Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ

Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative in worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause side and adverse effects. There is an imperative necessity...

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Autores principales:	Sih-Pei Chen, Shian-Ren Lin, Ting-Hsu Chen, Hui-Suan Ng, Hip-Seng Yim, Max K. Leong, Ching-Feng Weng
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Diabetes Insulin resistance Garcinia mangostana Gamma-mangostin Computer simulation Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4e4f22de34fa41f6b02b82a8d0a0d198
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spelling	oai:doaj.org-article:4e4f22de34fa41f6b02b82a8d0a0d1982021-11-14T04:29:54ZMangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ0753-332210.1016/j.biopha.2021.112333https://doaj.org/article/4e4f22de34fa41f6b02b82a8d0a0d1982021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011173https://doaj.org/toc/0753-3322Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative in worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause side and adverse effects. There is an imperative necessity to conduct preclinical and clinical trials for the discovery of alternative therapeutic agents that can overcome the drawbacks of current synthetic antidiabetic drugs. This study aimed to investigate the efficacy of lowering blood glucose and underlined mechanism of γ-mangostin, mangosteen (Garcinia mangostana) xanthones. The results showed γ-Mangostin had a antihyperglycemic ability in short (2 h)- and long-term (28 days) administrations to diet-induced diabetic mice. The long-term administration of γ-mangostin attenuated fasting blood glucose of diabetic mice and exhibited no hepatotoxicity and nephrotoxicity. Moreover, AMPK, PPARγ, α-amylase, and α-glucosidase were found to be the potential targets for simulating binds with γ-mangostin after molecular docking. To validate the docking results, the inhibitory potency of γ-mangostin againstα-amylase/α-glucosidase was higher than Acarbose via enzymatic assay. Interestingly, an allosteric relationship between γ-mangostin and insulin was also found in the glucose uptake of VSMC, FL83B, C2C12, and 3T3-L1 cells. Taken together, the results showed that γ-mangostin exerts anti-hyperglycemic activity through promoting glucose uptake and reducing saccharide digestion by inhibition of α-amylase/α-glucosidase with insulin sensitization, suggesting that γ-mangostin could be a new clue for drug discovery and development to treat diabetes.Sih-Pei ChenShian-Ren LinTing-Hsu ChenHui-Suan NgHip-Seng YimMax K. LeongChing-Feng WengElsevierarticleDiabetesInsulin resistanceGarcinia mangostanaGamma-mangostinComputer simulationTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112333- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diabetes Insulin resistance Garcinia mangostana Gamma-mangostin Computer simulation Therapeutics. Pharmacology RM1-950
spellingShingle	Diabetes Insulin resistance Garcinia mangostana Gamma-mangostin Computer simulation Therapeutics. Pharmacology RM1-950 Sih-Pei Chen Shian-Ren Lin Ting-Hsu Chen Hui-Suan Ng Hip-Seng Yim Max K. Leong Ching-Feng Weng Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ
description	Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative in worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause side and adverse effects. There is an imperative necessity to conduct preclinical and clinical trials for the discovery of alternative therapeutic agents that can overcome the drawbacks of current synthetic antidiabetic drugs. This study aimed to investigate the efficacy of lowering blood glucose and underlined mechanism of γ-mangostin, mangosteen (Garcinia mangostana) xanthones. The results showed γ-Mangostin had a antihyperglycemic ability in short (2 h)- and long-term (28 days) administrations to diet-induced diabetic mice. The long-term administration of γ-mangostin attenuated fasting blood glucose of diabetic mice and exhibited no hepatotoxicity and nephrotoxicity. Moreover, AMPK, PPARγ, α-amylase, and α-glucosidase were found to be the potential targets for simulating binds with γ-mangostin after molecular docking. To validate the docking results, the inhibitory potency of γ-mangostin againstα-amylase/α-glucosidase was higher than Acarbose via enzymatic assay. Interestingly, an allosteric relationship between γ-mangostin and insulin was also found in the glucose uptake of VSMC, FL83B, C2C12, and 3T3-L1 cells. Taken together, the results showed that γ-mangostin exerts anti-hyperglycemic activity through promoting glucose uptake and reducing saccharide digestion by inhibition of α-amylase/α-glucosidase with insulin sensitization, suggesting that γ-mangostin could be a new clue for drug discovery and development to treat diabetes.
format	article
author	Sih-Pei Chen Shian-Ren Lin Ting-Hsu Chen Hui-Suan Ng Hip-Seng Yim Max K. Leong Ching-Feng Weng
author_facet	Sih-Pei Chen Shian-Ren Lin Ting-Hsu Chen Hui-Suan Ng Hip-Seng Yim Max K. Leong Ching-Feng Weng
author_sort	Sih-Pei Chen
title	Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ
title_short	Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ
title_full	Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ
title_fullStr	Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ
title_full_unstemmed	Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ
title_sort	mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of ampk/pparγ
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/4e4f22de34fa41f6b02b82a8d0a0d198
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Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ

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