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Herbal medicine: culture resistance humbles TCM practise in the West
News & Comment
BDNF mediates rapid switch from excitatory to inhibitory transmission Sympathetic neurones grown in culture with cardiac myocytes are known to produce both classical autonomic neurotransmitters: noradrenaline, which excites the heart cells and speeds up their beat; and acetylcholine, which has the opposite effect. An exciting new study shows that the neurotrophin brain-derived neurotrophic factor (BDNF) alters the relative release of the transmitters, favouring that of acetylcholine over noradrenaline and transforming an excitatory synapse to an inhibitory synapse in minutes. This action is in marked contrast to that of another neurotrophin, nerve growth factor (NGF), which enhances the excitatory effects of nerve stimulation. The authors suggest that BDNF exerts its effects by modulating the relative release of the two transmitters present in colocalized populations of small synaptic vesicles. If such a mechanism also exists in central neurones containing colocalized smallmolecule neurotransmitters, an unexpected opportunity arises for the regulation of differential release by target-derived factors to contribute to mechanisms of synaptic plasticity. [Yang, B. et al. (2002) Nat. Neurosci. 5, 539–545] VR
Ghrelin levels out after gastric bypass surgery If losing weight is difficult, maintaining that new svelte figure is often even harder.
TRENDS in Pharmacological Sciences Vol.23 No.8 August 2002
Ghrelin, a gastrointestinal hormone, is one of the many factors implicated in the mechanisms that counteract weight loss, such as increased appetite and changes in metabolism. A clinical study recently published in the New England Journal of Medicine investigated plasma ghrelin levels in normal and obese subjects, as well as in patients who had lost weight either through caloric restriction or after gastric bypass surgery. The patients who had dieted successfully had markedly increased ghrelin levels. By contrast, the gastric surgery patients had much lower ghrelin levels without the typical meal-related diurnal fluctuations. The study is consistent with the hypothesis that ghrelin is involved in the regulation of mealtime hunger and long-term body weight. These observations suggest that ghrelin antagonists might have a role in the treatment of obesity. [Cummings, D.E. et al. (2002) New Engl. J. Med. 346, 1623–1630] AB
Non-invasive blood glucose monitoring Diabetic sufferers will be heartened to learn of two recent evaluations of a new non-invasive blood glucose monitoring device – the GlucoWatch Biographer. For diabetics, home glucose monitoring is a tedious but necessary means of achieving good glycaemic control to minimize complications and avoid serious hyper- or hypoglycaemic episodes. Most current methods involve meter testing a finger-prick blood sample, usually twice a day. The new device is worn like a wristwatch and gives readings every twenty minutes by analysing glucose concentration in interstitial fluid. An alarm sounds if an abnormally high or low reading occurs. In the current studies, diabetic
357
subjects found the Biographer easy to use, but skin irritation and a long calibration period were considered disadvantages. Nevertheless some patients found continuous monitoring and the alarms invaluable – a pending ‘hypo’ can be detected up to an hour before symptoms arise. [Chan, N.N. and Hurel, S.J. (2002) Pract. Diab. Int. 19, 97–100; Lenzen, H. et al. (2002) Pract. Diab. Int. 19, 101–103] VR
Atypical antipsychotics in the UK Atypical antipsychotics should be made available to British schizophrenia patients, according to a statement issued by The National Institute for Clinical Excellence, an advisory body affiliated with the British National Health Service (NHS). Drugs of this class, which include risperdone and clozapine, cause fewer side-effects than older drugs and have a higher response rate in many treatmentresistant patients. It is estimated that more than 200 000 people could benefit from the availability of these drugs. The cost to the NHS would be ~£70 million, but mental health professionals expect that the use of atypical neuroleptics would decrease the cost of hospital admissions and in-patient care. AB
This month’s In Brief articles were written by Ann Barbier ([email protected]) and Vasanta Raman ([email protected])
Letters
Herbal medicine: culture resistance humbles TCM practise in the West Comment from Li
