Chemical Constituents and Hypoglycemic Mechanisms of <i>Dendrobium nobile</i> in Treatment of Type 2 Diabetic Rats by UPLC-ESI-Q-Orbitrap, Network Pharmacology and In Vivo Experimental Verification
This study aimed to systematically explore the chemical constituents of <i>D. nobile</i> and its hypoglycemic effect by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experiment. The chemical constituents of <i>D. nobile</i> were qualitatively analyzed, and the hypogly...
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MDPI AG
2023-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/6/2683 |
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| author | Zhaoyang Li Meiling Zeng Keyong Geng Donna Lai Zhi Xu Wei Zhou |
| author_facet | Zhaoyang Li Meiling Zeng Keyong Geng Donna Lai Zhi Xu Wei Zhou |
| author_sort | Zhaoyang Li |
| collection | DOAJ |
| description | This study aimed to systematically explore the chemical constituents of <i>D. nobile</i> and its hypoglycemic effect by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experiment. The chemical constituents of <i>D. nobile</i> were qualitatively analyzed, and the hypoglycemic compounds were quickly identified. Network pharmacological analysis and molecular docking technique were applied to assist in the elucidation of the hypoglycemic mechanisms of <i>D. nobile</i>. A type 2 diabetic mellitus (T2DM) rat model was established using the HFD and STZ method for in vivo experimental verification, and these T2DM rats were treated with <i>D. nobile</i> extract and <i>D. nobile</i> polysaccharide for two months by gavage. The results showed that a total of 39 chemical constituents of <i>D. nobile</i>, including alkaloids, bibenzyls, phenanthrenes and other types of compounds, were identified. <i>D. nobile</i> extract and <i>D. nobile</i> polysaccharide could significantly ameliorate the body weight, hyperglycemia, insulin resistance, dyslipidemia and morphological impairment of the liver and pancreas in the T2DM rats. α-Linolenic acid, dihydroconiferyl dihydro-p-coumarate, naringenin, <i>trans-N</i>-feruloyltyramine, gigantol, moscatilin, 4-<i>O</i>-methylpinosylvic acid, venlafaxine, nordendrobin and tristin were regarded as the key hypoglycemic compounds of <i>D. nobile</i>, along with the hypoglycemic effect on the PI3K-AKT signaling pathway, the insulin signaling pathway, the FOXO signaling pathway, the improvement of insulin resistance and the AGE-RAGE signaling pathway. The Western blotting experiment results confirmed that <i>D. nobile</i> activated the PI3K/AKT pathway and insulin signaling pathway, promoted glycogen synthesis via regulating the expression of glycogen synthase kinase 3 beta (GSK-3β) and glucose transporter 4 (GLUT4), and inhibited liver gluconeogenesis by regulating the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6pase) in the liver. The results suggested that the hypoglycemic mechanism of <i>D. nobile</i> might be associated with liver glycogen synthesis and gluconeogenesis, contributing to improving insulin resistance and abnormal glucose metabolism in the T2DM rats. |
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| spelling | doaj.art-6f522a0e3cae4610a41abed9a37e95d22023-11-17T12:53:44ZengMDPI AGMolecules1420-30492023-03-01286268310.3390/molecules28062683Chemical Constituents and Hypoglycemic Mechanisms of <i>Dendrobium nobile</i> in Treatment of Type 2 Diabetic Rats by UPLC-ESI-Q-Orbitrap, Network Pharmacology and In Vivo Experimental VerificationZhaoyang Li0Meiling Zeng1Keyong Geng2Donna Lai3Zhi Xu4Wei Zhou5School of Pharmacy, Guizhou Medical University, Guiyang 550025, ChinaSchool of Pharmacy, Guizhou Medical University, Guiyang 550025, ChinaSchool of Pharmacy, Guizhou Medical University, Guiyang 550025, ChinaSchool of Medicine, Western Sydney University, Penrith, NSW 2751, AustraliaGuizhou Miaoaitang Health Management Co., Ltd., Guiyang 550025, ChinaSchool of Pharmacy, Guizhou Medical University, Guiyang 550025, ChinaThis study aimed to systematically explore the chemical constituents of <i>D. nobile</i> and its hypoglycemic effect