The pharmacology and toxicity of Traditional Chinese Herbal Medicines Introduction Traditional Chinese Medicine has a very long

history. Ancient man created primitive medicine during their struggle against nature. While in their quest for food, they found that some foods and plants had the specific property of relieving or eliminating certain diseases. That was the beginning of finding and using herbal medicines. Through practice and the elevation of ancient physicians experience into theory, literatures compiling actions of herbs, their localities of production, harvesting, processing, natures and flavours, toxicity and non-toxicity, combination, prohibitions, dispensing and dosage and administration laid down the foundation of the Pharmacology of Chinese Medicine. (Cui and Man, 2002.) Toxicity Traditional Chinese Herbs are generally very safe and easy to use. Usually normal administration doesnt cause any harmful effects to the human body but we should keep in mind what Zhang Jiegu said, All the medicinal are toxic. That explains what is recorded in the book, The Simple Question, To treat diseases with extremely toxic medicinal, discontinue the administration when the disease is eighty percent improved and with the non-toxic ones, discontinue the administration when the disease is ninety percent improved. (Yang, 1999) This is to prevent the accumulation of herbs (usually composed of a multitude of ingredients whose interactions with the body are extremely complex) that can lead to intoxication of Chinese herbs.

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Herbs Dan Dou Chi Tian Hua Fen Da Zhu Ye She Gan Ma Chi Xian Mu Don Pi Da Huang Mong Xiao or Xiong Ming Fen Fan Xie Ye Hu Hui Yu Li Ren Caon Sui Jing Da Ji Yuon Hua Shang Cu Qian Niu Zi Ba Dou Shang

Category Spicy cool herbs that release the ext? Clearing heat, purging fire Clearing heat, purging fire Clearing heat, purging fire, removing toxins Clearing heat, purging fire, removing toxins Clearing heat, purging fire, cooling blood Purging Purging Purging Purging Purging Moist laxative Harsh expellents Harsh expellents Harsh expellents Harsh expellents Harsh expellents Harsh expellents

Reason Inhibits lactation Induce labour CI pregnancy CI pregnancy CI pregnancy CI pregnancy CI pregnancy CI pregnancy CI pregnancy CI pregnancy CI pregnancy Caution in pregnancy Incorp with Ga Cao, CI preg Incorp with Ga Cao, CI preg Incorp with Ga Cao, CI preg Incorp with Ga Cao, CI preg With Ba Bou CI Preg With Qian Niu Zi CI Preg

There are particularly toxic herbs and these require careful notes. In books on herbal medicine, some drugs are labelled as toxic, slightly, extremely toxic or deadly poisonous. Toxicity is referred to as harmful effects of toxic effects of drugs on the human body. In general, the toxic dose of a poisonous drug is close to its therapeutic dose or is already with the toxic dosage and overdose may lead to toxic reaction or severe side effects. (Zhang, 1988) Modern Research and Traditional Chinese Medicine Since the early nineteenth century attempts have been made to understand the actions and properties of Traditional Chinese Medicinal substances through scientific research. The vast majority of this work has been conducted during the past sixty years, primarily in laboratories in China, Korea, Japan, Russia and Germany. It was also during this time that most of the drugs used in modern biomedicine have been developed. Some examples:

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Herbs Ma Huang

Sang Ye Zhi Mu

Zhi Zi Zi Cao

Research Findings Ingestion of as little as 15ml of a 1% solution can lead to diaphoresis, temperature elevation (up to 39.2 degrees C), epigastric pain, nausea, vomiting; In conjunction with cardiac glycosides, atrophine antidote can cause arrhythmias Long term use of 250 times the normal dose in mice produced both liver and kidney damage Intravenous injection of a moderate dose of Zhi Mu into rabbits caused respiratory depression and a slight reduction in blood pressure; At very high dose there was respiratory arrest, a sharp drop in blood pressure and death. The use of geniposide caused diarrhoea in mice. Oral administration of Zi Cao powder to rabbits in the extremely large dose of 5g/kg for three days led to pyuria, hematuria and diarrhoea. Two days after stopping medication the symptoms disappeared.

