Chinese Herbal Medicine (CHM) has been administered to animals in China for more than 4,000 years.1 Many clinical studies have indicated that CHM is effective for treating a wide variety of medical conditions in the areas of cardiology2, dermatology3, endocrinology4, gastroenterology5, reproduction6, oncology7, immunology8, pulmonology9 and musculoskeletal conditions10. However, Chinese herbs are drugs. We must treat them as pharmaceutical medications. As CHM is more widely used for the treatment and prevention of various diseases in both humans and animals in the United States and other western countries, reports of adverse reactions related to CHMs have increased.11-14 Therefore, toxicity and safety of CHM is one of the most important topics in veterinary practice. This article focuses on the analysis of the toxicity of Chinese herbs in order that toxic herbs can be identified, and properly prepared and used to reduce the incidence of adverse events.
History and Concept of Herbal Toxicity
Ancient Chinese people started to record their discovery that certain foods and plants had specific properties of relieving or eliminating certain illnesses 4,000 years ago when the initial Chinese written language (Jia-gu-wen) was created.1 In order to explore more plants and confirm these effects, ancient Chinese healers used themselves as guinea pigs to taste and test herbs for their medicinal properties. From generation to generation, the knowledge of pharmacological category, localities of production, harvesting, processing, natures and flavors, toxicity and non-toxicity, successful combinations, prohibitions, dispensing, dosage and administration has accumulated. A collection of information on 365 medicinal herbs discovered prior to the Han dynasty (206 BCE–220 CE) was compiled into the text Shen Nong Ben Cao Jing (Shen Nong's Book of Medical Herbs). This book was written between 100 BCE and 100 CE, and became the earliest Chinese Herbal materia medica.15,16 The herbs are divided into two categories in this text: with toxins and without toxins. The herbs "without toxins" are often tonic herbs which can be used relatively safely at a higher dosage or for a longer period of time. For example, Angelica (Dang Gui) is "with no toxicity," and can activate Blood and regulate the estrous cycle. Asinum Gelatinum (E Jiao) is "with no toxicity" and can tonify Blood and stop bleeding. The herbs "with toxicity" are often used for dispelling and eliminating pathogens (the cause of disease), and are labeled with warnings such as "Use with caution," are used at a lower dosage, or for a shorter period of time. For example, Melia (Ku Lian Zi) is "with toxicity," and can expel parasites. Pinellia (Ban Xia) is also "with toxicity," and can transform Phlegm and stop vomiting.
Three categories of herbal toxicity are documented in Huang Di Nei Jing (Yellow Emperor’s Internal Classic) published in the Warring States period (475 to 221 BC): strong, moderate and mild toxicity. After 30 years experience and consultation of more than 800 books including veterinary medical texts, Li Shizhen (1518-1593) wrote Ben Cao Gang Mu (Compendium of Materia Medica) which described 1,892 Chinese herbs and 11,096 Chinese herbal formulas. Not long after this book was published in 1596, it spread overseas and greatly contributed to the development of both the Chinese and western materia medica. Li Shizhen made four grades of herbal toxicity: potently toxic, toxic, mildly toxic and gently toxic.
Herbal Toxicity in Modern Practice
In modern medical practice, Chinese herbal medicines have officially been divided into three grades of toxicity: potently toxic, toxic and mildly toxic for both human and veterinary practice. This has been well documented in the Pharmacopoeia of the People's Republic of China17 and Veterinary Pharmacopoeia of the People's Republic of China,18 which has been approved by the Ministry of Health and the Ministry of Agriculture, PR China. In general, if an herb is labeled "potently toxic," it is very poisonous and can lead to strong and quick adverse reactions. For example, Aconite (Fu Zi) is "potently toxic." It can cause numb lips, tongue or extremities, nausea, irritability, decreased sensation, and eventually, heart rate and blood pressure decreases, weak and feeble respiration, and death. If an herb is labeled "toxic," its toxicity reaction occurs much more slowly and is less severe, even when using a large dose. For example, Pinellia (Ban Xia), may cause loss of voice, vomiting, watery diarrhea, and dyspnea. If an herb is "mildly toxic," its side effects won’t occur unless a very large dose is administered or/and it is administered for long-term use. For instance, Cnidium (She Chuang Zi) is categorized as "mildly toxic," but if used long-term, may cause a skin rash, pruritus, lethargy, abdominal pain, and diarrhea.
