The anti-inflammatory activity of licorice, a widely used Chinese herb

Figures & data

Figure 1. The licorice cuts.

Table 1. The anti-inflammatory activities of licorice extracts.

Species	Solvent	Inflammation tissue/disease	Model formation	Extract concentration	Inhibition rate	Toxic signs/mortality	Reference
G. glabra	Acetone	LPS (0.1 μg·mL^−1)- induced J774A.1 murine macrophage cell line	Stimulation with LPS (0.1μg·mL^−1).	20–40 μg·mL^−1	Dose-dependently inhibit IL-1β, up to 47.8%		(Thiyagarajan et al. 2011)
G. uralensis	Ethanol	The murine RAW264.7 macrophage cells	Stimulation with LPS (1 μg·mL^−1)	25 μg·mL^−1	Inhibit LPS-induced NO production (p<0.001) by 48%		(Wu et al. 2011)
G. uralensis	Ethanol	Human colon cancer cells HT-29 (HT-29-N9)	Stimulation with LPS (1 μg·mL^−1)	25 μg·mL^−1	Suppress the LPS-induced NF-κB luciferase activity (p<0.05)		(Wu et al. 2011)
G. uralensis	Ethanol	Human hepatoma HepG2 cell (HepG2-C8)	Stimulation with LPS (1 μg·mL^−1)	25 μg·mL^−1	Induce the luciferase activity in HepG2C8 cells by fourfolds (p<0.001)		(Wu et al. 2011)

Table 2. The anti-inflammatory properties of licorice compounds in vitro.

