[The safety of herbal medicines in the psychiatric practice].

The use of alternative medicines is increasing world-wide and in Israel. These drugs, considered by the Ministry of Health as food supplements, are to be obtained at pharmacies and health stores and are being sold freely, without any professional advice. Many of the herbs are used by patients to treat psychiatric disorders. These herbs have a pharmacological activity, adverse effects and interactions with conventional drugs, which can produce changes in mood, cognition, and behavior. We present the most commonly used herbal drugs, and discuss their safety and efficacy in psychiatric practice. Hypericum--used as an antidepressant and as an antiviral medicine, was reported in 23 randomized clinical trials reviewed from the MEDLINE. It was found to be significantly more effective than placebo and had a similar level of effectiveness as standard antidepressants. Recent studies almost clearly prove that this herb, like most of the conventional antidepressants, can induce mania. Valerian--is used as an anti-anxiety drug, and reported to have sedative as well as antidepressant properties. In contrast to the significant improvement in sleep that was found with the use of valerian, compared to placebo, there are several reports on the valerian root toxicity. This includes nephrotoxicity, headaches, chest tightness, mydriasis, abdominal pain, and tremor of the hands and feet. Ginseng--another plant that is widely used as an aphrodisiac and a stimulant. It has been associated with the occurrence of vaginal bleeding, mastalgia, mental status changes and Stevens-Johnson syndrome after it's chronic administration. It has interactions with digoxin, phenelzine and warfarin. Ginkgo--in clinical trials the ginkgo extract has shown a significant improvement in symptoms such as memory loss, difficulties in concentration, fatigue, anxiety, and depressed mood. Long-term use has been associated with increased bleeding time and spontaneous hemorrhage. Ginkgo should be used cautiously in patients receiving aspirin, NSAIDs, anticoagulants or other platelet inhibitors. Health care professionals can no longer ignore the widespread use of alternative medicines and cannot continue with the "don't ask, don't tell" policy. Clinicians should ask the patients about their use of herbs in a non-judgmental way, and should document the patient's use of these drugs. Finally, we must be more aware of the side effects and the potential drug interactions of these herbs, and advise our patients to avoid long term use of these drugs due to lack of information regarding the safety of these medicines.

A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects.

It is rare to see a day pass in which we are not told through some popular medium that the population is becoming older. Along with this information comes the "new" revelation that as we enter the next millennium there will be increases in age-associated diseases (e.g., cancer, cardiovascular disease) including the most devastating of these, which involve the nervous system (e.g., Alzheimer's disease [AD] and Parkinson's disease [PD]). It is estimated that within the next 50 years approximately 30% of the population will be aged 65 years or older. Of those between 75 and 84 years of age, 6 million will exhibit some form of AD symptoms, and of those older than 85 years, over 12 million will have some form of dementia associated with AD. What appears more ominous is that many cognitive changes occur even in the absence of specific age-related neurodegenerative diseases. Common components thought to contribute to the manifestation of these disorders and normal age-related declines in brain performance are increased susceptibility to long-term effects of oxidative stress (OS) and inflammatory insults. Unless some means is found to reduce these age-related decrements in neuronal function, health care costs will continue to rise exponentially. Thus, it is extremely important to explore methods to retard or reverse age-related neuronal deficits as well as their subsequent, behavioral manifestations. Fortunately, the growth of knowledge in the biochemistry of cell viability has opened new avenues of research focused at identifying new therapeutic agents that could potentially disrupt the perpetual cycle of events involved in the decrements associated with these detrimental processes. In this regard, a new role in which certain dietary components may play important roles in alleviating certain disorders are beginning to receive increased attention, in particular those involving phytochemicals found in fruits and vegetables.

American ginseng (Panax quinquefolius L.) attenuates postprandial glycemia in a time-dependent but not dose-dependent manner in healthy individuals.

