{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:02:40Z","timestamp":1790960560056,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guizhou Provincial Science and Technology Support Project","award":["2021-General 415"],"award-info":[{"award-number":["2021-General 415"]}]},{"name":"Guizhou Provincial Science and Technology Support Project","award":["2020-1Y404"],"award-info":[{"award-number":["2020-1Y404"]}]},{"name":"Guizhou Provincial Science and Technology Support Project","award":["S202110660009"],"award-info":[{"award-number":["S202110660009"]}]},{"name":"Guizhou Provincial Science and Technology Support Project","award":["S202210660145"],"award-info":[{"award-number":["S202210660145"]}]},{"name":"Guizhou Provincial Natural Science Foundation","award":["2021-General 415"],"award-info":[{"award-number":["2021-General 415"]}]},{"name":"Guizhou Provincial Natural Science Foundation","award":["2020-1Y404"],"award-info":[{"award-number":["2020-1Y404"]}]},{"name":"Guizhou Provincial Natural Science Foundation","award":["S202110660009"],"award-info":[{"award-number":["S202110660009"]}]},{"name":"Guizhou Provincial Natural Science Foundation","award":["S202210660145"],"award-info":[{"award-number":["S202210660145"]}]},{"name":"Guizhou Provincial Innovation and Entrepreneurship Training Project for College Students","award":["2021-General 415"],"award-info":[{"award-number":["2021-General 415"]}]},{"name":"Guizhou Provincial Innovation and Entrepreneurship Training Project for College Students","award":["2020-1Y404"],"award-info":[{"award-number":["2020-1Y404"]}]},{"name":"Guizhou Provincial Innovation and Entrepreneurship Training Project for College Students","award":["S202110660009"],"award-info":[{"award-number":["S202110660009"]}]},{"name":"Guizhou Provincial Innovation and Entrepreneurship Training Project for College Students","award":["S202210660145"],"award-info":[{"award-number":["S202210660145"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study aimed to systematically explore the chemical constituents of D. nobile and its hypoglycemic effect by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experiment. The chemical constituents of D. nobile 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 D. nobile. 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 D. nobile extract and D. nobile polysaccharide for two months by gavage. The results showed that a total of 39 chemical constituents of D. nobile, including alkaloids, bibenzyls, phenanthrenes and other types of compounds, were identified. D. nobile extract and D. nobile polysaccharide could significantly ameliorate the body weight, hyperglycemia, insulin resistance, dyslipidemia and morphological impairment of the liver and pancreas in the T2DM rats. \u03b1-Linolenic acid, dihydroconiferyl dihydro-p-coumarate, naringenin, trans-N-feruloyltyramine, gigantol, moscatilin, 4-O-methylpinosylvic acid, venlafaxine, nordendrobin and tristin were regarded as the key hypoglycemic compounds of D. nobile, 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 D. nobile activated the PI3K\/AKT pathway and insulin signaling pathway, promoted glycogen synthesis via regulating the expression of glycogen synthase kinase 3 beta (GSK-3\u03b2) 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 D. nobile might be associated with liver glycogen synthesis and gluconeogenesis, contributing to improving insulin resistance and abnormal glucose metabolism in the T2DM rats.<\/jats:p>","DOI":"10.3390\/molecules28062683","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T03:14:35Z","timestamp":1678936475000},"page":"2683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Chemical Constituents and Hypoglycemic Mechanisms of Dendrobium nobile in Treatment of Type 2 Diabetic Rats by UPLC-ESI-Q-Orbitrap, Network Pharmacology and In Vivo Experimental Verification"],"prefix":"10.3390","volume":"28","author":[{"given":"Zhaoyang","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyong","family":"Geng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Penrith, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8877-1392","authenticated-orcid":false,"given":"Zhi","family":"Xu","sequence":"additional","affiliation":[{"name":"Guizhou Miaoaitang Health Management Co., Ltd., Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4123-2276","authenticated-orcid":false,"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.diabres.2017.03.024","article-title":"IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040","volume":"128","author":"Ogurtsova","year":"2017","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1055\/a-1018-9078","article-title":"Definition, Classification and Diagnosis of Diabetes Mellitus","volume":"127","author":"Petersmann","year":"2019","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_3","first-page":"490","article-title":"Effects of Dendrobium nobile Lindl. alkaloids on blood glucose and liver fatty degeneration in diabetic rats","volume":"32","author":"Huang","year":"2013","journal-title":"Chin. J. New Drugs Clin. Rem."