药学学报

Compound	Number of literature	Experimental data		Compound	Number of literature	Experimental data
Albiflorin	19	0.60		Licoricone	1	-
Benzoic acid	1	0.66	Liquiritigenin	9	-
Benzoylpaeoniflorin	11	-	Liquiritin	14	-
Betulinic acid	2		Liquiritin apioside	1	-
Catechin	3	-	Maackiain	-	0.50
Dehydroglyasperin C	-	0.67	Medicarpin	-	0.58
Desbenzoylpaeoniflorin	-	0.58	Naringenin	14	-
DL-Arabinose	-	0.63	Naringin	7
D(+)-Glucose	2	0.75	Neoglycyrol	-	0.67
Formonetin	3	0.63	Odoratin	-	0.58
Gallic acid	5	-	Oxypaeoniflorin	12	-
Galloylpaeoniflorin	-	0.55	Paeoniflorin	54	-
Glycyrrhetinic acid	3	-	Paeonilactone C	-	0.71
Glycyrrhizic acid	15	-	Paeonin	11	-
Hispaglabridin A	-	0.65	Paeonol	10	0.63
Isolicoflavonol	1	-	Pinocembrin	-	0.71
Isoliquiritigenin	8	0.71	Quercetin	34	-
Isoliquiritin	8	-	Sigmoidin B	-	0.65
Isoschaftoside	-	0.77	Topazolin	-	0.80
Kaempferol	3	-	Trifolirhizin	-	0.62
Kaempferol-3-O-methyl ether	-	0.50	Uralenol	-	0.54
Licochalcone B	-	0.55	Vestitol	-	0.61
Licoflavone	1	-	1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose	1	-
Licorice saponin A3	-	0.56	3, 4-Dihydroxybenzoic acid	-	0.61
Licorice saponine E2	-	0.82		4', 7-Dihydroxy-flavone	-	0.70

Compound	Number of literature	Experimental data		Compound	Number of literature	Experimental data
Albiflorin	19	0.60		Licoricone	1	-
Benzoic acid	1	0.66	Liquiritigenin	9	-
Benzoylpaeoniflorin	11	-	Liquiritin	14	-
Betulinic acid	2		Liquiritin apioside	1	-
Catechin	3	-	Maackiain	-	0.50
Dehydroglyasperin C	-	0.67	Medicarpin	-	0.58
Desbenzoylpaeoniflorin	-	0.58	Naringenin	14	-
DL-Arabinose	-	0.63	Naringin	7
D(+)-Glucose	2	0.75	Neoglycyrol	-	0.67
Formonetin	3	0.63	Odoratin	-	0.58
Gallic acid	5	-	Oxypaeoniflorin	12	-
Galloylpaeoniflorin	-	0.55	Paeoniflorin	54	-
Glycyrrhetinic acid	3	-	Paeonilactone C	-	0.71
Glycyrrhizic acid	15	-	Paeonin	11	-
Hispaglabridin A	-	0.65	Paeonol	10	0.63
Isolicoflavonol	1	-	Pinocembrin	-	0.71
Isoliquiritigenin	8	0.71	Quercetin	34	-
Isoliquiritin	8	-	Sigmoidin B	-	0.65
Isoschaftoside	-	0.77	Topazolin	-	0.80
Kaempferol	3	-	Trifolirhizin	-	0.62
Kaempferol-3-O-methyl ether	-	0.50	Uralenol	-	0.54
Licochalcone B	-	0.55	Vestitol	-	0.61
Licoflavone	1	-	1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose	1	-
Licorice saponin A3	-	0.56	3, 4-Dihydroxybenzoic acid	-	0.61
Licorice saponine E2	-	0.82		4', 7-Dihydroxy-flavone	-	0.70

Compound	Number of literature	Proportion of HPLC/%	Component content/%	Component variability	Transfer rate/%
Albiflorin	28	0.786	0.643	0.578	0.366
Albiflorin R1	1	1.000	0.001	0.148	-
Benzoic acid	11	0.818	0.012	0.469	-
Benzoyloxypaeoniflorin	1	1.000	0.001	0.189	-
Benzoylpaeoniflorin	21	0.762	0.047	0.651	0.363
Catechin	10	0.700	0.065	1.251	-
D(+)-Glucose	1	-	0.519	0.164	-
Ethyl gallate	1	-	0.007	0.363	-
Formononetin	1	1.000	0.029	0.520	0.027
Gallic acid	20	0.750	0.201	0.278	-
Galloylpaeoniflorin	1	1.000	0.029	0.107	0.852
Glabridin	8	0.875	0.121	0.599	-
Glycycoumarin	2	0.001	0.084	0.608	-
Glycyrrhetinic acid	17	0.765	0.083	0.201	-
Glycyrrhizic acid	31	0.742	2.503	0.251	0.217
Glycyrrhizic acid ammonium salt	2	1.000	3.228	0.187	-
Glypallichalcone	1	1.000	0.024	1.200	-
Homopterocarpin	1	0.001	0.009	-	-
Isoglycyrol	1	0.001	0.007	0.297	-
Isoliquiritigenin	16	0.750	0.013	0.466	0.316
Isoliquiritin	11	0.818	0.095	0.386	0.366
Isoliquiritin apioside	8	0.750	0.119	0.563	0.301
Licochalcone A	8	0.750	0.017	0.409	-
Licochalcone B	2	0.500	0.042	1.373	-
Licochalcone C	1	0.001	-	-	-
Licorice saponine A3	1	-	0.110	0.155	-
Licorice saponine G2	3	0.667	1.272	0.088	-
Liquiritigenin	17	0.765	0.040	0.411	0.725
Liquiritin	30	0.767	1.243	0.308	0.253
Liquiritin apioside	8	0.750	0.493	0.380	0.392
Propanedioic acid	-	-	0.623	0.446	-
Methyl gallate	6	0.833	0.258	0.469	-
Mudanpioside F	1	1.000	0.007	0.272	-
Naringenin-7-O-β-D-glucoside	-	-	0.066	0.412	-
Ononin	1	1.000	0.080	0.677	0.287
Oxyalbiflorin	1	1.000	0.015	0.086	-
Oxypaeonidanin	1	1.000	0.011	0.076	-
Oxypaeoniflorin	14	0.857	0.111	0.549	0.074
Paeonidanin	1	1.000	0.004	0.223	-
Paeoniflorin	54	0.778	3.244	0.160	0.250
Paeoniflorin sulfonate	3	0.667	1.371	0.640	-
Paeonol	6	0.667	0.004	0.597	-
Protocatechuic aldehyde	1	1.000	0.026	1.081	-
Uralsaponin B	3	1.000	1.396	0.130	-
α-D-Lactose monohydrate	-	-	17.380	0.044	-
β-D-Fructopyranose	-	-	1.213	0.019	-
1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose	13	0.692	1.094	0.358	0.048
3, 4-Dihydroxybenzoic acid	2	0.500	0.015	0.450	-
4-O-Methyl-oxypaeoniflorin	1	1.000	0.023	0.111	-
4-O-Methyl-paeoniflorin	1	1.000	0.002	1.358	-
10-Hydroxypaeoniflorin	1	1.000	0.025	0.045	-
22β-Acetoxyl-glycyrrhizin	1	-	0.103	0.408	-

Compound	Number of literature	Proportion of HPLC/%	Component content/%	Component variability	Transfer rate/%
Albiflorin	28	0.786	0.643	0.578	0.366
Albiflorin R1	1	1.000	0.001	0.148	-
Benzoic acid	11	0.818	0.012	0.469	-
Benzoyloxypaeoniflorin	1	1.000	0.001	0.189	-
Benzoylpaeoniflorin	21	0.762	0.047	0.651	0.363
Catechin	10	0.700	0.065	1.251	-
D(+)-Glucose	1	-	0.519	0.164	-
Ethyl gallate	1	-	0.007	0.363	-
Formononetin	1	1.000	0.029	0.520	0.027
Gallic acid	20	0.750	0.201	0.278	-
Galloylpaeoniflorin	1	1.000	0.029	0.107	0.852
Glabridin	8	0.875	0.121	0.599	-
Glycycoumarin	2	0.001	0.084	0.608	-
Glycyrrhetinic acid	17	0.765	0.083	0.201	-
Glycyrrhizic acid	31	0.742	2.503	0.251	0.217
Glycyrrhizic acid ammonium salt	2	1.000	3.228	0.187	-
Glypallichalcone	1	1.000	0.024	1.200	-
Homopterocarpin	1	0.001	0.009	-	-
Isoglycyrol	1	0.001	0.007	0.297	-
Isoliquiritigenin	16	0.750	0.013	0.466	0.316
Isoliquiritin	11	0.818	0.095	0.386	0.366
Isoliquiritin apioside	8	0.750	0.119	0.563	0.301
Licochalcone A	8	0.750	0.017	0.409	-
Licochalcone B	2	0.500	0.042	1.373	-
Licochalcone C	1	0.001	-	-	-
Licorice saponine A3	1	-	0.110	0.155	-
Licorice saponine G2	3	0.667	1.272	0.088	-
Liquiritigenin	17	0.765	0.040	0.411	0.725
Liquiritin	30	0.767	1.243	0.308	0.253
Liquiritin apioside	8	0.750	0.493	0.380	0.392
Propanedioic acid	-	-	0.623	0.446	-
Methyl gallate	6	0.833	0.258	0.469	-
Mudanpioside F	1	1.000	0.007	0.272	-
Naringenin-7-O-β-D-glucoside	-	-	0.066	0.412	-
Ononin	1	1.000	0.080	0.677	0.287
Oxyalbiflorin	1	1.000	0.015	0.086	-
Oxypaeonidanin	1	1.000	0.011	0.076	-
Oxypaeoniflorin	14	0.857	0.111	0.549	0.074
Paeonidanin	1	1.000	0.004	0.223	-
Paeoniflorin	54	0.778	3.244	0.160	0.250
Paeoniflorin sulfonate	3	0.667	1.371	0.640	-
Paeonol	6	0.667	0.004	0.597	-
Protocatechuic aldehyde	1	1.000	0.026	1.081	-
Uralsaponin B	3	1.000	1.396	0.130	-
α-D-Lactose monohydrate	-	-	17.380	0.044	-
β-D-Fructopyranose	-	-	1.213	0.019	-
1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose	13	0.692	1.094	0.358	0.048
3, 4-Dihydroxybenzoic acid	2	0.500	0.015	0.450	-
4-O-Methyl-oxypaeoniflorin	1	1.000	0.023	0.111	-
4-O-Methyl-paeoniflorin	1	1.000	0.002	1.358	-
10-Hydroxypaeoniflorin	1	1.000	0.025	0.045	-
22β-Acetoxyl-glycyrrhizin	1	-	0.103	0.408	-

