Interaction Of Piperine Research Articles

Piperine, a phytochemical prevents the biofilm city of methicillin-resistant Staphylococcus aureus: A biochemical approach to understand the underlying mechanism

Methicillin-resistant Staphylococcus aureus (MRSA), a drug-resistant human pathogen causes several nosocomial as well as community-acquired infections involving biofilm machinery. Hence, it has gained a wide interest within the scientific community to impede biofilm-induced MRSA-associated health complications. The current study focuses on the utilization of a natural bioactive compound called piperine to control the biofilm development of MRSA. Quantitative assessments like crystal violet, total protein recovery, and fluorescein-di-acetate (FDA) hydrolysis assays, demonstrated that piperine (8 and 16 μg/mL) could effectively compromise the biofilm formation of MRSA. Light and scanning electron microscopic image analysis confirmed the same. Further investigation revealed that piperine could reduce extracellular polysaccharide production by down-regulating the expression of icaA gene. Besides, piperine could reduce the cell-surface hydrophobicity of MRSA, a crucial factor of biofilm formation. Moreover, the introduction of piperine could interfere with microbial motility indicating the interaction of piperine with the quorum-sensing components. A molecular dynamics study showed a stable binding between piperine and AgrA protein (regulator of quorum sensing) suggesting the possible meddling of piperine in quorum-sensing of MRSA. Additionally, the exposure to piperine led to the accumulation of intracellular reactive oxygen species (ROS) and potentially heightened cell membrane permeability in inhibiting microbial biofilm formation. Besides, piperine could reduce the secretion of diverse virulence factors from MRSA. Further exploration revealed that piperine interacted with extracellular DNA (e-DNA), causing disintegration by weakening the biofilm architecture. Conclusively, this study suggests that piperine could be a potential antibiofilm molecule against MRSA-associated biofilm infections.

Effect of piperine on the inhibitory potential of MexAB-OprM efflux pump and imipenem resistance in carbapenem-resistant Pseudomonas aeruginosa

The escalating prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant threat to global public health through the spread of its ‘high-risk’ clones. Immediate and decisive research into antimicrobial agents against CRPA is crucial for the development of effective measures and interventions. Overexpression of the MexAB-OprM efflux pump is one of the major mechanisms of CRPA. Since the active efflux of antibacterial agents plays a significant role in mediating drug resistance in CRPA, the inhibition of efflux pumps has become a promising strategy to restore antibacterial potency. Piperine (PIP) has been proven to be a promising efflux pump inhibitor in some bacteria. However, there are no studies on whether PIP can act as a potential efflux pump inhibitor in CRPA. The present study aimed to identify the antibacterial activity of PIP against CRPA and to evaluate the effect on the MexAB-OprM efflux pump. Molecular docking was used to analyze the possible interaction of PIP with the proteins of the MexAB-OprM efflux pump in CRPA. The effect of PIP on the expression of the MexAB-OprM efflux pump was investigated by real-time quantitative PCR (qPCR) and ethidium bromide accumulation efflux assay. The effect of PIP on CRPA imipenem (IPM) resistance was investigated by the checkerboard dilution method. The results demonstrated that PIP exhibited the lowest binding affinity of −9.1 kcal towards efflux pump proteins. A synergistic effect between PIP and IPM on CRPA was observed. More importantly, PIP effectively hindered the efflux of ethidium bromide and IPM by up-regulating MexR gene expression while down-regulating MexA, MexB, and OprM gene expressions. In conclusion, PIP could enhance the antibacterial activity of IPM by inhibiting the MexAB-OprM efflux pump. Our work proved that PIP had the potential to be an efflux pump inhibitor of CRPA.