The toxic grades can also be based on the known data of the LD50 (the median lethal dose) in quantization toxicology in modern Chinese medicine. When lab animals were treated orally with an herbal decoction, the herbs with an LD50 < 5 g/kg were labeled as potently toxic, the herbs with an LD50 of 5-15 g/kg as toxic, the herbs with an LD50 of 16-50 g/kg as mildly toxic, while the herbs with an LD50 > 50 g/kg were considered non-toxic.19-20
Commonly Seen Toxic Chinese herbs and Precautions
Herbs containing aconitine are toxic to the nervous system.
Any herb containing aconitine can be very toxic. Aconitine excites the vagus nerve and central nervous system first, and then leads to successive inhibition, and finally death because of paralysis. Herbs containing aconitine include Aconite (Chuan Wu), Aconite (Cao Wu), Aconite (Fu Zi ), and Aconite (Xue Shang Yi Zhi Hao). It has been reported that 0.2 mg aconitine per patient by mouth caused toxic reactions in people, and 2-6 mg per patient orally could kill a human. Signs of toxic reaction are tremors and numbness of lips and limbs, excessive salivation, nausea, vomiting, diarrhea, dizziness, anxiety, disorientation, convulsions, dyspnea, paresis or paralysis, fecal or urinary incontinence, arrhythmia, coma and death. Fu Zi is the most commonly used herb containing aconitine in veterinary practice.21 The LD50 for unprocessed Fu Zi in mice is 5.49 g/kg via oral administration and 0.49 g/kg via intravenous injection. The LD50 for processed Fu Zi is 161 g/kg via oral administration and 3.516 g/kg via intravenous injection. The LD50 for a water extract of Fu Zi given orally in mice is 26.30 g/kg. Eleven classical and twelve Jing-Tang herbal formulas containing aconitine are listed in Table 1.
Herbs containing aconitine including Fu Zi should be cautioned for use in weak or pregnant animals.
All herbs containing aconitine are hot and potent. They are contraindicated for use in cases with Excess Heat or Yin Deficiency.
Herbs containing aconitine may cause drug tests to be positive. They should be discontinued 7 days prior to competition.
Herbs containing aconitine are often used for Yang Deficiency, Excess Cold, or Excess Wind-Damp. They should be discontinued or their dosage should be decreased as soon as Heat signs (cool-seeking, panting, red tongue, fast pulse) appear.
