Potential of Piper spp. as a source of new compounds for the leishmaniases treatment.

Current treatment guidelines for leishmaniasis is based on chemotherapy with drugs that show a set of limitations such as high cost, toxicity, difficult route of administration, and lack of efficacy in endemic areas. In this context, phytopharmaceutical products and herbal medicines emerge as promising alternatives for developing new treatment against leishmaniasis. This review discusses the perspectives of leishmaniasis treatment based on natural products and phytotherapy highlighting the Piper genus, especially P. aduncun and P. mollicomum Kunth covering the period of 1998 to 2020. Leishmanicidal activity of pure compounds of Piper spp. [3-(3,4,5-trimethoxyphenyl) propanoic acid, 3-chlorosintenpyridone, 2'-hydroxy-3',4',6'-trimethoxy-chalcone, cardamonin, conocarpan, cubebin, eupomatenoid, flavokavain B, ( +)-(7R,8S)-epoxy-5,6-didehydrokavain, N-[7-(3',4'-methylenedioxypheny l-2(E),4(E)-heptadienoyl-pyrrolidine, N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl-pyrrolidine, piperovatine, pellitorine, and piplartine (piperlongumine)] were proved against the promastigote and amastigote forms of parasite related with cutaneous (L. (L.) amazonensis, L. (V.) braziliensis, and L. (V.) guyanensis) and visceral (L. (L.) donovani, L. (L.) chagasi, and L. (L.) infantum). We also discussed the perspective of leishmaniasis treatment, considering the potential synergism between different promising species of Piper, presenting some interesting interaction possibilities for future studies between plants. Finally, the necessary steps for technological development of phytomedicines and herbal medicines with the desirable quality requirements for medicines are highlighted. The data presented here highlight the use of Piper spp. as source of pharmacological compounds that can lead to effective, safe, and inexpensive treatments for leishmaniasis.