BACKGROUND: We previously showed that 3 g American ginseng administered 40 min before an oral glucose challenge significantly reduces postprandial glycemia in subjects without diabetes. Whether this effect can be replicated with doses <3 g and administration times closer to the oral glucose challenge is unclear. OBJECTIVE: Our objective was to study the dosing and timing effects of American ginseng on postprandial glycemia. DESIGN: In a random crossover design, 12 healthy individuals [X +/- SEM age: 42 +/- 7 y; body mass index (BMI; in kg/m2): 24.1 +/- 1.1] received 16 treatments: 0 (placebo), 1, 2, or 3 g American ginseng at 40, 20, 10, or 0 min before a 25-g oral glucose challenge. Capillary blood was collected before administration and at 0, 15, 30, 45, 60, and 90 min after the start of the glucose challenge. RESULTS: Two-way analysis of variance showed that the main effects of treatment and administration time were significant (P < 0.05). Glycemia was lower over the last 45 min of the test after doses of 1, 2, or 3 g ginseng than after placebo (P < 0.05); there were no significant differences between doses. The reductions in the areas under the curve for these 3 doses were 14.4 +/- 6.5%, 10.6 +/- 4.0%, and 9.1 +/- 6%, respectively. Glycemia in the last hour of the test and area under the curve were significantly lower when ginseng was administered 40 min before the challenge than when it was administered 20, 10, or 0 min before the challenge (P < 0.05). CONCLUSIONS: American ginseng reduced postprandial glycemia in subjects without diabetes. These reductions were time dependent but not dose dependent: an effect was seen only when the ginseng was administered 40 min before the challenge. Doses within the range of 1-3 g were equally effective.

Beneficial effect of ginseng root in SOD-1 (G93A) transgenic mice.

Many patients with amyotrophic lateral sclerosis (ALS; motor neuron disease) use natural or traditional therapies of unproven benefit. One such therapy is ginseng root. However, in some other disease models, ginseng has proven efficacious. Ginseng improves learning and memory in rats, and reduces neuronal death following transient cerebral ischemia. These effects of ginseng have been related to increases in the expression of nerve growth factor and its high affinity receptor in the rat brain, and antioxidant actions, inter alia. Since such actions could be beneficial in ALS as well, we studied the effect of ginseng (Panax quinquefolium), 40 and 80 mg/Kg, in B6SJL-TgN(SOD1-G93A)1Gur transgenic mice. The ginseng was given in drinking water, from age 30d onwards. We measured the time to onset of signs of motor impairment, and survival. There was no difference between the two ginseng groups (n=6, 6) in either measure. However, compared to controls (n=13), there was a prolongation in onset of signs (116d vs. 94d, P<0.001), and survival (139d vs. 132d, P<0.05). These experiments lend support to the use of ginseng root in ALS. Future experiments using this model could examine for symptomatic effects of ginseng, measure the effect of specific ginsenosides (which differ between ginseng species), and elucidate their mechanisms of action.

Effects of red ginseng upon vascular endothelial function in patients with essential hypertension.

This study is to estimate the effect of Korean red ginseng on vascular endothelial cell dysfunction in patients with hypertension. Seventeen patients with hypertension who were divided into ginseng-treated (7) and non-treated (10) groups and 10 normotensive subjects were included. To assess the function of the vascular endothelial cell, changes of forearm blood flow to infusion of acetylcholine, sodium nitroprusside and bradykinin in incremental doses were measured by venous occlusion plethysmography. In the ginseng-treated hypertensive group, forearm blood flows at the highest dose of acetylcholine and bradykinin were significantly higher than those of the non-treated hypertensive group and were not different from those of the control group. In the case of sodium nitroprusside infusion, no significant differences were observed between the control, non-treated and treated groups. In conclusion, Korean red ginseng can improve the vascular endothelial dysfunction in patients with hypertension possibly through increasing synthesis of nitric oxide.

Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes.

OBJECTIVE: We previously demonstrated that 3 g American ginseng (AG) reduced postprandial glycemia (PPG) in type 2 diabetic individuals. We investigated whether further reductions can be achieved with escalation of dose and time of AG administration. RESEARCH DESIGN AND METHODS: Ten type 2 diabetic patients (6 men, 4 women; age 63+/-2 years; BMI 27.7+/-1.5 kg/m2; HbA1c 7.3+/-0.3%) were randomly administered 0 g (placebo) or 3, 6, or 9 g ground AG root in capsules at 120, 80, 40, or 0 min before a 25-g oral glucose challenge. Capillary blood glucose was measured before ingestion of AG or placebo and at 0, 15, 30, 45, 60, 90, and 120 min from the start of the glucose challenge. RESULTS: Two-way analysis of variance (ANOVA) demonstrated that treatment (0, 3, 6, and 9 g AG) but not time of administration (120, 80, 40, or 0 min before the challenge) significantly affected PPG (P<0.05), with significant (P = 0.037) interaction for area under the curve (AUC). Pairwise comparisons showed that compared with 0 g (placebo), 3, 6, or 9 g significantly (P<0.05) reduced AUC (19.7, 15.3, and 15.9%, respectively) and incremental glycemia at 30 min (16.3, 18.4, and 18.4%, respectively), 45 min (12.5, 14.3, and 14.3%, respectively), and 120 min (59.1, 40.9, and 45.5%, respectively). However, pairwise comparisons showed no differences between the 3-, 6-, or 9-g doses and any of the times of administration. CONCLUSIONS: AG reduced PPG irrespective of dose and time of administration. No more than 3 g AG was required at any time in relation to the challenge to achieve reductions. Because these reductions included glycemia at the 2-h diagnostic end point, there may be implications for diabetes diagnosis and treatment.