},{"key":"ref_4","first-page":"946","article-title":"Effects of the aqueous extract of Dendrobium nobile lindl. on NF-\u03baB and IL-6 expression of renal tissue in diabetic rat model","volume":"43","author":"Jin","year":"2014","journal-title":"Chongqing Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1080\/17460441.2019.1582638","article-title":"Liquid chromatography coupled to mass spectrometry for metabolite profiling in the field of drug discovery","volume":"14","author":"Saurina","year":"2019","journal-title":"Expert Opin. Drug Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"416","DOI":"10.4103\/1735-5362.213987","article-title":"Effects of hydroalcoholic extract of Rhus coriaria seed on glucose and insulin related biomarkers, lipid profile, and hepatic enzymes in nicotinamide-streptozotocin-induced type II diabetic male mice","volume":"12","author":"Ahangarpour","year":"2017","journal-title":"Res. Pharm. Sci."},{"key":"ref_7","first-page":"30","article-title":"Analysis of Alkaloids from Dendrobium nobile Stem by UPLC-ESI-Orbitrap-MS","volume":"23","author":"He","year":"2017","journal-title":"Chin. J. Experiment. Tradit. Med. Formulae"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104208","DOI":"10.1016\/j.arabjc.2022.104208","article-title":"UPLC-Q\/TOF-MS coupled with multivariate analysis for comparative analysis of metabolomic in Dendrobium nobile from different growth altitudes","volume":"15","author":"Lu","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jpba.2015.10.040","article-title":"Metabolic profile of naringenin in the stomach and colon using liquid chromatography\/electrospray ionization linear ion trap quadrupole-Orbitrap-mass spectrometry (LC-ESI-LTQ-Orbitrap-MS) and LC-ESI-MS\/MS","volume":"120","year":"2016","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.sbi.2016.10.016","article-title":"Protein-protein interactions: Scoring schemes and binding affinity","volume":"44","author":"Gromiha","year":"2017","journal-title":"Curr. Opin. Struc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"112891","DOI":"10.1016\/j.jep.2020.112891","article-title":"A network pharmacology approach to investigate the mechanism of Shuxuening injection in the treatment of ischemic stroke","volume":"257","author":"Cui","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","first-page":"451","article-title":"Effects of Dendrobium nobile Lindl. Alkaloids on alloxan-induced hyperglycemia in rats","volume":"32","author":"Huang","year":"2009","journal-title":"J. Zunyi Med. Univ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1016\/j.clnu.2022.02.013","article-title":"Effects of supplementation with vegetable sources of alpha-linolenic acid (ALA) on inflammatory markers and lipid profile in individuals with chronic kidney disease: A systematic review and meta-analysis","volume":"41","author":"Copetti","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.arcmed.2013.09.010","article-title":"Effect of \u03b1-linolenic acid on streptozotocin-induced diabetic retinopathy indices in vivo","volume":"44","author":"Shen","year":"2013","journal-title":"Arch. Med. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejphar.2016.01.002","article-title":"Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats","volume":"773","author":"Ren","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.cbi.2013.12.014","article-title":"Naringenin inhibits \u03b1-glucosidase activity: A promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats","volume":"210","author":"Priscilla","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.fct.2019.05.021","article-title":"Effects of N-trans-feruloyltyramine isolated from laba garlic on antioxidant, cytotoxic activities and H2O2-induced oxidative damage in HepG2 and L02 cells","volume":"130","author":"Gao","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jbiotec.2021.04.002","article-title":"Immobilized lipase catalytic synthesis of phenolamides and their potential against \u03b1-glucosidase","volume":"334","author":"Zeng","year":"2021","journal-title":"J. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jdiacomp.2007.03.010","article-title":"The effect of venlafaxine HCl on painful peripheral diabetic neuropathy in patients with type 2 diabetes mellitus","volume":"22","author":"Kadiroglu","year":"2008","journal-title":"J. Diabetes Complicat."