A systematic review on black pepper (Piper nigrum L.): from folk uses to pharmacological applications.

Considered as the "King of spices", black pepper (Piper nigrum L.) is a widely used spice which adds flavor of its own to dishes, and also enhances the taste of other ingredients. Piper nigrum has also been extensively explored for its biological properties and its bioactive phyto-compounds. There is, however, no updated compilation of these available data to provide a complete profile of the medicinal aspects of P. nigrum. This study endeavors to systematically review scientific data on the traditional uses, phytochemical composition, and pharmacological properties of P. nigrum. Information was obtained using a combination of keywords via recognized electronic databases (e.g., Science Direct and Google Scholar). Google search was also used. Books and online materials were also considered, and the literature search was restricted to the English language. The country with the highest number of traditional reports of P. nigrum for both human and veterinary medicine was India, mostly for menstrual and ear-nose-throat disorders in human and gastrointestinal disorders in livestock. The seeds and fruits were mostly used, and the preferred mode of preparation was in powdered form, pills or tablets, and paste. Piper nigrum and its bioactive compounds were also found to possess important pharmacological properties. Antimicrobial activity was recorded against a wide range of pathogens via inhibition of biofilm, bacterial efflux pumps, bacterial swarming, and swimming motilities. Studies also reported its antioxidant effects against a series of reactive oxygen and nitrogen species including the scavenging of superoxide anion, hydrogen peroxide, nitric oxide, DPPH, ABTS, and reducing effect against ferric and molybdenum (VI). Improvement of antioxidant enzymes in vivo has also been reported. Piper nigrum also exhibited anticancer effect against a number of cell lines from breast, colon, cervical, and prostate through different mechanisms including cytotoxicity, apoptosis, autophagy, and interference with signaling pathways. Its antidiabetic property has also been confirmed in vivo as well as hypolipidemic activity as evidenced by decrease in the level of cholesterol, triglycerides, and low-density lipoprotein and increase in high-density lipoprotein. Piper nigrum also has anti-inflammatory, analgesic, anticonvulsant, and neuroprotective effects. The major bioactive compound identified in P. nigrum is piperine although other compounds are also present including piperic acid, piperlonguminine, pellitorine, piperolein B, piperamide, piperettine, and (-)-kusunokinin, which also showed biological potency. Most pharmacological studies were conducted in vitro (n = 60) while only 21 in vivo and 1 clinical trial were performed. Hence, more in vivo experiments using a pharmacokinetic and pharmacokinetic approach would be beneficial. As a conclusive remark, P. nigrum should not only be regarded as "King of spices" but can also be considered as part of the kingdom of medicinal agents, comprising a panoply of bioactive compounds with potential nutraceutical and pharmaceutical applications.