Compounds	Inflammation tissue/disease	Cell	Concentration	Inhibition rate	Method	Toxic signs/mortality	Reference
18β-GC	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	75 μM	51% reduction in NO	ELISA	Do not affect the viability of the RAW 264.7 cells at the concentration lower than 200 μM	(Wang et al. 2011)
18β-GC	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	75 μM	49% reduction in PGE2	ELISA		(Wang et al. 2011)
18β-GC	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	75 μM	46% reduction in TNF-α	ELISA		(Wang et al. 2011)
18β-GC	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	75 μM	42% reduction in IL-6.	ELISA		(Wang et al. 2011)
18β-GC	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	75 μM	51% reduction in IL-1β	ELISA		(Wang et al. 2011)
18β-GC	Leishmania donovani-infected macrophages	Peritoneal macrophages of Leishmania donovani-infected BALB/c mice (4–6 weeks old)	50 mg·mL^−1	90.94% reduction in the parasite load	ELISA	Optimal viability at mg·mL^−1 showing 88% survival	(Bhattacharjee et al. 2012)
18α-GC	Ischaemia/reperfusion in L02 cells	The human hepatic L02 cell line	10 mg·mL^−1	Increase the activities of SOD and GSH-Px	SOD and GSH-Px Detection Kits		(Huang et al. 2014)
18α-GC	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW264.7 macrophages	0.5 mg·mL^−1 or 1 mg·mL^−1	Suppress PGE2, PGI2, TXB2 and LTB4	ELISA		(Xie et al. 2015)
18β-GA	Indomethacin-induced small intestinal damage		Complex compound of 18β-GA and hydroxypropyl-γ-cyclodextrin	Reduce mRNA expressions of TNF-α, IL-1β and IL-6			(Ishida 2013)
18β-GA	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	75 μM	34% reduction in NO	ELISA	Do not affect the viability of the RAW 264.7 cells at the concentration lower than 150 μM	(Wang et al. 2011)
18β-GA			75 μM	58% reduction in PEG2	ELISA		(Wang et al. 2011)
18β-GA			75 μM	34% reduction in TNF-α	ELISA		(Wang et al. 2011)
18β-GA			75 μM	35% reduction in IL-6	ELISA		(Wang et al. 2011)
18β-GA			75 μM	42% reduction in IL-1β	ELISA		(Wang et al. 2011)
LCA	TNFα (10 ng·mL^−1)-induced NF-κB activation	NIH-3T3 cells	10/20/30 μM	Inhibit in a dose-dependent manner	EMSA		(Funakoshi-Tago et al. 2010)
LCA	LPS (1 μg·mL^−1)-induced mouse peritoneal macrophage cells	Mouse peritoneal macrophage cells	0.1/0.5/1 μg·mL^−1	Decrease PGE2 by 31.1, 58.3 and 80.3%	PGE2 kit		(Cui et al. 2008)
LCA	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	10 μM.	The PGE2 inhibition rates exceed 80%	DCFH-DA fluorometric assay		(Fu et al. 2013)
LCA	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	12.8 ± 1.45 μM.	The effective concentration of ABTS^+ radicals are scavenged by 50%	ABTS + radical scavenging capacity assay		(Fu et al. 2013)
LCA	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	11.6 ± 1.84 μM	Inhibitory activity on lipid peroxidation EC50	Fe2^+-ascorbic acid system		(Fu et al. 2013)
LCB	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	3 μM.	The inhibition rate of NO exceeds 50%.	DCFH-DA fluorometric assay
LCB	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	2.68 ± 0.09 μM.	The concentration of ABTS^+ radicals are scavenged by 50%	ABTS^+ radical scavenging capacity assay		(Fu et al. 2013)
LCB	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	3.92 ± 0.12 μM	Inhibitory activity on lipid peroxidation EC50	Fe^2+-ascorbic acid system		(Fu et al. 2013)
LCC	RBL-2H3 cells sensitized with anti-DNP IgE (100 ng·mL^−1)	RBL-2H3 cells	24 μM	Inhibition of β-hexosaminidase release	β-hexosaminidase release assay and trypan blue exclusion assay	30% cytotoxicity: > 30 μM	(Tanifuji et al. 2010)
LCD	RBL-2H3 cells sensitized with anti-DNP IgE (100 ng·mL^−1)	RBL-2H3 cells	21 μM	Inhibition of β-hexosaminidase release	β-hexosaminidase release assay and trypan blue exclusion assay	30% cytotoxicity: > 30 μM	(Tanifuji et al. 2010)
LCE	LPS-stimulated RAW 264.7 murine macrophage	RAW 264.7 murine macrophage	2.5–7.5 μmol·L^−1	Dose-dependently inhibit NO, PGE2; markedly suppress the expression of iNOS and COX-2 proteins; and the secretion of IL-6, IL-1β and TNF-α	ELISA		(Lee et al. 2013)
Echinatin	LPS (1 μg·mL^−1)-induced murine RAW 264.7 cells	RAW 264.7 cells	2.95 ± 0.11 μM	The effective concentration of ABTS^+ radicals are scavenged by 50%	ABTS^+ radical scavenging capacity assay		(Fu et al. 2013)