by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experiment. The chemical constituents of <i>D. nobile</i> were qualitatively analyzed, and the hypoglycemic compounds were quickly identified. Network pharmacological analysis and molecular docking technique were applied to assist in the elucidation of the hypoglycemic mechanisms of <i>D. nobile</i>. A type 2 diabetic mellitus (T2DM) rat model was established using the HFD and STZ method for in vivo experimental verification, and these T2DM rats were treated with <i>D. nobile</i> extract and <i>D. nobile</i> polysaccharide for two months by gavage. The results showed that a total of 39 chemical constituents of <i>D. nobile</i>, including alkaloids, bibenzyls, phenanthrenes and other types of compounds, were identified. <i>D. nobile</i> extract and <i>D. nobile</i> polysaccharide could significantly ameliorate the body weight, hyperglycemia, insulin resistance, dyslipidemia and morphological impairment of the liver and pancreas in the T2DM rats. α-Linolenic acid, dihydroconiferyl dihydro-p-coumarate, naringenin, <i>trans-N</i>-feruloyltyramine, gigantol, moscatilin, 4-<i>O</i>-methylpinosylvic acid, venlafaxine, nordendrobin and tristin were regarded as the key hypoglycemic compounds of <i>D. nobile</i>, along with the hypoglycemic effect on the PI3K-AKT signaling pathway, the insulin signaling pathway, the FOXO signaling pathway, the improvement of insulin resistance and the AGE-RAGE signaling pathway. The Western blotting experiment results confirmed that <i>D. nobile</i> activated the PI3K/AKT pathway and insulin signaling pathway, promoted glycogen synthesis via regulating the expression of glycogen synthase kinase 3 beta (GSK-3β) and glucose transporter 4 (GLUT4), and inhibited liver gluconeogenesis by regulating the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6pase) in the liver. The results suggested that the hypoglycemic mechanism of <i>D. nobile</i> might be associated with liver glycogen synthesis and gluconeogenesis, contributing to improving insulin resistance and abnormal glucose metabolism in the T2DM rats.https://www.mdpi.com/1420-3049/28/6/2683<i>Dendrobium nobile</i>diabetes mellitushypoglycemic mechanismUPLC-ESI-Q-Orbitrap |
| spellingShingle | Zhaoyang Li Meiling Zeng Keyong Geng Donna Lai Zhi Xu Wei Zhou Chemical Constituents and Hypoglycemic Mechanisms of <i>Dendrobium nobile</i> in Treatment of Type 2 Diabetic Rats by UPLC-ESI-Q-Orbitrap, Network Pharmacology and In Vivo Experimental Verification Molecules <i>Dendrobium nobile</i> diabetes mellitus hypoglycemic mechanism UPLC-ESI-Q-Orbitrap |
| title | Chemical Constituents and Hypoglycemic Mechanisms of <i>Dendrobium nobile</i> in Treatment of Type 2 Diabetic Rats by UPLC-ESI-Q-Orbitrap, Network Pharmacology and In Vivo Experimental Verification |
| title_full | Chemical Constituents and Hypoglycemic Mechanisms of <i>Dendrobium nobile</i> in Treatment of Type 2 Diabetic Rats by UPLC-ESI-Q-Orbitrap, Network Pharmacology and In Vivo Experimental Verification |
| title_fullStr | Chemical Constituents and Hypoglycemic Mechanisms of <i>Dendrobium nobile</i> in Treatment of Type 2 Diabetic Rats by UPLC-ESI-Q-Orbitrap, Network Pharmacology and In Vivo Experimental Verification |
| title_full_unstemmed | Chemical Constituents and Hypoglycemic Mechanisms of <i>Dendrobium nobile</i> in Treatment of Type 2 Diabetic Rats by UPLC-ESI-Q-Orbitrap, Network Pharmacology and In Vivo Experimental Verification |
| title_short | Chemical Constituents and Hypoglycemic Mechanisms of <i>Dendrobium nobile</i> in Treatment of Type 2 Diabetic Rats by UPLC-ESI-Q-Orbitrap, Network Pharmacology and In Vivo Experimental Verification |
| title_sort | chemical constituents and hypoglycemic mechanisms of i dendrobium nobile i in treatment of type 2 diabetic rats by uplc esi q orbitrap network pharmacology and in vivo experimental verification |
| topic | <i>Dendrobium nobile</i> diabetes mellitus hypoglycemic mechanism UPLC-ESI-Q-Orbitrap |
| url | https://www.mdpi.com/1420-3049/28/6/2683 |
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