Andrographolide enhances hippocampal BDNF signaling and suppresses neuronal apoptosis, astroglial activation, neuroinflammation, and spatial memory deficits in a rat model of chronic cerebral hypoperfusion.

Andrographolide is a medical herbal compound with documented anti-inflammatory activity and therapeutic efficacy in animal models of Alzheimer's disease, traumatic brain injury, and ischemic stroke. The present study examined the potential therapeutic effects of andrographolide on chronic cerebral hypoperfusion (CCH)-induced hippocampal neuronal damage and cognitive dysfunction. A CCH model was established in male Sprague Dawley (SD) rats using 2-vessel occlusion (2VO). After 4 weeks of CCH, spatial learning and memory were assessed in the Morris water maze and structural damage to the hippocampus by hematoxylin and eosin (HE) staining. Astrocyte activation was examined by immunohistochemical staining and Western blotting for glial fibrillary acid protein (GFAP), while expression levels of the pro-inflammatory cytokine-tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß), the apoptosis effector cysteinyl aspartate specific proteinase-3 (caspase-3), and the neuroprotectant brain-derived neurotrophic factor (BDNF) and the TrkB receptor were estimated by Western blotting. After 4 weeks of CCH, the hippocampus of 2VO rats exhibited marked neurodegeneration as well as elevated GFAP, TNF-α, IL-1ß, and caspase-3 compared to Sham controls. In addition, spatial learning was impaired compared to Sham controls. Andrographolide treatment during CCH suppressed astrocyte activation as evidenced by reduced GFAP expression, enhanced expression of BDNF and TrkB, improved impaired spatial learning and memory, and reversed upregulated TNF-α, IL-1ß, and caspase-3 expression. These results reveal a potential neuroprotective effect of andrographolide on hippocampal neuronal damage and cognitive impairment from CCH due to suppression of astrocyte activation and enhancement of BDNF-TrkB signaling.

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery.

AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation, such as diameters of arterioles and venules, velocity of RBCs in venules, leukocyte rolling, adhesion and emigration, free radicals released from post-capillary venules, FITC-albumin leakage and mast cell degranulation, were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile, the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils, and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation, including a significant increase in the positive region of venule stained with Monastral blue B, rolling and adhesion of leukocytes, production of oxygen radical in venular wall, albumin efflux and enhanced mast cell degranulation in vivo, all of which, except for the leukocyte rolling, were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils, and the expression of ICAM-1 in HUVECs were increased by exposure to LPS, and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.