Bioavailability of phytochemicals and its enhancement by drug delivery systems

Aqil, Farrukh; Munagala, Radha; Jeyabalan, Jeyaprakash; Vadhanam, Manicka V.

doi:10.1016/j.canlet.2013.02.032

Cited by 284 publications

(191 citation statements)

References 144 publications

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“…Assessment of the origin of their toxicity is necessary to find ways to decrease their cytotoxic properties. At the same time, the bioavailability of the compounds may be increased by introducing appropriate functional groups (76,77) or by using host guest-based drug delivery systems such as lipids, cyclodextrins, or liposomes (78,79).…”

Section: Discussionmentioning

confidence: 99%

Benzo[ b ]quinolizinium Derivatives Have a Strong Antimalarial Activity and Inhibit Indoleamine Dioxygenase

Jortzik

Zocher

Isernhagen

et al. 2016

Antimicrob Agents Chemother

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eThe heme-containing enzymes indoleamine 2,3-dioxygenase-1 (IDO-1) and IDO-2 catalyze the conversion of the essential amino acid tryptophan into kynurenine. Metabolites of the kynurenine pathway and IDO itself are involved in immunity and the pathology of several diseases, having either immunoregulatory or antimicrobial effects. IDO-1 plays a central role in the pathogenesis of cerebral malaria, which is the most severe and often fatal neurological complication of infection with Plasmodium falciparum. Mouse models are usually used to study the underlying pathophysiology. In this study, we screened a natural compound library against mouse IDO-1 and identified 8-aminobenzo[b]quinolizinium (compound 2c) to be an inhibitor of IDO-1 with potency at nanomolar concentrations (50% inhibitory concentration, 164 nM). Twenty-one structurally modified derivatives of compound 2c were synthesized for structure-activity relationship analyses. The compounds were found to be selective for IDO-1 over IDO-2. We therefore compared the roles of prominent amino acids in the catalytic mechanisms of the two isoenzymes via homology modeling, site-directed mutagenesis, and kinetic analyses. Notably, methionine 385 of IDO-2 was identified to interfere with the entrance of L-tryptophan to the active site of the enzyme, which explains the selectivity of the inhibitors. Most interestingly, several benzo[b]quinolizinium derivatives (6 compounds with 50% effective concentration values between 2.1 and 6.7 nM) were found to be highly effective against P. falciparum 3D7 blood stages in cell culture with a mechanism independent of IDO-1 inhibition. We believe that the class of compounds presented here has unique characteristics; it combines the inhibition of mammalian IDO-1 with strong antiparasitic activity, two features that offer potential for drug development.T ryptophan metabolism along the kynurenine (Kyn) pathway is a central component in neurodegenerative disorders and neuronal damage. The main metabolites of the kynurenine pathway include kynurenic acid, an antagonist of glutamate and nicotinic receptors; quinolinic acid, an agonist of N-methyl-D-aspartate receptors; and picolinic acid. Due to its potential role in diseases such as cancer (1), Alzheimer's disease (2), depression (3), stroke (4), and HIV infections (5), the kynurenine pathway is intensely studied with regard to chemotherapeutic applications in humans. Moreover, the pathway has been implicated in parasitic infections, such as trypanosomiasis (6), toxoplasmosis (7,8), and cerebral malaria (CM), as shown in mouse model systems (9, 10). CM is a potentially fatal consequence of infection with Plasmodium falciparum and can lead, in case of survival, to neurological or cognitive deficits (10). Severe malaria remains a global health problem. Although the mortality rate decreased by about 25% between 2000 and 2010, malaria caused 627,000 deaths in 2012. Currently, no specific treatment for CM is available, but a couple of immunomodulatory therapies are under investigation (11).As a...

