Radioprotective potential of ginseng

A majority of potential radioprotective synthetic compounds have demonstrated limited clinical application owing to their inherent toxicity, and thus, the seeking of naturally occurring herbal products, such as ginseng, for their radioprotective capability has become an attractive alternative. In general, ginseng refers to the roots of the species of the genus Panax. As a medicinal herb, ginseng has been widely used in traditional Chinese medicine for its wide spectrum of medicinal effects, such as tonic, immunomodulatory, antimutagenic, adaptogenic and antiaging activities. Many of its medicinal effects are attributed to the triterpene glycosides known as ginsenosides (saponins). This review addresses the issue of the radioprotective effects of ginseng on mammalian cells both in vitro and in vivo. Results indicate that the water-soluble extract of whole ginseng appears to give a better protection against radiation-induced DNA damage than does the isolated ginsenoside fractions. Since free radicals play an important role in radiation-induced damage, the underlying radioprotective mechanism of ginseng could be linked, either directly or indirectly, to its antioxidative capability by the scavenging free radicals responsible for DNA damage. In addition, ginseng's radioprotective potential may also be related to its immunomodulating capabilities. Ginseng is a natural product with worldwide distribution, and in addition to its antitumor properties, ginseng appears to be a promising radioprotector for therapeutic or preventive protocols capable of attenuating the deleterious effects of radiation on human normal tissue, especially for cancer patients undergoing radiotherapy.     

Autonomic regulation of insulin secretion is changed by pentobarbital in mice

It has been established that insulin secretion is regulated by autonomic nervous homeostasis. In the screen of plasma glucose level, anesthetized animals were widely used. However, effects of anesthetics on blood glucose remain unclear. In the present study, we compared the hypoglycemic action of ginseng that was induced by insulin secretion in mice between conscious and under anesthesia with pentobarbital. The hypoglycemic effect of ginseng was only produced in anesthetized BALB/c mice but not in the conscious mice. Similar results were also observed in C57BL/6 mice. However, the hypoglycemic action of ginseng failed to produce in anesthetized BALB/c mice received streptozotocin to induce type-1 like diabetes showing an insulin-dependent manner. The plasma insulin level in anesthetized BALB/c mice was markedly raised by ginseng but this effect was not observed in conscious mice. Blockade of muscarinic receptors by atropine inhibited ginseng-induced insulin secretion in anesthetized mice. Otherwise, the hypoglycemic action of ginseng was restored in conscious mice treated guanethidine at a sufficient dose to block sympathetic tone. In conclusion, the obtained results suggest that insulin secretion regulated by autonomic nervous homeostasis can be changed by pentobarbital through decrement in sympathetic tone to increase the insulin secretion induced by agent(s) via higher of parasympathetic tone. This finding is suitable to explain the critical hypoglycemia was not observed in subjects received ginseng.     

Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides

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.     

Ginseng leaf-stem: bioactive constituents and pharmacological functions

Ginseng root is used more often than other parts such as leaf stem although extracts from ginseng leaf-stem also contain similar active ingredients with pharmacological functions. Ginseng's leaf-stems are more readily available at a lower cost than its root. This article reviews the pharmacological effects of ginseng leaf-stem on some diseases and adverse effects due to excessive consumption. Ginseng leaf-stem extract contains numerous active ingredients, such as ginsenosides, polysaccharides, triterpenoids, flavonoids, volatile oils, polyacetylenic alcohols, peptides, amino acids and fatty acids. The extract contains larger amounts of the same active ingredients than the root. These active ingredients produce multifaceted pharmacological effects on the central nervous system, as well as on the cardiovascular, reproductive and metabolic systems. Ginseng leaf-stem extract also has anti-fatigue, anti-hyperglycemic, anti-obesity, anti-cancer, anti-oxidant and anti-aging properties. In normal use, ginseng leaf-stem extract is quite safe; adverse effects occur only when it is over dosed or is of poor quality. Extracts from ginseng root and leaf-stem have similar multifaceted pharmacological activities (for example central nervous and cardiovascular systems). In terms of costs and source availability, however, ginseng leaf-stem has advantages over its root. Further research will facilitate a wider use of ginseng leaf-stem.     

