Research Update: Huan Lian Jie Du Tang (Coptis & Scutellaria Decoction)

About the Author

Dr Tony Reid

Master of Acupuncture, Master of Traditional Chinese Medicine (UWS) Sun Herbal co-founder, Director of Education, Research and Development. www.SunHerbal.com

Introduction

Huang Lian Jie Du Tang (HLJDT) was first recorded in ‘Medical Secrets of an Official’ (wai tai mi yao), by Wang Tao, 752 CE, a work in 40 volumes that covers every branch of medicine and contains over 6,000 formulas. HLJDT was originally used for severe conditions in which a virulent pathogen (Heat Toxin or Fire Toxin) pervades the three Jiao (i.e. upper, middle and lower body compartments), thus affecting all bodily systems. (1, 2) In ancient times HLJDT was given to soldiers before battle, both to reduce their anger so they would not become confused as well as to prevent excessive bleeding when injured. (3)

Huang Lian Jie Du Tang

Two of the three ‘yellow’ (huang) herbs in this formula (Coptis – huang lian and Phellodendron – huang bai) contain a variety of potent alkaloids (including berberine and palmatine), while the other yellow herb (Scutellaria – huang qin) contains a multitude of different types of flavonoids. The fourth ingredient, Gardenia fruit (shan zhi zi) contains several different iridoids and iridoid glycosides. These compounds are collectively responsible for the biological activities of HLJDT, providing a broad-spectrum antimicrobial action as well as anti-inflammatory and antipyretic effects. (4) It is therefore suitable for treating a variety of acute infections and inflammatory conditions.

In China and Japan, it is used in the treatment of: septicemia, pyemia, dysentery, acute gastro-enteritis, acute hepatitis, acute cholecystitis, pneumonia, urinary tract infections, stomatitis, periodontitis, meningitis, encephalitis B, insomnia, hypertension and sequelae of stroke.  (1, 2) In Japan and Korea, HLJDT has been approved for use in palliative care and for atopic dermatitis by the Ministry of Health Labour and Welfare of Japan and the Korean Food and Drug Administration. (4)  In addition, recent research has focused on the formula’s actions on the central nervous system, in line with the description of the therapeutic actions of Coptis, the formula’s major herb, given in the earliest Chinese materia medica, the Shen Nong Ben Cao Jing (The Divine Farmer’s Classic on Materia Medica), circa 1st century BCE.

 

The Formula: Huang Lian Jie Du Tang

The original formula contains four ingredients:  Coptis, Scutellaria, Phellodendron and Gardenia

Coptis chinensis, root (huang lian):30%
Scutellaria baicalensis root (huang qin):20%
Phellodendron amurense, stem bark (huang bai):20%
Gardenia jasminoides, fruit (shan zhi zi):30%


The TCM actions of each ingredient are as follows (1, 2):

  • Coptis root: clears Damp-Heat, purges Fire from the Heart and from the middle and upper Jiao.
  • Scutellaria root: clears Damp-Heat and purges Fire from the upper and middle Jiao
  • Phellodendron stem bark: clears Damp-Heat and purges Fire from the lower Jiao
  • Gardenia fruit: drains Heat or Fire from the whole of the three Jiao, clears Damp-Heat and promotes diuresis, clears Heat Toxin.

The major herb in HLJDT, Coptis rhizome, is described in Shen Nong’s Materia Medica (shen nong ben cao jing), from the first century BCE, with the following actions:

‘Coptis is bitter. It is nontoxic, treating mainly heat qi, eye pain, injured canthi, and tearing. It brightens the eyes and it also treats intestinal afflux, abdominal pain, dysentery, and, in females, genital swelling and pain. Protracted taking may improve the memory.’ (5)

A commentary from Qing dynasty physician, Chen Nian-zu (1753-1823 CE), further explains:

‘When the Classic says it mainly treats Heat Qi, [it means that] it eliminates

all Heat in the Qi division. Intestinal afflux, abdominal pain and dysentery

are all diseases [that may be] ascribed to Damp-Heat in the middle [Jiao, i.e. Spleen-Stomach]. Genital pain and swelling is an illness caused by Damp-Heat below [in the lower Jiao]. Coptis eliminates Damp-Heat. So, these are all its indications.’ (5)

