Terpenoid-Rich Extract of Dillenia indica L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress

Abstract

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 Dillenia indica 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 (IC50) 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 IC50 value of 3.03 ± 1.01 µg/mL, which was 92-fold higher than the positive control, acarbose (IC50 = 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.

Methanol extract of Myelophycus caespitosus ameliorates oxidative stress-induced cytotoxicity in C2C12 murine myoblasts via activation of heme oxygenase-1

“…Our results support previous studies showing that antioxidant activities of various seaweed extracts and their constituents are due to activation of the Nrf2/HO-1 signaling (Jayawardena et al, 2018;Kang et al, 2015;Lekshmi et al, 2019;Niu et al, 2020;Park et al, 2018). Our results are also in good agreement with those of previous studies showing that Nrf2mediated activation of HO-1 in myoblasts can act as a protective mechanism against apoptosis induced after mitochondrial dysfunction caused by oxidative stimulation (Li et al, 2020;Park et al, 2021;Song et al, 2022).…”

The Hypoglycemic Activities and Underlying Mechanisms of Two Saponins‐Rich Components from Fried Ziziphus jujuba Mill. Kernel

“…Ge et al. [ 43 ] showed that the spinosin could ameliorate the insulin resistance of high‐fat diet mice. Besides, there are other literatures showed the hypoglycemic activities of jujuboside A.…”

“…Moreover, the IC 50 values of SZJs and acarbose against 𝛼-glucosidase and 𝛼-amylase are shown in Table 2, the results indicated that the SZJ- [40] , Kim et al, [41] and Song et al [42] have revealed the betulinic acid from Dillenia indica L. could increase the glucose-stimulated insulin secretion in insulinoma cells, and ameliorate hyperglycemia of high-fat diet fed mice. Ge et al [43] showed that the spinosin could ameliorate the insulin resistance of high-fat diet mice. Besides, there are other literatures showed the hypoglycemic activities of jujuboside A.…”

Phytochemical Analysis and Toxicity Assessment of Bouea Macrophylla Yoghurt

“…In this study, the terpenoid group of compounds is also abundant in ethanolic Boeau macrophylla, which possesses various health benefits. For instance, the previous study demonstrated that terpenoids or isoprenoid display antidiabetic action in mice [ 13 ] and also exhibit cytotoxicity against tumour cells [ 14 ].…”