Crude extract of Ceriporia lacerata has a protective effect on dexamethasone-induced cytotoxicity in INS-1 cells via the modulation of PI3K/PKB activity

Abstract

Abstract. Excessive and/or long-term glucocorticoid therapy reduces β-cell mass and induces hyperglycemia, which contribute to the development of steroid-induced diabetes. Ceriporia (C.) lacerata is one of the white-rot fungi and has been used in bioremediations, such as lignocellulose degradation, in nature. The pharmacologic effect of C. lacerata on steroid-induced β-cell toxicity is not known. In this study, we evaluated the effect of a crude extract from a submerged cultivation of C. lacerata on the survival and apoptosis of INS-1 rat insulin-secreting cells exposed to dexamethasone (Dex), a synthetic diabetogenic glucocorticoid. Treatment with the C. lacerata crude extract (CLCE) largely blocked the Dex-induced reduction in survival and apoptosis of INS-1 cells. Moreover, CLCE treatment inhibited Dex-induced protein kinase B (PKB) dephosphorylation without affecting Dex-induced extracellular signal-regulated protein kinase-1/2 dephosphorylation and MKP-1 upregulation. Importantly, the protective effect of CLCE on Dex-induced cytotoxicity in INS-1 cells was attenuated by LY294002, an inhibitor of PI3K/PKB. CLCE treatment, however, did not protect the INS-1 cells from the cytotoxic effects triggered by other insults, such as interleukin-1β (an inflammatory cytokine), streptozotocin (a diabetogenic drug), thapsigargin (a calcium mobilizing agent), and tunicamycin (an ER stress inducer).Collectively, these findings demonstrate for the first time the ability of CLCE to specifically protect INS-1 cells from Dex-induced cytotoxicity through the modulation of the PI3K/ PKB pathway. It is suggested that CLCE may be applied for the prevention and/or treatment of steroid diabetes in which reduction of β-cell survival and induction of β-cell apoptosis play pathogenic roles.

Ceriporia lacerata Mycelium Culture Medium as a Novel Anti-Aging Microbial Material for Cosmeceutical Application

“…Therefore, this study aimed to investigate the antioxidant, wound healing, wrinkle improvement, moisturizing, and whitening effects of CLM on the anti-aging mechanism of skin cells. To the best of our knowledge, this study is the first report to propose a new route for skincare at the cellular level based on the anti-aging mechanism using anti-diabetic ingredients derived from the culture of CLM, an emerging microorganism [14][15][16][17].…”

“…Ceriporia lacerata is a type of white putrefactive filamentous fungus that plays an important role in bioremediation by breaking down cellulose and lignin [12,13]. The bioactive efficacy of C. lacerata mycelium (CLM) culture has been studied to control hyperglycemia levels [14], insulin secretion through cytoprotective effects [15], and insulin signaling through activation of AMP-activated protein kinase (AMPK) and glucose transporter type 4 (GLUT4) [16,17]. However, the pharmacological effect of CLM on anti-oxidation and anti-aging is not yet known.…”

Immune-Enhancing Effect of Submerged Culture of Ceriporia lacerata Mycelia on Cyclophosphamide-Induced Immunosuppressed Mice and the Underlying Mechanisms in Macrophages

“…lacerata mycelia (CLM) and well-formulated antidiabetic nutraceutical tablets (Cepona TM ). Submerged culture medium of CLM has been used to control high blood glucose levels [ 17 , 18 ] and insulin secretion via cytoprotective effects [ 19 ]. CLM also exhibits antihyperglycemic efficacy by lowering insulin resistance [ 20 ] and promotes insulin signal transduction via the activation of AMPK and GLUT4 [ 20 , 21 ].…”

The Effects of C. lacerata on Insulin Resistance in Type 2 Diabetes Patients

“…C. lacerata mycelium was inoculated into the potato dextrose agar (Difco Co., Maryland, USA) medium and cultured at 25 °C for 9 days. Liquid medium of C. lacerata mycelium was then mixed with 4 g/L of starch, 20 g/L of glucose, and 600 mL of purified water at 23 °C for 10 days under pH 5 at a rotational speed of 300 rpm [11].…”