Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology

Figures & data

Table 1. Different processing methods of CR.

Processing method	Purpose of processing	Dynasty	Reference
Rubbing the fibrous roots with cloth, washing	Removing non-medicinal parts and impurities to ensure curative effect	Before the Tang Dynasty	(Lei 1985)
Stir-baking to dark brown	Enhancing the efficacy of digestion and invigorating the function of spleen	Song Dynasty	(Wang 1991)
Carbonizing by stir-frying	Producing hemostatic effect	Qing Dynasty	(Chen 2006)
Stir-baking with loess	Invigorating the function of spleen andstomach	Jin Yuan Period,Ming Dynasty	(Zhu 2012)
Stir-frying with wine	Treating insomnia, sore mouth, red and swelling eyes	Song Dynasty, Jin Yuan Period	(Zhu 2015)
Stir-frying with Ginger	Enhancing the effect preventing vomitting, and expelling phlegm	Song Dynasty	(Wang 1991)
Stir-frying with bile	Enhancing the function of clearing the fire of the liver and galllbladder	Ming Dynasty
Immersing into rice water	Strengthening the role of nourishing the spleen and harmonizing the spleen and stomach	Song Dynasty, Qing Dynasty	(Qian & Wang 2008)
Stir-baking with Evodiae Fructus	Curing diarrhea	Yuan Dynasty	(Zhu 2012)
Stir-baking with Rhizoma Zingiberis Recens	Enhancing the effect of preventing vomitting	Song Dynasty	(Dong 2003; Tang 2011)
Stir-baking with Sophorae Flos	Treatment of dysentery	Ming Dynasty	(Zhang 1996)
Steaming with wine	Curing diarrhea	Ming Dynasty
Steaming with milk	Curing acute conjunctivitis	Ming Dynasty	(Han 1985)

Table 2. The traditional and clinical uses of CR in China.

Preparation	Main compositions	Traditional and clinical uses	References
An Gong Niu Huang Pills	Coptidis Rhizoma, Bovis Calculus, Condensed powder of Bubali Corun, Moschusm or Artificial Moschusm, Margarita, Cinnabaris, Realgar, Scutellariae Radix, Gardeniae Fructus, Curcumae Radix, Syntheticum Borneolum	Curing febrile convulsions, delirious, and gibberish	(Chinese Pharmacopoeia Commission 2015)
Dang Gui Long Hui Pills	Coptidis Rhizoma, Angelicae Sinensis Radix, Gentianae Radix et Rhizoma, Rhei Radix et Rhizoma, Scutellariae Radix, Phellodendri Chinensis Cortex, Aloe, Ineigo Naturalis, Gardeniae Fructus, Aucklandiae Radix, Artificial Moschusm	Curing dizziness, tinnitus, deafness, rib pain, abdominal distension pain and constipation
Fu Fang Qing Dai Pill	Coptidis Rhizoma, Cnidii Frucutus, Sophorae Flavescentis Radix, Pseudolaricis Radix, Catechu, Alumen	Treating mycotic vaginitis, trichomonas vaginitis, and nonspecific vaginitis
Huang Lian Shang Qing Pills	Coptidis Rhizoma, Gardeniae Fructus, Forsythiae Fructus, Viticis Fructus, Saposhnikoviae Radix, Schizonepetae Spica, Angelicae Dahuricae Radix, Scutellariae Radix, Rhei Radix et Rhizoma, Chrysanthemi Flos, Menthae Haplocalycis Herba, Phellodendri Chinensis Cortex, Platycodonis Radix, Chuanxiong Rhizoma	Treating dizziness, tooth pain, tongue sores, sore throat, ear pain tinnitus and constipation
Huang Lian Yang Gan Pills	Coptidis Rhizoma, Rhizoma Picrohizae, Scutellariae Radix, Phellodendri Chinensis Cortex, Gentianae Radix et Rhizoma, Bupleuri Radix, Citri Reticulatae Pericarpium Viride, Equiseti Hiemalis Herba, Buddlejae Flos, Leonuri Fructus, Cassiae Semen, Haliotidis Concha	Treating red sore, eye, blurred vision
Kai Guang Fu Ming Pills	Coptidis Rhizoma, Gardeniae Fructus, Phellodendri Chinensis Cortex, Scutellariae Radix, Rhei Radix et Rhizoma, Saposhnikoviae Radix, Chrysanthemi Flos, Gentianae Radix et Rhizoma, Scrophulariae Radix, Paeoniae Radix Rubra, Alismatis Rhizoma, Rehmanniae Radix	Clearing heat and improving eyesight
Mu Xiang Bing Lang Pills	Coptidis Rhizoma, Aucklandiae Radix, Arecae Semen, Aurantii Fructus, Citri Reticulatae Pericarpium, Citri Reticulatae Pericarpium Viride, Cyperi Rhizoma, Sparganii Rhizoma, Curcumae Rhizoma, Phellodendri Chinensis Cortex, Rhei Radix et Rhizoma, Natrii Sulfas, Pharbitidis Semen	Treating abdominal distension pain and constipation
Niu Huang Qian Jin Powder	Coptidis Rhizoma, Scorpio, Bombyx Batryticatus, Bovis Calculus, Cinnabaris, Borneolum Syntheticum, Arisaema Cum Bile, Gastrodiae Rhizoma, Glycyrrhizae Radix et Rhizoma	Clearing heat and detoxifying, calming nerves, curing children convulsion with high fever, hand and foot convulsions
Qin Lian Tablets	Coptidis Rhizoma, Phellodendri Chinensis Cortex, Forsythiae Fructus, Scutellariae Radix, Paeoniae Radix Rubra, Glycyrrhizae Radix et Rhizoma	Treating headache and red eye, mouth and nose sores, hot dysentery, abdominal pain