In a recent TiPS article [1], Edzard Ernst stated that ‘Asian herbal medicines…are http://tips.trends.com
not regulated as medicines and are freely available to everyone’, which is not true. In mainland China, traditional Chinese medicine (TCM) shares an equal status with the modern medical system, and its continuous application and development is protected by the Constitution [2]. There are thousands of well-regulated TCM hospitals and herbal-drug manufacturers. Each year, thousands of TCM students with Bachelor, Master and PhD degrees
graduate from dozens of TCM universities, colleges and institutions all over the country. In Southern Korea [2], only certified oriental medical doctors or pharmacies with oriental medical doctors’ prescriptions are allowed to provide patients with any of the herbal medicines listed in the Korean Pharmacopoeia. In Japan [2], there is no significant difference between the methods of evaluation applicable to
0165-6147/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0165-6147(02)02058-8
358
News & Comment
herbal medicines and those applicable to chemical substances. Despite the fact that certain categories of plant preparations are commonly available over-the-counter (OTC), herbal medicines are indeed legally regulated as drugs, and a license is required for its practice in many Western countries, including Canada and most European countries, which is in contrast to the USA [2]. In his TiPS article, Ernst has probably mixed up OTC herbs and herbal medicines, which is rather misleading. Ernst also realized that ‘the majority of clinical problems occur with selfprescription’, but argued that ‘evidence is required to support this claim’ that consulting an experienced herbal practitioner might help avert adverse events [1]. Ernst has ignored the fact that many potentially toxic herbal medicines have continued to be used with care for several thousands of years because of their therapeutic value. The major problem is that Western physicians and pharmacists, in the majority of cases, have little knowledge about the traditional medicines and their properties. Therefore, they will not be helpful to patients, as in the unfortunate Belgian case that Ernst mentioned. A few mineral products are used in TCM, as Edzard Ernst indicated in his article [1], which is true, but the term ‘metals’ rather than the term ‘minerals’ might lead to misunderstanding by readers who are not familiar with TCM. It has to be emphasized that mineral products are processed using special methods to minimize their toxicities to a tolerable level, and are restricted to external usage in most cases. One should also be aware that the data from reports of metal poisoning might be problematic because of the nonspecific test used to detect heavy metals [3]. The use of processed minerals in TCM has been limited since the discovery of antibiotics, whereas the documented knowledge in this area is still invaluable for scientists to develop new modern drugs [4]. Traditional medicines apparently have evolved in different parts of the globe. Although no systematic traditional medical system was recorded, herbals as legal medicines in the UK can be traced back, at least to the London Pharmacopoeia (1628), the Edinburgh Pharmacopoeia (1699) and the first British Pharmacopoeia (1864) [3]. http://tips.trends.com
TRENDS in Pharmacological Sciences Vol.23 No.8 August 2002
Presumably due to the invention of paper in ancient China, the comprehensive traditional systems (both medical and medicinal) were systematically documented in China and in its neighboring countries. Unfortunately, in the name of science most of the well-recorded empirical and clinical knowledge is not legally acceptable in most Western countries, particularly in the Nordic countries [2], which has humbled the TCM practice in the West. Shi-Sheng Li* Division of Pharmacognosy, Dept of Medicinal Chemistry, Uppsala University, Biomedical Center, Box 574, SE-751 23 Uppsala, Sweden. *On leave from the College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, China. e-mail: [email protected] References 1 Ernst, E. (2002) Toxic heavy metals and undeclared drugs in Asian herbal medicines. Trends Pharmacol. Sci. 23, 136–139 2 World Health Organization (1998) Regulatory situation of herbal medicines – a worldwide review. (Document No. WHO/TRM/98.1) 3 British Herbal Medicine Association (1990) British Herbal Pharmacopoeia (Vol. 1) 4 Senior, K. (2002) Arsenic: carcinogen or cancer therapy? Drug Discov. Today 7, 156–157
Published online: 13 June 2002
Herbal medicine: the dangers of drug interaction Comment from Izzo et al.