Computational Insights into the interaction of Piperine with Immune Regulatory Proteins: A Docking Study

Computational Insights into the interaction of Piperine with Immune Regulatory Proteins: A Docking Study

Variations in the Piperine content in three varieties of Pepper and mapping its anti-inflammatory potential by molecular docking

Pepper known as the king of spices is one of the most widely used spice in the world, and it has its fair share of medicinal properties as well. It has been used in traditional medicine for many centuries owing to its medicinal properties apart from its flavour and pungent taste. Piperine is the most important bioactive compound present in different Piper species. Differences among the three Piper species common in South India viz. <i>Piper nigrum</i>, <i>Piper longum</i>, and <i>Piper cubeba</i> were evaluated by estimating the various phytochemicals such as alkaloids, flavonoids, and phenols in them. Further, the quantity of piperine in these three <i>Piper</i> species were determined using HPLC analysis. The piperine content in <i>Piper nigrum</i>, <i>Piper longum</i>, and <i>Piper cubeba</i> were found to be 235.05 μg/mL, 268.50 μg/mL, and 8.56 μg/mL respectively. Since inflammation is the major pathology involved in most of the disease conditions and since pepper is traditionally used in managing respiratory inflammation, we ventured to identify its anti-inflammatory potential. Herein, the anti-inflammatory properties of piperine were checked by in silico docking analysis of piperine with inflammatory proteins. The interaction of piperine with <i>NF</i>-κB, COX-2, COX-1, and <i>TNF</i>-α, as evidenced by the binding scores reveals that piperine interacts with them and modulates inflammation. Further <i>in-vitro</i> and in-vivo studies are warranted to scientifically validate the traditional claims.

Synergistic Antibiofilm Effect of Thymol and Piperine in Combination with Aminoglycosides Antibiotics against Four Salmonella enterica Serovars.

Biofilms related to human infection have high levels of pathogenicity due to their resistance to antimicrobial agents. The discovery of antibiofilm agents is necessary. One approach to overcome this problem is the use of antibiotics agents' combination. This study aimed to determine the efficacy of the combination of natural products thymol and piperine with three aminoglycosides antibiotics, amikacin, kanamycin, and streptomycin against biofilm-forming Salmonella enterica. The microtiter plate assay method was used to evaluate the biofilm-producing capacity of the isolates. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined by the broth microdilution method. The inhibition of biofilm formation and biofilm eradication was determined using the microtiter broth method. The checkerboard method was used to determine the combined effects of natural products with aminoglycosides antibiotics. All the tested isolates showed various levels of biofilm formation. Overall, combinations provided 43.3% of synergy in preventing the biofilm formation and 40% of synergy in eradicating preformed biofilms, and in both cases, no antagonism was observed. The combination of thymol with kanamycin showed a synergistic effect with 16- to 32-fold decrease of the minimum biofilm eradication concentration (MBEC) of kanamycin. The interaction of piperine with amikacin and streptomycin also revealed a synergistic effect with 16-fold reduction of the minimum biofilm inhibitory concentration (MBIC). The combination of thymol with the three antibiotics showed a strong synergistic effect in both inhibiting the biofilm formation and eradicating the preformed biofilm. This study demonstrates that thymol and piperine potentiate the antibiofilm activity of amikacin, kanamycin, and streptomycin. These combinations are a promising approach therapeutic to overcome the problem of Salmonella enterica biofilm-associated infections. In addition, these combinations could help reduce the concentration of individual components, thereby minimizing the nephrotoxicity of aminoglycosides antibiotics.

In silico investigation of spice molecules as potent inhibitor of SARS-CoV-2

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel infectious disease that is in rapid growth. Several trials are going on worldwide to find a solution for this pandemic. The viral replication can be blocked by inhibiting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (SARS-CoV-2 RBD Spro) and the SARS-CoV-2 main protease (SARS-CoV-2 Mpro). The binding of potential small molecules to these proteins can inhibit the replication and transcription of the virus. The spice molecules that are used in our food have antiviral, antifungal and antimicrobial properties. As spice molecules are consumed in the diet, hence its antiviral properties against SARS-CoV-2 will benefit in a significant manner. Therefore, in this work, the molecular docking of 30 selected spice molecules (screened through ADME property) was performed to identify the potential inhibitors for the RBD Spro and Mpro of SARS-CoV-2. We have found that though all the molecules bind actively with the SARS-CoV-2 RBD Spro and Mpro, but Piperine has the highest binding affinity among the 30 screened molecules. Besides, the comparative study between Piperine and currently used drugs show that Piperine is more effective. The interaction of Piperine with RBD Spro and Mpro is further validated by the molecular dynamics (MD) simulation studies. The free energy landscape and binding free energy results also, support for the stable complex formation of Piperine with RBD Spro and Mpro. We anticipate immediate wet-lab experiments and clinical trials in support of this computational study that might help to inhibit the SARS-CoV-2 virus. Communicated by Ramaswamy H. Sarma