Shen Shuai Ning Capsules	Coptidis Rhizoma, Radix Pseudostellariae, Praeparatum Pinelliae Rhizoma, Citri Reticulatae Pericarpium, Poria, Rhei Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Achyranthis Radix, Carthami Flos	Curing nausea, vomiting, poor appetite, bad urine, stool viscous
Wan Shi Niu Huang Qing Xin Pills	Coptidis Rhizoma, Bovis Calculus, Cinnabaris, Scutellariae Radix, Gardeniae Fructus, Curcumae Radix	Curing high fever irritability, insanity and children febrile convulsion
Wu Mei Pills	Coptidis Rhizoma, Mume Fructus, Asari Radix et Rhizoma, Zingiberis Rhizoma, Aconiti Lateralis Radix Praeparata, Zanthoxyli Pericarpium, Cinnamomi Ramulus, Ginseng Radix et Rhizoma, Phellodendri Chinensis Cortex, Angelicae Sinensis Radix	Curing abdominal pain, headache, mania, vomiting, and limbs cold.
Xiao Ke Ping Tablets	Coptidis Rhizoma, Ginseng Radix et Rhizoma, Trichosanthis Radix, Asparagi Radix, Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Lycii Fructus, Astragali Complanati Semen, Puerariae Lobatae Radix, Anemarrhenae Rhizoma, Galla Chinensis, Schisandrae Chinensis Fructus	Curing diabetes
Xiang Lian Pills	Coptidis Rhizoma, Aucklandiae Radix	Curing enteritis, and bacillary dysentery, relieving pain
Xiong Ju Shang Qing Pills	Coptidis Rhizoma, Chuanxiong Rhizoma, Scutellariae Radix, Viticis Fructus, Menthae Haplocalycis Herba, Schizonepetae Spica, Ligustici Rhizoma et Radix, Saposhnikoviae Radix, Angelicae Dahuricae Radix, Chrysanthemi Flos, Gardeniae Fructus, Forsythiae Fructus, Platycodonis Radix, Glycyrrhizae Radix et Rhizoma, Notopterygii Rhizoma et Radix	Treating migraine headache, nasal flow toothache, sore throat
Yi Qing Granules	Coptidis Rhizoma, Rhei Radix et Rhizoma, Scutellariae Radix	Treating pharyngitis, tonsil inflammation and gum inflammation
Zhu Che Pills	Coptidis Rhizoma, Zingiberis Rhizoma Praeparatum, Angelicae Sinensis Radix, Moschus	Nourishing Yin and stopping dysentery, curing abdominal pain, diarrhea
Zuo Jin Pills	Coptidis Rhizoma, Euodiae Fructus	Purging fire, soothing the liver, reconciling the intestines and stomach, analgesiastomach ache, mouth bitter noise, and vomiting
Niu Huang Qing Re Powder	Coptidis Rhizoma, Scutellariae Radix, Gardeniae Fructus, Curcumae Radix, Bovis Calculus, Bubali Corun, Cinnabaris, Borneolum Syntheticum	Treating high fever spasm, limbs twitch, irritability restless, and phlegm turbid congestion	(Zhong 1991)
Niu Huang Xing Nao Pills	Coptidis Rhizoma, Bovis Calculus, Bubali Corun, Borneolum Syntheticum, Scutellariae Radix, Gardeniae Fructus, Moschusm, Cinnabaris, Margarita, Curcumae Radix	Curing high fever, coma convulsion, irritable restlessness, infantile convulsionand insomnia	(Zhong 1998)
Qing Wei Huang Lian Pills	Coptidis Rhizoma, Glycyrrhizae Radix et Rhizoma, Platycodonis Radix, Gypsum Fibrosum, Anemarrhenae Rhizoma, Moutan Cortex, Trichosanthis Radix, Forsythiae Fructus, Scutellariae Radix, Gardeniae Fructus, Phellodendri Chinensis Cortex	Curing tongue sores, and sore throat	(Zhong 1998)
San Huang Pills	Coptidis Rhizoma, Rhei Radix et Rhizoma, Huang Cao	Curing dysentery, vomiting , hemoptysis and constipation
Xiao Er Qing Re Zhen Jing Powder	Coptidis Rhizoma, Arisaema Cum Bile, Scorpio, Bombyx Batryticatus, Glycyrrhizae Radix et Rhizoma, Bovis Calculus, Cinnabaris, Borneolum Syntheticum, Bambusae Concretio Silicea	Curing hot convulsion, hand-foot convulsions, cough, irritability and thirst	(Zhong 1991)
San Huang Qing Jie Pills	Coptidis Rhizoma, Scutellariae Radix, Forsythiae Fructus, Phellodendri Chinensis Cortex, Lonicerae Japonicae Flos	Curing fever, cough, sore throat, hot leaching and diarrhea	(Guo 2002)
Xie Li Xiao Pills	Coptidis Rhizoma, Atractylodis Rhizoma, Alba Paeoniae Radix, Aucklandiae Radix, Euodiae Fructus, Magnoliae Officinalis Cortex, Arecae Semen, Aurantii Fructus, Citri Reticulatae Pericarpium, Alismatis Rhizoma, Poria, Glycyrrhizae Radix et Rhizoma	Treating acute enteritis, colitis, and dysentery
Huang Lian Jie Du Pills	Coptidis Rhizoma, Phellodendri Chinensis Cortex, Scutellariae Radix, Rhei Radix et Rhizoma, Talcum, Clematidis Armandii Caulis, Gardeniae Fructus	Treating sore mouth, headache, constipation, red eyes, heartburn, sore throat,
Geng Nian Xin Capsules	Coptidis Rhizoma, Cinnamomi Cortex, Alpiniae Oxyphyliae Fructus, Lycii Fructus, Corni Fructus, Ligustri Lucidi Frucrus, Cuscutae Semen, Acori Tatarinowii Rhizoma, Rehmanniae Radix, Polygalae Radix, Ziziphi Spinosae Semen, Citri Reticulatae Pericarpium, Alismatis Rhizoma	Curing heart palpitations, insomnia, dizziness, tinnitus, and backache	(Chinese Pharmacopoeia Commission 2008)