Patients who have a past history of cardiovascular disorders or are taking antiarrhythmic medications should take Fu Zi with extreme caution. 22
Table 1. A List of Herbs Containing Aconitine
Herbs with aristolochic acid are toxic to the kidneys
Aristolochic acid is very toxic to the kidneys. The LD50 for aristolochic acid in female/male rats is 183.9/203.4 mg/kg via oral administration, and 74.0/82.5 mg/kg via intravenous injection. The LD50 for aristolochic acid in female/male mice is 106.1/55.9 mg/kg via oral administration, and 70.1/38.4 mg/kg via intravenous injection.23 On May 16, 2000, the FDA posted a warning to the industry about herbs containing aristolochic acid. Products containing aristolochic acid were associated with life-threatening adverse effects due to their nephrotoxicity. On April 9, 2001, the FDA posted a revised list of botanical ingredients which are known or suspected to contain aristolochic acid.24 Six herbs which have been identified to contain aristolochic acid are Guan Mu Tong, Ma Dou Ling, Qing Mu Xiang, Tian Xian Teng, Guang Fang Ji and Xi Xin.24,25
- Guan Mu Tong (Aristolochia manshuriensis) has been used for less than 100 years in a local Northeast region in China. It was not documented as an herbal medicine until 1963. Guan Mu Tong contains Aristolochic acid A, D. An overdose of Guan Mu Tong causes vomiting, diarrhea, poor appetite, frequent urination, edema, dysuria, anuria, hematuria, proteinuria, cylindruria, increased urea nitrogen in blood and urine, and hyperkalemia. Oral administration of 30 mg/kg of Guan Mu Tong in mice caused hematuria and nephropathy. Overdose of Guan Mu Tong (over 60 grams per patient via oral administration in people) has been associated with nephropathy.16, 22
- Ma Dou Ling, Qing Mu Xiang and Tian Xian Teng are associated with Aristolochiaceae plants including Aristolochia contorta and Aristolochia debilis. Ma Dou Ling is the fruit of Aristolochia contorta or Aristolochia debilis, and is classically used for coughing and wheezing caused by the accumulation of Phlegm and/or Lung Heat. It contains aristolochic acid A, C, D. The LD50 for an alcohol extract of Ma Dou Ling in mice via oral administration is 22.02 g/kg. An overdose of 30 grams per patient of Ma Dou Ling in a decoction via oral administration may cause side effects such as nausea, vomiting, irritability, dizziness, shortness of breath, hematemesis and hematuria, and proteinuria in people.16,22
- Qing Mu Xiang is the root of Aristolochia debilis and contains Aristolochic acid A, B, C; aristolochia lactan, aristolone, aristolenone, isoaristolone, and aristolin. An overdose of 150 grams per human patient of Qing Mu Xiang via oral administration may cause nausea, vomiting, anuria, edema, and nephropathy. Qing Mu Xiang is classically used for moving Qi to relieve pain.16,22
- Tian Xian Teng is the stem and leaf of Aristolochia contorta or Aristolochia debilis, and contains trace amounts of Aristolochic acid D. Tian Xian Teng is classically used for moving Qi and Blood to relieve pain.16, 22
- Guang Fang Ji is the root of Aristolochia fangchi, and contains Aristolochic acid I, II, which is very toxic to the kidney. Its use should be avoided.16, 22
- Xi Xin is the aerial part of Asarum heterotropoides (Bei Xi Xin) or Asarum sieboldii (Hua Xi Xin). It belongs in the Aristolochiaceae family, and contains safrole and trace amounts of Aristolochic acid. It is extremely dangerous when used in larger quantities than suggested, or if used in powder form. The toxic safrole in the essential oil of Xi Xin can be reduced or removed by decocting. The LD50 for essential oil of Xi Xin in mice is 1.2 ml/kg via intraperitoneal injection. Respiratory paralysis was associated with overdose.16, 22
Controlling the sources. These six herbs, including Guan Mu Tong, Ma Dou Ling, Qing Mu Xiang, Tian Xian Teng, Guang Fang Ji and Xi Xin are rarely used in classical herbal formulas. However, they are sometimes misused or mistakenly substituted for other herbs in an herbal formula. For example, Aristolochia (Guan Mu Tong) is misused as, or substituted for, Akebia (Mu Tong). Aristolochia (Qing Mu Xiang) is misused as Saussurea (Mu Xiang), Aristolochia (Guang Fang Ji) is misused as Stephania (Fang Ji). The major problems occur when the Aristolochiae are mistakenly substituted as Akebia (Mu Tong), Saussurea (Mu Xiang) and Stephania (Fang Ji), which are commonly used in the classical herbal formulas. For example, of the three types of Fang Ji sold in the market, only one contains aristolochic acid, Gang Fang Ji (Aristolochia fangchi). The roots of Han Fang Ji (Stephania tetrandra) and Mu Fang Ji (Cocculus trilobus) do not contain aristolochic acid. However, if Aristolochia (Guang Fang Ji) is mistakenly substituted, the resulting formula will contain aristolochic acid and could result in toxicity.26 Another lab confirmed that authentic Akebia (Mu Tong), Saussurea (Mu Xiang), and Stephania (Fang Ji) were tested and shown to contain no aristolochic acid (Table 2).25 Their efficacy and safety have been well documented since Shen Nong Ben Cao Jing (published about 2,000 years ago).27 Thus, their safety is secured if their sources are known and controlled.
