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In summary, different extracts of Piper nigrum reduced brain and serum levels of CRP, total NF-B, and MCP-1, reduced Cox-2, TNF-, and NOS-2 in the brain and reduced the proBDNF/mBDNF ratio and (p-JNK) and p-p38 MAPK proteins, (Bax/Bcl-2) ratio, and caspase activation in the brain at higher doses