Research Database –
International Updates

Herbal Medicine

Issue 93

FLICKER and colleagues, Biology Department, Carleton University, Ottawa, Ontario, Canada, report on the inhibition of human pathogenic fungi by ethnobotanically selected plant extracts.
Background: Many fungi that cause pathology in humans are becoming resistant to the commonly used fungicidal agents, amphotericin B and ketoconazole. The screening of plants for antifungal activity can provide a solution to this problem, at least for a while.
Methods: 36 extracts derived from 29 plant species selected using an
ethnobotanical approach were tested for antifungal activity against 13 human pathogenic fungi and compared to the activities of amphotericin B and ketoconazole, and the plant-derived antifungal, berberine.
Results: Several plant extracts showed antifungal activity. The most powerful ones were extracts of ginger and butternut (Juglans cinerea) that displayed antifungal activity against a wide variety of fungi some of which were highly resistant to amphotericin B and ketoconazole.
Conclusions: Further exploration of Zingiber officinale, or ginger, as an antifungal agent is warranted, especially as this plant is generally regarded as safe for human consumption.
Ficker CE, Arnason JT, Vindas PS, Alvarez LP, Akpagana K, Gbeassor M, de Souza C, Smith ML. Inhibition of human pathogenic fungi by ethnobotanically selected plant extracts. Mycoses 46 (1-2): 29-37, Feb 2003.

TEWTRAKUL and co-workers, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan, have described HIV-1 integrase inhibitory substances from the plant Coleus parvifolius.
Background: The enzyme HIV-1 integrase is essential for the replication of human immunedeficiency virus (HIV-1). Thus any natural compound that inhibits the activity of this enzyme can be expected to have the effect of inhibiting the spread of HIV.
Methods: Extracts from 50 Thai plants were screened for their inhibitory activity against HIV-1 integrase in vitro.
Results: An alcoholic extract of Coleus parvifolius Benth. showed potent activity against the HIV enzyme. From this extract, 11 different chemical compounds were isolated and identified. Of these, 4 showed inhibitory activity against the enzyme in the micromolar range.
Conclusions: The Thai plant, Coleus parvifolius, has the potential for anti-HIV activity.
Tewtrakul S, Miyashiro H, Nakamura N, Hattori M, Kawahata T, Otake T, Yoshinaga T, Fujiwara T, Supavita T, Yuenyongsawad S, Rattanasuwon P, Dej AS. HIV-1 integrase inhibitory substances from Coleus parvifolius. Phytotherapy Research 17 (3): 232-239, Mar 2003.

WILASRUSMEE and colleagues, Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, USA, kittur@upstate.edu, have shown an immunostimulatory effect of milk thistle extract.
Background: Many herbal products are used for their effects on the immune system. Milk thistle is known to inhibit the growth of certain tumours, although the mechanism of this action remains unknown. The authors have previously shown that milk thistle extracts stimulate
neurones in culture. Since other drugs that affect nerve cells tend to affect the immune system as well, the effects of milk thistle extracts on the immune system were investigated.
Methods: Standardized milk thistle extract was used in a mouse lymphocyte proliferation assay in vitro. All tests were performed in triplicate and carried out twice.
Results: Milk thistle is immunostimulatory in vitro. Lymphocyte proliferation was consistently increased. The effect was associated with an increase in interferon-gamma, interleukin-4 and interleukin-10. The effect increased in a dose-dependent manner.
Conclusions: This study has shown a novel effect of milk thistle on the immune system. It may be of benefit in increasing immunity to infectious diseases.
Wilasrusmee C, Kittur S, Shah G, Siddiqui J, Bruch D, Wilasrusmee S, Kittur DS. Immunostimulatory effect of Silybum Marianum (milk thistle) extract. Medical Science Monitor 8 (11): BR439-BR443, Nov 2002.
Comment: The above research demonstrates the powerful role that herbal medicines can play in treating serious, life-threatening diseases such as HIV, as well as their utility in the more practical applications, i.e. anti-fungals and immune-enhancement properties.

Issue 92

CHAINANI, Department of Stomatology, University of California, San Francisco, CA 9443-0658, USA, nitacwu@itsa.ucsf.edu, reviews (42 references) the safety and anti-inflammatory activity of curcumin, a component of turmeric.
Background: Turmeric, a spice from the root of Curcuma longa, has long been used in Ayurvedic medicine for various indications. The goal of this review is to summarize the available literature on the safety and anti-inflammatory activity of curcumin, its main component.
Methods: A search was conducted of Medline and the internet using multiple search engines. Reference lists of articles found on Medline were searched by hand. In addition, the PDR for Herbal Medicines and four textbooks on herbal medicine and their bibliographies were searched.
Results: Studies of curcumin included studies of the antioxidant, anti-inflammatory, antiviral, and antifungal properties of curcumoids. Studies on the toxicity and anti-inflammatory properties of curcumin included in vitro, animal, and human studies. A human trial with 25
subjects using up to 8,000 mg of curcumin per day for 3 months found no toxicity. Five other human trials of lower doses confirmed this. These studies found some evidence of anti-inflammatory action of curcumin, Laboratory studies have identified a number of molecules involved in inflammation that are inhibited by curcumin, amongst them phospholipases, lipoxygenase, cyclo-oxygenase 2, leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1, interferon-inducible protein, tumour necrosis factor, and interleukin-12.
Conclusions: Curcumin has been shown to be safe in six human trials. It may exert anti-inflammatory action by inhibiting a number of molecules involved in inflammatory processes.
Chainani WN. Safety and anti-inflammatory activity of curcumin: a componenet of tumeric (Curcuma longa). The Journal of Alternative and Complementary Medicine 9 (1): 161-168, Feb 2003.

TESCH, Division of General Internal Medicine, Medical College of Wisconsin, Milwaukee 53236, USA, has reviewed (184 references) the herbs commonly used by women.

Background: The objective of the paper was to review the herbs used by women.
Methods: Articles were located by searching Medline, the Cochrane Database of Systemic Reviews, and the Combined Health Information Database, and by hand searching the reference lists of recent systematic reviews. Databases were searched using the latin and common names for each herb. Preference was given to randomized controlled trials.
Results: Many women use herbal medicines, and many prospective randomized controlled trials are being funded. Gingko biloba seems to slow the progression of dementia but increases the risk of bleeding. St John’s Wort is efficient for the treatment of mild to moderate depression but has many drug interactions. Ginseng improves wellbeing in perimenopausal women but is often impure and has side effects and interactions. Garlic slightly lowers blood pressure and lipids. Echinacea slightly decreases the duration of colds but does not prevent them. Valerian is beneficial for insomnia but long-term safety data are lacking. Black cohosh may help the symptoms of menopause, and chasteberry may improve premenstrual syndrome. More study is needed on both herbs.
Conclusions: Some herbs are medically useful, but the public would benefit from more regulation.
Tesch BJ. Herbs commonly used by women: an evidence-based review. American Journal of Obstetrics and Gynecology 188 (5 Suppl): S44-S55, May 2003.

Issue 90

BARRETT, Department of Family Medicine, University of Wisconsin Medical School, Medison WI 53715, USA, bbarrett@wisc.edu, has critically reviewed (172 references) the medicinal properties of Echinacea.
Abstract: Preparations of Echinacea purpurea are among the most commonly used herbal medicines, and are generally used for enhancing immune function. Experiments have demonstrated numerous immunomodulatory effects of E. purpurea extracts such as macrophage activation, activation of polymorphonuclear leucocytes and natural killer cells, and changes in the numbers and activities of B- and T-cell lymphocytes. Despite this cellular and molecular evidence, pathways leading to enhanced resistance to disease have not been
adequately described. A number of randomized blinded trials have reported health benefits from E. purpurea extracts, particularly for upper respiratory tract disease. However these trials are limited in size and methodological quality although they suggest modest benefit. The author concludes that while there is a great deal of data showing effects of Echinacea in the immune system, it has not yet been proven beyond reasonable doubt that Echinacea treats illness or enhances health in human beings.
Barrett B. Medicinal properties of Echinacea: a critical review. Phytomedicine 10 (1): 66-86, Jan 2003.

