Terpenoid-Rich Extract of <i>Dillenia indica</i> L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress
Insulin resistance (IR) plays a key role in the pathogenesis and clinical outcome of patients with multiple diseases and diabetes. In this study, we examined the antidiabetic effects of a terpenoid-rich extract from <i>Dillenia indica</i> L. bark (TRDI) in palmitic acid-induced insulin r...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/7/1227 |
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| author | Bo-Rim Song Md Badrul Alam Sang-Han Lee |
| author_facet | Bo-Rim Song Md Badrul Alam Sang-Han Lee |
| author_sort | Bo-Rim Song |
| collection | DOAJ |
| description | Insulin resistance (IR) plays a key role in the pathogenesis and clinical outcome of patients with multiple diseases and diabetes. In this study, we examined the antidiabetic effects of a terpenoid-rich extract from <i>Dillenia indica</i> L. bark (TRDI) in palmitic acid-induced insulin resistance (PA-IR) in C2C12 myotube and a streptozotocin (STZ)-induced diabetic mice model and explored the possible underlying mechanism. TRDI showed potential DPPH- and ABTS-radical scavenging effects with a half-maximal inhibitory concentration (IC<sub>50</sub>) value of 9.76 ± 0.50 µg/mL and 17.47 ± 1.31 µg/mL, respectively. Furthermore, TRDI strongly mitigated α-glucosidase activity with an IC<sub>50</sub> value of 3.03 ± 1.01 µg/mL, which was 92-fold higher than the positive control, acarbose (IC<sub>50</sub> = 279.49 ± µg/mL). TRDI stimulated the insulin receptor substrarte-1 (INS-1), downregulated phosphoinositide-dependent kinase-1 (PDK1) and protein kinase B (Akt) in both normal and PA-IR C2C12 cells as well as in STZ-induced diabetic mice, enhanced glucose transporter 4 (GLUT4) translocation to the plasma membrane (PM), and increased glucose absorption. Furthermore, TRDI administration significantly reduced PA-induced reactive oxygen species (ROS) formation in C2C12 cells and increased the protein level of numerous antioxidant enzymes such as superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase-1 (GPx-1) and thioredoxin reductase (TrxR) both in vitro and in vivo. Furthermore, TRDI facilitated nuclear factor erythroid 2 related factor 2 (Nrf2) nuclear translocation and increased HO-1 expression in PA-IR C2C12 cells and STZ-induced diabetic mice. However, for the inhibition of Nrf2, TRDI failed to resist the effects of IR. Thus, this study provides new evidence to support the use of TRDI for diabetes treatment. |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T03:46:08Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj.art-19d8ac1609cf42cab82826ab6310b8fd2023-12-03T14:33:22ZengMDPI AGAntioxidants2076-39212022-06-01117122710.3390/antiox11071227Terpenoid-Rich Extract of <i>Dillenia indica</i> L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative StressBo-Rim Song0Md Badrul Alam1Sang-Han Lee2Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, KoreaDepartment of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, KoreaDepartment of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, KoreaInsulin resistance (IR) plays a key role in the pathogenesis and clinical outcome of patients with multiple diseases and diabetes. In this study, we examined the antidiabetic effects of a terpenoid-rich extract from <i>Dillenia indica</i> L. bark (TRDI) in palmitic acid-induced insulin resistance (PA-IR) in C2C12 myotube and a streptozotocin (STZ)-induced diabetic mice model and explored the possible underlying mechanism. TRDI showed potential DPPH- and ABTS-radical scavenging effects with a half-maximal inhibitory concentration (IC<sub>50</sub>) value of 9.76 ± 0.50 µg/mL and 17.47 ± 1.31 µg/mL, respectively. Furthermore, TRDI strongly mitigated α-glucosidase activity with an IC<sub>50</sub> value of 3.03 ± 1.01 µg/mL, which was 92-fold higher than the positive control, acarbose (IC<sub>50</sub> = 279.49 ± µg/mL). TRDI stimulated the insulin receptor substrarte-1 (INS-1), downregulated phosphoinositide-dependent kinase-1 (PDK1) and protein kinase B (Akt) in both normal and PA-IR C2C12 cells as well as in STZ-induced diabetic mice, enhanced glucose transporter 4 (GLUT4) translocation to the plasma membrane (PM), and increased glucose absorption. Furthermore, TRDI administration significantly reduced PA-induced reactive oxygen species (ROS) formation in C2C12 cells and increased the protein level of numerous antioxidant enzymes such as superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase-1 (GPx-1) and thioredoxin reductase (TrxR) both in vitro and in vivo. Furthermore, TRDI facilitated nuclear factor erythroid 2 related factor 2 (Nrf2) nuclear translocation and increased HO-1 expression in PA-IR C2C12 cells and STZ-induced diabetic mice. However, for the inhibition of Nrf2, TRDI failed to resist the effects of IR. Thus, this study provides new evidence to support the use of TRDI for diabetes treatment.https://www.mdpi.com/2076-3921/11/7/1227<i>Dillenia indica</i> L. barkGLUT4AktROSNrf2HO-1 |
| spellingShingle | Bo-Rim Song Md Badrul Alam Sang-Han Lee Terpenoid-Rich Extract of <i>Dillenia indica</i> L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress Antioxidants <i>Dillenia indica</i> L. bark GLUT4 Akt ROS Nrf2 HO-1 |
| title | Terpenoid-Rich Extract of <i>Dillenia indica</i> L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress |
| title_full | Terpenoid-Rich Extract of <i>Dillenia indica</i> L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress |
| title_fullStr | Terpenoid-Rich Extract of <i>Dillenia indica</i> L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress |
| title_full_unstemmed | Terpenoid-Rich Extract of <i>Dillenia indica</i> L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress |
| title_short | Terpenoid-Rich Extract of <i>Dillenia indica</i> L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress |
| title_sort | terpenoid rich extract of i dillenia indica i l bark displays antidiabetic action in insulin resistant c2c12 cells and stz induced diabetic mice by attenuation of oxidative stress |
| topic | <i>Dillenia indica</i> L. bark GLUT4 Akt ROS Nrf2 HO-1 |
| url | https://www.mdpi.com/2076-3921/11/7/1227 |
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