Figure 1. The whole plants and rhizomes of C. chinensis (A), C. chinensis (B) and C. teeta (C).

Figure 2. Subtypes of protoberberines in Coptidis Rhizoma.

Figure 3. Matrices of isoquinolines in Coptidis Rhizoma.

Figure 4. Alkaloids numbered 1–27 in Coptidis Rhizoma.

Figure 5. Alkaloids numbered 28–44 in Coptidis Rhizoma.

Figure 6. Lignans numbered 45–66 in Coptidis Rhizoma.

Figure 7. Lignans numbered 67–75 in Coptidis Rhizoma.

Figure 8. Simple phenylpropanoids in Coptidis Rhizoma.

Figure 9. Flavonoids in Coptidis Rhizoma.

Figure 10. Other compounds in Coptidis Rhizoma.

Table 3. Partial list of chemical compounds isolated from CR.

Classification	Number	Ingredient name	Reference
Alkaloids	1	Berberine	(Noguchi et al. 1978)
	2	Berberrubine	(Li ZF et al. 2012)
	3	Coptisine	(Wang et al. 2014)
	4	Palmatine
	5	Epiberberine	(Mizuno et al. 1992)
	6	Columbamine	(Ikuta and Itokawa 1989)
	7	Tetradehydroscoulerine	(Chen et al. 2008)
	8	Jatrorrhizine	(Li ZF et al. 2012)
	9	Groenlandicine
	10	Berberastine	(Li ZF et al. 2012)
	11	Worenine
	12	8-Oxyberberine	(Wang et al. 2014)
	13	8-Oxycoptisine
	14	3-Hydroxy-2-methoxy-9,10-methylenedioxy-8-oxyprotoberberine	(Zhao et al. 2010)
	15	8-Oxyepiberberine	(Yang et al. 2014)
	16	8-Oxyberberrubine
	17	(−)-5-Hydroxyl-8-oxyberberine	(Wang et al. 2014)
	18	(+)-5-Hydroxyl-8-oxyberberine
	19	Tetrahydroberberine	(Wang et al. 2014)
	20	8,13-Dioxocoptisine hydroxide	(Yang et al. 2014)
	21	1,3-Dioxolo[4,5-g]isoquinolin-5(6H)-one	(Wang et al. 2007)
	22	Noroxyhydrastinine
	23	Corydaldine	(Ma et al. 2013)
	24	Thalifoline	(Li ZF et al. 2012)
	25	6-([1,3]Dioxolo[4,5-g]isoquinoline-5-carbonyl)-2,3-dimethoxy benzoic acid methyl ester	(Wang et al. 2014)
	26	Berbithine
	27	Coptisonine	(Yang et al. 2014)
	28	Tetrandrine
	29	Obamegine
	30	Magnoflorine	(Tomita and Kura 1956)
	31	Sanguinarine	(Mizuno et al. 1988)
	32	Norsanguinarine
	33	Oxysanguinarine
	34	6-Acetonyl-5,6-dihydrosanguinarine
	35	Chilenine	(Yang et al. 2014)
	36	Z-N-Ferulyltyramine	(Li ZF et al. 2012)
	37	E-N-Feruloyltyramine	(Ma H et al. 2013)
	38	3-Hydroxy-1-(4-hydroxyphenethyl) pyrrolidine-2,5-dione	(Li ZF et al. 2013)
	39	4′-[Formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoate	(Ma H et al. 2013)
	40	8,9-Dihydroxy-1,5,6,10-β-tetrahydro-2H-pyrrolo[2,1-α]-isoquinolin-5-one	(Li, et al. 2012)
	41	Ehyl-2-pyrrolidinone-5(S)-carboxylate
	42	Methyl-5-hydroxy-2-pyridinecarboxylate
	43	1H-indole-3-carboxaldehyde
	44	Choline	(Chen L et al. 2012)
Lignans	45	Woorenogenin	(Chen et al. 2016)
	46	Woorenoside I	(Yoshikawa et al. 1995)
	47	Longifolroside A	(Meng et al. 2013)
	48	Woorenoside II	(Yoshikawa et al. 1995)
	49	Woorenoside V
	50	Woorenoside III
	51	Woorenoside IV
	52	(+)-Pinoresinol
	53	(+)-Medioresinol
	54	(+)-Pinoresinol glucoside
	55	(+)-Pinoresinol-4,4′-O-β-d-diglucopyranoside	(Yoshikawa et al.1997)
	56	(+)-Syringaresinol glucoside	(Meng et al. 2013)
	57	(+)-Lariciresinol	(Hirano et al. 1997)
	58	(±)-5,5′-Dimethoxylariciresinol	(Li XG et al. 2012)
	59	(+)-5′-Methoxylariciresinol	(Chen L et al. 2012)
	60	(+)-Lariciresinol glucoside	(Chen et al. 2016)
	61	7S, 8R, 8′R-(+)-Lariciresinol-4,4′-O-β-d-diglucopyranoside	(Yoshikawa et al.1997)
	62	Lanicepside A	(Chen et al. 2016)
	63	9-Acetyl lanicepside B
	64	(+)-Isolariciresinol
	65	Isolarisiresinol-9-O-β-d-glucopyranoside	(Li XG et al. 2012)
	66	Woorenoside XI	(Yoshikawa et al.1997)
	67	Cleomiscosin A	(Mizuno et al. 1992)
	68	Aquillochin	( Min et al. 1987)
	69	2,3-bis[(4-Hydroxy-3,5-dimethoxyphenyl)-methyl]-1,4-butanediol
	70	secoisolariciresinol	(Li XG et al. 2012)
	71	Erythro-gaiacylglycerol-8-O-4′-(coniferylalcohol) ether	(Chen L et al. 2012)
	72	Threo-guaiacylglycerol-8-O-4′-(coniferyl alcohol) ether
	73	Woorenoside X	(Yoshikawa et al.1997)
	74	Dihydrodehydrodiconiferyl alcohol	(Li XG et al. 2012)
	75	Wooreno	(Yoshikawa et al.1997)
Simple phenylpropanoids	76	Z-Octadecyl cafeate	(Yang et al. 2014)
	77	E-3-Methoxycinnamic acid	(Ma H et al. 2013)
	78	Ferulic acid	(Li XG et al. 2012)
	79	Ethyl ferulate	(Yoshikawa et al. 1995)
	80	N-Butyl ferulate	(Ma H et al. 2013)
	81	p-Hydroxyphenethyl E-ferulate	(Hirano et al. 1997)
	82	E-3,4-Dimethoxycinnamic acid	(Ma H et al. 2013)
	83	4-O-Feruloylquinic acid	(Li XG et al. 2012)
	84	Methyl 4-O-feruloylquicinate	(Li XG et al. 2012)
	85	Ethyl 4-O-feruloylquicinate	(Ma H et al. 2013)
	86	4-O-Feruloylquinic acid butyl ester	(Li XG et al. 2012)
	87	5-O-Feruloylquinic acid	(Li XG et al. 2012)
	88	Methyl 5-O-feruloylquicinate
	89	Ethyl 5-O-feruloylquicinate
	90	5-O-Feruloylquinic acid butyl ester	(Ma H et al. 2013)
	91	Chlorogenic acid	(Chen L et al. 2012)
	92	Methyl 3-O-feruloylquicinate	(Li XG et al. 2012)
	93	N-Butyl 3-O-feruloylquicinate	(Ma H et al. 2013)
	94	3-(4′-Hydroxyphenyl)-(2R)-lactic acid	(Li XG et al. 2012)
	95	3-(3′,4′-Hydroxyphenyl)-(2R)-lactic acid	(Yahara et al. 1985)
	96	3-(3′,4′-Dihydroxyphenyl)-(2R)-lactic acid-4′-O-β-d-glucopyranoside
	97	Methyl-3-(4′-O-β-d-glucopyranosyl-3′,4′-dihydroxyphenyl)-lactate	(Yoshikawa et al.1997)
	98	Methyl-3,4-dihydroxyphenyl lactate	(Li XG et al. 2012)
	99	Ethyl-3,4-dihydroxyphenyl lactate	(Ma H et al. 2013)
	100	N-Butyl-3,4-dihydroxyphenyl lactate
	101	3-(2,3,4-Trihydroxyphenyl) propanoic acid	(Li XG et al. 2012)
Flavonoids	102	6,8-Dimethyl-3,5,7-trihydroxyfavone	(Meng et al. 2013)
	103	Rhamnetin	(Chen L et al. 2012)
	104	Wogonin
	105	7,4′-Dihydroxy-5-methoxyfavanone	(Min et al. 1987)
	106	2′,4,4′-Trihydroxy-6′-methoxydihydrochalcone
	107	Coptiside I	(Fujiwara et al. 1976)
	108	Coptiside II
	109	Woorenoside XII	(Yoshikawa et al.1997)
Other compounds	110	Limonin	(Wang et al. 2007)
	111	3,4-Dihydroxyphenylethyl alcohol	(Li XG et al. 2012)
	112	3′,4′-Dihydroxyphenethyl alcohol 1-O-β-d-glucopyranoside	(Yahara et al. 1985)
	113	3,5-Dihydroxyphenethyl alcohol-3-O-β-d-glucopyranoside	(Meng et al. 2013)
	114	Protocatechuic aldehyde	(Ma H et al. 2013)
	115	Gentisic acid-5-O-β-d-glucopyranoside	(Yahara et al. 1985)
	116	Apocynol	(Ma H et al. 2013)
	117	1,2-Dihydroxy-benzene	(Li ZF et al. 2012)
	118	Protocatechuic acid	(Meng et al. 2013)
	119	Vanillic acid	(Li ZF et al. 2012)
	120	Vanillic acid-4-O-β-d-glucopyranoside
	121	Protocatechuic acid methyl ester	(Ma H et al. 2013)
	122	Protocatechuic acid ethyl ester	(Wang et al. 2012)
	123	Woorenoside VI	(Yoshikawa et al.1997)
	124	Woorenoside VII
	125	Woorenoside VIII
	126	Woorenoside IX
	127	cyclo-(Phe-Val)	(Li ZF et al. 2012)
	128	cyclo-(Phe-Leu)
	129	β-Sitosterol	(Yang et al. 2014)

