Mechanisms of Fuling Zexie decoction against metabolic dysfunction-associated steatotic liver disease: Integrative metabolomics, gut microbiota and serum pharmacochemistry

doi:10.3748/wjg.123034

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World Journal of Gastroenterology

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1007-9327

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Copyright: ©Author(s) 2027. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Jan 7, 2027; 33(1): 123034
Published online Jan 7, 2027. doi: 10.3748/wjg.123034

Table 1 Orthogonal least partial squares discriminant analysis model parameters

Model	Group	R²Y value			Q² value
Model	Group	Serum	Liver	Urine	Serum	Liver	Urine
ESI+	CON vs MOD	0.998	0.998	0.998	0.777	0.866	0.968
ESI+	FZD vs MOD	0.997	0.994	0.997	0.799	0.412	0.962
ESI-	CON vs MOD	0.998	0.992	0.993	0.873	0.882	0.962
ESI-	FZD vs MOD	0.999	0.998	0.998	0.906	0.576	0.979

CON: Control group; MOD: Model group; FZD: Fuling Zexie decoction group; ESI: Electrospray ionization; ESI+: Positive ion model; ESI-: Negative ion model.

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Table 2 Fuling Zexie decoction-derived compounds in serum of rats with metabolic dysfunction-associated steatotic liver disease