Effect of ginsenosides, active components of ginseng, on capsaicin-induced pain-related behavior.

Our recent study demonstrated that ginsenosides had antinociceptive effects by reducing some types of pain-related behavior in mice (Yoon et al., 1998. Ginsenosides induce differential antinociception and inhibit substance P-induced nociceptive response in mice. Life Science 62, PL319-PL325). In the present study we further investigated whether ginsenosides produce antinociceptive effects through an action at central or peripheral site(s) and whether these effects are mediated by the opioid system. Intraperitoneally injected ginsenosides suppressed in a dose-dependent manner the pain-related behavior produced by capsaicin injection into the plantar surface of the hind paw; the ED(50) was 49 mg/kg [26-92 mg/kg, 95% confidence interval (C.I.)]. Intrathecally or intracerebroventricularly administered ginsenosides also suppressed the capsaicin-induced pain-related behavior in a dose-dependent manner; the ED(50)s were 1.72 mg/kg (0.8-3.72 mg/kg, 95% C.I.) and 1. 48 mg/kg (0.8-2.6 mg/kg, 95% C.I.), respectively. On the other hand, subcutaneously injected ginsenosides to the plantar surface prior to the capsaicin injection did not alter the pain-related behavior. Naloxone pretreatment was without effect in blocking the antinociceptive effect of intrathecally administered ginsenosides. Intraperitoneally injected ginsenosides also did not significantly affect the motor response of animals. These results suggest that ginsenosides produce antinociceptive effects through their action at the spinal and/or supraspinal site(s), not at nociceptors in the periphery. In addition, the results suggest that the antinociceptive effects are not mediated by opioid receptors.

Effects of oral administration of Pfaffia paniculata (Brazilian ginseng) on incidence of spontaneous leukemia in AKR/J mice.

Pfaffia paniculata (Brazilian ginseng) administered subcutaneously and intraperitoneally inhibits growth of allogeneic cancer cells in mice. The goal of this study was to determine whether oral administration of P. paniculata inhibits development of spontaneous leukemia. Four-week-old female AKR/J mice were given oral doses of powdered roots from P. paniculata three times weekly for 8 weeks; controls received phosphate-buffered saline. Enlargement of thymic lymphoma in the mice treated with P. paniculata was significantly suppressed, as compared with controls (128 +/- 67.3 mg versus 219.9 +/- 84.2 mg, respectively; P < .01); proliferation of endogenous recombinant murine leukemia viruses (MuLV) in the thymus was markedly inhibited after the first oral treatment as compared with untreated controls (final age, 28 weeks; P < .05). In normal 3-week-old female AKR/J mice, mortality from thymic lymphoma was delayed markedly after injection into the thymus of cell-free extract of thymus from the experimental female 28-week-old AKR/J mice that received the oral P. paniculata preparation. These results suggest that the agent's suppressive effects on spontaneously occurring leukemia caused by endogenous recombinant MuLV in female AKR/J mice may depend on enhancement of nonspecific immune or cellular immune systems (or both) by the P. paniculata preparation.

The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence.

OBJECTIVE: We have reviewed the potential cancer-preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in Oriental countries. DATA IDENTIFICATION AND STUDY SELECTION: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983-1998) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were considered. RESULTS: Published results from a cohort and two case-control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. CONCLUSION: While Panax ginseng C. A. Meyer has shown cancer-preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.

Asian studies of cancer chemoprevention: latest clinical results.

Chemoprevention trials in Asia, including those already completed and those now ongoing, are reviewed. Information was mainly collected from Japan, Korea and China. Each country features its own characteristics. Cancer chemoprevention trials targeting, from various aspects, hepatocellular carcinoma, gastric cancer and colon cancer have been, and are now being, conducted in Japan. Japan also has a long history of basic carcinogenesis research and carcinogenic research using animal experiments. In Korea, ginseng is the main focus of studies of chemopreventive agents. A large body of information has been collected and prospective studies are also ongoing. In China, the Linxian study, a cooperative study participated in by China and the NCI of the USA, is well known and the results impressive. However, we must exercise caution because, for example, the population of Linxian are chronically deficient in multiple vitamins and trace minerals. This situation may, therefore, differ from that observed in other countries. In any event, chemoprevention studies will be popular from an economical point of view even in Asia because cancer is becoming the number one cause of death in these countries.

