Differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model

Abstract Background The medicinal plant Citrullus colocynthis (L.) Schrad. (C. colocynthis) may benefit patients at different phases of diabetes by attuning to contrasting situations. Our primary objective was to find the mechanism(s) behind the antidiabetic/anti-hyperlipidemic effects of C . c oloc...

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Autores principales:	Arezoo Afshari, Fouzieh Salimi, Azin Nowrouzi, Masoumeh Babaie Khalili, Salar Bakhtiyari, Gholamreza Hassanzadeh, Maryam Shabani, Ali Ahadi, Masoumeh Farhadiannezhad
Formato:	article
Lenguaje:	EN
Publicado:	SpringerOpen 2021
Materias:	Citrullus colocynthis (L.) Schrad Early- and late-stage diabetes mellitus Hyperglycemia Hyperlipidemia Gluconeogenesis Wistar-albino rats Medicine R Homeopathy RX1-681
Acceso en línea:	https://doaj.org/article/934884b0a27d40f09c030cad14853c55
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spelling	oai:doaj.org-article:934884b0a27d40f09c030cad14853c552021-11-21T12:27:07ZDifferential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model10.1186/s40816-021-00324-x2199-1197https://doaj.org/article/934884b0a27d40f09c030cad14853c552021-11-01T00:00:00Zhttps://doi.org/10.1186/s40816-021-00324-xhttps://doaj.org/toc/2199-1197Abstract Background The medicinal plant Citrullus colocynthis (L.) Schrad. (C. colocynthis) may benefit patients at different phases of diabetes by attuning to contrasting situations. Our primary objective was to find the mechanism(s) behind the antidiabetic/anti-hyperlipidemic effects of C . c olocynthis seed aqueous extract (CCAE) in two different stages of type 2 diabetes (T2D) in rats. Methods Fasting blood sugar (FBS) levels, body weights, and the degree of impaired glucose tolerance (IGT) were measured in healthy nondiabetic control rats (Con), as well as rats with early and late stages of T2D, denoted as ET2D and LT2D, respectively. CCAE was intraperitoneally (IP) injected for 28 days. In the end, the hepatic mRNA expression levels of the following genes were determined by RT-PCR: glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), insulin-dependent sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), peroxisome proliferator-activated receptor alpha (PPARα), and carnitine palmitoyltransferase I (CPT1). The liver was examined by hematoxylin and eosin (H&E) and Oil-Red O staining. CCAE was partially analyzed by HPLC-DAD. Results ET2D and LT2D were characterized by differentially elevated FBS, deteriorated bodyweight, and significant IGT compared to Con. Hepatosteatoses of varying morphologies and higher hepatic expression of G6Pase than PRPCK in ET2D versus the opposite in LT2D further confirmed the divergent nature of metabolic aberrations. At the end of 28 days, the high levels of FBS, alkaline phosphatase (ALP), triglyceride (TG), urea, hepatic protein carbonyl content (PCC), and alanine and aspartate aminotransferases (AST and ALT, respectively) persisted in untreated LT2D. CCAE ameliorated oxidative stress and upregulated PPARα expression in diabetic groups and Con; it downregulated CPT1 expression in the LT2D group. CCAE’s ability to lower FBS and serum and hepatic TG in both ET2D and LT2D indicated its ability to act via different mechanisms. Ferulic acid (Fer A) and rutin hydrate (RH) were detected in CCAE. Conclusion CCAE lowered the FBS in ET2D via inhibiting the hepatic G6Pase expression (glycogenolysis). In LT2D, CCAE abated sugar levels by diverting PEPCK activity, preferably towards glyceroneogenesis than gluconeogenesis. The preserved triglyceride/fatty acid (TG/FA) cycle, the upregulated PPARα, and the downregulated CPT1 gene expressions reduced serum and hepatic TG.Arezoo AfshariFouzieh SalimiAzin NowrouziMasoumeh Babaie KhaliliSalar BakhtiyariGholamreza HassanzadehMaryam ShabaniAli AhadiMasoumeh FarhadiannezhadSpringerOpenarticleCitrullus colocynthis (L.) SchradEarly- and late-stage diabetes mellitusHyperglycemiaHyperlipidemiaGluconeogenesisWistar-albino ratsMedicineRHomeopathyRX1-681ENClinical Phytoscience, Vol 7, Iss 1, Pp 1-22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Citrullus colocynthis (L.) Schrad Early- and late-stage diabetes mellitus Hyperglycemia Hyperlipidemia Gluconeogenesis Wistar-albino rats Medicine R Homeopathy RX1-681