Research on Huang Lian Jie Du Tang

A considerable number of studies on the effects of HLJDT in humans and animals has been carried out in China since the 1960’s and they often cited in more recent compilations, including the standard tertiary texts. (1, 2, 6) However, much of this material is of questionable quality, and many of the original papers are now unavailable for scrutiny. Additionally, Chinese researchers have only begun to adopt acceptable international standards, for both conducting as well as reporting clinical research since the early 2000’s. With this caveat, there are Chinese studies demonstrating the efficacy of HLJDT in the following conditions: septicemia, pyemia, acute gastroenteritis, bacteria dysentery, acute hepatitis, acute cholecystitis, encephalitis B, meningitis, cerebrovascular accident, sequelae of stroke, transient cerebral ischemia, pneumonia, otitis media, pelvic inflammatory disease, vaginitis, post-surgical infection, abscess, acne, impetigo herpetiformis, eczema of the anus, urinary tract infection, stomatitis, periodontitis. (1, 2) Additionally, and with the same caveats, HLJDT has been shown to have the following the pharmacological effects: antipyretic, antispasmodic (on the smooth muscle of the GIT), anti-ulcer, anti-diarrhea, hepatoprotective, antioxidant, analgesic, anti-inflammatory, antihypertensive, antihyperlipidemic, hypoglycemic, anticholesterolemic. (2)

Recent studies in human subjects

Good quality evidence in humans from studies undertaken since 2000, show that HLJDT is clinically effective in the following scenarios:

  • Prevention of stomatitis and diarrhea in patients undergoing cytotoxic chemotherapy for cancer. In a study on 40 patients with acute leukemia there was a significant preventive effect on mucositis caused by anticancer agents, with marked reductions in stomatitis and diarrhea in the group taking HLJDT.  (7)
  • Reduction of plasma triglyceride levels and enhancement of plasma albumin concentration, thus improving the microcirculation via lipid and protein metabolism, measured in 20 healthy male subjects. This helps to explain the formula’s effectiveness in the treatment of cerebrovascular accident. (8)
  • Augments the therapeutic actions of Yi Gan San (YGS) in the treatment of a) the behavioral and psychological symptoms of dementia, b) tardive dyskinesia due to antipsychotic medication, and c) irritability, impulsivity and aggression. Three case studies from Japan in which one dementia patient, one middle aged patient on risperidone (anti-psychotic) and one young adult responded partially to treatment with YGS, showed dramatic improvement (i.e. complete or almost complete resolution of symptoms) with the addition of HLJDT to the regimen. (9)
  • Improves intestinal barrier function in critically ill patients after abdominal surgery, to promote recovery of gastrointestinal function (together with electro-acupuncture treatment). (10)
  • Potential to delay the progression of Alzheimer’s disease by reducing production of amyloid beta-1-42 protein and phosphorylated Tau protein, which lead to amyloid plaque formation and the development of neurofibrillary tangles, respectively. (11)

Recent studies on animals

A 2019 review on the phytochemistry, pharmacology and pharmacokinetics of HLJDT cites 174 papers, most of which are in vivo animal studies, conducted within the past 15 years. (4) This material is of a far better quality than that upon which the above-mentioned textbooks have relied upon and give a much more accurate picture of the scope of HLJDT’s pharmacology and its potential therapeutic effects. The pharmacological actions of HLJDT are summarized below: (4,12,13)

  • Anti-tumor: inhibits proliferation of cancer cells (hepatocellular carcinoma and myeloma cell lines)
  • Hepatoprotective: restoration of liver function after cholestatic injury (bile duct ligation in rats)
  • Anti-inflammatory: reduces inflammatory response to a broad range of irritants via various pathways, effective in animal models of gingivitis, inflammatory bowel disease, gastritis, sepsis, rheumatoid arthritis and dermatitis.
  • Anti-allergy: suppresses allergic and inflammatory mediators in cultured mouse macrophage cells, which have been stimulated by lipopolysccharide
  • Hypolipidemic: lowers blood triglycerides in high fat diet induced hyperlipidemia (rat model).
  • Anticholesterolemic: lowers total cholesterol and LDL cholesterol in type 2 diabetic rats.
  • Hypogylcemic: in rat diabetes type 2 model, with actions on the gut (increased GLP-1 secretion) to promote insulin secretion and action on pancreatic beta cells (hypertrophy, hyperplasia and increased insulin secretion)
  • Neuroprotective in various CNS diseases, including animal models of ischemic stroke and Alzheimer’s disease.
  • Antimicrobial and anti-viral: against candida albicans, pseudomonas aeruginosa and N1HI influenza virus (swine ‘flu).
  • Modulates microbiota: reduction in pathogens and increase in short chain fatty acid producing (i.e. probiotic) bacteria in mouse model of type 2 diabetes. 
  • Protection of gastric mucosal barrier in ethanol- and aspirin-induced injury.

Thus, while good quality evidence for this formula’s therapeutic actions in humans is at present quite limited, the above pharmacological actions may serve to support its use in the treatment of hyperlipidemia, tumors, arthritis, sepsis, cardiac damage, liver injury, kidney disease, cerebral ischemia, type 2 diabetes, Alzheimer’s disease, fungal infection, inflammatory bowel disease, gastritis, atopic dermatitis and gingivitis.

