Xiăo Chái Hú Tāng (Minor Bupleurum Decoction)

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Xiăo Chái Hú Tāng (Minor Bupleurum Decoction) [1]

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Xiăo Chái Hú Tāng (Minor Bupleurum Decoction) 

By Tina Chen, L.Ac.

Xiao Chai Hu Tang (Minor Bupleurum Decoction) is one of those formulas you study in school but probably never really knew how to use because it’s a formula for Shaoyang syndrome, which is ideal to be used for a short period before the pathogen moves from the Taiyang to Yangming stage. Who would see all those symptoms described in the clinical manifestations below all at the same time?

However, after practicing for a while and using it on various patients, it’s one of my favorite formulas because of its wide application.

Other than the textbook indications, it can be used on the following two types of patients by itself or combined with other formulas or herbs. My herb teacher is from Taiwan and so I prescribe herbs according to the Fang Jia Fang method, which combines herbal formulas in the granular form. If you are unfamiliar with this method, Dr. John Chen offers a good explanation here. https://www.youtube.com/watch?v=Zjr48VSyQJ4 [2]

Type 1: Temperature Fluctuation

Anytime you see any patient with temperature fluctuation, 90% of the time they are females, you can consider using this formula. By temperature fluctuation, here are a few examples: they can feel hot during a certain time of the day, for example at sunrise, but won't feel hot the rest of the day; they can feel hot during a particular time of the month, for example before their period; they feel hot on a particular part of their body, like the head, but not the rest of the body, or only in the torso, but not the limbs, vice versa. Usually, if the heat sensation is higher, the patient may sweat a bit then possibly leading to the cold sensation. This type of patient is ideal for using Xiao Chai Hu Tang (Minor Bupleurum Decoction) as they fit the alternating chills and fever description.

Usually, I like to add a heat-clearing detoxifying formula with Xiao Chai Hu Tang (Minor Bupleurum Decoction) to clear the lingering heat or toxic pathogen. The overall effect is better.

Type 2: Lingering Common Cold or Allergy

Many people have what they think are allergies but are untreated common colds/flu. They generally have mild or no symptoms except some itchy nose, runny nose, occasional sneezing, postnasal drip, etc ESPECIALLY in the mornings. Some cases are due to allergy but many are simply untreated colds. People will either take over the counter drugs to suppress their cold symptoms or take Chinese herbs, but stop prematurely when they feel slightly better and stop completely because they want their immune system to do the rest. This is often counterproductive. In my opinion, I feel the bacteria and viruses are much stronger now because of the misuse of antibiotics. Many strands of bacteria and viruses are drug-resistant making them more difficult to completely get rid of. As a result, this pathogen lingers in the body and sometimes causes symptoms and sometimes not. This is called the shaoyang syndrome. Or, the pathogen can be stuck in between taiyang and yangming where the body isn’t strong enough to dispel it and the pathogen isn’t strong enough to further invade the body. As a result, you see cold and allergy symptoms that are sometimes there and sometimes not.

This is especially true for women who catch a cold during their periods. Imagine the wei (defensive) qi as an invisible barrier covering the entire body. During the period with bleeding, technically the pathogen can invade directly inside, bypassing the taiyang stage. So with women who caught a cold during their period, they won’t remember when and would likely experience symptoms when their period comes. For example, many women experience migraines or nausea before their periods. This would be the perfect case to use Xiao Chai Hu Tang (Minor Bupleurum Decoction). Any other symptoms that are period related, you can consider using this formula.

Speaking about catching a cold, many women don’t like to blow dry their hair for beauty reasons and that contributes directly to cold attacking the uterus and also quickly developing migraines. I learned from Dr. Peng I-Chun that the scalp and the uterus are connected. When the hair is wet, the uterus contracts, and the exterior cold pathogen can easily invade. Since the uterus contracts, it leads to poor circulation down below, and along with the cold, fibroids can form easily. This is the reason why Chinese women don’t wash their hair post-partum as they are afraid of blood stasis forming, thus impeding the lochia purging process. Years after I learned this from my teacher, I started asking my peri-menopausal friends and patients if they noticed after washing their hair during their period, would it shorten their periods? To my finding, the answer is yes. So to my conclusion, when the body is fairly healthy, one won’t notice small details like this. Blow drying the hair or not would make no difference. However, when the body is deficient or old to a certain point, one starts to experience subtle changes and symptoms like this. You may ask, “But the water is hot and the blow dryer heat is hot. Why would that matter?” I think perhaps it’s better, but there will be a time when the scalp and the hair exposed to being wet and not completely warm. It’s definitely better than washing with cold water and not drying the hair and going to bed, then waking up the next morning with a cold or with a headache. So dry your hair to prevent headaches and fibroids from developing.

Secondary formulas to consider adding can be formulas that address the symptoms such as Xin Yi San (Magnolia Flower Powder), Yin Qiao San (Honeysuckle and Forsythia Powder), Gui Zhi Tang (Cinnamon Twig Decoction), etc depending on what symptoms are manifested.

In conclusion, one does not have to show ALL the symptoms listed in the indication for you to prescribe this formula. If you see the key signs that the Liver is involved or there is fluctuating temperature or recurrent conditions, feel free to try this formula.

Below is the textbook explanation of Xiao Chai Hu Tang (Minor Bupleurum Decoction).

小柴胡湯 

小柴胡汤 

Pinyin Name: Xiao Chai Hu Tang

Literal Name: Minor Bupleurum Decoction 

Alternate Names: Hsiao Tsai Hu Tang, Minor Bupleurum Combination 

Original Source: Shang Han Lun (Discussion of Cold-Induced Disorders) by Zhang Zhong-Jing in the Eastern Han Dynasty 

COMPOSITION

DOSAGE / PREPARATION / ADMINISTRATION

The source text specifies to cook the ingredients in 12 cups [2,400 mL] of water until 6 cups [1,200 mL] of the liquid remain. Discard the residue, and cook the strained decoction again until it is reduced to 3 cups [600 mL]. Take 1 cup [200 mL] of warm decoction per dose, three times daily. Today, the decoction may be prepared using the doses suggested in brackets.

CHINESE THERAPEUTIC ACTIONS

Harmonizes shaoyang

CLINICAL MANIFESTATIONS

1.       Shaoyang syndrome: alternating spells of fever and chills, chest and hypochondriac fullness and discomfort, irritability, a bitter taste in the mouth, lack of appetite, nausea, vomiting, vertigo, a dry throat, a thin, white tongue coating, and a wiry pulse.

2.       Any of the following disorders with shaoyang characteristics: gynecological disorders with heat in the uterus, Liver, or chong (thoroughfare) channel; malaria; jaundice; or any internal injury characterized by shaoyang syndrome.

CLINICAL APPLICATIONS

Hepatitis, viral hepatitis, chronic hepatitis, hepatic fibrosis and carcinoma, hepatocellular carcinomas, jaundice, cholecystitis, cholelithiasis, pancreatitis, fever, fever in cancer, nephritis, chronic renal insufficiency, acute tonsillitis, infectious parotitis, stomatitis, common cold, influenza, measles, bronchitis, pneumonia, pulmonary tuberculosis, cough, allergic rhinitis, bronchial asthma, reflux esophagitis, antral gastritis, gastritis, gastric pain, gastric prolapse, constipation, Meniere’s syndrome, dizziness, seizures, migraine, angina, depression, chronic fatigue syndrome, morning sickness, postpartum infection, postpartum fever, dysmenorrhea, premenstrual syndrome, and malaria.

EXPLANATION

Xiao Chai Hu Tang (Minor Bupleurum Decoction) is the main formula for harmonizing shaoyang syndrome, one of the six stages of disease progression described in Shang Han Lun (Discussion of Cold-Induced Disorders). The shaoyang is situated between yang and yin, or between the exterior and interior; therefore, alternating spells of fever and chills may occur in shaoyang syndrome if the body is fighting both the pathogens outside and the disharmony inside.