Table 4. Anti-pathogenic microorganism effect.

Pathogenic microorganism	Extract/compounds (number)	In vivo/In vitro	Mechanism	Minimal active concentration/dose	Reference
Streptococcus agalactiae	1	in vitro	Damaging the structure of bacterial cell membrane and inhibiting synthesis of protein and DNA	MIC = 231.9 µM	(Peng et al. 2015)
Actinobacillus pleuropneumoniae	1	in vitro	Restraining DNA and protein syntheses, inhibiting the cleavage of bacteria, blocking the division and development of bacteria	MIC = 929.1 μM	(Kang et al. 2015)
Staphylococcus aureus	CRE	in vitro	Not mentioned	MIC = 77.8 μg/mL	(Feng et al. 2011)
Coagulase-negative Staphylococcus strains	1	in vitro	Not mentioned	MIC = 47.6 – 1522.2 μM	(Wojtyczka et al. 2014)
Shigella dysenteriae	1	in vitro	Not mentioned	MIC = 74.3 μM	(Kong et al. 2010)
Escherichia coli	1	in vitro	Heavily perturbing the formation of the Z-rings, inhibiting the cell division protein FtsZ	MIC = 1.5-4.5 mM	(Boberek et al. 2010)
Salmonella typhimuriummice	1	in vivo	As a LPS antagonist and blocking the LPS/TLR4 signaling	0.20 g/kg (mice), 0.05 g/kg (rabbit)	(Chu et al. 2014)
Helicobacter pylori	5	in vitro	Binding to the active-site sulfydryl groups	IC50 = 3.0 μM for HPU and 2.3 μM for JBU	(Tan et al. 2017)
Helicobacter pylori	1	in vitro	Not mentioned	74.3-743.2 μM	(Song et al. 2014)
Salmonella Typhimurium	CRE	in vitro	Regulation of the immune response	MBC = 12.5 mg/mLfor S. Typhimurium MBC = 25 mg/mL forST21	(Chang et al. 2014)
Aeromonas hydrophila	Total alklaoids	in vitro	Injuring membrane by increasing membrane lipid fluidity and changing conformation of membrane proteins, and reducing the secretion of virulence factors	MIC = 62.5 mg/L	(Xue D et al. 2015)
	1			MIC = 371.6 μM
Staphylococcus aureus	1	in vitro	Not mentioned	IC50 = 169.5 μM	(Fan et al. 2008)
	3			IC50 = 209.2 μM
	4			IC50 = 337.7 μM
	5			IC50 = 636.2 μM
	8			IC50 = 803.8 μM
Herpes simplex virus	1	in vitro	Downregulation of JNK and NF-kappa B Activation	EC50 = 6.77 µM for HSV-1	(Song et al. 2014)
				EC50 = 5.04 µM for HSV-2
Influenza virus	1	in vitro and in vivo	Inhibiting the virus infection, repressing inflammatory substances release	In vivo: 5 mg/kg;	(Wu et al. 2011)
				In vitro: IC50 = 74 µM
Respiratory syncytial virus	berberine chloride	in vitro	Inhibition of RSV-mediated early p38 MAPK activation	25 μM or 100 μM	(Shin et al. 2015)
Chikungunya virus	1	in vitro	Predominantly targeting the ERK arm of MAPK signaling	EC50 = 4.5 μM in human embryonic kidney cells	(Varghese et al. 2016b)
				EC50 = 12.2 μM in human osteosarcoma cells EC50 = 35.3 μM in CRL-2522 cells
Enterovirus 71	1	in vitro	Downregulating autophagy and MEK/ERK signaling pathway	IC50 = 7.43-10.25 μM	(Wang HQ et al. 2017)
H1N1 neuraminidase (NA-1)	CRE	in vitro	Inhibiting H1N1 neuraminidase (NA-1)	IC50 = 96.1 μg/mL	(Zhou et al. 2017)
	4			IC50 = 50.5 μM
	8			IC50 = 67 μM
	5			IC50 = 99.9 μM
	1			IC50 = 233.7μM
	coptisine			IC50 = 326.5 μM
Coronavirus	CRE	in vitro	Inhibition of RNA-dependent RNA polymerase or proteases, affecting virus assembly or release	EC50 = 2.0 mg/mL	(Kim et al. 2008)
Human cytomegalovirus (HCMV)	berberine chloride	in vitro	Interfering with intracellular events after virus penetration into the host cells and before viral DNA synthesis	IC50 = 0.68 μM	(Hayashi et al. 2007)
Candida albicans	1	in vitro	Impairment mitochondrial function, generation of ROS, targeting cell wall integrity pathway and also affecting HSF1	Not mentioned	(Dhamgaye et al. 2014)

Table 5. Protecting cardiovascular system related diseases effect.

