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Internet marketing of herbal products.

CONTEXT: Passage of the Dietary Supplement Health and Education Act in 1994 restricted the Food and Drug Administration's control over dietary supplements, leading to enormous growth in their promotion. The Internet is often used by consumers as a source of information on such therapies. OBJECTIVE: To assess the information presented and indications claimed on the Internet for the 8 best-selling herbal products. DATA SOURCES: We searched the Internet using the 5 most commonly used search engines. For each, we entered the names of the 8 most widely used herbal supplements (ginkgo biloba, St John's wort, echinacea, ginseng, garlic, saw palmetto, kava kava, and valerian root). We analyzed the health content of all Web sites listed on the first page of the search results. STUDY SELECTION: We analyzed all accessible, English-language Web sites that pertained to oral herbal supplements. A total of 522 Web sites were identified; of these, 443 sites met inclusion criteria for the analysis. DATA EXTRACTION: The nature of the Web site (retail or nonretail), whether it was a sponsored link, and all references, indications, claims, and disclaimers were recorded. Two reviewers independently categorized medical claims as disease or nondisease according to Food and Drug Administration criteria. DATA SYNTHESIS: Among 443 Web sites, 338 (76%) were retail sites either selling product or directly linked to a vendor. A total of 273 (81%) of the 338 retail Web sites made 1 or more health claims; of these, 149 (55%) claimed to treat, prevent, diagnose, or cure specific diseases. More than half (153/292; 52%) of sites with a health claim omitted the standard federal disclaimer. Nonretail sites were more likely than retail sites to include literature references, although only 52 (12%) of the 443 Web sites provided referenced information without a link to a distributor or vendor. CONCLUSIONS: Consumers may be misled by vendors' claims that herbal products can treat, prevent, diagnose, or cure specific diseases, despite regulations prohibiting such statements. Physicians should be aware of this widespread and easily accessible information. More effective regulation is required to put this class of therapeutics on the same evidence-based footing as other medicinal products.

Advertising↗

Diet and stomach cancer in Korea.

Stomach cancer is the most prevalent malignant neoplasm in Korea. As of 1991-1992 in Seoul, the cumulative rates reported for the age span 0-74 were 7.6% in males and 3.1% in females. A recent case-control study reported that several food items and cooking methods are associated with increased or decreased risk of stomach cancer among Koreans. An increased risk of stomach cancer was noted among people who frequently consume broiled meats and fishes, salted side dishes (salted/fermented fish products) and salty stewed foods, such as soybean paste thick stew. Frequent consumption of mung bean pancake, tofu, cabbage, spinach and sesame oil decreased the risk. Analysis by cooking method showed that risk of stomach cancer from the same foods varied with preparation. For meat and fish, pan frying was associated with decreased risk, whereas stewing or broiling was associated with increased risk. Pickled vegetables increased the risk, whereas fresh vegetables did not. In a recent cohort study in Seoul, green vegetables and soybean foods were associated with a decreased risk of stomach cancer. Case-control and cohort studies have reported that ginseng intake decreased the risk of gastric cancer.

Cooking↗

Ginsenosides Rb1 and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration.

Certain natural products and Asian herbal remedies have been used in Asia to attenuate neurodegenerative diseases, including senile dementia. We have examined derivatives of several natural products for potential neuroprotective activity in an in vitro test system. In the present study, we assayed a number of compounds that were isolated from Panax ginseng C.A. Meyer (Araliaceae) for an ability to protect rat cortical cell cultures from the deleterious effects of the neurotoxicant, glutamate. We found that ginsenosides Rb1 and Rg3 significantly attenuated glutamate-induced neurotoxicity. Brief exposure of cultures to excess glutamate caused extensive neuronal death. Glutamate-induced neuronal cell damage was reduced significantly by pretreatment with Rb1 and Rg3. Ginsenosides Rb1 and Rg3 inhibited the overproduction of nitric oxide, which routinely follows glutamate neurotoxicity, and preserved the level of superoxide dismutase in glutamate-treated cells. Furthermore, in cultures treated with glutamate, these ginsenosides inhibited the formation of malondialdehyde, a compound that is produced during lipid peroxidation, and diminished the influx of calcium. These results show that ginsenosides Rb1 and Rg3 exerted significant neuroprotective effects on cultured cortical cells. Therefore, these compounds may be efficacious in protecting neurons from oxidative damage that is produced by exposure to excess glutamate.