Best available evidence to date indicates that the complete formula composed of the four herbs, Coptis, Scutellaria, Phellodendron and Gardenia in a 3:2:2:3 ratio, has much better therapeutic effects that any one of the herbs on its own or any combination of three herbs used together. (4, 14, 15) Moreover, the neuroprotective effects of HLJDT are mediated, at least in part, by compounds formed by the interaction of components of Coptis with those of Scutellaria during decoction of the formula. (16)

Psychological effects of HLJDT

Although somewhat overshadowed by the formula’s powerful antimicrobial and anti-inflammatory effects, traditional use of HLJDT also involves conditions due to ‘Heart Fire’. In TCM this syndrome-pattern is conceptualized as follows.

The Heart is the seat of consciousness and the activities of consciousness (the Spirit, or shen in TCM). When the Heart is affected by pathogenic Heat, this readily develops into pathogenic Fire, as the Heart, belonging to the Fire phase of the Five Elements, is most susceptible to the effects of Heat. Pathogenic Fire is extreme Heat, which causes more severe disturbances to normal functioning and also tends to spread to other systems, disrupting their function. The normal functions of the Spirit are all of the nature of Fire: the clarity of conscious awareness, the reactivity of the emotions, as well as the motivating force provided by the emotions – all have the quality of Fire: illuminating, warming and activating. Thus, when Fire becomes excessive (i.e. pathogenic), it means that the normal controls that regulate our mental and emotional activities begin to fail and these activities now operate in an unconstrained manner and tend to become extreme. This may lead to mental confusion, and overly excitable emotions that demand expression. This is the psychological aspect of Heart Fire syndrome. (17,18)

The use of the formula, generally as an adjunct, in treating predominantly psychological disorders due to Heart Fire (e.g. agitated type of depression, insomnia, behavioral and psychological symptoms of Alzheimer’s disease, etc.) is supported by findings in animal studies. HLJDT has been shown to reduce glutamate and gamma-aminobutyric acid (GABA) induced excitotoxicity and maintain the function of cholinergic neurons under conditions of ischemic injury. (19, 20) In addition, the formula has marked anti-inflammatory effects within the CNS, which may be mediated, at least in part, by antioxidant actions and the effects on the liver (affecting the liver-brain axis) and on the gut microbiota (affecting the gut-brain axis). (21, 22)

Dosage

Based on the dosages used in the human trials cited above, the equivalent dose of HLJDT capsules is 9 – 10 capsules, twice daily; and for HLJDT pills (a.k.a. Coptis and Scute Formula) is 40 pills twice daily.

HLJDT is available as Antitox 2 Formula (CM175) in capsules, and Huang Lian Jie Du Wan pills (Coptis and Scute Formula) BP049 in pills, from Sun herbal Pty Ltd.

