Skip to content
2000
Volume 28, Issue 17
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

Diabetes mellitus (DM) is a chronic metabolic disease. The leaves of Lour. (LYY), a well-known traditional Chinese medicine (TCM) with Guangxi national characteristics often used in simple recipes to treat DM has attracted increasing attention. In this study, we investigated the therapeutic effects of LYY in diabetic rats from a metabolomic perspective.

Methods

The type 2 diabetes (T2DM) rat model was induced by a high-sugar and high-fat diet (HSFD) combined with 40 mg/kg streptozotocin (STZ). After oral administration of LYY (10.7 g/kg) for 28 d, their weight, fasted blood glucose (FBG), blood lipid levels, and inflammatory factors were assessed. The feces, urine, and serum samples of the rats were collected, and proton nuclear magnetic resonance (1H-NMR) technology was used to explore the changes in the sample's metabolism spectrum and analyze the relevant targeted metabolic pathways.

Results

Compared with the diabetes group, LYY rats significantly delayed the reduction of body weight and decreased the FBG level ( <0.01); the levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C), IL-6, and TNF-α in serum significantly reduced ( < 0.05, 0.01), and the level of high-density lipoprotein-cholesterol (HDL-C) significantly increased ( < 0.01). 2 candidate biomarkers were identified from feces samples, and 4 associated metabolic pathways were discovered. 13 potential biomarkers were screened from urine samples, leading to the identification of 16 related metabolic pathways. Similarly, 5 potential biomarkers were screened from serum samples, and 11 related metabolic pathways were found.

Conclusion

LYY can regulate the metabolic disorder caused by T2DM by regulating amino acid metabolism, amino acid synthesis, and tricarboxylic acid cycle, which provides a specific reference for the clinical treatment of T2DM.

Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073335304241023153906
2025-02-03
2025-12-24
Loading full text...

Full text loading...

