginseng [3,4].
Conclusion As partial agonists to multiple steroidal receptors, ginsenosides are important natural resources to be developed into new modalities, and may replace steroids in the current regimen to lessen undesirable side effects
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blood pressure-nitric oxide
http://www.ncbi.nlm.nih.gov/
J Agric Food Chem. 2012 Mar 28;60(12):3086-91. doi: 10.1021/jf204447y. Epub 2012 Mar 15.
Panax ginseng extract rich in ginsenoside protopanaxatriol attenuates blood pressure elevation in spontaneously hypertensive rats by affecting the Akt-dependent phosphorylation of endothelial nitric oxide synthase.
Hong SY, Kim JY, Ahn HY, Shin JH, Kwon O.
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Korea.
Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is a fundamental regulator of systemic blood pressure. Ginsenosides from Panax ginseng have been investigated in vitro for the molecular and biochemical mechanisms by which they stimulate NO release in vascular endothelial cells; however, little research has been done to confirm the physiological relevance of these in vitro studies. To address this research gap, the effects of a P. ginseng extract rich in ginsenosides from protopanaxatriol on spontaneously hypertensive rats (SHRs) was examined. Ginseng extract administration stimulated nongenomic Akt-mediated eNOS activation, enhanced NO production, improved vessel wall thickening, and alleviated hypertension in SHRs, confirming the physiological relevance of previous in vitro studies with ginsenosides.
http://www.ncbi.nlm.nih.gov/
Springerplus. 2013 Mar 9;2(1):96. Print 2013 Dec.
Panax ginseng extract rich in ginsenoside protopanaxatriol offers combinatorial effects in nitric oxide production via multiple signaling pathways.Ahn HY, Hong SY, Kim JY, Kwon O.
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 120-750 Republic of Korea.
The root of Panax ginseng C.A. Meyer has been shown to induce nitric oxide (NO) release resulting in a hypotensive effect. However, the main active component contributing to vascular endothelium relaxation remains uncertain. In this study, we hypothesized that multiple components of ginseng extract might have combinatory effects providing greater health benefits than a single ginsenosides. To test this hypothesis, we compared the NO-releasing and endothelial NO synthase (eNOS) activating potency of wide range of ginseng extracts (crude extract, CE; protopanaxatriol-enriched extract, TE; protopanaxadiol-enriched extract, DE) and individual ginsenosides (Rg1, Re and Rb1) in human umbilical vein endothelial cells. We found that TE had the highest potency in NO production, followed by CE, DE, and Rg1. We also observed that TE-treatment resulted in rapid activation of intracellular signaling pathways, immediate linear rise of NO, and increased eNOS activation. TE-induced activation of eNOS was abolished by pretreatment with wortmannin (inhibitor for PI3K-Akt), compound C (inhibitor for AMP activated protein kinase, AMPK) or L-NAME (inhibitor for NOS), whereas Rg1-induced eNOS phosphorylation was only partially attenuated. Further analysis revealed that TE, but not Rg1, results in AMPK phosphorylation at Thr172. These novel finding add evidence that the multiple components of Panax ginseng extract rich in protopanaxatriol offers combinatorial effects in NO production and vascular endothelium relaxation via multiple signaling pathways.
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http://www.ncbi.nlm.nih.gov/
Chin J Integr Med. 2009 Dec;15(6):403-8. doi: 10.1007/s11655-009-0403-6. Epub 2010 Jan 18.
New achievements in ginseng research and its future prospects.
Chu SF, Zhang JT. Institute of Material Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
In recent decades, scientists in Asian and Western countries have been paying great attention to ginseng research. Today, more than 200 ginsenosides and non-saponin constituents have been isolated and identified. Ginsenosides show biological activities only after being deglycosylated by intestinal bacteria. Aglycone protopanaxadiol and protopanaxatriol show the highest bioactivities. According to literature, the noticeable action of ginseng is that of delaying aging and especially increasing the nootropic effect, and it was found for the first time that Rg1 could increase hippocampal neurogenesis in vitro and in vivo under physiological and pathological circumstances. This is one of primary mechanisms underlying many of its pharmacological actions on the central nervous system. Rg1 was further shown to improve learning and memory in normal rats and mice. The nootropic signaling pathway has also been carried out in normal rats, and the Rg1-induced signaling pathway is similar to the memory formation that occurs in mammals, suggesting that Rg1 may have a potential effect in increasing intellectual capacity in normal people. Comparisons of chemical structures and pharmacologic functions between Panax ginseng and Panax quiquefolium were carried out by many scientists. The conclusion is that each has its own characteristics. There is no superiority or inferiority to the other.