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Section: Discussionmentioning

confidence: 99%

Benzo[ b ]quinolizinium Derivatives Have a Strong Antimalarial Activity and Inhibit Indoleamine Dioxygenase

Jortzik

Zocher

Isernhagen

et al. 2016

Antimicrob Agents Chemother

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“…Also, ethosomes can be used to increase the bioavailability of natural products [24] . For instance, in previous studies, ethosomes were used to enhance penetration of ligustrazine [25] and alkaloids from Sophora alopecuroides [26] .…”

Section: In Vitro Penetration and Bioavailability Of Novel Transdermamentioning

confidence: 99%

In vitro Penetration and Bioavailability of Novel Transdermal Quercetin-loaded Ethosomal Gel

Ramadon¹,

Anwar²,

Harahap³

2017

pharmaceutical-sciences

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Quercetin has been widely used to treat many diseases because of its high antioxidant activity. However, it has low oral bioavailability and penetration through the skin. The aim of this research was to enhance penetration and bioavailability of quercetin using transdermal ethosomal gel. Three ethosomal formulae, E1 (1 %), E2 (1.5 %) and E3 (2 %) with different concentration of quercetin were prepared using thin-film hydration method. Their physical properties were characterized, and then a selected ethosomal formula was incorporated into a gel dosage form. Two gels, one ethosomal and the other non-ethosomal were prepared. In vitro penetration using Franz diffusion cells and bioavailability study in Sprague Dawley male rats were carried out. Results showed that E2 was the chosen formula to be incorporated into the gel dosage form. According to the in vitro penetration study, the diffusion flux of quercetin from the ethosomal and non-ethosomal gels were 343.35±17.69 ng/cm 2 /h and 120.68±11.92 ng/cm 2 /h, respectively (P<0.05). In the bioavailability study, ethosomal gel showed higher maximum concentration (C max ) and area under curve (AUC 0-t ) when compared to non-ethosomal gel and oral suspension. C max from the ethosomal gel, nonethosomal gel, and oral suspension were 413.49±28.64, 189.46±49.68, and 61.92±14.31 ng/ml, respectively (P<0.05). AUC 0-t from the ethosomal gel, non-ethosomal gel, and oral suspension were 4035.15±560.60, 584.87±265.46, and 431.21±239.85, respectively (P<0.05). In conclusion, ethosomal gel could increase penetration and bioavailability of quercetin compared to non-ethosomal gel.

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“…After intravenous administration, they are rapidly captured by the mononuclear phagocytic system (MPS) and removed from the blood circulation. This behavior has been explored for the efficient delivery of antiparasitic drugs for treating infections in these cells (Aqil et al 2013). In this context, for example, plants from genus Piper have been investigated as a source of new natural products with potential antitumoral, antifungal, antiplasmodial, antioxidant and tripanocidal properties (da Silva et al 2014), as well as antimicrobial, antipyretic, aromatic, emetic, diuretic, hallucinogen, ornamental and insect repellent roles, among other applications (Parmar et al 1997;Wadt et al 2004;Ferreira et al 2010).…”

Section: Liposomal Systems As Carriers For Bioactive Compoundsmentioning

confidence: 99%

Liposomal systems as carriers for bioactive compounds

et al. 2015

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Since the revolutionary discovery that phospholipids can form closed bilayered structures in aqueous systems, the study of liposomes has become a very interesting area of research. The versatility and amazing biocompatibility of liposomes has resulted in their wide-spread use in many scientific fields, and many of their applications, especially in medicine, have yielded breakthroughs in recent decades. Specifically, their easy preparation and various structural aspects have given rise to broadly usable methodologies to internalize different compounds, with either lipophilic or hydrophilic properties. The study of compounds with potential biotechnological application(s) is generally related to evaluation and risk assessment of the possible cytotoxic or therapeutic effects of the compound under study. In most cases, undesirable sideeffects are associated with an interaction of the liposome with the cell membrane and/or its absorption and subsequent interaction with a cellular biomolecule. Liposomal carrier systems have an unprecedented potential for delivering bioactive substances to specific molecular targets due to their biocompatibility, biodegradability and low toxicity. Liposomes are therefore considered to be an invaluable asset in applied biotechnology studies due to their potential for interaction with both hydrophilic and lipophilic compounds.

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Bioavailability of phytochemicals and its enhancement by drug delivery systems

Cited by 284 publications

References 144 publications

Benzo[ b ]quinolizinium Derivatives Have a Strong Antimalarial Activity and Inhibit Indoleamine Dioxygenase

Benzo[ b ]quinolizinium Derivatives Have a Strong Antimalarial Activity and Inhibit Indoleamine Dioxygenase

In vitro Penetration and Bioavailability of Novel Transdermal Quercetin-loaded Ethosomal Gel

Liposomal systems as carriers for bioactive compounds

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