Spectroscopic, quantum chemical, hydrogen bonding, reduced density gradient analysis and anti-inflammatory activity study on piper amide alkaloid piperine and wisanine

A combined experimental and theoretical quantum chemical calculations have been carried out to study the geometry, vibrational wavenumbers, electronic transition and anti-inflammatory activity of piper amide alkaloid compound piperine (PP). Computational study is done on other piper amide alkaloid wisanine (WS) using B3LYP/6–311G(d,p) basis set. The conformational analysis is carried out to find the most stable geometry of PP and WS. Normal coordinate analysis (NCA) is performed to analyse the vibrational wavenumber and potential energy distribution (PED) assignments. The interaction of PP and WS with water molecule is also performed to know the effect of hydrogen bond on its geometry and vibrational spectra. Natural bond orbital (NBO) analysis was performed to study the charge delocalization, hyperconjugative interaction, inter and intramolecular hydrogen bonding interaction in the molecule to know about anti-inflammatory active site. Non-covalent interactions are analyzed using reduced density gradient (RDG) analysis. The UV–visible spectrum of PP in ethanol and water solvent is recorded and compared with calculated data. The 1H and 13C NMR spectra of PP are recorded and analyzed. The chemical stability and anti-inflammatory activity of title compound are evaluated by HOMO-LUMO analysis. The chemical reactivity descriptors are calculated to predict the reactivity and stability of the molecule. The intermolecular interactions and crystal packing of title compound are studied by Hirshfeld surface analysis techniques. PP is screened for its anti-inflammatory activity. Molecular docking study predicts the binding site of PP and WS into its target protein.

Ionic Liquid Green Assembly-Mediated Migration of Piperine from Calf-Thymus DNA: A New Possibility of the Tunable Drug Delivery System

Biocompatible surface-active ionic liquid (SAIL) was used first to study the deintercalation process of a well-known natural compound piperine (PIP) as an anticancer drug, obtained from PIP–calf thymus DNA (ctDNA) complex under controlled experimental conditions. In this study, we have been exploring the interaction of PIP in SAIL (1-butyl-3-methylimidazolium octyl sulfate ionic liquid ([C4mim][C8OSO3])), ctDNA, and deintercalation of PIP from the PIP–ctDNA complex through SAIL micelle using various spectroscopic techniques. Absorption, emission, and lifetime decay measurements provide strong evidence of the relocation of PIP molecules from ctDNA to SAIL micelle. Fluorescence quenching and steady-state fluorescence anisotropy were employed to examine the exact location of PIP in different media. Moreover, the surface tension technique was also employed to confirm the release of PIP molecules from the PIP–ctDNA complex in the presence of SAIL. Circular dichroism analysis suggested that SAIL micelle does not perturb the ctDNA structure, which supported the fact that SAIL micelle can be used as a safe vehicle for PIP. Overall, the study highlighted a novel strategy for deintercalation of drug using SAIL because the release of the drug can be controlled over a period by varying the concentration and composition of the SAIL.

Piperine Modulates Protein Mediated Toxicity in Fragile X-Associated Tremor/Ataxia Syndrome through Interacting Expanded CGG Repeat (r(CGG)exp) RNA.