Table 2. Measurement of aristolochic acid in herbs25
- Never Use Guan Mu Tong, Ma Dou Ling, Guang Fang Ji, Tian Xian Teng, Qing Mu Xiang and Xi Xin. All these herbs contain aristolochic acid (Table 2). Some practitioners or herbal pharmacies use them as a substitute, which can cause kidney toxicity. Contact your herbal pharmacies to find out what their policies are regarding these herbs. The author is very confident and proud to say that Jing Tang Herbal never uses these herbs.
- Monitor some classical formulas. Long Dan Xie Gan Tang and Ba Zheng San contain Akebia (Mu Tong) (Table 2). Authentic Mu Tong is used and all these herbal formulas should not cause the renal toxicity associated with aristolochic acid. However, testing patent herbal medicines by high performance liquid chromatography (HPLC) for aristolochic acid is very important especially if the sources are questionable. Ask your herbal suppliers if they routinely run these tests and only purchase products from those who do.
- For renal insufficiency patients, caution must be taken when using the following herbs, which may possibly cause nephropathy: Yun Nan Bai Yao (Yunnan White Medicine), Xanthium (Cang Er Zi), Corydalis (Yan Hu Suo), Alisma (Ze Xie), Cinnamomum (Rou Gui), Uncaria (Gou Teng). These herbs are not definitely associated with any renal toxicity. When these herbs are properly used in a balanced formula, they are less likely to cause toxicity than if used as single herbs. However, when these herbs are used as single ingredients, the author recommends that you monitor renal function regularly.
Herbs containing ephedrine
Ephedra (Ma Huang) contains ephedrine and pseudoephedrine, which are well-absorbed. Peak plasma concentration is reached 1-2 hours after oral ingestion of the herb. Ephedrine and pseudoephedrine are distributed throughout the body, with higher concentrations found in the liver and kidneys. The LD50 for water-extracted Ma Huang in mice via intraperitoneal injection is 650 mg/kg.22 Ma Huang is classically used for releasing the Exterior, relieving asthma and stopping cough for a short term period (less than 5 days). Because of its actions on increasing metabolic rate, it has widely been abused as a weight loss supplement in western countries. Ma Huang can cause increased heart rate and blood pressure and may cause a stroke, or heart attack. At least 155 deaths were associated with chronic consumption of Ephedra (Ma Huang). In 2004, the FDA issued a final ruling which prohibited the sale of dietary supplements containing ephedrine alkaloids due to the unreasonable risk of illness those products presented to the consumer.28
Ephedra Ma Huang is not very useful in TCVM practice. Thus, it is not recommended for any veterinary practice. Ask your herbal supplier what their policy is regarding Ephedra. Jing-tang Herbal never uses it.
Table 3. A List of Herbs which may damage the liver
Herbs that are hepatotoxic
If overdosed or used long-term, the following herbs have been found to be toxic to the liver: Melia (Chuan Lian Zi), Pinellia (Ban Xia), Xanthium (Cang Er Zi), Dioscorea (Huang Yao Zi), Asarum (Xi Xin), and Tripterygium (Lei Gong Teng). These herbs can cause elevations in serum Alkaline Phosphatase (AP), ALT (SGPT), AST (SGOT), and total bilirubin. These findings are based on patients who were given these herbs individually, not as part of an herbal formula. Their toxicity to the liver when they are included in an herbal formula has not been reported. Further study to confirm their safety is needed. The herbal formulas containing at least one of these herbs are listed in Table 3.