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diabetes
http://care.diabetesjournals.
Ginseng Therapy in Non-Insulin-Dependent Diabetic Patients: Effects on psychophysical performance, glucose homeostasis, serum lipids, serum aminoterminalpropeptide concentration, and body weight
Eero A Sotaniemi, MD, PHD, Eila Haapakoski, RN and Arja Rautio, MD, PHD Departments of Internal Medicine Oulu, Finland Pharmacology and Toxicology Oulu, Finland University of Oulu, and the Deaconess Institute of Oulu Oulu, Finland
OBJECTIVE To investigate the effect of ginseng on newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients.
RESEARCH DESIGN AND METHODS In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight.
RESULTS Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG.
CONCLUSIONS Ginseng may be a useful therapeutic adjunct in the management of NIDDM.
http://www.omicsgroup.org/
Antidiabetic Effects of Ginseng in Humans and Rodents
Zhanxiang Wang1* and Hongji Zhang2
1Herman B Wells Center for Pediatric Research, Basic Diabetes Group, Department of Pediatrics, Indiana University School of Medicine, USA
2Department of Urology, Indiana University School of Medicine, USA
Ginseng, one of the most commonly used herbs worldwide, has known anti-hyperglycemic effects. Twenty-eight (28) studies on diabetic mice and rats from 7 research centers (in 6 different nations) indicate that both Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) are effective anti-hyperglycemic supplements, putatively acting via improvements in insulin secretion, insulin sensitivity, islet protection, obesity reduction, antioxidation, energy expenditure, and fat absorption. Investigations in clonal beta-cells (MIN6, RINmF, INS-1, HIT-T15) and non-beta-cells (3T3-L1, C1C12, HepG2) further confirm that ginseng may protect against pancreatic beta-cell apoptosis and promote insulin secretion and glucose uptake. Among 18 human trials from 4 independent groups, 15 are single dose trials; whereas, 4 are long-term trials, with treatment periods lasting longer than 4 weeks. Eleven of the single dose trials observed anti-diabetic effects, while 4 observed no improvements. In the long-term studies, two-thirds of the studies on type 2 diabetic (T2D) patients observed anti-hyperglycemic effects. Based upon the sound evidence from cell lines and animal models, along with the improvements from the majority of human subject trials, ginseng appears to be a potent anti-diabetic supplement. Regardless, more long-term trials on T2D patients are required before ginseng can be safely recommended as a broadly-used anti-diabetic agent.
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excellent review 2011
GINSENG A UNIVERSAL PANACEA IN THE HERBAL MEDICINE WITH DIVERSE PHARMACOLOGICAL SPECTRUM –A REVIEW
Asian Journal of Pharmaceutical and Clinical Research
Vol. 4, Suppl 1, 2011 LAKSHMI T1 *, ANITHA ROY1 & GEETHA R.V2 1Department of Pharmacology, Saveetha Dental College, Velappanchavady, Chennai, 2Department of Microbiology, Saveetha Dental College, Velappanchavady, Chennai.
pdf file downloaded
review 2013 1415 studies
http://www.ncbi.nlm.nih.gov/
PLoS One. 2013;8(4):e59978. doi: 10.1371/journal.pone.0059978. Epub 2013 Apr 1.
Ginseng for health care: a systematic review of randomized controlled trials in Korean literature.
Choi J, Kim TH, Choi TY, Lee MS.
Medical Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
This systematic review was performed to summarise randomised clinical trials (RCTs) assessing the efficacy and safety of ginseng in the Korean literature.
METHOD:The study involved systematic searches conducted in eight Korean Medical databases. The methodological quality of all of the included studies was assessed using the Cochrane Risk of Bias tool. We included all RCTs on any type of ginseng compared to placebo, active treatment or no treatment in healthy individuals or patients regardless of conditions.