spellingShingle	Citrullus colocynthis (L.) Schrad Early- and late-stage diabetes mellitus Hyperglycemia Hyperlipidemia Gluconeogenesis Wistar-albino rats Medicine R Homeopathy RX1-681 Arezoo Afshari Fouzieh Salimi Azin Nowrouzi Masoumeh Babaie Khalili Salar Bakhtiyari Gholamreza Hassanzadeh Maryam Shabani Ali Ahadi Masoumeh Farhadiannezhad Differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model
description	Abstract Background The medicinal plant Citrullus colocynthis (L.) Schrad. (C. colocynthis) may benefit patients at different phases of diabetes by attuning to contrasting situations. Our primary objective was to find the mechanism(s) behind the antidiabetic/anti-hyperlipidemic effects of C . c olocynthis seed aqueous extract (CCAE) in two different stages of type 2 diabetes (T2D) in rats. Methods Fasting blood sugar (FBS) levels, body weights, and the degree of impaired glucose tolerance (IGT) were measured in healthy nondiabetic control rats (Con), as well as rats with early and late stages of T2D, denoted as ET2D and LT2D, respectively. CCAE was intraperitoneally (IP) injected for 28 days. In the end, the hepatic mRNA expression levels of the following genes were determined by RT-PCR: glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), insulin-dependent sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), peroxisome proliferator-activated receptor alpha (PPARα), and carnitine palmitoyltransferase I (CPT1). The liver was examined by hematoxylin and eosin (H&E) and Oil-Red O staining. CCAE was partially analyzed by HPLC-DAD. Results ET2D and LT2D were characterized by differentially elevated FBS, deteriorated bodyweight, and significant IGT compared to Con. Hepatosteatoses of varying morphologies and higher hepatic expression of G6Pase than PRPCK in ET2D versus the opposite in LT2D further confirmed the divergent nature of metabolic aberrations. At the end of 28 days, the high levels of FBS, alkaline phosphatase (ALP), triglyceride (TG), urea, hepatic protein carbonyl content (PCC), and alanine and aspartate aminotransferases (AST and ALT, respectively) persisted in untreated LT2D. CCAE ameliorated oxidative stress and upregulated PPARα expression in diabetic groups and Con; it downregulated CPT1 expression in the LT2D group. CCAE’s ability to lower FBS and serum and hepatic TG in both ET2D and LT2D indicated its ability to act via different mechanisms. Ferulic acid (Fer A) and rutin hydrate (RH) were detected in CCAE. Conclusion CCAE lowered the FBS in ET2D via inhibiting the hepatic G6Pase expression (glycogenolysis). In LT2D, CCAE abated sugar levels by diverting PEPCK activity, preferably towards glyceroneogenesis than gluconeogenesis. The preserved triglyceride/fatty acid (TG/FA) cycle, the upregulated PPARα, and the downregulated CPT1 gene expressions reduced serum and hepatic TG.
format	article
author	Arezoo Afshari Fouzieh Salimi Azin Nowrouzi Masoumeh Babaie Khalili Salar Bakhtiyari Gholamreza Hassanzadeh Maryam Shabani Ali Ahadi Masoumeh Farhadiannezhad
author_facet	Arezoo Afshari Fouzieh Salimi Azin Nowrouzi Masoumeh Babaie Khalili Salar Bakhtiyari Gholamreza Hassanzadeh Maryam Shabani Ali Ahadi Masoumeh Farhadiannezhad
author_sort	Arezoo Afshari
title	Differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model
title_short	Differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model
title_full	Differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model
title_fullStr	Differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model
title_full_unstemmed	Differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model
title_sort	differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of citrullus colocynthis (l.) schrad. seed extract on hyperglycemia and hyperlipidemia in wistar-albino rats model
publisher	SpringerOpen
publishDate	2021
url	https://doaj.org/article/934884b0a27d40f09c030cad14853c55
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Differential expression of gluconeogenic enzymes in early- and late-stage diabetes: the effect of Citrullus colocynthis (L.) Schrad. Seed extract on hyperglycemia and hyperlipidemia in Wistar-Albino rats model

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