Compound	Related herb		Compound	Related herb		Compound	Related herb
Albiflorin	12		Hispaglabridin A	5		Naringenin-7-O-β-D-glucoside	1
Albiflorin R1	2	Hispaglabridin B	7	Naringin	134
Apiopaeonoside	4	Homopterocarpin	1	Neoglycyrol	4
Astragalin	707	Isoglabrolide	1	Neoisoliquiritin	2
Benzoic acid	200	Isoglycyrol	7	Odoratin	1
Benzoyloxypaeoniflorin	2	Isolicoflavonol	1	Oleanolic acid	200
Benzoylpaeoniflorin	13	Isoliquiritigenin	132	Ononin	45
Betulinic acid	200	Isoliquiritin	21	Oxypaeoniflorin	15
Calycosin	197	Isoliquiritin apioside	1	Paeonidanin	4
Casuarictin	14	Isoononin	1	Paeoniflorigenone	6
Casuariin	14	Isoquercitrin	200	Paeoniflorin	16
Catechin	108	Isoschaftoside	116	Paeoniflorin sulfonate	1
Choerospondin	1	Isotrifoliol	1	Paeonilactone A	4
Dehydroglyasperin C	1	Isoviolanthin	6	Paeonilactone B	3
Desbenzoylpaeoniflorin	1	Kaempferol	1 248	Paeonilactone C	3
Dipropyl phthalate	1	Kaempferol-3-O-methyl ether	1	Paeonin	5
DL-Arabinose	1	Lactiflorin	5	Paeonol	78
D(+)-Glucose	1	Licoarylcoumarin	7	Paeonolide	6
Echinatin	15	Licobenzofuran	2	Paeonoside	7
Ethyl gallate	1	Licochalcone A	7	Palbinone	7
Eurycarpin A	2	Licochalcone B	2	Pedunculagin	24
Formonetin	3	Licochalcone C	1	Pinocembrin	296
Formononetin	1	Licochalcone D	1	Protocatechuic aldehyde	1
Gallic acid	1	Licocoumarone	7	Prunetin	43
Gancaonin G	1	Licoflavonol	1	Pyrethrin Ⅰ	4
Gancaonin H	1	Licoflavone	2	Pyrethrin Ⅱ	3
Gancaonin I	1	Licofuranocoumarin	2	Pyrogallol	36
Gancaonin L	1	Licoisoflavanone	2	Quercetin	2 006
Gancaonin M	1	Licoisoflavone A	6	Rutin	1 483
Gancaonin R	1	Licoisoflavone B	2	Schaftoside	48
Galloyloxypaeoniflorin	2	Licorice saponine A3	2	Sigmoidin B	1
Galloylpaeoniflorin	8	Licorice saponine B2	1	Sitogluside	186
Genkwanin	153	Licorice saponine E2	1	Sitosterol	200
Glabranine	3	Licorice saponine G2	2	Strictinin	69
Glabrene	5	Licorice saponine H2	2	Tellimagrandin Ⅰ	5
Glabridin	6	Licorice saponine J2	1	Topazolin	1
Glabrol	6	Licorice saponine K2	1	Trifolirhizin	1
Glabrolide	3	Licoricidin	5	Uralenin	3
Glabrone	11	Licoricone	2	Uralenol	2
Glicoricone	1	Licorisoflavan A	2	Uralenol-3-methylether	2
Glyasperin A	1	Licuraside	1	Uralsaponin B	1
Glyasperin B	1	Liquiritigenin	50	Uralstilbene	2
Glyasperin C	1	Liquiritin	15	Vestitol	62
Glyasperin D	1	Liquiritin apioside	1	Vicenin-2	9
Glycycoumarin	9	Liquoric acid	2	Violanthin	9
Glycyrin	4	Maackiain	1	1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose	13
Glycyrol	15	Propanedioic acid	1	2-Methylheptane	21
Glycyroside	3	Medicarpin	1	3-Hydroxyglabrol	6
Glycyrrhetinic acid	31	Methyl gallate	1	3, 4-Dihydroxybenzoic acid	200
Glycyrrhetol	2	Mudanpioside D	2	4', 7-Dihydroxy-flavone	1
Glycyrrhisoflavanone	1	Mudanpioside E	2	5-Desgalloylstachyurin	4
Glycyrrhizic acid	10	Mudanpioside F	1	7-Methoxy-4'-hydroxyflavone	1
Glypallichalcone	2	Mudanpioside H	3	7-Methoxy-4'-hydroxyflavonol	1
Glyzaglabrin	2	Mudanpioside J	3	22β-Acetoxyl-glycyrrhizin	1
Hederagenin	121	Narcissin	153
Hexadecanoic acid	200		Naringenin	188

Compound	Related herb		Compound	Related herb		Compound	Related herb
Albiflorin	12		Hispaglabridin A	5		Naringenin-7-O-β-D-glucoside	1
Albiflorin R1	2	Hispaglabridin B	7	Naringin	134
Apiopaeonoside	4	Homopterocarpin	1	Neoglycyrol	4
Astragalin	707	Isoglabrolide	1	Neoisoliquiritin	2
Benzoic acid	200	Isoglycyrol	7	Odoratin	1
Benzoyloxypaeoniflorin	2	Isolicoflavonol	1	Oleanolic acid	200
Benzoylpaeoniflorin	13	Isoliquiritigenin	132	Ononin	45
Betulinic acid	200	Isoliquiritin	21	Oxypaeoniflorin	15
Calycosin	197	Isoliquiritin apioside	1	Paeonidanin	4
Casuarictin	14	Isoononin	1	Paeoniflorigenone	6
Casuariin	14	Isoquercitrin	200	Paeoniflorin	16
Catechin	108	Isoschaftoside	116	Paeoniflorin sulfonate	1
Choerospondin	1	Isotrifoliol	1	Paeonilactone A	4
Dehydroglyasperin C	1	Isoviolanthin	6	Paeonilactone B	3
Desbenzoylpaeoniflorin	1	Kaempferol	1 248	Paeonilactone C	3
Dipropyl phthalate	1	Kaempferol-3-O-methyl ether	1	Paeonin	5
DL-Arabinose	1	Lactiflorin	5	Paeonol	78
D(+)-Glucose	1	Licoarylcoumarin	7	Paeonolide	6
Echinatin	15	Licobenzofuran	2	Paeonoside	7
Ethyl gallate	1	Licochalcone A	7	Palbinone	7
Eurycarpin A	2	Licochalcone B	2	Pedunculagin	24
Formonetin	3	Licochalcone C	1	Pinocembrin	296
Formononetin	1	Licochalcone D	1	Protocatechuic aldehyde	1
Gallic acid	1	Licocoumarone	7	Prunetin	43
Gancaonin G	1	Licoflavonol	1	Pyrethrin Ⅰ	4
Gancaonin H	1	Licoflavone	2	Pyrethrin Ⅱ	3
Gancaonin I	1	Licofuranocoumarin	2	Pyrogallol	36
Gancaonin L	1	Licoisoflavanone	2	Quercetin	2 006
Gancaonin M	1	Licoisoflavone A	6	Rutin	1 483
Gancaonin R	1	Licoisoflavone B	2	Schaftoside	48
Galloyloxypaeoniflorin	2	Licorice saponine A3	2	Sigmoidin B	1
Galloylpaeoniflorin	8	Licorice saponine B2	1	Sitogluside	186
Genkwanin	153	Licorice saponine E2	1	Sitosterol	200
Glabranine	3	Licorice saponine G2	2	Strictinin	69
Glabrene	5	Licorice saponine H2	2	Tellimagrandin Ⅰ	5
Glabridin	6	Licorice saponine J2	1	Topazolin	1
Glabrol	6	Licorice saponine K2	1	Trifolirhizin	1
Glabrolide	3	Licoricidin	5	Uralenin	3
Glabrone	11	Licoricone	2	Uralenol	2
Glicoricone	1	Licorisoflavan A	2	Uralenol-3-methylether	2
Glyasperin A	1	Licuraside	1	Uralsaponin B	1
Glyasperin B	1	Liquiritigenin	50	Uralstilbene	2
Glyasperin C	1	Liquiritin	15	Vestitol	62
Glyasperin D	1	Liquiritin apioside	1	Vicenin-2	9
Glycycoumarin	9	Liquoric acid	2	Violanthin	9
Glycyrin	4	Maackiain	1	1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose	13
Glycyrol	15	Propanedioic acid	1	2-Methylheptane	21
Glycyroside	3	Medicarpin	1	3-Hydroxyglabrol	6
Glycyrrhetinic acid	31	Methyl gallate	1	3, 4-Dihydroxybenzoic acid	200
Glycyrrhetol	2	Mudanpioside D	2	4', 7-Dihydroxy-flavone	1
Glycyrrhisoflavanone	1	Mudanpioside E	2	5-Desgalloylstachyurin	4
Glycyrrhizic acid	10	Mudanpioside F	1	7-Methoxy-4'-hydroxyflavone	1
Glypallichalcone	2	Mudanpioside H	3	7-Methoxy-4'-hydroxyflavonol	1
Glyzaglabrin	2	Mudanpioside J	3	22β-Acetoxyl-glycyrrhizin	1
Hederagenin	121	Narcissin	153
Hexadecanoic acid	200		Naringenin	188

Factor layer	Factor layer weight/%	Control layer	Control layer weight/%	Comprehensive weight/%
F1-Effectiveness	59	C1-Number of literatures	67.60	39.88
C2-Experimental data	32.40	19.12
F2-Testability	31	C3-Number of literatures	18.90	5.86
C4-Proportion of HPLC	14.17	4.39
C5-Component content	27.58	8.55
C6-Component variability	14.48	4.49
C7-Transfer rate	24.88	7.71
F3-Specificity	10	C8-Related herbs	100	10

Factor layer	Factor layer weight/%	Control layer	Control layer weight/%	Comprehensive weight/%
F1-Effectiveness	59	C1-Number of literatures	67.60	39.88
C2-Experimental data	32.40	19.12
F2-Testability	31	C3-Number of literatures	18.90	5.86
C4-Proportion of HPLC	14.17	4.39
C5-Component content	27.58	8.55
C6-Component variability	14.48	4.49
C7-Transfer rate	24.88	7.71
F3-Specificity	10	C8-Related herbs	100	10

