Therapeutic mechanism of Yīn-Chén-Hāo decoction in hepatic diseases

Table 1 Clinical trials using Yīn-Chén-Hāo decoction

Herb or compound	Dose and course of treatment	Combined medication	Case/control	Disease type	Symptoms	Efficacy	Positive control drug	Side effects	Ref.
YCHD	From 28th wk of pregnancy, decocted with water, daily, 4 wk	From 36th wk of pregnancy, both groups, + administration of 30 mg phenobarbital, twice a day, orally	81/76	Maternal-fetal ABO blood group incompatibility	IgG anti-A/B antibody titer, growth in fetus, neonatal jaundice	Reduced antibody titer, reduced jaundice incidence rate, reduced TBIL	Vitamin C 0.5 g + 100 IU coenzyme A + 40 mg adenosine triphosphate, IVGTT	None	[61]
YCHD	Modified YCHD, decocted with water daily; orally, twice a day	1000 mg transmetil injection, IVGTT	38/30	Hyperbilirubinemia induced by viral hepatitis	Clinical symptoms, liver function, bilirubin	Symptoms, bilirubin levels significantly improved due to liver function	Vitamin C, vitamin B6, diammonium	None	[62]
Modified YCHD	Decocted with water, daily, 10 d	Routine Western medical treatment	34/34	Pathological neonatal jaundice	Time of jaundice disappearance, jaundice degree, TBIL	Time jaundice disappearance is shut down, liver TBIL significantly decreased	Routine Western medicine therapy, etiological treatment, light therapy, phenobarbital, albumin for patients with high bilirubin, gamma globulin for patients with hemolytic disease	None	[63]
Modified YCHD	Decocted with water, daily, 14 d	Plasma exchange	20/20	Hepatitis B combined with hyperbilirubinemia	Liver function, prothrombin activity	TBIL significantly decreased effective rate of treatment group compared with significantly increased control group	Plasma exchange	None	[64]
Modified YCHD	Decocted with water, daily, orally, 28 d	Mask with the function of removing heat and eliminating stasis	31/29	Gastrointestinal damp-heat acne	Acne coalescence condition	Increased total effective rate of acne coalescence, average efficacy index statistically significantly decreased	Danshentong capsules for oral use, vitamin E emulsifiable paste for external use	None	[65]
Modified YCHD	Decocted with water, daily, orally, 7 d	None	32/34	Juvenile bronchial asthma	Asthma symptoms	Curative effect of treatment group significantly better than control group; fade time of cough, sputum, and wheezing in treatment group significantly shorter than control group (P < 0.05)	Normal saline, dexamethasone injection, ambroxol hydrochloride injection, aerosol inhalation, twice a day, 3-7 days, additional antibiotics for infected individual	None	[66]
Modified YCHD	Decocted with water, daily, orally	EST + endoscopic stone extraction + ENBD	24/24	Choledocholithiasis	TBIL, DBIL, AKP, GGT, ALT, daily bile reflux	Observed indicators improved significantly, daily bile reflux significantly higher than control group (P < 0.05)	Anti-infection, hepatoprotective, prevents fluid and electrolyte imbalance, symptomatic supportive care	None	[67]
Yin-Zhi-Huang injection	10 mL + 20 mL glucose solution, IVGTT, daily, 15 wk	Kadai surgery, antibiotic treatment, hormone treatment, +vitamin K1, +ursodeoxycholic acid	18/14	Biliary atresia	TBIL, DBIL, ALT, AST	Observation target significantly improved (P < 0.05)	None	None	[68]
Yin-Zhi-Huang granule	1.0 g, 3 times a day, orally, 7 d	Blue light irradiation, 8 h daily + 105 mg bifid-triple viable capsule, twice a day orally, 7 d	150/133/141	Neonatal jaundice	Time of jaundice disappearance, transcutaneous bilirubin	Time of jaundice disappearance significantly reduced, transcutaneous bilirubin level significantly reduced (P < 0.05)	Blue light irradiation	None	[69]
Yin-Zhi-Huang granule	3.3 mL, 3 times a day, orally, 5 d	None	120/120/120	Pathological neonatal jaundice	Bilirubin concentration, time of jaundice disappearance	Plasma bilirubin level significantly reduced, total effective rate significantly increased	Tuihuang mixture	None	[70]
Yin-Zhi-Huang injection	5 mL + 10% glucose solution 50 mL, IVGTT, daily, 10 d	ATP, coenzyme A, inosine, vitamin C, glucuronolactone	46/12	Infantile hepatitis syndrome	Treatment results (cured, improved, invalid), serum TBIL, ALT value, size of liver and spleen	Cure rate, total effective rate significantly increased, plasma bilirubin level significantly reduced, obvious change to liver and spleen size	ATP, coenzyme A, inosine, vitamin C, glucuronolactone	None	[71]
