Effects of andrographolide and 14-deoxy-11,12-didehydroandrographolide on cultured primary astrocytes and PC12 cells.

AIMS: To test the effects of andrographolide (AP1) and 14-deoxy-11,12-didehydroandrographolide (AP2) on pheochromocytoma cell line 12 (PC12) cells in an astrocyte-rich environment. MAIN METHODS: The abilities of AP1 and AP2 to reduce the secretion of pro-inflammatory cytokines Interleukin (IL)-1, IL-6, and Tumor necrosis factor (TNF)-α from stimulated astrocytes were tested. In addition, the abilities of AP1 and AP2 to reduce oxidative stress in astrocytes were tested using an oxidative-sensitive fluorescent dye. The reduction of chondroitin sulfate proteoglycan (CSPG) in stimulated astrocytes was tested using the dot blot method. Reduction of H(2)O(2)-induced death was tested in PC12 cells. Astrocyte-conditioned medium (ACM) and TNF-α-stimulated astrocyte-conditioned medium (SACM) were used to assess the effects of AP2 on PC12 cells treated with H(2)O(2). KEY FINDINGS: AP1 and AP2 reduced pro-inflammatory cytokines, reactive oxygen species (ROS), and CSPG in TNF-α stimulated astrocytes. AP1 protected H(2)O(2)-treated PC12 cells cultured in ACM. Co-incubation of PC12 cells in H(2)O(2), and ACM collected from AP1 treated astrocytes did not prevent cell death. SIGNIFICANCE: AP1 and AP2 effectively ameliorated astrocytic pro-inflammatory reactions and prevented PC12 cell death with different efficacies. These compounds may be candidates for treatment of spinal-cord injury and neurodegeneration.