Echinatin			47.2 ± 2.64 μM	Inhibitory activity on 50% lipid peroxidation	Fe^2+-ascorbic acid system		(Fu et al. 2013)
ISL	LPS (0.1 μg·mL^−1)-induced J774A.1 murine macrophage cell line	J774A.1 murine macrophage cell line	2.5–10 μg·mL^−1	NO levels with 50% inhibition attain at 7.5 μg·mL^−1 (29 μM).	ELISA		(Thiyagarajan et al. 2011)
ISL	LPS (0.1 μg·mL^−1)-induced J774A.1 murine macrophage cell line	J774A.1 murine macrophage cell line	1.85 μg·mL^−1 (7.2 μM)	IL-1 levels with 50% inhibition	ELISA		(Thiyagarajan et al. 2011)
ISL	LPS (0.1 μg·mL^−1)-induced J774A.1 murine macrophage cell line	J774A.1 murine macrophage cell line	1.92 μg·mL^−1 (7.16 μm)	IL-6 levels with 50% inhibition	ELISA		(Thiyagarajan et al. 2011)
ISL	PMA (50 ng·mole^−1)-exposed human umbilical vein endothelial cells	Human umbilical vein endothelial cells	10 μM	Nearly abolish the expression of MMP-2 mRNA	MTT	Nontoxic concentrations showed up 25 ≤ μM for 24h serum-free culture experiments	(Kang et al. 2010)
GLD	LPS (0.1 μg·mL^−1)-induced J774A.1 murine macrophage cell line	J774A.1 murine macrophage cell line	10 μg·mL^−1	33% inhibition in NO levels	ELISA		(Thiyagarajan et al. 2011)
GLD	LPS (0.1 μg·mL^−1)-induced J774A.1 murine macrophage cell line	J774A.1 murine macrophage cell line	10 μg·mL^−1 (30.8 μM)	IL-1 levels with 50% inhibition	ELISA		(Thiyagarajan et al. 2011)
LIA	LPS (0.1 μg·mL^−1)-induced U937 cells line	U937 cells (ATCC CRL-1593.2; human monoblastic leukaemia cell line	0.1, 0.5, 1 μg·mL^−1	Decreased the secretion of IL-6		No obvious cytotoxic effects were detected at 1mg·mL^−1 with the cell viability of 85%	(La et al. 2011)
LIA	LPS (0.1 μg·mL^−1)-induced U937 cells line	U937 cells (ATCC CRL-1593.2; human monoblastic leukaemia cell line	1 μg·mL^−1	Decreased the secretion of CCL5			(La et al. 2011)
LIA	LPS (0.1 μg·mL^−1)-induced U937 cells line	U937 cells (ATCC CRL-1593.2; human monoblastic leukemia cell line	0.1, 0.5, 1 μg·mL^−1	Decreased the secretion of MMP-8			(La et al. 2011)
LIA	LPS (0.1 μg·mL^−1)-induced U937 cells line	U937 cells (ATCC CRL-1593.2; human monoblastic leukaemia cell line	0.5, 1 μg·mL^−1	Decreased the secretion of MMP-7			(La et al. 2011)
LIA	LPS (0.1 μg·mL^−1)-induced U937 cells line	U937 cells (ATCC CRL-1593.2; human monoblastic leukaemia cell line	1 μg·mL^−1	Decreased the secretion of MMP-9			(La et al. 2011)
LID	LPS (0.1 μg·mL^−1)-induced U937 cells line	U937 cells (ATCC CRL-1593.2; human monoblastic leukaemia cell line	0.1, 0.5, 1 μg·mL^−1	Decreased the secretion of IL-6		No obvious cytotoxic effects were detected at 1mg·mL^−1 with the cell viability of 85%	(La et al. 2011)
LID	LPS (0.1 μg·mL^−1)-induced U937 cells line	U937 cells (ATCC CRL-1593.2; human monoblastic leukaemia cell line	0.1, 0.5, 1 μg·mL^−1	Decreased the secretion of MMP-7 and MMP-8			(La et al. 2011)
LID	LPS (0.1 μg·mL^−1)-induced U937 cells line	U937 cells (ATCC CRL-1593.2; human monoblastic leukaemia cell line	0.5, 1 μg·mL^−1	Decreased the secretion of MMP-9			(La et al. 2011)
DGC			0.5 mM	Ferric reducing antioxidant power 855.07 ± 84.14 μmole·L^−1	Ferric reducing antioxidant power assay		(Kim HJ et al. 2012b)
DGC			0.205 ± 0.005 mM	IC50 for DPPH	DPPH radical scavenging assay		(Kim HJ et al. 2012b)
DGC			0.465 ± 0.081 mM	IC50 value for ABTS^+	ABTS^+ radical cation-decolourization assay		(Kim HJ et al. 2012b)
DGC	Glutamate (5 mM)-induced HT22 cells	HT22 cells	2 μM	Dose-dependently inhibit ROS production	2,7-dichlorofluorescein (DCF) assay and western-blot		(Kim HJ et al. 2012a)
DGD			0.5 mM	Ferric reducing antioxidant power 812.04 ± 40.35 μmole·L^−1	Ferric reducing antioxidant power assay		(Kim HJ et al. 2012b)
DGD			0.309 ± 0.002 mM	IC50 for DPPH	DPPH radical scavenging assay		(Kim HJ et al. 2012b)
DGD			0.635 ± 0.035 mM	IC50 value for ABTS^+	ABTS^+ radical cation-decolourization assay		(Kim HJ et al. 2012b)
ISOA			0.5 mM	Ferric reducing antioxidant power 231.57 ± 24.44 μmole·L^−1	Ferric reducing antioxidant power assay		(Kim HJ et al. 2012b)
ISOA			0.418 ± 0.015 mM	IC50 for DPPH	DPPH radical scavenging assay		(Kim HJ et al. 2012b)
ISOA			0.655 ± 0.042 mM	IC50 value for ABTS^+	ABTS^+ radical cation-decolourization assay		(Kim HJ et al. 2012b)

