Promising Antituberculosis Activity of Piperine Combined with Antimicrobials: A Systematic Review

Abstract

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.

Functional and Structural Roles of the Major Facilitator Superfamily Bacterial Multidrug Efflux Pumps

“…Furthermore, CCCP has been shown to be effective, albeit in an indirect manner, as an inhibitor of antimicrobial efflux in a great variety of major facilitator superfamily transporters by collapsing the proton motive force [38,89,122]. Along these lines, reserpine and piperine have served as general inhibitors for many efflux pumps, independent of the mode of energy, substrates, and superfamily membership [159][160][161].…”

Piperine: A review of its biological effects

“…Similarly, a recent review by Christodoulou, Tchoumtchoua, Skaltsounis, Scorilas, and Halabalaki (2019) discussed concepts on the anti‐diabetic effect of certain alkaloids, including piperine, with special reference to their molecular targets throughout the insulin‐signaling pathway. In addition, reviews related to the anti‐tuberculosis (Hegeto et al, 2019), autophagy regulators (Liang et al, 2019), chemoprevention, and anticancer (Mokbel, Wazir, & Mokbel, 2019; Zadorozhna et al, 2019) effects of piperine have been published. Furthermore, Joshi, Shrestha, and Adhikari (2018) published a review that aimed to provide the literature on recent advancement of the chemistry, pharmacognosy, pharmacological activities of piper, including new piperine‐based formulations and other general use of P .…”

Potent anti‐mycobacterial and immunomodulatory activity of some bioactive molecules of Indian ethnomedicinal plants that have the potential to enter in TB management

“…Immunomodulatory activity of Piperine is isolated from Piper nigrum L. and Piper lungum L. Piperine is an alkaloid the principal compound of Piper nigrum and Piper lungum belongs to the family Piperaceae which are widely distributed in all parts of India (Hegeto et al 2019). The pungent fruits of these plants are considered to be stomachic, laxative, anti-helminthic, aphrodisiac, anti-dysenteric, carminative, and appetizer properties (Barua et al 2014).…”

“…A similar finding was also reported by Hegeto et al . (2019) where they have found piperine in combination with RIF increased the bioavailability of the drug and this effect synergizes with piperine and streptomycin combination in clinical isolates of M.tb (Hegeto et al . 2019).…”