Inhibitory potential of herbal medicines on human cytochrome P450-mediated oxidation: properties of umbelliferous or citrus crude drugs and their relative prescriptions.
To investigate the possible drug interaction with herbal medicine, hot water decoctions or 40% ethanol infusions of several Umbelliferous or Citrus crude drugs and their prescriptions were examined in vitro for their abilities to inhibit human cytochrome P450 3A (CYP3A). Addition of each decoction or infusion from Baizhi (Angelica dahurica and varieties), Qianghuo (Notopterygium incisum or N. forbesii), Duhuo (Angelica biserrata), Fangfeng (Saposhnikovia divaricata), Danggui (Angelicasinensis), Zhishi or Zhiqiao (Citrus aurantium) resulted in various degrees of human CYP3A inhibition as determined by microsomal testosterone 6beta-hydroxylation. The inhibitory potency was consistent with the abundance of the hydrophobic components for each sample. Experiments on the infusion of a Japanese Baizhi (BZ1) showed the major role of furanocoumarins on human CYP3A inhibition. Some of the crude drugs and a related prescription showed increased inhibition after the preincubation, suggesting the involvement of a mechanism-based inhibition. Some formulated prescriptions, however, showed intense inhibition with their hydrophobic fractions rather than with their hydrophobic fractions, suggesting that components other than furanocoumarins in herbal prescriptions may also cause CYP3A inhibition. These results indicate the necessity of intensive investigations on the possible drug interaction with traditional medicines. (+info)
An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic.
PURPOSE: Garlic has been used as a flavouring agent, traditional medicine, and functional food to improve physical or mental well-being. Garlic and garlic products generally have been regarded as safe but a number of conflicting reports in the literature and confounding factors make it difficult to unequivocally establish the clinical efficacy and safety of these products either alone or in the presence of therapeutic products. A preliminary study was undertaken with fresh garlic and garlic products using the major cDNA-expressed human cytochrome P-450 isozymes associated with the metabolism of HIV/AIDS drugs, and purified P-glycoprotein (P-gp) cell membranes to ascertain the risk potential for generating interactions with therapeutic products. METHODS: A broad screening was undertaken with 10 garlic products (aged, odourless, oil, freeze-dried) and 3 varieties of fresh garlic bulbs (common, Elephant and Chinese), all purchased from local outlets, to examine their potential to affect human cytochrome P-450 2C9*1, 2C9*2, 2C19, 2D6, 3A4, 3A5 and 3A7 mediated-metabolism of marker substrates using an in vitro fluorometric microtiter plate assay. Four garlic products were screened for their potential to interact with P-gp using an in vitro colourmetric ATPase assay. RESULTS: Extracts of fresh garlic, different brands and lots of odourless garlic and representative samples of garlic oil, freeze dried garlic, and aged garlic exhibited an inhibitory effect on cytochrome P450 2C9*1, 2C19, 3A4, 3A5 and 3A7 mediated metabolism of a marker substrate. The activity of 2D6 mediated-metabolism was generally unaffected by garlic. Extracts of the fresh garlic stimulated CYP2C9*2 metabolism of the marker substrate. With the extracts tested, garlic had very low to moderate P-gp interaction as compared with the positive control verapamil. CONCLUSIONS: Our in vitro findings demonstrate that garlic components can affect cytochrome P-450 2C, 2D and 3A mediated-metabolism of the isoforms studied. The safety and efficacy of conventional therapeutic products metabolized by the affected isozymes, particularly those with a narrow therapeutic index, taken concomitantly with garlic needs to be examined further under clinical settings. (+info)
Systematic reviews of complementary therapies - an annotated bibliography. Part 2: herbal medicine.
BACKGROUND: Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with herbal medicine. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of herbal medicines; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pre-tested form and summarized descriptively. RESULTS: From a total of 79 potentially relevant reviews pre-selected in the screening process 58 met the inclusion criteria. Thirty of the reports reviewed ginkgo (for dementia, intermittent claudication, tinnitus, and macular degeneration), hypericum (for depression) or garlic preparations (for cardiovascular risk factors and lower limb atherosclerosis). The quality of primary studies was criticized in the majority of the reviews. Most reviews judged the available evidence as promising but definitive conclusions were rarely possible. CONCLUSIONS: Systematic reviews are available on a broad range of herbal preparations prescribed for defined conditions. There is very little evidence on the effectiveness of herbalism as practised by specialist herbalists who combine herbs and use unconventional diagnosis. (+info)
Self-treatment by Kenyan and Ugandan schoolchildren and the need for school-based education.
Studies on Kenyan and Ugandan primary schoolchildren's knowledge of medicines and self-treatment practices show that children aged between 10 and 18 years have a broad knowledge of herbal and biomedical remedies and that they use them frequently, often without adults' involvement. They use pharmaceuticals, including prescription-only drugs, but lack knowledge about indications and dosages. There is a gap between the children's life worlds and the school health education as it is presently designed and taught in Kenya and Uganda. It limits itself to disease prevention and health promotion, and does not teach treatment or medicine-use. Self-treatment based on insufficient knowledge poses a threat to children's health and to the health of the wider community. Therefore, education on the critical and appropriate use of medicines needs to be developed and tested for possible use in Kenya, Uganda and other countries in which home-treatment is common. The proposed education on medicines should go beyond providing information on accurate dosage and indication: it should create critical awareness with regard to medicine-use, enabling children to use them appropriately and cautiously. Kenyan and Ugandan primary schoolchildren are active agents within pluralistic medical fields. By taking the children seriously as competent health care agents, the dangers of self-treatment could be reduced, and the potential of children could be guided to fruitful use. Educational interventions cannot solve the problems of self-treatment, which are related to the wider social and economic context, but they could contribute to increased awareness as a necessary condition for change. (+info)
Identification in traditional herbal medications and confirmation by synthesis of factors that inhibit cholera toxin-induced fluid accumulation.