(Bensky, 1993) Summary of labelled toxic herbs

Herbs Gan Sui Functions and Indications Good for draining downwards water and expelling rheum to eliminate water retention through defecation Toxicity Toxic Remarks Incompatible with Gan Cao; if used with Gan Cao, the toxicity will be enhanced. (Cui &Man 2002) Causes side effects: including vomiting, nausea, palpitations, abdominal pain, backache and hematuria (Bensky, 1993) Incompatible with Gan Cao; if used with Gan Cao, the toxicity will be enhanced. (Cui &Man 2002); Frying in vinegar reduces its toxicity (Bensky, 1993)

Jing Da Ji

Good for draining downwards water and expelling rheum to eliminate water retention through defecation

Toxic

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Yuan Hua

Drains water, dispels rheum for oedema and ascites, kills parasites and treat sores in the head and obstinate tinea

Toxic (more toxic than Gan Sui and Jing Da Ji)

Shang Lu

Expel water and purgative for oedema, ascites, constipation and dysuria, reduce swelling and dissipate nodules

Toxic

Qian Niu Zi

Promotes both urination and defecation and as a drastic precipitating herbs but less strong than Gan Sui, Da Ji and Yuan Hua

Toxic

Ba Dou

Strong purgation for constipation due to accumulation of cold, evil, expels water and reduces oedema for abdominal distension and ascites to cause cauterisation

Extremely Toxic

Bai Hua She

Powerfully unblocks the channels and expels wind, arresting wind and convulsion

Toxic

Incompatible with Gan Cao; if used with Gan Cao, the toxicity will be enhanced. (Cui &Man 2002); Symptoms of toxicity include tremors and dyspnea (Bensky, 1993) Effects of overdose can be quite severe; mild signs include fever, tachypnea, tachycardia, nausea and vomiting and diarrhoea with abdominal pain. This can progress to headache, delirium, mydriasis and coma. Toxic in large dose; Nausea and vomiting due to direct stimulating of the gastrointestinal tract, a large dose can affect the kidneys leading to hematuria as well as neurological symptoms. (Bensky, 1993) to 1 drop of croton oil producing burning in the mouth and stomach often emesis, several extensive fluid evacuations, much colic and tenesmus; toxic doses produces gastroenteritis is and collapse. (Keys, 1993) intake of 20 drops of the oil may cause death. (Yang, 1999) The extract of Bai Hua She can lower blood pressure by dilating of blood vessels. It also has an analgesic and

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Chuan Wu/Cao Wu

Expels wind, cold and dampness evils for wind-damp-cold Bi syndrome, disperse cold and relieve pain for pain, trauma and local anaesthetics (Cui and Man 2002)

Extremely Toxic

sedative effects. (Long, 1998) Toxic effects are convulsions, stupor, shock, central paralysis of the respiratory system leading to asphyxiation and death, slowing of the heartbeat and heart failure leading to death (Rxlist, 1999)

Processing (PaoZhi) Chinese medicinal herbs, which are mostly natural and crude in the first place, are processed in a variety of processing procedures, which are guided by Traditional Chinese Medicine theory and the Traditional Chinese Materia Medica (TCMM). One of the main reasons why raw herbs should be processed is to reduce or eliminate the toxic effects of drugs. For example, Cao Wu, an extremely toxic herb, if steamed with Gan Cao and Hei Dou will become less toxic; Bai Dou is extremely toxic, being drastically purgative and when defatted the toxicity will be diminished. (Yang, 1999) 9Long, 1998) Another example is Bai Tou Wen; it has to be processed before use. This fresh herb produces severe local irritation, vesicating the skin and internally inducing gastroenteritis accompanied by emesis; it is a cardiac and nervous sedative, producing a hypnotic state with diminuation of senses, followed by a paralysing action. (Keys, 1993). Correct Administration of Herbs Another way of preventing intoxification of herbs is to prepare and use different drugs in different ways. Some toxic herbs should be taken in pill or powder but not in decoction; some should be externally applied but taken orally; and some should be decocted for a long time. Intoxication is often clinically caused by the improper use of a toxic herb.

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For example, intoxication of Sichuan aconite root or prepared aconite root is mainly attributed to inadequate decoction. (Long, 1998) Pu Gong Ying is a relatively safe herb but can cause heart burn with oral administration. (Bensky, 1993) Compatibility Another factor to be reviewed is compatibility and avoiding incompatibility. This will also avoid intoxification of Chinese herbs with specific attention being paid to the clinical use of the herbs. In the application of herbs, sometimes a single herb is used alone and sometimes two or more drugs are used together. Using one drug to treat the disease is called going alone. The combined application of two or more herbs is known as: a) Mutual reinforcement herbs in similar characters and functions are used in coordination to strengthen their effects; b) Mutual assistance herbs similar in certain aspects of their characters and function can be used together, with one a the principal and the other or others as subsidiary, to help increase the effects of the principal; c) Mutual restraint when herbs are used in combination, the side effects and toxicity of one herb can be reduced or eliminated by the other d) Mutual detoxification one herb can lessen or remove the side effects and toxicity of the other e) Mutual inhibition when two herbs are used together. They inhibit or check each other so they reduce or even lose their original efficacy f) Incompatibility when two herbs are used in combination, side effects or toxicity may be the result As a whole, when two herbs are used in on prescription, they usually cause interactions. Sometimes they co-ordinate to increase their effects; sometimes counteract with each other to lessen or completely remove the toxicity or side effects or sometimes even increase side effects and toxicity. So, when two or more herbs are needed, they should be chosen carefully according to the condition of the patient and the characters and functions of the herbs. (Zhang, 1988)

