Rational Druggability Investigation Toward Selection of Lead Molecules: Impact of the Commonly Used Spices on Inflammatory Diseases

Abstract

Herbal remedies and phytochemicals have been used in traditional medicine. Most of the herbs used in human diet have some major effective elements that can affect various pathways in the human body and play a therapeutic role in healing disorders or diseases. Among the inflammatory diseases, worldwide common disorders possess well-known pathways that can be controlled by diet and behavior. There are some well-established targets that are used for anti-inflammatory drugs like cyclooxygenase type 1 and 2 (COX-1 and COX-2), lipoxygenase, prostaglandin D2 receptor, DP1, CRTH2, and so on. In this article, we investigated the role of phytochemicals, extracted from different commonly used spices in the food industry, in preventing or healing the inflammatory disorders. The ability of such bioactives to inhibit COX-2 enzyme has been investigated and compared with marketed selective and nonselective NSAIDs, aspirin and celecoxib. Thereafter, the pharmacokinetic and pharmacodynamic properties of such ingredients have been evaluated for their druggability potential. The results indicated that piperine showed the best ADME (absorption, distribution, metabolism, and excretion) and toxicity profiles among all bioactives. Also, it possessed better affinity value, -7.80518 kcal/mol and energy binding -85.08 kcal/mol, in inhibition of COX-2 with PDB Id: 1CVU rather than other compounds and significantly the higher dock score than aspirin, close to celecoxib. Therefore, piperine has been suggested to be used as the major ingredient in daily diet as a potent anti-inflammatory and anticancer agent.

Diet-Related Metabolomic Signature of Long-Term Breast Cancer Risk Using Penalized Regression: An Exploratory Study in the SU.VI.MAX Cohort

“…In this study, piperine, an exogenous active alkaloid with no endogenous origin reported so far, was highlighted as potential predictor of breast cancer risk (inverse association), with high stability across penalized models (selection frequencies >90% on the 1,000 bootstraps). Piperine is contained in black and long pepper (33) and is used as feed additive in animal feed, in particular for poultry (34). The human exposure to piperine via this latter source has been estimated at 0.93 mg/metabolic body weight per day (34).…”

“…Several animal or cellular studies suggested a promising spectrum of properties for piperine such as anti-oxidant (35,36), anti-inflammatory (33,35,36), immunomodulatory, bioavailability and absorption promoter for many active molecules (33,37), antiasthmatic, anticonvulsing, antimutagenic, antimycobacterial, and anticancer activities (ref. 33; chemopreventive properties, including inhibition of angiogenesis and increased cell apoptosis), especially in breast cancer models (38)(39)(40). In our study, piperine was in particular positively associated with alcohol intake and with a "Western" dietary pattern.…”

Structure-Based Virtual Screening, Molecular Docking, MolecularDynamics Simulation of VEGF Inhibitors for the Clinical Treatment of Ovarian Cancer

“…Similarly, the complex structures were recaptured from the virtual screening result and the same method was iterated. An excel sheet was xed to investigate all the a nities, hydrogen interaction, steric energy and high re-rank score to recognize the best inhibitor [104][105][106][107][108][109][110][111][112].…”

Piperine: Chemical, biological and nanotechnological applications

“…Inflammatory disorders are caused by enzymes such as cyclooxygenase types 1 and 2 (COX-1 and COX-2), lipooxygenase, prostaglandin receptor (DP 1 ) and prostaglandin D2 receptor (2CRTH2). Zakerali et al (47) selected different spices commonly used in the food industry to observe their ability to inhibit the enzymes that cause inflammatory processes. PIP demonstrated an inhibitory effect of COX-2 and a better affinity value (-7.8 kcal mol -1 ) and energy binding (-85.08 kcal mol -1 ) than aspirin and celecoxib.…”