In his recent TiPS article [1], Edzard Ernst reviewed evidence suggesting that some herbal medicines contain toxic heavy metals or undeclared compounds that might constitute a serious health risk. Here, we wish to draw attention to another relevant and timely aspect of the safety of herbal medicines: the possibility of interactions between herbal and synthetic drugs. The adage ‘what goes around comes around’ seems applicable to the current popularity of herbal remedies. Plants have been used throughout human history for their medicinal properties. Five hundred years ago botanical gardens were maintained as a source of medicinal
plants. At the beginning of the 20th century, however, when scientific method predominated, ‘modern medicine’ relegated herbal medicines to the level of quackery. By contrast, today, patients have become enlightened consumers and are again embracing herbal remedies. This is not without reason: there is growing evidence supporting the efficacy of some of these products [e.g. St John’s wort (Hypericum perforatum) for managing mild to moderate depression, saw palmetto (Serenoa repens) for the symptomatic treatment of benign prostate hyperplasia, ginkgo (Ginkgo biloba) for the treatment of dementia and intermittent claudication, and kava (Pyper methysticum) for the treatment of anxiety] [2]. However, some herbal medicines are marketed without compelling evidence of their benefits [e.g. cranberries (Vaccinium macrocarpon) for the treatment of urinary tract infections, and ginseng (Panax ginseng) for increased capacity to work and concentrate] [2]. Because all herbal medicines are mixtures of more than one active ingredient, such combinations of many substances obviously increase the likelihood of interactions taking place. Moreover, combining the presence of many compounds with the fact that herbal medicines are of variable and often undefined composition renders analysis of interactions a complex and difficult task. Importantly, the majority of people who use herbal medicines do not reveal this use to their physician or pharmacist, thereby greatly increasing the risk of side-effects from the interactions between herbal components and concurrent pharmacotherapy [3]. In recent years, multiple case reports of herb–drug interactions have been published. Obviously, case reports have to be interpreted with great caution because causality is not usually established beyond reasonable doubt. A recent systematic review retrieved 108 cases of suspected herb–drug interactions [4], among which 68.5% were classified as ‘unable to be evaluated’, 18.5% were classified as ‘possible’ and 13% as ‘well documented’. The anticoagulant warfarin was the most common drug involved and St John’s wort the most common herb. Interactions can have both a pharmacokinetic (changes to plasma drug concentration) and pharmacodynamic (drugs interact at receptors on target organs) basis.
0165-6147/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0165-6147(02)02059-X
BDNF mediates rapid switch from excitatory to inhibitory transmission Sympathetic neurones grown in culture with cardiac myocytes are known to produce both classical autonomic neurotransmitters: noradrenaline, which excites the heart cells and speeds up their beat; and acetylcholine, which has the opposite effect. An exciting new study shows that the neurotrophin brain-derived neurotrophic factor (BDNF) alters the relative release of the transmitters, favouring that of acetylcholine over noradrenaline and transforming an excitatory synapse to an inhibitory synapse in minutes. This action is in marked contrast to that of another neurotrophin, nerve growth factor (NGF), which enhances the excitatory effects of nerve stimulation. The authors suggest that BDNF exerts its effects by modulating the relative release of the two transmitters present in colocalized populations of small synaptic vesicles. If such a mechanism also exists in central neurones containing colocalized smallmolecule neurotransmitters, an unexpected opportunity arises for the regulation of differential release by target-derived factors to contribute to mechanisms of synaptic plasticity. [Yang, B. et al. (2002) Nat. Neurosci. 5, 539–545] VR
Ghrelin levels out after gastric bypass surgery If losing weight is difficult, maintaining that new svelte figure is often even harder.