Inhibition by ginseng of 1,2-dimethylhydrazine induction of aberrant crypt foci in the rat colon.

The modifying effects of dietary administration of ginseng on the induction and development of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) were investigated in Fischer 344 (F-344) rats. In Experiment 1, starting at six weeks of age, 65 rats were injected with DMH or saline alone once a week for four weeks. Rats in Groups 1 and 2 were fed diets containing 1% ginseng for five weeks, starting one week before the first dose of DMH. Animals in Groups 3 and 4 received ginseng for eight weeks after DMH treatment; Group 5 served as a carcinogen control group. In Experiment 2, 60 rats were injected with DMH or saline alone four times at one-week intervals. They were also fed diets containing 1% ginseng or the control diet throughout the 30 days of the experiment. In Experiment 1, numbers of foci with at least four crypts were significantly reduced in Group 2 treated with red ginseng during the initiation phase (p < 0.005). In Experiment 2, treatment with red ginseng also resulted in a decrease in the total number of DMH-induced ACF accompanied by a reduction in 5-bromo-2'-deoxyuridine labeling indexes in colonic crypts comprising ACF (p < 0.005 and p < 0.05, respectively). These findings suggest that dietary administration of red ginseng in combination with DMH suppresses colon carcinogenesis of rats, and the inhibition may be associated, in part, with suppression of cell proliferation in the colonic mucosa.

The role of ginsenoside-Rd in cisplatin-induced acute renal failure.

Ginsenoside-Rd has been proved to decrease the severity of renal injury induced by cisplatin, in which proximal urinaferous tubules represent the main site of injury. When ginsenoside-Rd was given orally at a dose of 1 or 5 mg/kg body weight/day for 30 consecutive days prior to cisplatin injection, the activities of the antioxidation enzymes superoxide dismutase and catalase were higher, while malondialdehyde levels in serum and renal tissue were lower in the treated rats than in the controls. The levels of urea nitrogen and creatinine in serum were decreased in rats given ginsenoside-Rd. Decreased urinary levels of glucose, sodium and potassium reflected a protective action against the renal dysfunction caused by cisplatin. In addition, it was demonstrated that ginsenoside-Rd affected cultured proximal tubule cells exposed to cisplatin.

Panax (ginseng)--panacea or placebo? Molecular and cellular basis of its pharmacological activity.

INTRODUCTION: The use of ethnobotanical drugs amongst Asians as complementary medicine is prevalent and is also gaining increasing popularity in the West. The most well-known herb traditionally used as a drug is the root of the ginseng species. There are many traditional and anecdotal claims to the therapeutic properties of ginseng. In recent years, there have been systematic efforts to analyse the bioactivities of ginseng saponins. METHODS: A comprehensive review of published literature covering molecular and cellular research as well as animal and human studies on ginseng and its derivatives. RESULTS AND CONCLUSION: Current published data would serve as a framework to understand the pharmacology of ginseng in its entirety, from its molecular action to actual therapeutic effects observed in human use. A new paradigm is emerging whereby the pharmacological effects of traditional herbs such as ginseng can be understood in the light of their polyvalent actions as demonstrated by ginseng saponins with their positive anti-mutagenic, anti-cancer, anti-inflammatory, anti-diabetes and neurovascular effects. With increasing understanding, evidence-based incorporation of traditional herbs as complementary medicine into mainstream medical science can be achieved in the near future.

American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus.