Disorders in the shaoyang may cause qi stagnation and eventual heat formation in the Gallbladder channel (a shaoyang channel), giving rise to chest and hypochondriac fullness and discomfort, a bitter taste in the mouth, vertigo, a dry throat, and irritability. Lack of appetite, nausea, and vomiting are the results of Gallbladder heat invading the Stomach. The tongue coating is thin and white because the pathogenic factors have not yet transformed into internal heat. The wiry pulse is the result of qi stagnation in the shaoyang channel.

Because the disease resides between the exterior and the interior, it is not suitable to use only exterior-releasing herbs or only purgative herbs. Use of only exterior-releasing herbs will not treat the interior condition, and use of only heat-clearing or downward draining herbs will bring the pathogens from the exterior into the interior. Therefore, the harmonizing method is the most appropriate treatment approach in this condition.

Chai Hu (Radix Bupleuri) is the main herb for treating shaoyang disorders. The light quality of Chai Hu (Radix Bupleuri) lifts and disperses stagnation, as well as releases to the exterior. Huang Qin (Radix Scutellariae), a bitter and cold herb that enters the Gallbladder channel, is ideal for clearing shaoyang heat. Together, Chai Hu (Radix Bupleuri) disperses the exterior while Huang Qin (Radix Scutellariae) clears the interior to achieve the harmonizing effect. Ban Xia (Rhizoma Pinelliae), besides harmonizing the Stomach to relieve nausea and vomiting, disperses stagnation in the body. Sheng Jiang (Rhizoma Zingiberis Recens) helps Ban Xia (Rhizoma Pinelliae) harmonize the middle jiao. It also reduces the toxicity of Ban Xia (Rhizoma Pinelliae). Ren Shen (Radix et Rhizoma Ginseng), Zhi Gan Cao (Radix et Rhizoma Glycyrrhizae Praeparata cum Melle), and Da Zao (Fructus Jujubae) tonify Stomach qi, nourish body fluids, and harmonize the ying (nutritive) and wei (defensive) levels. The combination of Chai Hu (Radix Bupleuri) and Ren Shen (Radix et Rhizoma Ginseng) also provides mutual check and balance for each others: Chai Hu (Radix Bupleuri) prevents the tonic effect of Ren Shen (Radix et Rhizoma Ginseng) from retaining the pathogens in the body, while Ren Shen (Radix et Rhizoma Ginseng) prevents the dispersing effect of Chai Hu (Radix Bupleuri) from damaging qi. Combined, these herbs expel the pathogens and strengthen bodily constitution.

Because the shaoyang stage is unstable and often short and transient, the symptoms listed above may not be clinically present all at the same time. Therefore, as suggested in Shang Han Lun (Discussion of Cold-Induced Disorders), this formula can be applied even if there is only one shaoyang symptom present clinically.

MODIFICATIONS

General Signs and Symptoms

·         If accompanied by headache, add Chuan Xiong (Rhizoma Chuanxiong).

·         If there is thirst, remove Ban Xia (Rhizoma Pinelliae) and add Tian Hua Fen (Radix Trichosanthis).

·         With thirst and irritability from deficiency heat, add Mai Dong (Radix Ophiopogonis) and Wu Wei Zi (Fructus Schisandrae Chinensis).

·         If there is no thirst, but a slight fever and exterior symptoms are present, remove Ren Shen (Radix et Rhizoma Ginseng) and add Gui Zhi (Ramulus Cinnamomi).

·         With irritability, add Dan Zhu Ye (Herba Lophatheri) and Geng Mi (Semen Oryzae).

·         With more irritability but absence of nausea or vomiting, remove Ban Xia (Rhizoma Pinelliae) and Ren Shen (Radix et Rhizoma Ginseng), and add Gua Lou (Fructus Trichosanthis).

·         With abdominal pain, remove Huang Qin (Radix Scutellariae) and add Bai Shao (Radix Paeoniae Alba).

·         With more vomiting or nausea, add Sheng Jiang (Rhizoma Zingiberis Recens) and Chen Pi (Pericarpium Citri Reticulatae).

·         When there is indigestion in children, add Bai Zhu (Rhizoma Atractylodis Macrocephalae), Chen Pi (Pericarpium Citri Reticulatae), Fu Ling (Poria), and Shan Zha (Fructus Crataegi).

·         If there is gum pain caused by yin deficiency, add Shi Gao (Gypsum Fibrosum).

·         With palpitations and dysuria, remove Huang Qin (Radix Scutellariae) and add Fu Ling (Poria).

·         With distention and hardness of the hypochondriac area caused by phlegm accumulation, remove Da Zao (Fructus Jujubae) and add Mu Li (Concha Ostreae).

·         If the hypochondriac pain is severe, add Qing Pi (Pericarpium Citri Reticulatae Viride), Bai Shao (Radix Paeoniae Alba) and Xiang Fu (Rhizoma Cyperi).

·         With a stifling sensation in the chest, add Zhi Shi (Fructus Aurantii Immaturus) and Qing Pi (Pericarpium Citri Reticulatae Viride).

Liver and Gallbladder Disorders

·         For icteric jaundice and hepatitis, add Zhi Shi (Fructus Aurantii Immaturus), Yin Chen (Herba Artemisiae Scopariae), Bai Shao (Radix Paeoniae Alba), and Jin Qian Cao (Herba Lysimachiae).

·         For damp-heat jaundice, add Yin Chen (Herba Artemisiae Scopariae), Zhi Zi (Fructus Gardeniae), and Ban Lan Gen (Radix Isatidis).

·         For jaundice with more heat, add Zhi Zi (Fructus Gardeniae) and Huang Bo (Cortex Phellodendri Chinensis).

Infectious Disorders

·         For common colds, add Jing Jie (Herba Schizonepetae), Fang Feng (Radix Saposhnikoviae), and Ge Gen (Radix Puerariae Lobatae).

·         For influenza, add Jin Yin Hua (Flos Lonicerae Japonicae), Lian Qiao (Fructus Forsythiae), and Ban Lan Gen (Radix Isatidis).

·         For acute bronchitis, add Jie Geng (Radix Platycodonis), Zhi Qiao (Fructus Aurantii), Ku Xing Ren (Semen Armeniacae Amarum), and Bai Bu (Radix Stemonae).

·         For chronic bronchitis, add Fu Ling (Poria), Chen Pi (Pericarpium Citri Reticulatae), Zi Wan (Radix et Rhizoma Asteris), and Kuan Dong Hua (Flos Farfarae).

·         For acute otitis media, add Long Dan (Radix et Rhizoma Gentianae) and Zhi Zi (Fructus Gardeniae).

·         For urinary tract infection, add Bian Xu (Herba Polygoni Avicularis), Che Qian Cao (Herba Plantaginis), and Hai Jin Sha (Spora Lygodii).

·         For malaria, add Chang Shan (Radix Dichroae), Bing Lang (Semen Arecae) and Wu Mei (Fructus Mume).

Gynecological Disorders

·         For postpartum wind invasion with perspiration, remove Chai Hu (Radix Bupleuri).

·         For postpartum wind invasion without fever, remove Huang Qin (Radix Scutellariae).

·         For postpartum wind invasion with increased vomiting or nausea, increase the dose of Sheng Jiang (Rhizoma Zingiberis Recens).

·         For postpartum wind invasion with marked deficiency, increase the dose of Ren Shen (Radix et Rhizoma Ginseng).

·         When there is wind invasion during the menstrual period, add Niu Xi (Radix Achyranthis Bidentatae), Tao Ren (Semen Persicae), and Mu Dan Pi (Cortex Moutan).

CAUTIONS / CONTRAINDICATIONS

·         Xiao Chai Hu Tang should be used with caution in patients with yin and/or blood deficiencies, in patients with upper excess and lower deficiency, or in patients with Liver fire. Inappropriate use of this formula may result in headache, dizziness, or bleeding gums.

