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Chinese herbal medicine and the cardiovascular system: looking through the mirror. (Symposium).

Cardiovascular Disease and Chinese Herbal Medicine

Cardiovascular diseases, the top killers in the US, encompass conditions afflicting the cardiac and vascular system such as coronary artery disease, arteriosclerosis, hypertension, heart failure, arrhythmia and valvular disease. Many of these problems have often developed significantly before any clinical symptoms can be noticed. Numerous contributing or risk factors have been identified including high fat intake, menopause, type A behavior, family history, smoking, stress, obesity, diabetes, and high cholesterol or triglycerides. The advancement of modern health care, mainly under mainstream allopathic or Western medicine, has improved the quality of life of patients suffering from cardiovascular diseases. However, each year, more and more people (over 60 million Americans) use herbal remedies and other types of alternative medicine instead of, or in additional to, mainstream allopathic medicine to cure or prevent disease. The growing use of herbal medicine is largely due to its "natural" properties, making it inherently safer than drugs produced artificially. Herbal medicine also offers hope in those patients who have lost faith in allopathic medicine, especially when it has failed.

Herbal remedy, a discipline originating from Traditional Chinese medicine, has been developed over a thousand years into a unique system of theory and healing, in conjunction with the use of animal medicines, acupuncture and moxibustion. It covers the disciplines of microbiology, biochemistry, physiology, and pharmacology. Herbal remedies have been used in patients with cardiovascular diseases such as congestive heart failure, hypertension, angina pectoris, atherosclerosis, stroke, venous insufficiency, and arrhythmia. A number of theories have been postulated for the mechanism of the tonic effect, represented by the `Yin-Yang and Orbit Doctrine' concept. However, careful scientific assessment of herbal remedies is still lacking. Being "tonic", herbs appear to be less toxic and unlikely to jeopardize human health, although some have the potential to cause serious toxic effects and major drug-to-drug interactions. With the high prevalence of herbal use in the US for treatment or for nutrition, the potential benefit and harm of prescribing or dispensing of herbal medicine frequently becomes an important issue. Continuing research is necessary to elucidate the pharmacological activities of the many herbal remedies now being used to treat cardiovascular diseases.

The goal of modern herbal research is to derive preparations from medicinal herbs to meet present-day international standards of quality, safety and efficacy. Major constituents of herbal drugs should always be identified, isolated and structurally characterized, to understand the overall pharmacological activity and efficacy. Elucidation of the complete pharmacological profile should include the cellular and molecular biological mechanisms followed by toxicological studies. For example, the study on ephedrine proceeded the discovery of norepinephrine and contributed to modern investigation and understanding of sympathomimetic agents. It needs to be pointed out that herbal medicine as a unique system has its own integrity. Although herbal treatments play the most important role in Traditional Chinese medicine, they are small parts of the whole. In ancient China, there were no clear-cut divisions between medicines and tonic products in form of foods, e.g. ginger and cassia bark are described as both flavorings and herbal medicines. It is important to investigate these medicines or those with similar origin, determining which surfaces as a `tonic effect' instead of a `therapeutic one.' Thus, herbal remedies should be more beneficial to mankind, not only in curing disease but also in disease prevention.

Therapeutic Potential of Herbal Medicine in Cardiovascular Diseases by Classes

Herbal medicine has a lot to offer in keeping the cardiovascular system healthy, as long as it is supported by appropriate exercise and a healthy diet. Proper use of these gentle medicines has been proven to be beneficial. Traditional Chinese herbal medicine may be classified into many categories according to their clinical effects, comparable to allopathic medicine. However, one classification system is considered indispensable although not familiar or accepted by allopathic medicine. This system views the herbs as being `tonic', `restorative' or `strengthening', and classifies the herbs, based on the pharmacological actions, into four categories: a) Energy-promoter; b) Blood-promoter; c) Yin-promoter; d) Yang-promoter. Both clinical and experimental researchers have shown that each category has novel but distinct effects on the cardiovascular system.