Modified compound Yīn-Chén recipe	Twice a day	None	215/120	Maternal-fetal ABO blood group incompatibility-induced neonatal jaundice	Antibody titer, neonatal jaundice incidence, jaundice degree	Antibody titer and neonatal jaundice incidence much lower post-treatment, TCM treatment before delivery failed to reduce jaundice degree	None	None	[72]
ICKT	7.5 g, daily, orally	None	1	Acute cholestatic hepatitis	Clinical course of patient	TBIL level began to decrease, liver biopsy showed chronic active hepatitis with mild fibrosis	Predonine	None	[73]
ICKT	7.5 g, daily, orally	None	50/50	Persistent hyperbilirubinemia as a symptom of post-operative liver failure after hepatectomy	Choleretic effect	ICKT group showed significant decrease compared with control group in indirect bilirubin levels	None	None	[74]
Modified compound Yīn-Chén recipe	Modified compound Yīn-Chén recipe decoction, orally	Routine Western medical treatment	30/30	Chronic severe hepatitis	Liver function indices, complication incidences, score of TCM syndromes, clinical effects	Treatment group better than control group (P < 0.05)	Basic Western medical treatment	None	[75]
Modified YCHD	Retention enema, daily	Routine comprehensive treatment	30/30	Chronic severe hepatitis	Liver function indices, endotoxin, blood ammonia	Treatment group better than control group (P < 0.05) in improvement of clinical symptoms, endotoxin, blood ammonia, ALT, AST, and TBIL	Lactulose medicated by retention enema	None	[76]
Modified Artemisiae	Twice a day	Ursodeoxycholic acid	30/30	Primary biliary cirrhosis	Clinical effect, biochemistry indicators, immunoglobulin levels	Treatment group better than control group (P < 0.05) in clinical effect and biochemistry indicators, insignificantly decreased immunoglobulin levels (P > 0. 05)	Ursodeoxycholic acid	None	[77]
Scopariae decoction
Modified YCHD	Twice a day	Conventional treatment, phenobarbital (blue light-struck)	30/29	Neonatal hyperbilirubinemia	Clinical effect	Treatment group better than control group (P < 0.05) in clinical effect	Conventional treatment (phenobarbital, blue light-struck)	None	[78]
Lidan Xiaohuang decoction	50-100 mL 2-3 times a day, orally	Routine	35/31	Obstructive jaundice, post-operative persistent jaundice	Bilirubin	Treatment group better than control group (P < 0.01)	Acupuncture therapy	None	[79]
		Western medical treatment
Qing-Re-Li-Shi formula	Twice a day, 90 d	None	60	Chronic hepatitis B	Liver function comparison, hepatitis B virus marker comparison	Contents of ALT, AST, AKP, G, TBIL, DBIL improved (P < 0.01); negative conversion rates of 16.7% HbsAg, 21.2% HbeAg, and 35.0% HBV	None	None	[80]
Modified compound Yīn-Chén recipe	Twice a day	Triple anti-Hp therapy	30/30	Hp-positive rosacea	Clinical effective rate, Hp- positive rate, serum IL-8, TNF-α	Clinical effective rate in treatment group better than control group (P < 0.05); Hp- positive rate, serum IL-8, and TNF-α in treatment group significantly lower than control group (P < 0.01)	Triple anti-Hp therapy	None	[81]
Modified compound Yīn-Chén recipe	Twice a day	Routine	120/90	Viral hepatitis jaundice	Jaundice disappearance, liver function improvement	Clinical effective rate and liver function in treatment group better than control group (P < 0.05)	Routine	None	[82]
		Western medical treatment					Western medical treatment
Obstructive jaundice	Twice a day	Obstructive jaundice	28/26	Obstructive jaundice	TBIL, DBIL	More obvious decline of TBIL and DBIL in experimental group (P < 0.05)	Obstructive jaundice	None	[83]
Supplement YCHD	Twice a day	Routine	30/30	Severe chronic hepatitis B	Liver function, gross effective rate, mortality rate	YCHD significantly improved liver function and gross effective rate, mortality rate lower than control group (P < 0.05)	Routine	None	[84]
		Western medical treatment for protective liver, plasma exchange					Western medicinal treatment for protective liver, plasma exchange
YCHD	Twice a day	Routine	30/30	Intrahepatic cholestasis of pregnancy	Pruritus score, serum bile acid level, Apgar score, body weight	Pruritus score and serum bile acid level lower than control group (P < 0.05, P < 0.01, respectively); Apgar score and body weight better than control group (P < 0.01)	Routine	None	[85]
		Western medical treatment for protective liver					Western medical treatment for protective liver