Table 3. The anti-inflammatory properties of licorice compounds in vivo.

Compounds	Inflammation tissue/disease	Models	Treatment	Outcomes	Reference
18β-GC	An intratracheal instillation of LPS (1 mg·kg^−1)	Male BALB/C mice weighing 20–25 g	Intraperitoneal injection of 10, 25 and 50 mg·kg^−1	Markedly decrease the MPO activity and NO concentrations	(Ni et al. 2011)
	Injection of 0.94 nmole (0.2 μg) of kainic acid (KA)-induced neuronal death model	Male BALB/c mice (25-30 g)	Intraperitoneal injection of 10 or 50 mg·kg^−1	Iβ-1-positive cells are almost completely suppressedby 50 mg·kg^−118β-GC	(Luo et al. 2013)
18α-GC	20% paraquat poisoning solution at 15 mg·kg^−1 dose	30 male Sprague Dawley rats from 180 g to 200 g	Intraperitoneal injection of 30 mg·kg^−1	Significantly decrease intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9)	(Xiao et al. 2014)
LCA	Noninfectious mouse model of asthma	BALB/c mice	50 mg·kg^−1	Inhibit the increase in T-helper type 2 cytokines, reduce serum levels of ovalbumin-specific IgE and IgG	(Chu et al. 2013)
	Topical inflammation was instantly induced on the posterior surface of the same ear by the application of xylene (0.05 mL)	Kunming mice 20–25 g and Wistar rats (150–200 g)	5 mg·kg^−1	Decrease the ear oedema rate by30.3%	(Cui et al. 2008)
	0.1 mL freshly prepared carrageenan was injected into the right hind paw	Kunming mice 20–25 g and Wistar rats (150–200 g)	2.5, 5 and 10 mg·kg^−1 body weight	Dose-dependentreduce the paw oedema rateby 41.3, 39.7 and 30.7%, respectively	(Cui et al. 2008)
LCE	5 nmoles of TPA 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear oedema	ICR mice	0.5–2 mg	Dose-dependently reduce the TPA-induced increase in ear weight and ear thickness	(Lee et al. 2013)
ISL	Male, 5-week-old C57BL/6 mice were fed a HFD containing 60% fat	C57BL/6 mice	10 μM	Inhibit HFD-induced IL-1 and caspase-1 production	(Honda et al. 2014)
GLD	5% dextran sulphate sodium-induced BALB/c mice	BALB/c mice	10 or 50 mg·kg^−1	Attenuate mortality, loss of body weight, shortening of the colon and severe clinical symptoms.	(Kwon et al. 2008)

Table 4 The preparations from licorice approved by CFDA.