Other herbs which may cause liver damage include Typha (Pu Huang), Indigo (Qing Dai), Tussilago (Kuan Dong Hua), Croton (Ba Dou), Chebula (He Zi), Myristica (Rou Dou Kou), Melaphis (Wu Bei Zi ), Punica (Shi Liu Pi), and Artemesia (Ai Ye).
- Make sure the dosage and usage are correct. Most cases of liver toxicity with Chinese herbs are caused by overdose or long-term use.
- Make sure the herbal processing is correct. For example, the toxicity of Pinellia (Ban Xia) is significantly reduced after being processed in water and ginger juice. For an average herbal practitioner to make sure of this, ask your herbal supplier what their procedures are.
- These herbs are contraindicated for use in patients that have liver disease.
- Monitor liver enzymes and liver function regularly where these herbs are used as individual herbs.
Herbs that upset the gastrointestinal (GI) system
GI upset is a common side effect of Chinese herbal medicine in veterinary practice. Individual herbs that can cause GI upset include: Sparganium (San Leng), Zedoaria (E Zhu), Sophora (Ku Shen), Rheum (Da Huang), Xanthium (Cang Er Zi), Cassia (Jue Ming Zi), Pharbitis (Qian Niu Zi), Croton (Ba Dou), Phytolacca (Shang Lu), Euphorbia (Gan Sui), Genkwa (Yuan Hua), Brucea (Ya Dan Zi). They can cause nausea, vomiting, anorexia, colic, diarrhea, or even GI hemorrhage. The most commonly used herbal formulas that contribute to GI upset are Ku Shen Si Wu, Stasis Breaker, and Double P II (modified Da Huo Luo Dan).
- Most common GI side effects associated with Chinese herbs are dose-related. Make sure the dosage and usage are correct.
- Administer 1/3 of normal dose in individuals susceptible to GI upset for 2 weeks, and then gradually increase to the desired dosage.
Common Reasons Chinese Herbs Cause Toxicity
True Chinese Herbal Toxicity
As discussed above, herbs can directly cause adverse effects on the central nerve system, kidneys, cardiovascular system, the liver and the GI system. The aconitine-containing herbs including Aconite (Fu Zi) can damage the nervous system. The herbs containing aristolochic acid are toxic to the kidneys. Ephedra (Ma Huang), containing ephedrine and pseudoephedrine, can cause adverse cardiovascular effects. Melia (Chuan Lian Zi) damages the liver. Techniques for minimizing toxicity and precautions are discussed above.
Herbs are Mistakenly Substituted or Used Inappropriately
Renal failure in human patients observed in Belgium from 1992-1993 was related to a slimming herbal regimen involving the herb Guang Fang Ji (Aristolochia fangchi) was mistakenly substituted for Han Fan Ji (Stephania tetrandra). Progressive interstitial fibrosis with tubular atrophy was seen in these patients after ingestion of Guang Fang Ji containing nephrotoxic Aristolochic acid.29-30 Since then, five other herbs containing Aristolochic acid have been found, Guan Mu Tong (Aristolochia manshuriensis), Xi Xin (Asarum heterotropoides or Asarum sieboldii), Ma Dou Ling, Qing Mu Xiang and Tian Xian Teng. The last three are associated with Aristolochiaceae plants including Aristolochia contorta and Aristolochia debilis.23, 25, 31-32 It is the author’s opinion that all these herbs should be banned in herbal practice since the pharmaceutical studies confirmed their toxicity and propensity to cause nephropathy.