Animals↗

Usage and users of natural remedies in a middle-aged population: demographic and psychosocial characteristics. Results from the Malmö Diet and Cancer Study.

BACKGROUND: In Sweden, large amounts of money are spent annually on natural remedies (NRs), in spite of the fact that most products in this category lack scientific documentation of their efficacy and side-effects. The usage and users of natural remedies are not well defined. This paper describes NR use and NR users in a city in southern Sweden, and tests the hypothesis that the use of natural remedies is a strategy for coping with psychosocial stressors. METHODS: The study cohort consisted of 6545 men and women, aged 45-65 years, who during 1991 and 1992 participated in the Malmö Diet and Cancer Study, a large-scale prospective cohort study. Data on consumption of natural remedies were recorded during seven consecutive days, as part of a dietary assessment. Each participant also completed a questionnaire, covering education, work history, alcohol and smoking habits, perceived health, and psychosocial factors such as social network, social support, job strain and global control. Body composition was also measured. RESULTS: The prevalence of NR consumption was 26% among women and 17% among men. NR use was most common during winter and spring. The most popular products were ginseng, garlic, and various herb and plant extracts. Important determinants of NR usage were higher education, Swedish origin, and lifestyle factors like low body weight fat percentage and high alcohol consumption among women. Other determinants were higher age and non-smoking among men. None of the psychosocial factors appeared to influence the prevalence of NR consumption. CONCLUSIONS: The prevalence of NR consumption is influenced by sex, demographic factors, season of the year, and lifestyle. Use of NRs does not appear to be a common strategy for coping with psychosocial stress.

Journal Article↗

Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.

Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defence mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation.

Adaptation, Physiological↗

Ethnomedicinally selected plants as sources of potential analgesic compounds: indication of in vitro biological activity in receptor binding assays.

A number of plant species used in traditional medicine for the relief of pain have been selected from the medicinal and scientific literature of China, South America, Asia and West Africa. Extracts were prepared and tested in three in vitro receptor radioligand binding assays to determine whether there was an indication of biological activity, in particular their selectivity to a single receptor implicated in the mediation of pain. The three neuropeptide receptors chosen were Bradykinin (BK II), expressed in Chinese hamster ovary cells (CHO), neurokinin 1 (NK 1) expressed in astrocytoma cells, and calcitonin gene related peptide (CGRP) which were all implicated in the mediation of acute pain in the mammaliancentral nervous system. The plant species chosen to investigate were Ageratum conyzoides, Barringtonia edulis, Croton tiglium, Ipomea pes-caprae, Panax ginseng, Physostigma venenosum, Sinomenium acutum, Solidago virgaurea, Symplocos leptophylla and Typhonium giganteum. The results showed that there was a strong indication of biological activity for some of the plants which are used ethnomedicinally to treat pain, in the three in vitro receptor binding assays used, and particular plant extracts exhibited selective action to a single receptor.

Analgesics, Non-Narcotic↗

Inhibitory effect of Byakko-ka-ninjin-to on itch in a mouse model of atopic dermatitis.

Byakko-ka-ninjin-to (BN) is composed of gypsum, the root of anemarrhena, ginseng, licorice and rice. The effect of BN on the inhibition of itch was studied using an NC mouse model of atopic dermatitis. BN (200 mg/kg, p.o.) significantly inhibited the scratching frequency in NC mice, and decreased the skin temperature by 1.97 degrees C. The cooling action on the skin by BN may be involved in the inhibitory mechanism of itch, at least in part, since cooling the skin is known to inhibit the itch sensation in humans. Although the myocyte-specific enhancer binding factor 2C (MEF2C) mRNA is known to be increased in the cerebral cortex correlated with the itch sensation and skin lesions in NC mice, BN did not affect the expression level of the MEF2C mRNA. This result suggests that the inhibitory effect of BN on itch does not relate to inhibition of MEF2C expression in the cerebral cortex. The present study indicates that BN has an inhibitory effect on itch, and may be a useful antipruritic drug for atopic dermatitis.

Animals↗

New applications of low-C0tDNA as a DNA fingerprint probe.

