Carnosic Acid Protects INS-1 β-Cells against Streptozotocin-Induced Damage by Inhibiting Apoptosis and Improving Insulin Secretion and Glucose Uptake

Abstract

Carnosic acid (CA), a natural polyphenolic diterpene derived from Rosmarinus officinalis, has been proven to possess a broad spectrum of medicinal properties. Nevertheless, no studies on its impact on pancreatic β-cells have been conducted to date. Herein, clonal rat INS-1 (832/13) cells were pretreated with CA for 24 h and then incubated with streptozotocin (STZ) for 3 h. Several functional experiments were performed to determine the effect of CA on STZ-induced pancreatic β-cell damage, including cell viability assay, apoptosis analysis, and measurement of the level of insulin secretion, glucose uptake, malondialdehyde (MDA), reactive oxygen species (ROS), and proteins expression. STZ treatment decreased cell survival, insulin secretion, glucose uptake, and increased apoptosis, MDA, and ROS production in INS-1 cells. Furthermore, protein expression/phosphorylation analysis showed significant down-regulation in insulin, PDX-1, PI3K, AKT/p-AKT, and Bcl2. On the other hand, expression of BAX and BAD and cleaved PARP were significantly increased. Interestingly, preincubation with CA reversed the adverse impact of STZ at the cellular and protein expression levels. In conclusion, the data indicate that CA protects β-cells against STZ-induced damage, presumably through its modulatory effect on the different pathways, including the Pi3K/AKT/PDX-1/insulin pathway and mitochondria-mediated apoptosis.

Relative Molecular Similarity in Compound Structures Modulating Neurodegenerative Apoptosis

“…Malfunctions in redox parameters and apoptosis are also characteristics of tumour cells, and so it is unsurprising to find drugs with efficacy against cancer being applied to neurodegenerative conditions, or to discover that experimental models developed to study different neurodegenerative conditions are responsive to the same compounds. Examples of such pluripotent compounds include resveratrol, carnosic acid, vitamin D and statins [73] [74] [75] [76]. Although neurodegenerative conditions are characterised by neurocellular changes involving complex molecular mechanisms and different clinical symptoms, a fundamental flaw in the control of cell redox parameters may initiate a pathological process that develops clinically in a manner dependent on the cell types involved to become manifest as different diseases.…”

Mechanistic Insights into the Ameliorative Effect of Cichoriin on Diabetic Rats—Assisted with an In Silico Approach

“…Many patients with type 2 DM have a resistance to insulin-mediated glucose disposal that is highly associated with impaired insulin secretion [ 30 , 31 ]. Based on previous studies, HFD is considered to be a well-established model for inducing insulin resistance through the accumulation of lipids in various tissues [ 32 ].…”

“…The immuno-histochemical findings presented in the current study demonstrated that cichoriin (50 and 100 mg/kg) can induce significant improvements in the functioning of beta-cells ( Figure 2 ), which was evidenced by the elevated serum insulin level ( Table 1 ). Elevated levels of BG, TC, and TG, as well as the disturbance in levels of oxidative stress markers, including, lipid peroxidation product (MDA) and antioxidant SOD, are often concomitant with the development of DM [ 30 ]. In this study, TAC, catalase and SOD levels were markedly decreased and MDA was increased in the HFD/STZ group.…”

Antidiabetic Effect of Green Vegetable Leaf Powders in Diabetic Rats

“…According to HPLC results resveratrol and rosmarinic acid were the main identified flavonoids in the investigated leaf powders. Both compounds have the potential to be useful adjuvants in the treatment of diabetes, since resveratrol improved peripheral insulin sensitivity [52] and rosmarinic acid preserved β-cells function against STZ-induced damage [53].…”