ERGIN and ARIKAN, University of Hacettepe, School of Health Services, Department of Microbiology and Clinical Microbiology, Ankara, Turkey, have compared two different in vitro methods for assessing the activity of tea tree oil against vaginal Candida as compared with the drug, fluconazole.
Background: The aim of the study was to test the activity of fluconazole and Melaleuca alternifolia (tea tree) oil against 99 vaginal Candida strains by two different methods.
Methods: The broth microdilution method and the disc diffusion method were performed according to standard protocols.
Results: Fluconazole had significantly higher Minimal Inhibitory Concentrations (MICs) against two of the strains, C. krusei and C. norvegensis, than the others. Tea tree oil was found to be effective against all strains tested in concentrations ranging between 0.25% and 4% at 24 hours.
Conclusions: Tea tree oil was effective against 99 strains of vaginal Candida. Its basically unaltered effectiveness against fluconazole- resistant strains is of particular interest.
Ergin A, Arikan S. Comparison of microdilution and disc diffusion methods in assessing the in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil against vaginal Candida isolates. Journal of Chemotherapy 14 (5): 465-472, Oct 2002.
Comment: In view of the increasingly difficult problems of antibiotic resistance, these results with Tea Tree ought to be widely disseminated, particularly since Tea Tree remained effective against fluconazole-resistant strains.

Issue 89

KOH and colleagues, Department of Dermatology, Flinders Medical Centre, Bedford Park, South Australia, Australia, have found that tea tree oil reduces histamine-induced skin inflammation.
Background: Tea tree oil, the distillate from Melaleuca alternifolia, has become increasingly popular as an antimicrobial agent for the treatment of conditions such as Tinea pedis and acne. The object of this study was to investigate the anti-inflammatory properties of tea tree oil on
histamine-induced weal and flare.
Methods: 27 volunteers were injected intradermally in both forearms (study and control sides assigned on an alternating basis) with histamine diphosphate (5 micrograms in 50 microlitres). Flare and weal diameters and double skin thickness were measured every 10 min for an hour to calculate flare area and weal volume. At 20 min, 25 microlitres of 100% tea tree oil were applied topically to one forearm of 21 volunteers. In six volunteers, the same amount of paraffin oil was applied instead.
Results: Application of liquid paraffin had no effect on histamine-induced weal and flare. There was also no significant difference in flare area between control arms and those treated with tea tree oil. However mean weal volume significantly decreased after the application of tea tree oil within 10 minutes (p = 0.0004).
Conclusions: This is the first study to show experimentally that tea tree oil can reduce histamine-induced skin inflammation.
Koh KJ, Pearce AL, Marshman G, Finlay-Jones JJ, Hart PH. Tea tree oil reduces histamine-induced skin inflammation. The British Journal of Dermatology 147 (6): 1212-1217, Dec 2002.

KITTUR and colleagues, Department of Neurology, SUNY Upstate Medical University, Syracuse, NY 13210, USA, kitturs@upstate.edu, habe investigated neurotrophic and neuroprotective effects of milk thistle on neurones in culture.
Background: Herbal medicines are used as dietary supplements or therapeutic agents. However the understanding of the biological basis of the clinical effects of such products is often poor. This study attempts to help fill that gap.
Methods: The effects of milk thistle (Silybum marianum) on the differentiation and survival of cultured neural cells were measured.
Results: Milk thistle enhanced Nerve Growth Factor (NGF)-induced neurite outgrowth in PC-12 neural cells and prolonged their survival in culture. It also protected cultured rat hippocampal neurones against oxidative stress induced cell death.
Conclusions: These data demonstrate that milk thistle extract can
promote neuronal differentiation and survival, suggesting potential benefits of chemicals contained in this plant for the nervous system.
Kittur S, Wilasrusmee S, Pedersen WA, Mattson MP, Straube-West K, Wilasrusmee C, Lubelt B, Kittur DS. Neurotrophic and neuroprotective effects of milk thistle (Silybum marianum) on neurons in culture. Journal of Molecular Neuroscience 18 (3): 265-269, Jun 2002.

TESCH has reviewed (183 references) the herbs commonly used by women.
Background: The aim of the review is to study the evidence for herbs commonly used by women.
Methods: Articles were identified by searching MedLine, the Cochrane Database of Systemic Reviews, and the Combined Health Information Database as well as searching by hand. Preference was given to randomized controlled trials.
Results: Many women use herbal medicines, and many prospective randomized controlled trials are funded. Gingko biloba slows the progression of dementia but increases the risk of bleeding. St John’s Wort is effective in the treatment of mild to moderate depression but has many drug interactions. Ginseng improves wellbeing in perimenopausal women but has side effects and drug interactions. Garlic slightly lowers blood pressure and lipids. Echinacea decreases the duration of colds but does not prevent them. Valerian is beneficial for insomnia; long-term safety data are lacking. Black cohosh may help the symptoms of menopause, and chasteberry may improve premenstrual symptoms.
Conclusions: Some herbs are medically useful, but the American public would benefit from improved regulation. Manufacturers should be able to ensure that herbs contain pure ingredients. Side effects and drug interactions need to be listed. Well-designed studies are being conducted, and the results will be helpful to physicians and patients.
Tesch BJ. Herbs commonly used by women: an evidence-based review. Disease-a-month 48 (10): 671-696, Oct 2002.

Issue 88

ALBERT and colleagues, Institute of Pharmaceutical Chemistry, University of Frankfurt, D-60439 Frankfurt, Germany, found that hyperforin is a dual inhibitor of cyclo-oxygenase 1 and 5-lipoxygenase.
Background: 5-lipoxygenase (5-LO) and cyclo-oxyghenase (COX) are key enzymes in the formation of pro-inflammatory eicosanoids. The aim of this study was to determine if the main fat-soluble component of St John’s Wort (Hypericum perforatum), hyperforin, can suppress the activity of these enzymes.
Methods: The activities of 5-LO and COX were measured in freshly isolated human polymorphonuclear leukocytes stimulated with the calcium-ionophore A23187.
Results: Hyperforin inhibited the activity of 5-LO with IC(50) values of about 1-2 micromolar. It also inhibited isolated 5-LO. The effective doses are comparable to the well-known 5-LO inhibitor zileuton (IC(50) = 0.5-1 micromolar). Hyperforin also suppressed the activity of COX-1 with an IC(50) of about 90 nanomolar or 3 to 18 times more efficiently than aspirin. Hyperforin had no effect on COX-2, 12-LO or 15-LO.
Conclusions: Hyperforin acts as a dual inhibitor of 5-LO and COX-1, suggesting therapeutic potential of St John’s Wort in inflammatory and allergic diseases connected to eicosanoids.
Albert D, Zuendorf I, Dingermann T, Mueller WE, Steinhilber D, Werz O. Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochemical Pharmacology 64 (12): 1767-1775, Dec 15, 2002.

FAHEY and STEPHENSON, The Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland 21205, USA, jfahey@jhmi.edu, described pinotstrobin from honey and Thai ginger, a flavonoid inducer of antioxidant enzymes.
Background: An assay was developed to measure the ability of extracts from different types of honey to induce mammalian phase 2 detoxification enzymes, notably quinone reductase (QR). The assay was further used to test natural and synthetic inducers from plants.
Methods: Mouse hepatoma cells on microtiter plates were used for the quantification of quinone reductase activity.
Results: Of 35 different honeys, all elevated QR activity ranging from 153 to 2155 units/g. The amount of prominent flavonoids found in honey required to double QR activity was determined to be 0.5 micromolar for pinostrobin; 110 micromolar for pinocambrin; and 25 micromolar for chrysin. This compares very favourably to the amounts of more commonly described flavonoids such as quercetin (2.7 micromolar) and myricetin (58 micromolar). Subsequently, a bioassay-guided search was conducted which revealed a very rich source of pinostrobin, Boesenbergia pandurata (Thai ginger or fingerroot). The potency of fingerroot rhizomes to induce QR is about 110,000 units/g which makes it even higher than broccoli.
Conclusions: The potency of fingerroot oils and powdered rhizomes rivals that of broccoli sprouts, elevating the activity of quinone reductase by about 500,000 units per gram.
Fahey JW, Stephensoon KK. Pinostrobin from honey and Thai ginger (Boesenbergia pandurata): a potent flavonoid inducer of mammalian phase 2 chemoprotective and antioxidant enzymes. Journal of Agricultural and Food Chemistry 50 (25): 7472-7476, Dec 4, 2002.

Comments: The above 3 detailed biochemical studies regarding herbal medicines honey, ginger and St John’s Wort demonstrates the potential of herbal medicines as antioxidants.

