Chrysanthemi Flos extract alleviated acetaminophen-induced rat liver injury via inhibiting oxidative stress and apoptosis based on network pharmacology analysis

Figures & data

Figure 1. The compound-target network of C. Flos. The ellipse in purple indicates the bioactive compounds and the rectangle in green indicates potential targets.

Table 1. The bioactive compounds in Chrysanthemum Flos collected from TCMSP database.

Compound no.	Name	MW	MF	OB (%)	DL
No. 1	(24r)-Saringosterol	428.77	C29H48O2	39.36	0.79
No. 2	24-Ethylcholest-4-en-3-one	412.77	C29H48O	36.08	0.76
No. 3	Acacetin	284.28	C16H12O5	34.97	0.24
No. 4	Artemetin	388.4	C20H20O8	49.55	0.48
No. 5	beta-Sitosterol	414.79	C29H50O	36.91	0.75
No. 6	Chryseriol	300.28	C16H12O6	35.85	0.27
No. 7	Clionasterol	414.79	C29H50O	36.91	0.75
No. 8	Cynarine	516.49	C25H24O12	31.76	0.68
No. 9	Diosmetin	300.28	C16H12O6	31.14	0.27
No. 10	Eupatorin	344.34	C18H16O7	30.23	0.37
No. 11	Hesperetin	302.3	C16H14O6	47.74	0.27
No. 12	Isorhamnetin	316.28	C16H12O7	49.6	0.31
No. 13	Kaempferol	286.25	C15H10O6	41.88	0.24
No. 14	Linarin	592.6	C28H32O14	39.84	0.71
No. 15	Luteolin	286.25	C15H10O6	36.16	0.25
No. 16	Naringenin	272.27	C15H12O5	59.29	0.21
No. 17	Quercetin	302.25	C15H10O7	46.43	0.28

MW: molecular weight; MF: molecular formula; OB: oral bioavailability; DL: drug-likeness.

Figure 2. The protein–protein interaction (PPI) of the common targets. The protein with higher degree was presented with larger node and darker colour.

Table 2. The main pathways and biological processes in KEGG and GO enrichment analysis.

Pathway no.	KEGG pathway	Number of gene	p Value	GO no.	Biological process in GO analysis	Number of gene	p Value
hsa04151	PI3K–Akt signalling pathway	8	6.94E-04	0007165	Signal transduction	10	9.16E-04
hsa04015	Rap1 signalling pathway	7	2.93E-04	0008284	Positive regulation of cell proliferation	9	7.79E-06
hsa04915	Oestrogen signalling pathway	6	7.04E-05	0045893	Positive regulation of transcription	9	1.61E-05
hsa04931	Insulin resistance	6	1.07E-04	0001934	Positive regulation of protein phosphorylation	8	1.24E-08
hsa04510	Focal adhesion	6	0.0021	0043066	Negative regulation of apoptotic process	8	6.24E-05
hsa04014	Ras signalling pathway	6	0.0031	0051897	Positive regulation of protein kinase B signalling	6	1.22E-06
hsa04068	FoxO signalling pathway	5	0.0029	0030522	Intracellular receptor signalling pathway	5	1.56E-06
hsa04932	Non-alcoholic fatty liver disease	5	0.0044	0070301	Cellular response to hydrogen peroxide	5	8.08E-06
hsa04370	VEGF signalling pathway	4	0.0025	0006979	Response to oxidative stress	4	0.002
hsa04012	ErbB signalling pathway	4	0.0068	1900182	Positive regulation of protein localization to nucleus	3	0.001

Figure 3. The effects of BZE on APAP-induced liver injury and oxidative stress. (A, B) The levels of ALT and AST; (C) the representative images of liver H&E staining (bar = 100 μm); (D–F) the measurement of ROS in liver, and SOD and GSH in serum of rats (means ± SD, n = 6); ^##p < 0.01 compared to control group; *p < 0.05, **p < 0.01 compared to APAP group. APAP: acetaminophen; BZE: extract of Bianliang ziyu flower.

Figure 4. Effects of BZE on the AMPK/GSK3β–Nrf2 antioxidant signalling pathway. (A, D) The representative protein bands; (B, C and E–H) relative expression levels of p-AMPK, p-GSK3β, Nrf2 (cytoplasm), Nrf2 (nuclear), HO-1 and NQO1 (means ± SD, n = 3); ^#p < 0.05, ^##p < 0.01 compared to control group; *p < 0.05, **p < 0.01 compared to APAP group. APAP: acetaminophen; BZE: extract of Bianliang ziyu flower.

Figure 5. Effects of BZE on PI3K–Akt pathway and APAP-induced apoptosis. (A) Representative protein bands; (B–E) the relative expression levels of p-Akt, caspase-3, Bax and Bcl-2 (means ± SD, n = 6); ^##p < 0.01 compared to control group; *p < 0.05, **p < 0.01 compared to APAP group. APAP: acetaminophen; BZE: extract of Bianliang ziyu flower.

Figure 6. Effects of BZE on the APAP-induced mitochondrial membrane potential and mitochondrial biosynthesis-related proteins. (A) The measurement of mitochondrial membrane potential; (B) representative protein bands; (C–F) the relative expression levels of PPAR-γ, PGC-1α, NRF1 and TFAM (means ± SD, n = 6). ^#p < 0.05, ^##p < 0.01 compared to control group; *p < 0.05, **p < 0.01 compared to APAP group. APAP: acetaminophen; BZE: extract of Bianliang ziyu flower.