Investigating the Underlying Mechanisms of Ardisia japonica Extract’s Anti-Blood-Stasis Effect via Metabolomics and Network Pharmacology
Abstract
:1. Introduction
2. Results
2.1. Main Components in AJ
2.2. Anti-Blood-Stasis Effect of AJ
2.3. Pathological Section
2.4. Hemorheological Index
2.4.1. Effect on Blood Viscosity
2.4.2. The Impact on Red Blood Cell Aggregation and Deformability Indicators
2.5. Non-Targeted Metabolomics
2.5.1. Stability of Equipment
2.5.2. Principal Component Analysis
2.5.3. Screening and Identification of Potential Biomarkers
2.6. Network Pharmacological Analysis
2.7. Molecular Docking Results
3. Materials and Methods
3.1. Herbal Remedies and Techniques of Preparation
3.2. Experiments on Animals
3.2.1. Animals
3.2.2. Animal Care and Diet
3.2.3. Rat Appearance Index Detection
3.2.4. Metabolomics Blood Sampling
3.3. Analysis of AJ Extract Components
3.4. Analysis of Non-Targeted Metabolomics
3.5. Network Pharmacology and Molecular Docking
3.5.1. Prediction of AJ’s Drug Targets
3.5.2. GO and KEGG Analysis
3.5.3. Molecular Docking
3.6. Statistical Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
Abbreviations
References
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No. | Rt (min) | Name | Formula | Ms/Ms | m/z |
---|---|---|---|---|---|
1 | 11.44 | Arachidonic acid | C20H32O2 | [M − H]− | 303.2325 |
2 | 1.28 | Benzoic acid | C7H6O2 | [M − H]− | 121.0296 |
3 | 11.19 | Isopalmitic acid | C16H32O2 | [M − H]− | 255.2327 |
4 | 0.73 | Kynurenic acid | C10H7NO3 | [M − H]− | 188.0354 |
5 | 12.50 | Linoleic acid | C18H32O2 | [M − H]− | 279.2329 |
6 | 7.57 | Undecanoic acid | C11H22O2 | [M − H]− | 185.1547 |
7 | 1.99 | Galangin | C15H10O5 | [M + H]+ | 271.0597 |
8 | 2.04 | 5,7-Dihydroxychromone | C9H6O4 | [M − H]− | 177.0192 |
9 | 2.59 | Sodium 4-hydroxy-benzoate | C7H6O3 | [M − H]− | 137.0246 |
10 | 1.47 | Myricetin | C21H20O12 | [M + H]+ | 465.1030 |
11 | 4.18 | Demethylwedelolactone | C15H8O7 | [M − H]− | 299.0202 |
12 | 12.86 | Gallic acid | C7H6O5 | [M − H]− | 169.0143 |
13 | 2.14 | Citrate | C6H8O7 | [M − H]− | 191.0195 |
14 | 2.62 | m-Xylene | C8H10 | [M + H]+ | 107.0854 |
15 | 0.61 | Nicotinamide | C6H6N2O | [M + H]− | 123.0551 |
16 | 0.70 | Catechol | C6H6O2 | [M − H]− | 109.0296 |
17 | 0.82 | Methylgallate | C8H8O5 | [M − H]− | 183.0300 |
18 | 11.80 | Oleic acid | C18H34O2 | [M − H]− | 281.2483 |
19 | 12.53 | alpha-Linolenic acid | C18H30O2 | [M + H]+ | 279.2318 |
20 | 0.56 | Adenine | C5H5N5 | [M + H]+ | 136.0618 |