GONG and SUCHER, Department of Biology and Biotechnology Research Institute, Hong Kong University of Science and Technology, Kowloon, Hong Kong SAR, China, reviewed (39 references) stroke therapy in traditional Chinese medicine and its prospects for the discovery and development of new drugs.
Background: Brain injuries resulting from stroke are a major and increasing public health problem worldwide. China’s long experience in traditional Chinese medicine (TCM) in stroke therapy indicates that TCM preparations are effective and safe.
Results and conclusions: There are more than 100 traditional medicines used for stroke therapy in China. Some of their effects have been confirmed in recent clinical studies. A large number of chemical compounds have been isolated from TCMs most of which have not yet been characterized in terms of their pharmaceutical potential. This article explains how TCM provides an extensive and well-informed foundation for implementing a strategically focused pharmacological research programme aimed at the development of new drugs.
Gong X, Sucher NJ. Stroke therapy in traditional Chinese medicine (TCM): prospects for drug discovery and development. Phytomedicine ( (5): 478-484, Jul 2002.

Comments: As detailed in Stroke Disease and Approaches to Rehabilitation by PaTrisha Anne (see page 37), approaches to rehabilitation including Traditional Chinese Medicine are greatly required.

Issue 87

BEAN, Rogers Memorial Hospital, Oconomowac, WI, USA, pambean@charter.net, reviewed (14 references) the use of alternative medicine in the treatment of Hepatitis C.
Background: More than a third of Americans use herbs for health purposes. Patients and physicians usually lack accurate information about the safety and efficacy of herbal remedies. The author advocates keeping an open mind to the possibility that some of these remedies may be beneficial.
Results and conclusions: Silymarin extract from milk thistle is most widely prescribed for liver diseases. Its beneficial effects are most often seen in patients suffering from cirrhosis of the liver as a result of excess alcohol consumption. An ongoing clinical trial will show whether there are any benefits for Hepatitis C. The safety record of this preparation is good.
The active component of liquorice root has been shown to inhibit immune-mediated liver cytotoxicity and may indicate some function in Hepatitis C treatment. Finally, St John’s Wort and ginger are used by some patients to alleviate side effects associated with interferon treatment.
Bean P. The use of alternative medicine in the treatment of hepatitis C. American Clinical Laboratory 21 (4): 19-21, May 2002.

BARAK et al., Immunology Laboratory for Tumor Diagnosis, Department of Oncology, Hadassah University Hospital, Jersualem, Israel, barak845@yahoo.com, investigated the effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines in monocytes.
Background: Some herbal remedies are believed to have immune-enhancing properties. The aim of this study was to investigate the effect of five commonly used herbal remedies, all claimed to be immune-enhancers, on the production of cytokines, one of the main components of the immune system.
Methods: The production of four inflammatory cytokines (interleukin-1 (IL-1) beta, tumor necrosis factor (TNF) alpha, IL-6 and IL-8) and one anti-inflammatory cytokine (IL-10) in blood-derived monocytes from 12 healthy donors was measured in response to the following 5 herbal remedies: Sambucol Black Elderberry Extract, Sambucol Active Defense Formula, Sambucol for Kids, Protec, and Chizukit N (containing propolis and Echinacea).
Results: The Sambucol products increased production of the five cytokines compared to controls. Protec induced only a moderate production of IL-8 and IL-10. Chizukit caused only a moderate increase in IL-10 production. Both Protec and Chizukit caused moderate decreases in IL-1 beta, TNF alpha, and IL-6 production. Lipopolysaccharide, a known activator of monocytes, induced the highest levels of cytokine production.
Conclusions: The three Sambucol formulations activate the healthy immune system by increasing inflammatory and anti-inflammatory cytokine production. The effect of Protec and Chizukit is much less. Sambucol could have immunostimulatory properties for patients suffering from influenza, or for immunodepressed cancer or AIDS patients.
Barak V, Berkenfeld S, Halperin T, Kalickman I. The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines. The Israel Medical Association Journal 4 (11S): 919-922, Nov 2002.

Issue 86

BRAND and colleagues, Department of Microbiology and Infectious Diseases, School of Medicine, Flinders Medical Research Institute, Flinders University, Adelaide, Australia, report that tea tree oil reduces the swelling associated with the efferent phase of a contact hypersensitivity response.

Background: The object of this study was to examine the anti- inflammatory properties of tea tree oil in mice.

Methods: Mice were sensitized to the chemical trinitrochlorobenzene on their ventral skin. 7 days later, they were re-exposed to the same chemical on the dorsal skin.

Results: Tea tree oil applied 30 minutes before or up to 7 hours after to the same site as the chemical caused significant reduction in skin swelling after one day. Tea tree oil reduced oedema but not the influx of inflammatory cells. This finding is supported by the inability of tea tree oil to suppress TNF alpha-induced E-selectin expression in human umbilical vein endothelial cells.

Conclusions: Topical tea tree oil can regulate the efferent phase of a contact hypersensitivity response.

Brand C,Grimbaldeston MA, Gamblle JR, Drew J, Finlay-Jones JJ, Hart PH, et al. Tea tree oil reduces the swelling asociated with the efferent phase of a contact hypersensitivity response. Inflammation Research 51 (5): 236-244, May 2002.

JACOBS and colleagues, Department of Medicine, University of California, San Francisco 94143, USA, jacobsb@ocim.ucsf.edu, review and meta- analyze milk thistle in the treatment of liver disease.

Background: Milk thistle is taken most frequently by patients with chronic liver disease. The purpose of this review is to determine the safety and efficacy of this treatment.

Methods: Reports through to 1999 were searched using 13 databases and reference lists, and contacting manufacturers and technical experts. All reports were screened for randomized controlled trials that evaluated milk thistle in the treatment of liver disease. Outcomes included mortality, histological findings on liver biopsy specimens, serum aminotransferase and serum albumin levels, and prothrombin times.

Results: 14 trials met inclusion criteria. The overall summary odds ratio for mortality in the milk thistle group compared to placebo was 0.8 (p = 0.6). There were no differences found in either histological findings or biochemical parameters. The frequency of adverse effects was low and indistinguishable from placebo.

Conclusions: Treatment with milk thistle appears to be safe and well tolerated. However this study finds no evidence for beneficial effects in terms of histological findings or markers of liver function. Data are too limited to exclude a substantial benefit or harm of milk thistle on mortality, and also to recommend this herbal compound for the treatment of liver disease.

Jacobs BP, Dennehy C, Ramirez G, Sapp J, Lawrence VA, et al. Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. The American Journal of Medicine 113 (6): 506-515, Oct 2002.

MITRA and co-workers, Department of Payachikitsa, Institute of Post Graduate Ayurvedic Education and Research, Calcutta 700 009, India, describe the chemical constituents and antioxidant activity of the Ayurvedic drug, Swarnabhasma (gold ash).

Background: Since ancient times Swarmabhasma has been used to treat many degenerative conditions. Ayurvedic physicians use it to treat diseases like bronchial asthma, rheumatoid arthritis, diabetes mellitus, and nervous disorders.

Methods: Swarmabhasma was prepared according to Ayurvedic pharmacy.

Results: The gold ash consisted of Realgar (Arsenous sulphide), lead oxide, pure gold, and latex. Qualitative analysis showed the presence of several microelements such as Fe, Al, Cu, Zn, Co, Mg, Ca, As, Pb. The material was free from organic compounds. Oral administration showed no mortality in mice in acute doses of up to 1 ml/20 g using a Swarmabhasma suspension containing 1 mg of the drug. Chronic administration also showed to toxicity as judged by SGPT, SGOT, serum creatinine and serum urea levels. Animals treated chronically with Swarmabhasma showed significantly increased activity of superoxide dismutase and catalase, two enzymes that reduce free radical concentration in the body.

Mitra A, Chakraborty S, Auddy B, Tripathis P, Sen S, Saha AV, Mukherjee B, et al. Evaluation of chemical constituents and free-radical scavenging activity of Swarmaghasma (gold ash), and ayurvedic drug. Journal of Ethnopharmacology 80 (2-3): 147-153, May 2002.

WILASRUSMEE and colleagues, Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, USA, conducted an in vitro investigation of immunomodulatory effects of herbal products.

Background: The effect of herbal products on immune response has not been investigated. Because these products can affect the host immune system, they may induce either rejection of tolerance after a transplant procedure.