Pharmacological effects	Extract/compounds	Material or model	Mechanism	Dose	Reference
Lipid lowering effect	8	High fat (HF) diet C57BL/6J mice	Suppressing of lipogenesis and the enhancement of lipid oxidation in the liver	100 mg/kg, 56 d	(Yang et al. 2016)
Hypolipidemic Effect	3, 1, 8, 4, 5, Total alkaloids of CR (TACR)	High fat and high choesterol (HFHC) diet hamsters	Down-regulating the expression of HMGCR and up-regulating the expression of LDLR and CYP7A1 as well as promoting the excretion of TBA in the feces	46.7 mg/kg, for 140 d	(He et al. 2016)
Synergetic cholesterol-lowering effects of main alkaloids	3, 1, 8, 4, 5, TACR	HC diet hamsters; HepG2 cell	Up-regulating LDLR and CYP7A1, down-regulating HMGCR	in vivo: 70.05 mg/kg, 28 d; in vitro: 5 μg/mL	(Kou et al. 2016)
Antihyperlipidemia	4, 8, 1, 5,	Diabetic KK-Ay mice; HepG2 cell	not mentioned	in vivo: 225 mg/kg, 40 d; in vitro: 5 μg/mL	(Ma et al. 2016)
Antihypercholesterole	berbamine	HC diet adult zebrafish; zebrafish larvae; embryos	Up-regulating cholesterol transport and bile acid synthesis, inhibiting cholesterol synthesis and lipoprotein assembly or secretion	Adult: 2.25, 4.5 or 9 mg/fish, 28 d; Larvae: 10, 20 or 40 μg/mL, 10 d; embryo: 5, 10, 20, 40 or 80 μg/mL In vitro: 5, 10, 20, 40 or 80 μg/mL	(Han et al. 2017)
Antihyperlipidemia	3, 1, 4, TACR	HF diet C57BL/6J mice	Modulating of the enterohepatic circulation of bile acids and cross-talk between the gut microbiota and the liver	140 mg/kg, 35 d	(He et al. 2017)
Treating obesity	Ethanol extracts of CR, 1	HF diet C57BL/6J mice	Decreasing degradation of dietary polysaccharides, lowering potential calorie intake, activating mitochondrial energy metabolism, regulating on gut microbes	200 mg/kg, 42 d	(Xie W et al. 2011)
Treating obesity	1	High fat and high carbohydrate diet Wistar rats	Increasing the production of adiponectin and regulating the AMPK mechanism	380 mg/kg, 56 d	(Wu et al. 2016)
Anti-adipogenic activity	1, 3, 4, 5, 30	3T3-L1 cells	Downregulating C/EBP-α and PPAR-gamma	12.5-50 μM	(Choi et al. 2014)
Anti-adipogenic effect	5	3T3-L1 cells	Downregulating Raf/MEK1/ERK1/2 and AMPKα/Akt pathways during 3T3-L1 adipocyte differentiation	12.5, 25, 50 μM	(Choi et al. 2015)
Supressing adipocyte differentiation	1	3T3-L1 cells	Inhibiting cAMP/PKA-mediated CREB pathway	5 μM	(Zhang et al. 2015)
Treating atherosclerosis and other chronic inflammatory disease	3	ApoE(-/-) mice	Inhibiting activation of MAPK signaling pathways and NF-kappa B nuclear translocation	150 mg/kg, 84 d	(Feng et al. 2017)
Anti-atherosclerosis	1	Apolipoprotein E-deficient mice	Inhibiting oxidation and inflammation cytokine expressions	150 mg/kg, 84 d	(Feng et al.2016)
Suppressing atherogenesis	1	Western diet ApoE (ApoE^-/-) mice and ApoE^-/-/AMPK alpha 2^-/- mice; HUVECs	Suppressing atherogenesis via stimulation of AMPK-dependent UCP2 expression	in vivo: 1 mM in drinking water, 56 d; in vitro: 10 μM	(Wang et al. 2011)
Anti-atherogenic effect	1	THP-1-derived macrophages	Activating AMPK-SIRT1-PPAR-γ pathway and diminishing the uptake of ox-LDL	14.9, 29.7, 59.5 mg/L	(Chi et al. 2014)
Anti-atherogenesis	1	THP-1 cells	Suppressing the activation of p38 pathway	5, 10, 25, 50 μM	(Huang et al. 2011)
Against I/R injury	1	T2DM Wistar rats exposed to I/R	AMPK activation, AKT phosphorylation, and GSK3 inhibition in the nonischemic areas of the diabetic heart	100 mg/kg, 7 d	(Chang et al. 2016)
Alleviating cardiac I/R injury	1	I/R C57BL/6 mice, H9c2 myocytes,	Suppressing autophagy activation by decreasing the expression of SIRT1, BNIP3, and Beclin- p-AMPK and p-mTORC2 (Ser2481)	in vivo: 5 mg/kg, 10 mg/kg; in vitro: 5, 10, 20 μM	(Huang et al. 2015)
Anti- I/R injury	1	I/R SD rats	Attenuating mitochondrial dysfunction and myocardial apoptosis	200 mg/kg, 28 d	(Wang Y et al. 2015)
Anti-I/R injury	1	I/R SD rats, SIR H9c2 cells	Modulating Notch1/Hes1-PTEN/Akt signaling	in vivo: 200 mg/kg, 14 d; in vitro: 50 μM	(Yu et al. 2015)
Anti- I/R injury	1	I/R SD rats, SI/R H9c2 cells	Activating the JAK2/STAT3 signaling pathway and attenuating ER stress-induced apoptosis	in vivo: 200 mg/kg, 14 d; in vitro: 50 μM	(Zhao et al. 2016)
Anti- I/R injury	1	I/R SD rats	Suppressing the activation of PI3K/AKT signaling,	100 mg/kg, 14 d	(Zhu and Li2016)
Anti-cardiac I/R injury	1	H/R H9c2 cells	Inhibiting apoptosis through the activation of Smad7	50 μM	(Yao et al. 2017)
Inhibition of autophagy induced by hypoxia	1	H9c2 cells under hypoxia	Inhibition of autophagy and suppression of AMPK activation	5, 10 or 25 µM	(Jia et al. 2017)
Attenuating MI/R injury	1	I/R SD rats, SI/R H9c2	Reducing oxidative damage and inflammation response, and SIRT1 signaling plays a key role	in vivo: 200 mg/kg, 14 d; in vitro: 50 μM	(Yu et al. 2016)
Anti- hypertrophy	1	High Glucose-and Insulin-Induced Cardiomyocyte	Activating the PPARα/NO signaling pathway	0.01-10 μM.	(Wang M et al. 2013)
Anti- acute myocardial ischemia	1	SD rats with isoproterenol	Anti-inflammatory and antioxidative activity through regulating HMGB1-TLR4 Axis	30, 60 mg/kg, 14 d	(Zhang T et al. 2014)
Anti-H/R damage	3	H/R H9c2 cell	Inhibition of autophagy	0.3, 1, 3, 10 μM	(Wang Y et al. 2017)
Anti-I/R injury	3	I/R SD rats	Suppressing myocardial apoptosis and inflammation by inhibiting the Rho/ROCK pathway	3, 10, and 30 mg/kg	(Guo et al. 2013)
Reducing I/R injury	4	I/R SD rats, HAEC cells, RAW 264.7 cells	Reducing oxidative stress and modulating inflammatory mediators	in vivo: 25, 50 mg/kg; in vitro: 1, 2, 5, 10 μM in HAEC; 1, 5, 10 μM in RAW 264.7 cells	(Kim et al. 2009)
Anti-nonalcoholic steatohepatitis	1	HF diet Balc/c mice	Normalizing gut microbiota, decreasing expression of endotoxin receptor, inflammatory cytokines	200 mg/kg, 56 d	(Cao et al. 2016)
Decreasing hepatic steatosis	1	HF C57BL/6J mice, H4IIE cells	Anti-inflammation	in vivo: 100 mg/kg, 28 d; in vitro: 10, 25, 50 μM	(Guo et al. 2016)
Attenuating hepatic steatosis	1	High fat and high-sucrose C57BL/6 mice, mouse primary hepatocytes, HepG2 cells	Inducing autophagy and fibroblast growth factor 21 in SIRT1-dependent manner	in vivo: 5 mg/kg, ip., 35 d; in vitro: 10 μM	(Sun et al. 2017)
Attenuating hepatic steatosis	1	HF diet SD rats, Huh7 cells	Global modulation of hepatic mRNA and lncRNA expression profiles	in vivo: 200 mg/kg, 112 d; in vitro: 10 μM	(Yuan et al. 2015)
Attenuating hepatic steatosis	1	Db/db mice and methionine-choline-deficient diet mice, tunicamycin-induced mice, HepG2 cells	Reducing endoplasmic reticulum stress through the ATF6/SREBP-1c pathway	in vivo: 200 mg/kg, 35 or 20 or 3 d respectively; in vitro: 5 μM	(Zhang et al. 2016)

Table 6. Antidiabetes effect.