21 | 3.35 | Morin | C15H10O7 | [M + H]+ | 303.0495 |
22 | 0.60 | Nicotinic acid | C6H5NO2 | [M + H]+ | 124.0392 |
23 | 4.20 | Kaempferol | C15H10O6 | [M + H]+ | 287.0546 |
24 | 0.92 | Gentisic acid | C7H6O4 | [M − H]− | 153.0193 |
25 | 3.25 | 4-hydroxyphenylacetic acid | C8H8O3 | [M − H]− | 151.0402 |
26 | 0.03 | Wogonin | C16H12O5 | [M + H]+ | 285.0758 |
27 | 2.15 | Isorhamnetin | C16H12O7 | [M + H]+ | 317.0648 |
28 | 1.33 | Ellagic Acid | C14H6O8 | [M − H]− | 300.9989 |
29 | 0.83 | Caffeine | C8H10N4O2 | [M + H]+ | 195.0875 |
30 | 1.22 | 7,8-Dihydroxycoumarin | C9H6O4 | [M + H]+ | 179.0337 |
31 | 0.80 | Kojic Acid | C6H6O4 | [M + H]+ | 143.0340 |
32 | 2.70 | cuminyl alcohol | C10H14O | [M + H − H2O]− | 133.1012 |
33 | 1.62 | vanillic acid | C8H8O4 | [M − H]− | 167.0351 |
34 | 4.58 | 3,4-Dimethoxybenzaldehyde | C9H10O3 | [M + H]+ | 167.0702 |
35 | 3.36 | Quercetin | C15H10O7 | [M − H]− | 301.0349 |
36 | 11.79 | Fraxetin | C10H8O5 | [M + H]+ | 209.0444 |
37 | 1.55 | Deoxyvasicinone | C11H10N2O | [M + H]+ | 187.0865 |
38 | 11.86 | Phthalic anhydride | C8H4O3 | [M + H]+ | 149.0232 |
39 | 12.29 | 2-Hydroxy-4-methoxybenzaldehyde | C8H8O3 | [M + H]+ | 153.0546 |
40 | 4.03 | Zingerone | C11H14O3 | [M − H]− | 193.0872 |
41 | 1.38 | p-Hydroxy-cinnamic acid | C9H8O3 | [M − H]− | 163.0402 |
42 | 0.85 | Sesamol | C7H6O3 | [M + H]+ | 139.0388 |
43 | 0.67 | Bergenin | [M − H]− | 327.0722 | |
44 | 8.52 | 2-Phenylethyl formate | C9H10O2 | [M + H]+ | 151.0753 |
45 | 7.92 | Di-2-furanylmethane | C9H8O2 | [M + H]+ | 149.0597 |
46 | 1.09 | p-Mentha-1,3,8-triene | C10H14 | [M + H]+ | 135.1167 |
47 | 5.21 | Diethyl-phthalate | C12H14O4 | [M − H]− | 221.0821 |
48 | 1.74 | Caffeic acid | C9H8O4 | [M + H]+ | 181.0494 |
49 | 2.52 | 2′,4′-Dimethylacetophenone | C10H12O | [M + H]+ | 149.0961 |
50 | 13.70 | Pyridoxine | C8H11NO3 | [M + H]+ | 170.0811 |
51 | 4.14 | Thymol | C10H14O | [M + H]+ | 151.1118 |
52 | 2.15 | Quercetin | C21H20O11 | [M − H]− | 447.0933 |
53 | 9.84 | 4-tert-Butylphenol | C10H14O | [M + H]+ | 151.1118 |
54 | 1.75 | 2,4-Dimethylbenzaldehyde | C9H10O | [M + H]+ | 135.0805 |
55 | 0.35 | 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one | C16H12O5 | [M + H]+ | 285.0757 |
56 | 1.97 | P-Anisic acid | C8H8O3 | [M + H]+ | 153.0547 |
57 | 8.36 | 2-Methoxybenzaldehyde | C8H8O2 | [M + H]+ | 137.0598 |
58 | 4.31 | 4-Hydroxybenzoic acid | C7H6O3 | [M + H]+ | 139.0388 |
59 | 4.05 | Dihydrocapsaicin | C18H29NO3 | [M + H]+ | 308.2220 |
60 | 1.59 | Suberic acid | C8H14O4 | [M − H]− | 173.0819 |