Methods: In vitro lymphocyte proliferation tests were performed using phytohaemagglutinin, mixed lymphocyte culture assay, and interleukin-2 and interleukin-10 production. 10 commonly used herbal products were assessed for their effects.

Results: Dong quai, ginseng, and milk thistle had nonspecific immunostimulatory effects. Ginger and green tea had immunosuppressive effects. The immunosuppressive effect of ginger and green tea was mediated through a decrease in interleukin-2 production.

Conclusions: Green tea, dong quai, ginseng, milk thistle, and ginger have effects on in vitro immunoassays that may be relevant to patients who have had transplants.

Wilasrusmee C, Siddiqui J, Bruch D, Wilasrusmee S, Kittur S, Kittur DS et al. In vitro immunomodulatory effects of herbal products. The American Surgeon 68 (10): 860-864, Oct 2002.

Issue 85

MCCULLOCH and colleagues, Pine Street Clinic, San Anselmo, CA, USA, analyze Chinese herbal medicine and interferon in the treatment of chronic hepatitis B.

Background: This meta-analysis was performed in order to evaluate the effectiveness of Chinese herbal medicine alone or in combination with interferon-alpha in treating chronic hepatitis B.

Methods: TCMLARS, AMED, CISCOM, EMBASE, MEDLINE,and Cochrane Collaboration databases were searched and the articles’ bibliographies were handsearched.

Results: Chinese herbal medicine significantly reduced sero-reversion of HbsAg and was equivalent to interferon-alpha in sero-reversion of HbeAg and Hepatitis B virus DNA. Chinese herbal medicine combined with interferon-alpha significantly increased seor-reversion of HBsAg, HBeAg, and viral DNA. The Chinese herb active component bufotoxin combined with Interferon-alpha significantly increased HbeAg and viral DNA sero-reversion. The Chinese herb active component kurorinone was equivalent to interferon-alpha in sero-reversion of HbeAg and viral DNA.

Conclusions: Although the quality of existing studies is poor, the data nevertheless suggest that further studies of Chinese herbal medicine and interferon in chronic hepatitis B infection are justified.

Background: The aim of the study was to evaluate the effects of herbal extracts from plants commonly prescribed by traditional practitioners for typhoid fever.

Methods: Microbiological assays testing methanolic extracts of plant parts for antibacterial activity against Salmonella typhi, S. paratyphi, and S. typhimurium. Minimum Inhibitory Concentrations (MIC) and Minimum Bactericidal Concentrations (MBC) were measured. The extracts tested contained Cymbogogon citratus leaves, Carica papaya leaves and roots, Maize silk, Mangifera indica leaves, Citrus fruit, Emilia coccinea plant, Comelia bengalensis leaves, Telfaria occidentalis leaves, and Gossypium arboreum plant.

Results: The best results were obtained with an extract from C. citratus leaves, C. papaya leaves, and Maize silk. Equally a formulation of C. papaya roots, M. indica leaves, citrus fruit and C. citratus leaves inhibited bacterial growth at very low concentrations. The least active extract was from C. bengalensis leaves. S. papatyphi was the most sensitive bacterium and S. typhimurium the least sensitive.

Conclusions: These traditionally used herbal extracts exhibit antibacterial activity against several strains of bacteria causing typhoid fever.

Background: Women with chronic kidney disease are at increased risk of menstrual disorders, early menopause, and osteoporosis, but rarely discuss gynaecologic and reproductive issues with their nephrologists. Various CAM products are of interest to women who have these disorders. However little is known about the specifics of using herbal medicines in patients on chronic dialysis, resulting in numerous problems when patients and doctors try to ascertain the safety and efficacy of these products.

Results and Conclusions: The article reviews evidence regarding the safety and efficacy of black cohosh, ginseng, chastetree, dong quai, evening primrose oil, soy products, and the so-called natural hormones. Pharmacological parameters important to evaluating the quality of botanical products are discussed, along with recommendations and information resources.

Background: Chronic prostate inflammation is a very common and poorly understood condition. Conventional therapies such as antibiotics yield equivocal results. Patients often turn to herbal medicines and other alternative treatments. However few of those have been subjected to controlled clinical trials.

Methods: The therapies with published data are discussed. They include zinc, cernitin pollen extract (bee pollen), quercetin, saw palmetto (Serenoa repens), and acupuncture.

Results and Conclusions: Complementary therapies may indeed have something to offer to patients with a chronic degenerative condition like prostatitis. However these treatments require the same scientific criteria for validation as conventional medical ones.

Issue 84

MUR and colleagues, Department of Internal Medicine, Innsbruck University Hospital, Austria, erich.mur@uibk.ac.at, conducted a randomized, double-blinded trial of an extract from Uncaria tomentosa for the treatment of rheumatoid arthritis.

Methods: Randomized two-phase study involving 40 patients with rheumatoid arthritis on sulfasalazine or hydroxy-chloroquine treatment. In phase 1 (24 weeks, double-blinded, placebo controlled), patients were treated with either an extract from the pentacyclic chemotype of U. tomentosa or with placebo. In phase 2 (28 weeks), all patients received the plant extract. The number of painful joints and the number of swollen joints were assessed before treatment, at 24 weeks, and after treatment.

Results: At 24 weeks, the number of painful joints was decreased to 45% in the treatment group compared to placebo (p = 0.044). The patients who received the plant extract only in the second phase of the trial experienced a reduction in the number of painful joints (p = 0.003) and in the number of swollen joints (p = 0.004) compared to baseline. Only minor side effects were observed.

Conclusions: This preliminary study demonstrates relative safety and modest benefit of a highly purified extract from the pentacyclic chemotype of U. tomentosa in patients with active rheumatoid arthritis.

Mur E, Hartig F, Eibl G, Schirmer M. Randomized double blind trial of an extract from the pentacyclic chemotype of Uncaria tomentosa for the treatment of rheumatoid arthritis. The Journal of Rheumatology 29 (4): 678—681, Apr 2002.

SATCHELL et al., Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia, studied the treatment of tinea pedis [fungal infection of the feet] with 25% and 50% tea tree oil.

Background: Tea tree oil has been shown in vitro to be active against dermatophytes. The study aimed to confirm this in vivo.

Methods: Randomized, controlled, double-blinded trial on 158 patients with interdigital tinea pedis treated twice daily with either a placebo solution, a solution of 25% tea tree oil, or a solution of 50% tea tree oil. They were reviewed at 2 and 4 weeks of treatment.

Results: A marked clinical response was seen in the 50% tea tree group (68%), compared to 72% in the 25% tea tree group and 39% in the placebo group. The mycological cure rate after 4 weeks was 64% in the 50% tea tree group, compared to 31% in the placebo group. 3.8% of patients developed moderate to severe dermatitis on application of tea tree oil. This improved quickly after stopping the medication.

Conclusions: Tea tree oil has activity against dermatophytes in vivo as well as in vitro.

Satchell AC, Saurajen A, Bell C, Barnetson-Ross SC. Treatment of interdigital tinea pedis with 25% and 50% tea tree oil solution: a randomized, placebo-controlled, blinded study. The Australasian Journal of Dermatology 43 (3): 175-178, Aug 2002.

STEINER, ggsteiner@yahoo.com, supplies preliminary data on Kava as an anti-craving agent.

Background: In the effort to reduce the incidence of drug and alcohol abuse, an important area of research is the chemistry of craving. The active ingredients found in kava, known as kavapyrones, have been shown to bind to many sites in the brain that are associated with craving.

Methods: Pilot study where cravings for alcohol, tobacco, cocaine, and heroin were surveyed.

Results: Preliminary results suggest that kava may reduce the cravings associated with addiction. Reduced craving for their drug of choice was reported by participants. In another part of the study, a standardized amount of kavapyrones led to a difference in alcohol abstinence between experimental and placebo groups.

Conclusions: If these findings are confirmed in larger and more systematic studies, kava may become a useful component in the treatment of addictions.

Steiner GG. Kava as an anticraving agent: preliminary data. Pacific Health Dialog 8(2): 335-339, Sep 2001.

DENHAM and colleagues, University of Central Lancashire, Preston, UK, adenham@uclan.ac.uk, report on the unfolding story of Kava.

Methods: Review (48 references). Report on work in progress.

Background: The paper originated as a report to the Medicines Control Agency and Committee for the Safety of Medicines, in response to concerns raised by the German Federal Institute for Drugs and Medical Products (BfArM) about adverse events associated with the use of concentrated standardized preparation of Kava. As not only the public wishing to use Kava preparations for medicinal use is concerned but also the livelihood of Kava farmers throughout Polynesia, it was felt to be important to update the general public on the controversy.