No.	Comprehensive score	Compound	Molecular formula	Molecular weight	Content/%	Source
1	2 158.622	Paeoniflorin	C₂₃H₂₈O₁₁	480.466	5.081 ± 1.211	Paeoniae Radix Alba
2	1 556.520	Quercetin	C₁₅H₁₀O₇	302.236	0.047 ± 0.020	Glycyrrhizae Radix et Rhizoma
3	760.819	Albiflorin	C₂₃H₂₈O₁₁	480.466	1.143 ± 0.299	Paeoniae Radix Alba
4	601.291	Glycyrrhizic acid	C₄₂H₆₂O₁₆	822.942	2.965 ± 3.251	Glycyrrhizae Radix et Rhizoma
5	577.120	Naringenin	C₁₅H₁₂O₅	272.253	0.092 ± 0.026	Glycyrrhizae Radix et Rhizoma
6	561.751	Liquiritin	C₂₁H₂₂O₉	418.395	0.361 ± 0.057	Glycyrrhizae Radix et Rhizoma
7	480.958	Oxypaeoniflorin	C₂₃H₂₈O₁₂	496.461	0.135 ± 0.061	Paeoniae Radix Alba
8	441.305	Benzoylpaeoniflorin	C₃₀H₃₂O₁₂	584.571	0.106 ± 0.021	Paeoniae Radix Alba
9	365.028	Liquiritigenin	C₁₅H₁₂O₄	256.253	ND	Glycyrrhizae Radix et Rhizoma
10	333.393	Isoliquiritigenin	C₁₅H₁₂O₄	256.253	ND	Glycyrrhizae Radix et Rhizoma

No.	Comprehensive score	Compound	Molecular formula	Molecular weight	Content/%	Source
1	2 158.622	Paeoniflorin	C₂₃H₂₈O₁₁	480.466	5.081 ± 1.211	Paeoniae Radix Alba
2	1 556.520	Quercetin	C₁₅H₁₀O₇	302.236	0.047 ± 0.020	Glycyrrhizae Radix et Rhizoma
3	760.819	Albiflorin	C₂₃H₂₈O₁₁	480.466	1.143 ± 0.299	Paeoniae Radix Alba
4	601.291	Glycyrrhizic acid	C₄₂H₆₂O₁₆	822.942	2.965 ± 3.251	Glycyrrhizae Radix et Rhizoma
5	577.120	Naringenin	C₁₅H₁₂O₅	272.253	0.092 ± 0.026	Glycyrrhizae Radix et Rhizoma
6	561.751	Liquiritin	C₂₁H₂₂O₉	418.395	0.361 ± 0.057	Glycyrrhizae Radix et Rhizoma
7	480.958	Oxypaeoniflorin	C₂₃H₂₈O₁₂	496.461	0.135 ± 0.061	Paeoniae Radix Alba
8	441.305	Benzoylpaeoniflorin	C₃₀H₃₂O₁₂	584.571	0.106 ± 0.021	Paeoniae Radix Alba
9	365.028	Liquiritigenin	C₁₅H₁₂O₄	256.253	ND	Glycyrrhizae Radix et Rhizoma
10	333.393	Isoliquiritigenin	C₁₅H₁₂O₄	256.253	ND	Glycyrrhizae Radix et Rhizoma

基于层次分析-熵权法的中药质量标志物量化辨识方法研究——以芍药甘草汤为例

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冯利梅 , 陈艳琰 ^* , 乐世俊 , 徐顶巧 , 付瑞嘉 , 杨洁 , 唐于平 *

药学学报 | 研究论文 2021,56(1): 296-305

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药学学报 | 研究论文 2021, 56(1): 296-305

基于层次分析-熵权法的中药质量标志物量化辨识方法研究——以芍药甘草汤为例

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冯利梅, 陈艳琰^*, 乐世俊, 徐顶巧, 付瑞嘉, 杨洁, 唐于平*

作者信息

陕西中医药大学陕西省中医药管理局中药配伍重点研究室, 陕西西安 712046

通讯作者:

*陈艳琰, Tel: 86-29-38184350, E-mail: chenyanyan59@163.com

唐于平, E-mail: yupingtang@sntcm.edu.cn

Quantitative identification of TCM Q-markers based on analytical hierarchy and the entropy weight comprehensive method by taking Shaoyao Gancao decoction as an example

Li-mei FENG, Yan-yan CHEN^*, Shi-jun LE, Ding-qiao XU, Rui-jia FU, Jie YANG, Yu-ping TANG*

Affiliations

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi'an 712046, China

出版时间: 2021-01-12 doi: 10.16438/j.0513-4870.2020-1412

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摘要

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中药质量标志物是近年来中药质量研究的热点, 虽有较多相关探讨与研究实践, 但如何科学合理地表征质量标志物仍未有突破性进展。本文尝试建立了基于层次分析(analytic hierarchy process, AHP)-熵权法的中药质量标志物辨识方法, 在构建涵盖目标层、要素层、控制层的评价体系基础上, 首先采用AHP法对中药成分有效性、可测性、特有性3个核心质量属性进行权重分析, 其次对各属性下的具体指标基于文献和实验数据应用熵权法进行分析, 得到各具体指标的权重后加权计算各成分的综合评分并排序, 从而确认中药质量标志物。采用该方法以解痉止痛经典名方芍药甘草汤为例进行研究, 结果发现其质量标志物重要性排序靠前的8个成分为: 芍药苷 > 槲皮素 > 芍药内酯苷 > 甘草酸 > 柚皮素 > 甘草苷 > 氧化芍药苷 > 苯甲酰芍药苷, 为相关方剂质量标准建立与全程质量控制提供了重要支撑。该研究也为中药质量标志物的量化评价与精准辨识提供了创新思路与方法。

关键词

层次分析法 / 熵权法 / 质量标志物 / 量化辨识 / 芍药甘草汤

Abstract

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The quality markers(Q-markers) of traditional Chinese medicine(TCM) have become a topic of interest in TCM research in recent years. Nonetheless, there is still no consensus on how to scientifically characterize TCM Q-markers. Our study establishes an identification method for TCM Q-markers based on the analytical hierarchy process(AHP) and the entropy weight comprehensive method. By constructing an evaluation system encompassing the target layer, the factor layer and the control layer, AHP can be used to analyze the weight of three core TCM quality attributes, including effectiveness, testability and specificity. Following that, the entropy weight method is employed to analyze the specific indicators for each attribute based on the literature and experimental data. Finally, the comprehensive weight of each index is obtained by combining the two weights, and the comprehensive weight and the specific value of each component is multiplied and summed to obtain the integrated score ranking, and thereby identify the TCM Q-markers. Taking Shaoyao Gancao decoction as an example, the analysis revealed that the top 8 components are as follows: paeoniflorin > quercetin > albiflorin > glycyrrhizic acid > naringenin > liquiritin > oxypaeoniflorin > benzoylpaeoniflorin, and can be identified as Q-markers of Shaoyao Gancao decoction. This study not only provides support for the establishment of quality standards and process quality control of TCM formulae, but also provides innovative ideas and methods for quantitative evaluation and accurate identification of TCM Q-markers.

Key words

analytic hierarchy process / entropy weight method / Q-marker / quantitative identification / Shaoyao Gancao decoction

引用本文

冯利梅, 陈艳琰, 乐世俊, 徐顶巧, 付瑞嘉, 杨洁, 唐于平. 基于层次分析-熵权法的中药质量标志物量化辨识方法研究——以芍药甘草汤为例. 药学学报, 2021 , 56 (1) : 296 -305 . DOI: 10.16438/j.0513-4870.2020-1412

Li-mei FENG, Yan-yan CHEN, Shi-jun LE, Ding-qiao XU, Rui-jia FU, Jie YANG, Yu-ping TANG. Quantitative identification of TCM Q-markers based on analytical hierarchy and the entropy weight comprehensive method by taking Shaoyao Gancao decoction as an example[J]. Acta Pharmaceutica Sinica, 2021 , 56 (1) : 296 -305 . DOI: 10.16438/j.0513-4870.2020-1412

正文

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中药质量是保障中药产业可持续发展的生命线, 而中药质量标准的研究与应用是关系到中医药科学和产业发展的国家战略问题^[1]。中药质量研究是一项复杂的系统工程, 近年来, 中药质量研究水平虽然有了长足的进步, 但仍未能满足人民群众日益提高的对质量安全与可控的要求。《中华人民共和国药典》是目前国内重要质量标准控制的基础, 许多是通过测定一种或几种成分的含量评价中药质量, 是否真实地反映了其质量特点被许多学者所质疑。中药质量控制指标与中药的传统功效的关联性不强、质量控制指标的专属性差、质量研究系统性差、重复性研究等现象, 一直是从药材到成药全过程质量控制和发展的共性问题。

基于此, 刘昌孝团队^[2]于2016年提出了“中药质量标志物(quality markers, Q-markers)”这一中药质量控制的新概念, 明确了质量标志物的基本条件: ①存在于中药材和中药产品中固有的次生代谢物, 或加工制备过程中形成的化学物质; ②来源于某药材(饮片)特有的化学物质; ③有明确的化学结构和生物活性; ④可以进行定性鉴别和定量测定的物质; ⑤按中医配伍组成的方剂“君”药首选原则, 兼顾“臣”、“佐”、“使”药的代表性物质。2019年张铁军等^[3]再次解析了中药质量标志物的科学内涵, 并从“有效性”、“特有性”、“传递与溯源”、“配伍环境”以及“可测性”五个方面概述了质量标志物的核心理论和研究方法。近年来中药质量标志物已成为中药质量研究的前沿和热点, 业内学者也纷纷在研究模式、方法和示范性研究等方面进行了广泛的探讨与实践。然而大多数研究工作者仅对中药化学成分特有性、有效性、可测性进行一定的分析预测, 但如何将这些碎片化信息进行有机的整合, 得到中药质量标志物全貌信息和重要性排序是需要适宜的技术与方法才能解决。