Pharmacological effects	Extract/compounds	Material or mode	Mechanism	Dose	Reference
Antihyperglycemia	1, 3, 4, 5, 8	Diabetic KK-Ay Mice; HepG2 cells	Not mentioned	in vivo: 225 mg/kg, 40 d; in vitro: 5 μg/mL	(Ma et al. 2016)
Lowering glucose concentration	1	HepG2 cells and betaTC3 cells	insulin independent but has no effect on insulin secretion	5 to 200 μM	(Xie X et al. 2011)
Activating glucose uptake	1	3T3-L1 adipocytes	Activating GLUT1 through AMPK stimulation	1, 5 μM	(Kim et al. 2007)
Treating type 2 DM	1	HF diet C57BL/6J mice, NIT-1 cells	Inhibiting mouse insulin gene promoter through activation of AMPK and exerting beneficial effect on pancreatic β-cell	in vivo: 50 mg/kg, 70 d; in vitro: 0.01-10 μM	(Shen et al. 2012)
Against insulin resistance	1	HF-diet and STZ induced Wistar rats, KK-Ay mice, HepG2, Bel-7402, L6 cells	Through PKC–dependent up-regulation of insulin receptor expression	in vivo: 150, 300 mg/kg, 15 d, 200 mg/kg, 21 d; in vitro: 22.3 μM	(Kong WJ et al. 2009)
Antihyperglycemic	1	HF diet C57BL/6J mice, db/db mice, 3T3-L1 and L6 cells	Inhibiting PTP1B activity and mimicing insulin action	in vivo: 100 mg/kg, 14 d; in vitro: 1.25-100 μM	(Chen et al. 2010)
Increasing glucose uptake	1	Insulin-sensitive and insulin-resistant rat skeletal muscle cells	Improving tyrosine-phosphorylation of IRS-1 and the recruitment of p85 to IRS-1, PKC and PKB activity, inhibiting mTOR	14.8 μM	(Liu LZ et al. 2010)
Treating type 2 DM	1	Alloxan-induced Wistar rats	Hypoglycemic effect, modulating lipids metabolic effects and to scavenge free radical	100, 200 mg/kg, 21 d	(Tang et al. 2006)
Insulinotropic effect	1	Primary rat islets	Activating HNF4α and GK	1, 3, 10 and 30 μM	(Wang et al. 2008)
Treating T1DM	1	Nonobese diabetic (NOD) mice	Protcting pancreatic islets and serum lipids	50, 150, 500 mg/kg, 98 d	(Chueh & Lin 2011)
Protecting pancreatic islets	1	STZ-treated primary pancreatic islet cells	Down-regulating Bax/Bcl-2 gene expression ratio	1, 3, 5 μM	(Chueh & Lin 2012)
Treating T2DM	1	HF diet and STZ induced rats	Lowering RBP4 levels and up-regulating the expression of GLUT4 protein in tissues	380 mg/kg, 28 d	(Zhang et al. 2008)
Antidiabetic effects	1	SD rats, NCI-H716 cells	Promoting GLP-1 secretion and GLP-1 biosynthesis in PKC-dependent pathway	in vivo: 60, 120 mg/kg, 35 d; in vitro: 1, 10, 100 μM	(Yu Y et al. 2010)
Ameliorating insulin resistance	1	HepG2 cells	Improving insulin sensitivity via its anti-inflammatory activity	0.1, 1, 10 μM	(Lou et al. 2011)
Treating T2DM	1	RAW264.7 microphages	Attenuating inflammation by SIRT1	5 μM	(Chuanchong 2016)
Treating T2DM	1	STZ induced ddY mice	Antioxidative stress via down regulating GPx and up-regulating CuZn-SOD	200 mg/kg, 14 d	(Lao-Ong et al. 2012)
Treating T2DM	1	high-carbohydrate/high-fat diet Wistar rats	Antioxidation and up-regulating P-TEFb expression	75, 150, 300 mg/kg, 42 d	(Zhou and Zhou 2011)
Treating diabetic neuropathy	1	SH-SY5Y cells	As an Nrf2 activator	0.1-10 nM	(Hsu et al. 2013)
Hypoglycemic	1	STZ induced diabetic SD rats, Caco-2 cells	Suppressing disaccharidase activities and the mRNA expression of SI complex in PKA-dependent pathway	in vivo: 100, 200 mg/kg, 35 d; in vitro: 2, 10, 50 μM	(Liu L et al. 2010)
Moderating glucose metabolism	1	HF diet SD rats	Regulating the MAPK and GnRh-Glp-1 pathways in the ileum	120, 240 mg/kg, 56 d	(Zhang Q et al. 2014)

Table 7. Anticancer effect.