TRENDS in Pharmacological Sciences Vol.23 No.8 August 2002
Ghrelin, a gastrointestinal hormone, is one of the many factors implicated in the mechanisms that counteract weight loss, such as increased appetite and changes in metabolism. A clinical study recently published in the New England Journal of Medicine investigated plasma ghrelin levels in normal and obese subjects, as well as in patients who had lost weight either through caloric restriction or after gastric bypass surgery. The patients who had dieted successfully had markedly increased ghrelin levels. By contrast, the gastric surgery patients had much lower ghrelin levels without the typical meal-related diurnal fluctuations. The study is consistent with the hypothesis that ghrelin is involved in the regulation of mealtime hunger and long-term body weight. These observations suggest that ghrelin antagonists might have a role in the treatment of obesity. [Cummings, D.E. et al. (2002) New Engl. J. Med. 346, 1623–1630] AB
Non-invasive blood glucose monitoring Diabetic sufferers will be heartened to learn of two recent evaluations of a new non-invasive blood glucose monitoring device – the GlucoWatch Biographer. For diabetics, home glucose monitoring is a tedious but necessary means of achieving good glycaemic control to minimize complications and avoid serious hyper- or hypoglycaemic episodes. Most current methods involve meter testing a finger-prick blood sample, usually twice a day. The new device is worn like a wristwatch and gives readings every twenty minutes by analysing glucose concentration in interstitial fluid. An alarm sounds if an abnormally high or low reading occurs. In the current studies, diabetic
357
subjects found the Biographer easy to use, but skin irritation and a long calibration period were considered disadvantages. Nevertheless some patients found continuous monitoring and the alarms invaluable – a pending ‘hypo’ can be detected up to an hour before symptoms arise. [Chan, N.N. and Hurel, S.J. (2002) Pract. Diab. Int. 19, 97–100; Lenzen, H. et al. (2002) Pract. Diab. Int. 19, 101–103] VR
Atypical antipsychotics in the UK Atypical antipsychotics should be made available to British schizophrenia patients, according to a statement issued by The National Institute for Clinical Excellence, an advisory body affiliated with the British National Health Service (NHS). Drugs of this class, which include risperdone and clozapine, cause fewer side-effects than older drugs and have a higher response rate in many treatmentresistant patients. It is estimated that more than 200 000 people could benefit from the availability of these drugs. The cost to the NHS would be ~£70 million, but mental health professionals expect that the use of atypical neuroleptics would decrease the cost of hospital admissions and in-patient care. AB
This month’s In Brief articles were written by Ann Barbier ([email protected]) and Vasanta Raman ([email protected])
Letters
Herbal medicine: culture resistance humbles TCM practise in the West Comment from Li
In a recent TiPS article [1], Edzard Ernst stated that ‘Asian herbal medicines…are http://tips.trends.com
not regulated as medicines and are freely available to everyone’, which is not true. In mainland China, traditional Chinese medicine (TCM) shares an equal status with the modern medical system, and its continuous application and development is protected by the Constitution [2]. There are thousands of well-regulated TCM hospitals and herbal-drug manufacturers. Each year, thousands of TCM students with Bachelor, Master and PhD degrees
graduate from dozens of TCM universities, colleges and institutions all over the country. In Southern Korea [2], only certified oriental medical doctors or pharmacies with oriental medical doctors’ prescriptions are allowed to provide patients with any of the herbal medicines listed in the Korean Pharmacopoeia. In Japan [2], there is no significant difference between the methods of evaluation applicable to
0165-6147/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0165-6147(02)02058-8
358
News & Comment
herbal medicines and those applicable to chemical substances. Despite the fact that certain categories of plant preparations are commonly available over-the-counter (OTC), herbal medicines are indeed legally regulated as drugs, and a license is required for its practice in many Western countries, including Canada and most European countries, which is in contrast to the USA [2]. In his TiPS article, Ernst has probably mixed up OTC herbs and herbal medicines, which is rather misleading. Ernst also realized that ‘the majority of clinical problems occur with selfprescription’, but argued that ‘evidence is required to support this claim’ that consulting an experienced herbal practitioner might help avert adverse events [1]. Ernst has ignored the fact that many potentially toxic herbal medicines have continued to be used with care for several thousands of years because of their therapeutic value. The major problem is that Western physicians and pharmacists, in the majority of cases, have little knowledge about the traditional medicines and their properties. Therefore, they will not be helpful to patients, as in the unfortunate Belgian case that Ernst mentioned. A few mineral products are used in TCM, as Edzard Ernst indicated in his