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    Summary of Professor Tong Xiaolin’s clinical experience of applying Rhizoma Coptidis (Huang Lian)

    2017-03-09 12:34:12GuChengjuan顧成娟WangHan王涵PangBing逄冰andTongXiaolin仝小林
    關(guān)鍵詞:小林

    Gu Chengjuan(顧成娟), Wang Han(王涵), Pang Bing(逄冰), and Tong Xiaolin(仝小林)

    Summary of Professor Tong Xiaolin’s clinical experience of applying Rhizoma Coptidis (Huang Lian)

    Gu Chengjuan(顧成娟), Wang Han(王涵), Pang Bing(逄冰), and Tong Xiaolin(仝小林)*

    With the advantages of less toxicity and side effects, traditional Chinese medicine (TCM) is showing a bright future with a good clinical practice. Chinese herbal medicine, which usually contains various active ingredients, could provide multiple therapeutic effects. Professor Tong Xiaolin has accumulated abundant experience during many years of clinical practice and applies Rhizoma Coptidis(RC) well with the treatment of diabetes and its complications. Rhizoma coptidis is a classical natural herb which is used frequently by professor Tong Xiaolin. In this review, we summarize Tong Xiaolin’s clinical experience of applying Rhizoma Coptidis (Huang Lian) in the treatment of disease from two aspects as well as introducing some traditional Chinese medical theory and clinical experience, with a prospect of guiding clinician to use RC more suitably and reasonably.

    Rhizoma Coptidis (Huang Lian); Tong Xiaolin; Experience

    INTRODUCTION

    Professor Tong Xiaolin (Prof. Tong) is a doctor of Guang’anmen Hospital of China, born in January 1956. He successively studied medical skill from Professor Zhou Zhongying, Professor Li Jiren and began to run his own private clinic at twenty-five. Now he is a professor skilled in diabetes, doctoral supervisor and chief physician in Guang’anmen Hospital of China Academy of Chinese Medical Sciences. He has been engaged in clinical treatment and scientific research for more than 30 years and is rich in knowledge and experience. He has abundant experience in using a lot of Chinese herbs, particularly in RC. Therefore, he is nicknamed “Tong Huanglian”. RC is a herb frequently used in many traditional formulas for its properties of “clearing dampheat, quenching fire, and counteracting poison” in Asia for centuries. In this summary, we will summarize the application experience of Prof. Tong from two aspects of contents. Firstly, theoretical principles are explained, including the properties and related records on RC in ancient references and modern pharmacological researches, Secondly, the clinical application of RC is mainly reviewed, such as applicable stage and syndrome, the reasonable dose range, compatible with different traditional Chinese medicines and the toxicity and side effects and solutions to its adverse actions.

    THEORETICAL PRINCIPLES OD USING RC

    Properties of RC and records in ancient references

    RC is a herb of bitter flavor and cold property, entering channels of heart, spleen, stomach, gallbladder, and large intestine. It is a herb frequently used in“clearing damp-heat, quenching fire, and counteracting poison”. TheNewly Revised Herbal Foundation(X?n X?u Ben Cao) recorded that “RC in Sichuan had a large size and the most bitter flavor, which was the best for treatment of Xiaokezheng diabetes.” During Ming Dynasties, theCompendium of Materia Medica(Ben Cao Gang Mu) written by Li Shi-Zhen, recorded that “RC was mainly used to deplete thirst and treat copious urine.” In conclusion, the pathogenesis of diabetes is in line with Rhizoma Coptidis indications in the monograph of traditional Chinese Medicine till nowadays, Rhizoma Coptidis has used in the treatment of Xiaokezheng, which has been recorded in the long history and is still widely used in clinical application.

    Modern pharmacological researches on RC

    RC is mainly composed of a diversity of alkaloids, including berberine (6.88%to13.64%), palmatine (1.28% to 2.12%), jateorrhizine (0.77% to 1.32%), coptisine(0.42% to 0.85%), epiberberine (0.42% to 0.92%) et al, all of which are considered to be its active components1. Berberine (BBR) is the major active component of RC. Modern pharmacological researches have proved multiple mechanisms of BBR to lower blood glucose, such as the improvement of insulin sensitivity. The increasing of insulin secretion2, the inhibition of hepatic gluconeogenesis3et al. Kong4et al identify BBR, a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. RC extracts may be more effective than its single alkaloid; the mechanisms are related to the fact that different components may regulate targets in multiple pathways, therefore enhancing pharmacological potency in a synergistic way is involved in hepatic and intestinal metabolism to improve oral drug bioavailability.5

    CLINICAL APPLICATION

    Clinical application of RC is summarized by Prof. Tong as follows: regulating the spleen and stomach by opening with acridity and down bearing with bitterness, modulating intestinal microf l ora by clearing heat and dispelling dampness, stabilizing arrhythmia by clearing heat and draining fire and treating furuncle and carbuncle by clearing heat and resolving toxin. we should pay attention to the scientific compatibility of RC with other herbs and make sure the rational dosage in clinical practice. Besides, how to take decoction and how to balance the efficacy and safety are also very important.

