Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.

Oral therapeutics used to treat type 2 diabetes and cardiovascular disease often fail to prevent the progression of disease and their comorbidities. Rooibos (Aspalathus linearis), an endemic South African plant used as an herbal tea, has demonstrated positive effects on glycemia and hypercholesterol...

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Autores principales:	Oelfah Patel, Christo J F Muller, Elizabeth Joubert, Bernd Rosenkranz, Johan Louw, Charles Awortwe
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5db923952a7d4afbb43dccac2027af97
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spelling	oai:doaj.org-article:5db923952a7d4afbb43dccac2027af972021-12-02T20:05:38ZTherapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.1932-620310.1371/journal.pone.0251069https://doaj.org/article/5db923952a7d4afbb43dccac2027af972021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251069https://doaj.org/toc/1932-6203Oral therapeutics used to treat type 2 diabetes and cardiovascular disease often fail to prevent the progression of disease and their comorbidities. Rooibos (Aspalathus linearis), an endemic South African plant used as an herbal tea, has demonstrated positive effects on glycemia and hypercholesterolemia. However, the treatment efficacy of rooibos extract in combination with conventional hypoglycemic and hypolipidemic medications on blood glucose and lipid profiles has not been established. This study aimed to investigate the effects of combining an aspalathin-rich green rooibos extract (Afriplex GRT™) with pioglitazone and atorvastatin, on blood glucose and lipid levels in obese diabetic (db/db) mice. Six-week-old male db/db mice and their nondiabetic lean littermate controls (db+) were divided into 8 experimental groups (n = 6/group). Db/db mice were treated daily either with pioglitazone (25 mg/kg), atorvastatin (80 mg/kg) and GRT (100 mg/kg), a combination of either drug with GRT or a combination of GRT-pioglitazone and atorvastatin for 5 weeks. Untreated vehicle controls were given dimethyl sulfoxide (0.1%) and phosphate buffered saline solution. At termination, serum and liver tissue were collected for lipid and gene expression analysis. Treatment with GRT, pioglitazone and atorvastatin combination effectively lowered fasting plasma glucose (FPG) levels in db/db mice (p = 0.02), whilst increasing body weight, liver weight, and reducing retroperitoneal fat weight. Atorvastatin monotherapy was effective at reducing cholesterol (from 4.00 ± 0.12 to 2.93 ± 0.13, p = 0.0003), LDL-C (from 0.58 ± 0.04 to 0.50 ± 0.00, p = 0.04), HDL-C (from 2.86 ± 0.05 to 2.50 ± 0.04, p = 0.0003) and TG (from 2.77 ± 0.50 to 1.48 ± 0.23, p = 0.04), compared to the untreated diabetic control. The hypotriglyceridemic effect of atorvastatin was enhanced when used in combination with both GRT and pioglitazone. The addition of pioglitazone to GRT significantly lowered FPG and TG. In db/db mice, Apoa1 was significantly downregulated in the liver, whilst Pparγ was significantly upregulated compared to their db+ counterparts. GRT monotherapy downregulated Apoa1 expression (p = 0.02). Atorvastatin combined with GRT significantly downregulated mRNA expression of Apoa1 (p = 0.03), whilst upregulating the expression of Pparγ (p = 0.03), Pparα (p = 0.002), Srebp1 (p = 0.002), and Fasn (p = 0.04). The GRT-pioglitazone-atorvastatin combination therapy downregulated Apoa1 (p = 0.006), whilst upregulating Fasn (p = 0.005), Pparα (p = 0.041), and Srebp1 (p = 0.03). Natural products can improve the efficacy of current drugs to prevent diabetes-associated complications. GRT in combination with pioglitazone enhanced the reduction of FPG, whilst the addition of atorvastatin to the combination, significantly lowered triglyceride levels. However, when GRT was used in combination with atorvastatin only cholesterol levels were affected. Although these results confirm both glucose- and lipoprotein-lowering biological effects of GRT in combination with pioglitazone and atorvastatin, increased expression of genes involved in lipogenesis, cholesterol, and fatty acid transport, β-oxidation, and synthesis and storage of fatty acids, may exacerbate the hepatotoxic effects of atorvastatin.Oelfah PatelChristo J F MullerElizabeth JoubertBernd RosenkranzJohan LouwCharles AwortwePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251069 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Oelfah Patel Christo J F Muller Elizabeth Joubert Bernd Rosenkranz Johan Louw Charles Awortwe Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.
