Efficacy of Tounongsan decoction (透脓散方) on pyogenic liver abscess: network pharmacology and clinical trial validation

doi:10.19852/j.cnki.jtcm.20231110.006

Abstract

Abstract:

OBJECTIVE: To elucidate the molecular mechanisms governing the effect of Tounongsan decoction (透脓散方, TNS) on the pyogenic liver abscess.

METHODS: Based on oral bioavailability and drug-likeness, the main active components of TNS were screened using the Traditional Chinese Medicine Systems Pharmacology platform. The GeneCard and UniProt databases were used to establish a database of pyogenic liver abscess targets. The interactive network map of drug-ingredients-target-disease was constructed using Cytoscape software (Version 3.7.2). A protein-protein interaction network was constructed using the STRING database, and the related protein interaction relationships were analyzed. biological process of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the core targets. Finally, a clinical trial was performed to verify the reliability of the network pharmacology.

RESULTS: Forty active components of TNS decoction were obtained, and 61 potential targets and 11 proteins were identified. Pathways involved in the treatment of pyogenic liver abscess include the phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT), advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), and tumor necrosis factor (TNF) signaling pathways. The results of network pharmacology analysis combined with clinical trials validated that TNS decoction could alleviate the inflammatory response of pyogenic liver abscesses by decreasing interleukin 6 (IL-6) levels.

CONCLUSIONS: TNS decoction has the characteristics of being multi-system, multi-component, and multi-target. Active ingredients in TNS, such as quercetin, kaempferol, fisetin, and β-sitosterol, have strong potential to be candidate drugs for treating pyogenic liver abscesses. The possible mechanism of TSN decoction includes regulating immune and inflammatory responses and reducing IL-6 production to control inflammatory development.

Key words: network pharmacology, clinical trial, liver abscess, pyogenic, Tounongsan decoction

ZHANG Qi, CHEN Dexuan, ZHU Guixiang, ZHANG Shihu, FENG Xiao, MA Chaoqun, ZHANG Yi. Efficacy of Tounongsan decoction (透脓散方) on pyogenic liver abscess: network pharmacology and clinical trial validation[J]. Journal of Traditional Chinese Medicine, 2024, 44(1): 145-155.

Figures/Tables 7

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Herb	Molecular number	Active ingredients	OB (≥30%)	DL (≥0.18)
Huangqi (Radix Astragali Mongolici)	MOL000211	Mairin	55.38	0.78
	MOL000239	Jaranol	50.83	0.29
	MOL000296	Hederagenin	36.91	0.75
	MOL000033	(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-^{2R,5S)-5-propan-2-yloctan-2-yl}-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta^aphenanthren-3-ol	36.23	0.78
	MOL000354	Isorhamnetin	49.60	0.31
	MOL000371	3,9-di-O-methylnissolin	53.74	0.48
	MOL000374	5'-hydroxyiso-muronulatol-2',5'-di-O-glucoside	41.72	0.69
	MOL000378	7-O-methylisomucronulatol	74.69	0.30
	MOL000379	9,10-dimethoxypterocarpan-3-O-β-D-glucoside	36.74	0.92
	MOL000380	(6aR,11aR)-9,10-dimethoxy-6a,11a-dihydro-6H-benzofurano^3,2-cchromen-3-ol	64.26	0.42
	MOL000387	Bifendate	31.10	0.67
	MOL000392	Formononetin	69.67	0.21
	MOL000398	Isoflavanone	109.99	0.30
	MOL000438	(3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol	67.67	0.26
	MOL000439	Isomucronulatol-7,2'-Di-O-Glucosiole	49.28	0.62
	MOL000442	1,7-Dihydroxy-3,9-dimethoxy pterocarpene	39.05	0.48
	MOL005016	Odoratin	49.95	0.30
	MOL000173	Wogonin	30.68	0.23
	MOL002565	Medicarpin	49.22	0.34
	MOL000239	Kumatakenin	50.83	0.29
	MOL001494	Mandenol	42.00	0.19
Chuanxiong (Rhizoma Chuanxiong)	MOL002135	Myricanone	40.60	0.51
	MOL002140	Perlolyrine	65.95	0.27
	MOL002151	Senkyunone	47.66	0.24
	MOL002157	Wallichilide	42.31	0.71
	MOL006358	Stigmast-4-ene-3,6-dione	39.12	0.79
Zaojiaoci (Spina Gleditsiae)	MOL002914	Eriodyctiol	41.35	0.24
	MOL000073	Ent-Epicatechin	48.96	0.24
	MOL013296	Fustin	50.91	0.24
	MOL013179	Fisetin	52.60	0.24
	MOL001736	(-)-taxifolin	60.51	0.27
	MOL013305	Garbanzol	83.67	0.21
	MOL000433	Folic Acid	68.96	0.71
Danggui (Radix Angelicae Sinensis)	MOL000433	2-^{4-(2-Amino-4-Oxo-1H-Pteridin-6-Yl)Methylamino}BenzoylAminoPentanedioic Acid	68.96	0.71
	MOL004792	Nodakenin	57.12	0.69
	MOL001506	Squalene	33.55	0.42
	MOL001941	Pentosalen	34.55	0.22
	MOL000098	Quercetin	46.43	0.28
Huangqi (Radix Astragali Mongolici)-Zaojiaoci (Spina Gleditsiae)	MOL000422	Kaempferol	41.88	0.24
	MOL000433	FA	68.96	0.71
Huangqi (Radix Astragali Mongolici)-Chuanxiong (Rhizoma Chuanxiong)	MOL000359	Sitosterol	36.91	0.75
Huangqi (Radix Astragali Mongolici)-Chuanxiong- Zaojiaoci (Spina Gleditsiae)	MOL000358	Beta-Sitosterol	36.91	0.75
Danggui (Radix Angelicae Sinensis)-Zaojiaoci (Spina Gleditsiae)	MOL000449	Stigmasterol	43.83	0.76
Huangqi (Radix Astragali Mongolici)-Danggui (Radix Angelicae Sinensis)	MOL000417	Calycosin	47.75	0.24

