Linderane

Linderane is an orally active natural sesquiterpene lactone with blood-brain barrier permeability. Linderane indirectly activates PDE3 by activating ERK/STAT3, thereby inhibiting the cAMP/PKA/CREB signaling pathway and hepatic gluconeogenesis. Linderane protects pancreatic β cells against oxidative damage by inhibiting the activation of the p38 MAPK pathway and activating the Nrf2 pathway. Linderane inhibits cell apoptosis and ameliorates intestinal mucosal inflammation by suppressing the IL-6/JAK/STAT3 signaling pathway. Linderane reduces pain sensitivity and alleviates anxiety-like behaviors by activating cannabinoid receptor 2 (CB2R). Linderane can be used in studies related to type 2 diabetes, ulcerative colitis, and chronic inflammatory pain with anxiety^[1][2][3][4]. In Vitro:Linderane (2.5-20 µM; 5.5 h) inhibits gluconeogenesis in primary rat hepatocytes in a dose-dependent manner under both basal and Forskolin (HY-15371)-stimulated conditions, reduces the expression of Pck1 and G6pc, and this effect depends on the activation of PDE3^[1].
Linderane (2.5-20 µM; 2 h) reduces cAMP levels and inhibits CREB phosphorylation in rat primary hepatocytes in a dose- and time-dependent manner under both basal and Forskolin (HY-15371)-stimulated conditions, and this effect depends on the activation of PDE3^[1].
Linderane (10-20 µM) indirectly enhances the activities of total PDE and PDE3 (but does not affect PDE4 activity) in primary rat hepatocytes, while exerting no direct effect on purified PDE enzymes^[1].
Linderane (2.5-20 µM; 2 h) indirectly activates PDE3 via the ERK/STAT3 pathway in rat primary hepatocytes, and this pathway mediates its inhibitory effects on cAMP accumulation and gluconeogenesis^[1].
Linderane (5-20 μM; 24 h) does not impair the viability of untreated INS-1 pancreatic β-cells, but reduces their viability at 40 μM^[2].
Linderane (5-20 μM; 14 h) significantly improves the survival rate of INS-1 pancreatic β-cells induced by streptozotocin (STZ) (HY-13753)^[2].
Linderane (5-20 μM; 14 h) significantly restores insulin secretion in streptozotocin (STZ)-induced INS-1 pancreatic β cells^[2].
Linderane (5-20 μM; 14 h) significantly reduces the apoptosis level of streptozotocin (STZ)-induced INS-1 pancreatic β cells^[2].
Linderane (5-20 μM; 14 h) reverses STZ-induced changes in bax and bcl-2 expression, thereby reducing apoptosis of INS-1 pancreatic β-cells^[2].
Linderane (5-20 μM; 14 h) significantly inhibits the activation of the p38 MAPK pathway in STZ-induced INS-1 pancreatic β-cells^[2].
Linderane (5-20 μM; 14 h) significantly enhances the activation of the Nrf2 signaling pathway in streptozotocin (STZ)-induced INS-1 pancreatic β-cells^[2].
Linderane (5-20 μM; 14 h) significantly inhibits reactive oxygen species (ROS) production in streptozotocin (STZ)-induced INS-1 pancreatic β cells^[2].
Linderane (5-20 μM; 14 h) significantly restores the activities of antioxidant enzymes SOD, CAT and GPx in streptozotocin (STZ)-induced INS-1 pancreatic β cells^[2].
Linderane (12.5-50 μM; 48 h) dose-dependently inhibits IL-6 production and inflammatory responses in LPS (HY-D1056)-stimulated RAW264.7 macrophages^[3].
Linderane (3-25 μM) dose-dependently inhibits the IL-6/STAT3 signaling pathway and attenuates IL-6-mediated apoptosis resistance in mouse lymphocytes^[3].
Linderane (2.5-10 μM; 3-5 days) effectively inhibits the differentiation of naive CD4⁺ T cells isolated from splenocytes of C57BL/6 mice into Th17 cells^[3].
Linderane (2.5-10 μM; 3-4 days) exerts no significant effect on the differentiation of naive CD4⁺ T cells isolated from splenocytes of C57BL/6 mice into Treg cells^[3].
Linderane (0.1-10 μM; 24 h) dose-dependently inhibits LPS-induced release of IL-6, TNF-α and IL-1β from mouse BV2 microglial cells, with significant effects observed at concentrations of 0.1, 1 and 10 μM after 24 h^[4].
Linderane (10 μM; 24 h) promotes the polarization of LPS-stimulated mouse BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype after 24 h^[4]. In Vivo:Linderane (50 mg/kg; p.o.; single dose) activates hepatic PDEs via the ERK/STAT3 pathway and suppresses the hepatic cAMP/PKA/CREB pathway in healthy male C57BL/6J mice^[1].
Linderane (50 mg/kg; p.o.; twice daily; 20 days) improves glucose and lipid metabolism, suppresses hepatic gluconeogenic gene expression, and modulates hepatic PDE, cAMP^[1].
Linderane (chronic) improves glucose and lipid metabolism in ob/ob mice with type 2 diabetes mellitus^[2].
Linderane (50-100 mg/kg; p.o.; daily; 8 days) alleviates clinical symptoms and histopathological damage in DSS-induced ulcerative colitis in male C57BL/6J mice^[3].
Linderane (50 mg/kg; i.g.; once daily; 14 days) alleviates CFA (HY-153808)-induced chronic inflammatory pain and associated anxiety-like behavior in male C57BL/6 mice, reduces pro-inflammatory cytokine levels, and attenuates ACC microglial activation^[4].