Efficacy of Ginseng Supplements on Fatigue and Physical Performance: a Meta-analysis

We conducted a meta-analysis to investigate the efficacy of ginseng supplements on fatigue reduction and physical performance enhancement as reported by randomized controlled trials (RCTs). RCTs that investigated the efficacy of ginseng supplements on fatigue reduction and physical performance enhancement compared with placebos were included. The main outcome measures were fatigue reduction and physical performance enhancement. Out of 155 articles meeting initial criteria, 12 RCTs involving 630 participants (311 participants in the intervention group and 319 participants in the placebo group) were included in the final analysis. In the fixed-effect meta-analysis of four RCTs, there was a statistically significant efficacy of ginseng supplements on fatigue reduction (standardized mean difference, SMD = 0.34; 95% confidence interval [CI] = 0.16 to 0.52). However, ginseng supplements were not associated with physical performance enhancement in the fixed-effect meta-analysis of eight RCTs (SMD = −0.01; 95% CI = −0.29 to 0.27). We found that there was insufficient clinical evidence to support the use of ginseng supplements on reducing fatigue and enhancing physical performance because only few RCTs with a small sample size have been published so far. Further lager RCTs are required to confirm the efficacy of ginseng supplements on fatigue reduction.     

A Case of Korean Ginseng-Induced Anaphylaxis Confirmed by Open Oral Challenge and Basophil Activation Test

Two case reports discussing Korean ginseng-induced allergic reactions have been published; both were inhalation-induced respiratory allergies in occupational settings. In this report we discuss the first case of anaphylaxis that developed after an oral intake of ginseng, confirmed by an open oral challenge, a skin prick test (SPT), and a basophil activation test (BAT). A 44-year-old man experienced rhinorrhea and nasal stiffness, followed by respiratory difficulty with wheeze and abdominal pain 10 minutes after oral intake of fresh ginseng. He had suffered from episodes of allergic rhinitis during the spring season for several years. Upon presentation, a physical examination, chest radiograph, and routine laboratory tests were unremarkable. Total serum IgE level was 41 IU/mL. The SPT results showed strong positive responses to alder, birch pollens, and ginseng extracts (1:500 w/v). The methacholine bronchial challenge test revealed a positive result at PC20 of 5.83 mg/mL. The open oral challenge was performed using 50 g of fresh ginseng and showed immediate onset of facial flushing, cough, respiratory difficulty with wheeze, and abdominal pain combined with a significant decrease in FEV1 levels (54% from the baseline). Serum-specific IgE and IgG4 antibodies were not detectable by enzyme-linked immunosorbent assay. BAT showed a remarkable increase in the expression of CD203c and CD63 with the addition of ginseng extract in a dose-dependent manner, while no changes were noted in the controls. In conclusion, oral intake of Korean ginseng could induce anaphylaxis, which is mediated by non-IgE-dependent direct activation of basophil/mast cells.     

Effect of Asian and Siberian ginseng on serum digoxin measurement by five digoxin immunoassays. Significant variation in digoxin-like immunoreactivity among commercial ginsengs

Asian and Siberian ginsengs contain glycosides with structural similarities to digoxin. We studied potential interference of ginseng in 5 digoxin immunoassays in 3 Asian (2 liquid extracts, 1 capsule) and 3 Siberian ginseng preparations (1 liquid extract, 2 capsules). With the fluorescence polarization immunoassay (FPIA), we observed apparent digoxin activity in 1 Asian liquid preparation and in the liquid extract and 1 capsule form of Siberian ginseng. In mice fed ginseng, we observed digoxin activities in the serum (Asian, 0.48-0.68 ng/mL [0.6-0.9 nmol/L]; Siberian, 0.20-0.47 ng/mL [0.3-0.6 nmol/L]), indicating that such interferences also occur in vivo. Serum pools prepared from samples from patients receiving digoxin and then supplemented with Asian or Siberian ginseng showed falsely increased digoxin values using the FPIA (e.g., for Asian ginseng, 1.54 ng/mL [2.0 nmol/L] vs control value, 1.10 ng/mL [1.4 nmol/L]) and falsely decreased values using the microparticle enzyme immunoassay (MEIA; 0.73 ng/mL [0.9 nmol/L] vs control value, 1.04 ng/mL [1.3 nmol/L]). Digoxin-like immunoreactive substances (DLISs) showed synergistic effects with ginsengs in interfering with the FPIA and MEIA for digoxin. No interference was observed with 3 other digoxin assays, even in the presence of elevated DLISs.     