The correct processing of Chinese herbs is one of the most important traditional methods to remove herbal toxicity. Many herbs’ original toxicity is reduced greatly after they are processed properly. Toxic alkaloids contained in some herbs will be degraded into mildly toxic or non-toxic forms throughout the decocting process. For example, raw (non-processed) Aconite root (including Chuan Wu, Cao Wu and Fu Zi) contains high concentrations of toxic aconitine. With the traditional decoction process (boiling and heating), aconitine can be easily hydrolyzed and becomes a mildly toxic alkaline. The toxicity of Aconite Chuan Wu, Cao Wu or Fu Zi can be reduced 2000-4000 times using heat-processing.15 Another traditional method used to reduce herbal toxicity is combining the herbs in an herbal formula. One Chinese herb can decrease or eliminate the toxicity or side effects of another herb in the formula. For example, fresh ginger can eliminate or decrease the toxicity and side effects of fresh Pinellia (Ban Xia) and Arisaema tuber (Tian Nan Xing). Similarly, Ledebouriella root (Fang Feng) suppresses the toxic effect of Arsenic (Pi Shuang), and Mung bean, Phaseolus (Lu Dou), can suppress the toxic effect of Croton seed (Ba Dou).27
Dosage and Usage:
Chinese herbal medicine was originally called "Cao Yao". Cao is herb, or plant. Yao is drug. Thus, we need to treat the Chinese herbs as "drugs." Like any pharmaceutical drugs, Chinese herbs can have side effects or cause toxicity. Unfortunately, they are listed as dietary supplements, or sometimes as "natural" supplements in western countries. This can lead to their inappropriate use for long periods or to overdose, leading to toxicity. For example, Armeniaca (Ku Xing Ren) is often used in people for stopping cough and relieving asthma. The normal safe oral dose of Ku Xing Ren given as a decoction is 3-10 grams per patient for 3 to 5 days in people. Its overdose or long-term use causes dizziness, palpitation, nausea, vomiting, coma, convulsion, or death. This is because Ku Xing Ren contains amygdalin, which can become hydrocyanic acid in the presence of gastric acid after ingestion. One gram of Ku Xing Ren yields approximately 30 mg of amygdalin and 2.5 mg of hydrocyanic acid. Hydrocyanic acid is a toxic substance, and can be lethal at 50 mg per patient in people by inhibiting respiration and leading to asphyxiation. The lethal dose of Ku Xing Ren was reported to be 50-60 kernels (60 grams) in adult people and 30-40 kernels (about 40 grams) in children. However, small doses and short-term use of Ku Xing Ren is highly unlikely to cause toxicity as there is a metabolic system to excrete Ku Xing Ren gradually and continuously. 15-16, 22
The Inappropriate Compatibility of Herbs
Incompatibility occurs when an herb can cause or enhance toxicity or side effects when used with another herb. Traditionally, Licorice root Glycyrrhiza (Gan Cao) causes toxicity when combined with Kansui root Euphorbia (Gan Sui). Modern pharmaceutical studies also help practitioners avoid incompatibility issues. For instance, Armeniaca (Ku Xing Ren) and Persica (Tao Ren) both contain amygdalin. When they are combined in a formula, quantization toxicology has demonstrated that the amount of amygdalin and hydrocyanic acid is doubled, which makes such a combination incompatible.
Interaction and Incompatibility of Western and Chinese Medicine
Chinese herbal medicines can usually be used safely with Western pharmaceuticals. In fact, treatment with Western medications can cause imbalances in the body, so herbal formulas may be used to treat the patterns resulting from the side effects of the pharmaceutical. However, there are some situations in which Chinese herbal and Western medicines should not be used together (Table 4).
Table 4. Precautions when using a Combination of Herbs and Western Pharmaceutical Drugs
Herbs containing flavonoids [Scutellaria (Huang Qin), Lonicera (Jin Yin Hua), Citrus (Chen Pi), and Inula (Xuan Fu Hua) should not be used with aluminium hydroxide, magnesii trisilicas and calcium carbonate. The metal ions in these Western medications interact with the flavonoids in the herbs to form metal complexes. This changes the herbs’ original properties and can significantly reduce their effect.