Conclusions: It is found that of about 30 adverse events reported by BfArM, some are duplicated. It has also been argued by the European Herbal Medicines Evaluation Committee that some of the adverse events should not be attributed to Kava. Moreover, it is thought that the properties of concentrated standardized preparations of Kava are for more likely to contribute to adverse events than preparations created for traditional use. This report proposes a number of simple measures to ensure that safe Kava preparations continue to be available in the UK.

Denham A, McIntyre M, Whitehouse J. Kava – the unfolding story: report on a work-in-progress. The Journal of Alternative and Complementary Medicine 8 (3): 237—263, Jun 2002.

Issue 83

FOSTER et al, Office of Science, Therapeutic products Directorate, Health Canada, Ottawa, Ontario, Canada; Centre for Research in Biopharmaceuticals, University of Ottawa, Ontario K1A 1B6, Canada, E: brian_foster@hc-sc.gc.ca investigated the effect of several Chinese natural health products upon cytochrome P-450 metabolism.

Background: Certain traditional Chinese medicines have been associated with adverse reactions in which cytochrome P-450 was thought to be involved.

Methods: In vitro assay of cytochrome P-450 metabolizing enzymes 2C9, 2C19, 2D6 , and 3A4 in the presence of 12 different traditional Chinese medicines, directly or as extracts.

Results: Most extracts of traditional Chinese medicines inhibited between 25 to 100%.of the activity of the enzymes tested.

Conclusions: Cytochrome P-450 metabolism can be affected by traditional Chinese medicines in vitro, and this effect needs to be further investigated in order to assess the safety and efficacy of conventional therapeutic products.

Background: Intubation during anaesthesia often leads to post-operative sore throats. The trial was set up in order to investigate if this could be prevented by using a spray containing chamomile extract.

Methods: Randomized controlled double-blinded study comparing the effect of chamomile extract spray with the same spray containing no chamomile extract. 161 patients undergoing elective surgery were treated before intubation with either chamomile extract spray or control spray. Sore throats and hoarseness were assessed post-operatively.

Results: 52.5% of patients in the chamomile group and 50.6% of patients on the placebo group scored no sore throat or hoarseness (p = 0.159).

Conclusions: Chamomile extract spray administered before surgery does not prevent sore throat or hoarseness post intubation.

Issue 80

MORI and colleagues, Research and Development Division, Institute of Cosmetic Science, Club Cosmetics Co., Ltd., 145-1, Ichibu-cho, Ikoma City, Nara 630-0222, Japan, analysed the amounts and relative ratios of the main constituents in commercially available essential oils.
Methods: The researchers analysed commercially available essential oils using gas chromatography-mass spectrometry (GC-MS) – including essential oils of Lavandula officinalis (lavender oil), Melaleuca alternifolia (tea tree oil) and Mentha piperita (peppermint oil) – and quantified the main ingredients. They compared the results of analyses of some commercial lavender oils with those of Lavandula flagrans (lavandin oil) and the reference standard.
Results: Analyses of the lavender oils showed that oils from different sources had different ratios of the contents of the main ingredients – such as linalool, linalyl acetate and camphor. Although the components of nearly all of the commercial lavender oils were roughly the same as those of the reference standard, a few products contained more than 0.5% of the amount of camphor in lavandin oil. This latter finding suggested that some commercial lavender oils were mixed with lavandin oil to lower the cost of manufacture and/or sale price. Tea tree oils from different sources differed with respect the amount of terpinens in each oil. Each of the different samples of peppermint oils contained a different ratio of the main ingredients.
Conclusion: The observed variations in the contents of commercially available essential oils are a cause for concern with respect to the expected versus the actual efficacy of the oils. It is important that accurate information regarding the relative and absolute amounts of constituents of essential oils is available to the consumer. The authors recommend that quality control, using instrumental analysis, be introduced.
Mori M et al. (Quality evaluation of essential oils.) Yakugaku Zasshi 122 (3): 253-61. Mar 2002.

DEY and colleagues, Tang Center for Herbal Medicine Research and Department of Anesthesia Critical Care, The Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA, reviewed (108 references) literature on the use of medicinal herbs and other complementary/ alternative therapies in the management of type 2 diabetes.
Background: Type 2 diabetes affects the health, quality of life and life expectancy of sufferers, as well as placing a significant burden on healthcare resources. Modification of lifestyle factors – exercise, diet and weight control – is important in helping to control and stabilize blood glucose levels. For many patients, this is insufficient and they therefore also need to take drug therapies such as glucose-lowering agents and insulin injections. Drug treatments come with their own problems – they may elicit unwanted side effects, they may also be insufficient to fully stabilize glucose levels, and frequently they may be ineffective in preventing late-stage complications of diabetes. Increasingly, patients with diabetes and healthcare professionals are exploring the potentials of medicinal herbs that have glucose-lowering effects.
Discussion: The authors present a review of herbs and other alternative/complementary therapies most commonly used in the management of type 2 diabetes that are less likely to have side effects than conventional treatments.
Dey L et al. Alternative therapies for type 2 diabetes. Alternative Medicine Review 7 (1): 45-58. Feb 2002.

Issue 77

GIESE [no affiliation provided) reviewed (12 references) literature on the beneficial effects of milk thistle (silybum marianum) on liver function.
Background: Milk thistle, or its derivative silymarin, has a long history of use in folk medicine for the treatment of liver ailments and has few documented side effects. Silymarin has gained renewed recognition and popularity since the 1970s.
Discussion: Several small research studies have investigated the effects of silymarin on liver function, and findings suggest that it has liver-protective, anti-inflammatory and regenerative properties and may also be beneficial in the treatment of some types of hepatitis. There is uncertainty over whether silymarin might interact with the drugs interferon or ribavirin, indicating the need for a large, well-designed, placebo-controlled clinical study. One such study, investigating the effect of milk thistle therapy in hepatitis C, is currently underway, sponsored by the NCCAM, the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Updates on the progress of the trial can be obtained online at www.nccam.nih.gov and by phoning the NCCAM Clearinghouse on (+1)-888-644-6226.
Giese LA. Milk thistle and the treatment of hepatitis. Gastroenterology Nursing 24 (2): 95-7. Mar-Apr 2001.

KHAN and BALICK, Institute of Economic Botany, The New York Botanical Garden, Bronx 10458, USA, mbalick@nybg.org, reviewed (5 references) available literature on the clinical or other biological effects of 166 species of plants used in Ayurvedic medicine.
Background: It is generally believed that most herbal medicines used in non-Western systems of medicine have not been studied experimentally in humans or animals. In contradiction to this view, at least in the case of Ayurvedic medicine, the authors were able to identify a wide range of clinical and other studies on many of the botanicals used in the Ayurvedic system.
Results: Of 166 different plant species investigated, 72 (43%) had been the subject of analysis in at least one human study, and 103 (62%) had been investigated in one or more animal studies. Some of the studies were quite small and/or lacked the methodological rigor of clinical studies reported in major medical journals.
Discussion: Using the existing standards for evidence-based medicine, many of the studies identified would probably be discarded because of inadequacies regarding sample sizes, randomization procedures, controls, and so on. Nevertheless, the results from such studies should be given some consideration, as they may be useful for identifying what plant species might warrant study in more rigorous trials in the future. With this in mind, the authors of this paper present a summary of the 166 plants and their therapeutic applications, and an evaluation of the clinical and other experimental literature.
Khan S, Balick MJ. Therapeutic plants of Ayurveda: a review of selected clinical and other studies for 166 species. The Journal of Alternative and Complementary Medicine 7 (5): 405-515. Oct 2001.