    Applicable stage and syndrome

    Acrid medicinals helps to open and bitter medicinals helps to direct things downward—Regulating spleen and stomach

    Prof. Tong is an expert with abundant experience in applying RC in treating full internal organs in the middle burner and internal heat pathogenes of Type 2 diabetes mellitus (T2DM). Full internal organs in the middle burner and internal heat are the principal pathogens of T2DM, accompanied by spleen-stomach’s Qi activity imbalance. Its principal pathology is spleen-stomach disharmony, “acrid medicinals helps to open and bitter medicinals helps to direct things downward” is the most powerful treatment strategy. The patient who is partial to full internal organs in the middle burner shows the real heat in the stomach, whose principal formula is Banxia Xiexin Decoction or Ganjiang Huanglian Huangqin Renshen Decoction; while, the patient who is partial to internal heat shows the Bile Ref l ux Gastritis, whose principal formula is Dachaihu Decoction (the radix scutellariae in RC). In addition, the theopy of “Acrid medicinals helps to open and bitter medicinals helps to direct things downward” which gives priority to RC is also used in the treatment of diabetes gastrointestinal lesions. Diabetic gastroparesis is the main part of the diabetes gastrointestinal lesions, clinical manifestation is nausea and vomiting, abdominal distension, early cough, belching and other symptoms. The occurrence of diabetic gastroparesis could distract agent application, disturb the control of blood sugar, deduce the easy occurrence of hypoglycemia or ketosis dangerous conditions, so, it catches the attention of many scholars consequently. A research7which is under Prof. Tong’s guidance “preliminary research on the intervention of diabetes gastroparesis” suggests it has the function of lowering blood sugar, and promoting the intestinal peristalsis. For those who suffer from severe diabetes gastroparesis vomiting or hardly eating, Prof. Tong applies the strategy of “Acrid medicinals helps to open and bitter medicinals helps to direct things downward”plus of “Acrid medicinals helps to open and bitter medicinals helps to direct things downward”spleenstomach, increasing Qi activity of spleen-stomach. In this strategy, the small dosage of RC plays a vital rule in the treatment.

    Clearing away the heat and dry dampness—Regulating intestinal microf l ora

    Recent years, many domestic and foreign studies have proved the correlation between obesity, glucose and lipid metabolism and intestinal dysbacteriosis. Intestinal dysbacteriosis generates excess fat polysaccharide, which is absorbed into the blood, causes inf l ammation, promote a high-fat diet related to obesity and metabolic syndrome. In the context of gut microbiota affecting weight, insulin sensitivity and glucolipid metabolism, researchers have put forward the related hypothesis on the pathogenesis of obesity and diabetes. People alsobegan to try to use antibiotics and probiotics, etc., to adjust the gut microbiota, which affects its interactions with the host. Therefore, adjusting gut microbiota imbalance provides a new solution for the treatment of some diseases. In the early and medium stage of type 2 diabetes, the intestinal damp heat syndrome is one of common evidence type. Professor Tong summarizes the two main points in syndrome differentiation : one is sticky smelly Defecate, the other one is yellow thick tongue coating. He frequently chooses Gegen Qinliang Decotion to treat this symdome.

    Draining the fire and resolving the toxins—treating furunculosis and swollen sore

    RC has the function of dissipating heat and drying the damp, purging fire and detoxification, it has particular effect in treating furuncle. Huanglian Jiedu Decoction could effectively treat furuncle, Huanglian Decoction could effectively treat sore red swollen eyes, Qinwei Powder could effectively treat toothache because of stomach fire, these are used widely in clinical practice. Diabetes is frequently complicatied with furuncle due to its special pathological features. Prof. Tong uses Gegen Qinlian Decoction and Dahuang Huanglian Xiexie Decoction because these Chinese herbal remedies have the actions of clearing heat and removing toxin to reduce blood glucose and treat the furuncle, which has received good clinical efficacy.