China Approved Drug Names (CADN)	Component	Dosage forms	Batch number	Drug standard code
Licorice extract powder	Licorice extract	Powder	H65020417	86905972000020
Bismuth glycyrrhetate powder	Bismuth glycyrrhetate	Powder	H62021142	86905894000351
Trisodium glycyrrhetate	Trisodium glycyrrhetate	Raw material	H65020217	86906000000098
Glycyrrhetinic acid	Glycyrrhetinic acid	Raw material	H15021234	86904264000083
MgIG	MgIG	Raw material	H20051941	86901523001461
Glycyrrhizic acid A	Glycyrrhizic acid A	Raw material	H65020210	86906000000081
Licorzine	Licorzine	Raw material	H15021235	86904264000168
Diammonium glycyrrhizinate	Diammonium glycyrrhizinate	Raw material	H20065456	86901375000735
Dipotassium glycyrrhetate	Dipotassium glycyrrhetate	Raw material	H65020215	86906000000111
Monopotassium glycyrrhiznate A	Monopotassium glycyrrhiznate A	Raw material	H61022582	86902362000219
Monoammonium glycyrrhizinate S	Monoammonium glycyrrhizinate S	Raw material	H20057930	86901498000025
Potassium glycyrrhefate M	Potassium glycyrrhefate M	Raw material	H20057335	86901498000018
Mono potassium glycyrrhizinate tablets	Mono potassium glycyrrhizinate	Tablets	Z15021799	86903911000452
Compound Licorice tablets	Licorice extract, opioid, camphor, star anise oil, sodium benzoate	Tablets	Z53020718	86905614002672
Ephedrine Hydrochloride and Glycyrrhizia Extract Tablets	Ephedrine hydrochloride, glycyrrhizia extract	Tablets	H61023525	86902503000504
Compound Glycyrrhizin tablets	Glycyrrhizin, glycine and cysteine hydrochloride	Tablets	H20073723	86903094000386
Compound licorice Aluminium and Magnesium tablets	Aluminium hydroxide, magnesium trisilicate, magnesium oxide, calcium carbonate, Bletilla striata, Radix aucklandiae, Extractum glycyrrhizae liquidum, Belladonna liquid extract	Tablets	H42022362	86901984002199
Diammonium glycyrrhizinate enteric-coated tablets	Diammonium glycyrrhizinate	Enteric-coated tablets	H20150025	86904797000703
Extractum glycyrrhizae	Licorice extract	Extractum	Z61021679	86902331000028
Licorzine granules	Licorzine	Granules	H32022277	86901474000070
Mono potassium glycyrrhizinate capsule	Mono potassium glycyrrhizinate	Capsule	Z20060085	86904313000217
Licorzine capsule	Licorzine	Capsule	H31022339	86900727000478
Diammonium glycyrrhizinate capsules	Diammonium glycyrrhizinate	Capsules	H20093489	86901651001531
Compound glycyrrhizin capsules	Glycyrrhizin, glycine and cysteine hydrochloride	Capsules	H20110056	86904152003899
Compound glycyrrhiza oral solution	Extractum glycyrrhizae liquidum, paregoric, glycerinum, guaiamar, concentrated ammonia solution	Oral solution	H46020470	86905840001623
Diammonium glycyrrhizinate for injecton	Diammonium glycyrrhizinate	Injection	H20052225	86900151000082
Compound glycyrrhizin for injection	Glycyrrhizin, glycine and cysteine hydrochloride	Injection	H20070217	86900234000039
MgIG injection	MgIG	Injection	H20051942	86901523001478
Compound monoammonium glycyrrhizinate S for injection	Glycyrrhizin, glycine and cysteine hydrochloride	Injection	H20041998	86900356001242
Diammonium glycyrrhizinate and glucose injection	Diammonium glycyrrhizinate and glucose	Injection	H20030421	86901523001126
Diammonium glycyrrhizinate and sodium chloride injection	Diammonium glycyrrhizinate and sodium chloride	Injection	H20010630	86901523001218
Monoammonium glycyrrhizinate and cysteine and sodium chloride injection	Monoammonium glycyrrhizinate, cysteine and sodium	Injection	H22026458	86903282000280

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