Novel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats

Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from <i>Cassia fistula</i> stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg bod...

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Autores principales:	Sabapathy Indu, Periyasamy Vijayalakshmi, Jayaraman Selvaraj, Manikkam Rajalakshmi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Cassia fistula</i> novel triterpenoids diabetes mellitus insulin signaling in vivo in silico Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/d09cd8b953ad46df8f787b4aa0fdd6b9
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spelling	oai:doaj.org-article:d09cd8b953ad46df8f787b4aa0fdd6b92021-11-25T18:27:27ZNovel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats10.3390/molecules262268121420-3049https://doaj.org/article/d09cd8b953ad46df8f787b4aa0fdd6b92021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6812https://doaj.org/toc/1420-3049Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from <i>Cassia fistula</i> stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (<i>p</i> < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (<i>p</i> < 0.05). Plasma insulin (<i>p</i> < 0.0001)/C-peptide (<i>p</i> < 0.0006), tissue glycogen (<i>p</i> < 0.0034), glycogen phosphorylase (<i>p</i> < 0.005), glucose 6-phosphatase (<i>p</i> < 0.0001) and lipid markers were significantly increased (<i>p</i> < 0.0001) in diabetic rats, whereas glucokinase (<i>p</i> < 0.0047), glycogen synthase (<i>p</i> < 0.003), glucose oxidation (<i>p</i> < 0.001), GLUT4 mRNA (<i>p</i> < 0.0463), GLUT4 protein (<i>p</i> < 0.0475) and the insulin-signaling molecules IR mRNA (<i>p</i> < 0.0195), IR protein (<i>p</i> < 0.0001), IRS-1 mRNA (<i>p</i> < 0.0478), p-IRS-1<sup>Tyr612</sup> (<i>p</i> < 0.0185), Akt mRNA (<i>p</i> < 0.0394), p–Akt<sup>Ser473</sup> (<i>p</i> < 0.0162), GLUT4 mRNA (<i>p</i> < 0.0463) and GLUT4 (<i>p</i> < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1–C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1–C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.Sabapathy InduPeriyasamy VijayalakshmiJayaraman SelvarajManikkam RajalakshmiMDPI AGarticle<i>Cassia fistula</i>novel triterpenoidsdiabetes mellitusinsulin signalingin vivoin silicoOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6812, p 6812 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Cassia fistula</i> novel triterpenoids diabetes mellitus insulin signaling in vivo in silico Organic chemistry QD241-441
spellingShingle	<i>Cassia fistula</i> novel triterpenoids diabetes mellitus insulin signaling in vivo in silico Organic chemistry QD241-441 Sabapathy Indu Periyasamy Vijayalakshmi Jayaraman Selvaraj Manikkam Rajalakshmi Novel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats
description	Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from <i>Cassia fistula</i> stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (<i>p</i> < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (<i>p</i> < 0.05). Plasma insulin (<i>p</i> < 0.0001)/C-peptide (<i>p</i> < 0.0006), tissue glycogen (<i>p</i> < 0.0034), glycogen phosphorylase (<i>p</i> < 0.005), glucose 6-phosphatase (<i>p</i> < 0.0001) and lipid markers were significantly increased (<i>p</i> < 0.0001) in diabetic rats, whereas glucokinase (<i>p</i> < 0.0047), glycogen synthase (<i>p</i> < 0.003), glucose oxidation (<i>p</i> < 0.001), GLUT4 mRNA (<i>p</i> < 0.0463), GLUT4 protein (<i>p</i> < 0.0475) and the insulin-signaling molecules IR mRNA (<i>p</i> < 0.0195), IR protein (<i>p</i> < 0.0001), IRS-1 mRNA (<i>p</i> < 0.0478), p-IRS-1<sup>Tyr612</sup> (<i>p</i> < 0.0185), Akt mRNA (<i>p</i> < 0.0394), p–Akt<sup>Ser473</sup> (<i>p</i> < 0.0162), GLUT4 mRNA (<i>p</i> < 0.0463) and GLUT4 (<i>p</i> < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1–C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1–C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.
format	article
author	Sabapathy Indu Periyasamy Vijayalakshmi Jayaraman Selvaraj Manikkam Rajalakshmi
author_facet	Sabapathy Indu Periyasamy Vijayalakshmi Jayaraman Selvaraj Manikkam Rajalakshmi
author_sort	Sabapathy Indu
title	Novel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats
title_short	Novel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats
title_full	Novel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats
title_fullStr	Novel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats
title_full_unstemmed	Novel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats
title_sort	novel triterpenoids from <i>cassia fistula</i> stem bark depreciates stz-induced detrimental changes in irs-1/akt-mediated insulin signaling mechanisms in type-1 diabetic rats
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d09cd8b953ad46df8f787b4aa0fdd6b9
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Novel Triterpenoids from <i>Cassia fistula</i> Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats

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