03094nas a2200301   4500008004100000022001400041245008000055210006900135260000800204300001200212490000700224520220800231653001402439653001602453653002002469653001302489653001502502653001202517100002002529700002302549700001702572700001902589700002002608700001802628700001802646700002202664856010602686       2021                        eng d  a1369-378600aOxidative stress induced by piperine leads to apoptosis in Candida albicans0 aOxidative stress induced by piperine leads to apoptosis in Candi  cAPR  a366-3780 v593 a<p>Candida albicans is a member of pathogens with potential drug resistance threat that needs novel chemotherapeutic strategies. Considering the multifarious biological activities including bioenhancer activity, anti-Candida potential of piperine was evaluated against planktonic/biofilm and hyphal growth of C. albicans alone or in combination as a synergistic agent with fluconazole. Piperine inhibits planktonic growth at or less than 15 mu g/ml, hyphae induction at 5 mu g/ml concentration, and exhibits stage-dependent activity against biofilm growth of a fluconazole-resistant strain of C. albicans (ATCC10231). Though piperine couldn't kill inoculum completely at minimum inhibitory concentration (MIC), it is fungicidal at higher concentrations, as shown in apoptosis assay. FIC index values indicate that piperine exhibits excellent synergistic activity with fluconazole against planktonic (0.123) and biofilm (0.215) growth of an FLC resistant strain. Mode of anti-Candida activity was studied by identifying piperine responsive proteins wherein the abundance of 25 proteins involved in stress response, signal transduction and cell cycle were modulated (22 up and 3 downregulated) significantly in response to piperine (MIC50). Modulation of the proteins involved suggests that piperine affectsmembrane integrity leading to oxidative stress followed by cell cycle arrest and apoptosis in C. albicans. Flow cytometry-basedmitochondrialmembrane potential (MMP), cell cycle and apoptosis assay, as well as real-time quantitative polymerase chain reaction analysis of selected genes, confirms piperine induced oxidative stress (TRR1), cell cycle arrest and apoptosis (CaMCA1). Based on our results, we conclude that piperine inhibits planktonic and difficult-to treat-biofilm growth of C. albicans by affecting membrane integrity thereby inducing oxidative stress and apoptosis. Lay Abstract Piperine inhibit Candida albicans growth (planktonic and biofilm) significantly in our study. Piperine exhibits excellent synergistic potential with fluconazole The proteome analysis suggests that piperine induced membrane damage leads to oxidative stress followed by cell cycle arrest and apoptosis.</p>10aApoptosis10aC. albicans10adrug resistance10apiperine10aproteomics10asynergy1 aThakre, Archana1 aJadhav, Vyankatesh1 aKazi, Rubina1 aShelar, Amruta1 aPatil, Rajendra1 aKharat, Kiran1 aZore, Gajanan1 aKaruppayil, Mohan  uhttps://library.ncl.res.in/content/oxidative-stress-induced-piperine-leads-apoptosis-candida-albicans