Piperine is the main compound present in black pepper, and is the carrier of its specific pungent taste, which is responsible for centuries of human dietary utilization and worldwide popularity as a food ingredient. Along with the application as a food ingredient and food preservative, it is used in traditional medicine for many purposes, which has in most cases been justified by modern scientific studies on its biological effects. It has been confirmed that piperine has many bioactive effects, such as antimicrobial action, as well as many physiological effects that can contribute to general human health, including immunomodulatory, hepatoprotective, antioxidant, antimetastatic, antitumor, and many other activities. Clinical studies demonstrated remarkable antioxidant, antitumor, and drug availability-enhancing characteristics of this compound, together with immunomodulatory potential. All these facts point to the therapeutic potential of piperine and the need to incorporate this compound into general health-enhancing medical formulations, as well as into those that would be used as adjunctive therapy in order to enhance the bioavailability of various (chemo)therapeutic drugs.

Piperine-A Major Principle of Black Pepper: A Review of Its Bioactivity and Studies

Introduction: Piperine has various pharmacological effects and can modulate the functional activity of metabolic enzymes and drug transporters. Consequently, there is a great interest in th...

Piperine-mediated drug interactions and formulation strategy for piperine: recent advances and future perspectives.

Recent trends in analytical methods for water-soluble vitamins.

Interest in botanical insecticides derived from plants has increased as a result of environmental concerns and insect resistance to chemical insecticides. In this study, we explored the insecticidal activity of Urginea maritima bulbs extract and its inhibitory effect on acetylcholinesterase enzyme system in the rice weevil Sitophilus oryzae (L.) (Coleoptera: Curculionidae). Phytochemical screening and HPLC-ESI/TOF-MS analysis revealed the presence of bioactive molecules with high insecticidal potential. Content of polyphenols (130.88 ± 0.44 mg GAE/g FW), flavonoids (50.81 ± 0.25 mg RE/g FW) as well as alkaloids (12.09 ± 0.16 mg AE/g FW) were high. HPLC-ESI/TOF-MS analysis results demonstrated that ferulic acid (124.19 μg/g FW), vanillic acid (75.84 μg/g FW) and 4-hydroxybenzoic acid (59.73 μg/g FW) were the major phenolic compounds of U. maritima bulbs extract. The toxic potential against the rice weevil using contact and repellent bioassays showed the highest insecticidal potential of U. maritima bulbs extract. The LD50, LC50 and RC50 values were 19.03 μg/insect, 2.35 μg/cm2 and 0.009 μg/cm2 for contact bioassay by topical application, contact bioassay by treated filter paper method and repellent bioassay, respectively. Furthermore, U. maritima bulbs extract inhibited acetylcholinesterase (AChE) activity and median inhibition concentration IC50 was evaluated to 66.08 μg/ml. The findings of the present investigation confirmed that Urginea maritima may be recommended as an eco-friendly alternative to synthetic insecticides.

Screening for insecticidal potential and acetylcholinesterase activity inhibition of Urginea maritima bulbs extract for the control of Sitophilus oryzae (L.)

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Molecular and pharmacological aspects of piperine as a potential molecule for disease prevention and management: evidence from clinical trials

Linarin is a flavone glycoside in the plants Flos chrysanthemi indici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii, and has been reported to possess analgesic, antipyretic, anti-inflammatory and neuroprotective activities. In this paper, linarin was investigated for its AChE inhibitory potential both in-vitro and ex-vivo. Ellman's colorimetric method was used for the determination of AChE inhibitory activity in mouse brain. In-vitro assays revealed that linarin inhibited AChE activity with an IC50 of 3.801 ± 1.149 μM. Ex-vivo study showed that the AChE activity was significantly reduced in both the cortex and hippocampus of mice treated intraperitoneally with various doses of linarin (35, 70 and 140 mg/Kg). The inhibition effects produced by high dose of linarin were the same as that obtained after huperzine A treatment (0.5 mg/Kg). Molecular docking study revealed that both 4'-methoxyl group and 7-O-sugar moiety of linarin played important roles in ligand-receptor binding and thus they are mainly responsible for AChE inhibitory activity. In view of its potent AChE inhibitory activity, linarin may be a promising therapeutic agent for the treatment of some diseases associated with AChE, such as glaucoma, myasthenia gravis, gastric motility and Alzheimer's disease.

http://ijpr.sbmu.ac.ir/article_1702_239be0d92204be974e344e0e0efee090.pdf

Linarin Inhibits the Acetylcholinesterase Activity In-vitro and Ex-vivo

Although linarin possesses diverse pharmacological activities, its poor oral bioavailability has been a concern for further development. The present study aimed to demonstrate the feasibility of improving the oral absorption of linarin in rats with a bioenhancer‒piperine. First, the intestinal permeability of linarin in the presence and absence of verapamil or piperine was investigated using an in situ single-pass rat intestinal perfusion method. A significant increase in the P eff when co-perfused with verapamil or piperine indicated that piperine effectively inhibited P-glycoprotein mediated efflux of linarin. Then, the pharmacokinetic profiles of linarin in rats after oral administration of linarin (50 mg/kg) alone and in combination with piperine (20 mg/kg) were determined using a validated LC–MS/MS method. The results showed that piperine increased the plasma exposure (AUC) of linarin by 381% along with an increase in the C max by 346% and the T max from 0.05 h to 0.2 h. The present study revealed that piperine significantly enhanced the oral absorption of linarin in rats by inhibiting P-glycoprotein mediated cellular efflux during the intestinal absorption and likely simultaneously by inhibiting the metabolism of linarin.

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Effects of Piperine on the Intestinal Permeability and Pharmacokinetics of Linarin in Rats

Liquid chromatography–ion trap mass spectrometry was employed to investigate the metabolism of linarin in rats. Identification and structural elucidation of the metabolites were performed by comparing the differences in molecular masses, retention times, and full scan MSn spectra between linarin and its metabolites. Six metabolites (acacetin, apigenin, acacetin glucuronide, apigenin glucuronide, acacetin sulfate, apigenin sulfate) were detected in rat urine after oral administration of linarin at the dose of 50 mg kg−1. Furthermore, a selective and sensitive liquid chromatography–triple quadruple mass spectrometry assay was developed and validated for the simultaneous determination of linarin and acacetin (the major metabolite of linarin) in rat urine. Chromatographic separation was carried out on a C18 column, and mass spectrometric detection was performed using a triple-quadrupole mass spectrometer coupled with an electrospray ionization source in the positive ion mode. Quantitation of linarin and acacetin was performed using selected reaction monitoring of precursor–product ion transitions at m/z 593 → 285 for linarin, 285 → 242 for acacetin, and 303 → 153 for hesperitin (internal standard), respectively. The assay exhibited good linearity (r > 0.9900) for both linarin and acacetin. The intra- and inter-day precisions were <13.4 % and the accuracy was between −8.1 and 3.1 %. The method was successfully applied to the urinary excretion study of linarin in rats after oral administration of linarin.

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Xinchi Feng

Papers

Linarin Inhibits the Acetylcholinesterase Activity In-vitro and Ex-vivo

Effects of Piperine on the Intestinal Permeability and Pharmacokinetics of Linarin in Rats

Analysis of Linarin and Its Metabolites in Rat Urine by LC–MS/MS