Antidepressant-like effect of altered Korean red ginseng in mice

Altered Korean red ginseng has been used as a treatment for patients suffering from anxiety. We assessed whether red ginseng hydrolyzed by malted barley (HRG) and acetate-fermented red ginseng (ARG) would improve brain activity, by using forced swimming test (FST) in mice. The effect of the fluoxetine (a classical antidepressant), ginsenoside Rg3 (Rg3), red ginseng (RG), HRG, and the ARG groups for two weeks on the immobility time was significantly decreased in comparison with the control group (p<0.05). The immobility time of HRG and ARG in FST was lower than that of RG. The plasma level of glucose and total protein was significantly increased in the HRG and ARG group compared with the control group (p<0.05), whereas albumin, lactate dehydrogenase, creatine kinase, and blood urea nitrogen levels were not changed. In conclusion, altered Korean red ginsengs, HRG, and ARG therapy appeared to be effective in improving depression.     

Korean ginseng-induced occupational asthma and determination of IgE binding components

A number of case reports on occupational asthma caused by herbal medicines have been issued, for example, on Sanyak, Chunkung, Banha, and Brazilian ginseng. Recently, cases of occupational asthma induced by Sanyak and Korean ginseng have been reported, but the pathogenic mechanisms involved are unknown. This study was carried out to evaluate the immunologic mechanism underlying Korean ginseng-induced occupational asthma. A patient engaged in Korean ginseng wholesale was referred for recurrent dyspnea, wheezing, and nasal symptoms, which were aggravated at work. Allergen bronchial provocation testing to Korean ginseng extract showed a typical immediate response, and skin prick testing to Korean ginseng extract also showed a strong positive response. Moreover, serum-specific IgE levels to Korean ginseng extract were significantly higher than in controls. Enzyme-linked immunosorbent assay (ELISA) inhibition tests showed a dose-dependent inhibition by Korean ginseng, but not by Dermatophagoides farinae, wheat flour, or Chinese balloon flower. Sodium dodecylsulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and immunoblotting revealed four specific Immunoglobulin E (IgE) binding components at 26, 30, 47, and 60 kDa, which were not bound by control sera. These results strongly suggest that occupation asthma induced by Korean ginseng is induced via an IgE-mediated mechanism.     

Red ginseng ameliorated place navigation deficits in young rats with hippocampal lesions and aged rats

Effects of hippocampal lesions and aging on spatial learning and memory and ameliorating effects of red ginseng on learning deficits were investigated in the following two experiments: performance of young rats with selective hippocampal lesions with red ginseng by mouth (p.o.; Experiment 1) and aged rats with red ginseng (p.o.; Experiment 2) in the spatial tasks was compared with that of sham-operated or intact young rats. Each rat in these two behavioral experiments was tested with the three types of spatial-learning tasks (distance movement task, DMT; random-reward place search task, RRPST; and place-learning task, PLT) in a circular open field using intracranial self-stimulation as reward. The results in the DMT and RRPST tasks indicated that motivational and motor activity of young rats with hippocampal lesions with and without ginseng were not significantly different from that of sham-operated young rats in Experiment 1. However, young rats with hippocampal lesions displayed significant deficits in the PLT task. Treatment with red ginseng significantly ameliorated place-navigation deficits in young rats with hippocampal lesions on the PLT task. Similarly, red ginseng improved performance of aged rats on the PLT task in Experiment 2. The results, along with previous studies showing significant effects of red ginseng on the central nervous system, suggest that red ginseng ameliorates learning and memory deficits through effects on the central nervous system, partly through effects on the hippocampal formation.     

Increase of acetylcholine release by Panax ginseng root enhances insulin secretion in Wistar rats

The present study was designed to ascertain the effect of Panax ginseng root on plasma glucose and investigate the possible mechanisms for the effect. Ninety minutes after the oral administration of P. ginseng root to fasting Wistar rats, plasma glucose decreased in a dose-dependent manner. Simultaneous with the reduction in plasma glucose, an increase in the plasma level of insulin and C-peptide was also observed. Moreover, disruption of the available synaptic acetylcholine (ACh), using the inhibitor for choline uptake (hemicholinium-3), or the inhibitor for vesicular choline transport (vesamicol), abolished the metabolic actions of P. ginseng root. Conversely, physostigmine, at a concentration sufficient to inhibit acetylcholinesterase, enhanced the metabolic effect of P. ginseng root. It is possible that P. ginseng root mediates the release of ACh from nerve terminals to enhance insulin secretion. Blockade of the actions of P. ginseng root by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP) suggested that the site of action is the muscarinic M(3) receptor. Taken together, the results suggest that P. ginseng root has the ability to increase the release of ACh from nerve terminals in rats so as to stimulate muscarinic M(3) receptors activity located in the pancreatic cells for the secretion of insulin, which in turn lower plasma glucose.     