通过对中药质量研究的认识与长期实践, 本课题组提出了“以有效性为核心, 以可测性和特有性为条件, 复方中药结合配伍关系, 遴选确认中药质量标志物, 进而考察其传递与溯源的功能属性”的中药质量标志物研究思路^[4]。基于此, 本文旨在构建一个中药质量标志物量化评价体系, 首先采用层次分析法(analytic hierarchy process, AHP)对一级指标有效性、可测性和特有性进行权重分析, 其次在各一级指标下应用熵权法对有文献及实验数据支撑的二级指标进行分析, 计算指标层各因素的权重后加权计算各成分的综合得分并排序, 并以芍药甘草汤作为示范性研究对象, 希望建立一个中药质量标志物量化辨识与系统确认的方法, 以服务于中药产品全程质量控制。

材料与方法

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中药质量标志物综合评判指标体系构建 通过对中药质量标志物辨识目标问题分析, 结合专家打分、文献调研及实验数据, 最终确定了质量标志物综合评判体系。该体系包括目标层、要素层、控制层, 其中, 目标层为质量标志物量化辨识, 要素层包括有效性、可测性、特有性3个方面, 控制层包括8项指标, 数据来源于文献或实验, 如可根据文献对效应成分报道篇数及实验中效应成分的排序数据评价有效性, 根据成分测定文章数、成分测定方法难易程度、成分含量、成分变异系数、成分转移率等评价可测性, 根据成分在植物种、属、科不同层面是否特有评价特有性, 综合以上即为中药质量标志物核心评判体系。若为复方配伍, 可结合配伍关系进一步分析, 提高质量控制的针对性, 聚焦中药质量标志物, 其综合评价体系如图 1所示。

中药质量标志物综合评价方法 中药质量标志物是存在于中药材和中药产品(饮片、中药煎剂、中药提取物、中成药制剂等)中固有的或加工制备过程中形成的、与中药的功能属性密切相关的化学物质, 作为反映中药有效性和安全性的标示性物质进行质量控制^[2]。因此, 中药质量标志物的判别需要将化学成分的有效性、可测性、特有性等多项指标信息加以汇集, 得到一个综合指标从整体来评价, 这就需应用多指标综合评价方法。

目前国内外提出的综合评价方法不断丰富, 已有几十种之多, 但总体上可归为两大类: 主观赋权评价法和客观赋权评价法。前者多是采取定性的方法, 由专家根据经验进行主观判断而得到权数, 如Delphi法、AHP法、模糊综合评判法等; 后者根据指标之间的变异系数或相关关系来确定权数, 如熵权法、CITRIC法、TOPSIS法、灰色关联度法等^[5]。

本文应用AHP-熵权法, 对质量标志物体系中的一级指标采用基于专家评分的主观赋权法(AHP法)进行权重分析, 在各一级指标下对有文献及实验数据支撑的二级指标应用客观赋权法(熵权法)进行权重分析, 计算指标层各因素的权重后加权计算各成分的综合得分并排序, 从而实现对中药质量标志物的量化辨识。

层次分析法计算要素层权重 AHP法是一种定性和定量有机结合的科学决策方法, 将决策者依靠主观经验来判断的定性问题进行量化评价^[6]。在本研究中将专家对中药质量标志物各要素重要性的认识给予量化, 从而评价中药成分的有效性、可测性、特有性等一级指标的权重。AHP法通过分析复杂系统所包含的因素及相关关系, 将问题条理化、层次化, 构造一个层次分析结构模型, 将每一层次的各要素两两比较, 按照一定的标度理论, 得到相对重要程度的比较标度并建立判断矩阵, 计算判断矩阵的最大特征值及其特征向量, 得到各层次要素对上层次某要素的重要性次序, 从而建立权重向量^[7]。AHP法计算中药质量标志物要素层各权重的方法如下:

① 行业专家打分建立判断矩阵。根据中药质量标志物综合评价指标体系, 将要素层F中的指标进行两两比较, 邀请三位行业专家根据1~5标度方法对判断矩阵A的要素a_ij进行对比并赋值, 构建判断矩阵A, 如图 2。

② 计算各指标权重。计算各判断矩阵的最大特征根λ_max以及权向量W, 即可得到本层次各要素相对于上一层次质量标志物的相对重要性。以判断矩阵A为例, 根据式2将判断矩阵A的各列做归一化处理, 再根据式3求判断矩阵A各行之和, 即各指标权向量W, 根据式4对W进行标准化处理得w, 即各评价指标权重。

③ 一致性检验。为验证得到的权向量是否合理, 还需对判断矩阵进行一致性检验, 保证可以在接受范围之内, 即式中一致性比率CR < 0.1, 才能满足一致性要求。式6中, λ_max为根据式5求得的最大特征根, RI为随机一致性指标(取值为: n=1, RI=0;n=2, RI=0;n=3, RI=0.52;n=4, RI=0.89;n=5, RI=1.12)。

(1)$\mathrm{A}=\left(a_{i j}\right)_{n \times n}, a_{j i}=1 / a_{i j}(i, j=1, 2, \cdots, n)$

(2)$\bar{a}_{i j}=a_{i j} / \sum\limits_{i=1}^{n} a_{i j}(i, j=1, 2, \cdots, n)$

(3)$W_{i}=\sum\limits_{j=1}^{n} \bar{a}_{i j}(i=1, 2, \cdots, n)$

(4)$w_{i}=W_{i} / \sum\limits_{i=1}^{n} W_{i}(i=1, 2, \cdots, n)$

(5)$\lambda_{\max }=\frac{1}{n} \sum\limits_{i=1}^{n} \frac{\mathrm{A} W}{W_{i}}(i=1, 2, \cdots, n)$

(6)$\mathrm{CR}=\frac{\lambda_{\max }-n}{(n-1) \mathrm{RI}}$

对构建的判断矩阵A求解w, 见式7, 最大特征根λ_max=3.00, 一致性比率CR=0 < 0.1, 满足一致性要求。即有效性、可测性、特有性的权重为59%、31%、10%。

(7)$\begin{aligned} \mathrm{A} &=\left[\begin{array}{ccc}1 & 1 / 5 & 5 / 18 \\ 5 & 1 & 7 / 3 \\ 11 / 3 & 4 / 9 & 1\end{array}\right] \rightarrow \mathrm{A} W=\left[\begin{array}{l}0.30 \\ 1.77 \\ 0.93\end{array}\right] \rightarrow \\ w &=\left[\begin{array}{l}0.10 \\ 0.59 \\ 0.31\end{array}\right] \end{aligned}$

熵权法计算控制层权重 熵权法是一种客观赋权法, 用来判断某个指标的离散程度, 离散程度越大, 该指标对综合评价的影响越大。熵是不确定性的一种度量。信息量越大, 不确定性就越小, 熵也就越小; 信息量越小, 不确定性越大, 熵也越大^[8]。因而利用熵值携带的信息进行权重计算, 结合各项指标的变异程度, 利用信息熵这个工具, 计算出各项指标的权重, 为多指标综合评价提供依据。

根据建立的中药质量标志物综合评价体系指标, 可知要素层F的指标集是有n个评价指标组成的集合, 研究区域是由m个成分组成的集合, 由此可形成原始矩阵Y=(y_ij)_m×n, 先根据式8进行标准化处理得到标准化矩阵P=(p_ij)_m×n, 再根据式9计算第j个指标信息熵H_j, 根据计算得到的各指标信息熵按照式10转化为熵权w_j, 即得各评价指标的熵值。

(8)$p_{i j}=y_{i j} / \sum\limits_{i=1}^{m} y_{i j}(i=1, 2, \cdots, m ; j=1, 2, \cdots, n)$

(9)$H_{j}=-k \sum\limits_{i=1}^{m} p_{i j} \ln \left(p_{i j}\right) \quad k=1 / \ln (m)$

(10)$w_{i}=\left(1-H_{j}\right) /\left(\sum\limits_{j=1}^{n} H_{j}\right)$

层次分析/熵权法结合确定指标综合权重 将运用AHP法得到的指标权重与熵权法得到的指标熵权相结合, 得到权重之后还需要计算出综合得分, 即将具体值与权重值进行相乘后累加, 计算各成分的重要性排序用于中药质量标志物的辨识, 若为复方, 可结合配伍关系进一步分析评价。

结果

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以芍药甘草汤为例, 基于上述构建的层次分析/熵权法综合评判体系对其质量标志物进行了辨识采用AHP量化评价, 得到有效性、可测性、特有性一级指标的权重分别为59%、31%、10%。在各一级指标下应用熵权法对有文献及实验数据支撑的二级指标进行分析, 具体如下。

1 芍药甘草汤有效性成分分析

质量控制的根本目的是对中药有效性的确定, 因此“有效性”是中药质量标志物的核心要素^[3]。本研究选取芍药甘草汤主要功效止痛作用表征其有效性, 采用熵权法, 对由文献统计所得止痛成分数据以及由实验所得成分与止痛功效的皮尔逊相关数据的原始矩阵, 经标准化、求信息熵、求熵权, 获得有效性下二级指标文献数据和实验数据的权重, 为芍药甘草汤质量标志物辨识提供有效性的科学量化指标。

检索2000年1月至2020年7月万方数据库、中国期刊全文数据库(CNKI)、及Pub Med数据库中, 芍药甘草汤止痛作用的实验性研究文献。以“芍药甘草汤”或“Shaoyao Gancao decoction”、“疼痛”或“止痛”或“relieve pain”、芍药甘草汤中常见成分等为检索词, 纳入实验性研究文献, 排除综述类文献、临床个案、病例报告等, 最终筛选出165篇国内外相关文献, 以此作为芍药甘草汤止痛有效性的数据。如Wang等^[9]研究了芍药甘草汤镇痛的药效物质, 经分析得到芍药苷、氧化芍药苷、芍药内酯苷、苯甲酰芍药苷、甘草酸、甘草苷、异甘草苷、甘草素、异甘草素对止痛功效表现出明显的调节作用。通过此种方法查阅并统计文献, 分析发现: 芍药苷、芍药内酯苷、甘草酸、甘草苷、氧化芍药苷、苯甲酰芍药苷、柚皮素、甘草素、芍药花苷、异甘草素、槲皮素、异甘草苷、没食子酸、甘草次酸、芹糖甘草苷、丹皮酚、芒柄花黄素、1, 2, 3, 4, 6-五-O-没食子酰-β-D-葡萄糖、柚皮苷、白桦脂酸、苯甲酸、儿茶素、山柰酚、甘草利酮、甘草黄酮、异甘草黄酮醇等成分与止痛功效密切相关。各发挥止痛功效的活性成分在文献中出现的次数越多, 说明该成分与止痛功效越密切, 有效性越好, 各成分出现的频次如表 1所示。本课题研究组前期进行了芍药甘草汤治疗神经病理性疼痛的实验研究, 并采用皮尔逊相关分析筛选出了芍药甘草汤中与疼痛密切相关的化学成分^[10], 相关系数越高, 与疼痛关系越密切, 包括芍药内酯苷、没食子酰芍药苷、去苯甲酰芍药苷、丹皮酚、白芍内酯C、苯甲酸、原儿茶酸、异甘草素、芒柄花黄素、甘草皂苷E2、甘草皂苷A3、甘草查耳酮B、异夏佛塔苷、4', 7-二羟基黄酮、去氢粗毛甘草素C、新甘草酚、欧甘草素A、乌拉尔醇、sigmoidin B、vestitol、红车轴草根苷、美迪紫檀素、黄宝石羽扇豆素、松属素、芳香膜菊素、高丽槐素、山柰酚-3-O-甲醚等, 数据如表 1所示。采用熵权法, 根据公式7~9, 计算得到文献数据和实验数据的权重分别为67.60%和32.40%。

