Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy
Keluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of her...
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| Format: | Article |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.728256/full |
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| author | Ling Kong Ye Sun Hui Sun Ai-hua Zhang Bo Zhang Nan Ge Xi-jun Wang |
| author_facet | Ling Kong Ye Sun Hui Sun Ai-hua Zhang Bo Zhang Nan Ge Xi-jun Wang |
| author_sort | Ling Kong |
| collection | DOAJ |
| description | Keluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of herbal medicines and investigating the effective mechanisms. The research results from electroretinography and electron microscope showed that KLX could reduce retinal dysfunction and pathological changes by the DR mouse model. Based on effectiveness, we discovered 64 blood biomarkers of DR by nontargeted metabolomics analysis, 51 of which returned to average levels after KLX treatment including leukotriene D4 and A4, l-tryptophan, 6-hydroxymelatonin, l-phenylalanine, l-tyrosine, and gamma-linolenic acid (GLA). The metabolic pathways involved were phenylalanine metabolism, steroid hormone biosynthesis, sphingolipid metabolism, etc. Adenosine monophosphate-activated protein kinase (AMPK), extracellular signal-regulated protein kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K), and protein 70 S6 kinase (p70 S6K) might be potential targets of KLX against DR. This was related to the mammalian target of rapamycin (mTOR) signaling and AMPK signaling pathways. We applied the chinmedomics strategy, integrating serum pharm-chemistry of traditional Chinese medicine (TCM) with metabolomics, to discover astragaloside IV (AS-IV), emodin, rhein, chrysophanol, and other compounds, which were the core effective constituents of KLX when against DR. Our study was the first to apply the chinmedomics strategy to discover the effective constituents of KLX in the treatment of DR, which fills the gap of unclear effective constituents of KLX. In the next step, the research of effective constituents can be used to optimize prescription preparation, improve the quality standard, and develop an innovative drug. |
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| last_indexed | 2024-12-13T01:12:32Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-3af14191a6194297b9fe2e6f0ccc187d2022-12-22T00:04:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-03-011310.3389/fphar.2022.728256728256Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic RetinopathyLing KongYe SunHui SunAi-hua ZhangBo ZhangNan GeXi-jun WangKeluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of herbal medicines and investigating the effective mechanisms. The research results from electroretinography and electron microscope showed that KLX could reduce retinal dysfunction and pathological changes by the DR mouse model. Based on effectiveness, we discovered 64 blood biomarkers of DR by nontargeted metabolomics analysis, 51 of which returned to average levels after KLX treatment including leukotriene D4 and A4, l-tryptophan, 6-hydroxymelatonin, l-phenylalanine, l-tyrosine, and gamma-linolenic acid (GLA). The metabolic pathways involved were phenylalanine metabolism, steroid hormone biosynthesis, sphingolipid metabolism, etc. Adenosine monophosphate-activated protein kinase (AMPK), extracellular signal-regulated protein kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K), and protein 70 S6 kinase (p70 S6K) might be potential targets of KLX against DR. This was related to the mammalian target of rapamycin (mTOR) signaling and AMPK signaling pathways. We applied the chinmedomics strategy, integrating serum pharm-chemistry of traditional Chinese medicine (TCM) with metabolomics, to discover astragaloside IV (AS-IV), emodin, rhein, chrysophanol, and other compounds, which were the core effective constituents of KLX when against DR. Our study was the first to apply the chinmedomics strategy to discover the effective constituents of KLX in the treatment of DR, which fills the gap of unclear effective constituents of KLX. In the next step, the research of effective constituents can be used to optimize prescription preparation, improve the quality standard, and develop an innovative drug.https://www.frontiersin.org/articles/10.3389/fphar.2022.728256/fullchinmedomicspharmacological effectsbioactive compoundsherbal medicinebiomarkers |
| spellingShingle | Ling Kong Ye Sun Hui Sun Ai-hua Zhang Bo Zhang Nan Ge Xi-jun Wang Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy Frontiers in Pharmacology chinmedomics pharmacological effects bioactive compounds herbal medicine biomarkers |
| title | Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy |
| title_full | Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy |
| title_fullStr | Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy |
| title_full_unstemmed | Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy |
| title_short | Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy |
| title_sort | chinmedomics strategy for elucidating the pharmacological effects and discovering bioactive compounds from keluoxin against diabetic retinopathy |
| topic | chinmedomics pharmacological effects bioactive compounds herbal medicine biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.728256/full |
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