YCHD: Yīn-Chén-Hāo decoction; TBIL: Total bilirubin; IVGTT: Intravenous glucose tolerance test; EST: Endoscopic sphincterotomy; ENBD: Endoscopic nasobiliary drainage; DBIL: Direct bilirubin; AKP: Alkaline phosphatase; GTT: Gamma-glutamyl transferase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ATP: Adenosine triphosphate; TCM: Traditional Chinese medicine; ICKT: In-Chin-Ko-To; HBV: Hepatitis B virus; Hp: Haptoglobin.

Table 2 Mechanisms of action of compounds found in Yīn-Chén-Hāo decoction

Compound	Pharmacological activities	Mechanisms of action	Ref.
Chlorogenic acid	Antibacterial, antiviral, antioxidation,	Reversed liver reduced GSH levels and expression of TRX, triggering GSH and TRX antioxidant systems and MAPK signaling cascade	[8]
	free radical scavenging,
	mutation suppression, anti-tumor
Scoparone	Anti-inflammatory, analgesia, antioxidant, immunosuppressive, cholagogue, blood pressure, hypolipidemic, anti-asthmatic	Inhibition of protein tyrosine kinase and release of arachidonic acid metabolites, reduced expression of tissue factor at mRNA level and thrombus generation; enhancement of prostacyclin release, protection against endothelium derived relaxing factor inactivation, and activating guanylate cyclase, relaxed bronchial smooth muscle	[86-89]
Geniposide	Anti-inflammatory, analgesia, cholagogue, laxness, soft tissue injury repair, gastric acid secretion inhibition, amylopsin secretion reduction	Enhancing antioxidative defense system and reducing apoptotic signaling pathways; regulating adipocytokine release and the expression of PPARα expression	[9,90]
Rhein	Antineoplastic, anti-inflammatory, antimicrobial, immunosuppressive, diuresis and purgation, improve glycometabolic	Inhibiting cytochrome P450 enzymes in liver microsomes	[91]
Emodin	Antineoplastic, anti-inflammatory, antimicrobial, immunosuppressive, diuresis and purgation	Inhibiting HSC activation	[92]

GSH: Glutathione; TRX: Thioredoxin; MAPK: Mitogen-activated protein kinase; PPARα: Peroxisome proliferator activated receptor-α; HSC: Hepatic stellate cell.

Table 3 Patents containing Yīn-Chén-Hāo decoction

Patent	Patent number
YCHD preparation methods	CN101371882
Damp-proof TCM granule and its preparation method	CN1781499
Composition for improving the composition/kind of composition of crude drug powder containing rhubarb and/or its extract that can improve constipation	JP2005179316
Medical treatment for heterotopic calcification/medicine root in TCM prescription treatment for heterotopic calcification	JP5000961
Kind of formula granules, including YCHD and its preparation and detection methods	CN103230453
Method which can filtrate the material foundation of YCHD efficacy	CN104101674

YCHD: Yīn-Chén-Hāo decoction; TCM: Traditional Chinese medicine.