·         In general, there is no sweating associated with relief of symptoms, following the administration of Xiao Chai Hu Tang, since it harmonizes, rather than releases the exterior. However, some patients do show sweating prior to recovery. They should be monitored closely to prevent excessive sweating from injuring yin.

·         Avoid cold, raw, pungent, and spicy foods while taking this formula.[1] [3]

PHARMACOLOGICAL EFFECTS

1.       Hepatoprotective: Administration of Xiao Chai Hu Tang was associated with preventive and beneficial effects against various types of drug- or chemical-induced liver damage. In one study, intraperitoneal injection of the formula in rats effectively controlled galactose-induced liver disorder in 65-70% of subjects by lowering the SGOT and SGPT.[2] [4] Other studies have indicated that the formula is also effective against liver cirrhosis induced by carbon tetrachloride.[3] [5] Yet another study reported that Xiao Chai Hu Tang was effective in treating liver inflammation and fibrosis.[4] [6] One proposed mechanism of this hepatoprotective effect is the augmentation of natural killer (NK) cell activity in the liver.[5] [7] Another proposed mechanism is a dose-dependent increase in the production of granulocyte colony-stimulating factor (G-CSF) on peripheral blood mononuclear cells.[6] [8]

2.       Cholagogic: Administration of Xiao Chai Hu Tang was associated with a marked effect of increasing the secretion of bile acid from the gallbladder and its excretion into the intestines in animals.[7] [9]

3.       Immunostimulant: Administration of Xiao Chai Hu Tang has marked effect on the immune system. In one study of mice, 100 mg/kg of the herb was associated with stimulating natural killer (NK) cells activities, while 200 mg/kg was associated with inhibition of NK cell activity.[8] [10]

4.       Anti-inflammatory: Intraperitoneal injection of the formula in rats at 200 mg/kg was associated with marked anti-inflammatory effects for up to 4 hours.[9] [11] The anti-inflammatory effects were also present in rats whose adrenal glands had been surgically removed.[10] [12]

5.       Effect on temperature regulation: Administration of Xiao Chai Hu Tang was associated with effectiveness in reducing body temperature in rabbits with artificially-induced fever,[11] [13] but it had little effect in rabbits with normal body temperature.[12] [14]

6.       Gastrointestinal: Administration of Xiao Chai Hu Tang was associated with inhibiting gastric acid production in rats. However, it had a stimulating effect on the intestines to increase peristalsis.[13] [15]

7.       Effect on hypercholesterolemia and hyperlipidemia: Administration of Xiao Chai Hu Tang and Da Chai Hu Tang (Major Bupleurum Decoction) was associated with beneficial effects in treating rats with cholesterol-induced hypercholesterolemia and aging-induced hyperlipidemia. Both formulas reduced total cholesterol in the liver and triglycerides in the liver and blood.[14] [16]

8.       Antiallergic: Administration of Xiao Chai Hu Tang had a dose-dependent effect to significantly inhibit histamine release to treat allergies. The proposed mechanism of this effect was attributed to the ability of Xiao Chai Hu Tang to inhibit IgE receptor-associated protein phosphorylation in the histamine release pathway.[15] [17]

9.       Antiulcer: Xiao Chai Hu Tang was effective in treating gastric ulcers in rats. Xiao Chai Hu Tang had a comparable effect to sucralfate in protecting the gastric mucosa, and had effects similar to cimetidine or atropine in inhibiting gastric acid secretions.[16] [18] Xiao Chai Hu Tang also showed an antiulcer effect against both water-immersion stress-induced gastric lesions and ethanol-induced gastric injury in a dose-dependent manner.[17] [19]

10.    Antitumor: Administration of Xiao Chai Hu Tang was associated with antitumor activity, presumably because it stimulates host-mediated factors such as the phagocytic function of the reticuloendothelial system and C3 cleavage producibility, and is closely related to TNF production. It is unclear whether Xiao Chai Hu Tang has a direct antitumor effect.[18] [20]

11.    Antitumor and antimetastatic: Administration of Xiao Chai Hu Tang in mice with malignant melanoma was associated with slowing tumor development and the transition to malignancy, decreasing incidence of distant metastasis to brain and kidney, and, at the malignant stage, prolonging life span.[19] [21] The mechanism of this action was attributed to the ability of Xiao Chai Hu Tang to inhibit the growth of malignant melanoma cells by up-regulating Fas-mediated apoptosis and arresting the cell cycle through down-regulation of cyclin dependent kinases.[20] [22] Xiao Chai Hu Tang also inhibited lung carcinoma growth and metastasis, with special reference to macrophage activation.[21] [23]

12.    Radioprotective: Administration of Xiao Chai Hu Tang and/or methylprednisolone was associated with protective effects against radiation-induced damage to lung tissues. The efficacy of radioprotective effect from the mildest to the most potent were Xiao Chai Hu Tang, methylprednisolone, and the combination of both (more effective than either alone).[22] [24]

13.    Bioavailability: Oral administration of Xiao Chai Hu Tang before or after meals did not show any significant difference in the maximum plasma concentration or the plasma concentration-time curve. The study concluded that timing of administration (before or after meals) did not affect the blood concentration (bioavailability) of Xiao Chai Hu Tang.[23] [25]

CLINICAL STUDIES AND RESEARCH

1.    Chronic hepatitis: In a double-blind multicenter clinical study involving 222 patients with chronic active hepatitis, use of Xiao Chai Hu Tang was associated with a decrease of HBeAg and an increase of anti-HBe antibodies. No remarkable side effects were noticed.[24] [26] In another study, two groups of patients with chronic hepatitis were treated with modified Xiao Chai Hu Tang with good results. In one group of 41 patients with chronic infectious hepatitis, 26 patients had significant improvement and 13 patients had moderate improvement. In another group of 21 patients with chronic active hepatitis, 10 patients had significant improvement and 8 patients had moderate improvement. The formula used contained Chai Hu (Radix Bupleuri) 12g, Huang Qin (Radix Scutellariae) 12g, Tai Zi Shen (Radix Pseudostellariae) 15g, Ban Xia (Rhizoma Pinelliae) 10g, Gan Cao (Radix et Rhizoma Glycyrrhizae) 6g, and dry-fried Zhi Zi (Fructus Gardeniae) 10g.[25] [27] In another study, administration of Xiao Chai Hu Tang for 2-3 months was associated with marked symptomatic relief and improvement of liver function among 45 chronic hepatitis patients who did not respond to prednisone.[26] [28]

2.    Viral hepatitis: Use of Xiao Chai Hu Tang has been shown in many studies to effectively treat hepatitis. In one study, 307 patients with viral hepatitis were treated with 87.75% effectiveness using Xiao Chai Hu Tang plus Zhi Zi (Fructus Gardeniae) and Hua Shi (Talcum) as the base formula.[27] [29] For 50 patients with chronic hepatitis B, one study reported 86.0% effectiveness using Xiao Chai Hu Tang plus Zhu Ling (Polyporus), Huang Qi (Radix Astragali), and Zao Xiu (Rhizoma Paridis) as the main herbal treatment.[28] [30]

3.     Hepatitis C: One study investigated the mechanism of action on the therapeutic effect of Xiao Chai Hu Tang to suppress liver cancer development. The study found that in hepatitis C patients, use of Xiao Chai Hu Tang could adjust the decreased IL-10 production and the increased IL-4 and IL-5 production of mononuclear cells, indicating that this moderate regulation of the cytokine production system may be useful in the prevention of disease progression.[29] [31]

