Hypoglycaemic activity of Bauhinia holophylla through GSK3-beta inhibition and glycogenesis activation

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dc.contributor.authorDe Paula Camaforte, Nathalia Ap [UNESP]
dc.contributor.authorSaldanha, Luiz Leonardo [UNESP]
dc.contributor.authorPonce Vareda, Priscilla Maria [UNESP]
dc.contributor.authorRezende-Neto, Joao M.
dc.contributor.authorSenger, Mario R.
dc.contributor.authorDelgado, Aislan Q. [UNESP]
dc.contributor.authorMorgan, Henrique J. N. [UNESP]
dc.contributor.authorViolato, Natalia Moretti [UNESP]
dc.contributor.authorPieroni, Lais Goyos [UNESP]
dc.contributor.authorDokkedal, Anne Ligia [UNESP]
dc.contributor.authorSilva, Floriano P.
dc.contributor.authorBosqueiro, Jose Roberto [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionOswaldo Cruz Inst FIOCRUZ
dc.date.accessioned2019-10-04T12:36:58Z
dc.date.available2019-10-04T12:36:58Z
dc.date.issued2019-01-01
dc.description.abstractContext: Bauhinia L. species, including Bauhinia holophylla (Bong.) Steud. (Fabaceae), have traditionally been used to treat diabetes. Bauhinia is a complex botanical genus, and the indiscriminate use of the diverse Bauhinia species is reflected in the experimental divergence of their medicinal potential. Objective: The hypoglycaemic and hypolipidaemic effects, molecular mechanism of action and phytochemical properties of an authentic extract of B. holophylla leaves were evaluated. Materials and methods: A phytochemical study of a 70% EtOH extract was performed using FIA-ESI-IT-MS/MSn and HPLC-PAD-ESI-IT-MS. The extract (200 or 400 mg/kg b.w.) was administered for 14 days to streptozotocin-induced diabetic Swiss mice. Glucose tolerance and insulin sensitivity, blood parameters, gene and protein expression, and the in vivo and in vitro inhibition of intestinal glucosidases were assessed. Results: HPLC-PAD-ESI-IT-MS analysis identified flavonoid derivatives of quercetin, myricetin, luteolin and kaempferol. Treatment with 400 mg/kg of the extract reduced blood glucose (269.0 +/- 32.4 mg/dL vs. 468.0 +/- 32.2 mg/dL for diabetic animals), improved glucose tolerance, decreased cholesterol and triglyceride levels, and increased the mRNA expression of proteins involved in glucogenesis in the liver and muscle, such as PI3-K/Akt, GS, GSK3-beta (ser-9), AMPK and Glut4. The activity of intestinal maltase was inhibited in vitro (IC50: 43.0 mu g/mL for the extract compared to 516.4 mu g/mL for acarbose) and in vivo. Discussion and conclusions: Treatment with B. holophylla was associated with a marked hypoglycaemic effect through the stimulation of glycogenesis and inhibition of gluconeogenesis and intestinal glucose absorption, without increasing basal insulinaemia.en
dc.description.affiliationSao Paulo State Univ, Inst Biosci, Botucatu, SP, Brazil
dc.description.affiliationOswaldo Cruz Inst FIOCRUZ, Lab Expt & Computat Biochem Drugs, Rio De Janeiro, Brazil
dc.description.affiliationSao Paulo State Univ, Dept Biol Sci, Bauru, SP, Brazil
dc.description.affiliationSao Paulo State Univ, Dept Phys Educ, Bauru, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Inst Biosci, Botucatu, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Dept Biol Sci, Bauru, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Dept Phys Educ, Bauru, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2009/52237-9
dc.description.sponsorshipIdFAPESP: 2013/10708-0
dc.description.sponsorshipIdFAPESP: 2016/18628-4
dc.format.extent269-279
dc.identifierhttp://dx.doi.org/10.1080/13880209.2019.1599962
dc.identifier.citationPharmaceutical Biology. Abingdon: Taylor & Francis Ltd, v. 57, n. 1, p. 269-279, 2019.
dc.identifier.doi10.1080/13880209.2019.1599962
dc.identifier.issn1388-0209
dc.identifier.urihttp://hdl.handle.net/11449/185627
dc.identifier.wosWOS:000465130400001
dc.language.isoeng
dc.publisherTaylor & Francis Ltd
dc.relation.ispartofPharmaceutical Biology
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.subjectAntidiabetic
dc.subjectFabaceae
dc.subjectflavonoid-O-glycosides
dc.subjectliver
dc.subjectplasma lipids
dc.titleHypoglycaemic activity of Bauhinia holophylla through GSK3-beta inhibition and glycogenesis activationen
dc.typeArtigo
dcterms.licensehttp://journalauthors.tandf.co.uk/permissions/reusingOwnWork.asp
dcterms.rightsHolderTaylor & Francis Ltd
unesp.author.lattes5569977655658319[10]
unesp.author.orcid0000-0002-0213-8551[10]
unesp.departmentCiências Biológicas - FCpt
unesp.departmentEducação Física - FCpt

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