Charred herbs [Sanguisorba (Di Yu), Acacia (Er Cha), Rhus (Wu Bei Zi), Polygonum (Hu Zhang) and Rheum (Da Huang) should not be used with Vitamin B because the herbal charcoal combines with the Vitamin B and this complex is then eliminated from the body. Therefore, efficiency of both the herbs and the vitamin B is decreased.
It is important to carefully monitor patients who are receiving Western cardiac drugs, diuretics, anti-diabetic drugs, anti-hypertensive medications and blood thinners in addition to herbal formulas with similar actions. These patients are more susceptible to overdose.15-16, 22, 33
The Difference of Individual Susceptibility
Each individual has different sensitivity and tolerance to herbal medication. Thus, the same herbal medication has no side effects at all in the majority of patients, but may cause adverse reactions in others. For example, Rehmannia (Shu Di Huang), Paeonia (Bai Shao Yao), Lonicera (Jin Yin Hua), Ostrea (Mu Li) cause no adverse reactions in the majority of patients. However, they have occasionally caused allergic skin reactions in some sensitive patients.
Wrong TCVM Pattern Differentiation
Chinese herbs treat a pattern, not a disease. Adverse reactions may be seen when an herb is prescribed for the wrong pattern. Chinese Ginseng (Ren Shen) can be used for chronic fatigue syndrome due to Qi Deficiency (anorexia, chronic diarrhea or urinary leakage, pale or wet tongue, weak pulse). It can cause hematuria, hypertension, or anxiety if used for chronic fatigue syndrome due to Yin Deficiency (red and dry tongue, thin and fast pulse, cool-seeking, panting worse at night). Traditionally, Chinese Ginseng is contraindicated for Yin Deficiency Pattern because of its hot property. This is an example of an herb being used for an inappropriate pattern and causing adverse effects.
The toxicity or adverse effects of traditional Chinese medicine is cause for concern nationally and internationally. Chinese herbal toxicity and adverse effects are mainly caused by improper processing procedures, over dosage, the inappropriate substitution of one herb for another in a formula, individual differences of each patient, and application of an incorrect pattern diagnosis. In order to practice Chinese herbal medicine properly and avoid many adverse reactions, a well-trained veterinary herbalist is needed to practice this discipline. As more pharmaceutical studies are conducted to evaluate CHM, the safer the practice of CHM will be.
Yu C. Traditional Chinese Veterinary Medicine (2nd edition). Beijing: China Agriculture Press. 1985. Page 1-6
Zhao P, Su G, Xiao X, Hao E, Zhu X, Ren J. Chinese medicinal herb Radix Astragali suppresses cardiac contractile dysfunction and inflammation in a rat model of autoimmune myocarditis. Toxicol Lett. 2008 Nov 10;182(1-3):29-35.
Dai Y, But PP, Chan YP, Matsuda H, Kubo M. Antipruritic and antiinflammatory effects of aqueous extract from Si-Wu-Tang. Biol Pharm Bull. 2002 Sep;25(9):1175-8.
Wilcox DL, Liu H, Ma Y, Xie H, Tangjitjaroen W. Comparison of the Chinese Herbal Formula Hai Zao Yu Hu Tang and Methimazole for the Treatment of Feline Hyperthyroidism. American Journal of Traditional Chinese Veterinary Medicine. 2009 Vol 4 (1): 27-38
Xie H, Liu H, Merritt, AM. Ott EA Equine chronic diarrhea: Traditional Chinese veterinary medicine review. Journal of Equine Veterinary Science, 1997, Vol 17 (12): 667-674
Shmalberg J, Xie H. The Clinical Application of Equine Acupuncture. Journal of Equine Veterinary Science. 2009 Vol 29 (10): 753-760
Kim MS, Xie H. and Bannai Y. Application of Acupuncture and Chinese Herbal Medicine for the Treatment of Acanthomatous Epulis in a Dog J Vet Clin 2008 25(1): 27-30.