    Reasonable dose

    Prof. Tong believes that the dose varies according to the different diseases. The recommended dose of RC in regulating spleen and stomach should be 1.5~ 6g; in draining fire and resolving toxins, the recommended dose should be 15~30g with a short time6; in reducing the blood glucose, the recommended dose of RC should be 15~ 45g, even to a maximum dose of 60 g for alleviating the diabetic ketoacidosis (DKA)8, and 120g for diabetes mellitus ketoacidosis6whereas the routine dose in Chinese Pharmacopoeia (2010 edition) is 2~5 g is usually ineffective9. Liu10made a survey of the dose of RC in 1,321 effective formulas to treat T2DM and the result showed that the common dose of RC to lower blood glucose was 15~ 45g. In the review, the decreasing percentage of fasting blood glucose (FBG) and postload plasma glucose (PBG) was >20% of those before treatment or the decreasing percentage of Hemoglobin A1c (HbA1C) was >10% of that before treatment within 12 weeks, the formula was thought of as an effective formula, and other else was thought of as an ineffective formula). The dose of RC for treating T2DM was large; but the dose was small for treating the complications of T2DM11. Generally speaking, compound formula decoction including RC is used for patients with high level of blood glucose, while pill and tablet are suitable for the control in stable level of blood glucose and long-term use, but this conclusion needs to be verified by more researches.

    Compatibility of medicines

    Prof. Tong cures diseases, including spleen fever, insomnia, emesis, diarrhea, heart diseases and dermatosis, through flexible modification and compatibility on the basis of prescription of goldthread series. He also puts forwards different dosage and proportion according to different syndromes and patients' conditions. The compatibility of formulas and medicinals is a feature of TCM, which may greatly decrease the adverse reactions caused by RC.

    Compatibility with rheum of ficinale

    Compatibility with rheum officinale is regarded as the representative of the treatment of gastrointestinal heat syndrome, which is from Dahuang Huanglian Xiexie Decoction. Prof. Tong always uses this drug as the basis treatment for diabetes and metabolic syndrome in gastric and intestinal heat. RC has the function of clearing damp-heat, quenching fire, and counteracting poison, and rheum officinale can prevent the dampness of RC. They are complementing each other.12

    Compatibility with Scutellaria baicalensis

    RC combined with Scutellaria baicalensis comes from Gegen Qinlian Decoction, all of them can clear away the bowel heat. The key to use this drug by Prof. Tong is to see the symptom “yellow thick greasy tongue fur”and “Sticky stool foul”.13

    Compatibility with ginger or rhizoma zingiberis

    In clinical practice, RC is commonly combined with some warm and acrid herbs, because warm and acridmedicine could restrain cold and bitterness; moreover, the compatibility of warmth & acridity and cold & bitterness could promote the function of the spleen and stomach and harmonize the middle energizer14. Ganjiang or Shengjiang is commonly combined with RC in the clinical practice; the regular proportion of RC to Ganjiang is 6 : 1 and the regular proportion of RC to Shengjiang is 4 : 1. If the patient has a weak function of spleen and stomach, the dose of Ganjiang or Shengjiang can be increased; the proportion of RC to the ginger may be 2 : 1, or even 1 : 115-17.

    Toxicity/Side effects and solutions to its adverse actions

    According to the regulations of Singapore government in 1976, RC and BBR were forbidden to be used because it was deemed that a shortage of glucose 6 phosphate dehydrogenase (G6PD) could be caused after a pregnant woman or a newborn baby takes RC and BBR, which may lead to hemolytic jaundice of the newborn baby18. Liao19carried out a study where he provided RC decoction to 22 newborn babies in hospital, among which three were short of G6PD. According to his observation, they concluded that the intake of RC within the dose range was safe and would not cause hemolytic jaundice or any other side effects for either newborn babies that were short of G6PD or normal ones. And in March 2016, the ban on RC is finally dismissed. Pro.Tong concluded that the use of RC within the dose range was safe and would not cause jaundice or kernicterus. If RC is taken over long period or used with large dose, it may cause “impairment of the stomach due to cold and bitterness,” which mainly means that it may damage yang qi. The adverse actions are closely related to the dosage of the drug, the constitution of the patients, and the drug compatibility, housing the spleen, stomach, liver, and gallbladder, marked by diminished function of the spleen and stomach in digestion and absorption [90], thus resulting in discomforts of gastrointestinal tracts. After repeatedly clinical practices, we solve the contradiction of using RC by means of compatibility of medicinals.

    SUMMARY

    Rhizoma coptidis, a kind of classical heat-clearing and detoxifying herb, is playing an important role in treating T2DM, thus arouse strong interests in the mechanisms of its hypoglycemic activity. In this review, on one hand, we provide scientific evidence on the effective components, pharmacological researches, toxicity, and the randomized controlled trials (RCTs) on the effectiveness and safety of RC. Natural plants, especially Chinese herbal medicines, have built up a characteristic medical system directed by traditional Chinese medical theory and provided rational means for various diseases including DM12.The treatment of T2DM and its complications mainly depend on western hypoglycemic drugs, and/or insulin, but more and more patients have been concerned about the potential toxicity and side effects, and they failed to delay the progression of diabetic complications; sometimes the clinical efficiency is far from being satisfactory. Due to positive views of patients towards complementary and alternative medicine (CAM) therapies, and the increased availability of them, CAM therapies are increasingly and frequently used globally; the commonly used therapies are traditional Chinese medicines, acupuncture, nutritional supplements and advice, spiritual healing, and relaxation techniques.20-22

    REDERENCES

    1 J. Sun, J. S. Ma, J. Jin, et al. Qualitative and quantitative determination of the main components of Huanglian Jie Du Decoction by HPLC-UV/MS. Acta Pharmaceutica Sinica,2006, 41(4):380-384.