4.     Hepatic fibrosis and carcinoma: Xiao Chai Hu Tang demonstrated chemopreventive and anti-carcinogenic effects against the development of hepatocellular carcinoma in cirrhotic patients. Evidence showed that Xiao Chai Hu Tang suppressed oxidative stress in hepatocytes and hepatic stellate cells, inhibited chemical hepatocarcinogenesis in animals, and acted as a biological response modifier by suppressing the proliferation of hepatoma cells by inducing apoptosis and arresting the cell cycle. Baicalin, baicalein, and saikosaponin-a are believed to be three of the main active compounds in Xiao Chai Hu Tang .[30] [32] In another study, administration of Xiao Chai Hu Tang inhibited collagen production, while an increase in retinoid level inhibited activation of Ito cells, leading to inhibition and prevention of liver fibrosis.[31] [33]

[33]

5.     Hepatocellular carcinomas: In a prospective, randomized, non-blind controlled study, 260 patients with liver cirrhosis were randomly assigned to 2 groups: patients in the trial group were given 7.5 g/day of Xiao Chai Hu Tang orally in addition to the conventional drugs given to the control patients. After monitoring the patients for 60 months, the study reported that the incidence of hepatocellular carcinomas was lower and the survival rate was higher for the trial group compared with the control group. The researchers concluded that Xiao Chai Hu Tang helped to prevent the development of hepatocellular carcinomas in patients with cirrhosis, particularly in patients without HBs antigen.[32] [34]

6.     Cholecystitis and cholelithiasis: One hundred patients with cholecystitis and cholelithiasis were treated with a combination of Xiao Chai Hu Tang and Xiao Cheng Qi Tang (Minor Order the Qi Decoction) with an 85% success rate of passing the stones.[33] [35]

7.     Cholecystitis: One study reported 98.9% effectiveness using Xiao Chai Hu Tang to treat cholecystitis. Of 285 patients (134 males, 151 females, average of 40.1 years of age, 2.7 years average duration of illness), 61 had acute cholecystitis and 224 had chronic cholecystitis. The treatment protocol was to administer the herbs in decoction one time daily for 15 days per course of treatment. The study reported complete recovery in 273 patients, improvement in 9 patients, and no effect in 3 patients.[34] [36]

8.     Pancreatitis: Fifty patients with acute pancreatitis were treated with marked improvement using acupuncture, modified Xiao Chai Hu Tang, and atropine. The average duration of treatment was 6.8 days, with most patients showing improvement after about 3 days.[35] [37]

9.     Fever in cancer: Thirty-two cancer patients with high fever were treated with good results using modified Xiao Chai Hu Tang. The treatment protocol was to use Xiao Chai Hu Tang plus Bai Hua She She Cao (Herba Hedyotis) and Ban Zhi Lian (Herba Scutellariae Barbatae) as the base formula. Yu Ping Feng San (Jade Windscreen Powder) and Bie Jia (Carapax Trionycis) were added for qi and yin deficiencies; Yin Chen (Herba Artemisiae Scopariae) and Yi Yi Ren (Semen Coicis) for damp-heat; and Shi Gao (Gypsum Fibrosum) and Zhi Mu (Rhizoma Anemarrhenae) for persistent high fever due to heat and toxins. Out of 32 patients, 17 had marked improvement, 13 had moderate improvement, and 2 had no improvement.[36] [38]

10. Fever: Eighty-six patients with high fever (36 due to respiratory tract infection, 20 due to infection of the bile duct, 9 due to urinary tract infection, 4 due to postpartum infection, 2 due to toxemia, 3 due to hepatitis, 2 due to encephalitis, 2 due to influenza, 2 due to parotitis, 3 due to bacterial dysentery, and 3 due to unknown causes) were treated successfully. The study reported reduction of body temperature in 29 patients after 1-2 doses, 36 patients after 3-4 doses, and 21 patients after 4 doses.[37] [39] According to another study, 128 patients with high fever were treated with Xiao Chai Hu Tang plus Ban Lan Gen (Radix Isatidis), Mian Ma Guan Zhong (Rhizoma Dryopteridis Crassirhizomatis), Bai Wei (Radix et Rhizoma Cynanchi Atrati) and others. Ge Gen (Radix Puerariae Lobatae) was added for body aches and pains; and Mu Dan Pi (Cortex Moutan) and Di Huang (Radix Rehmanniae) were added for red tongue body. Within 5 doses of herbs, the study reported normal temperature (37.2°C / 98.96°F or below) without recurrence of fever in 119 of 128 patients.[38] [40]

11. Nephritis: Forty patients of acute and chronic nephritis were treated with electro-acupuncture and Xiao Chai Hu Tang with significant improvement. There were significant reductions of protein and cells in the urine.[39] [41] Another study reported that the combination of Xiao Chai Hu Tang and Ba Wei Di Huang Wan (Eight-Ingredient Pill with Rehmannia) is beneficial in treating patients with chronic nephritis refractory to steroid therapy.[40] [42]

12. Chronic renal insufficiency: Modified Xiao Chai Hu Tang was used with good results in treating 60 patients with chronic renal insufficiency. The herbal treatment included Xiao Chai Hu Tang plus Dan Shen (Radix et Rhizoma Salviae Miltiorrhizae), Da Huang (Radix et Rhizoma Rhei), Yi Mu Cao (Herba Leonuri), and other herbs as the base formula. Tai Zi Shen (Radix Pseudostellariae), Di Huang (Radix Rehmanniae), and Gou Qi Zi (Fructus Lycii) were added for qi and yin deficiencies with accumulation of dampness and toxins. Fu Zi (Radix Aconiti Lateralis Praeparata) and dry-fried Bai Zhu (Rhizoma Atractylodis Macrocephalae) were added for accumulation of water and dampness due to inability of Spleen and Kidney to regulate water circulation. The herbs were given for 3 months per course of treatment. Of 60 patients, the study reported significant improvement in 12 patients, moderate improvement in 24 patients, stabilization in 14 patients, and no benefit in 10 patients. The overall rate of effectiveness was 83.33%.[41] [43]

13. Cough: Xiao Chai Hu Tang plus Xi Xin (Radix et Rhizoma Asari), Gan Jiang (Rhizoma Zingiberis), Ku Xing Ren (Semen Armeniacae Amarum), and others were used to treat 52 patients with chronic cough with marked improvement in 13 patients, moderate improvement in 35 patients, and no effect in 4 patients. The overall rate of effectiveness was 92.3%.[42] [44]

14. Bronchial asthma: Use of Xiao Chai Hu Tang was reported to have a 64.3% effectiveness rate in treating chronic bronchial asthma dependent on steroid drugs for treatment. Of 28 patients, 4 had significant improvement and 14 had moderate improvement.[43] [45]

15. Reflux esophagitis: Seventy-eight patients (40 males and 38 females) with reflux esophagitis for an average of 14 months (4 months to 3 years) were treated with modified Xiao Chai Hu Tang one time daily for 30 days. The base formula contained Chai Hu (Radix Bupleuri) 15g, Huang Qin (Radix Scutellariae) 10g, Dang Shen (Radix Codonopsis) 10g, Ban Xia (Rhizoma Pinelliae) 10g, Gan Cao (Radix et Rhizoma Glycyrrhizae) 6g, and Da Zao (Fructus Jujubae) 5 pieces. In addition, 30 grams of calcined Wa Leng Zi (Concha Arcae) were added for acid reflux; 20 grams of Dan Shen (Radix et Rhizoma Salviae Miltiorrhizae) were added for blood stagnation; and 30 grams each of Wu Mei (Fructus Mume) and Bai Shao (Radix Paeoniae Alba) were added for burning sensations and pain. The study reported complete recovery in 69 patients, moderate improvement in 6 patients, and no improvement in 3 patients. The overall success rate was 96.2%.[44] [46]

16. Antral gastritis: Xiao Chai Hu Tang plus Xuan Fu Hua (Flos Inulae), Tao Ren (Semen Persicae), and others were used to treat 107 patients with antral gastritis with 90.70% effectiveness. The duration of treatment ranged from 1-3 courses, with 15 packs of herbs per course of treatment.[45] [47]