Pharmacological effects	Extract or compounds	Material or model	Mechanism	Dose	Reference
Treating melanoma	1	A375 cells	Up-regulating p38 MAPK, GR and down-regulating DHODH	5, 10, 20, 40, 80 μM	(Liu B et al. 2017)
Treating melanoma	1	B16 cells	Modulating the PI3K/Akt pathway, RARα/RARβ expression	10, 20, 40 μM	(Kou et al. 2016)
Treating hepatocellular carcinoma	1	HepG2 cells	Promoting apoptosis through the NF-κB p65 pathway	10, 50, 100 μM	(Li M et al. 2017)
Treating hepatocellular carcinoma	CRE	HepG2 cells, MHCC97-L and HepG2 cells xenograft mice	Suppressing vascular endothelial growth factor via inactivation of eukaryotic elongation factor 2	in vitro: IC50 of 500 and 150 µg/mL at 24 and 48 h in MHCC97L cells, 250 and 120 µg/mL in HepG2 cells; in vivo: 50 mg/kg/2 d, 21 d	(Tan et al. 2014)
Treating hepatocellular carcinoma	CRE	MHCC97-L cells	Downregulating the Rho/ROCK signaling pathway	300, 150 μM at 24 h and 48 h	(Wang N et al. 2010)
Treating hepatocellular carcinoma	1	HepG2 and MHCC97-L cells	Increasing Bax expression, activating Beclin‐1, inhibiting mTOR‐signaling pathway by suppressing the activity of Akt and up‐regulating P38 MAPK signaling	IC50: 100 µM in HepG2 cells, 250 µM in MHCC97‐L cells
Treating hepatocellular carcinoma	berberine hydrochloride	HepG2 cells	AMPK activation	50, 100 μM	(Yu et al. 2014)
Treating hepatocellular carcinoma	3	SMMC7721 xenograft mice, SMMC7721 and HepG2 cells	Induction of apoptosis through a 67LR/cGMP pathway	in vivo: 50 mg/kg; in vitro: 12.5, 25, 50,100 μM;	(Zhang et al. 2018)
Treating glioma	Coptis Chinensis granules	Xenograft mice, U87 cells	Down-regulating phosphorylation of STAT3 by reducing HDAC3	in vivo: 20, 10 mg/per mouse, 1 month at intervals of 1 d; in vitro: 0.625, 1.25, 2.5, 5 or 10 mg/mL;	(La et al. 2017)
Inducing autophagic cell death	1	HCT-116, HepG2, DLD1cells	enhancing GRP78 levels and The ability of GRP78 to bind to VPS34	IC50: 80, 100, 200 μM in HCT-116, HepG2, DLD1 respectively
Treating osteosarcoma	1	Xenograft mice, Saos-2 and MG-63 cells	Downregulating caspase-1/IL-1β inflammatory signaling	in vivo: 20 mg/kg, 21 d; in vitro: 50 μM	(Jin et al. 2016)
Treating osteosarcoma	1	MG-63 cells	Inducing apoptosis and DNA damage	20, 40, 60, 80 μM	(Zhu et al. 2014)
Treating osteosarcoma	3	xenografted mice; MG63, SW1353, Saos-2, and U-2OS cells	Downregulating the expression of CDK4, cyclin D1, VE-cadherin and integrin ß3, diminishing STAT3 phosphorylation	in vivo: 50 mg/kg, 24 d; in vitro: IC50: 12.99 ± 0.77, 14.10 ± 2.17, 22.56 ± 2.94, and 28.54 ± 5.71 µM, respectively	(Yu D et al. 2014)
Treating esophageal cancer	1	KYSE-30 cells	Anti-migration and anti-metastasis mediated by chemokine receptors	IC50: 60, 45 and 40 µM after 24, 48 and 72 h, respectively	(Mishan et al. 2015)
Treating lung cancer	1	H460, H1975 cells	Suppressing both phosphorylated and total levels of STAT3 protein and promoting STAT3 degradation by enhancing ubiquitination	IC50: 13.4 and 62.43 μM for H460 and H1975 cells	(Zhu et al. 2015)
Treating human gastric cancer	1	xenograft nude mice, BGC-823 and SGC7901 cells;	Ihibiting the Akt/mTOR/p70S6/S6 pathway	in vivo: 10 mg/kg injected intratumorally once every 3 d for 18 d in vitro: 10, 25, 50, 75, 100 μM	(Yi et al. 2015)
Treating breast cancer	3	MDA-MB-231 cells	Anti-metastatic function through down-regulation of MMP-9 in combination with the increase of TIMP-1	16, 32, 64 μM	(Li J et al. 2014)
Treating nasopharyngeal carcinoma	berberine hydrochloride	CNE-1 cells	Blocking proliferation, migration and invasion, inducing apoptosis	IC50: 31.5 µM	(Li CH et al. 2014)
Treating tongue squamous cancer	1	SCC-4 cells	Inhibiting FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9	62.5, 125 μM	(Ho et al. 2009)
Treating human colon cancer	1	SW620 cells	Generating reactive oxygen species and activation of JNK/p38 MAPK and FasL	50 μM	(Hsu et al. 2007)
Treating colorectal cancer	3	Xenograft mice; HCT116 cells	Inhibiting epithelial–mesenchymal transition, the growth, adhesion and metastasis, down-regulating MFG-E8	in vivo: 30, 60, 90 mg/mL, 14 d; in vitro: 62.4, 124.8, 249.6 μM;	(Cao et al. 2018)
Treating pancreatic cancer	4	PSC cells, HPNE, MIA PaCa-2, CFPaC-1 and PANC-1 cells	Inhibiting glutamine-mediated PSC-PCC interaction through simultaneous inhibition of survivin and COL1A1	212.8, 425.6 μM	(Chakravarthy et al. 2018)
Treating esophageal cancer	Coptidis Rhizoma, 1	Xenograft mice, YES-2, YES-2 cells	Down-regulating tumor IL-6 production	in vivo: oral food supplement of final concentration of 1%; in vitro: 8-32 mM	(Iizuka et al. 2000)

Table 8. The pharmacokinetic parameters of component in animals and humans.