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chen, M.F., Liou, S.S., Hong, T.Y., Kao, S.T., and Liu, I.M. (2018). Gigantol has Protective Effects against High Glucose-Evoked Nephrotoxicity in Mouse Glomerulus Mesangial Cells by Suppressing ROS\/MAPK\/NF-\u03baB Signaling Pathways. Molecules, 24.","DOI":"10.3390\/molecules24010080"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lai, M.C., Liu, W.Y., Liou, S.S., and Liu, I.M. (2020). A Bibenzyl Component Moscatilin Mitigates Glycation-Mediated Damages in an SH-SY5Y Cell Model of Neurodegenerative Diseases through AMPK Activation and RAGE\/NF-\u03baB Pathway Suppression. Molecules, 25.","DOI":"10.3390\/molecules25194574"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.bjp.2017.05.005","article-title":"\u03b1-Glucosidase and pancreatic lipase inhibitory activities and glucose uptake stimulatory effect of phenolic compounds from Dendrobium formosum","volume":"27","author":"Inthongkaew","year":"2017","journal-title":"Braz. J. Pharmacogn."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jnutbio.2018.03.016","article-title":"Tocotrienol-rich fraction supplementation reduces hyperglycemia-induced skeletal muscle damage through regulation of insulin signaling and oxidative stress in type 2 diabetic mice","volume":"57","author":"Lee","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.biopha.2017.09.153","article-title":"Swertisin rich fraction from Enicostema littorale ameliorates hyperglycemia and hyperlipidemia in high-fat fed diet and low dose streptozotacin induced type 2 diabetes mellitus in rats","volume":"96","author":"Mokashi","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.nutres.2015.10.001","article-title":"Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet","volume":"36","author":"Huang","year":"2016","journal-title":"Nutr. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1007\/s11695-014-1308-9","article-title":"Duodenal-jejunal bypass surgery suppresses hepatic de novo lipogenesis and alleviates liver fat accumulation in a diabetic rat model","volume":"24","author":"Han","year":"2014","journal-title":"Obes. Surg."},{"key":"ref_27","first-page":"1264","article-title":"Research Progress of PI3K\/AKT Signaling Pathway and Diabetes Mellitus","volume":"21","author":"Song","year":"2019","journal-title":"World Sci. Technol. Modern. Tradit. Chin. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100657","DOI":"10.1016\/j.jbior.2019.100657","article-title":"Class I phosphoinositide 3-kinase (PI3K) regulatory subunits and their roles in signaling and disease","volume":"75","author":"Rathinaswamy","year":"2020","journal-title":"Adv. Biol. Regul."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.yjmcc.2015.02.029","article-title":"EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model","volume":"82","author":"Liang","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jff.2017.11.004","article-title":"Dendrobium officinale polysaccharide attenuates type 2 diabetes mellitus via the regulation of PI3K\/Akt-mediated glycogen synthesis and glucose metabolism","volume":"40","author":"Wang","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"112863","DOI":"10.1016\/j.jep.2020.112863","article-title":"Agriophyllum oligosaccharides ameliorate hepatic injury in type 2 diabetic db\/db mice targeting INS-R\/IRS-2\/PI3K\/AKT\/PPAR-\u03b3\/Glut4 signal pathway","volume":"257","author":"Bao","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104501","DOI":"10.1016\/j.jff.2021.104501","article-title":"The glucuronide metabolites of kaempferol and quercetin, targeting to the AKT PH domain, activate AKT\/GSK3\u03b2 signaling pathway and improve glucose metabolism","volume":"82","author":"Fang","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.diabet.2014.01.005","article-title":"Molecular mechanisms of GLUT4 regulation in adipocytes","volume":"40","author":"Govers","year":"2014","journal-title":"Diabetes Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111325","DOI":"10.1016\/j.biopha.2021.111325","article-title":"Puerarin suppresses the hepatic gluconeogenesis via activation of PI3K\/Akt signaling pathway in diabetic rats and HepG(2) cells","volume":"137","author":"Liu","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"122729","DOI":"10.1016\/j.jchromb.2021.122729","article-title":"Chemical profile and potential mechanisms of Huo-Tan-Chu-Shi decoction in the treatment of coronary heart disease by UHPLC-Q\/TOF-MS in combination with network pharmacology analysis and experimental verification","volume":"1175","author":"He","year":"2021","journal-title":"J. Chromatogr. B"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/6\/2683\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:56:31Z","timestamp":1760122591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/6\/2683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,16]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["molecules28062683"],"URL":"https:\/\/doi.org\/10.3390\/molecules28062683","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,16]]}}}