2 芍药甘草汤可测性成分分析

质量标志物最终是为建立中药质量标准服务的, 从质量标志物应用的角度, 成分的“可测性”是必备条件^[11]。基于测定文章数、测定方法难易程度、成分含量均值、成分含量变异性、药材-方剂转移率5个方面的考察及分级评分, 为中药质量标志物辨识提供可测性方面的量化评分数据。

检索2000年1月至2020年7月万方数据库、CNKI及Pubmed数据库中, 白芍、炙甘草和芍药甘草汤含量测定的实验性研究文献。以“白芍”或“Paeoniae Radix Alba”、“炙甘草”或“Glycyrrhizae Radix et Rhizoma”、“芍药甘草汤”或“Shaoyao Gancao decotion”、“含量”或“content”为检索词, 纳入实验性研究文献, 排除综述类文献、测定入血成分的文献等, 最终筛选出201篇国内外相关文献, 以此作为芍药甘草汤可测性的数据。白芍和炙甘草药材中主要成分的含量测定的文章数越多, 说明该成分可测性强; 成分的检测方法包括HPLC、UPLC、UPLC-Q-TOF-MS等, 统计HPLC检测方法的占比情况, 若统计的占比越大, 说明测定方法比较容易; 各成分的含量均值越大, 说明含量越高, 各成分的变异系数, 体现该成分在不同批次药材中的变化, 若变异系数越大, 说明该成分含量更需要限定; 各化学成分存在于药材-方剂中含量的转移率越大, 说明该成分能体现方剂药效的可能性越大。经芍药甘草汤的统计数据发现: 测定文章数排名前三依次为芍药苷(54次) > 甘草酸(31次) > 甘草苷(30次), 但经过测定芍药甘草汤的含量发现, 其含量由高到低依次为: 芍药苷 > 甘草酸 > 甘草苷, 结果说明测定文章数、测定方法难易程度、成分含量均值之间的确存在一定的关联性, 但含量的高低顺序不一定是测定文章数的高低。根据各评价指标包含的原始矩阵, 数据见表 2, 经由标准化、求信息熵、求熵权, 即公式7~9, 计算得到测定文章数、测定方法、药材含量均值、药材含量变异性、药材-方剂转移率的权重分别为18.90%、14.17%、27.58%、14.48%和24.88%。

3 芍药甘草汤特有性成分分析

一个好的中药质量评价方法或质量标准应具有对特定药材的“针对性”和“专属性”, 才能避免“张冠李戴”、“以假乱真”^[11]。因此, “特有性”对中药质量标志物的辨识也不可或缺。

白芍为毛茛科植物芍药Paeonia lactiflora Pall.的干燥根, 主要含单萜及其苷类、三萜类、多元酚类、黄酮类等成分^[12]。芍药P. lactiflora源于毛茛科Ranunculaceae芍药亚科Subfam. Paeonioideae芍药属Paeonia。毛茛科有约50属, 2 000余种。芍药属分为2个组, 芍药组Sect. Paeonia和牡丹组Sect. Moutan, 芍药组约30种, 主要分布在欧、亚大陆温带地区, 少数种类也产美洲, 我国有8种: 芍药P. lactiflora、窄叶芍药P. anomala、多花芍药P. emodi、美丽芍药P. mairei、草芍药P. obovata、新疆芍药P. sinjiangensis、白花芍药P. sterniana、川赤芍P. veitchii。牡丹组3种, 分布于我国西南部和西北部, 牡丹P. suffruticosa、野牡丹P. delavayi、四川牡丹P. szechuanica。目前已经从芍药属中分离出单萜及其苷类成分约65种, 具有系统分类学价值的是芍药苷、芍药内酯苷、氧化芍药苷、苯甲酰芍药苷等。单萜及其苷类不同结构类型的化合物在各种群中的分布情况可以反映出这些种群之间的亲缘关系及进化状况。

甘草为豆科多年生草本植物甘草Glycyrrhiza uralensis Fisch.、胀果甘草G. inflata Bat.或光果甘草G. glabra L.的干燥根及根茎, 其中以甘草G. uralensis为主要来源。甘草主要含有三萜皂苷类、黄酮类、香豆素类、多糖类、生物碱类、挥发性成分、氨基酸类成分等^[13]。甘草源于豆科Leguminosae蝶形花亚科Papilionoideae甘草属Glycyrrhiza。豆科有约650属, 18 000种。豆科下级分3个亚科, 云实亚科Caesalpinioideae、含羞草亚科Mimosoideae、蝶形花亚科Papilionoideae。甘草属分为2组, 甘草组Sect. Glycyrrhiza和刺果甘草组Sect. Pseudoglycyrrhiza, 约20余种, 分布全球各大洲, 以欧亚大陆为多。甘草组在我国有5种, 甘草G. uralensis、胀果甘草G. inflata、粗毛甘草G. aspera、无腺毛甘草G. eglandulosa、光果甘草G. glabra。刺果甘草组在我国有3种, 刺果甘草G. pallidiflora、圆果甘草G. squamulosa、云南甘草G. yunnanensis。目前已经从甘草属中分离出黄酮类成分约254种, 具有系统分类学价值的是甘草苷、异甘草苷、甘草素、异甘草素、芹糖甘草苷和芹糖异甘草苷等成分。从甘草属种分离出三萜皂苷类成分约32种, 具有系统分类学价值的是甘草酸、甘草次酸、甘草皂苷、白桦脂酸等。三萜皂苷类和黄酮类不同结构类型的化合物在各种群中的分布情况可以反映出这些种群之间的亲缘关系及进化状况。

在明确中药化学物质组的前提下, 通过化学成分的生源途径及特有性分析, 选择具有代表性、特异性的化学成分, 可提高中药质量控制的针对性和指向性。本文以芍药和甘草中的各成分为关键词, 检索中药与有效成分数据库(http://www.organchem.csdb.cn/scdb/main/slogin.asp)、中国天然产物化学成分库(http://www.pharmdata.ac.cn/cnpconline/usercenter.asp)、TCMSP(http://tcmspw.com/tcmsp.php)、TM-MC (http://infor-matics.kiom.re.kr/compound)、TCMID (http://119.3.41.228:8000/tcmid/)、NPASS (http://bidd2.nus.edu.sg/NPASS)、ETCM (http://www.nrc.ac.cn:9090/ETCM/index.php/Home/Index)、Symmap (https://www.symmap.org)数据库, 可发现这些成分存在于多少种植物中, 数值越低, 表明该化学成分的特有性越强。相关数据如表 3所示。

4 基于有效性、可测性与特有性整合评分的芍药甘草汤质量标志物量化辨识

根据成分有效性、可测性与特有性评分, 将运用AHP得到的一级指标权重与熵权法得到的二级指标熵权相结合得到综合权重值, 如表 4所示, 再将具体值与综合权重值相乘后累加, 即得整合评分排序, 从而发现芍药甘草汤的质量标志物。

综合评分后, 分值排名靠前的10个成分为: 芍药苷 > 槲皮素 > 芍药内酯苷 > 甘草酸 > 柚皮素 > 甘草苷 > 氧化芍药苷 > 苯甲酰芍药苷 > 甘草素 > 异甘草素, 为了验证该方法的正确性和可测性, 通过高效液相色谱法测定了3个批次芍药甘草汤中这10个成分的含量(批次1:安徽白芍-甘肃乌拉尔甘草; 批次2:河南白芍-新疆乌拉尔甘草; 批次3:浙江白芍-内蒙古乌拉尔甘草。三批白芍经陕西中医药大学颜永刚教授鉴定均为毛茛科植物芍药Paeonia lactiflora Pall.的干燥根, 三批甘草经鉴定均为豆科植物甘草Glycyrrhiza uralensis Fisch.的干燥根和根茎)。结果表明, 排名前八的成分含量均可测出, 位于第九位和第十位的甘草素和异甘草素低于检测限, 分析原因可能是因为两者均为黄酮苷元, 作者在提取芍药甘草汤的时候遵循古方, 以水为溶剂, 而苷元极性较低, 在水溶液中难以煎出, 所以导致芍药甘草汤中未能测出甘草素和异甘草素的含量。最终选择排名前八的成分(芍药苷、槲皮素、芍药内酯苷、甘草酸、柚皮素、甘草苷、氧化芍药苷和苯甲酰芍药苷)为芍药甘草汤的质量标志物, 具体信息见表 5。

讨论

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中药质量是中医临床疗效的保障, 中药质量标准决定着中药有效性和安全性。中药质量研究和质量标准的建立是一项复杂的系统工程, 如何研究和制定标准有不同方法, 也有不同意见和认识。刘昌孝基于中医药体系的特点, 整合多学科知识, 提出核心质量概念——中药质量标志物, 以此统领中药质量研究, 为中药的质量体系建立与应用提供了新的思路^[14]。本文围绕中药成分有效性、可测性、特有性3个核心属性采用AHP-熵权法进行分析, 综合评判其质量标志物, 提出了中药质量标志物研究的一个具体实施路径与策略方法, 并成功应用于经典名方芍药甘草汤质量标志物发现与确认。一级指标有效性、可测性和特有性的权重根据行业专家对这三个核心要素重要性的认识而打分确定, 虽然具有一定的主观性, 但采用AHP法可有效地将主观指标定量化, 既吸收了主观的逻辑判断和分析, 又发挥客观的精确计算和推演, 从而使决策过程更科学、评价结果更可信。有效性、可测性和特有性的二级指标采用熵权法评价, 客观性较强, 但各指标体系中指标数据所蕴含的信息量也影响着最终评价结果。以本文分析的芍药甘草汤为例, 从有效性来说, 如所纳入统计范围的文献数量相对较少, 且部分数据有缺失; 其特有性的统计来源于各数据库, 而每个数据库量的大小也影响了其特有性的准确性。最理想的应该是各要素的权重应由客观性的数值确定, 纳入统计范围的文献数据量越大越准确, 并选择数据较全的文献, 从数据库的结果体现成分特有性的时候, 应选择数据库量大, 且所含数量均衡的数据库, 减小导致结果不准确的因素。该研究突出了中药质量标志物量化辨识的概念, 其方法与策略可推广应用于其他中药与复方质量标志物研究。