References

  1. SantonocitoS. PolizziA. MarchettiE. DalessandriD. MiglioratiM. LupiS.M. CicciùM. IsolaG. Impact of Periodontitis on glycemic control and metabolic status in diabetes patients: Current knowledge on early disease markers and therapeutic perspectives.Mediators Inflamm.202220221710.1155/2022/4955277 35996409
    [Google Scholar]
  2. SaeediP. PetersohnI. SalpeaP. MalandaB. KarurangaS. UnwinN. ColagiuriS. GuariguataL. MotalaA.A. OgurtsovaK. ShawJ.E. BrightD. WilliamsR. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.Diabetes Res. Clin. Pract.201915710784310.1016/j.diabres.2019.107843 31518657
    [Google Scholar]
  3. FurmanB.L. Streptozotocin-induced diabetic models in mice and rats.Curr. Protoc.202114e7810.1002/cpz1.78 33905609
    [Google Scholar]
  4. FeinbergT. WielandL.S. MillerL.E. MunirK. PollinT.I. ShuldinerA.R. AmoilsS. GallagherL. Bahr-RobertsonM. D’AdamoC.R. Polyherbal dietary supplementation for prediabetic adults: Study protocol for a randomized controlled trial.Trials20192012410.1186/s13063‑018‑3032‑6 30616613
    [Google Scholar]
  5. LiangJ. HPLC fingerprint study on the ethyl acetate site of the leaves of Dimocarpus longan Lour.J. Shenyang Pharm. Univ.2019368688
    [Google Scholar]
  6. LiangJ. Experimental study on the hypoglycemic effect of different extracts of the leaves of Dimocarpus longan Lour.Shizhen Guo Yi Guo Yao201324820572058
    [Google Scholar]
  7. LiangJ. Study on hypoglycemic effects of different polar parts from the leaves of Dimocarpus longan on type 2 diabetes mellitus mice.China Pharmacy2018297950954
    [Google Scholar]
  8. LiangJ. Study on hypoglycemic mechanism of ethylacetate extracts from the leaves of Longan Arillus in type 2 diabetes mellitus rats.Zhonghua Zhongyiyao Zazhi2019342563568
    [Google Scholar]
  9. ZhengF.P. GaoB.Z. ChenX.Q. Research progress of type 2diabetes mellitus metabolomics based on ~1H-NMR technology.Medical Review.20212743054309
    [Google Scholar]
  10. SuZ. RuanJ. LiuX. ZhengH. RuanJ. LuY. ChengB. WuF. WuJ. LiuX. SongF. ChenZ. SongH. LiangY. GuoH. Combining 1H-NMR-based metabonomics and network pharmacology to dissect the mechanism of antidepression effect of Milletia speciosa Champ on mouse with chronic unpredictable mild stress-induced depression.J. Pharm. Pharmacol.202173788189210.1093/jpp/rgaa010 33836071
    [Google Scholar]
  11. YangL. LinH. LinW. XuX. Exercise ameliorates insulin resistance of type 2 diabetes through motivating short-chain fatty acid-mediated skeletal muscle cell autophagy.Biology (Basel)20209820310.3390/biology9080203 32756447
    [Google Scholar]
  12. HuJ. Metabolism analysis of ethyl acetate fractions of leaves of longyan (Dimocarpus longan Lour.) in vivo based on UHPLC-Q-Orbi trap MS.Zhonghua Zhongyiyao Xuekan2023417173180
    [Google Scholar]
  13. LijuanS. Distribution of nardosinone and its metabolites in rats analyzed by UPLC-Q-exactive orbitrap MS/MS.Chin. J. Exp. Tradit. Med. Formulae110
    [Google Scholar]
  14. ChenX. HuangZ.F. LiuY.H. LiuY.H. ChenY. QinD.Y. YiJ.H. Study on metabolites in vivo of Dangefentong Capsules based on UHPLC-Q/Orbitrap-MS/MS.Zhongguo Zhongyao Zazhi2022471850525063 36164915
    [Google Scholar]
  15. OkobiO. The role of gut microbiota in the development of type 2 diabetes mellitus.Med. Res. Arch.202412710.18103/mra.v12i7.5454
    [Google Scholar]
  16. ZhaoF. LiuQ. CaoJ. XuY. PeiZ. FanH. YuanY. ShenX. LiC. A sea cucumber (Holothuria leucospilota) polysaccharide improves the gut microbiome to alleviate the symptoms of type 2 diabetes mellitus in Goto-Kakizaki rats.Food Chem. Toxicol.202013511088610.1016/j.fct.2019.110886 31626838
    [Google Scholar]
  17. DarkoS.N. YarD.D. Owusu-DaboE. AwuahA.A.A. DapaahW. AddofohN. SalifuS.P. Awua-BoatengN.Y. Adomako-BoatengF. Variations in levels of IL-6 and TNF-α in type 2 diabetes mellitus between rural and urban Ashanti Region of Ghana.BMC Endocr. Disord.20151515010.1186/s12902‑015‑0047‑9 26391589