Subjects/animals	Drug administered	Dosages	Detected compounds	Pharmacokinetic parameters	References
Male SD rats	TACR (i.g.)	1.3 g/kg	1	AUC0–24 (ng·h·mL^−1): 147.66 ± 14.19,	(Yu et al. 2007)
				Cmax (ng·mL^-1): 11.39 ± 1.62,
				Tmax (h): 3.40 ± 1.47,
				MRT (h): 9.31 ± 0.81
			3	AUC0–24 (ng·h/mL): 11.74 ± 7.24,
				Cmax (ng/mL): 1.52 ± 0.74,
				Tmax (h): 2.25 ± 1.82,
				MRT (h): 6.69 ± 2.07
			5	AUC0–24 (ng·h/mL): 10.19 ± 6.67,
				Cmax (ng/mL): 2.40 ± 0.88,
				Tmax (h): 1.30 ± 1.56,
				MRT (h): 5.09 ± 2.44
			8	Cmax (ng/mL): 0.84 ± 0.47,
				Tmax (h): 1.69 ± 1.72
			4	AUC0–24 (ng·h/mL): 14.80 ± 2.25,
				Cmax (ng/mL): 1.74 ± 0.56,
				Tmax (h): 0.90 ± 0.95,
				MRT (h): 10.12 ± 1.16
Male diabetic SD rats	CRE (i.g.)	1.3 g/kg	1	AUC0–24 (ng·h/mL): 255.10 ± 8.04	(Yu et al. 2008)
				Cmax (ng/mL): 24.97 ± 8.39
				Tmax (h): 3.10 ± 1.52
				MRT (h): 9.44 ± 1.52
			3	AUC0–24 (ng·h/mL): 35.53 ± 10.32
				Cmax (ng/mL): 4.88 ± 1.40
				Tmax (h): 2.80 ± 1.44
				MRT (h): 8.17 ± 1.30
			5	AUC0–24 (ng·h/mL): 35.97 ± 11.14
				Cmax (ng/mL): 6.26 ± 2.37
				Tmax (h): 2.80 ± 1.44
				MRT (h): 7.28 ± 1.71
			8	AUC0–24 (ng·h/mL): 8.17 ± 3.30
				Cmax (ng/mL): 1.30 ± 0.23
				Tmax (h): 3.00 ± 1.06
				MRT (h): 6.84 ± 1.45
			4	AUC0–24 (ng·h/mL): 22.02 ± 4.39
				Cmax (ng/mL): 2.93 ± 1.14
				Tmax (h): 4.00 ± 3.79
				MRT (h): 9.30 ± 0.61
Male pseudo germ-free Wistar rats	1 (i.g.)	40 mg/kg	1	AUC0-limt (ng·h/mL): 40.89	(Zuo et al. 2006)
				MTT (h): 10.25
			Berberrubie,	AUC0-limt (ng·h/mL): 437.29,
				MTT (h): 7.45
			Thalifendine	AUC0-limt (ng·h/mL): 287.85
				MTT (h): 4.84
			Emethylen-eberberine	AUC0-limt (ng·h/mL): 735.22
				MTT (h): 15.08
			8	AUC0-limt (ng·h/mL): 101.98
				MTT (h): 4.05
Male Wistar rats	1 (i.g.)	40 mg/kg	1	AUC0-limt (ng·h/mL): 37.42,
				MTT (h): 10.53
			Berberrubie	AUC0limt (ng·h/mL): 1879.64,
				MTT (h): 18.32
			Thalifendine	AUC0-limt (ng·h/mL): 811.05,
				MTT (h): 7.62
			Emethylen-eberberine	AUC0-limt (ng·h/mL): 1763.62,
				MTT (h): 24.68
			8	AUC0-limt (ng·h/mL): 356.05,
				MTT (h): 10.32
Post inflammation irritable bowel syndrome male Wistar rats	berberine hydrochloride (i.g.)	25 mg/kg	1	AUC0-t (ng·min/mL): 2,763.43 ± 203.14	(Gong et al. 2014)
				Cmax (ng/mL): 18.53 ± 0.61
				Tmax (min): 15.00 ± 0.00
				T1/2,λz (min): 941.45 ± 60.39
				Vd/Fλz (L/kg): 41,202.89 ± 4,112.68
				CL/F (L/h/kg): 3,270.57 ± 58.32
Male SD rats	berberine hydrochloride (i.g.)	25 mg/kg	1	AUC0-t (ng·min/mL): 2,039.49 ± 492.24Cmax (ng·mL^-1): 1
				6.74 ± 4.47
				Tmax (min): 15.00 ± 0.00
				T1/2,λz (min): 770.36 ± 65.01
				Vd/Fλz (L/kg): 60,036.51 ± 19,704.59
				CL/F (L/h/kg): 4,999.34 ± 1,198.79
Male Beagle Dog	1 (i.v.)	100 mg/kg	1	AUC (mg/h/L): 1979.31 ± 1140.31,	(Sheng et al. 1993)
				Ka (h): 10.2843 ± 2.5,
				t1/2α (h): 0.15 ± 0.26,
				t1/2β (h): 12.59 ± 8.83,
				CL (h): 60.70 ± 24.38,
				Vd (L): 699.53 ± 219.05
	1 (i.g.)	280 mg/kg	1	AUC (μg·h/L): 777.29 ± 150.10,
				Cmax (μg/L): 15.46 ± 4.20,
				Tmax (h): 3.71 ± 0.95,
				t1/2α (h): 0.63 ± 0.14,
				t1/2β (h): 34.82 ± 14.36,
				CL (h): 2.64 ± 0.55,
				Vd (L): 125.41 ± 32.55
Male Wistar rats	CRE (i.g.)	1.2 g/kg	1	AUC (h·ng/mL): 707.91,	(Bao et al. 2010)
				T1/2 (h): 1.89,
				Cmax (ng/mL): 315.78,
				Tmax (h): 1
			4	AUC (h·ng/mL): 130.29,
				T1/2 (h): 1.71,
				Tmax (h): 1
		2.4 g/kg	1	AUC (h·ng/mL): 1220.32,
				T1/2 (h): 2.29,
				Cmax (ng/mL): 501.58,
				Tmax (h): 1
			4	AUC (h·ng/mL): 348.61,
				T1/2 (h): 2.64,
				Tmax (h): 1
		4.8 g/kg	1	AUC (h·ng/mL): 2424.62,
				T1/2 (h): 4.79,
				Cmax (ng/mL): 584.57,
				Tmax (h): 1
			4	AUC (h·ng/mL): 872.76,
				T1/2 (h): 5.89,
				Tmax (h): 1
Male Wistar rats	CRE (i.v.)	10.2 mg/kg	1	Hippocampus:	(Wang et al. 2005)
				AUC (ng·h/g): 6940 ± 206,
				Cmax (ng/g): 272 ± 12,
				T1/2Kα (h): 4.48 ± 1.7
				T1/2α (h): 0.215 ± 0.063
				T1/2β (h): 12.0 ± 1.5,
				Tmax (h): 3.67 ± 0.48
				Plasma:
				AUC (ng·h/mL): 473 ± 18,
				T1/2α (h): 0.227 ± 0.017,
				T1/2β (h): 1.13 ± 0.18
				Vd (mL/kg): 2400 ± 300
				CL (mL·kg/h): 6400 ± 200
Male healthy volunteers	300 mg 1 (p.o.)	300 mg/kg	1	AUC (mg·h/L): 2799 ± 1128.5,	(Li & Zhang 1997)
				Cmax (mg/L): 394.7 ± 155.4,
				Tmax (h): 2.37 ± 0.04,
				T1/2Kα(h): 0.87 ± 0.03,
				T1/2β (h): 2.94 ± 0.14
Male Wistar rats	CRE (i.g.)	300 mg/kg	1	AUC0–t (ng·h/mL): 92.71 ± 15.03,	(Liu et al. 2014)
				Cmax (ng/mL): 12.27 ± 3.30,
				Tmax (h): 1.90 ± 0.58,
				T1/2 (h): 3.96 ± 0.92
			4	AUC0–t (ng·h/mL): 4.72 ± 0.79,
				Cmax (ng/mL): 0.74 ± 0.44,
				Tmax (h): 1.30 ± 0.40,
				T1/2 (h): 3.91 ± 0.80
			3	AUC0–t (ng·h/mL): 1.39 ± 0.60,
				Cmax (ng/mL): 1.38 ± 0.54,
				Tmax (h): 14.28 ± 2.38,
				T1/2 (h): 4.02 ± 1.83
			5	AUC0–t (ng·h/mL): 6.63 ± 1.70,
				Cmax (ng/mL): 1.05 ± 0.75,
				Tmax (h): 1.38 ± 0.54,
				T1/2 (h): 5.28 ± 1.44
			8	AUC0–t (ng·h/mL): 7.11 ± 0.65,
				Cmax (ng/mL): 0.67 ± 0.23,
				Tmax (h) 1.38 ± 0.54,
				T1/2 (h): 4.35 ± 0.67

Notes: AUC: area under curve; C_max: maximum concentration; CL: body clearance; i.g.: intragastric; i.v.: intravenous; MTT: mean transit time; p.o.: per os; T_1/2: half-life; T_1/2a: distribution half-life; T_1/2β: elimination half-life; T_1/2Kα: absorption half-life; T_max: time to peak concentration; Vd: volume of distribution.

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