中药成分结构复杂多样, 同一味中药可能会因不同配伍表现出不同的药效^[12], 合理的配伍往往能起到增效、减毒等作用^[3]。因此, 研究对象若为中药复方, 在进行质量标志物整体评价时除上述重点关注的有效性、可测性和特有性三个属性, 将配伍因素纳入分析可能也是有必要的, 应考虑到方中各药的君臣佐使配伍原则、药物配伍比例、成分配伍相互作用等因素。本研究中作为综合权重排名第一的芍药苷和第六的甘草苷就有联用研究报道, 如Guo等^[15]研究了芍药苷和甘草苷联合使用的药代动力学和镇痛作用, 并与芍药苷和甘草苷单独使用进行了比较。结果表明, 芍药苷和甘草苷组合给药后, 达到最大血浆浓度所需的时间远远小于芍药苷和甘草苷单独使用, 相比较单独应用, 芍药苷和甘草苷组合的吸收迅速, 能明显增大神经病理性疼痛的机械痛阈值。Sun等^[16]研究也证明芍药苷与甘草酸联合给药后有协同作用, 疗效更为显著。中药成分配伍相互作用非常复杂, 目前仅是一些碎片化的研究报道, 如进行系统的成分配伍研究设计, 其研究结果也可纳入质量标志物确定的一个因素, 以进一步实现中药质量标志物的精准辨识。

本文所构建的质量标志物综合评判指标体系对于中药质量的综合评价具有较好的普适性。对于中药的特定功效, 有效性数据来源聚焦于对应功效的文献和实验数据即可, 如本文以芍药甘草汤的止痛功效为例, 结合可测性和特有性, 确定了芍药甘草汤发挥止痛功效效的的质质量量标标志志物物。。但但大大多多数数中中药药具具有有多多功功效效的的特特点点, , 如2020版《中国药典》中记载甘草有补脾益气、清热解毒、祛痰止咳、缓急止痛、调和诸药的功效, 此时一级指标有效性、可测性、特有性不变, 只需在有效性的二级指标中根据各功效的数据源权重评分即可。通过构建合理的质量评价体系, 能很好地体现中药质量标志物整体性、系统性和可量化的优势, 从而对质量标志物进行重要性排序, 发挥其在中药质量综合评价方面的作用。

质量是中药产业的生命线, 中药质量诸多问题是阻碍中药现代化、国际化的瓶颈之一^[17]。中药成分复杂、作用广泛, 成分间相互影响, 整体药效不是单一成分药效的简单加合, 而是成分间多维度、多层次的非线性协同作用的结果^[18]。中药质量标志物的提出, 着眼于全过程的中药成分特有、差异、动态变化和质量的传递性、溯源性, 有利于建立中药全程质量控制及质量溯源体系^[19]。本文整合中药成分有效性、可测性、特有性三大核心要素, 构建质量标志物系统评价体系, 首次建立了AHP-熵权法综合评判的中药质量标志物量化辨识方法, 并成功应用于经典名方芍药甘草汤质量标志物研究, 为中药质量标志物的量化评价与精准辨识提供了创新思路与方法, 为有力提升中药质量控制水平提供支撑。

作者贡献: 冯利梅查阅文献、撰写文章、修改文章; 陈艳琰指导撰写思路、撰写文章、修改文章; 乐世俊、徐顶巧、付瑞嘉和杨洁指导文章修改; 唐于平指导撰写思路和文章修改。

利益冲突: 本文无任何利益冲突。

基金

收起

陕西省重点研发计划项目(2019SF-300)
陕西省重点研发计划项目(2019ZDLSF04-05)
陕西中医药大学学科创新团队项目(2019-YL10)
陕西高校青年创新团队(2020)
陕西省青年科技新星培育计划(2021)

参考文献

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文献

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参考文献引证文献

排序方式：

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Zhang TJ, Bai G, Liu CX. The concept, core theory and research methods of Chinese medicine quality markers[J]. Acta Pharm Sin(药学学报), 2019, 54: 187-196. https://www.cnki.com.cn/Article/CJFDTOTAL-YXXB201902002.htm

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Guo JY, Zhang ZB, Sun QY. Study and applications of analytic hierarchy process[J]. China Saf Sci J(中国安全科学学报), 2008, 18: 148-153. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGRK201701015.htm

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Cheng QY. Structure entropy weight method to confirm the weight of evaluating index[J]. Syst Eng-Theory Pract(系统工程理论与实践), 2010, 30: 1225-1228.

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Wang M, Yan YH, Zou HQ, et al. Analgesic effects of Shaoyao Gancao Tang and the correlation between analgesic effects and compatibility proportion[J]. Chin J Tradit Chin Med Pharm(中华中医药杂志), 2015, 30: 1767-1773. https://www.cnki.com.cn/Article/CJFDTOTAL-DYJD401.015.htm

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Feng LM, Chen YY, Xu DQ, et al. An integrated strategy for discovering effective components of Shaoyao Gancao decoction for treating neuropathic pain by the combination of partial leastsquares regression and multi-index comprehensive method[J]. JEthnopharmacol, 2020, 260: 113050.

https://doi.org/10.1016/j.jep.2020.113050

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Zhang TJ, Bai G, Chen CQ, et al. Research approaches of quality marker(Q-marker)of Chinese materia medica formula based on"five principles"[J]. Chin Tradit Herb Drugs(中草药), 2018, 49: 1-13. https://www.cnki.com.cn/Article/CJFDTOTAL-JCKJ199301005.htm

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Ye XW, Xia LT, Ren HM, et al. Research progress on processing history evolution, chemical constituents and pharmacological action of Paeoniae Radix Alba[J]. Chin Tradit Herb Drugs(中草药), 2020, 51: 1951-1969. https://www.cnki.com.cn/Article/CJFDTOTAL-JCKJ199301005.htm

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Sun Z. Research progress on chemical constituents of Glycyrrhiza uralensis Fisch[J]. Sci Technol Inf(科技资讯), 2020, 18: 64-65. https://www.cnki.com.cn/Article/CJFDTOTAL-SJKF201805007.htm

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Zhang TJ, Xu J, Han YQ, et al. Quality markers research on Chinese materia medica: quality evaluation and quality standards of Corydalis Rhizoma[J]. Chin Tradit Herb Drugs(中草药), 2016, 47: 1458-1467. https://www.cnki.com.cn/Article/CJFDTOTAL-JCKJ199301005.htm

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Guo QY, Li WJ, Wang C, et al. Biomolecular network-based synergistic drug combination discovery: a combination of paeoniflorin and liquiritin alleviates neuropathic pain by inhibiting neuroinflammation via suppressing the chemokine signaling pathway[J]. Signal Transduct Target Ther, 2020, 5: 73.

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Sun YM, Yang Y, Li D, et al. Effect of paeoniflorin on the pharmacokinetics of glycyrrhizic acid and glycyrrhetinic acid in rats[J]. Chin Pharm J(中国药学杂志), 2012, 47: 599-603. https://www.cnki.com.cn/Article/CJFDTOTAL-JCKJ199202004.htm

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2021年第56卷第1期

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doi: 10.16438/j.0513-4870.2020-1412

接收时间：2020-08-27
首发时间：2025-12-18
出版时间：2021-01-12

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文章信息

作者

出版历史

收稿日期：2020-08-27
修回日期：2020-10-23

基金

陕西省重点研发计划项目(2019SF-300)

陕西省重点研发计划项目(2019ZDLSF04-05)

陕西中医药大学学科创新团队项目(2019-YL10)

陕西高校青年创新团队(2020)

陕西省青年科技新星培育计划(2021)

作者信息

陕西中医药大学陕西省中医药管理局中药配伍重点研究室, 陕西西安 712046

通讯作者:

*陈艳琰, Tel: 86-29-38184350, E-mail: chenyanyan59@163.com

唐于平, E-mail: yupingtang@sntcm.edu.cn

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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Compound	Number of literature	Experimental data		Compound	Number of literature	Experimental data
Albiflorin	19	0.60		Licoricone	1	-
Benzoic acid	1	0.66	Liquiritigenin	9	-
Benzoylpaeoniflorin	11	-	Liquiritin	14	-
Betulinic acid	2		Liquiritin apioside	1	-
Catechin	3	-	Maackiain	-	0.50
Dehydroglyasperin C	-	0.67	Medicarpin	-	0.58
Desbenzoylpaeoniflorin	-	0.58	Naringenin	14	-
DL-Arabinose	-	0.63	Naringin	7
D(+)-Glucose	2	0.75	Neoglycyrol	-	0.67
Formonetin	3	0.63	Odoratin	-	0.58
Gallic acid	5	-	Oxypaeoniflorin	12	-
Galloylpaeoniflorin	-	0.55	Paeoniflorin	54	-
Glycyrrhetinic acid	3	-	Paeonilactone C	-	0.71
Glycyrrhizic acid	15	-	Paeonin	11	-
Hispaglabridin A	-	0.65	Paeonol	10	0.63
Isolicoflavonol	1	-	Pinocembrin	-	0.71
Isoliquiritigenin	8	0.71	Quercetin	34	-
Isoliquiritin	8	-	Sigmoidin B	-	0.65
Isoschaftoside	-	0.77	Topazolin	-	0.80
Kaempferol	3	-	Trifolirhizin	-	0.62
Kaempferol-3-O-methyl ether	-	0.50	Uralenol	-	0.54
Licochalcone B	-	0.55	Vestitol	-	0.61
Licoflavone	1	-	1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose	1	-
Licorice saponin A3	-	0.56	3, 4-Dihydroxybenzoic acid	-	0.61
Licorice saponine E2	-	0.82		4', 7-Dihydroxy-flavone	-	0.70