New applications of low-C0t DNA are reported as probes for genetic identification and genome characterization. These fast and intermediately reannealing fractions have sometimes either been discarded in genomic library construction to enhance the probability of finding single copy genes, or they are used as resources for identifying individual repetitive sequences. In addition, they are used as blockers to enhance hybridization signals. C0t-1 DNA serves as a probe for DNA fingerprinting of human yeast artificial chromosomes. We have isolated low-C0t DNA from bacteria, fungus, plant, mussel, chicken, rat and fish from the sheared genomic DNA of the respective species. Low-C0t DNA is labeled to generate DNA fingerprints and for in situ hybridization. Individual specific DNA fingerprint profiles are observed and species-specific DNA fragments can be identified in bacteria, fungus, plants (Ginseng and Amaranthus) and mussel. When low-C0t DNA probes from rat, chicken and fish were employed, only smear profiles and no distinct DNA banding patterns were evident. In these species, individual clones can be used as a probe for DNA fingerprinting containing repetitive sequences after subcloning. The advantage of this approach is to quickly develop a useful probe for DNA fingerprinting for genetic identification and analysis without sequencing knowledge a priori. This represents an innovative approach to the use of these repetitive components of the genome.

Animals↗

Rapid identification of saponins in plant extracts by electrospray ionization multi-stage tandem mass spectrometry and liquid chromatography/tandem mass spectrometry.

Electrospray ionization multi-stage tandem mass spectrometry (ESI-MS(n)) and liquid chromatography coupled with on-line mass spectrometry (LC/MS/MS) were applied to characterize saponins in crude extracts from Panax ginseng. The MS(n) data of the [M - H](-) ions of saponins can provide structural information on the sugar sequences of the saccharide chains and on the sapogins of saponins. By ESI-MS(n), non-isomeric saponins and isomeric saponins with different aglycones can be determined rapidly in plant extracts. LC/MS/MS is a good complementary analytical tool for determination of isomeric saponins. These approaches constitute powerful analytical tools for rapid screening and structural assignment of saponins in plant extracts.

Chromatography, Liquid↗

The ameliorating effects of the cognitive-enhancing Chinese herbs on scopolamine-induced amnesia in rats.

Ameliorating effects were investigated of the cognitive-enhancing Chinese herbs administered orally for 1 week-Panax ginseng (PG), Panax notoginseng (PNG), Dioscorea opposita (DO), Gastrodia elata (GE), Salvia miltiorrhiza (SM), Acorus gramineus (AG), Coptis chinensis (CC), Polygonum multiflorum (PM), Cyperus rotundus (CR) and Psoralea corylifolia (PC)-on the scopolamine (SCOP)-induced amnesia by using a passive avoidance task in rats. Of ten Chinese herbs, only PG, PNG, GE and CC prolonged the SCOP-shortened STL. These results revealed that PG, PNG GE and CC administered orally for 1 week improved the SCOP-induced learning and memory deficit in rats.

Administration, Oral↗

Herbal medicines for viral myocarditis.

BACKGROUND: Herbal medicines are being used for treating viral diseases including viral myocarditis, and many controlled trials have been done to investigate their efficacy. OBJECTIVES: To assess the effects of herbal medicines on clinical and indirect outcomes in patients with viral myocarditis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library 2003, Issue 3, MEDLINE (January 1966 to October 2003), EMBASE (January 1998 to October 2003), Chinese Biomedical Database (1979-2003), AMED (1985-2003), LILACS accessed in October 2003 and the trials register of the Cochrane Complementary Medicine Field. We handsearched Chinese journals and conference proceedings. No language or publication restrictions were used. SELECTION CRITERIA: Randomised controlled trials of herbal medicines (with a minimum of seven days treatment duration) compared with placebo, no intervention, or conventional interventions were included. Trials of herbal medicine plus conventional drug versus drug alone were also included. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and evaluated trial quality. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Forty randomised trials, involving 3448 people were included. All trials were conducted and published in China, and the methodological quality was assessed as generally low. No trial had diagnosis of viral myocarditis confirmed histologically, and few trials attempted to establish viral aetiology for the myocarditis. Twenty-five different herbal medicines were tested in the included trials, which compared herbs with supportive therapy (17 trials), other controls (three trials), or treatment of herbs plus supportive therapy with supportive therapy alone (20 trials). The trials reported electrocardiogram, myocardial enzymes, cardiac function, symptoms, and adverse effects. Astragalus membranaceus (either as single herb or compound of herbs) showed significantly effects on improving arrhythmia, CPK levels, and cardiac function. Salviae miltiorrhizae injection showed significant effects on decreasing the arrhythmia and reducing LDH levels. Shenmai and Shengmai injection (Ginseng preparation) showed significantly effects on reducing myocardial enzymes and improving cardiac function. No serious adverse effect was reported. REVIEWERS' CONCLUSIONS: Some herbal medicines may have anti-arrhythmia effect in suspected viral myocarditis. However, interpretation of these findings should be careful due to the low methodological quality, small sample size, and limited number of trials on individual herbs. In the light of the findings, some herbal medicines deserve further examination in rigorous trials.

