Haijun Zhang1, Chunping Zhu2, Zhe Sun3, Xiaoguang Yan3, Huihui Wang3, Haibo Xu3, Jiani Ma3, Yanrong Zhang3. 1. The Second Department of Endocrinology, The First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang Province, China; The Second Department of Endocrinology, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar 161005, Heilongjiang Province, China. Electronic address: zhang_haijun3@126.com. 2. Department of Cardiac Function, The First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang Province, China; Department of Cardiac Function, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar 161005, Heilongjiang Province, China. 3. The Second Department of Endocrinology, The First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang Province, China; The Second Department of Endocrinology, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar 161005, Heilongjiang Province, China.
Abstract
AIMS: Linderane, an important bioactive compound in Linderae, improved glucose and lipid metabolism in ob/ob mice. However, the effect of linderane on streptozotocin (STZ)-induced oxidative damage in INS-1 cells remains unclear. MAIN METHODS: INS-1 cells were pre-treated with different doses of linderane for 2 h and then treated with 3 mM STZ for 12 h. Cell viability was determined by MTT assay. Cell apoptosis was detected using an Annexin V-FITC Apoptosis Detection Kit. The level of intracellular ROS was determined using dichlorofluorescein-diacetate (DCFH-DA). The activities of insulin secretion, SOD, catalase (CAT) and GPx were measured using ELISA kits. The expression levels of bax, bcl-2, p38, p-p38, nuclear Nrf2 and HO-1 were measured using western blot. KEY FINDINGS: The results showed that STZ-caused inhibitory effects on cell viability and insulin secretion were mitigated by linderane. Furthermore, linderane inhibited apoptosis and oxidative stress in STZ-induced INS-1 cells. Finally, linderane suppressed the activation of p38 MAPK pathway, as well as enhanced the activation of Nrf2 pathway in STZ-induced INS-1 cells. Activation of p38 MAPK pathway or inhibition of Nrf2 significantly reversed the protective effects of linderane against STZ-induced ROS production and cell apoptosis. SIGNIFICANCE: The protective effects of linderane on STZ-induced INS-1 cells might be attributed to the inhibition of p38 MAPK and activation of Nrf2 pathway.
AIMS: Linderane, an important bioactive compound in Linderae, improved glucose and lipid metabolism in ob/ob mice. However, the effect of linderane on streptozotocin (STZ)-induced oxidative damage in INS-1 cells remains unclear. MAIN METHODS: INS-1 cells were pre-treated with different doses of linderane for 2 h and then treated with 3 mM STZ for 12 h. Cell viability was determined by MTT assay. Cell apoptosis was detected using an Annexin V-FITC Apoptosis Detection Kit. The level of intracellular ROS was determined using dichlorofluorescein-diacetate (DCFH-DA). The activities of insulin secretion, SOD, catalase (CAT) and GPx were measured using ELISA kits. The expression levels of bax, bcl-2, p38, p-p38, nuclear Nrf2 and HO-1 were measured using western blot. KEY FINDINGS: The results showed that STZ-caused inhibitory effects on cell viability and insulin secretion were mitigated by linderane. Furthermore, linderane inhibited apoptosis and oxidative stress in STZ-induced INS-1 cells. Finally, linderane suppressed the activation of p38 MAPK pathway, as well as enhanced the activation of Nrf2 pathway in STZ-induced INS-1 cells. Activation of p38 MAPK pathway or inhibition of Nrf2 significantly reversed the protective effects of linderane against STZ-induced ROS production and cell apoptosis. SIGNIFICANCE: The protective effects of linderane on STZ-induced INS-1 cells might be attributed to the inhibition of p38 MAPK and activation of Nrf2 pathway.