17. Gastritis: Thirty-six patients with gastritis due to regurgitation of bile were treated with modified Xiao Chai Hu Tang for 30 days with marked results. Modifications of the herbs were as follows: Dan Shen (Radix et Rhizoma Salviae Miltiorrhizae) was added for chronic gastritis with blood stagnation; Huang Lian (Rhizoma Coptidis) for accumulation of heat; Zhi Qiao (Fructus Aurantii) for abdominal distention and fullness; San Qi (Radix et Rhizoma Notoginseng), Hai Piao Xiao (Endoconcha Sepiae) and Bai Fan (Alumen) for ulceration. Most patients reported complete recovery or resolution of all symptoms. Endoscopy also confirmed varying degrees of recovery.[46] [48]

18. Gastric pain: Modified Xiao Chai Hu Tang was used to treat 151 patients with stomach pain with complete recovery reported in 84 patients, improvement in 49 patients, and no effect in 18 patients. Modifications included the addition of Wu Mei (Fructus Mume), Dan Shen (Radix et Rhizoma Salviae Miltiorrhizae), Wu Ling Zhi (Faeces Trogopteri), Mu Dan Pi (Cortex Moutan) and others as deemed necessary.[47] [49]

19. Gastric prolapse: Administration of modified Xiao Chai Hu Tang for one month in 60 patients with gastric prolapse was associated with complete recovery in 29 patients, marked improvement in 22 patients, and slight improvement in 9 patients. The base formula contained Xiao Chai Hu Tang plus Mai Ya (Fructus Hordei Germinatus) and Ji Nei Jin (Endothelium Corneum Gigeriae Galli). Xuan Fu Hua (Flos Inulae) and Zhe Shi (Haematitum) were added for belching, distention, and pain. For epigastric pain, Dang Shen (Radix Codonopsis) was removed, and Shi Xiao San (Sudden Smile Powder) and Da Huang (Radix et Rhizoma Rhei) were added. For individuals with emotional disturbance, Dang Gui (Radix Angelicae Sinensis), Bai Shao (Radix Paeoniae Alba), and dry-fried Xiang Fu (Rhizoma Cyperi) were added. For feeling of coldness in the stomach region, Wu Zhu Yu (Fructus Evodiae) and Gao Liang Jiang (Rhizoma Alpiniae Officinarum) were added. For dampness affecting the Spleen, Cang Zhu (Rhizoma Atractylodis), Zi Su Geng (Caulis Perillae), and Chen Pi (Pericarpium Citri Reticulatae) were added. For food stagnation, Sha Ren (Fructus Amomi) and Jian Shen Qu (Massa Fermentata Praeparata) were added. For yin deficiency, Shi Hu (Caulis Dendrobii) and Sha Shen (Radix Glehniae seu Adenophorae) were added.[48] [50]

20. Constipation: Modified Xiao Chai Hu Tang was used successfully to treat constipation in geriatric patients. Of 48 patients, 30 had complete recovery, 16 had marked improvement, and 2 had slight improvement. The base formula included Xiao Chai Hu Tang plus Tao Ren (Semen Persicae), dry-fried Lai Fu Zi (Semen Raphani), and others. In addition, Bai Jiang Cao (Herba cum Radice Patriniae) and Huang Qin (Radix Scutellariae) were added for heat; Yan Hu Suo (Rhizoma Corydalis) and Bai Shao (Radix Paeoniae Alba) were given in larger doses for severe abdominal pain; and Hou Po (Cortex Magnoliae Officinalis) and Da Fu Pi (Pericarpium Arecae) were given for a feeling of heaviness and distention in the abdomen.[49] [51]

21. Acute tonsillitis: Use of modified Xiao Chai Hu Tang was found to have 94% effectiveness (102 of 108 patients) in treating acute tonsillitis. The herbal treatment used Xiao Chai Hu Tang plus She Gan (Rhizoma Belamcandae) and Xia Ku Cao (Spica Prunellae) as the base formula, with the addition of Ban Lan Gen (Radix Isatidis) for severe sore throat; Ma Bo (Lasiosphaera seu Calvatia) and Pu Gong Ying (Herba Taraxaci) for abscesses; Sang Bai Pi (Cortex Mori) and Gua Lou (Fructus Trichosanthis) for coughing with profuse sputum; charred Da Huang (Radix et Rhizoma Rhei) for constipation; Can Sha (Faeces Bombycis) and Che Qian Zi (Semen Plantaginis) for loose stools; Xin Yi Hua (Flos Magnoliae) and Cang Er Zi (Fructus Xanthii) for profuse nasal discharge; and Shi Gao (Gypsum Fibrosum) and Lu Gen (Rhizoma Phragmitis) for thirst.[50] [52]

22. Infectious parotitis: Modified Xiao Chai Hu Tang was effective in treating acute parotitis. The herbal treatment was based on Xiao Chai Hu Tang, with the addition of Xia Ku Cao (Spica Prunellae) and elimination of Ren Shen (Radix et Rhizoma Ginseng). Jie Geng (Radix Platycodonis) and Niu Bang Zi (Fructus Arctii) were added for early stages of infection; Jing Jie (Herba Schizonepetae) and Fang Feng (Radix Saposhnikoviae) for presence of exterior signs and symptoms; Jiang Can (Bombyx Batryticatus) and Jin Yin Hua (Flos Lonicerae Japonicae) for wind-heat and epidemic toxin; Huo Xiang (Herba Agastaches) and Pei Lan (Herba Eupatorii) for damp-heat in the interior; Da Huang (Radix et Rhizoma Rhei) for constipation; Ju He (Semen Citri Reticulatae) for mastitis; and Li Zhi He (Semen Litchi) for orchitis. Of 47 patients, 45 had complete recovery and 2 had no improvement.[51] [53]

23. Stomatitis: Complete recovery was reported in all 40 patients with stomatitis using Xiao Chai Hu Tang plus Huang Lian (Rhizoma Coptidis) as a mouth gargle. The duration of treatment ranged from 3 to 15 doses of herbs.[52] [54]

24. Allergic rhinitis: In one comparison study, patients with allergic rhinitis were treated with either herbs or drugs (antihistamine). In the herb group, Xiao Chai Hu Tang was used as the base formula, with the addition of Xin Yi Hua (Flos Magnoliae) and Ju Hua (Flos Chrysanthemi) for severe nose itching and sneezing; Cang Zhu (Rhizoma Atractylodis) and Sheng Ma (Rhizoma Cimicifugae) for profuse nasal discharge; Bai Zhi (Radix Angelicae Dahuricae) and Bo He (Herba Menthae) for severe sinus swelling and congestion; Huang Qin (Radix Scutellariae) and Chuan Xiong (Rhizoma Chuanxiong) for severe inflammation; Tao Ren (Semen Persicae) and Ge Gen (Radix Puerariae Lobatae) for nasal polyps; and other modifications as deemed necessary. The study reported 90.8% effectiveness for 65 patients in the herb group, and 76.9% effectiveness for 65 patients in the drug (antihistamine) group.[53] [55]

25. Meniere’s syndrome: One study involving 268 patients with Meniere’s syndrome reported marked improvement in most of the patients when they were treated with modified Xiao Chai Hu Tang. The herbal treatment contained Xiao Chai Hu Tang with Chuan Xiong (Rhizoma Chuanxiong), Ju Hua (Flos Chrysanthemi), and others as needed. The overall rate of effectiveness was 97%.[54] [56]

26. Dizziness: Administration of Xiao Chai Hu Tang plus Fang Feng (Radix Saposhnikoviae), Huo Xiang (Herba Agastaches), and others was effective within 24 hours in treating acute onset dizziness. Of 20 patients, 14 had complete recovery and 6 had slight to moderate improvement.[55] [57]

27. Migraine: Administration of Xiao Chai Hu Tang plus Chuan Xiong (Rhizoma Chuanxiong), Bai Zhi (Radix Angelicae Dahuricae), and Xi Xin (Radix et Rhizoma Asari) in 50 patients with migraine headache was associated with complete recovery in 32 patients, improvement in 15 patients, and no effect in 3 patients. The overall rate of effectiveness was 94%.[56] [58]

