Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of <i>Acacia arabica</i> Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents
<i>Acacia</i> <i>arabica</i> is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of <i>A. arabica</i> bark together with the isolation of bioactive molecules. Insulin secretion and signal transdu...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Plants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2223-7747/10/6/1190 |
| _version_ | 1797530536598568960 |
|---|---|
| author | Prawej Ansari Peter R. Flatt Patrick Harriott J. M. A. Hannan Yasser H. A. Abdel-Wahab |
| author_facet | Prawej Ansari Peter R. Flatt Patrick Harriott J. M. A. Hannan Yasser H. A. Abdel-Wahab |
| author_sort | Prawej Ansari |
| collection | DOAJ |
| description | <i>Acacia</i> <i>arabica</i> is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of <i>A. arabica</i> bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes, and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation, and phytoconstituents were isolated and characterised by RP-HPLC followed by LC-MS and NMR. Hot-water extract of <i>A. arabica</i> (HWAA) increased insulin release from clonal β cells and mouse islets by 1.3–6.8-fold and 1.6–3.2-fold, respectively. Diazoxide, verapamil and calcium-free conditions decreased insulin-secretory activity by 30–42%. In contrast, isobutylmethylxanthine (IBMX), tolbutamide and 30 mM KCl potentiated the insulin-secretory effects. The mechanism of actions of HWAA involved membrane depolarisation and elevation of intracellular Ca<sup>2+</sup> together with an increase in glucose uptake by 3T3-L1 adipocytes, inhibition of starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity and protein glycation. Acute HWAA administration (250 mg/5 mL/kg) enhanced glucose tolerance and plasma insulin in HFF obese rats. Administration of HWAA (250 mg/5 mL/kg) for 9 days improved glucose homeostasis and β-cell functions, thereby improving glycaemic control, and circulating insulin. Isolated phytoconstituents, including quercetin and kaempferol, increased insulin secretion in vitro and improved glucose tolerance. The results indicate that HWAA has the potential to treat type 2 diabetes as a dietary supplement or as a source of antidiabetic agents, including quercetin and kaempferol. |
| first_indexed | 2024-03-10T10:30:23Z |
| format | Article |
| id | doaj.art-8b0e0f6f1977490a871517b366105e95 |
| institution | Directory Open Access Journal |
| issn | 2223-7747 |
| language | English |
| last_indexed | 2024-03-10T10:30:23Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Plants |
| spelling | doaj.art-8b0e0f6f1977490a871517b366105e952023-11-21T23:41:43ZengMDPI AGPlants2223-77472021-06-01106119010.3390/plants10061190Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of <i>Acacia arabica</i> Bark in Type-2 Diabetes and Isolation of Active PhytoconstituentsPrawej Ansari0Peter R. Flatt1Patrick Harriott2J. M. A. Hannan3Yasser H. A. Abdel-Wahab4School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UKSchool of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UKSchool of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UKDepartment of Pharmacy, Independent University, Dhaka 1229, BangladeshSchool of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK<i>Acacia</i> <i>arabica</i> is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of <i>A. arabica</i> bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes, and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation, and phytoconstituents were isolated and characterised by RP-HPLC followed by LC-MS and NMR. Hot-water extract of <i>A. arabica</i> (HWAA) increased insulin release from clonal β cells and mouse islets by 1.3–6.8-fold and 1.6–3.2-fold, respectively. Diazoxide, verapamil and calcium-free conditions decreased insulin-secretory activity by 30–42%. In contrast, isobutylmethylxanthine (IBMX), tolbutamide and 30 mM KCl potentiated the insulin-secretory effects. The mechanism of actions of HWAA involved membrane depolarisation and elevation of intracellular Ca<sup>2+</sup> together with an increase in glucose uptake by 3T3-L1 adipocytes, inhibition of starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity and protein glycation. Acute HWAA administration (250 mg/5 mL/kg) enhanced glucose tolerance and plasma insulin in HFF obese rats. Administration of HWAA (250 mg/5 mL/kg) for 9 days improved glucose homeostasis and β-cell functions, thereby improving glycaemic control, and circulating insulin. Isolated phytoconstituents, including quercetin and kaempferol, increased insulin secretion in vitro and improved glucose tolerance. The results indicate that HWAA has the potential to treat type 2 diabetes as a dietary supplement or as a source of antidiabetic agents, including quercetin and kaempferol.https://www.mdpi.com/2223-7747/10/6/1190glucoseinsulinobesitydiabetesDPP-IVislets |
| spellingShingle | Prawej Ansari Peter R. Flatt Patrick Harriott J. M. A. Hannan Yasser H. A. Abdel-Wahab Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of <i>Acacia arabica</i> Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents Plants glucose insulin obesity diabetes DPP-IV islets |
| title | Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of <i>Acacia arabica</i> Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents |
| title_full | Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of <i>Acacia arabica</i> Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents |
| title_fullStr | Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of <i>Acacia arabica</i> Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents |
| title_full_unstemmed | Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of <i>Acacia arabica</i> Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents |
| title_short | Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of <i>Acacia arabica</i> Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents |
| title_sort | identification of multiple pancreatic and extra pancreatic pathways underlying the glucose lowering actions of i acacia arabica i bark in type 2 diabetes and isolation of active phytoconstituents |
| topic | glucose insulin obesity diabetes DPP-IV islets |
| url | https://www.mdpi.com/2223-7747/10/6/1190 |
| work_keys_str_mv | AT prawejansari identificationofmultiplepancreaticandextrapancreaticpathwaysunderlyingtheglucoseloweringactionsofiacaciaarabicaibarkintype2diabetesandisolationofactivephytoconstituents AT peterrflatt identificationofmultiplepancreaticandextrapancreaticpathwaysunderlyingtheglucoseloweringactionsofiacaciaarabicaibarkintype2diabetesandisolationofactivephytoconstituents AT patrickharriott identificationofmultiplepancreaticandextrapancreaticpathwaysunderlyingtheglucoseloweringactionsofiacaciaarabicaibarkintype2diabetesandisolationofactivephytoconstituents AT jmahannan identificationofmultiplepancreaticandextrapancreaticpathwaysunderlyingtheglucoseloweringactionsofiacaciaarabicaibarkintype2diabetesandisolationofactivephytoconstituents AT yasserhaabdelwahab identificationofmultiplepancreaticandextrapancreaticpathwaysunderlyingtheglucoseloweringactionsofiacaciaarabicaibarkintype2diabetesandisolationofactivephytoconstituents |