    [Google Scholar]
  18. WangT.J. LarsonM.G. VasanR.S. ChengS. RheeE.P. McCabeE. LewisG.D. FoxC.S. JacquesP.F. FernandezC. O’DonnellC.J. CarrS.A. MoothaV.K. FlorezJ.C. SouzaA. MelanderO. ClishC.B. GersztenR.E. Metabolite profiles and the risk of developing diabetes.Nat. Med.201117444845310.1038/nm.2307 21423183
    [Google Scholar]
  19. ConnellyM.A. Wolak-DinsmoreJ. DullaartR.P.F. Branched chain amino acids are associated with insulin resistance independent of leptin and adiponectin in subjects with varying degrees of glucose tolerance.Metab. Syndr. Relat. Disord.201715418318610.1089/met.2016.0145 28437198
    [Google Scholar]
  20. LiT. ZhangZ. KolwiczS.C. AbellL. RoeN.D. KimM. ZhouB. CaoY. RitterhoffJ. GuH. RafteryD. SunH. TianR. Defective branched-chain amino acid catabolism disrupts glucose metabolism and sensitizes the heart to ischemia-reperfusion injury.Cell Metab.201725237438510.1016/j.cmet.2016.11.005 28178567
    [Google Scholar]
  21. JustP.A. CharawiS. DenisR.G.P. SavallM. TraoreM. ForetzM. BastuS. MagassaS. SenniN. SohierP. WursmerM. Vasseur-CognetM. SchmittA. Le GallM. LeducM. GuillonneauF. De BandtJ.P. MayeuxP. RomagnoloB. LuquetS. BossardP. PerretC. Lkb1 suppresses amino acid-driven gluconeogenesis in the liver.Nat. Commun.2020111612710.1038/s41467‑020‑19490‑6 33257663
    [Google Scholar]
  22. ChenK.H. ChenY.L. TangH.Y. HungC.C. YenT.H. ChengM.L. ShiaoM.S. ChenJ.K. Dietary leucine supplement ameliorates hepatic steatosis and diabetic nephropathy in db/db mice.Int. J. Mol. Sci.2018197192110.3390/ijms19071921 29966331
    [Google Scholar]
  23. YuD. RichardsonN.E. GreenC.L. SpicerA.B. MurphyM.E. FloresV. JangC. KaszaI. NikodemovaM. WakaiM.H. TomasiewiczJ.L. YangS.E. MillerB.R. PakH.H. BrinkmanJ.A. RojasJ.M. QuinnW.J. ChengE.P. KononE.N. HaiderL.R. FinkeM. SonsallaM. AlexanderC.M. RabinowitzJ.D. BaurJ.A. MaleckiK.C. LammingD.W. The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine.Cell Metab.2021335905922.e610.1016/j.cmet.2021.03.025 33887198
    [Google Scholar]
  24. ZhenyukhO. González-AmorM. Rodrigues-DiezR.R. EstebanV. Ruiz-OrtegaM. SalaicesM. MasS. BrionesA.M. EgidoJ. Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation.J. Cell. Mol. Med.2018221049484962https://pubmed.ncbi.nlm.nih.gov/30063118/
    [Google Scholar]
  25. YuH. UPLC-QTOF-MS-based metabolomics study on ischemic stroke patients.Chem. J. Chin. Univ.2017381017421750
    [Google Scholar]
  26. MagnussonM. WangT.J. ClishC. EngströmG. NilssonP. GersztenR.E. MelanderO. Dimethylglycine deficiency and the development of diabetes.Diabetes20156483010301610.2337/db14‑1863 25795213
    [Google Scholar]
  27. Yan-DoR. MacDonaldP.E. Impaired Glycine-mia in type 2 diabetes and potential mechanisms contributing to glucose homeostasis.Endocrinology201715851064107310.1210/en.2017‑00148 28323968
    [Google Scholar]
  28. PrassK. RoylG. LindauerU. FreyerD. MegowD. DirnaglU. Stöckler-IpsirogluG. WallimannT. PrillerJ. Improved reperfusion and neuroprotection by creatine in a mouse model of stroke.J. Cereb. Blood Flow Metab.200727345245910.1038/sj.jcbfm.9600351 16773141
    [Google Scholar]
  29. DickinsonH. Davies-TuckM. ElleryS.J. GriegerJ.A. WallaceE.M. SnowR.J. WalkerD.W. CliftonV.L. Maternal creatine in pregnancy: A retrospective cohort study.BJOG2016123111830183810.1111/1471‑0528.14237 27550725
    [Google Scholar]
  30. YuX.Y. Abnormalities and mechanisms of tricarboxylic acid cycle metabolism in a cellular model of diabetic nephropathy: A preliminary study.Chin. J. Clin. Pharm. Ther.2017225481489
    [Google Scholar]
  31. HaraY. KumeS. KataokaY. WatanabeN. Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats.Heliyon2021712e0850110.1016/j.heliyon.2021.e08501 34934832