Therapeutic effects of fermented red ginseng in allergic rhinitis: a randomized, double-blind, placebo-controlled study

Purpose

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.     

Post-exposure treatment with ginsenoside compound K ameliorates auditory functional injury associated with noise-induced hearing loss in mice

Noise-induced hearing loss (NIHL) is thought to primarily involve damage to the sensory hair cells of the cochlea via mechanical and metabolic mechanisms. Unfortunately, initial studies assessing the effectiveness of post-exposure treatment after hearing loss have yielded largely disappointing results. This study explored the effects of oral treatment with Korean red ginseng (RG) and with two bioavailable ginsenoside metabolites, ginsenoside Rh1 and ginsenoside compound K (GCK), in response to NIHL in a murine model. Pharmacological treatments began 24h after noise exposure and were continued once daily for 7 days. Central auditory function was evaluated using auditory middle latency responses, and cochlear function was determined based on transient evoked otoacoustic emissions. Additionally, cochlear hair cell morphology was investigated after noise exposure. Both Korean red ginseng and compound K reduced threshold shifts, central auditory function damage, and cochlear functional and morphological deficits. In contrast, treatment with ginsenoside Rh1 did not result in recovery of NIHL in mice. These results suggest that consumption of Korean red ginseng may facilitate recovery from noise-induced hearing loss. Furthermore, one of the active constituents in ginseng is likely ginsenoside compound K.     

Antidepressant-like Effect of Altered Korean Red Ginseng in Mice

Altered Korean red ginseng has been used as a treatment for patients suffering from anxiety. We assessed whether red ginseng hydrolyzed by malted barley (HRG) and acetate-fermented red ginseng (ARG) would improve brain activity, by using forced swimming test (FST) in mice. The effect of the fluoxetine (a classical antidepressant), ginsenoside Rg3 (Rg3), red ginseng (RG), HRG, and the ARG groups for two weeks on the immobility time was significantly decreased in comparison with the control group (p < 0.05). The immobility time of HRG and ARG in FST was lower than that of RG. The plasma level of glucose and total protein was significantly increased in the HRG and ARG group compared with the control group (p < 0.05), whereas albumin, lactate dehydrogenase, creatine kinase, and blood urea nitrogen levels were not changed. In conclusion, altered Korean red ginsengs, HRG, and ARG therapy appeared to be effective in improving depression.     

Study designs of randomized controlled trials not based on Chinese medicine theory are improper

Current biomedical research methods to evaluate the efficacy of Chinese medicine interventions are often conceptually incompatible with the theory and clinical practice of Chinese medicine. In this commentary, we (1) highlight the theory and principles underlying Chinese medicine clinical practice; (2) use ginseng as an example to describe clinical indications in Chinese medicine; (3) propose a framework guided by Chinese medicine theory for the evaluation of study designs in Chinese medicine research; and (4) evaluate 19 randomized, double-blind, placebo-controlled trials of ginseng. Our analysis indicates that all 19 trials with both positive and negative results confirm the specific effects of ginseng indicated by Chinese medicine theory. Study designs guided by Chinese medicine theory are necessary to validate and improve future randomized controlled clinical trials in Chinese medicine.     

