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Piperine, a bioactive compound from Piper nigrum and Piper longum, has shown promising activity as efflux pump (EP) inhibitor and as adjunct in treatment of tuberculosis (TB). The present systematic review investigated scientific studies of the activity of piperine against mycobacteria, with a focus on its mechanism of action, drug interactions, and antimycobacterial activity. A broad and rigorous literature search of three electronic databases (PubMed, Web of Knowledge, and LILACS) was performed according to the PRISMA statement. We considered studies that were published up to December 1, 2017. Google Scholar was also searched to increase the number of publications. We searched for articles using the search terms "piperine" and "Mycobacterium spp." The search yielded a total of 225 articles. After removing duplicate publications, 208 publications remained. Of these, we evaluated the full text of 13 articles. After applying the inclusion criteria, eight studies were included in the present systematic review. The results of the systematic review showed that piperine has promising anti-TB activity, mainly when combined with antimicrobials, and plays an important role as an EP inhibitor.

Tuberculosis (TB) is an important public health problem worldwide and the emergence of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB worsened the global context. The resistance in Mycobacterium tuberculosis, the causative agent of TB, can partially derive from efflux pumps (EPs) activity in plasma membrane. Due to the recent discovery of piperine (PIP), an organic alkaloid compound, increasing the bioavailability of various drugs, the current assay evaluated the combined activity of PIP and anti-TB drugs in susceptible and resistant M. tuberculosis clinical isolates. The minimum inhibitory concentrations for isoniazid, rifampicin, ethambutol, streptomycin and PIP were determined by resazurin microtiter assay and the combined effects of anti-TB drugs with PIP determined by resazurin drug combination microtiter assay and time-kill curve. The efflux pump inhibitor activity of PIP was determined by bromide accumulation assay and cytotoxicity carried out in VERO cells and J774. A1 macrophages. PIP showed to have EPI activity and RIF + PIP and SM + PIP combinations showed synergistic effect, but low effect in enhancing the killing in M. tuberculosis H 37 Rv and in the clinical isolates studied, which had different resistance profiles. Future studies are needed to further clarify the importance of PIP as an adjunctive drug in the therapy against TB., (Copyright © 2018 Elsevier Ltd. All rights reserved.)