An expansion of CGG tandem repeats in the 5' untranslated region (5'-UTR) of fragile X mental retardation 1 (FMR1) gene causes fragile X-associated tremor/ataxia syndrome (FXTAS). The transcripts of these expanded repeats r(CGG)exp either form RNA foci or undergo the repeat-associated non-ATG (RAN) translation that produces toxic homopolymeric proteins in neuronal cells. The discovery of small molecule modulators that possess a strong binding affinity and high selectivity to these toxic expanded repeats RNA could be a promising therapeutic approach to cure the expanded repeat-associated neurological diseases. Therefore, here we sought to test the therapeutic potential of a natural alkaloid, piperine, by assessing its ability to bind and neutralize the toxicity of r(CGG)exp RNA motif. To accomplish this first, we have determined the affinity of piperine to r(CGG)exp RNA using fluorescence-based binding assay and isothermal titration calorimetry assay. These assays showed that piperine forms a thermodynamically favorable interaction with r(CGG)exp RNA with high selectivity to the G-rich RNA motif. Interaction of piperine with r(CGG)exp motif was further validated using several biophysical techniques such as CD, CD melting, NMR spectroscopy, and gel retardation assay. Moreover, piperine was also found to be effective for improving the r(CGG)exp associated splicing defects and RAN translation in a FXTAS cell model system. Our results effectively provided the evidence that piperine strongly interacts with r(CGG)exp RNA and could be used as a suitable candidate for therapeutic development against FXTAS.

Piperine : A Bioenhancer

Piperine is a major alkaloid of Pepper fruits belonging to family Piperaceae which has a number of medicinal proper-ties. Pepper fruits are one of them which have been established as bioenhancer for some selected drugs. In Ayureveda since centuries it is called as “Yogvahi”. Black pepper fruits are the supporting evidence where piperine was one of the ingredients of “Trikatu”. Black pepper fruits are used in different food, drink, dessert, perfume as a brandy flavors and preservative of pickles. It is well known as “King of Spices”. Piperine enhances the bioavailability of structurally and therapeutically differ-ent drugs, either by increasing the absorption or by delaying the metabolism of the drug or by a combination of both processes. It is evident that black pepper fruits have been used as bio-enhancer in allopathic system of medicine. Piperine has been used as bioenhancer for certain antibacterial- antibiotics with promising results. The interaction of piperine with drug-metabolizing enzymes is responsible for oxidation, hydroxylation and glucuronidation. Piperine appears to top in the list of bioenhancers as it has been used as bioenhancer for Allopathic, Ayurvedic and Unani drugs. Piperine enhances Cmax of different drugs significantly.

La présence chronique d’un mélange de polluants faiblement dosés dans un régime enrichi en lipides, aggrave les altérations métaboliques provoquées par ce régime

A combined experimental and theoretical quantum chemical calculations have been carried out to study the geometry, vibrational wavenumbers, electronic transition and anti-inflammatory activity of piper amide alkaloid compound piperine (PP). Computational study is done on other piper amide alkaloid wisanine (WS) using B3LYP/6–311G(d,p) basis set. The conformational analysis is carried out to find the most stable geometry of PP and WS. Normal coordinate analysis (NCA) is performed to analyse the vibrational wavenumber and potential energy distribution (PED) assignments. The interaction of PP and WS with water molecule is also performed to know the effect of hydrogen bond on its geometry and vibrational spectra. Natural bond orbital (NBO) analysis was performed to study the charge delocalization, hyperconjugative interaction, inter and intramolecular hydrogen bonding interaction in the molecule to know about anti-inflammatory active site. Non-covalent interactions are analyzed using reduced density gradient (RDG) analysis. The UV–visible spectrum of PP in ethanol and water solvent is recorded and compared with calculated data. The 1H and 13C NMR spectra of PP are recorded and analyzed. The chemical stability and anti-inflammatory activity of title compound are evaluated by HOMO-LUMO analysis. The chemical reactivity descriptors are calculated to predict the reactivity and stability of the molecule. The intermolecular interactions and crystal packing of title compound are studied by Hirshfeld surface analysis techniques. PP is screened for its anti-inflammatory activity. Molecular docking study predicts the binding site of PP and WS into its target protein.

Interaction of piperine with rat liver microsomes

Pretreatment of adult male albino rats with piperine did not induce cytochrome P-450 whereas safrole did cause such induction. Piperine and safrole interacted with different forms of cytochrome P-450 as indicated by their in vivo effect on drug metabolising enzymes and mixed function oxidases and electrophoretic patterns. Incubation of piperine or safrole with dithionite- or NADPH-reduced microsomes from untreated rats resulted in a modified type II difference spectrum with an absorption maximum at 427 nm and a trough at 408 nm.