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Contraindications Herbs are capable of curative effects and equally so, toxic effects. To allow their curative effects and avoid their toxic side effects are the basic principles for making up a prescription. Precaution in herb application and the possible harmful side effects are known as contraindications. These also include contraindications for food, pregnancy and incompatability of herbs. Incompatibility of drug Traditionally, it is prohibited to combine herbs when two or more of them are used together and may produce severe side effects and possible toxicity. These are known as the Eighteen Incompatibilities. The 18 Incompatibilities Ban Xia (Radix Pinella) Gua Lou (Fructus Trichosanthis) Bei Mu (Bulbus Fritillariae Cirrhosae Bai Lian (Radix Ampelopsis Bai Ji (Rhizoma Bletillae) Gan Sui (Radix Kansui) Da Ji (Radix Euphorbiae Pekinensis) Yuan Hua (Flos Genkwa) Hai Zao (Herba Sargassii) Ren Shen (Radix Ginseng) Sha Shen (Radix Adenophorae) Dan Shen (Radix Salviae Miltiorrhizae) Xuan Shen (Radix Scrophulariae) Xi Xin (Herba Asari) Bai Shao (Radix Paeoniae Lactiflorae)

Wu Tou (Radix Aconiti) Gan Cao (Radix Glycyrrhizae)

Li Lu (Rhizoma et Radix Veratri) (Cui & Man, 2002)

It is also prohibited to combine herbs when two or more herbs are used in the same prescription, they become less effective which is known as Nineteen Antagonists. The 19 Antagonisms Liu Huang (Sulfur) Mang Xiao (Natrii Sulfas) Shui Yin (Hydrargyrum) = Mercurio Pi Shuang (Arsenicum) Lang Du (Radix Euphorbiae Mi Tuo Seng (Lithargyrum) Fischerianae) Ba Dou (Fructus Crotonis) Qian Niu Zi (Semen Pharbitidis) Ding Xiang (Flos Caryophylli) Yu Jin (Radix Curcumae) Wu Tou (Radix Aconiti) & Cao Wu Xi Jiao (Cornu Rhinocerotis) (Radix Aconiti Kusnezoffii) Ya Xiao (Nitrum Depuratum) = Nitrico San Leng (Rhizoma Sparganii) depurado Rou Gui (Cortex Cinnamomi) Chi Shi Zhi (Halloysitum Rubrum) Ren Shen (Radix Ginseng) Wu Ling Zhi (Faeces Trogopterori) (Cui & Man, 2002)

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Contraindications during pregnancy Some herbs can cause damage to the primordial Qi of the fetus and may even cause miscarriage. Therefore, there are many herbs that a woman should not use during pregnancy because of their highly toxic qualities. These include Ba Dou, Qian Niu Zi, Da Ji, Gan Sui, Yuan Hua, Shang Lu, She Xiang, San Leng and more. There are some herbs that help relieve Qi and blood stasis but still should be used with caution. Some examples of these are Tao Ren, Hong Hua, Da Huang, Fu Zi, Gan Jiang and Rou Gui etcContraindicated herbs should be absolutely prohibited and carefully used herbs should not be used unless absolutely obliged and safety is guaranteed. (Long, 1998) Food Taboo During treatment with herbs, there are foods that are not fit for some diseases and can be contraindicative to some herbs and therefore should be avoided or not used. Some foods used daily can diminish or even offset the effect of some herbs. Some in combination with the herbs may cause toxicity or side effects. Some ancient texts showed that Chang Suan counteracts raw scallion, Di Huang and He Shou Wu counteract raw scallion, garlic and radishes; Bo He counteracts turtle flesh; Gan Cao counteracts silver carp; Fu Ling is antagonistic to vinegar; Tu Fu Ling and Shi Jun Zi are against tea and honey is antagonistic to raw scallion. These should be taken into consideration when using these herbs. (Zhang, 1988) Dosage When the dosage (amount of raw herb in decoction orally taken by an adult per day) of a herb is the proper amount or not really influences the curative effect and safety use. It is difficult for a small dosage to cure severe illness and when the illness is light vital Qi has a tendency to be damaged. Dosages that are excessive can be one of the common causes for intoxification of Chinese herbs. A reasonable dosage can be determined by: 1. Properties of the herbs whether they are neutral, heavy, non-toxic i.e. mineral and shells should be used in large dosages; drastic, light and toxic herbs should be used in small dosages. 2. State of illness, age and constitution of the patients: In this case a large dosage should be used for the patients with acute and heavy illness and small dosages for the patient with mild and light illnesses. Old and weak patients require tonifying herbs in Qi Health Clinic 2007 8