Herb	Molecular number	Active ingredients	OB (≥30%)	DL (≥0.18)
Huangqi (Radix Astragali Mongolici)	MOL000211	Mairin	55.38	0.78
	MOL000239	Jaranol	50.83	0.29
	MOL000296	Hederagenin	36.91	0.75
	MOL000033	(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-^{2R,5S)-5-propan-2-yloctan-2-yl}-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta^aphenanthren-3-ol	36.23	0.78
	MOL000354	Isorhamnetin	49.60	0.31
	MOL000371	3,9-di-O-methylnissolin	53.74	0.48
	MOL000374	5'-hydroxyiso-muronulatol-2',5'-di-O-glucoside	41.72	0.69
	MOL000378	7-O-methylisomucronulatol	74.69	0.30
	MOL000379	9,10-dimethoxypterocarpan-3-O-β-D-glucoside	36.74	0.92
	MOL000380	(6aR,11aR)-9,10-dimethoxy-6a,11a-dihydro-6H-benzofurano^3,2-cchromen-3-ol	64.26	0.42
	MOL000387	Bifendate	31.10	0.67
	MOL000392	Formononetin	69.67	0.21
	MOL000398	Isoflavanone	109.99	0.30
	MOL000438	(3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol	67.67	0.26
	MOL000439	Isomucronulatol-7,2'-Di-O-Glucosiole	49.28	0.62
	MOL000442	1,7-Dihydroxy-3,9-dimethoxy pterocarpene	39.05	0.48
	MOL005016	Odoratin	49.95	0.30
	MOL000173	Wogonin	30.68	0.23
	MOL002565	Medicarpin	49.22	0.34
	MOL000239	Kumatakenin	50.83	0.29
	MOL001494	Mandenol	42.00	0.19
Chuanxiong (Rhizoma Chuanxiong)	MOL002135	Myricanone	40.60	0.51
	MOL002140	Perlolyrine	65.95	0.27
	MOL002151	Senkyunone	47.66	0.24
	MOL002157	Wallichilide	42.31	0.71
	MOL006358	Stigmast-4-ene-3,6-dione	39.12	0.79
Zaojiaoci (Spina Gleditsiae)	MOL002914	Eriodyctiol	41.35	0.24
	MOL000073	Ent-Epicatechin	48.96	0.24
	MOL013296	Fustin	50.91	0.24
	MOL013179	Fisetin	52.60	0.24
	MOL001736	(-)-taxifolin	60.51	0.27
	MOL013305	Garbanzol	83.67	0.21
	MOL000433	Folic Acid	68.96	0.71
Danggui (Radix Angelicae Sinensis)	MOL000433	2-^{4-(2-Amino-4-Oxo-1H-Pteridin-6-Yl)Methylamino}BenzoylAminoPentanedioic Acid	68.96	0.71
	MOL004792	Nodakenin	57.12	0.69
	MOL001506	Squalene	33.55	0.42
	MOL001941	Pentosalen	34.55	0.22
	MOL000098	Quercetin	46.43	0.28
Huangqi (Radix Astragali Mongolici)-Zaojiaoci (Spina Gleditsiae)	MOL000422	Kaempferol	41.88	0.24
	MOL000433	FA	68.96	0.71
Huangqi (Radix Astragali Mongolici)-Chuanxiong (Rhizoma Chuanxiong)	MOL000359	Sitosterol	36.91	0.75
Huangqi (Radix Astragali Mongolici)-Chuanxiong- Zaojiaoci (Spina Gleditsiae)	MOL000358	Beta-Sitosterol	36.91	0.75
Danggui (Radix Angelicae Sinensis)-Zaojiaoci (Spina Gleditsiae)	MOL000449	Stigmasterol	43.83	0.76
Huangqi (Radix Astragali Mongolici)-Danggui (Radix Angelicae Sinensis)	MOL000417	Calycosin	47.75	0.24