Energy-promoters are beneficial to angina pectoris, myocardial infarction, and heart failure, conditions that are often accompanied by tissue anoxia. The best example of this class is the famous Ginseng. Ginseng means "root of man" and has the ability to increase physical and mental endurance. It is capable of bringing a person into his/her physical peak and has been used by athletes as a performance enhancer. Ginseng has `adaptogenic' characteristics due to its unique ability to normalize body function. Ginseng may enhance glyceric acid diphosphate and decrease the affinity of hemoglobin to oxygen, therefore allowing tissues to release more oxygen to compensate for the additional needs of the damaged area. The therapeutic effects of ginseng have been attributed to its active ingredients, ginsenosides, sugar conjugates of dihydroxyl or trihydroxyl dammarane triterpenes known as panaxadiol and panaxatriol. Ginseng extracts rich in ginsenosides have been found to facilitate learning and memory, delay the aging process, and prevent neuronal loss under hypoxia. Data regarding the effect of ginseng or ginsenosides on the cardiovascular system has, however, been controversial. Some studies reported enhanced cardiac function (1), others have claimed little or depressed cardiac function (2). Ginseng and ginsenoside have been reported to regulate membrane [Ca.sup.2+] channel activity and stimulate nitric oxide production (3), both of which play crucial roles in cardiovascular function. It was demonstrated that ginsenosides can protect anoxia/reoxygenation and reperfusion injury of cultured myocytes and isolated rat hearts. Our group recently reported that ginsenosides [Rb.sub.1] and Re directly depressed ventricular myocyte contraction, consistent with the notion of reduced oxygen demand in the heart (4). Ginseng is currently sold in the U.S. as a food additive and thus needs not meet specific safety and efficacy requirements of the Food and Drug Administration. With the growing use of ginseng, it is important to know the direct cardiac effects of ginseng.

Blood-promoters are a group of medicines that enhance hematopoietic actions such as thrombolysis and invigoration of blood production. Experiments both in vivo and in vitro showed that Chinese angelica, Salvia miltiorrhiza (DANSHEN), Paeonia lactiflora (CHISHAO), safflower and their main principles could increase coronary blood flow, decrease myocardial oxygen consumption, antagonize experimental myocardial ischemia and arrthymia (5). Chinese angelica can lengthen the effective refractory period, eliminate refraction, extend the platform phase, inhibit ectopic rhythms and reduce ventricular fibrillation; all of these are crucial in antagonizing arrhythmia. Salvia miltiorrhiza and its effective components may prolong hypoxia toleration time, dilate coronary artery, protect from ischemic EKG changes and shrink the myocardial infraction range. It is concluded that Salvia miltiorrhiza or its effective components may be similar or even better than dipyridamole and propranolol. The anti-arrhythmic effect has also been reported in Stephania tetrandra. Ligusticum wallichii (CHUANXIONG) and S. miltorrhiza exhibited a beneficial effect in dilating vessels especially renal arterioles which could result in a decrease of arterial blood pressure and an improvement in the microcirculation of the lung and kidney. The effect of Lingusticum wallichii and safflower in lowering arterial resistance might be stronger than that of 654-2, but of a shorter duration. Paeonia lactiflora lowers experimental portal hypertension. Tetramethylpyrazine, which is the effective component of L. wallichii, was shown to improve blood flow in acute renal failure and prevent sodium re-absorption through inhibiting angiotensin-II synthesis. Combined use of L. wallichii, Salvia miltiorrhiza and Chinese angelica may antagonize adrenaline-induced microvascular contraction even to an opposite dilating state, benefiting microcirculation. If used with certain energy-promoters, marked pharmacological effects may develop including antagonizing shock-induced drop of blood pressure, reducing endotoxin-induced declination of plasma viscosity, disturbing the formation of microthrombus and eliminating the obstruction by plates and leukocytic aggregation. A [Ca2.sup.2+]-antagonism similar to that of verapamil was noted in Stephania tetrandra.

Yin (negative)-promoters regulate the metabolic processes. They have been defined as drugs that replenish cellular constitutes, promote anabolism and the feedback system in cellular activities. The representatives are Wolfberry fruit (GOUJIZI), Lingustrum lucidum Ait (NUZHENZI), Rehmannia root (DIHUANG), Schisandra chinensis (Turcs) Bail (WUWEIZI), Ophiopogen japonica (Thunb) Ker-Gawl (MAIMENDONG), and Scrophularia ningpoensis Hemsl (XUANSHEN). Some yin-promoters have been shown to facilitate myocardial metabolism, enhance hypoxia tolerating capacity, decrease oxygen consumption, increase artery-vein blood oxygenic pressure difference and coronary blood flow, and maintain ATP as well as glucagon content in hypoxia myocardium at a comparably high level. In addition, Ganoderm lucidum may stimulate the formation of 2, 3-DPG in erythrocyte in vivo and the function of hemoglobin. An anti-arrhythmia effect of Ophiopogen japonica was noted in restoring [Bacl.sub.2]-induced tachycardia. Furthermore, studies on O. japonica injection verified it could antagonize ischemic T wave changes evoked by the posterior pituitary lobe and increase cardiac coronary blood flow so as to strengthen myocardial hypoxia tolerance and contractility.