Effects of nonsaponin fraction of red ginseng on learning deficits in aged rats

Previously we reported that oral application of red ginseng significantly ameliorated learning deficits in aged rats and young rats with hippocampal lesions. In the present study, we investigated the effects of the nonsaponin fraction of red ginseng on learning deficits in aged rats in behavioral studies and those on long-term potentiation (LTP) in the hippocampal CA3 subfield in young rats in electrophysiological studies. In the behavioral studies, three groups of rats [aged rats with and without oral administration of the nonsaponin fraction of red ginseng and young rats] were tested with the three types of spatial-learning task [distance movement task (DMT), random-reward place search task (RRPST), and place-learning task (PLT)] in a circular open field. The results in the DMT and RRPST indicated that motivational and motor activity was not significantly different among the three groups of rats. However, performance of the aged rats without nonsaponin was significantly impaired in the PLT when compared with the young rats. Treatment with nonsaponin significantly ameliorated deficits in place-navigation learning in the aged rats in the PLT. In the electrophysiological studies, effects of nonsaponin on the LTP in the CA3 subfield of the hippocampal slices were investigated in vitro. Pretreatment with nonsaponin significantly augmented the increase in population spike amplitudes in the CA3 subfield after LTP induction. These results suggest that the nonsaponin fraction of red ginseng contains important substances to improve learning and memory in aged rats and that this amelioration by nonsaponin might be attributed partly to augmentation of LTP in the CA3 subfield.     

Possible Mechanisms Underlying the Effect of Natural Preparations on Erythropoiesis Under Conditions of Conflict Situation

We studied the effects of various natural preparations, including extracts of Siberian ginseng, Rhodiola rosea, bergenia, and ginseng and pantohematogen on erythropoiesis under conditions of conflict situation. The test preparations were divided into 2 groups depending on their modulatory effect on intensified erythropoiesis under conditions of conflict situation. Some of them reduced (extracts of ginseng, bergenia, and Rhodiola rosea), while others increased the degree of hyperplasia in the erythropoietic stem (extract of Siberian ginseng and pantohematogen). The regulatory effect of preparations depended on activity of the corresponding neurotransmitter systems in the brain and local regulatory mechanisms of hemopoiesis.     

Short-term oral administration of ginseng extract induces type-1 cytokine production

Ginseng radix (Panax ginseng C.A. Meyer) is a popular herbal medicine used as a major ingredient in tonic recipes in eastern Asian countries. In our study, male BALB/c mice were treated orally with various doses of ginseng root extract for 5 consecutive days. The extract reduced the serum level of IgG but elevated the level of IgA. Under in vitro condition, the lipopolysaccharide-stimulated spleen cells from the ginseng-treated mice also showed a significant decrease in IgG production but an increase in IgA production. The serum level and production of IgM was unaffected. The interleukin-2, interferon-γ (Th1-type cytokines), and interleukin-10 (Tr1-type cytokine) production by Con A-stimulated spleen cells from the ginseng-treated mice showed an upregulation relative to the control group. However, the production of interleukin-4 (Th2-type cytokine) showed no significant change. The activity of natural killer cells was increased in the ginseng group, but the percentages of T-lymphocytes (CD3⁺) and CD4⁺8^-, CD4^-8⁺ subset were reduced. Thus, short-term oral administration of ginseng extract appears to enhance Th1-type cytokine production.     

人参复方对噪声所致小鼠某些脑递质和血浆皮质酮含量变化的影响

小鼠在纺织噪声104dB(A)环境下,每天暴露8小时,连续2周,脑皮层5-HT,间脑和脑干DA、血浆皮质酮含量都有较明显降低的趋势(0.1>P>0.05),而噪声刺激下服人参复方组小鼠,上述指标均保持在正常范围。上述两组间脑和脑干NA含量变化不明显。     

Short-Term Oral Administration of Ginseng Extract Induces Type-1 Cytokine Production

Ginseng radix (Panax ginseng C.A. Meyer) is a popular herbal medicine used as a major ingredient in tonic recipes in eastern Asian countries. In our study, male BALB/c mice were treated orally with various doses of ginseng root extract for 5 consecutive days. The extract reduced the serum level of IgG but elevated the level of IgA. Under in vitro condition, the lipopolysaccharide-stimulated spleen cells from the ginseng-treated mice also showed a significant decrease in IgG production but an increase in IgA production. The serum level and production of IgM was unaffected. The interleukin-2, interferon-γ (Th1-type cytokines), and interleukin-10 (Tr1-type cytokine) production by Con A-stimulated spleen cells from the ginseng-treated mice showed an upregulation relative to the control group. However, the production of interleukin-4 (Th2-type cytokine) showed no significant change. The activity of natural killer cells was increased in the ginseng group, but the percentages of T-lymphocytes (CD3⁺) and CD4⁺8^?, CD4^?8⁺ subset were reduced. Thus, short-term oral administration of ginseng extract appears to enhance Th1-type cytokine production.