t_R (minute)	[M+H]⁺ [M+Na]⁺ m/z	ESI-MSⁿ (+) m/z	[M-H]^- m/z	ESI-MSⁿ (-) m/z	Predicted formula	Predicted (m/z)	Measured (m/z)	Diff (ppm)	Assigned identification	Source	Type
1.572	118.0864	118.0854			C₅H₁₁NO₂	118.0863	118.0864	0.85	Betaine	AMR	Alkaloid
2.729	263.1673	263.878, 163.1489, 145.0991, 117.0701			C₁₆H₂₂O₃	263.1649	263.1673	9.12	8beta-Methoxyatractylenolide I	AMR	Sesquiterpenoids
3.091	133.0648	105.0697, 115.0542			C₉H₈O	133.0647	133.0648	0.75	Trans-cinnamaldehyde	CR	Aromatic aldehydes
3.195	119.0350	119.0863			C₄H₆O₄	119.0339	119.0350	9.24	Succinic acid	CR	Aliphatic dicarboxylic acids
3.352	149.0595	130.9506, 119.9283, 103.944, 102.9436			C₉H₈O₂	149.0597	149.0595	-1.34	Cinnamic acid	CR	Aromatic carboxylic acids
5.184	217.1585	217.0204, 199.0299, 189.0469, 175.0313, 161.018, 119.0869, 107.0496			C₁₅H₂₀O	217.1587	217.1585	-0.92	Atractylone	AMR	Sesquiterpenoids
7.496	475.3741	457.3129			C₃₀H₅₀O₄	475.3782	475.3741	-8.62	11-deoxyalisol A	AR	Triterpenoids
8.113	455.3501	295.1916			C₃₀H₄₆O₃	455.352	455.3501	-4.17	Dehydrotrametenolic acid	PR	Triterpenoids
10.392	433.1126	416.8033, 398.7295, 367.146, 323.2313, 165.1012			C₂₁H₂₀O₁₀	433.1129	433.1126	-0.69	Vitexin	GRR	Flavonol glycosides
10.401	433.1134	257.0902, 239.0705, 137.0232			C₂₁H₂₀O₁₀	433.1129	433.1134	1.15	Liquiritigenin-4-O-glucuronide	GRR	Flavanone glycosides
11.530	271.0964	148.9916			C₁₆H₁₄O₄	271.0965	271.0964	-0.37	4,4’-dihydroxy-2-methoxychalcone	GRR	Chalcones
11.834	277.1800	259.5875, 189.0878			C₁₇H₂₄O₃	277.1798	277.1800	0.72	6-Shogaol	ZRR	Shogaols
12.867	163.0393	163.1483, 135.0831, 107.0865			C₉H₆O₃	163.039	163.0393	1.84	7-Hydroxycoumarin	AMR	Coumarins
13.118	347.2215	177.1277, 137.0955			C₂₁H₃₀O₄	347.2217	347.2215	-0.58	1-Dehydro-[10]-gingerdione	ZRR	Dehydrogingerdiones
13.3	429.1734	295.1494, 163.1091			C₂₀H₂₈O₁₀	429.1755	429.1734	-4.89	Cinnamylalcohol-6’-o-α-furanara-binose-O-β-glucopyranoside	CR	Aromatic alcohol glycosides
14.149	233.1538	233.1524, 205.0327, 189.0586, 159.0813, 145.0636, 133.1017, 131.0857, 105.0699			C₁₅H₂₀O₂	233.1536	233.1538	0.86	Atractylenolide II	AMR	Sesquiterpenoids
16.872	415.3211	157.0082, 143.0864, 129.0775, 105.0696			C₂₇H₄₂O₃	415.3207	415.3211	0.96	Diosgenin	AMR	Steroids
18.027	231.1380	231.0799, 189.0884, 161.0607, 128.0625, 105.0311			C₁₅H₁₈O₂	231.138	231.1380	0.00	Atractylenolide Ι	AMR	Sesquiterpenoids
