Piperine and Its Metabolite’s Pharmacology in Neurodegenerative and Neurological Diseases

Abstract

Piperine (PIP) is an active alkaloid of black and long peppers. An increasing amount of evidence is suggesting that PIP and its metabolite’s could be a potential therapeutic to intervene different disease conditions including chronic inflammation, cardiac and hepatic diseases, neurodegenerative diseases, and cancer. In addition, the omnipresence of PIP in food and beverages made this compound an important investigational material. It has now become essential to understand PIP pharmacology and toxicology to determine its merits and demerits, especially its effect on the central nervous system (CNS). Although several earlier reports documented that PIP has poor pharmacokinetic properties, such as absorption, bioavailability, and blood–brain barrier permeability. However, its interaction with metabolic enzyme cytochrome P450 superfamily and competitive hydrophobic interaction at Monoamine oxide B (MAO-B) active site have made PIP both a xenobiotics bioenhancer and a potential MAO-B inhibitor. Moreover, recent advancements in pharmaceutical technology have overcome several of PIP’s limitations, including bioavailability and blood–brain barrier permeability, even at low doses. Contrarily, the structure activity relationship (SAR) study of PIP suggesting that its several metabolites are reactive and plausibly responsible for acute toxicity or have pharmacological potentiality. Considering the importance of PIP and its metabolites as an emerging drug target, this study aims to combine the current knowledge of PIP pharmacology and biochemistry with neurodegenerative and neurological disease therapy.

Bacterial Efflux Pump Inhibitors Reduce Antibiotic Resistance

“…Piperine ( Figure 2 ) is an important natural compound with a variety of health benefits. Despite its low absorption and bioavailability due to hydrophobicity, its ability to participate in herb–drug or herb–herb interactions also contributes to the pharmacokinetic and dynamic properties of other drugs/nutraceuticals [ 52 ]. The activity of ciprofloxacin against S. aureus is increased by piperine and its analogues, which also act as NorA inhibitors by lowering the minimum inhibitory concentration (MIC) of ciprofloxacin in S. aureus 1199B.…”

Exploring the potential of spice‐derived phytochemicals as alternative antimicrobial agents

“…Piperine has high absorption rate (up to 97%) in mammals due to its large hydrophobic group, which enables it to cross the non-polar molecular barrier in the intestine (Azam et al, 2022). Metabolism of piperine mostly takes place in the liver where around 20 metabolites could be observed as a result of hydroxylation, ring-opening, methylation, decarboxylation, reduction, glucuronidation and glutathione conjugation (Li et al, 2020).…”

Therapeutic considerations of bioactive compounds in Alzheimer's disease and Parkinson's disease: Dissecting the molecular pathways

“…Interestingly, galantamine is reported to possess a good bioavailability of around 80%–100% in blood, however, poor BBB permeability renders galantamine a lower bioavailability in the brain (Farlow, 2003; Marucci et al, 2021; Misra et al, 2016; Wang, Pavurala, et al, 2018). Again piperine , an alkaloid principally derived from Piper nigrum plant has been found to exert therapeutic effects against several neurodegenerative diseases like AD, PD and HD (Azam et al, 2022; Salman et al, 2022). The effective dose of piperine can be suggested to range between 5 and 50 mg/kg i.p.…”