BACKGROUND: Despite a lack of medical evidence to support its therapeutic efficacy, the use of herbal medicine has increased considerably. Ginseng, one of the most widely used herbs, is hypothesized to play a role in carbohydrate metabolism and diabetes mellitus. We therefore undertook a preliminary short-term clinical study to assess whether American ginseng (Panax quinquefolius L) affects postprandial glycemia in humans. DESIGN: On 4 separate occasions, 10 nondiabetic subjects (mean [+/-SD] age, 34+/-7 years; mean [+/-SD] body mass index [BMI], 25.6 +/- 3 kg/m2) and 9 subjects with type 2 diabetes mellitus (mean [+/-SD] age, 62 +/- 7 years; mean [+/-SD] BMI, 29 +/- 5 kg/m2; mean [+/-SD] glycosylated hemoglobin A1c, 0.08+/-0.005) were randomized to receive 3-g ginseng or placebo capsules, either 40 minutes before or together with a 25-g oral glucose challenge. The placebo capsules contained com flour, in which the quantity of carbohydrate and appearance matched the ginseng capsules. A capillary blood sample was taken fasting and then at 15, 30, 45, 60, 90, and 120 (only for subjects with type 2 diabetes mellitus ) minutes after the glucose challenge. RESULTS: In nondiabetic subjects, no differences were found in postprandial glycemia between placebo and ginseng when administered together with the glucose challenge. When ginseng was taken 40 minutes before the glucose challenge, significant reductions were observed (P<.05). In subjects with type 2 diabetes mellitus, the same was true whether capsules were taken before or together with the glucose challenge (P<.05). Reductions in area under the glycemic curve were 18%+/-31% for nondiabetic subjects and 19+/-22% and 22+/-17% for subjects with type 2 diabetes mellitus administered before or together with the glucose challenge, respectively. CONCLUSIONS: American ginseng attenuated postprandial glycemia in both study groups. For nondiabetic subjects, to prevent unintended hypoglycemia it may be important that the American ginseng be taken with the meal.

Evaluation of the ergogenic properties of ginseng: an update.

Ginseng has been used in the Orient for several thousand years as an 'adaptogenic' as well as a 'restorative' agent. It has been used to treat nervous disorders, anaemia, wakefulness, dyspnoea, forgetfulness and confusion, prolonged thirst, decreased libido, chronic fatigue, angina and nausea. Although the mechanisms underlying the alleged effects of ginseng remain to be elucidated, there is an extensive animal literature dealing with the effects of ginseng on the cardiovascular system, central nervous system, endocrine system, metabolism, and immune system. In our previous review dealing with the efficacy of ginseng, we concluded that while studies with animals show that ginseng, or its active components, may prolong survival to physical or chemical stress, there is generally a lack of controlled research demonstrating the ability of ginseng to improve or prolong performance in fatigued humans. In this review, we extend our earlier analysis on the potential efficacy of ginseng use in the enhancement of physical performance and modification of fatigue states. Our analysis reveals that published literature appearing since our earlier review has not resolved the equivocal nature of research evidence involving animals or humans. Also, the lack of unanimity in this research can be explained on the basis of various methodological problems such as inadequate sample size and lack of double-blind, control and placebo paradigms. In addition, the absence of acceptable approaches to the problem of 'sourcing', in concert with an absence of compliance data in human research, further complicates the interpretation of this research literature. Nevertheless, the use of ginseng continues to grow, and current sales are estimated to be over $US300 million annually. There is clearly a need for systematic research dealing with the efficacy of ginseng, and this research needs to take into account basic, fundamental design considerations if there is to be any hope of establishing whether or not ginseng possesses efficacy.

American ginseng improves glycemia in individuals with normal glucose tolerance: effect of dose and time escalation.

OBJECTIVE: We studied the effect of escalating the dose and administration time of American ginseng (AG, Panax quinquefolius L.) in nondiabetic individuals to achieve further improvements in glucose tolerance seen previously when 3 g of AG was taken 40 minutes before a 25 g glucose challenge. METHODS: Ten nondiabetic individuals (6M:4F; mean +/- STD: age = 41 +/- 13 years, BMI = 24.8 +/- 3.5 kg/m2, FBG = 4.5 +/- 0.1 mmol L(-1)) on 12 separate occasions, randomly received 0 (placebo), 3, 6 or 9 g of ground AG root at 40, 80, or 120 minutes before a 25 g oral glucose challenge. Capillary blood glucose was measured prior to ingestion of AG or placebo capsules and at 0, 15, 30, 45, 60 and 90 minutes from start of challenge. RESULTS: Compared with the placebo, 3, 6 and 9 g of AG reduced (p<0.05) postprandial incremental glucose at 30, 45 and 60 minutes; also, 3 and 9 g of AG did so at 90 minutes. At 60 minutes, 9 g of AG reduced incremental postprandial glucose relative to 3 g of AG (p<0.05). All AG doses reduced (p<0.05) area under the incremental glucose curve (3 g, 26.6%; 6 g, 29.3%; 9 g, 38.5%). AG taken at different times did not have an additional influence on postprandial glycemia. CONCLUSIONS: In nondiabetic individuals, 3, 6 or 9 g of AG taken 40, 80 or 120 minutes before a glucose challenge similarly improved glucose tolerance.