Drugs, Chinese Herbal↗

Enhancement of insulin sensitivity in adipocytes by ginger.

Antidiabetic and hypoglycemic drugs have been reported to enhance adipocyte differentiation of 3T3-L1 preadipocytes. We previously reported that ginseng (active constituents: ginsenosides) enhanced the differentiation [1]. In this experiment, effect of some ginger group food extracts on the adipocyte differentiation was investigated using cultured mouse 3T3-L1 preadipocytes. 3T3-L1 cells were grown as monolayer cultures at 37 degrees C in DMEM supplemented by 10% FBS under the atmosphere of 5% CO(2)-95% air. Ginger extracts were found to enhance the adipocyte differentiation. Active constituent was purified and identified as gingerol. In the gingerol-treated cells, insulin-sensitive glucose uptake was increased. It is expected that ginger enhance the insulin-sensitivity, and improve chronic disease, such as diabetes.

3T3 Cells↗

The immunomodulator ginsan induces resistance to experimental sepsis by inhibiting Toll-like receptor-mediated inflammatory signals.

Ginsan, a polysaccharide extracted from Panax ginseng, has multiple immunomodulatory effects. In this study, we show that pretreatment of ginsan (25 mug/kg) protected mice from lethality induced by Staphylococcus aureus challenge. This survival benefit was associated with enhanced bacterial clearance from circulation, spleen and kidney. The phagocytic activity of macrophages treated with ginsan was significantly enhanced against S. aureus. However, the production of proinflammatory cytokines, such as TNF-alpha, IL-1beta, IL-6, IFN-gamma, IL-12, and IL-18, was markedly down-regulated in ginsan-treated mice compared with those of control-infected mice. The expression of Toll-like receptor (TLR) 2 and the adaptor molecule MyD88, which was greatly increased in septic macrophages, was significantly reduced by ginsan treatment in vitro. Similarly, the expression of phospho-JNK1/2, phospho-p38 MAPK, and NF-kappaB was decreased in the same culture system. These results illustrate that the antiseptic activity of ginsan can be attributed to enhanced bacterial clearance, and reduced proinflammatory cytokines via the TLR signaling pathway.

Adaptor Proteins, Signal Transducing↗

A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.

Hormone-related supplements (HRS), many of which contain phytoestrogens, are widely used to manage menopausal symptoms, yet their relationship with breast cancer risk has generally not been evaluated. We evaluated whether use of HRS was associated with breast cancer risk, using a population-based case-control study in 3 counties of the Philadelphia metropolitan area consisting of 949 breast cancer cases and 1,524 controls. Use of HRS varied significantly by race, with African American women being more likely than European American women to use any herbal preparation (19.2% vs. 14.7%, p=0.003) as well as specific preparations including black cohosh (5.4% vs. 2.0%, p=0.003), ginseng (12.5% vs. 7.9%, p<0.001) and red clover (4.7% vs. 0.6%, p<0.001). Use of black cohosh had a significant breast cancer protective effect (adjusted odds ratio 0.39, 95% CI: 0.22-0.70). This association was similar among women who reported use of either black cohosh or Remifemin (an herbal preparation derived from black cohosh; adjusted odds ratio 0.47, 95% CI: 0.27-0.82). The literature reports that black cohosh may be effective in treating menopausal symptoms, and has antiestrogenic, antiproliferative and antioxidant properties. Additional confirmatory studies are required to determine whether black cohosh could be used to prevent breast cancer.

Black or African American↗

Hypothalamic neuronal histamine modulates adaptive behavior and thermogenesis in response to endogenous pyrogen.

