002C-3 protects the brain against ischemia-reperfusion injury by inhibiting autophagy and stimulating CaMKK/CaMKIV/HDAC4 pathways in mice

This study was designed to investigate the effect of 002C-3, a derivative of magnolol, on transient cerebral middle occlusion （tMCAO） in a mice model and to identify the underlying mechanisms. 002C-3 （100 and 150 pg/kg, i.v. after ending occlusion） significantly reduced neurological deficit scores, infarct volumes, and brain water contents after 1.5 h MCAO and 24 h reperfusion. 002C-3 （75 150μg/kg） decreased the exudation of Evans blue from brain capillaries. 002C-3 （100 μg/kg） significantly inhibited the activity of MMP-9 and MMP-2 in the injured hemisphere. 002C-3 decreased the expression of autophagy-associated proteins, Beclin-1 and LC3B-Ⅱ, and increased the level of p62 in injured hemisphere. 002C-3 （100 pg/kg） significantly increased the expression of p-CaMKIV and p-HDAC4 in injured hemisphere. In conclusion, 002C-3 shows a neuroprotective effect on tMCAO injury in mice, and its mechanisms may be associated with alleviation of blood-brain barrier damage caused by the activation of MMPs, inhibition of autophagy, and stimulation of calcium signals related to cell survival. These findings suggest that 002C-3 is a neuroprotective agent that acts on multiple pathways.

Protection of Total Flavonoid Fraction from Nervilia fordii on Lipopolysaccharide-induced Acute Lung Injury in Rats

Objective To investigate the effects of total flavonoid fraction(TFF) from Nervilia fordii on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats,and to explore their protective mechanism.Methods LPS-induced ALI model was established by LPS(5 mg/kg) injection via left cervical vein.Blood samples were collected from the cervical artery of all rats at 5 and 6 h after LPS challenge for arterial blood gas test and cytokines measurements,and pulmonary microvascular permeability(PMP),lung wet/dry weight ratio(W/D),and pathological features were observed.Results Phytochemical study showed that the TFF contained 67.3% of flavonoids expressed in rutin and three flavone glycosides.The TFF pretreatment(6.24 and 12.48 mg/kg) attenuated the partial arterial pressure of oxygen decline in blood significantly,and decreased the PMP and lung W/D in ALI rats.In addition,the TFF(6.24 and 12.48 mg/kg) also ameliorated the LPS-induced lung damages including alveolar edema,neutrophils infiltration,alveolar hemorrhage,and thickening of the alveolar wall.Furthermore,the treatment with the TFF(6.24 and 12.48 mg/kg) also down-regulated the levels of pro-inflammatory cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and intercellular adhesion molecule-1(ICAM-1),and up-regulated the level of anti-inflammatory cytokine IL-10 in serum of ALI rats simultaneously.Conclusion These results suggest that the TFF could protect LPS-induced ALI in rats,which may be mediated,at least in part,by adjusting the production of inflammatory cytokines including TNF-α,IL-6,ICAM-1,and IL-10.