Evidence Construction of Chuankezhi Injection Against Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Pharmacology

Figures & data

Table 1 Characteristics of Included Studies

Study (Year)	Sample Size			Average Age (Year)		Male/Female		Treatment Duration (Week)	Interventions		Outcomes
	C	E	Total	C	E	C	E		C	E
Huang 2009^Citation22	29	27	56	68.52±8.48	66.41±9.95	2/27	1/26	12	Bronchodilators, corticosteroids	CT+CKZ 4mL im, qod	1,2,4,6,7,8,10
Jiang 2015^Citation23	57	59	116	57.80±5.30	58.20±5.20	47/10	46/13	4	Budesonide, formoterol inhalant	CT+CKZ 4mL im, bid	1,2,5,6,10,
Li 2020^Citation24	25	25	50	57.20±13.80	56.90±14.10	13/12	14/11	12	Theophylline, sustained-release tablets	CT+CKZ 4mL acupoint injection, biw	3,7,10,11,12,14,15
Li 2022^Citation25	39	39	78	62.14±9.74	62.75±9.83	23/16	22/17	2	Budesonide, oxygen	CT+CKZ 4mL iv, qd	1,2,3,10,12
Xiao 2020^Citation26	44	44	88	68.71±4.38	68.03±4.51	27/17	31/13	4	Budesonide aerosol	CT+CKZ 4mL im, bid	6,10,11
Pan 2016^Citation17	58	60	118	72.49± 5.69	74. 05±5.28	41/17	41/19	12	Bronchodilators, corticosteroids, oxygen	CT+CKZ 2mL acupoint injection, qd	1,9,10,11,16
Shan 2019^Citation18	80	80	160	58. 40±4.20	59. 20±3. 90	46/34	42/38	12	Oxygen, tiotropium bromide	CT+CKZ 4mL acupoint injection, biw	2,3,4,6,7,10 12,13,14,15
Wang 2014^Citation27	30	30	60	66.80±3.80	67.60±6.30	17/13	16/14	2	Salmeterol xinafoate and fluticasone	CT+CKZ 4mL im, bid	1,2,10,14,15
Wang 2017^Citation28	30	30	60	72.50±8.50	71.50±8.50	20/10	18/12	2	Salmeterol xinafoate and fluticasone	CT+CKZ 4mL iv, bid	7,8,10
Xu 2015^Citation29	58	60	118	72.49±5.69	74.05±5.28	41/17	41/19	12	Bronchodilators, corticosteroids	CT+CKZ 2mL acupoint injection, qd	1,9,10,11,16
Yu 2010^Citation30	30	30	60	83.00 ±4.50	82.00±5.30	23/7	22/8	4	Oxygen, tiotropium, Bromide	CT+CKZ 4mL im, qd	2,3,10,11,13
Yuan 2021^Citation31	49	49	98	66.12±4.15	66.75±4.03	27/22	28/21	12	Oxygen, tiotropium, Bromide	CT+CKZ 4mL im, bid	10,11
Zhan 2016^Citation32	15	15	30	56.27±8.47	58.40±7.71	7/8	9/6	12	Conventional therapy	CT+CKZ 4mL im, qd	2,3,4,7,10,11
Zhang 2021^Citation33	32	32	64	64.91±7.47	68.63±8.93	9/23	12/20	12	Conventional therapy	CT+CKZ 2mL acupoint injection, qd	1,2,3,4,7
Zheng 2010^Citation34	24	24	48	59	60	15/9	16/8	4	Conventional therapy	CT+CKZ 2mL aerosol inhalation, bid	3,10,11

Notes: Outcomes: 1. FEV₁/FVC; 2. FEV₁%pre; 3. clinical effective rates; 4. CAT scores/mMRc scores; 5. acute exacerbations; 6. 6MWD; 7. TCM syndrome scores; 8. SGRQ scores; 9. QLICD-COPD scores; 10. adverse events; 11. FEV₁(L)/FVC(L); 12. immunoglobulin; 13. T cell; 14. PaO₂; 15. PaCO₂; 16. Barthel scores.

Abbreviations: E, experiment group; C, control group; CT, conventional treatment group.

Figure 1 Flow chart of meta-analysis.

Figure 2 Risk bias of included studies.

Notes: (A) Overall risk; (B) Detailed risk.

Figure 3 Forest plot of clinical effective rate.

Figure 4 Forest plot of acute exacerbation rate.

Figure 5 Forest plot of FEV₁% pre.

Figure 6 Forest plot of FEV₁/FVC.

Figure 7 Forest plot of quality of life score. (A) CAT score. (B) QLICD-COPD score. (C) SGRQ score.

Figure 8 Forest plot of 6MWD.

Figure 9 Forest plot of TCM Syndrome Score.