Compound

Number of
literature

Experimental
data

Compound

Number of
literature

Experimental
data

Albiflorin

0.60

Licoricone

Benzoic acid

0.66

Liquiritigenin

Benzoylpaeoniflorin

Liquiritin

Betulinic acid

Liquiritin apioside

Catechin

Maackiain

0.50

Dehydroglyasperin C

0.67

Medicarpin

0.58

Desbenzoylpaeoniflorin

0.58

Naringenin

DL-Arabinose

0.63

Naringin

D(+)-Glucose

0.75

Neoglycyrol

0.67

Formonetin

0.63

Odoratin

0.58

Gallic acid

Oxypaeoniflorin

Galloylpaeoniflorin

0.55

Paeoniflorin

Glycyrrhetinic acid

Paeonilactone C

0.71

Glycyrrhizic acid

Paeonin

Hispaglabridin A

0.65

Paeonol

0.63

Isolicoflavonol

Pinocembrin

0.71

Isoliquiritigenin

0.71

Quercetin

Isoliquiritin

Sigmoidin B

0.65

Isoschaftoside

0.77

Topazolin

0.80

Kaempferol

Trifolirhizin

0.62

Kaempferol-3-O-methyl ether

0.50

Uralenol

0.54

Licochalcone B

0.55

Vestitol

0.61

Licoflavone

1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose

Licorice saponin A3

0.56

3, 4-Dihydroxybenzoic acid

0.61

Licorice saponine E2

0.82

4', 7-Dihydroxy-flavone

0.70

Compound	Number of literature	Proportion of HPLC/%	Component content/%	Component variability	Transfer rate/%
Albiflorin	28	0.786	0.643	0.578	0.366
Albiflorin R1	1	1.000	0.001	0.148	-
Benzoic acid	11	0.818	0.012	0.469	-
Benzoyloxypaeoniflorin	1	1.000	0.001	0.189	-
Benzoylpaeoniflorin	21	0.762	0.047	0.651	0.363
Catechin	10	0.700	0.065	1.251	-
D(+)-Glucose	1	-	0.519	0.164	-
Ethyl gallate	1	-	0.007	0.363	-
Formononetin	1	1.000	0.029	0.520	0.027
Gallic acid	20	0.750	0.201	0.278	-
Galloylpaeoniflorin	1	1.000	0.029	0.107	0.852
Glabridin	8	0.875	0.121	0.599	-
Glycycoumarin	2	0.001	0.084	0.608	-
Glycyrrhetinic acid	17	0.765	0.083	0.201	-
Glycyrrhizic acid	31	0.742	2.503	0.251	0.217
Glycyrrhizic acid ammonium salt	2	1.000	3.228	0.187	-
Glypallichalcone	1	1.000	0.024	1.200	-
Homopterocarpin	1	0.001	0.009	-	-
Isoglycyrol	1	0.001	0.007	0.297	-
Isoliquiritigenin	16	0.750	0.013	0.466	0.316
Isoliquiritin	11	0.818	0.095	0.386	0.366
Isoliquiritin apioside	8	0.750	0.119	0.563	0.301
Licochalcone A	8	0.750	0.017	0.409	-
Licochalcone B	2	0.500	0.042	1.373	-
Licochalcone C	1	0.001	-	-	-
Licorice saponine A3	1	-	0.110	0.155	-
Licorice saponine G2	3	0.667	1.272	0.088	-
Liquiritigenin	17	0.765	0.040	0.411	0.725
Liquiritin	30	0.767	1.243	0.308	0.253
Liquiritin apioside	8	0.750	0.493	0.380	0.392
Propanedioic acid	-	-	0.623	0.446	-
Methyl gallate	6	0.833	0.258	0.469	-
Mudanpioside F	1	1.000	0.007	0.272	-
Naringenin-7-O-β-D-glucoside	-	-	0.066	0.412	-
Ononin	1	1.000	0.080	0.677	0.287
Oxyalbiflorin	1	1.000	0.015	0.086	-
Oxypaeonidanin	1	1.000	0.011	0.076	-
Oxypaeoniflorin	14	0.857	0.111	0.549	0.074
Paeonidanin	1	1.000	0.004	0.223	-
Paeoniflorin	54	0.778	3.244	0.160	0.250
Paeoniflorin sulfonate	3	0.667	1.371	0.640	-
Paeonol	6	0.667	0.004	0.597	-
Protocatechuic aldehyde	1	1.000	0.026	1.081	-
Uralsaponin B	3	1.000	1.396	0.130	-
α-D-Lactose monohydrate	-	-	17.380	0.044	-
β-D-Fructopyranose	-	-	1.213	0.019	-
1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose	13	0.692	1.094	0.358	0.048
3, 4-Dihydroxybenzoic acid	2	0.500	0.015	0.450	-
4-O-Methyl-oxypaeoniflorin	1	1.000	0.023	0.111	-
4-O-Methyl-paeoniflorin	1	1.000	0.002	1.358	-
10-Hydroxypaeoniflorin	1	1.000	0.025	0.045	-
22β-Acetoxyl-glycyrrhizin	1	-	0.103	0.408	-

Compound

Number of
literature

Proportion of HPLC/%

Component
content/%

Component
variability

Transfer
rate/%

Albiflorin

0.786

0.643

0.578

0.366

Albiflorin R1

1.000

0.001

0.148

Benzoic acid

0.818

0.012

0.469

Benzoyloxypaeoniflorin

1.000

0.001

0.189

Benzoylpaeoniflorin

0.762

0.047

0.651

0.363

Catechin

0.700

0.065

1.251

D(+)-Glucose

0.519

0.164

Ethyl gallate

0.007

0.363

Formononetin

1.000

0.029

0.520

0.027

Gallic acid

0.750

0.201

0.278

Galloylpaeoniflorin

1.000

0.029

0.107

0.852

Glabridin

0.875

0.121

0.599

Glycycoumarin

0.001

0.084

0.608

Glycyrrhetinic acid

0.765

0.083

0.201

Glycyrrhizic acid

0.742

2.503

0.251

0.217

Glycyrrhizic acid ammonium salt

1.000

3.228

0.187

Glypallichalcone

1.000

0.024

1.200

Homopterocarpin

0.001

0.009

Isoglycyrol

0.001

0.007

0.297

Isoliquiritigenin

0.750

0.013

0.466

0.316

Isoliquiritin

0.818

0.095

0.386

0.366

Isoliquiritin apioside

0.750

0.119

0.563

0.301

Licochalcone A

0.750

0.017

0.409

Licochalcone B

0.500

0.042

1.373

Licochalcone C

0.001

Licorice saponine A3

0.110

0.155

Licorice saponine G2

0.667

1.272

0.088

Liquiritigenin

0.765

0.040

0.411

0.725

Liquiritin

0.767

1.243

0.308

0.253

Liquiritin apioside

0.750

0.493

0.380

0.392

Propanedioic acid

0.623

0.446

Methyl gallate

0.833

0.258

0.469

Mudanpioside F

1.000

0.007

0.272

Naringenin-7-O-β-D-glucoside

0.066

0.412

Ononin

1.000

0.080

0.677

0.287

Oxyalbiflorin

1.000

0.015

0.086

Oxypaeonidanin

1.000

0.011

0.076

Oxypaeoniflorin

0.857

0.111

0.549

0.074

Paeonidanin

1.000

0.004

0.223

Paeoniflorin

0.778

3.244

0.160

0.250

Paeoniflorin sulfonate

0.667

1.371

0.640

Paeonol

0.667

0.004

0.597

Protocatechuic aldehyde

1.000

0.026

1.081

Uralsaponin B

1.000

1.396

0.130

α-D-Lactose monohydrate

17.380

0.044

β-D-Fructopyranose

1.213

0.019

1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose

0.692

1.094

0.358

0.048

3, 4-Dihydroxybenzoic acid

0.500

0.015

0.450

4-O-Methyl-oxypaeoniflorin

1.000

0.023

0.111

4-O-Methyl-paeoniflorin

1.000

0.002

1.358

10-Hydroxypaeoniflorin

1.000

0.025

0.045

22β-Acetoxyl-glycyrrhizin

0.103

0.408

Compound	Related herb		Compound	Related herb		Compound	Related herb
Albiflorin	12		Hispaglabridin A	5		Naringenin-7-O-β-D-glucoside	1
Albiflorin R1	2	Hispaglabridin B	7	Naringin	134
Apiopaeonoside	4	Homopterocarpin	1	Neoglycyrol	4
Astragalin	707	Isoglabrolide	1	Neoisoliquiritin	2
Benzoic acid	200	Isoglycyrol	7	Odoratin	1
Benzoyloxypaeoniflorin	2	Isolicoflavonol	1	Oleanolic acid	200
Benzoylpaeoniflorin	13	Isoliquiritigenin	132	Ononin	45
Betulinic acid	200	Isoliquiritin	21	Oxypaeoniflorin	15
Calycosin	197	Isoliquiritin apioside	1	Paeonidanin	4
Casuarictin	14	Isoononin	1	Paeoniflorigenone	6
Casuariin	14	Isoquercitrin	200	Paeoniflorin	16
Catechin	108	Isoschaftoside	116	Paeoniflorin sulfonate	1
Choerospondin	1	Isotrifoliol	1	Paeonilactone A	4
Dehydroglyasperin C	1	Isoviolanthin	6	Paeonilactone B	3
Desbenzoylpaeoniflorin	1	Kaempferol	1 248	Paeonilactone C	3
Dipropyl phthalate	1	Kaempferol-3-O-methyl ether	1	Paeonin	5
DL-Arabinose	1	Lactiflorin	5	Paeonol	78
D(+)-Glucose	1	Licoarylcoumarin	7	Paeonolide	6
Echinatin	15	Licobenzofuran	2	Paeonoside	7
Ethyl gallate	1	Licochalcone A	7	Palbinone	7
Eurycarpin A	2	Licochalcone B	2	Pedunculagin	24
Formonetin	3	Licochalcone C	1	Pinocembrin	296
Formononetin	1	Licochalcone D	1	Protocatechuic aldehyde	1
Gallic acid	1	Licocoumarone	7	Prunetin	43
Gancaonin G	1	Licoflavonol	1	Pyrethrin Ⅰ	4
Gancaonin H	1	Licoflavone	2	Pyrethrin Ⅱ	3
Gancaonin I	1	Licofuranocoumarin	2	Pyrogallol	36
Gancaonin L	1	Licoisoflavanone	2	Quercetin	2 006
Gancaonin M	1	Licoisoflavone A	6	Rutin	1 483
Gancaonin R	1	Licoisoflavone B	2	Schaftoside	48
Galloyloxypaeoniflorin	2	Licorice saponine A3	2	Sigmoidin B	1
Galloylpaeoniflorin	8	Licorice saponine B2	1	Sitogluside	186
Genkwanin	153	Licorice saponine E2	1	Sitosterol	200
Glabranine	3	Licorice saponine G2	2	Strictinin	69
Glabrene	5	Licorice saponine H2	2	Tellimagrandin Ⅰ	5
Glabridin	6	Licorice saponine J2	1	Topazolin	1
Glabrol	6	Licorice saponine K2	1	Trifolirhizin	1
Glabrolide	3	Licoricidin	5	Uralenin	3
Glabrone	11	Licoricone	2	Uralenol	2
Glicoricone	1	Licorisoflavan A	2	Uralenol-3-methylether	2
Glyasperin A	1	Licuraside	1	Uralsaponin B	1
Glyasperin B	1	Liquiritigenin	50	Uralstilbene	2
Glyasperin C	1	Liquiritin	15	Vestitol	62
Glyasperin D	1	Liquiritin apioside	1	Vicenin-2	9
Glycycoumarin	9	Liquoric acid	2	Violanthin	9
Glycyrin	4	Maackiain	1	1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose	13
Glycyrol	15	Propanedioic acid	1	2-Methylheptane	21
Glycyroside	3	Medicarpin	1	3-Hydroxyglabrol	6
Glycyrrhetinic acid	31	Methyl gallate	1	3, 4-Dihydroxybenzoic acid	200
Glycyrrhetol	2	Mudanpioside D	2	4', 7-Dihydroxy-flavone	1
Glycyrrhisoflavanone	1	Mudanpioside E	2	5-Desgalloylstachyurin	4
Glycyrrhizic acid	10	Mudanpioside F	1	7-Methoxy-4'-hydroxyflavone	1
Glypallichalcone	2	Mudanpioside H	3	7-Methoxy-4'-hydroxyflavonol	1
Glyzaglabrin	2	Mudanpioside J	3	22β-Acetoxyl-glycyrrhizin	1
Hederagenin	121	Narcissin	153
Hexadecanoic acid	200		Naringenin	188

