Recent Articles on Andrographis sp.

Andrographolide nanoparticles in leishmaniasis: characterization and in vitro evaluations

Int J Nanomedicine. 2010 Dec 9;5:1113-1121.

Andrographolide nanoparticles in leishmaniasis: characterization and in vitro evaluations.

Roy P, Das S, Bera T, Mondol S, Mukherjee A.

Department of Chemical Technology, University of Calcutta, Kolkata, West Bengal, India.

Andrographolide (AG) is a diterpenoid lactone isolated from the leaves of Andrographis paniculata. AG is a potent and low-toxicity antileishmanial agent. Chemotherapy applications of AG are, however, seriously constrained because of poor bioavailability, short plasma half-life, and inappropriate tissue localization. Nanoparticulation of AG was therefore envisaged as a possible solution. AG nanoparticles (AGnp) loaded in 50:50 poly(DL-lactide-co-glycolic acid) were prepared for delivery into the monocyte-macrophage cells infested with the amastigote form of leishmanial parasite for evaluation in the chemotherapy of leishmaniasis. Particle characteristics of AGnp were optimized by proportionate application of a stabilizer, polyvinyl alcohol (PVA). Physicochemical characterization of AGnp by photon correlation spectroscopy exhibited an average particle size of 173 nm and zeta potential of -34.8 mV. Atomic force microscopy visualization revealed spherical nanoparticles with a smooth surface. Antileishmanial activity was found to be significant for the nanoparticle preparation with 4% PVA (IC(50) 34 µM) in about one-fourth of the dosage of the pure compound AG (IC(50) 160 µM). AGnp therefore have significant potential to target the infested macrophage cells and prove valuable in chemotherapy of neglected tropical diseases such as leishmaniasis.

PMID: 21270962 [PubMed - as supplied by publisher]

Andrographolide and 14-deoxy-11, 12- didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells

Life Sci. 2011 Jan 7. [Epub ahead of print]

Andrographolide and 14-deoxy-11, 12- didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells.

Ping OJ, Kuroyanagi M, Sulaiman SF, Muhammad TS, Tan ML.

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia.

Abstract

AIMS: Cytochrome P450 (CYP) enzymes have been implicated in a large number of preventable drug-herb interactions. Andrographis paniculata Nees, a tropical herb widely used for various health conditions contains two major diterpenoids, andrographolide and 14-deoxy-11, 12-didehydroandrographolide. These compounds were evaluated systematically for their effects on CYP1A2, CYP2D6 and CYP3A4 expressions in HepG2 cells.

MAIN METHODS: Quantitative RT-PCR and Western blot analysis were used to assess the mRNA and protein expression of the three CYPs. CYP3A4 enzyme activity was evaluated using P450-Glo™ Assays. The LanthaScreen® TR-FRET PXR (SXR) Competitive Binding Assay was used to determine if the compounds are potential PXR-ligands.

KEY FINDINGS: Both diterpenoids inhibited the mRNA and protein expressions of CYP1A2, CYP2D6, and CYP3A4. Interestingly, the lowest concentration of both diterpenoids produced a more than 50% reduction in the mRNA and protein expression of CYP3A4 and this reduction was consistent with the enzyme activitiy. Further experiments revealed that both diterpenoids were also capable of attenuating the ability of dexamethasone to induce CYP3A4 expression, and 14-deoxy-11, 12-didehydroandrographolide tended to bind to the PXR -LBD site in a concentration-dependent manner.

SIGNIFICANCE: These diterpenoids are potential CYP3A4 inhibitors and the effects on CYP3A4 may be clinically significant. 14-deoxy-11, 12-didehydroandrographolide inhibits CYP3A4 by binding and antagonizing PXR function.

Copyright © 2010. Published by Elsevier Inc.
PMID: 21219911 [PubMed - as supplied by publisher]