    [Google Scholar]
  32. ChangJ.X. LiuW.H. ZhangJ.W. Antidiabetic effect of Acanthopanax senticosus extracts in diabetic mice: A serum metabonomic study by UPLC-MS/MS.J. Int. Pharm. Res.2017447730737
    [Google Scholar]
  33. JiT. ZhangL.L. HuangX.C. SuS.L. OuyangZ. ZhuZ.H. GuoS. ShangE.X. QianD.W. DuanJ.A. The action mechanisms of Morus alba leaves extract for the treatment of diabetes based on plasma metabolomics.Yao Xue Xue Bao2015507830835 26552143
    [Google Scholar]
  34. ZhangX. OjanenX. ZhuangH. WuN. ChengS. WiklundP. Branched-chain and aromatic amino acids are associated with insulin resistance during pubertal development in girls.J. Adolesc. Health201965333734310.1016/j.jadohealth.2019.01.030 30905504
    [Google Scholar]
  35. Rivas-TumanyanS. PachecoL.S. HaslamD.E. Morou-BermudezE. LiangL. TuckerK.L. JoshipuraK.J. BhupathirajuS.N. Branched-chain and aromatic amino acids, type 2 diabetes, and cardiometabolic risk factors among puerto rican adults.Nutrients20241615256210.3390/nu16152562 39125441
    [Google Scholar]
  36. JieY. YanM. CailiW. Analysis on the changes of serum phenylalanine metabolites in diabetic renal disease based on targeted metabolomics.J. Baotou Med. Coll.202440032128
    [Google Scholar]
  37. Inam-u-llah PiaoF. AadilR.M. SulemanR. LiK. Zhang, M.; Wu, P.; Shahbaz, M.; Ahmed, Z. Ameliorative effects of taurine against diabetes: A review.Amino Acids201850548750210.1007/s00726‑018‑2544‑4 29492671
    [Google Scholar]
  38. TaiE.S. TanM.L.S. StevensR.D. LowY.L. MuehlbauerM.J. GohD.L.M. IlkayevaO.R. WennerB.R. BainJ.R. LeeJ.J.M. LimS.C. KhooC.M. ShahS.H. NewgardC.B. Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men.Diabetologia201053475776710.1007/s00125‑009‑1637‑8 20076942
    [Google Scholar]
  39. ZhaoL.C. GaoH.C. 1H NMR based metabonomics analysis of serum from mice with diabetic nephropathy.J. Wenzhou Med. Univ.2018485313318
    [Google Scholar]
  40. LiuX. ZhengY. Guasch-FerréM. Ruiz-CanelaM. ToledoE. ClishC. LiangL. RazquinC. CorellaD. EstruchR. FitoM. Gómez-GraciaE. ArósF. RosE. LapetraJ. FiolM. Serra-MajemL. PapandreouC. Martínez-GonzálezM.A. HuF.B. Salas-SalvadóJ. High plasma glutamate and low glutamine-to-glutamate ratio are associated with type 2 diabetes: Case-cohort study within the PREDIMED trial.Nutr. Metab. Cardiovasc. Dis.201929101040104910.1016/j.numecd.2019.06.005 31377179
    [Google Scholar]
  41. LuoG. CaiL.Y. Effect of qishen yiqi dripping pills on the expression of glutamate transporter and glutamine synthetase in diabetic rats.World Chin. Med.20161191852
    [Google Scholar]
  42. UmedaM. HiramotoM. WatanabeA. TsunodaN. ImaiT. Arginine-induced insulin secretion in endoplasmic reticulum.Biochem. Biophys. Res. Commun.2015466471772210.1016/j.bbrc.2015.09.006 26348775
    [Google Scholar]
  43. XuA.Y. Influence of different glucose rising velocity on hypoglycemic brain injury in diabetic model rats.J. Clin. Neurol.2018312126129
    [Google Scholar]
  44. InzucchiS.E. BergenstalR.M. BuseJ.B. DiamantM. FerranniniE. NauckM. PetersA.L. TsapasA. WenderR. MatthewsD.R. Management of hyperglycemia in type 2 diabetes: A patient-centered approach: Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetes Care20123561364137910.2337/dc12‑0413 22517736
    [Google Scholar]
/content/journals/cchts/10.2174/0113862073335304241023153906
Loading
/content/journals/cchts/10.2174/0113862073335304241023153906
Loading

Data & Media loading...

Supplements

Attribution was made according to Chenomx NMR suite 8.6 software, using the BMRB website and compound structure knowledge. The two-dimensional 1H-1H COSY identification results of different metabolites in feces, urine, and serum of different groups are shown in Fig. S1-S3.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test