Compound

Related herb

Compound

Related herb

Compound

Related herb

Albiflorin

Hispaglabridin A

Naringenin-7-O-β-D-glucoside

Albiflorin R1

Hispaglabridin B

Naringin

134

Apiopaeonoside

Homopterocarpin

Neoglycyrol

Astragalin

707

Isoglabrolide

Neoisoliquiritin

Benzoic acid

200

Isoglycyrol

Odoratin

Benzoyloxypaeoniflorin

Isolicoflavonol

Oleanolic acid

200

Benzoylpaeoniflorin

Isoliquiritigenin

132

Ononin

Betulinic acid

200

Isoliquiritin

Oxypaeoniflorin

Calycosin

197

Isoliquiritin apioside

Paeonidanin

Casuarictin

Isoononin

Paeoniflorigenone

Casuariin

Isoquercitrin

200

Paeoniflorin

Catechin

108

Isoschaftoside

116

Paeoniflorin sulfonate

Choerospondin

Isotrifoliol

Paeonilactone A

Dehydroglyasperin C

Isoviolanthin

Paeonilactone B

Desbenzoylpaeoniflorin

Kaempferol

1 248

Paeonilactone C

Dipropyl phthalate

Kaempferol-3-O-methyl ether

Paeonin

DL-Arabinose

Lactiflorin

Paeonol

D(+)-Glucose

Licoarylcoumarin

Paeonolide

Echinatin

Licobenzofuran

Paeonoside

Ethyl gallate

Licochalcone A

Palbinone

Eurycarpin A

Licochalcone B

Pedunculagin

Formonetin

Licochalcone C

Pinocembrin

296

Formononetin

Licochalcone D

Protocatechuic aldehyde

Gallic acid

Licocoumarone

Prunetin

Gancaonin G

Licoflavonol

Pyrethrin Ⅰ

Gancaonin H

Licoflavone

Pyrethrin Ⅱ

Gancaonin I

Licofuranocoumarin

Pyrogallol

Gancaonin L

Licoisoflavanone

Quercetin

2 006

Gancaonin M

Licoisoflavone A

Rutin

1 483

Gancaonin R

Licoisoflavone B

Schaftoside

Galloyloxypaeoniflorin

Licorice saponine A3

Sigmoidin B

Galloylpaeoniflorin

Licorice saponine B2

Sitogluside

186

Genkwanin

153

Licorice saponine E2

Sitosterol

200

Glabranine

Licorice saponine G2

Strictinin

Glabrene

Licorice saponine H2

Tellimagrandin Ⅰ

Glabridin

Licorice saponine J2

Topazolin

Glabrol

Licorice saponine K2

Trifolirhizin

Glabrolide

Licoricidin

Uralenin

Glabrone

Licoricone

Uralenol

Glicoricone

Licorisoflavan A

Uralenol-3-methylether

Glyasperin A

Licuraside

Uralsaponin B

Glyasperin B

Liquiritigenin

Uralstilbene

Glyasperin C

Liquiritin

Vestitol

Glyasperin D

Liquiritin apioside

Vicenin-2

Glycycoumarin

Liquoric acid

Violanthin

Glycyrin

Maackiain

1, 2, 3, 4, 6-penta-O-Galloyl-β-D-glucose

Glycyrol

Propanedioic acid

2-Methylheptane

Glycyroside

Medicarpin

3-Hydroxyglabrol

Glycyrrhetinic acid

Methyl gallate

3, 4-Dihydroxybenzoic acid

200

Glycyrrhetol

Mudanpioside D

4', 7-Dihydroxy-flavone

Glycyrrhisoflavanone

Mudanpioside E

5-Desgalloylstachyurin

Glycyrrhizic acid

Mudanpioside F

7-Methoxy-4'-hydroxyflavone

Glypallichalcone

Mudanpioside H

7-Methoxy-4'-hydroxyflavonol

Glyzaglabrin

Mudanpioside J

22β-Acetoxyl-glycyrrhizin

Hederagenin

121

Narcissin

153

Hexadecanoic acid

200

Naringenin

188

Factor layer	Factor layer weight/%	Control layer	Control layer weight/%	Comprehensive weight/%
F1-Effectiveness	59	C1-Number of literatures	67.60	39.88
C2-Experimental data	32.40	19.12
F2-Testability	31	C3-Number of literatures	18.90	5.86
C4-Proportion of HPLC	14.17	4.39
C5-Component content	27.58	8.55
C6-Component variability	14.48	4.49
C7-Transfer rate	24.88	7.71
F3-Specificity	10	C8-Related herbs	100	10

Factor layer

Factor layer weight/%

Control layer

Control layer weight/%

Comprehensive weight/%

F1-Effectiveness

C1-Number of literatures

67.60

39.88

C2-Experimental data

32.40

19.12

F2-Testability

C3-Number of literatures

18.90

5.86

C4-Proportion of HPLC

14.17

4.39

C5-Component content

27.58

8.55

C6-Component variability

14.48

4.49

C7-Transfer rate

24.88

7.71

F3-Specificity

C8-Related herbs

100

No.	Comprehensive score	Compound	Molecular formula	Molecular weight	Content/%	Source
1	2 158.622	Paeoniflorin	C₂₃H₂₈O₁₁	480.466	5.081 ± 1.211	Paeoniae Radix Alba
2	1 556.520	Quercetin	C₁₅H₁₀O₇	302.236	0.047 ± 0.020	Glycyrrhizae Radix et Rhizoma
3	760.819	Albiflorin	C₂₃H₂₈O₁₁	480.466	1.143 ± 0.299	Paeoniae Radix Alba
4	601.291	Glycyrrhizic acid	C₄₂H₆₂O₁₆	822.942	2.965 ± 3.251	Glycyrrhizae Radix et Rhizoma
5	577.120	Naringenin	C₁₅H₁₂O₅	272.253	0.092 ± 0.026	Glycyrrhizae Radix et Rhizoma
6	561.751	Liquiritin	C₂₁H₂₂O₉	418.395	0.361 ± 0.057	Glycyrrhizae Radix et Rhizoma
7	480.958	Oxypaeoniflorin	C₂₃H₂₈O₁₂	496.461	0.135 ± 0.061	Paeoniae Radix Alba
8	441.305	Benzoylpaeoniflorin	C₃₀H₃₂O₁₂	584.571	0.106 ± 0.021	Paeoniae Radix Alba
9	365.028	Liquiritigenin	C₁₅H₁₂O₄	256.253	ND	Glycyrrhizae Radix et Rhizoma
10	333.393	Isoliquiritigenin	C₁₅H₁₂O₄	256.253	ND	Glycyrrhizae Radix et Rhizoma

No.

Comprehensive score

Compound

Molecular formula

Molecular weight

Content/%

Source

2 158.622

Paeoniflorin

C₂₃H₂₈O₁₁

480.466

5.081 ± 1.211

Paeoniae Radix Alba

1 556.520

Quercetin

C₁₅H₁₀O₇

302.236

0.047 ± 0.020

Glycyrrhizae Radix et Rhizoma

760.819

Albiflorin

C₂₃H₂₈O₁₁

480.466

1.143 ± 0.299

Paeoniae Radix Alba

601.291

Glycyrrhizic acid

C₄₂H₆₂O₁₆

822.942

2.965 ± 3.251

Glycyrrhizae Radix et Rhizoma

577.120

Naringenin

C₁₅H₁₂O₅

272.253

0.092 ± 0.026

Glycyrrhizae Radix et Rhizoma

561.751

Liquiritin

C₂₁H₂₂O₉

418.395

0.361 ± 0.057

Glycyrrhizae Radix et Rhizoma

480.958

Oxypaeoniflorin

C₂₃H₂₈O₁₂

496.461

0.135 ± 0.061

Paeoniae Radix Alba

441.305

Benzoylpaeoniflorin

C₃₀H₃₂O₁₂

584.571

0.106 ± 0.021

Paeoniae Radix Alba

365.028

Liquiritigenin

C₁₅H₁₂O₄

256.253

Glycyrrhizae Radix et Rhizoma

333.393

Isoliquiritigenin

C₁₅H₁₂O₄

256.253

Glycyrrhizae Radix et Rhizoma