28. Angina: Xiao Chai Hu Tang demonstrated good results in treating 41 patients with angina. While 35 had resolution of symptoms, they showed varying degrees of improvement based on ECG reports. The herbal treatment used Xiao Chai Hu Tang plus Dang Gui (Radix Angelicae Sinensis), Chuan Xiong (Rhizoma Chuanxiong), and Fu Zi (Radix Aconiti Lateralis Praeparata) as the base formula. Larger doses of certain herbs were used depending on the differential diagnosis of the condition: Ren Shen (Radix et Rhizoma Ginseng) for severe qi deficiency; Fu Zi (Radix Aconiti Lateralis Praeparata) for severe yang deficiency; Chai Hu (Radix Bupleuri), Dang Gui (Radix Angelicae Sinensis), and Chuan Xiong (Rhizoma Chuanxiong) for qi and blood stagnation; and Ban Xia (Rhizoma Pinelliae) and Sheng Jiang (Rhizoma Zingiberis Recens) for phlegm stagnation.[57] [59]

29. Depression: One study reported 78.8% effectiveness using modified Xiao Chai Hu Tang to treat depression. Modifications to the formula included the addition of Zeng Ye Tang (Increase the Fluids Decoction) for yin-deficient heat; Xiang Fu (Rhizoma Cyperi), Yu Jin (Radix Curcumae), and Zhi Qiao (Fructus Aurantii) for Liver qi stagnation; and Hou Po (Cortex Magnoliae Officinalis), Bai Zhu (Rhizoma Atractylodis Macrocephalae) and Fu Ling (Poria) for damp and phlegm in the Spleen. Of 90 patients, the study reported complete recovery in 64 patients and improvement in 7 patients. Poor results were noted in 19 patients who were then treated with drugs.[58] [60]

30. Chronic fatigue syndrome: Modified Xiao Chai Hu Tang was used to treat 36 patients with chronic fatigue syndrome characterized by low-grade fever, chills, depression, muscle aches and pains in the entire body, lack of energy, bitter taste in the mouth, poor appetite, etc. The herbal treatment used Xiao Chai Hu Tang plus Ban Lan Gen (Radix Isatidis) and Gui Zhi (Ramulus Cinnamomi) as the base formula, with more herbs added when necessary. Herbs were given for 10 days per course of treatment, for 1-4 courses. The study reported complete recovery in 26 patients, and improvement in 10 others.[59] [61]

31. Morning sickness: One study reported 88% effectiveness using Xiao Chai Hu Tang to treat nausea and vomiting during pregnancy. Of 320 patients, the study reported complete relief in 180 patients, improvement in 100 patients, and no effect in 40 patients.[60] [62]

32. Postpartum infection: Use of modified Xiao Chai Hu Tang had 96.6% effectiveness in treating 178 patients with postpartum viral infection (common cold or influenza). The herbal treatment contained Xiao Chai Hu Tang plus Huang Qi (Radix Astragali), Yi Mu Cao (Herba Leonuri) and Dang Gui (Radix Angelicae Sinensis) as the base formula. Modifications were made as needed. For dry mouth and stuffy or runny nose, Sheng Jiang (Rhizoma Zingiberis Recens) was removed and Sang Ye (Folium Mori), Ju Hua (Flos Chrysanthemi), Bo He (Herba Menthae), and Lu Gen (Rhizoma Phragmitis) were added. For nasal obstruction, Zi Su Ye (Folium Perillae) was added. For high fever without perspiration, Qing Hao (Herba Artemisiae Annuae) was added. For thick sticky sputum, Zhi Mu (Rhizoma Anemarrhenae) and Zhe Bei Mu (Bulbus Fritillariae Thunbergii) were added. For white foamy sputum, Chen Pi (Pericarpium Citri Reticulatae) and Fu Ling (Poria) were added. For sore throat, Ban Lan Gen (Radix Isatidis), She Gan (Rhizoma Belamcandae), and Ma Bo (Lasiosphaera seu Calvatia) were added. For red tongue body with little tongue coating, Yu Zhu (Rhizoma Polygonati Odorati) was added. After 1-2 packs of herbal treatment, the study reported complete recovery in 154 patients, improvement in 18 patients, and no effect in 6 patients.[61] [63]

33. Postpartum fever: Modified Xiao Chai Hu Tang effectively reduced body temperature within an average of 10 hours in all 60 postpartum women with fever. The herbal treatment contained Xiao Chai Hu Tang plus Dang Gui (Radix Angelicae Sinensis), Yi Mu Cao (Herba Leonuri), and others as the base formula. In addition, Jin Yin Hua (Flos Lonicerae Japonicae) and Jing Jie (Herba Schizonepetae) were added for sore throat; Tao Ren (Semen Persicae) and Hong Hua (Flos Carthami) for lower abdominal pain with spotting; and Pu Gong Ying (Herba Taraxaci) and dry-fried Chuan Shan Jia (Squama Manis) for breast distention and pain.[62] [64]

34. Dysmenorrhea: Administration of Xiao Chai Hu Tang was associated with 96.5% effectiveness in relieving primary dysmenorrhea. The treatment protocol was to take the herbs starting the first day of the period for 10 days, for 3 months per course of treatment. Of 57 patients, the study reported complete recovery in 28 patients, significant improvement in 22 patients, slight improvement in 5 patients, and no effect in 2 patients.[63] [65]

35. Premenstrual syndrome (PMS): Use of modified Xiao Chai Hu Tang had 93.41% effectiveness in treating 167 women with PMS (complete relief in 77 patients, significant improvement in 57 patients, and moderate improvement in 22 patients). Modifications to the formula were made based on the condition of the patient. For breast distention and hypochondriac pain, Chuan Lian Zi (Fructus Toosendan), Xia Ku Cao (Spica Prunellae), and Bai Shao (Radix Paeoniae Alba) were added. For edema, Fu Ling (Poria), Ze Xie (Rhizoma Alismatis), and Che Qian Zi (Semen Plantaginis) were added. For irritability, restlessness, and elevated body temperature, Ren Shen (Radix et Rhizoma Ginseng) and Ban Xia (Rhizoma Pinelliae) were removed, and Mu Dan Pi (Cortex Moutan), Zhi Zi (Fructus Gardeniae) and Di Huang (Radix Rehmanniae) were added. For diarrhea, dry-fried Bai Zhu (Rhizoma Atractylodis Macrocephalae) and Yi Yi Ren (Semen Coicis) were added. For palpitations and insomnia, Yuan Zhi (Radix Polygalae), Dang Gui (Radix Angelicae Sinensis) and dry-fried Suan Zao Ren (Semen Ziziphi Spinosae) were added. For nausea and vomiting, Gan Cao (Radix et Rhizoma Glycyrrhizae) and Da Zao (Fructus Jujubae) were removed, and Zhu Ru (Caulis Bambusae in Taenia), and Zi Su Geng (Caulis Perillae) were added. For dizziness and headache, Ju Hua (Flos Chrysanthemi) and Chuan Xiong (Rhizoma Chuanxiong) were added.[64] [66]

HERB-DRUG INTERACTION

§  Interferon: Increased risk of acute pneumonitis may be associated with the use of interferon, Xiao Chai Hu Tang, or both in combination. Among patients with chronic hepatitis or liver cirrhosis, the frequency of drug-induced pneumonitis was 0.5% in those given only interferon-alpha, 0.7% in those given only Xiao Chai Hu Tang, and 4.0% in those given both interferon-alpha and Xiao Chai Hu Tang.[65] [67] Many theories have been proposed on the mechanism of this interaction. One theory states that the herbs have not been shown to injure the lung tissues, but may over stimulate the neutrophils to release granulocytes, elastase and oxygen radicals, which subsequently damage lung tissue. The fibroblasts that repair the damaged tissue may increase the risk of pulmonary fibrosis.[66] [68] Another theory states that acute pneumonitis associated with concurrent use of interferon and Xiao Chai Hu Tang may be due to allergic-immunological mechanisms.[67] [69]