Song D, Song J, Song X. Traditional Chinese Veterinary Medicine Immunology and its Application in the Treatment of Canine and Feline Diseases. American Journal of Traditional Chinese Veterinary Medicine. 2008 Vol 3 (1): 24-30
Tangjitjaroen W, Xie H, Colahan P. The Therapeutic Actions of Traditional Chinese Herbal Medicine Used for the Treatment of Equine Respiratory Diseases. American Journal of Traditional Chinese Veterinary Medicine. 4(1): 7-21, 2009.
Xie H, Ortiz-Umpierre C. What acupuncture can and cannot treat. Journal of the American Animal Hospital Association, July/August; 2006. Vol. 42 (4): 244-248
Trina Ward. Safety Concerns involving Chinese Herbal Medicine. In: Mills & Bone (ed) The Essential Guide to Herbal Safety. St. Louis, Missouri: Elsevier Churchill Livingstone. 2005. Pages 119-127
Poppenga RH. Herbal Medicine: Potential for intoxication and interactions with conventional drugs. In: Wynn & Fougere (ed) Veterinary Herbal Medicine. St. Louis, Missouri: Mosby. 2007. Pages 183-207.
Stedman C. Herbal hepatotoxicity. Seminars in Liver Disease. 2002. Vol 22 (2):195-206.
Chavez ML Jordan MA, Chaves PI. Evidence-based drug-herbal interactions. Life Sciences. 2006, 78: 2146-2157.
Xu XY. Pharmacology of Chinese Herbal Materia Medica. Beijing: People’s Health Press. 2005. Pages 11-18.
Gao XM. Chinese Herbal Materia Medica. Beijing: China Traditional Chinese Medicine Publishing House. 2002.
Pharmacopoeia Committee of the People's Republic of China. Pharmacopoeia of the People's Republic of China. Chemical Industry Publishing House, Beijing. 2005.
Veterinary Pharmacopoeia Committee of the People's Republic of China. Veterinary Pharmacopoeia of the People's Republic of China, 2005.
Xu X W. Toxicity classification exploration of toxic herbs. Zhejiang Journal of Traditional Chinese Medicine, 2006, 41(5)?308
He X Y. Classified Study on the Toxicity of 615 Kinds of Common Traditional Chinese Medicines. China Pharmacy, 2007,18(30), 2392, 2394
Liu ZJ, Xu JQ. Traditional Chinese Veterinary Medicine (3rd edition). Beijing: China Agriculture Press. 2005.
Chen JK, Chen TT. Chinese Medical Herbology & Pharmacology, Art of Medicine Press, 2004.
Jiang GZ, Chen L. New Research Progress of Toxicity of Aristolochic acid in Traditional Chinese Medicine. Chinese Agricultural Science Bulletin. 2008, 24 (9): 84-87.
Ying XX, Yuan CL, Qu XG, Zhang H, Fang XM, Shu XM. Measurement of Aristolochic acid of Chinese herbs. Liaoning Journal of Traditional Chinese Medicine. 2003, 30(5): 404.
Ellis A. 2000. In Response to FDA Concern About Aristolochic Acid and Chinese Herbs. American Herbal Products Association Report Fall:15,17
Xie H, Preast V. Xie’s Chinese Veterinary Herbology. Wiley-Blackwell. 2010.
Vanherweghem JL. A new form of nephropathy secondary to the absorption of Chinese herbs. Bull Mem Acad R Med Belg. 1994;149(1-2):128-35.
Violon C. Belgian (Chinese herb) nephropathy: why? J Pharm Belg. 1997 Jan-Feb;52(1):7-27.
Fu GX, Zhao SP. Chinese herbs and formulas containing aristolochic acid. Journal of China-Japan Friendship Hospital. 2003, 17(2): 110-112.
Zhou GJ, Ying HP. Studies on herbs containing aristolochic acid. Chin J Nat Med. 2005, 7(3): 271-275.
Bensky D, Clavey S and Stoger E. Chinese Herbal Medicine Materia Medica (3rd Edition), Eastland Press, 2004.