Table 2 Other Outcomes

Study (Year)	N(C/E)	Outcome Indicator	C		E		P
			Before	After	Before	After	P1	P2
Li 2020^Citation24	25/25	IgM	0.2±0.1	0.3±0.1	0.2±0.1	0.6±0.2	>0.05	<0.05
		IgA	0.5±0.1	0.8±0.2	0.5±0.2	1.1±0.4	>0.05	<0.05
		IgG	7.2±0.5	7.7±0.9	7.2±0.6	8.8±0.7	>0.05	<0.05
Li 2022^Citation25	39/39	IgM	0.86±0.08	1.34±0.12	0.87±0.08	1.65±0.15	0.583	<0.05
		IgA	1.38±0.13	2.34±0.21	1.40±0.13	3.17±0.30	0.499	<0.05
		IgG	6.41±0.63	8.92±0.88	6.37±0.62	11.52±1.13	0.778	<0.05
Zhang 2021^Citation33	32/32	BODE score	3.72±2.89	3.72±1.67	3.81±2.39	2.53±2.02	0.888	0.008

Notes: P1: p-value of the comparison between the control and the experimental groups before intervention; P2: p-value of the comparison between control and experimental groups after intervention.

Abbreviations: E, experiment group; C, control group;

Table 3 List of CKZ Ingredients

Mol ID	Molecule Name	MW	DL	HL
MOL000006	Luteolin	286.25	0.25	15.94
MOL000098	Quercetin	302.25	0.28	14.40
MOL000359	Sitosterol	414.79	0.75	5.37
MOL000422	Kaempferol	286.25	0.24	14.74
MOL001510	24-epicampesterol	400.76	0.71	4.5
MOL001645	Linoleyl acetate	308.56	0.2	7.48
MOL001771	Poriferast-5-en-3beta-ol	414.79	0.75	5.07
MOL001792	DFV	256.27	0.18	17.89
MOL003044	Chryseriol	300.28	0.27	16.31
MOL003542	8-Isopentenyl-kaempferol	354.38	0.39	15.37
MOL004373	Anhydroicaritin	368.41	0.44	15.01
MOL004380	C-Homoerythrinan,1,6-didehydro-3,15,16-trimethoxy- (3.beta)	329.48	0.49	6.58
MOL004382	Yinyanghuo A	420.49	0.77	14.44
MOL004384	Yinyanghuo C	336.36	0.5	15.74
MOL004386	Yinyanghuo E	352.36	0.55	15.47
MOL004391	8-(3-methylbut-2-enyl)-2-phenyl-chromone	290.38	0.25	18.73
MOL002883	Ethyl oleate (NF)	310.58	0.19	4.85
MOL000358	Beta-sitosterol	414.79	0.75	5.36
MOL000359	Sitosterol	414.79	0.75	5.37
MOL006147	Alizarin-2-methylether	254.25	0.21	30.82
MOL009495	2-hydroxy-1,5-dimethoxy-6-(methoxymethyl)-9,10-anthraquinone	328.34	0.37	29.98
MOL009496	1,5,7-trihydroxy-6-methoxy-2-methoxymethylanthracenequinone	330.31	0.38	28.25
MOL009500	1,6-dihydroxy-5-methoxy-2-(methoxymethyl)-9,10-anthraquinone	314.31	0.34	29.02
MOL009503	1-hydroxy-3-methoxy-9,10-anthraquinone	254.25	0.21	30.78
MOL009504	1-hydroxy-6-hydroxymethylanthracenequinone	254.25	0.21	30.8
MOL009513	2-hydroxy-1,8-dimethoxy-7-methoxymethylanthracenequinone	328.34	0.37	29.44
MOL009519	(2R,3S) - (+)-3’,5-Dihydroxy-4,7-dimethoxydihydroflavonol	332.33	0.33	14.13
MOL009524	3beta,20(R),5-alkenyl-stigmastol	414.79	0.75	5.22
MOL009525	3beta-24S(R)-butyl-5-alkenyl-cholestol	456.88	0.82	7.04
MOL009558	2-hydroxyethyl-5-hydroxy-2-(2-hydroxybenzoyl)-4-(hydroxymethyl)benzoate	332.33	0.26	17.61
MOL009562	Ohioensin-A	372.39	0.76	15.09

Abbreviations: MW, molecular weight; DL, drug-likeness; HL, drug half-life.

Figure 10 Common targets and PPI network of hub genes.

Notes: (A) Common targets between CKZ and COPD; (B)PPI network of 10 hub genes.

Figure 11 Active ingredient-target network.

Notes: Green oval represent targets, orange rhombus represent active ingredients of CKZ.

Figure 12 GO and KEGG enrichment bubble diagram.

Notes: (A) GO enrichment bubble diagram; (B) KEGG enrichment bubble diagram.

Figure 13 Molecular docking results.

Notes: (A) Heat map of molecule docking affinity; (B) Molecular docking visualization results.

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