description	Oral therapeutics used to treat type 2 diabetes and cardiovascular disease often fail to prevent the progression of disease and their comorbidities. Rooibos (Aspalathus linearis), an endemic South African plant used as an herbal tea, has demonstrated positive effects on glycemia and hypercholesterolemia. However, the treatment efficacy of rooibos extract in combination with conventional hypoglycemic and hypolipidemic medications on blood glucose and lipid profiles has not been established. This study aimed to investigate the effects of combining an aspalathin-rich green rooibos extract (Afriplex GRT™) with pioglitazone and atorvastatin, on blood glucose and lipid levels in obese diabetic (db/db) mice. Six-week-old male db/db mice and their nondiabetic lean littermate controls (db+) were divided into 8 experimental groups (n = 6/group). Db/db mice were treated daily either with pioglitazone (25 mg/kg), atorvastatin (80 mg/kg) and GRT (100 mg/kg), a combination of either drug with GRT or a combination of GRT-pioglitazone and atorvastatin for 5 weeks. Untreated vehicle controls were given dimethyl sulfoxide (0.1%) and phosphate buffered saline solution. At termination, serum and liver tissue were collected for lipid and gene expression analysis. Treatment with GRT, pioglitazone and atorvastatin combination effectively lowered fasting plasma glucose (FPG) levels in db/db mice (p = 0.02), whilst increasing body weight, liver weight, and reducing retroperitoneal fat weight. Atorvastatin monotherapy was effective at reducing cholesterol (from 4.00 ± 0.12 to 2.93 ± 0.13, p = 0.0003), LDL-C (from 0.58 ± 0.04 to 0.50 ± 0.00, p = 0.04), HDL-C (from 2.86 ± 0.05 to 2.50 ± 0.04, p = 0.0003) and TG (from 2.77 ± 0.50 to 1.48 ± 0.23, p = 0.04), compared to the untreated diabetic control. The hypotriglyceridemic effect of atorvastatin was enhanced when used in combination with both GRT and pioglitazone. The addition of pioglitazone to GRT significantly lowered FPG and TG. In db/db mice, Apoa1 was significantly downregulated in the liver, whilst Pparγ was significantly upregulated compared to their db+ counterparts. GRT monotherapy downregulated Apoa1 expression (p = 0.02). Atorvastatin combined with GRT significantly downregulated mRNA expression of Apoa1 (p = 0.03), whilst upregulating the expression of Pparγ (p = 0.03), Pparα (p = 0.002), Srebp1 (p = 0.002), and Fasn (p = 0.04). The GRT-pioglitazone-atorvastatin combination therapy downregulated Apoa1 (p = 0.006), whilst upregulating Fasn (p = 0.005), Pparα (p = 0.041), and Srebp1 (p = 0.03). Natural products can improve the efficacy of current drugs to prevent diabetes-associated complications. GRT in combination with pioglitazone enhanced the reduction of FPG, whilst the addition of atorvastatin to the combination, significantly lowered triglyceride levels. However, when GRT was used in combination with atorvastatin only cholesterol levels were affected. Although these results confirm both glucose- and lipoprotein-lowering biological effects of GRT in combination with pioglitazone and atorvastatin, increased expression of genes involved in lipogenesis, cholesterol, and fatty acid transport, β-oxidation, and synthesis and storage of fatty acids, may exacerbate the hepatotoxic effects of atorvastatin.
format	article
author	Oelfah Patel Christo J F Muller Elizabeth Joubert Bernd Rosenkranz Johan Louw Charles Awortwe
author_facet	Oelfah Patel Christo J F Muller Elizabeth Joubert Bernd Rosenkranz Johan Louw Charles Awortwe
author_sort	Oelfah Patel
title	Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.
title_short	Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.
title_full	Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.
title_fullStr	Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.
title_full_unstemmed	Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.
title_sort	therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5db923952a7d4afbb43dccac2027af97
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Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.

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