RESULTS:In total, 1415 potentially relevant studies were identified, and 30 randomised clinical trials were included. Nine RCTs assessed the effects of ginseng on exercise capacity, cognitive performance, somatic symptoms, quality of life, and sleeping in healthy persons. Six RCTs tested ginseng compared with placebo for erectile dysfunction, while another four studies evaluated the effects of ginseng against no treatment for gastric and colon cancer. Two RCTs compared the effect of red ginseng on diabetes mellitus with no treatment or placebo, and the other nine RCTs assessed the effects of ginseng compared with placebo or no treatment on various conditions. The methodological caveats of the included trials make their contribution to the current clinical evidence of ginseng somewhat limited. However, the 20 newly added trials (66.7% of the 30 trials) may provide useful information for future trials. Ginseng appears to be generally safe, and no serious adverse effects have been reported.
CONCLUSIONS:The clinical effects of ginseng have been tested in a wide range of conditions in Korea. Although the quality of RCTs published in the Korean literature was generally poor, this review is useful for researchers to access studies that were originally published in languages that they would otherwise be unable to read and due to the paucity of evidence on this subject.
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ED
http://www.ncbi.nlm.nih.gov/
Br J Clin Pharmacol. 2008 Oct;66(4):444-50. doi: 10.1111/j.1365-2125.2008.
Red ginseng for treating erectile dysfunction: a systematic review.
Jang DJ, Lee MS, Shin BC, Lee YC, Ernst E.
Korea Food Research Institute, Sungnam, South Korea.
Korean red ginseng (unskinned Panax ginseng before it is steamed or otherwise heated and subsequently dried) is one of the most widely used herbal remedies. This systematic review evaluates the current evidence for the effectiveness of red ginseng for treating erectile dysfunction.
METHODS:Systematic searches were conducted on 20 electronic databases without language restrictions. Hand-searches included conference proceedings and our files. All randomized clinical studies (RCT) of red ginseng as a treatment of erectile dysfunction were considered for inclusion. Methodological quality was assessed using the Jadad score.
RESULTS:Seven RCTs met all the inclusion criteria. Their methodological quality was low on average. Six of the included RCTs compared the therapeutic efficacy of red ginseng with placebo. The meta-analysis of these data showed a significant effect (n = 349, risk ratio, 2.40; 95% CI of 1.65, 3.51, p < 0.00001, heterogeneity: tau(2) = 0.05, chi(2) = 6.42, p = 0.27, I(2) = 22%). Subgroup analyses also showed beneficial effects of red ginseng in psychogenic erectile dysfunction (n = 135, risk ratio, 2.05; 95% CI of 1.33, 3.16, p = 0.001, heterogeneity: chi(2) = 0.08, p = 0.96, I(2) = 0%).
CONCLUSIONS:Collectively these RCTs provide suggestive evidence for the effectiveness of red ginseng in the treatment of erectile dysfunction. However, the total number of RCTs included in the analysis, the total sample size and the methodological quality of the primary studies were too low to draw definitive conclusions. Thus more rigorous studies are necessary.
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pdf file downloaded
Asian Journal of Drug Metabolism and Pharmacokinetics
Ginseng, the king of traditional and herbal medicines
Li-Qin Sun
Liqin Sun Acupuncture and Herbs Clinic, 1720 S. San Gabril Blvd., Sulte 106, San Gabril, CA 91776, USA
http://www.ncbi.nlm.nih.gov/
Am J Chin Med. 1981 Summer;9(2):112-8.
Ginseng and the hypothalamic-pituitary control of stress. Fulder SJ.
In one series of experiments mice were given ginseng throughout their lifespan. At intervals their behavior response to mild stress was examined and found to be exaggerated compared to controls without ginseng. However, normal ambulatory behavior in the absence of stress was unaffected. A second series of experiments indicated that the binding of corticosteroid to certain brain regions was increased in adrenalectomized rats given ginseng saponin, compared to saline treated controls. This can be interpreted as a result of an increase in hypothalamic-pituitary-adrenal sensitivity caused by ginseng saponin. This is in accord with traditional concepts of the use of these remedies.
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