Homeostatic involvement of hypothalamic neuronal histamine in adaptive behavior and thermogenesis was investigated when interleukin-1 beta (IL-1 beta), one of the endogenous pyrogens, was infused peripherally in rats. IL-1 beta decreased food and water intake and elevated body temperature. Depletion of neuronal histamine in the hypothalamus induced by alpha-fluoromethylhistidine, a suicide inhibitor of the histamine synthesizing enzyme histidine decarboxylase (HDC), attenuated the suppressive effect of IL-1 beta on food intake, facilitated the inhibitory effect on water intake, and enhanced its thermogenic effect. Simultaneously IL-1 beta increased activity of HDC and histamine-N-methyltransferase (HMT), a neuronal histamine catabolizing enzyme. Pretreatment with indomethacin completely blocked those increases in turnover of neuronal histamine induced by IL-1 beta. Hypothalamic prostaglandin E2 (PGE2) activated by peripheral IL-1 beta, but not peripheral PGE2, increased both activities of HDC and HMT. Ginsenoside Rg1, a major component of panax ginseng, modulated the suppressive effects of IL-1 beta on ingestive behavior, resulting in a lowering of body temperature. The findings suggest that the effects of IL-1 beta on ingestive behavior and thermogenesis may be modulated by dynamics of hypothalamic neuronal histamine through activation of hypothalamic PGE2 which is elevated by peripheral IL-1 beta.

Adaptation, Physiological↗

A capsule review of recent studies on the application of mass spectrometry in the analysis of Chinese medicinal herbs.

Chinese herbal medicine is gaining increasing popularity worldwide as an alternative approach to the development of pharmaceuticals in therapeutic applications. Chemical characterization and compositional analysis of Chinese medicines provide the necessary scientific basis for the discovery and development of new drugs of natural origin. Applications of mass spectrometry in the analysis of Chinese herbal medicines have been growing rapidly in recent years owing to the rapid technical advances and increasing availability of the instrumentation. This paper reviews the current status of how different mass spectrometric techniques are being used to support research studies of Chinese medicines. The focus is on crude herbal medicines and their derived products. The review is not meant to be exhaustive, but rather to provide a general overview of the various research activities in this rapidly expanding field. In the discussion of specific herbs, the emphasis is placed on ginseng and Danshen, two of the herbs for which active experimental work is on-going in the authors' laboratories. Other selected herbs will be discussed only briefly, aiming primarily to illustrate the current status of research in the area.

DNA Fingerprinting↗

Ginsenoside Re promotes human sperm capacitation through nitric oxide-dependent pathway.

The regulation of sperm capacitation is important for successful fertilization. Ginsenosides, the biologically effective components of ginseng, have been found to enhance intracellular nitric oxide (NO) production and the latter has recently been indicated to play a significant role in modulation of sperm functions. We investigated the effect of Ginsenoside Re on human sperm capacitation in vitro and the mechanism by which the Ginsenosides play their roles. Spermatozoa were separated by Percoll and incubated with 0, 1, 10, or 100 microM of Ginsenoside Re. The percentages of spontaneous and lysophosphatidylcholine (LPC)-induced acrosome reaction (AR), as a measure of sperm capacitation, were assayed with fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA). The intracellular cGMP level was measured by [(3)H] cGMP radioimmunoassay system. The results showed that the percentages of both spontaneous and LPC-induced AR and intracellular cGMP level were significantly enhanced by Ginsenoside Re with a concentration-dependent manner. Sodium nitroprusside (SNP, 100 nM), a NO donor, mimicked the effects of Ginsenoside Re. And pretreatment with a NOS inhibitor N(omega)-nitro-l-arginine methyl ester (L-NAME, 100 microM) or a NO scavenger N-acetyl-l-cysteine (LNAC, 1 mM) completely blocked the effects of Ginsenoside Re. Furthermore, the AR-inducing effect of Ginsenoside Re was significantly reduced in the presence of the soluble guanylate cyclase inhibitor LY83583 or cGMP-dependent protein kinase (PCK) inhibitor KT5823, whereas addition of the cGMP analogue 8-Br-cGMP significantly increased the AR of human spermatozoa. Data suggested that Ginsenoside Re is beneficial to sperm capacitation and AR, and that the effect is accomplished through NO/cGMP/PKG pathway.

Acrosome Reaction↗

Adaptogenic activity of a novel withanolide-free aqueous fraction from the roots of Withania somnifera Dun. (Part II).

In the Indian traditional system of medicine Withania somnifera Dun. is widely regarded as the Indian Ginseng. A new withanolide-free hydrosoluble fraction was isolated from the roots of Withania somnifera Dun. and was evaluated for putative antistress activity against a battery of tests to delineate the activity of this fraction. The latter fraction exhibited significant antistress activity in a dose-related manner (Singh et al., 2001) and was further studied against chemical and physical induced stress in rats and mice. The extract of Withania somnifera root (a commercial preparation available locally) was also used to compare the results. A preliminary acute toxicity study in mice showed a good margin of safety with a high therapeutic index.

Adjuvants, Immunologic↗