61 | 5.25 | 2-Phenylethyl octanoate | C16H24O2 | [M + H]+ | 249.1851 |
62 | 9.90 | Arachidonic acid (not validated) | C20H32O2 | [M + H]+ | 305.2472 |
63 | 3.38 | Flavonol base + 4O, 1MeO | C16H12O8 | [M − H]− | 331.0461 |
64 | 2.22 | Methylisoeugenol | C11H14O2 | [M + H]+ | 179.1065 |
65 | 2.22 | Methylisoeugenol | C11H14O2 | [M + H]+ | 179.1065 |
66 | 1.02 | alpha-Methylstyrene | C9H10 | [M + H]+ | 119.0855 |
67 | 1.71 | 7-Methoxycoumarin | C10H8O3 | [M + H]+ | 177.0545 |
68 | 11.09 | 9-Trans-Palmitelaidic acid | C16H30O2 | [M − H]− | 253.2173 |
69 | 2.86 | Meperidine | C15H21NO2 | [M + H]+ | 248.1642 |
70 | 1.91 | 4-Hydroxyphthalide | C8H6O3 | [M + H]+ | 151.0389 |
71 | 5.81 | Sinensetin | C20H20O7 | [M + H]+ | 373.1286 |
72 | 0.86 | Epicatechin | C15H14O6 | [M − H]− | 289.0718 |
73 | 5.56 | 1-(2-Furanyl)-1-propanone | C7H8O2 | [M + H]+ | 125.0596 |
74 | 0.97 | Piperonylic Acid | C8H6O4 | [M − H]− | 165.0194 |
75 | 0.95 | Xanthoxyline | C10H12O4 | [M + H] | 197.0810 |
76 | 10.06 | Dibutylphthalate | C16H22O4 | [M + H]+ | 279.1585 |
77 | 3.84 | Valerophenone | C11H14O | [M + H]+ | 163.1116 |
78 | 0.67 | Monomethyl phthalate | C9H8O4 | [M + H]+ | 181.0494 |
79 | 0.94 | 2,6-Dimethoxyphenol | C8H10O3 | [M + H]+ | 155.0702 |
80 | 10.12 | Acetophenone | C8H8O | [M + H]+ | 121.0647 |
81 | 1.52 | Rubrofusarin | C15H12O5 | [M + H]+ | 273.0754 |
82 | 13.70 | Methyl 2-aminobenzoate | C8H9NO2 | [M + H]+ | 152.0706 |
83 | 3.19 | Loureirin A | C17H18O4 | [M + H]+ | 287.1280 |
84 | 3.87 | dihydrodamascenone | C13H20O | [M + H]+ | 193.1585 |
85 | 10.83 | 3-(4-Methoxyphenyl)-2-propen-1-ol | C10H12O2 | [M + H]+ | 165.0911 |
86 | 4.69 | Methyl linoleate | C19H34O2 | [M + H] | 295.2631 |
87 | 11.58 | Phenylacetaldehyde | C8H8O | [M + H]+ | 121.0647 |
88 | 6.95 | Atractylodin | C13H10O | [M + H]+ | 183.0806 |
89 | 1.17 | Eugenin | C11H10O4 | [M + H]+ | 207.0650 |
90 | 0.60 | Formononetine | C16H12O4 | [M − H]− | 267.0724 |
91 | 5.84 | Asarylaldehyde | C10H12O4 | [M + H]+ | 197.0810 |
92 | 2.15 | Dimethyl succinate | C6H10O4 | [M + H]+ | 147.0650 |
93 | 0.52 | 1-Hexanethiol | C6H14S | [M + H]+ | 119.0896 |
94 | 0.71 | Indole | C8H7N | [M + H]+ | 118.0649 |
No. | ESI | Rt (min) | Name of Metabolite | Molecular Formula | Molecular Weight | Measured Value | Ms/Ms | Trend |
---|---|---|---|---|---|---|---|---|
1 | − | 7.91 | L-Palmitoyl Carnitine | C23H45NO4 | 399.3349 | 458.3469 | M + CH3COO | ↑ |
2 | − | 2.61 | Quinolinic acid | C7H5NO4 | 167.0219 | 226.0357 | M + CH3COO | ↓ |