Kampo formulations are traditional herbal medications used in China and Japan for many centuries to treat diarrheal diseases such as cholera. Our studies were undertaken to identify and verify by chemical synthesis the active components that inhibited cholera toxin (CT), the virulence factor secreted by Vibrio cholerae, the causative agent of cholera. The Kampo formulation, Daio-kanzo-to, inhibited CT activities (i.e., ADP-ribosylation, Chinese hamster ovary cell elongation); in Daio-kanzo-to, Daio (Rhei rhizoma) was responsible for this effect. Among several components purified from Daio extract, rhubarb galloyl-tannin, a compound characterized by a polygallate structure, was the most effective. To define the active component, gallate analogues similar to rhubarb galloyl-tannin were synthesized. These gallate compounds inhibited all CT activities including ADP-ribosylation, elongation of Chinese hamster ovary cells, and importantly, fluid accumulation in ileal loops. Thus, Kampo formulations or their gallate components might be effective adjunctive therapy with oral rehydration solution for the severe diarrhea of cholera. (+info)
Disease prevention and health promotion in the aging with a traditional system of natural medicine: Maharishi Vedic Medicine.
OBJECTIVE: This review focuses on a comprehensive, sophisticated system of natural medicine that appears to hold promise for prevention of chronic diseases and disabilities, loss of independence, suffering, and health care costs often associated with "usual" aging. METHODS: The authors discuss the negative impact of usual aging on our society, with its rapidly growing percentage of elderly, and the challenge of promoting "successful aging." Emphasis is given to research literature suggesting that Maharishi Vedic Medicine (MVM) is particularly effective in retarding usual aging. RESULTS: Proposed mechanisms for the antiaging effects of MVM include reductions in physiological and psychological stress and enhancement of homeostatic and self-repair processes. CONCLUSIONS: The authors conclude that this set of innovative strategies may help society achieve recommended health objectives for disease prevention and health promotion in older adults and that widespread implementation of this self-empowering, prevention-oriented approach in the elderly is feasible, cost effective, and timely. (+info)
Herbal medicine and anaesthesia.
Herbal medicines are increasingly used in both western and Chinese societies. This is partly attributed to the alleged limitations of scientific medicine in the cure and control of chronic diseases. Many patients do not disclose that they have used herbs before surgery and hence their physicians remain unaware of the potential herb-drug interactions. With respect to anaesthesia, herbs can cause coagulation disorders, cardiovascular side-effects, water and electrolyte disturbances, endocrine effects, hepatotoxicity, and prolongation of the effects of anaesthetic agents. Anaesthesiologists should obtain a history of herbal medicine use from patients and work out the adverse perioperative herb-drug interactions in advance of the actual operation. If in doubt, the herbal medicine should be stopped for 2 weeks prior to anaesthesia and surgery. (+info)
Aristolochic acid as a probable human cancer hazard in herbal remedies: a review.
The old herbal drug aristolochic acid (AA), derived from Aristolochia spp., has been associated with the development of a novel nephropathy, designated aristolochic acid nephropathy (AAN), and urothelial cancer in AAN patients. There is clear evidence that the major components of the plant extract AA, aristolochic acid I (AAI) and aristolochic acid II (AAII), both nitrophenanthrene carboxylic acids, are genotoxic mutagens forming DNA adducts after metabolic activation through simple reduction of the nitro group. Several mammalian enzymes have been shown to be capable of activating both AAI and AAII in vitro and in cells. The activating metabolism has been elucidated and is consistent with the formation of a cyclic nitrenium ion with delocalized charge leading to the preferential formation of purine adducts bound to the exocyclic amino groups of deoxyadenosine and deoxyguanosine. The predominant DNA adduct in vivo, 7-(deoxyadenosin-N(6)-yl)aristolactam I (dA-AAI), which is the most persistent of the adducts in target tissue, is a mutagenic lesion leading to AT-->TA transversions in vitro. This transversion mutation is found at high frequency in codon 61 of the H-ras oncogene in tumours of rodents induced by AAI, suggesting that dA-AAI might be the critical lesion in the carcinogenic process in rodents. DNA-binding studies confirmed that both AAs bind to the adenines of codon 61 in the H-ras mouse gene and preferentially to purines in the human p53 gene. In contrast, the molecular mechanism of renal interstitial fibrosis in humans after chronic administration of AA remains to be explored. However, preliminary findings suggest that DNA damage by AA is not only responsible for the tumour development but also for the destructive fibrotic process in the kidney. It is concluded that there is significant evidence that AA is a powerful nephrotoxic and carcinogenic substance with an extremely short latency period, not only in animals but also in humans. In particular, the highly similar metabolic pathway of activation and resultant DNA adducts of AA allows the extrapolation of carcinogenesis data from laboratory animals to the human situation. Therefore, all products containing botanicals known to or suspected of containing AA should be banned from the market world wide. (+info)