    2 B. S. Ko, S. B. Choi, S. K. Park, J. S. Jang, Y. E. Kim. Insulin sensitizing and insulinotropic action of berberine from Cortidis Rhizoma. Biological and Pharmaceutical Bulletin, 2005,28(8):1431-1437.

    3 X. Xia, J. Yan, Y. Shen, et al. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS ONE, 2011, 6(2),Article ID e16556.

    4 Kong W, Wei J, Abidi P, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004,10(12):1344.

    5 Y. Yang, Z. Zhang, S. Li, et al. Synergy effects of herb extracts: pharmacokinetics and pharmacodynamics basis. Fitoterapia, 2014,92: 133-147.

    6 Song wang, Linhua zhao,Yuan zhou. ProfessorXiaolin Tong’s thinking on toxic, dose and effect of Rhizoma Coptidis. World Journal of traditional Chinese Medicine,2014(10):1325-1327.

    7 Junlin li. The treatment of diabetic gastroparesis case study and experience on gastrointestinal motility in diabetic rats by professor Xiaolin tong. Beijing: Beijing University of Chinese Medicine,2013.

    8 G.X. Zhu, Q. Zhou, X.L.Tong. Points on the clinical practice of Rhizoma Coptidis in the treatment of diabetes mellitus. Journal of Traditional Chinese Medicine, 2014,55(22):1969-1971.

    9 Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China. Beijing: China Medical Science Press, 2010.

    10 W. K. Liu. The Analysis of Regularity of Treating Diabetes with Kusuanzhitian Method on the Basis of Clinic Data Mining. Beijing: China Academy of Chinese Medical Sciences, 2010.

    11 X. Y. Li. Data mining on dosage rules of treating diabetes mellitus with classical formulas by Professor Tong. Beijing: Beijing University of Traditional Chinese Medicine, 2010:42-43.

    12 X.L.Tong,W. K. Liu. On the muddy disease. Journal of traditional Chinese Medicine,2011,52(10):816-818.

    13 L.H.Zhao,H.Y.Ji,B.W.Ji,etc. To explore the theory of Gegenqinlian Decoction Treatment of diabetes. Chinese Journal of traditional Chinese Medicine,2012, 27(2):280-283.

    14 Y. Zhao, L. B. Zhou, L. Dong, et al. Clinical research of obesity type 2 diabetes with treating method of “acrid medicinals helps to open and bitter medicinals helps to direct things downward. CHINESE ARCHIVES OF TRADITIONAL CHINESE MEDICI NE,2016,25(12):2575-2578.

    15 X. L. Tong.Application of classical formulas with Rhizomacoptidis as main medicinals in treating diabetes mellitus. Journal of Traditional Chinese Medicine,2015, 54(3):209-211.

    16 X. L. Tong, W. K. Liu, G. L. Xu, et al. Clinical dosage and medicinal method of Rhizoma coptidis in the treatment of diabetes. Journal of Traditional Chinese Medicine, 2016,52(18):1604-1605.

    17 Y. Zhou. The Application and Summary of Rhizoma Coptidis on Its Hypoglycemic Activity. Beijing: Beijing University of Traditional Chinese Medicine,2011.

    18 S. Y. Yang, X. H. Wang. Discussion between Chinese herbal researches on skin infections of newborn infants and jaundice of the newborn baby caused by Rhizoma coptidis. Medical Research,2008(7):5.

    19 C. L. Liao. reliminary Observation on Physiological Jaundice (Fetal Jaundice) of the Newborn Baby Related by Yinchen Hao Decoction and Rhizoma Coptidis. Private School of Chinese Medicine Researches of Annual Report, 1982(13).

    20 C. Vincent and A. Furnham. Why do patients turn to complementary medicine? An empirical study. British Journal of Clinical Psychology,1996,35(1):37-48.

    21 R. A. Bell, C. K. Suerken, J. G. Grzywacz, et al. Complementary and alternative medicine use among adults with diabetes in the United States. Alternative Therapies in Health and Medicine,2006,12(5):16-22.

    22 M.-S. Lee, M. S. Lee, H.-J. Lim, et al. Survey of the use of complementary and alternative medicine among Korean diabetes mellitus patients. Pharmacoepidemiology and Drug Safety,2004,13(3):167-171.

    (Accepted: February 18, 2017)

    Department of Endocrinology, Guang’anmen Hospital of China, Academy of Chinese Medical Sciences, Beijing 100054, China

    *Corresponding author: Email: xiaolintong66@163.com

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