3 | − | 0.77 | D-Mannose | C6H12O6 | 180.0634 | 215.0333 | M + Cl | ↓ |
4 | + | 1.47 | 7-Methylxanthine nucleoside | C11H15N4O6 + | 299.099 | 384.0649 | M + K + HCOOH | ↑ |
5 | − | 12.17 | Ceramide | C42H81NO3 | 647.6216 | 706.6345 | M + CH3COO | ↓ |
6 | − | 5 | D-Cysteine | C3H7NO2S | 121.0197 | 241.0389 | 2M − H | ↓ |
7 | − | 7.73 | L-Tartaric acid | C4H6O6 | 150.0164 | 299.0261 | 2M − H | ↓ |
8 | − | 1.57 | L-(-)-3-Phenyl lactic acid | C9H10O3 | 166.063 | 331.1139 | 2M − H | ↑ |
9 | − | 3.31 | 3-Iodotyrosine | C9H10INO3 | 306.9705 | 327.947 | M + Na − 2H | ↓ |
10 | − | 0.76 | L-Glutamine | C5H10N2O3 | 146.0691 | 145.062 | M − H | ↑ |
11 | − | 7.68 | Puromycin | C22H29N7O5 | 471.223 | 523.2173 | M + Cl + NH3 | ↓ |
12 | − | 1.15 | O-Acetyl-L-serine | C5H9NO4 | 147.0532 | 146.0459 | M − H | ↑ |
13 | − | 5.68 | L-Thyroxine | C15H11I4NO4 | 776.6867 | 775.6784 | M − H | ↑ |
14 | − | 10.79 | Neuronic acid | C24H46O2 | 366.3498 | 366.3452 | M− | ↑ |
15 | − | 8.35 | α-Aminopropionitrile | C3H6N2 | 70.0531 | 91.0222 | M + Na-2H | ↓ |
16 | − | 10.06 | 9,12-Octadecatetraenoic acid | C18H28O2 | 276.2089 | 275.2016 | M − H | ↑ |
17 | − | 8.78 | Trichloroethylene epoxide | C2HCl3O | 145.9093 | 197.9061 | M + Cl + NH3 | ↓ |
18 | − | 1.54 | S-sulfo-L-cysteine | C3H7NO5S2 | 200.9766 | 259.9989 | M + CH3COO | ↑ |
19 | − | 3.04 | Molybdate | H2MoO4 | 163.9007 | 326.7945 | 2M − H | ↓ |
20 | − | 2.4 | cis,cis-muconic acid | C6H6O4 | 142.0266 | 163.0926 | M + Na − 2H | ↓ |
21 | − | 3.05 | trichloroacetic acid | C2HCl3O2 | 161.9042 | 160.8968 | M − H | ↓ |
22 | − | 8.6 | 1-Behenoyl-2-hydroxy-sn-glycero-3-phosphocholine | C30H62NO7P | 579.4264 | 638.4395 | M + CH3COO | ↓ |
23 | − | 6.95 | (20S)-Cholesta-5-ene-3beta,17,20-triol | C27H46O3 | 418.3447 | 453.3114 | M + Cl | ↓ |
24 | − | 9.9 | 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine | C40H76NO8P | 729.5309 | 748.5461 | M + F | ↓ |
25 | − | 6.97 | Chlorophyll | C33H32MgN4O3 | 556.2325 | 555.2222 | M − H | ↓ |
26 | − | 12.15 | Glucose ceramide (d18:1/16:0) | C40H77NO8 | 699.5649 | 758.5798 | M + CH3COO | ↑ |
27 | − | 4.48 | Piperidine | C5H11N | 85.0891 | 166.0692 | M + Cl + HCOOH | ↑ |
28 | + | 4.11 | (E)-3-Hexen-1-ol | C6H12O | 100.089 | 218.2116 | 2M + NH4 | ↑ |
29 | + | 5.9 | Sterols | C27H46O | 386.355 | 450.3783 | M + CH3CN + Na | ↓ |
30 | + | 6.54 | Sphingomyelin | C18H39NO2 | 301.298 | 302.3059 | M + H | ↑ |
31 | + | 4.8 | 5β-hydrocortisone | C21H30O5 | 362.209 | 363.2164 | M + H | ↓ |
