Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment （intravenous injection） re- duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-a in brain tissue. Pretreatment with puerarin （intravenous injection） attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 （JAK2） and signal transducers and activators of transcription 3 （STAT3） activation and nuclear factor kappa B （NF-KB） inhibition. These observa- tions were inhibited by the alpha7 nicotinic acetylcholine receptor （a7nAchR） antagonist a-bungarotoxin （a-BGT）. In addition, puerarin pretreatment increased the expression of a7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re- sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi- ated through the activation of the cholinergic anti-inflammatory pathway.

JAK2 and MAPK pathways are involved in the inhibitory effect of berberine hydrochloride on gastric cancer cell proliferation and IL-8 secretion

Acknowledgements This work was supported by Educational Commission of Shanghai of China （2012JW19）; Key Research Innovation Project （13ZZ099）; Key Project from Department of Education of China （20123107130002）; Shanghai Eastern Scholar Program （2013-59） and Shanghai E-research Institute of Bioactive Constituent in TCM plan. Abstract： Aim This investigation was to identify whether Janus-activated kinase 2 （JAK2） and mitogen-activated protein kinase （MAPK） pathways were involved in the inhibitory effect of berberine hydrochloride （BER） on gastric cancer cell proliferation and IL-8 expression in vitro and in vivo. Methods CCK- 8 assay was used to assess the cell proliferation. IL-8 production was determined by ELISA and qPCR assay. Mo- lecular pathways involved were evaluated by ELISA and western-blotting methods. Results BER time- and dose- dependently inhibited the proliferation of MGC 803 and AGS cells. It also suppressed tumor growth in nude mice xenografted with MGC 803 cells. In addition, BER reduced interleukin-8 （IL-8） secretion of AGS cells as well as MGC 803 cells both in vitro and in vivo. Further study disclosed that inactivation of JAK2, p38 MAPK, ERK1/2 and JNK by BER contributed to the decreased proliferation and tumor growth as well as IL-8 expression in gastric cancer. Although there was no significantly synergistic inhibitory effect between BER and evodiamine on gastric cancer cell proliferation and tumor growth, BER could counteract the up-regulation of IL-8 induced by evodiamine in vitro and vivo. Conclusions Our results suggested that BER might be an efficient and safe drug candidate for treating gastric cancer through JAK2 and MAPK pathways.