article [1], which is true, but the term ‘metals’ rather than the term ‘minerals’ might lead to misunderstanding by readers who are not familiar with TCM. It has to be emphasized that mineral products are processed using special methods to minimize their toxicities to a tolerable level, and are restricted to external usage in most cases. One should also be aware that the data from reports of metal poisoning might be problematic because of the nonspecific test used to detect heavy metals [3]. The use of processed minerals in TCM has been limited since the discovery of antibiotics, whereas the documented knowledge in this area is still invaluable for scientists to develop new modern drugs [4]. Traditional medicines apparently have evolved in different parts of the globe. Although no systematic traditional medical system was recorded, herbals as legal medicines in the UK can be traced back, at least to the London Pharmacopoeia (1628), the Edinburgh Pharmacopoeia (1699) and the first British Pharmacopoeia (1864) [3]. http://tips.trends.com
TRENDS in Pharmacological Sciences Vol.23 No.8 August 2002
Presumably due to the invention of paper in ancient China, the comprehensive traditional systems (both medical and medicinal) were systematically documented in China and in its neighboring countries. Unfortunately, in the name of science most of the well-recorded empirical and clinical knowledge is not legally acceptable in most Western countries, particularly in the Nordic countries [2], which has humbled the TCM practice in the West. Shi-Sheng Li* Division of Pharmacognosy, Dept of Medicinal Chemistry, Uppsala University, Biomedical Center, Box 574, SE-751 23 Uppsala, Sweden. *On leave from the College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, China. e-mail: [email protected] References 1 Ernst, E. (2002) Toxic heavy metals and undeclared drugs in Asian herbal medicines. Trends Pharmacol. Sci. 23, 136–139 2 World Health Organization (1998) Regulatory situation of herbal medicines – a worldwide review. (Document No. WHO/TRM/98.1) 3 British Herbal Medicine Association (1990) British Herbal Pharmacopoeia (Vol. 1) 4 Senior, K. (2002) Arsenic: carcinogen or cancer therapy? Drug Discov. Today 7, 156–157
Published online: 13 June 2002
Herbal medicine: the dangers of drug interaction Comment from Izzo et al.
In his recent TiPS article [1], Edzard Ernst reviewed evidence suggesting that some herbal medicines contain toxic heavy metals or undeclared compounds that might constitute a serious health risk. Here, we wish to draw attention to another relevant and timely aspect of the safety of herbal medicines: the possibility of interactions between herbal and synthetic drugs. The adage ‘what goes around comes around’ seems applicable to the current popularity of herbal remedies. Plants have been used throughout human history for their medicinal properties. Five hundred years ago botanical gardens were maintained as a source of medicinal
plants. At the beginning of the 20th century, however, when scientific method predominated, ‘modern medicine’ relegated herbal medicines to the level of quackery. By contrast, today, patients have become enlightened consumers and are again embracing herbal remedies. This is not without reason: there is growing evidence supporting the efficacy of some of these products [e.g. St John’s wort (Hypericum perforatum) for managing mild to moderate depression, saw palmetto (Serenoa repens) for the symptomatic treatment of benign prostate hyperplasia, ginkgo (Ginkgo biloba) for the treatment of dementia and intermittent claudication, and kava (Pyper methysticum) for the treatment of anxiety] [2]. However, some herbal medicines are marketed without compelling evidence of their benefits [e.g. cranberries (Vaccinium macrocarpon) for the treatment of urinary tract infections, and ginseng (Panax ginseng) for increased capacity to work and concentrate] [2]. Because all herbal medicines are mixtures of more than one active ingredient, such combinations of many substances obviously increase the likelihood of interactions taking place. Moreover, combining the presence of many compounds with the fact that herbal medicines are of variable and often undefined composition renders analysis of interactions a complex and difficult task. Importantly, the majority of people who use herbal medicines do not reveal this use to their physician or pharmacist, thereby greatly increasing the risk of side-effects from the interactions between herbal components and concurrent pharmacotherapy [3]. In recent years, multiple case reports of herb–drug interactions have been published. Obviously, case reports have to be interpreted with great caution because causality is not usually established beyond reasonable doubt. A recent systematic review retrieved 108 cases of suspected herb–drug interactions [4], among which 68.5% were classified as ‘unable to be evaluated’, 18.5% were classified as ‘possible’ and 13% as ‘well documented’. The anticoagulant warfarin was the most common drug involved and St John’s wort the most common herb. Interactions can have both a pharmacokinetic (changes to plasma drug concentration) and pharmacodynamic (drugs interact at receptors on target organs) basis.
0165-6147/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0165-6147(02)02059-X