Black pepper prevents anemia of inflammation by inhibiting hepcidin over-expression through BMP6-SMAD1/ IL6-STAT3 signaling pathway

Free Radic Biol Med. 2021 Mar 23:S0891-5849(21)00178-7. doi: 10.1016/j.freeradbiomed.2021.03.019. Online ahead of print.ABSTRACTHepcidin, a circulatory hepatic peptide hormone, is associated with systemic iron homeostasis. Inflammation leads to an increase in hepcidin expression, which dysregulates body iron level. The related disorder, anemia of inflammation, is the second most prevalent anemia-related disorder worldwide. In the present study, we conducted in vitro and in vivo studies to evaluate the effect of black pepper and its major alkaloid, piperine, on anemia of inflammation. The initial in vitro study using human hepatocyte cell line, HepG2, confirmed that among different black pepper extracts: methanol (BPME), ethanol (BPEE) and aqueous (BPAE), BPME to be most effective in downregulating transcription of hepcidin gene. Further, BPME and piperine (the major bioactive alkaloid of black pepper) significantly downregulated hepcidin protein expression at 200 μg/ml and 100 μM concentrations, respectively. In the next phase, BPME and piperine were found to significantly attenuate the BMP-6 and IL-6 induced hepcidin overexpression by downregulating the increased level of pSMAD1 and pSTAT3 proteins. For in in vivo study, we first subcutaneously injected male BALB/c mice with oil of turpentine, thrice within a period of two weeks, in order to enhance the expression of hepcidin. After that, the intraperitoneal administration of BPME and piperine at 70 and 25 mg/kg body weigh...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Source Type: research