32 | + | 3.28 | Dimethyl sulfoxide | C2H6O2S | 94.009 | 141.018 | M + HCOO + 2H | ↓ |
33 | + | 0.86 | Dimethyl sulfoxide | C2H6OS | 78.014 | 79.0215 | M + H | ↑ |
34 | + | 2.05 | Thymine | C5H6N2O2 | 126.043 | 127.05 | M + H | ↓ |
35 | + | 0.76 | L-Gulose | C6H12O6 | 180.063 | 383.1162 | 2M + Na | ↓ |
36 | + | 3.28 | Ascorbic acid | C6H8O6 | 176.032 | 353.0712 | 2M + H | ↓ |
37 | + | 1.54 | L-Ascorbic acid | C14H17NO7 | 311.101 | 312.111 | M + H | ↓ |
38 | + | 9.19 | Osteotriol (Vitamin D3) | C27H44O3 | 416.329 | 417.3361 | M + H | ↓ |
39 | + | 1.5 | 3-Hydroxybutyric acid | C4H8O3 | 104.047 | 105.0539 | M + H | ↑ |
40 | + | 1.49 | N-succinyl-LL-2,6-diaminopimelic acid | C11H18N2O7 | 290.111 | 337.1159 | M + HCOO + 2H | ↑ |
41 | + | 2.79 | 5-deoxy-5-methylthioadenosine | C11H15N5O3S | 297.09 | 298.0969 | M + H | ↓ |
42 | + | 1.46 | (2S,3S)-Butane-2,3-diol | C4H10O2 | 90.068 | 73.0647 | M + H − H2O | ↓ |
43 | + | 9.9 | dihomo-γ-linolenic acid | C20H34O2 | 306.256 | 348.2906 | M + CH3CN + H | ↓ |
44 | + | 7.67 | LPC(22:6/0:0) | C30H50NO7P | 567.333 | 569.3326 | M + H | ↓ |
45 | + | 1.49 | Ketodeoxynonanoic acid | C9H16O9 | 268.079 | 233.0672 | M + H − 2H2O | ↑ |
46 | + | 1.47 | 3,7-Dimethyluronic acid | C7H8N4O3 | 196.06 | 265.0532 | M + Na + HCOOH | ↑ |
47 | + | 0.77 | Hydroxyacetone | C3H6O2 | 74.037 | 97.028 | M + Na | ↓ |
48 | + | 12.01 | Oleate | C18H34O2 | 282.256 | 283.2638 | M + H | ↓ |
49 | + | 1.48 | Nicotinamide mononucleotide | C11H15N2O8P | 334.057 | 352.0822 | M + NH4 | ↑ |
50 | + | 12.61 | 5-Hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate | C5H6N4O5 | 202.034 | 316.9047 | M − 2H + 3K | ↑ |
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He, C.; Hao, E.; Du, C.; Wei, W.; Wang, X.; Liu, T.; Deng, J. Investigating the Underlying Mechanisms of Ardisia japonica Extract’s Anti-Blood-Stasis Effect via Metabolomics and Network Pharmacology. Molecules 2023, 28, 7301. https://doi.org/10.3390/molecules28217301
He C, Hao E, Du C, Wei W, Wang X, Liu T, Deng J. Investigating the Underlying Mechanisms of Ardisia japonica Extract’s Anti-Blood-Stasis Effect via Metabolomics and Network Pharmacology. Molecules. 2023; 28(21):7301. https://doi.org/10.3390/molecules28217301
Chicago/Turabian StyleHe, Cuiwei, Erwei Hao, Chengzhi Du, Wei Wei, Xiaodong Wang, Tongxiang Liu, and Jiagang Deng. 2023. "Investigating the Underlying Mechanisms of Ardisia japonica Extract’s Anti-Blood-Stasis Effect via Metabolomics and Network Pharmacology" Molecules 28, no. 21: 7301. https://doi.org/10.3390/molecules28217301