Issue 76

BARNES and colleagues, Centre for Pharmacognosy Phytotherapy, School of Pharmacy, University of London, UK, reviewed (172 references) extensive literature reporting on the clinical effects, chemistry and pharmacology of St. John’s wort (SJW) (Hypericum perforatum L.).
Discussion: Traditional claims for the activities of SJW include antidepressant, antiviral and antibacterial effects, and studies of its pharmacological activities have provided evidence to support such claims. The constituent hypericin and flavonoid constituents seem to be responsible for many of the observed pharmacological effects. It seems likely that hypericin is also responsible for reported photosensitivity reactions with SJW. It now appears that the constituent hyperforin, rather than hypericin (as was initially thought), is one of the major contributors among the constituents of SJW responsible for its antidepressant effects; however, other constituents may also contribute to these effects and this remains to be clarified by further research. Randomized controlled clinical trials have demonstrated that SJW extracts are effective in comparison with placebo for treating mild-to-moderately severe depression. Further such studies have suggested that SJW extracts have efficacy similar to established antidepressants (including the ‘older’ selective serotonin reuptake inhibitors [SSRIs] fluoxetine and sertraline) in patients with mild-to-moderate depression. Further studies are still needed, however, to compare SJW extracts with newer antidepressant agents (including newer SSRIs); to investigate the use of SJW in well-defined groups of patients and in different types of depression; and to provide safety data on the long-term use of SJW. Used in the short term, SJW seems to have a better safety profile than standard antidepressants. However, there are concerns that SJW may interact with prescribed medications such as warfarin, cyclosporin, theophylline, digoxin, HIV protease inhibitors, anticonvulsants, SSRIs, triptans and oral contraceptives. Patients taking any of these medications should stop taking SJW and seek medical advice, since continuing on SJW may require that the dosage(s) of their prescribe medicine(s) be adjusted.
Barnes J et al. St. John’s wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties. The Journal of Pharmacy and Pharmacology 53 (5): 583-600. May 2001.

BRAND and colleagues, Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, Australia, investigated the effects of tea tree (Melaleuca alternifolia) essential oil (TTO) on production of oxygen-derived free radicals by human white blood cells in vitro.
Methods: The investigators studied the effects of TTO on superoxide production by neutrophils and monocytes stimulated with N- formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA).
Results: The water-soluble fraction of TTO had no significant effect on agonist-stimulated superoxide production by neutrophils, but significantly suppressed agonist-stimulated superoxide production by monocytes in a dose-dependent manner. This suppression was not due to cell death. The water-soluble components of TTO were chemically identified as terpinen-4-ol, alpha-terpineol and 1,8-cineole. Terpinen-4-ol significantly suppressed fMLP- and LPS- but not PMA-stimulated superoxide production. Alpha-terpineol significantly suppressed fMLP-, LPS- and PMA-stimulated superoxide production. 1.8-cineole had no effect.
Conclusion: Water-soluble components of TTO suppress superoxide production by monocytes but not neutrophils. The findings suggest potential for selective regulation of immune cell types by TTO during inflammation.
Brand C et al. The water-soluble components of the essential oil of Melaleuca alternifolia (tea tree oil) suppress the production of superoxide by human monocytes, but not neutrophils, activated in vitro. Inflammation Research 50 (4): 213-9. Apr 2001.
Comment: The result that tea tree oil selectively regulates certain immune cells during inflammation is the sort of evidence which builds up a picture of how and why essential oils such as tea tree are such powerful antibacterial and antifungal agents. This evidence may become very precious as standard antibiotic drugs lose their effectiveness against antibiotic resistant strains of bacteria.

GU and colleagues, Institute of Neurosurgery PLA, Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China, gujian@pub.xaonline.com.cn, investigated the possible benefits of the Chinese medicinal herb Rhubarb in patients with severe brain injury.
Methods: 20 patients with severe cerebral injury and associated hyperthermia, renal failure, haemorrhage in the upper digestive tract and increased intracranial pressure (ICP) were treated with ethanol/water extracts of Rhubarb. 20 similar patients served as controls and did not receive treatment with Rhubarb extract. Experimental outcome measures included: vital signs, variations on the Glasgow coma scale (GCS), ICP, degree of haemorrhage in the digestive tract and changes in creatinine values.
Results: Improvements in the Rhubarb-treated patients were more marked than in the controls. On Day 3 after treatment, mean body temperature decreased by 1.1°C, mean ICP by 0.4 kPa (1 mmHg=0.13333 kPa), incidence of haemorrhage in the digestive tract by 30%, volume of haemorrhage in the digestive tract by 700±250 ml, and the time for occult blood to turn negative by 10%.
Conclusion: The Chinese medicinal herb Rhubarb had many beneficial clinical effects in patients with severe brain injury.
Gu J et al. (Rhubarb extracts in treating complications of severe cerebral injury.) Chinese Medical Journal 113 (6): 529-31. Jun 2000.

Issue 75

KORMAN and colleagues, Departments of Clinical Biochemistry, Hadassah University Hospital, Jerusalem, Israel, korman@hadassah.org.il, reported on false suspicion of maple-syrup urine disease (MSUD) in newborns in mothers who consumed fenugreek prenatally.
Discussion: Fenugreek, maple syrup and urine from patients with MSUD contain a common component, sotolone, which has a characteristic odour. In this case report study, the authors reported on the occurrence of newborn infants with a maple-syrup-like odour falsely suspected to indicate MSUD. It was found that the odour in the newborns was associated with ingestion of fenugreek by the mothers during labour.
Korman SH et al. Pseudo-maple syrup urine disease due to maternal prenatal ingestion of fenugreek. Journal of Pediatrics and Child Health 37 (4): 403-4. Aug 2001.

SILVERSTEIN and SPIEGEL, of the Beth Israel Medical Center, New York, USA, conducted a survey to investigate physicians’ knowledge about their patients’ use, side effects, drug interactions and contraindications of commonly used herbs/dietary supplements.
Methods: The investigators randomly distributed a questionnaire to medical students and faculty of the State University of New York, Health Science Center at Brooklyn, posing three questions: 1) Do physicians ask their patients about their use of herbs/dietary supplements? 2) Do physicians use available resources to evaluate possible drug interactions and/or side-effects of the dietary supplements? and 3) Are physicians aware of the side effects, drug interactions and contraindications of 10 commonly used herbs?
Results: The questionnaire response rate was 85% (165/193). Many physicians asked patients about their use of alternative medicines. Most failed to check these remedies in a reference text. Younger and less-highly trained doctors were significantly more likely to 1) prescribe alternative medicines; 2) check side effects and drug interactions of over-the-counter and prescription medicines in a reference text; 3) ask patients specifically about alternative medicines; 4) check side effects and drug interactions of alternative medicines in a reference text. When asked to match 10 herbs and side effects, physicians scored up to 6 out of 10 correct; the average number correct was 1.32 ± 1.39 (mean ± SD).
Conclusion: Many physicians are aware of different forms of alternative medicines, but most do not treat herbs in the same manner as other types of medicines. Patient care would be greatly improved in physicians were better educated about alternative medicines and familiarized themselves with their patients’ beliefs and healthcare behaviour.
Silverstein DD, Spiegel AD. Are physicians aware of the risks of alternative medicine? Journal of Community Health 26 (3): 159-74.

MARK and colleagues, Department of Pediatrics, College of Pharmacy, University of Arizona, Tucson, Arizona 85724, USA, reviewed (28 references) details pertaining to available preparations of the herbal product Echinacea.
Discussion: The popularity of alternative medicines continues to increase and, although patients visiting their GPs may not always give details about their use of such products, it is not uncommon for them to ask for information about their use for themselves and their families including children. As herbal products are not yet fully regulated and standardized, doctors have a problem when it comes to judging safety and efficacy of such products and in being able to recommend any specific product. Nevertheless, in the case of a number of herbal medicines, including Echinacea, anecdotal reports and/or limited scientific research for health benefits is compelling, and the University of Arizona has recently initiated a study into the possible ability of Echinacea to prevent recurrent otitis media. In the present article, Mark and coworkers present details of the number and diversity of Echinacea preparations available, discuss the complexities surrounding its use, and explore the potential role of the family doctor as a ‘botanical advisor’ to patients.
Mark JD et al. The use of dietary supplements in pediatrics: a study of echinacea. Clinical Pediatrics 40 (5): 265-9. May 2001.
Comment: If doctors are to become prescribers of complementary therapies, then obviously they will have to master knowledge of their subject.

AFZAL and colleagues, Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait, reviewed (99 references) the medicinal properties and chemical and molecular characteristics of ginger (Zingiber officinale).
Discussion: Medicinal and/or pharmacological properties reported for ginger include anticholesterol, antioxidant and antirheumatic effects, beneficial effects on stomach ulcers, and effects on blood pressure and platelet aggregation. The authors describe the individual medicinal activities reported and provide details of the plant’s chemical (including volatile components and trace elements) components and the molecular structures and synthesis of identified organic metabolites.
Afzal M et al. Ginger: an ethnomedical, chemical and pharmacological review. Drug Metabolism and Drug Interactions 18 (3-4): 159-90. 2001.