18.314	469.3314	391.0493			C₃₀H₄₄O₄	469.3312	469.3314	0.43	3-oxo-16α-hydroxylanosta-7, 9(11), 24-trien-21-oic acid	PR	Triterpenoids
18.314	469.3314	471.2854, 337.0586			C₃₀H₄₄O₄	469.3312	469.3314	0.43	Alisol L	AR	Triterpenoids
27.023	471.3465	453.336, 435.3262, 425.3419			C₃₀H₄₆O₄	471.3469	471.3465	-0.85	16α-hydroxydehydrotrametenolic acid	PR	Triterpenoids
27.084	453.3363	435.3329, 339.2752			C₃₀H₄₄O₃	453.3363	453.3363	0.00	Dehydrotrametenonic acid	PR	Triterpenoids
27.627	471.3467	471.3462, 453.3377			C₃₀H₄₆O₄	471.3469	471.3467	-0.42	16,23-oxidoalisol B	AR	Triterpenoids
28.744	471.3474	453.3377, 189.1636			C₃₀H₄₆O₄	471.3469	471.3474	1.06	Glycyrrhetinic acid	GRR	Triterpenoids
28.849	203.1792	161.0607, 105.0697			C₁₅H₂₂	203.1794	203.1792	-0.98	Atractylenolide VI	AMR	Sesquiterpenoids
33.482	293.1774	155.0371, 112.9707			C₁₇H₂₄O₄	293.1747	293.1774	9.21	[6]-gingerdione	ZRR	Gingerdiones
33.962	331.2841	331.2614			C₁₉H₃₈O₄	331.2843	331.2841	-0.60	2-monopalmitin	AMR	Monoacylglycerols
34.949	319.1932	151.0802			C₁₉H₂₆O₄	319.1904	319.1932	8.77	1-dehydro-[8]-gingerdione	ZRR	Gingerdiones
35.241	531.3684	167.1446			C₃₂H₅₀O₆	531.3680	531.3684	0.75	3-O-acetyl-16α, 26-dihydroxytrametenolic acid	PR	Triterpenoids
4.398			167.0352	167.0228, 123.0091	C₈H₈O₄	167.035	167.0352	1.20	Vanillic acid	CR	Phenolic acids
7.341			499.3416	437.1592, 421.3151	C₃₁H₄₈O₅	499.3429	499.3416	-2.60	16α, 25-dihydroxyeburiconic acid	PR	Triterpenoids
8.385			255.0665	237.2247, 135.7461	C₁₅H₁₂O₄	255.0663	255.0665	0.78	Liquiritigenin	GRR	Flavanones
13.728			281.1395	281.2485, 263.238, 245.2271	C₁₅H₂₂O₅	281.1394	281.1395	0.36	4, 6-dihydroxy-3, 3a-dihydro atractylenolide III	AMR	Sesquiterpenoids
17.552			469.3658	339.2162	C₃₁H₅₀O₃	469.3687	469.3658	-6.18	Eburcoic acid	PR	Triterpenoids
17.792			499.3066	367.1447	C₃₀H₄₄O₆	499.3065	499.3066	0.20	3-oxo-16-oxo-11-anhydroalisol A	AR	Triterpenoids
18.757			487.3426	453.279, 435.0019, 381.019	C₃₀H₄₈O₅	487.3429	487.3426	-0.62	Alisol F	AR	Triterpenoids
25.201			497.3272	423.8392, 379.2716	C₃₁H₄₆O₅	497.3272	497.3272	0.00	Poricoic acid A	PR	Triterpenoids
34.320			347.2204	211.843	C₂₁H₃₂O₄	347.2227	347.2204	-6.62	10-gingerdione	ZRR	Gingerdiones
35.423	531.3683	309.2785, 391.1912			C₃₂H₅₀O₆	531.368	531.3683	0.56	Alisol F-24-acetate	AR	Triterpenoids