large dosages and for eliminating pathogenic factors in small dosages. For children over six months and under 5 years old, herbs can be used in a half and quarter of the adult dosage respectively. Of course even smaller dosages for babies and infants. (Long, 1998) It is advisable when using a toxic remedy so that the dose remains a safe dose that the patient should discontinue its use after the disease is mostly cured. Also that they do not take an excessive dose, nor is the dose for a long time and this is to avoid excessive or accumulation intoxication. Herbs Effects if overdose Used too much or for too long may cause heavy sweating that weakens the body, may raise blood pressure or cause restlessness and tremors Too large a dosage is prohibited (Yang, 1988) Can lead to CNS symptoms of toxicity, consisted of reduced movement and lowered reaction to outside stimuli and irregular breathing, followed by difficulty in breathing and coma. Pathological examination revealed damage to all the major organs esp. the liver and kidneys Overdose in humans causes headaches, dizziness, vomiting, tremors, gastroenteritis and pathogenic reactions Over-dosage can lead to nausea and vomiting, diarrhoea, numbness of the extremities, irritability, chorea, miosis and in very severe cases- coma and death Human taking a relatively high dosage of this herb has developed nausea and vomiting A large dosage of arctiin led to convulsion and respiratory arrest in experiments on both cold-blooded and warm blooded animals

Ma Huang

Cang Er Zi Sheng Ma

Huo Ma Ren Qin Jao

Luo Shi Teng (Bensky, 1993) Conclusion

It is very important to know whether a herb is toxic or not and the degree of its toxicity. Traditional Chinese Medicine practitioners have also been very aware of this and attached a great significance to this point. That is the toxicity of herbs is harmful to the human body. What is interesting is that some herbs treat disease because of their toxicity i.e. Using poison to counteract poison, means to fight pathogenic Qi Health Clinic 2007 9

factors with toxic substances. Therefore poisonous herbs if used according to established principles and with care can produce excellent therapeutic results. Bibliography Texts: 1. Cui J. and Man S. Lecture Notes for KP613: Pharmacology of Chinese Medicine 2002. The Chinese Medicine Uni, Faculty of Life Science, RMIT University, Bundoora Campus pg. 5-60. 2. Zhang E.Q The Chinese Materia Medica 1988. Publishing House of Shanghai University of Traditional Chinese Medicine pg 2-195 3. Yang Y.L. Textbook for TCM Higher Education: Traditional Chinese Materia Medica. 1999. Wuhan University Press. Pg 1-92 4. Bensky D. And Gamble A. Chinese Herbal Medicine: Materia Medica Revised Edition, 1993. Eastland Press, Incorporated pg. 3-19 5. Long Z.X. The Chinese Materia Medica. 1998 Academy Press pg. 3-109 6. Keys J.D. Chinese Herbs: Their Botany, Chemistry and Pharmacodynamics 1st Edition, 3rd printing 1993. Charles E. Tuttle Company Inc. Japan pg. 103 and 347 Websites: 1. Blackwell, R. Cases of Herb Toxicity http://www.acupuncutre.com/Herbology/Toxic.htm. 2002 pg. 1-3 2. Rxlist. Aconite Frequently Asked Question. http://www.rxlist.com/cgi/alt/aconite_faq.htm. 1999 pg, 2 3. Dharmanananda, S. Safety issues affecting Chinese Herbs: The case of Asarum. http://www.itmonline.org/arts/asarum.htm. 2002 pg 1-14 4. Hing, J.K.C. Herb Toxicity. http://alternativehealing.org/herb.toxicity.htm. May 2002 pg. 1-3

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