Project	Group	Pre-treatment	Post-treatment	t value	P value
IL-1β	A	19.6±20.7	29.6±23.0	2.036	0.048^a
IL-1β	B	36.9±48.0	20.6±15.0	2.036	0.048^a
IL-2	A	4.6±12.1	2.3±1.6	0.51	0.613
IL-2	B	3.5±5.0	2.4±1.8	0.51	0.613
IL-4	A	4.6±12.3	2.2±2.4	1.246	0.219
IL-4	B	2.0±1.5	2.8±2.2	1.246	0.219
IL-5	A	4.0±4.4	4.2±3.6	1.371	0.177
IL-5	B	2.2±1.7	3.8±2.3	1.371	0.177
IL-6	A	37.5±43.9	27.8±40.9	2.041	0.047^b
IL-6	B	41.9±45.6	12.5±14.8	2.041	0.047^b
IL-8	A	28.3±24.0	25.6±29.3	1.004	0.32
IL-8	B	33.6±49.8	20.1±17.9	1.004	0.32
IL-10	A	4.5±3.6	2.0±0.9	2.293	0.026^c
IL-10	B	3.4±3.9	4.2±4.1	2.293	0.026^c
IL-17	A	5.5±8.4	5.3±10.5	0.243	0.809
IL-17	B	4.4±4.0	4.1±3.5	0.243	0.809
IL-12P70	A	2.8±1.6	2.8±2.3	2.13	0.039^d
IL-12P70	B	1.9±1.6	3.4±2.4	2.13	0.039^d
TNF-α	A	10.1±11.0	14.8±16.4	0.35	0.728
TNF-α	B	9.9±12.2	13.4±14.6	0.35	0.728
IFN-α	A	3.6±3.8	4.5±9.4	0.43	0.669
IFN-α	B	2.0±2.0	2.2±1.1	0.43	0.669
IFN-γ	A	13.4±13.9	18.3±27.0	0.264	0.794
IFN-γ	B	8.8±8.1	12.4±9.6	0.264	0.794

Project	Group	Pre-treatment	Post-treatment	t value	P value
IL-1β	A	19.6±20.7	29.6±23.0	2.036	0.048^a
IL-1β	B	36.9±48.0	20.6±15.0	2.036	0.048^a
IL-2	A	4.6±12.1	2.3±1.6	0.51	0.613
IL-2	B	3.5±5.0	2.4±1.8	0.51	0.613
IL-4	A	4.6±12.3	2.2±2.4	1.246	0.219
IL-4	B	2.0±1.5	2.8±2.2	1.246	0.219
IL-5	A	4.0±4.4	4.2±3.6	1.371	0.177
IL-5	B	2.2±1.7	3.8±2.3	1.371	0.177
IL-6	A	37.5±43.9	27.8±40.9	2.041	0.047^b
IL-6	B	41.9±45.6	12.5±14.8	2.041	0.047^b
IL-8	A	28.3±24.0	25.6±29.3	1.004	0.32
IL-8	B	33.6±49.8	20.1±17.9	1.004	0.32
IL-10	A	4.5±3.6	2.0±0.9	2.293	0.026^c
IL-10	B	3.4±3.9	4.2±4.1	2.293	0.026^c
IL-17	A	5.5±8.4	5.3±10.5	0.243	0.809
IL-17	B	4.4±4.0	4.1±3.5	0.243	0.809
IL-12P70	A	2.8±1.6	2.8±2.3	2.13	0.039^d
IL-12P70	B	1.9±1.6	3.4±2.4	2.13	0.039^d
TNF-α	A	10.1±11.0	14.8±16.4	0.35	0.728
TNF-α	B	9.9±12.2	13.4±14.6	0.35	0.728
IFN-α	A	3.6±3.8	4.5±9.4	0.43	0.669
IFN-α	B	2.0±2.0	2.2±1.1	0.43	0.669
IFN-γ	A	13.4±13.9	18.3±27.0	0.264	0.794
IFN-γ	B	8.8±8.1	12.4±9.6	0.264	0.794

Project	Group	Pre-treatment	Post-treatment	t value	P value
CD4+	A	521.4±246.9	479.5±169.8	2.51	0.016^a
CD4+	B	410.6±199.6	557.3±225.6	2.51	0.016^a
CD8+	A	327.5±156.7	385.6±278.0	0.414	0.681
CD8+	B	252.3±103.3	336.3±155.8	0.414	0.681
CD3+	A	902.1±361.9	919.9±419.6	1.79	0.08
CD3+	B	705.6±304.3	957.7±341.6	1.79	0.08
CD4/CD8	A	1.8±0.9	1.5±0.5	1.792	0.08
CD4/CD8	B	1.7±0.5	1.8±0.7	1.792	0.08

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