ERNST, Department of Complementary Medicine, School of Sport and Health Sciences, University of Exeter, 25 Victoria Park Road, Exeter, Devon EX2 4NT, UK, E.Ernst@exeter.ac.uk, reviewed (76 references) published data from clinical studies of commonly used herbs to assess their risk-benefit profiles.
Background: The use of herbal remedies is on the increase, so a critical assessment of their risks versus benefits is warranted.
Methods: Ernst reviews available clinical evidence for the safety and efficacy of Ginkgo, St. John’s wort, Ginseng, Echinacea, Saw palmetto and Kava. Wherever possible, the author draws his conclusions from the findings of systematic reviews of randomized clinical trials.
Results: Ginkgo appears to have some benefits in dementia and intermittent claudication; claims for its usefulness for memory loss and tinnitus, however, remain questionable. St. John’s wort can reduce the symptoms of mild-to-moderate depression; however, its potential to interact with a number of conventional medicines is a cause for concern. Ginseng has been investigated in some well-conducted clinical trials, but the results provide no evidence of its efficacy in any condition so far examined. The data on Echinacea indicate that it may help to prevent or attenuate the symptoms of upper respiratory tract infections – more extensive trials are needed to confirm this. In short-term studies, Saw palmetto was able to reduce the symptoms of benign prostatic hyperplasia. Kava is an effective treatment for anxiety in the short term.
Conclusion: The evidence indicates that some of these herbal medicines are efficacious. Each of the herbal medicines has some side effects, but their potential benefits are probably greater than their risks. The available data, however, does not provide a complete picture, and further well-designed, larger trials are needed to provide reliable risk-benefit assessments.
Ernst E. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John’s Wort, Ginseng, Echinacea, Saw Palmetto, and Kava. Annals of Internal Medicine 136 (1): 42-53. Jan 2002.

Issue 74

BANES-MARSHALL and colleagues, Department of Microbiology, Kettering General Hospital NHS Trust, Northamptonshire, UK, evaluated the antibacterial and antifungal activities of tea tree oil (TTO) (Melaleuca alternifolia) in vitro against microorganisms isolated from leg ulcers and pressure sores.
Methods: Activity of TTO was measured as minimum inhibitory concentration (MIC) and minimum bactericidal (MBC) or fungicidal (MFC) concentration. Microorganisms tested included: methicillin-resistant Staphylococcus aureus (MRSA), S aureus, faecal streptococci, beta-haemolytic streptococci, coagulase-negative staphylococci, Pseudomonas spp. and coliform bacilli; and 11 Candida spp. isolated from skin and vaginal swabs.
Results: In an agar dilution assay, the MICs of TTO in were 0.5-1.0% (v/v) in 88 out of 90 microorganism isolates and >2% (v/v) for P aeruginosa. Using a broth microdilution method, MIC and MBC/MFC were 3% and 4% (v/v) respectively in 64 out of 80 isolates. The microorganisms most susceptible to TTO were S aureus and Candida spp, with MICs and MBCs of 0.5% and 1% respectively. The most resistant microbes were P aeruginosa and the faecal streptococci isolates, with MICs and MBCs of >8%.
Banes-Marshall L et al. In vitro activity of Melaleuca alternifolia (tea tree) oil against bacterial and Candida spp. isolates from clinical specimens. British Journal of Biomedical Science 58 (3): 139-45. 2001.

BONIEL and DANNON, Pharmaceutical Service, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel reviewed (27 references) the most commonly used herbal drugs and their safety and efficacy in psychiatric disorders.
Background: Use of alternative medicines is increasing throughout the world. Government ministries class herbal remedies as food supplements, and so they can be obtained freely from pharmacies and health stores without professional advice. Many herbs are used to self-treat psychiatric disorders. These herbs have pharmacological activities and side effects and can interact with prescribed and over-the-counter medicines, resulting in changes in mood, cognition and behaviour. The present article discusses such effects of the most commonly used herbal remedies.
Discussion: Hypericum is used as an antidepressant and antiviral agent. In reports of 23 randomized clinical trials reviewed from MEDLINE, it was found to be significantly more effective than placebo and similarly effective as standard antidepressants. Recent studies also report that this herb (like conventional antidepressants) can cause mania. Valerian is used as an antianxiety agent. It is reported to have both sedative and antidepressant effects. Valerian has been found to significantly improve sleep compared with placebo. There are also several reports of toxicity with Valerian root, including nephrotoxicity, headaches, chest tightness, mydriasis, abdominal pain and hand and foot tremor. Ginseng is widely used as a stimulant and aphrodisiac. Reported side effects with chronic use include: vaginal bleeding, mastalgia, mental status changes and Stevens-Johnson syndrome. Ginseng interacts with digoxin, phenelzine and warfarin. Gingko extract has been shown in clinical trials to significantly improve memory loss, concentration difficulties, fatigue, anxiety and depressed mood. Increased bleeding time and spontaneous haemorrhage have been reported with its long-term use. Gingko may interact with aspirin, NSAIDs, anticoagulants or other platelet inhibitors.
Conclusion: Clinicians should ask their patients about their use of herbal remedies in a non-judgemental manner and document this. It is vital that we become more aware of the side effects and potential drug interactions of these herbs. At present, patients should be advised to avoid long-term use of these herbs due to the lack of safety information.
Boniel T, Dannon P. (The safety of herbal medicines in the psychiatric practice.) Harefuah 140 (8): 780-3. Aug 2001.

GUSTAFSON and colleagues, Microbiology Group, School of Biomedical Sciences, Curtin University of Technology, Perth, Western Australia, studied the bactericidal actions of tea tree oil (TTO) on antibiotic-resistant (mutant) strains of Escherichia coli (E coli).
Methods: The investigators compared the antibacterial actions of TTO in vitro on the parent strain of E coli (AG100) and on mutants of the parent strain demonstrating the multiple antibiotic resistance (Mar) phenotype. The researchers also attempted to isolate Mar mutants of Staphylococcus aureus using tetracycline gradients; however, this was unsuccessful. The bactericidal actions of TTO against S aureus strain BB255 grown in the presence or absence of salicylate were compared.
Results: Mutant E coli strains exhibiting the Mar phenotype were found to be more resistant to the killing action of TTO compared with the parent strain. TTO’s bactericidal actions were greater at 37oC than at 30oC for all E. coli strains studied. Parent strain E coli showed increased tolerance to TTO when grown in the presence of salicylate, which is known to induce the mar operon leading to the Mar phenotype. The killing actions of antimicrobial terpines found in TTO were reduced in E coli Mar mutant YL1 in comparison with parent strain AG100. S aureus strain BB255 was more resistant to TTO when grown in the presence of salicylate than in its absence.
Conclusion: Bacterial Mar phenotypes increase resistance to the bactericidal action of TTO. The results also suggest that TTO’s site of action is the bacterial cell membrane.
Gustafson JE et al. The bacterial multiple antibiotic resistant (Mar) phenotype leads to increased tolerance to tea tree oil. Pathology 33 (2): 211-5. May 2001.

Issue 73

GUPTA and colleagues, Department of Medicine, Medical College Jammu, JK, India, studied the gum resin of Boswellia serrata for the treatment of patients with chronic colitis.
Background: The inflammatory process in colitis is associated with increased formation of leukotrienes causing chemotaxis, chemokinesis, synthesis of superoxide radicals and release of lysosomal enzymes by phagocytes. The key enzyme for leukotriene biosynthesis is 5-lip oxygenase. Boswellic acids were found to be non-redox, non-competitive specific inhibitors of 5-lipoxygenase.
Methods: This clinical trial involved 30 patients (17m, 13f; age range 18-48 years) with chronic colitis characterized by vague lower abdominal pain, bleeding per rectum with diarrhoea, and palpable tender descending and sigmoid colon. 20 of the patients received a preparation of the gum resin of Boswellia serrata (900 mg daily in three divided doses) and 10 patients (controls) received sulfasalazine (3 g daily in three divided doses) for 6 weeks.
Results: 18 out of the 20 patients in the Boswellia group showed an improvement on one or more of the following [after the 6-week treatment]: stool properties, histopathology, scanning electron microscopy, haemoglobin, serum iron, calcium, phosphorus, proteins, total leukocytes and eosinophils. 6 of the 10 patients in the control group showed similar results with the same parameters. 14 of the 20 patients in the Boswellia group and 4 out of 10 in the sulfasalazine group [subsequently] went into remission. The authors reported ‘minimal side effects’ with Boswellia.
Conclusions: The findings suggest that a gum resin preparation from Boswellia serrata might be useful in the treatment of chronic colitis.
Gupta I et al. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Medica 67 (5): 391-5. Jul 2001.

