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      Cardioprotective effect of curcumin and piperine combination against cyclophosphamide-induced cardiotoxicity

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          Abstract

          Objective:

          Curcumin is a well-established cardioprotective phytoconstituent, but the poor bioavailability associated with it is always a matter of therapeutic challenge. The present study was undertaken to increase the therapeutic efficacy of curcumin by combining with bio-enhancer like piperine against cyclophosphamide (CP)-induced cardiotoxicity in rats.

          Materials and Methods:

          Rats ( n = 8) were treated with curcumin (200 mg/kg, p.o.) alone and different dose combination of curcumin (100, 50, 25 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 10 days. All the treated groups were subjected to CP (200 mg/kg, i.p.) toxicity on day 1. Twenty-four hours after the last treatment, the effects were evaluated by changes in electrocardiographic (ECG) parameters, serum biomarkers, lipid profile, tissue antioxidants, and histopathological examination. Serum and tissue homogenate parameters were measured by semi-autoanalyzer and spectrophotometer, respectively. Results obtained were assessed by one-way analysis of variance followed by Tukey–Karmer multiple comparison test.

          Results:

          Incorporation of piperine with the doses of 50 and 25 mg/kg with curcumin exhibited significant beneficial effect compared to curcumin alone-treated group. The best effective group was a combination of curcumin 50 mg/kg with piperine 20 mg/kg which showed extremely significant ( P < 0.001) decrease and increase in ECG and serum biomarker level, respectively, and moderate significant ( P < 0.01) decrease in lipid profile, antioxidant levels, and histopathological score, compared to curcumin alone-treated group.

          Conclusion:

          From this study, it can be concluded that a novel dose combination of curcumin (50 mg/kg) with piperine (20 mg/kg) exhibited profound cardioprotection compared to curcumin (200 mg/kg) alone-treated group.

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          Most cited references14

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          Piper nigrum and piperine: an update.

          Black pepper (Piper nigrum L.) is a very widely used spice, known for its pungent constituent piperine. However, in addition to its culinary uses, pepper has important medicinal and preservative properties, and, more recently, piperine has been shown to have fundamental effects on p-glycoprotein and many enzyme systems, leading to biotransformative effects including chemoprevention, detoxification, and enhancement of the absorption and bioavailability of herbal and conventional drugs. Based on modern cell, animal, and human studies, piperine has been found to have immunomodulatory, anti-oxidant, anti-asthmatic, anti-carcinogenic, anti-inflammatory, anti-ulcer, and anti-amoebic properties. In this review, the chemical constituents, biological activities, effects of processing, and future potential of black pepper and piperine have been discussed thoroughly.
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            Bioavailability enhancers of herbal origin: an overview.

            Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds.
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              Suppression of Neuroinflammatory and Apoptotic Signaling Cascade by Curcumin Alone and in Combination with Piperine in Rat Model of Olfactory Bulbectomy Induced Depression

              Objectives Bilateral destruction of the olfactory bulbs is known to cause behavioral changes analogous to symptoms of depression. Curcumin, a traditional Indian spice is currently being investigated in different psychiatric problems including depression. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study is an attempt to elucidate the neuroprotective mechanism of curcumin and its co-administration with piperine against olfactory bulbectomy induced depression in rats. Methods Rats undergone olfactory bulbs ablations were analyzed after post-surgical rehabilitation period of 2 weeks. Animals were then treated with different doses of curcumin (100, 200 and 400 mg/kg; p.o.), piperine (20 mg/kg; p.o.) and their combination daily for another 2 weeks. Imipramine (10 mg/kg; i.p.) served as a standard control. Various behavioral tests like forced swim test (FST), open field behaviour and sucrose preference test (SPT) were performed, followed by estimation of biochemical, mitochondrial, molecular and histopathological parameters in rat brain. Results Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in FST, hyperactivity in open field arena, and anhedonic like response in SPT along with alterations in mitochondrial enzyme complexes, increased serum corticosterone levels and oxidative damage. These deficits were integrated with increased inflammatory cytokines (TNF-α) and apoptotic factor (caspase-3) levels along with a marked reduction in neurogenesis factor (BDNF) in the brain of olfactory bulbectomized (OBX) rats. Curcumin treatment significantly and dose-dependently restored all these behavioral, biochemical, mitochondrial, molecular and histopathological alterations associated with OBX induced depression. Further, co-administration of piperine with curcumin significantly potentiated their neuroprotective effects as compared to their effects alone. Conclusions The present study highlights that curcumin along with piperine exhibits neuroprotection against olfactory bulbectomy induced depression possibly by modulating oxidative-nitrosative stress induced neuroinflammation and apoptosis.
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                Author and article information

                Journal
                Indian J Pharmacol
                Indian J Pharmacol
                IJPharm
                Indian Journal of Pharmacology
                Medknow Publications & Media Pvt Ltd (India )
                0253-7613
                1998-3751
                Jan-Feb 2017
                : 49
                : 1
                : 65-70
                Affiliations
                [1] Department of Pharmacology, Shree Devi College of Pharmacy, Mangalore, Karnataka, India
                Author notes
                Address for correspondence: Dr. Manodeep Chakraborty, E-mail: manodeep.chakraborty@ 123456gmail.com
                Article
                IJPharm-49-65
                10.4103/0253-7613.201015
                5351241
                28458425
                aa396328-6b4a-4eaf-8766-6311325fb6d7
                Copyright: © 2017 Indian Journal of Pharmacology

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 07 September 2016
                : 08 December 2016
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                cardioprotective,cardiotoxicity,curcumin,cyclophosphamide,piperine

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