ESI: Electrospray ionization; MS: Mass spectrometry; PR: Poria; AR: Alismatis Rhizoma; AMR: Atractylodis Macrocephalae Rhizoma; CR: Cinnamomi Ramulus; GRR: Glycyrrhizae Radix et Rhizoma; ZRR: Zingiberis Rhizoma Recens.

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Table 3 Docking information between Fuling Zexie decoction-derived key compounds and core targets

Component	Target	Binding-energy (kcal/mol)	Amino acid residues
8beta-Methoxyatractylenolide I	PLA2G2A	-5.2	Gly-32
Liquiritigenin	PLA2G2A	-6.1	Lys-62
Atractylenolide II	MAOA	-9	Ile-325, Ile-335, Ile-180, Phe-208, Phe-352, Leu-337, and Glu-216
7-Hydroxycoumarin	MAOA	-7.8	Val-244, Leu-277, and Ala-44
[6]-gingerdione	MAOA	-7.9	Glu-216, Tyr-407
4,4’-Dihydroxy-2-methoxychalcone	MAOA	-9.3	Glu-43, Ala-44, and Arg-51
1-Dehydro-[8]-gingerdione	MAOA	-8.9	Val-244, Glu-43, Arg-45, Gly-21, and Gly-22
1-Dehydro-[10]-gingerdione	MAOA	-8.1	Tyr-444
Atractylenolide II	MPO	-5.1	Glu-181
7-Hydroxycoumarin	XDH	-5.8	Arg-1053, Ser-1185, and Gln-562
7-Hydroxycoumarin	MIF	-8	Asn-97, Ile-64, and Lys-32
[6]-gingerdione	MIF	-7.1	Tyr-36, Tyr-95, Lys-32, and Pro-1
6-Shogaol	MIF	-6.8	Lys-32, Asn-97
Dehydrotrametenonic acid	MIF	-4.7	Pro-15, Glu-21
1-dehydro-[8]-gingerdione	MIF	-6.3	His-40, His-62, Asn-97, and Tyr-99
1-dehydro-[10]-gingerdione	MIF	-6.1	Tyr-99, His-62, Ser-60, and Asn-6
10-gingerdione	MIF	-6.5	Tyr-99, His-62
7-Hydroxycoumarin	CYP1A2	-8.8	Gly-316, Asp-313
[6]-gingerdione	CYP1A2	-7.8	Thr-124
7-Hydroxycoumarin	ALDH2	-5.9	Arg-329
6-Shogaol	ALDH2	-7.3	Asp-457, Gln-289
10-gingerdione	ALDH2	-8.8	Leu-269, Trp-168
7-Hydroxycoumarin	ACHE	-7.6	His-447
[6]-gingerdione	ACHE	-8.1	Ser-125, Tyr-124, Gly-121, and Ser-203
4,4’-dihydroxy-2-methoxychalcone	ACHE	-10.0	His-447, Tyr-341
Liquiritigenin	ACHE	-9.6	Trp-86, Gly-121, Gly-122, and Ser-203
Eburcoic acid	ACHE	-9.2	Phe-295
16,23-oxidoalisol B	NOS2	-11.2	Arg-381
Alisol F-24-acetate	NOS2	-9.3	Trp-463, Tyr-491, Phe-369, Trp-194, and Ile-201
Trans-cinnamaldehyde	NOS2	-7.5	Phe-369, Leu-209, and Trp-194
Glycyrrhetinic acid	NOS2	-8.9	Lys-497
4,4’-dihydroxy-2-methoxychalcone	NOS2	-9.5	Trp-372, Tyr-489
Dehydrotrametenonic acid	NOS2	-10	Trp-372
Eburcoic acid	NOS2	-10	Trp-372
16α, 25-dihydroxyeburiconic acid	NOS2	-10	Arg-381
Dehydrotrametenolic acid	NOS2	-9.8	Trp-461, Ile-462, Phe-476, Trp-463, and Ile-201
16α-hydroxydehydrotrametenolic acid	NOS2	-10.2	Arg-381, Val-465
11-deoxyalisol A	NOS2	-9.1	E377, Y347
Alisol F-24-acetate	GSTM1	-6.4	Trp-7, Leu-59, and Asn-58
Alisol F	TKT	-8.5	Gln-290, Lys-144, Lys-140, and Lys-232
Trans-cinnamaldehyde	ADH4	-6	Phe-325, Tyr-95, and Thr-184
Cinnamic acid	MAOB	-7.5	Gly-12, Gly-13, and Arg-36
4,4’-dihydroxy-2-methoxychalcone	MAOB	-10.1	Thr-196
Liquiritigenin	MAOB	-9.1	Gly-434
6-Shogaol	GSTP1	-5.6	Arg-70, Asp-94, Arg-70, Asn-66, and Gln-64
Dehydrotrametenonic acid	PLA2G4A	-5.6	Asp-99, Arg-59, and Asp-55
Poricoic acid A	PLA2G4A	-4.8	Thr-104, Thr-90, and Arg-59
16α-hydroxydehydrotrametenolic acid	PLA2G4A	-5.8	Asp-55, Lys-58
Betaine	GOT1	-4	Gly-109, Ser-258, and Ala-110
Betaine	GOT2	-3.5	Ser-118, Glu-119

Gly: Glycine; Lys: Lysine; His: Histidine; Ile: Isoleucine; Phe: Phenylalanine; Leu: Leucine; Glu: Glutamate; Val: Valine; Ala: Alanine; Tyr: Tyrosine; Arg: Arginine; Ser: Serine; Gln: Glutamine; Asn: Asparagine; Pro: Proline; Thr: Threonine; Asp: Aspartate; Trp: Tryptophan.

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Citation: Wang PQ, Yang H, Tang YM, Tao YX, Han SC, Zhou QD, Yu J, Yang XX. Mechanisms of Fuling Zexie decoction against metabolic dysfunction-associated steatotic liver disease: Integrative metabolomics, gut microbiota and serum pharmacochemistry. World J Gastroenterol 2027; 33(1): 123034
URL: https://www.wjgnet.com/1007-9327/full/v33/i1/123034.htm
DOI: https://dx.doi.org/10.3748/wjg.123034

Wang PQ, Yang H, Tang YM, Tao YX, Han SC, Zhou QD, Yu J, Yang XX. Mechanisms of Fuling Zexie decoction against metabolic dysfunction-associated steatotic liver disease: Integrative metabolomics, gut microbiota and serum pharmacochemistry. World J Gastroenterol 2027; 33(1): 123034 [DOI: 10.3748/wjg.123034]

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