Comment: A more extensive study with larger numbers of patients per group and possibly a longer treatment period is needed to confirm these initial promising findings.

ZHANG and colleagues, Division of Natural Products Chemistry, Shen Yang Pharmaceutical University, China, zywlcell@yahoo.com, examined the effects of 27 ginsenosides isolated from Panax ginseng on gap junction-mediated intercellular communication (GJIC).
Background: Gap junctions may be involved in the pathogenesis of many inherited and acquired human diseases. Agents that regulate the GJIC function may facilitate prevention and treatment of GJIC-involved diseases.
Methods: The isolated ginsenosides examined were as follows: oleanolic acid (compound (C) 1), ginsenoside-R0 (G-R0; C2), G-Rb1 (C3), G-Rc (C4), G-Rb2 (C5), G-Rb3 (C6), G-Rd (C7), G-Rg3 (C8), G-Rd2 (C9), notoginsenoside-Fe (C10), G-Rh2 (C11), panaxadial (C12), notoginsenoside-R4 (C13), G-Ra1 (C14), G-Re (C15), G-Rg2 (20R) (C16), G-Rg2 (20S) (C17), G-Rf (C18), G-Ia (C19), G-Rh1 (20S) (C20), G-Rh1 (20R) (C21), G-F1 (C22), protopanaxatriol (C23), panaxatriol (C24), G-Rg1 (C25), G-F3 (C26) and chikusetsaponin-L8 (C27).
Results: The following compounds did not obviously affect GJIC: C1, C2, C3, C5, C7, C8, C12, C13, C17, C18 and C26. The following compounds induced various degrees of GJIC reductions: C4, C6, C9, C10, C11, C14, C15, C16, C19, C20, C21, C22, C23, C24, C25 and C27. C2, C7 and C8 protected against the vanadate-induced GJIC reduction (vanadate is a tyrosine phosphatase inhibitor). C1, C5, C7 and C17 inhibited the GJIC reduction induced by the cytokine interleukin 1 alpha (IL-1alpha). No compounds protected against the GJIC inhibition induced by the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA). The tyrosine kinase (TK) inhibitor genistein inhibited the GJIC reductions induced by C6, C9, C10, C20, C21, C22, C24 and C25. The PKC inhibitor calphostin C attenuated the GJIC reductions induced by C6, C9, C14, C16, C19, C21 and C24. Neither genistein nor calphostin C inhibited the GJIC reductions induced by C4, C23 and C27.
Conclusions: The results indicate that a variety of mechanisms are responsible for the effects of ginsenosides on GJIC.
Zhang YW et al. Effects of ginsenosides from Panax ginseng on cell-to-cell communication function mediated by gap junctions. Planta Medica 67 (5): 417-22. Jul 2001.

Issue 72

LONG and colleagues, Department of Complementary Medicine, School of Postgraduate Medicine and Health Studies, University of Exeter, 25 Victoria Park Road, Exeter EX2 4NT, UK, aimed to systematically review (46 references) all randomized controlled trials on the effectiveness of herbal medicines in the treatment of osteoarthritis.
Background: Limitations in the conventional medical treatment of osteoarthritis indicate a real need for safe and effective [alternative or complementary] treatments. Herbal medicines may provide a solution to this problem.
Methods: The investigators conducted computerized literature searches on five electronic databases. Trial data were extracted in a standardized, pre-defined manner and assessed independently.
Results: 12 trials and two systematic reviews met the inclusion criteria. The reported data provided promising evidence for the effective use of some herbal preparations in the treatment of osteoarthritis and evidence suggesting that some herbal preparations reduced the need for non-steroidal anti-inflammatory drugs. The reviewed herbal medicines appeared to be relatively safe.
Conclusion: Some herbal medicines may offer a much-needed alternative for patients with osteoarthritis.
Long L et al. Herbal medicines for the treatment of osteoarthritis: a systematic review. Rheumatology 40 (7): 779-93. Jul 2001.

MARININ and colleagues, Russia investigated the effects of aerotherapy with olesan oil in patients with chronic obstructive pulmonary disease.
Methods: 44 male and female adult patients with chronic obstructive bronchitis or bronchial asthma were treated with olesan oil [administered as a aerosol].
Results: 28 patients (64%) showed positive clinical changes and improved external respiratory function following aerophytotherapy.
Marinin VF et al. (Aerophytotherapy with olesan oil in the treatment of patients with chronic obstructive bronchitis and bronchial asthma.) Klinicheskaia Meditsina (Mosk) 79 (4): 54-6. 2001.

Issue 70

SCHULTEN and colleagues, Company Medical Service, Madaus AG, Cologne, Germany, b.schulten@madaus.de, investigated the efficacy and speed of onset of action of Echinaceae purpureae herba in relieving common cold symptoms.
Background: Common colds are one of the most frequent acute illnesses with major economical impact. Echinaceae purpureae herba (Echinacin, EC31JO) has shown promising results in the relief of common cold symptoms and the time taken to improvement compared with placebo. The present study aimed to confirm these findings.
Methods: 80 adult male and female patients with first signs of a cold were recruited into this randomized, double-blind, placebo-controlled clinical trial. The primary endpoint measure was the number of days of illness with a complete picture of the common cold (defined by the modified Jackson score of at least 5 points and experience of rhinorrhoea and/or a subjective sensation of having a cold).
Results: Median time to illness in the Echinaceae-treated group was significantly lower than in the placebo group (6.0 days versus 9.0 days; p=0.0112, one-sided test), assigning zero time for patients without a complete picture.
Conclusion: EC31JO was well tolerated and clinically effective in alleviating symptoms more rapidly than placebo in patients with a common cold.
Schulten B et al. Efficacy of Echinacea purpurea in patients with a common cold. A placebo-controlled, randomised, double-blind clinical trial. Arzneimittel Forschung 51 (7): 563-8. 2001.

SUGAYA and colleagues, Division of Oriental Medicine, Tokyo Hospital, School of Medicine, Tokai University, Japan, examined the gene expression regulatory activities of a Japanese herbal mixture, Saiko-keishi-to-ka shakuyaku (SK, TJ-960).
Background: Japanese herbal medicine has long been considered as only supplementary therapy to Western medicine.
Results: The investigators found that the herbal mixture, Saiko-keishi-to-ka shakuyaku (SK, TJ-960), displayed activities that suggested regulation of gene expression, including increased expression of seizure-related gene PTZ-17, proto-oncogene c-fos and heat shock protein HSP 72.
Conclusion: According to the authors, their results provide a scientific basis for an important ancient concept and the use of herbal mixtures as ‘therapy against diseases which will be suffered in the future’. The authors also suggest that the findings may lead to the development of therapies and even perhaps prevention of intractable epilepsy, Alzheimer’s disease and developmental disorders occurring during pregnancy and the postnatal period, and to prevention of metastasis or relapse of various cancers.
Sugaya E et al. Regulation of gene expression by herbal medicines – a new paradigm of gene therapy for multifocal abnormalities of genes. Research Communications in Molecular Pathology and Pharmacology 106 (3): 171-80. 1999.

VERMA and BORDIA, Department of Medicine and Indigenous Drug Research Centre, R. N. T. Medical College, Udaipur-313 001,India, investigated the effects of supplementing a fatty meal with ginger powder on fibrinolytic activity in healthy adults.
Methods: In a randomized, controlled clinical trial, 30 healthy adult volunteers were administered 50g fat as a fatty meal with or without supplementation with 5g ginger powder. Effects on fibrinolytic activity were measured.
Results: Administration of 50g fat decreased fibrinolytic activity from a mean of 64.25.31 to 52.13.2 units (p<0.001). Supplementation with 5g ginger powder not only prevented the fall in fibrinolytic activity, but actually increased it significantly (p<0.001).
Conclusion: This fibrinolytic enhancing property is a further addition to the therapeutic potential of ginger.
Verma SK, Bordia A. Ginger, fat and fibrinolysis. Indian Journal of Medical Sciences 55 (2): 83-6. Feb 2001.

More Herbal Medicine Updates