§  Interleukin 2: Concurrent use of Xiao Chai Hu Tang and interleukin 2 showed a synergistic antitumor effect against murine renal cell carcinoma cell line in mice. The treatment protocol was to administer Xiao Chai Hu Tang at 2.5 g/kg daily over 30 days, and interleukin 2 at 10(4) U/subject by subcutaneous injection every other day for a total of 8 doses. The combination of these two substances inhibited growth of the tumor and prolonged survival significantly as compared with the untreated mice.[68] [70]

§  Lamivudine (Epivir; 3TC): One study reported synergistic antiviral effect when Xiao Chai Hu Tang is combined with antiviral drugs such as zidovudine (AZT), lamivudine (3TC) or AZT plus 3TC. Used alone, Xiao Chai Hu Tang moderately inhibited HIV-1 replication at a concentration of 25 mcg/mL. Used together, Xiao Chai Hu Tang enhanced the anti-HIV-1 activity of 3TC. The researchers suggested that the combination of Xiao Chai Hu Tang and 3TC has potential as a chemotherapeutic modality for HIV-1 infection.[69] [71]

§  5-fluorouracil (5-FU): The combination of 5-FU and Xiao Chai Hu Tang had a synergistic effect for treatment of cancer in mice by increasing the life span by 56% and alleviating side effects of 5-FU.[70] [72]

§  Drug-induced liver damage: Administration of Xiao Chai Hu Tang has been shown to have beneficial effects in preventing and/or treating damage induced by drugs, such as halothane, danazol, D-galactosamine, and carbon tetrachloride.[71] [73]^{,[72] [74],[73] [75],[74] [76]}

§  Liver enzyme inhibition: The effect of Xiao Chai Hu Tang on cytochrome P450 enzymes was evaluated in 26 healthy subjects. Use of this herbal formula (2.5g twice daily for 5 days) was associated with a decreased mean activity of CYP1A2 by 16% on both day 1 and day 5 compared with the baseline (P=0.001).[75] [77] In another study on the metabolic activity of different cytochrome P450 (CYP) isoforms, Xiao Chai Hu Tang was reported to be a competitive inhibitor of CYP2C9, but not CYP2D6. The study concluded that because of this inhibitory effect on liver metabolism, care should be taken with concurrent use of Xiao Chai Hu Tang and drugs.[76] [78]

§  Pentobarbital: Administration of Xiao Chai Hu Tang was associated with significantly shortened pentobarbital-induced sleeping time in mice. The mechanism of this interaction was attributed to the up-regulation of the mRNA expression of CYP2B, CYP3A1, CYP2E1 and CYP4A1.[77] [79]

§  Carbamazepine: Administration of one dose of Xiao Chai Hu Tang was associated with decreased peak concentration, and the time needed to reach the peak concentration, of carbamazepine in rats. However, two-week repeated treatments of Xiao Chai Hu Tang did not affect plasma concentration-time profile or any pharmacokinetic parameter of carbamazepine, an indication that Xiao Chai Hu Tang did not affect the liver metabolism of carbamazepine. The study attributed the mechanism of this interaction to decreased gastrointestinal absorption of carbamazepine due to delayed gastric emptying.[78] [80]

§  Tolbutamide: Xiao Chai Hu Tang demonstrably reduced the bioavailability of tolbutamide after oral administration in rats. The formula was found to accelerate the initial absorption rate, reduce the area under the plasma concentration-time curve, and decrease the overall bioavailability of tolbutamide.[79] [81] The mechanism of this interaction was attributed to the inhibitory effect of Xiao Chai Hu Tang on the function of gastric emptying, thereby decreasing gastrointestinal absorption of tolbutamide.[80] [82]

§  Ofloxacin: In an open, random-crossover investigation study with seven volunteers, a single dose of ofloxacin and a one-week dose of Xiao Chai Hu Tang were given concurrently. Using high-performance liquid chromatography to evaluate the bioavailability of ofloxacin, it was determined that there is no significant effect on the rate or extent of bioavailability of ofloxacin when given concurrently with Xiao Chai Hu Tang.[81] [83]

TOXICOLOGY

§  Xiao Chai Hu Tang has a very low toxicology profile. In one study, rats were given up to 640 mg/kg of the extract per day continuously for 6 months. At the end of the study, the animals were examined for body weight, general behavior, water and food intake, and function of vital organs. The study concluded that no abnormality could be observed.[82] [84]

§  Interstitial pneumonia: Over 200 patients of interstitial pneumonia have been associated with the use of Xiao Chai Hu Tang in Japan. While the exact mechanism of this adverse reaction is not completely understood, it was suggested that phenolic compounds (lignans and flavonoids) present in this formula may induce apoptosis in human lung fibroblasts and peripheral blood mononuclear cells. Two phenolic compounds, baicalein and medicarpin, were found to significantly inhibit the growth and reduce the viability of lung fibroblasts. The researchers suggested that the phenolic compounds of Xiao Chai Hu Tang (especially baicalein and medicarpin) may have a direct effect on human lung fibroblasts and immune cells to induce apoptosis.[83] [85] Note: Xiao Chai Hu Tang is one of the most commonly used herbal formulas in Japan. According to a study published in 1999, this formula has been administered to 1.5 million Japanese patients with chronic liver diseases.[84] [86] In addition, there have been numerous other reports that document the safe and effective use of this formula. Thus, it is important to keep a proper perspective on the relative frequency of events, as well as risk-to-benefit analysis, in evaluating toxicology reports.

RELATED FORMULAS

Chái Hú Zhĭ Jié Tāng (Bupleurum, Bitter Orange, and Platycodon Decoction) 

柴胡枳桔湯 

柴胡枳桔汤 

Pinyin Name: Chai Hu Zhi Jie Tang  

Literal Name: Bupleurum, Bitter Orange, and Platycodon Decoction 

Original Source: Chong Ding Tong Su Shang Han Lun (Revised Popular Guide to the Discussion of Cold-Induced Disorders) by Yu Gen-Chu in the Qing Dynasty

Chai Hu Zhi Jie Tang (Bupleurum, Bitter Orange, and Platycodon Decoction) mainly harmonizes the shaoyang, releases the exterior, and regulates the chest and diaphragm. The main indication is shaoyang syndrome, with slightly greater emphasis on the exterior than the interior. Clinically, patients will show symptoms such as alternating fever and chills, headache (especially on the two corners of the forehead), deafness, vertigo, hypochondriac fullness and pain, a white, slippery tongue coating, a wiry, slippery pulse on the right hand, and a wiry, superficial and big pulse on the left hand. This formula can be taken with Cha Ye (Folium Camelliae) to enhance the overall heat-clearing and damp-dispelling effects.

In comparison to Xiao Chai Hu Tang, which treats shaoyang syndrome with equal emphasis on both the exterior and interior, Chai Hu Zhi Jie Tang focuses on shaoyang syndromes in which there are more exterior symptoms than interior. For this reason, Ren Shen (Radix et Rhizoma Ginseng), Zhi Gan Cao (Radix et Rhizoma Glycyrrhizae Praeparata cum Melle), and Da Zao (Fructus Jujubae) are not used in this formula.

Chái Hú Jiĕ Dú Tāng (Bupleurum Decoction to Relieve Toxicity) 

柴胡解毒湯 

柴胡解毒汤 

Pinyin Name: Chai Hu Jie Du Tang 

Literal Name: Bupleurum Decoction to Relieve Toxicity 

Original Source: An Hui Zhong Yi Xue Yuan (Anhui University School of Medicine) in 1990

Chai Hu Jie Du Tang (Bupleurum Decoction to Relieve Toxicity) treats shaoyang disorders characterized by chronic illness with heat and toxins accumulated in the body. This formula contains herbs that release the exterior, clear heat and eliminate toxins from the interior, and drain damp-heat from the Liver and Gallbladder. Clinically, it treats liver disorders, such as hepatitis, cirrhosis, and elevated liver enzyme levels.