Yang (positive)-promoters activate cellular metabolism especially catabolism, through production of the release factor in cellular activity. Epimedium grandiflorum (YINYANGHUO), Psoralea corylifolia L. (BUGUZHI), Encommia ulmoides (DUZHONG), pilose antler, Cuscuta chinensis Lam. and Curculigo orchioides Gaertn., are the most important compositions in this category of tonic medicines. Encommia ulmoides, psoralea corylifolia L. and Epimedium grandiflorum could exert diverse cardiovascular actions such as a hypotensive effect, coronary artery dilation, and/or an increase in coronary blood flow.

Other herbs are also available to strengthen the cardiovascular system but may not fall into a particular category listed above. One cardiac tonic is Hawthorn berry, which is rich in bioflavonoids. Hawthorn normalizes the heart by either stimulating or depressing cardiac activity depending upon the need. It may be safely used in heart weakness and palpitations by improving coronary flow and oxygen supply. Another example is Motherwort for treating racing heartbeat caused by anxiety and tension. Special emphasis has been given to the wonder herb, Garlic. This amazing herbal medicine and food does everything from treating ear infections to preventing heart disease. The most important cardiovascular effect of garlic is on blood pressure and blood cholesterol depression.

The intake of flavonoids has been reported to reduce the risk of cardiovascular disease. Gingko biloba,, which contains flavonoids and terpenoids, has been shown to be cardiovascular protective. It has been shown that Gingko biloba prevents ischaemia-induced oxidation, improves cerebral circulation and antagonizes the action of platelet-activating factor (PAF). In Europe, Gingko biloba, designated as `EGB 761', has been used clinically to treat peripheral vascular disease and cerebrovascular insufficiency. The mechanism of anti-ischemic/ reperfusion action of EGB 761 has been attributed to its antioxidant/free radical scavenging effects. EGB 761 improves cardiac function and reduces free radical formation during ischemia in both non-preconditioned and preconditioned, nondiabetic and diabetic rats: Morphological studies revealed that EGB 761 treatment could prevent loss of myofibriles and myocyte growth defects, diminish interstitial fibrosis and reduce endothelial and muscular basement membrane thickening of the diabetic myocardium. This effect was believed to be helpful to prevent !ate diabetic complications (6). Furthermore, as a powerful antioxidant, EGB 761 may also slow the aging process.

SUMMARY

Herbal remedies can facilitate disease cure or prevention. Thus, if modern allopathic medicine had been applied to the studies from the very beginning of the usage of herbal medicine, there would have been but one system of medical doctrines today, and a priori theory would have been but one single discipline of pharmacology. However, unfortunately or fortunately, history has witnessed different courses of development of the two systems, each with its own characteristic ideology and methodology. Fortunately in Asia, especially in China and Japan, we have persevered traditional tonic medicines, both through resources and knowledge. At this time, it is a very important but complex task for herbal biomedical researchers to absorb and assimilate Western modern techniques. The examples of work on herbal medicine mentioned here illustrate in part the efforts made by herbal medicine researchers along with herbal medical doctors in trying to narrow the gap between herbal medicine and allopathic medicines by studying the pharmacological actions of the former with modern methods, many even at the cellular level. Successes and failures, more or less, have brought about different opinions and arguments. It appears that many difficulties will have to be overcome, among which differences in terminology and way of thinking are most notable. Herbal medicine seems to put more on the concept of integrity than analytical methods. For these reasons it appears that much work remains to be done before achieving a unified medical science, including a unified pharmacology. Advances in the pharmacological studies of tonic herbal medicines by all means would help shorten the distance and the time required for approaching this goal.

ACKNOWLEDGEMENT

The skillful assistance of Bonnie H. Ren in running the herbal medicine research project is especially appreciated.

REFERENCES

(1.) Toh HT(1994) Am. J. Chinese Med., 22:275-284.

(2.) Chen X, Yang S, Chen L, Ma X, Chen Y, Wang L, and Shu C (1994) J. Trad. Chin. Med., 19:617-621.

(3.) Chen X, Salwinski S, and Lee TJ-F (1997) Clin. Exp. Pharmacol. Physiol., 24:958-959.

(4.) Scott GI, Colligan PB, Ren BH, Ren J. Br. J. Pharmacol., in revision.

(5.) Wang ZG and Ren J (1988) In, Current Problems in Nutrition, Pharmacology and Toxicology, McLean A & Wahlqvist ML, eds. London: John Libbey & Company Limited Press, pp. 44-49.

(6.) Welt K, Weiss J, Koch S, Fitzl G. (1999) Exper. Toxicol. Path., 51:213-222.

Jun Ren * Department of Pharmacology, Physiology and Therapeutics, University of North Dakota, Grand Forks
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Author:Ren, Jun
Publication:Proceedings of the North Dakota Academy of Science
Geographic Code:1U4ND
Date:Apr 1, 2001
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