REFERENCES

  1. Scheid, V., Bensky, D, Ellis, A., Barolet, R. (2015). Chinese Herbal Medicine Formulas & Strategies. Seattle WA: Eastland Press Inc. (pp.167-9)
  2. Chen, J., Chen, T. (2009). Chinese Herbal Formulas and Applications Pharmacological Efects and Clinical Research. City of Industry CA: Art of Medicine Press, Inc. (pp.341-6)
  3. Okamoto, H., Chino, A., Hirasaki, Y., Ueda, K., Iyo, M., & Namiki, T. (2013). Orengedoku-to augmentation in cases showing partial response to yokukan-san treatment: a case report and literature review of the evidence for use of these Kampo herbal formulae. Neuropsychiatr Dis Treat, 9: 151–155.
  4. Qi, Y., Zhang, Q., & Zhu, H. (2019). Huang-Lian Jie-Du decoction: a review on phytochemical, pharmacological and pharmacokinetic investigations. Chin Med, 14: 57.
  5. Yang, S. (1998). The Divine Farmer’s Materia Medica; A Translation of the Shen Nong Ben Cao Jing. Boulder, CO: Blue Poppy Press (p.14)
  6. Chang, H., But, P. (1986). Pharmacology and Applications of Chinese Materia Medica, Vol 1. Singapore: World Scientific Publishing Co. P/L (pp.1061-77)
  7. Yuki F, Kawaguchi T, Hazemoto K, Asou N. (3003). Preventive effects of oren-gedoku-to on mucositis caused by anticancer agents in patients with acute leukemia. Gan To Kagaku Ryoho. 30(9):1303-7. 
  8. Sekiya N, Kogure T, Kita T, Kasahara Y, Sakakibara I, Goto H, Shibahara N, Shimada Y, Terasawa K. (2002) Reduction of Plasma Triglyceride Level and Enhancement of Plasma Albumin Concentration by Oren-gedoku-to Administration. Phytomedicine. 9(5):455-60.
  9. Okamoto, H., Chino, A., Hirasaki, Y., Ueda, K., Iyo, M., & Namiki, T. (2013). Orengedoku-to augmentation in cases showing partial response to yokukan-san treatment: a case report and literature review of the evidence for use of these Kampo herbal formulae. Neuropsychiatr Dis Treat. 9, 151–155.
  10. Effect of Modified Huanglian Jiedu Decoction Purgation Combined Electroacupuncture in Intervening Gastrointestinal Dysfunction of Critically Ill Patients Undergoing Abdominal Surgery. Zhongguo Zhong Xi Yi Jie He Za Zhi. 35(8):966-70.
  11. Chen, H., Guan, F. (2016). Effect of Huanglian Jiedu Decoction on pitavastatin treatment of Alzheimer’s disease. Journal of Hainan Medical College, 22:71-74.
  12. Chen Y, Xian YF, Loo S, Lai Z, Chan WY, Liu L, Lin ZX. (2020). Huang-Lian-Jie-Du extract ameliorates atopic dermatitis-like skin lesions induced by 2,4-dinitrobenzene in mice via suppression of MAPKs and NF-κB pathways. J Ethnopharmacol. 249:112367
  13. Wu W, He X, Xie S, Li B, Chen J, Qu Y, Li B, Lei M, Liu X. (2020). Protective effects of Huang-Lian-Jie-Du-Tang against Aβ25-35-induced memory deficits and oxidative stress in rats. J Int Med Res. 48(3):300060519893859. 
  14. Xu D, Lv Y, Wang J, Yang M, Kong L. (2017).Deciphering the mechanism of Huang-Lian-Jie-Du-Decoction on the treatment of sepsis by formula decomposition and metabolomics: Enhancement of cholinergic pathways and inhibition of HMGB-1/TLR4/NF-κB signaling. Pharmacol Res.121:94-113.
  15. Zhang Q, Wang J, Zhang C, Liao S, Li P, Xu D, Lv Y, Yang M, Kong L. (2016). The components of Huang-Lian-Jie-Du-Decoction act synergistically to exert protective effects in a rat ischemic stroke model. Oncotarget. 7(49):80872-80887.
  16. Wang H, Li T, Xiang H, Zhang X, Fang K, Wu G, Yan M, Xue N, Chen M, Xie T, Zhang Y, Wang P, Lei H. (2017). Origin and Formation Mechanism Investigation of Compound Precipitation from the Traditional Chinese Prescription Huang-Lian-Jie-Du-Tang by Isothermal Titration Calorimetry. Molecules. 22(9). pii: E1456. 
  17. Maciocia, G. (2009). The Psyche in Chinese Medicine: Treatment of Emotional and Mental Disharmonies with Acupuncture and Chinese Herbs. Edinburgh: Churchill Livingstone Elsevier. (pp.222, 457-8)
  18. Reid, T. (2017). The Emotions in Traditional Chinese Medicine, Parts 1 & 2. The Natural Therapist, 32(1): 23-9; The Natural Therapist,33(2):40-5
  19. Zhang, Q., Wang, J., Liao, S., Li, P., Xu, D., Lv, Y., Yang, M., & Kong, L. (2017). Optimization of Huang-Lian-Jie-Du-Decoction for Ischemic Stroke Treatment and Mechanistic Study by Metabolomic Profiling and Network Analysis. Front Pharmacol, 8:65.
  20. Zhu B, Cao H, Sun L, Li B, Guo L, Duan J, Zhu H, Zhang Q. (2018). Metabolomics-based mechanisms exploration of Huang-Lian Jie-Du decoction on cerebral ischemia via UPLC-Q-TOF/MS analysis on rat serum. J Ethnopharmacol; 216:147-156.
  21. Zhang, Q., Wang, J., Zhang, C., Liao, S., Li, P., Xu, D., Lv, Y., Yang, M., & Kong, L. (2016). The components of Huang-Lian-Jie-Du-Decoction act synergistically to exert protective effects in a rat ischemic stroke model. Oncotarget, 7(49), 80872–80887.
  22. Chen, M., Liao, Z., Lu, B., Wang, M., Lin, L., Zhang, S., Li, Y., Liu, D., Liao, Q., & Xie, Z. (2018). Huang-Lian-Jie-Du-Decoction Ameliorates Hyperglycemia and Insulin Resistant in Association With Gut Microbiota Modulation. Front Microbiol, 9:2380.