AUTHORS’ COMMENTS

Xiao Chai Hu Tang is traditionally used to treat alternating chills and fever, but can also be used for patients showing temperature differences in the body, such as cold limbs but a warm body, or warm limbs and a cold body. Another condition that can also be treated with this formula is drastic temperature differences on the dorsal and palmar aspects of the hands, with the palmar aspect being cold and the dorsal aspect being warm.

Xiao Chai Hu Tang can be used for unremitting fever in children approximately one week after contracting an exterior condition. These patients exhibit fever that is not alleviated with antipyretic or antibiotic drugs. Though these drugs work well to temporarily bring down body temperature, the fever tends to return as soon as the therapeutic effect is over.

One unique application of Xiao Chai Hu Tang that requires additional explanation is the treatment of an exterior condition in women with blood deficiency. Loss of blood during menstruation and childbirth creates an emptiness in the uterus and the chong (thoroughfare) channel. Due to this void, pathogenic factors directly and easily invade into deeper levels of the body instead of lingering at the wei (defensive) level. The Liver stores blood, travels around the genital region, and traverses up the lower abdomen, and is closely related to the uterus and chong channel. If heat enters the uterus and chong channel, it affects the Liver, which in turn affects its paired organ, the Gallbladder. This stagnant heat creates disharmony in the shaoyang stage, leading to alternating chills and fever, hypochondriac fullness/discomfort, a bitter taste in the mouth, a dry throat, irritability, lack of appetite, nausea, and vomiting. Xiao Chai Hu Tang harmonizes the shaoyang and pushes the heat outward to relieve the heat trapped in the uterus and chong channel.[85] [87]

Alternating chills and fever is a key symptom that can be treated with Xiao Chai Hu Tang or Xiao Yao San (Rambling Powder). However, the diagnostic criteria and clinical application guidelines are very different.

·       Xiao Chai Hu Tang treats alternating chills and fever caused by exterior pathogenic factors that enter the shaoyang level and get trapped in the half-exterior and half-interior location. Ren Shen (Radix et Rhizoma Ginseng), Da Zao (Fructus Jujubae), and Gan Cao (Radix et Rhizoma Glycyrrhizae) strengthen the interior to push the pathogens outward and prevent them from invading further into the body, not to tonify the deficiencies. Sheng Jiang (Rhizoma Zingiberis Recens) is used with Ban Xia (Rhizoma Pinelliae) to treat nausea and irritability caused by Gallbladder heat invading the Stomach.

·       Xiao Yao San treats alternating fever and chills caused by disharmony among the Liver, Spleen, and Gallbladder and accompanied by blood deficiency and Liver qi stagnation; the chills and fever are not the result of an exterior invasion. Dang Gui (Radix Angelicae Sinensis), Bai Shao (Radix Paeoniae Alba), Fu Ling (Poria), and Bai Zhu (Rhizoma Atractylodis Macrocephalae) strengthen the Spleen to prevent the Liver from overacting. Sheng Jiang (Rhizoma Zingiberis Recens) warms the middle jiao to strengthen the Spleen.

Fever and chills (aversion to cold) are a common complaint in exterior conditions, but they must be differentiated correctly.

·       In taiyang syndrome, fever and chills are present simultaneously.

·       In yangming syndrome, there is high fever and absence of chills.

·       In shaoyang syndrome, there are alternating spells of fever and chills.

Xiao Chai Hu Tang and Xiao Yao San (Rambling Powder) both contain Chai Hu (Radix Bupleuri) as the chief herb, but with different intent and at different doses:

·       Xiao Chai Hu Tang treats shaoyang syndrome in which the pathogenic heat is trapped between the exterior and interior. In this case, signs of alternating chills and fever are more severe. As a result, a large dose of Chai Hu (Radix Bupleuri) is needed to harmonize shaoyang and clear the heat.

·       Xiao Yao San (Rambling Powder) treats Liver qi stagnation accompanied by Spleen deficiency, manifesting in emotional complaints but involving less severe physical symptoms compared to that of Xiao Chai Hu Tang. Although Chai Hu (Radix Bupleuri) is also the chief herb, only a moderate dose is needed to regulate Liver qi. In this case, this herb serves more as a channel-guiding herb in this formula to address Liver qi stagnation. Using a large dose of Chai Hu (Radix Bupleuri) in Xiao Yao San is not appropriate because it shifts the effect of the formula from harmonizing to exterior-releasing. Moreover, patients with Liver qi stagnation often have underlying deficiencies, and using Chai Hu (Radix Bupleuri) at a large dose may exacerbate such deficiencies.

Xiao Chai Hu Tang and Da Chai Hu Tang (Major Bupleurum Decoction) both treat shaoyang disorders with alternating chills and fever, a bitter taste in the mouth, and chest and hypochondriac distention. Both formulas contain Chai Hu (Radix Bupleuri), Huang Qin (Radix Scutellariae), Ban Xia (Rhizoma Pinelliae), Sheng Jiang (Rhizoma Zingiberis Recens), and Da Zao (Fructus Jujubae). Despite the similarities, they have contrasting differences:

·         Xiao Chai Hu Tang contains Chai Hu (Radix Bupleuri) and Huang Qin (Radix Scutellariae) as chief herbs to harmonize the shaoyang. Ren Shen (Radix et Rhizoma Ginseng) strengthens the interior to prevent the pathogenic factors from moving further inward. This formula treats a variety of conditions, including exterior invasion in women during their menstruation, jaundice, and symptoms of malaria.

·         Da Chai Hu Tang is mainly used for yangming fu (hollow organs) syndrome with excess heat in the body. Da Huang (Radix et Rhizoma Rhei), Zhi Shi (Fructus Aurantii Immaturus), and Bai Shao (Radix Paeoniae Alba) sedate heat in the yangming channel. The key sign for differential diagnosis is constipation with abdominal pain.[86] [88]

Xiao Chai Hu Tang and Hao Qin Qing Dan Tang (Artemisia Annua and Scutellaria Decoction to Clear the Gallbladder) both harmonize shaoyang and treat chief manifestations of alternating chills and fever, as well as chest and hypochondriac distention and pain. Their main differences are as follows:

·         Xiao Chai Hu Tang lifts clear yang qi and pushes pathogenic factors outward. Containing Huang Qin (Radix Scutellariae), Ren Shen (Radix et Rhizoma Ginseng), Da Zao (Fructus Jujubae), Gan Cao (Radix et Rhizoma Glycyrrhizae), Ban Xia (Rhizoma Pinelliae), and Sheng Jiang (Rhizoma Zingiberis Recens), this formula harmonizes shaoyang, dispels pathogenic factors, and restores zheng (upright) qi to treat alternating chills and fever, hypochondriac pain and distention, a bitter taste in the mouth, a dry throat, a thin, white tongue coating, and a wiry pulse.

·         Hao Qin Qing Dan Tang clears damp-heat in the Stomach and Gallbladder, using Qing Hao (Herba Artemisiae Annuae) and Huang Qin (Radix Scutellariae) as the two main ingredients. The formula further contains Zhu Ru (Caulis Bambusae in Taenia), Ban Xia (Rhizoma Pinelliae), Chi Fu Ling (Poria Rubra), Bi Yu San (Jasper Powder), Chen Pi (Pericarpium Citri Reticulatae), and Zhi Qiao (Fructus Aurantii), to treat damp-heat with turbid phlegm accumulation in the shaoyang channel. Symptoms include alternating chills and fever with a greater degree of heat than cold, a bitter taste in the mouth, acid regurgitation, a thick, greasy tongue coating, and a slippery, rapid pulse on the right hand and a wiry, rapid pulse on the left hand.[87] [89]

REFERENCES