Recent Articles on Andrographis sp.

Herb-drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats

Chem Biol Interact. 2010 Jan 22. [Epub ahead of print]

Herb-drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats.

Chien CF, Wu YT, Lee WC, Lin LC, Tsai TH.

Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Herb-drug interaction has become a serious problem since herbal medicine is extensively used in the modern world. This study investigates effects of Andrographis paniculata extract (APE) and its major component, andrographolide (AG), on the pharmacokinetics of theophylline, a typical substrate of cytochrome P450 1A2 enzyme, in rats. After APE or AG pretreatment for 3 days, on the fourth day rats were administered theophylline via femoral vein cannula. The blood theophylline levels were monitored by microdialysis sampling combined with HPLC-UV. The results indicated that the clearance of theophylline was significantly increased and the area under concentration-time curve (AUC) was reduced in both AG and APE pretreated groups at low-dose theophylline administration (1mg/kg). The elimination half-life (t(1/2beta)) and mean residence time (MRT) of theophylline were shortened by 14% and 17%, respectively, in the AG pretreated group when high-dose theophylline (5mg/kg) was given. However, theophylline accumulated in rat of the group with APE pretreatment. This phenomenon suggests that some other herbal components contained in APE may interact with theophylline and retard its elimination when theophylline was administered at a high dose. Our results suggest that patients who want to use CYP1A2-metabolized drugs such as caffeine and theophylline should be advised of the potential herb-drug interaction, to reduce therapeutic failure or increased toxicity of conventional drug therapy. Copyright © 2010. Published by Elsevier Ireland Ltd.

PMID: 20096675 [PubMed - as supplied by publisher]

Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer

Eur J Pharmacol. 2010 Jan 21. [Epub ahead of print]

Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer A549 cells via down-regulation of PI3K/Akt signaling pathway.

Lee YC, Lin HH, Hsu CH, Wang CJ, Chiang TA, Chen JH.

Department of Biological Science and Technology and Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan 717, Taiwan.

Lung cancer is the leading cause of death among cancers worldwide and non-small cell lung cancer (NSCLC) comprises more than 80% of lung cancer cases. Treatment options for patients with advanced NSCLC have evolved in the last decade with the advent of novel biological agents. Andrographolide, a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to have the potential to be developed as a chemotherapeutic agent. In order to understand the anti-cancer properties of andrographolide, we examined its effect on migration and invasion in human NSCLC A549 cells. The results of wound-healing assay and in vitro transwell assay revealed andrographolide inhibited dose-dependently the migration and invasion of A549 cells under non-cytotoxic concentrations. Molecular data showed the effect of andrographolide in A549 cells might be mediated via sustained inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt signal involved in the up-regulation of matrix metalloproteinases (MMPs). Our results showed andrographolide exerted an inhibitory effect on the activity and the mRNA and protein levels of MMP-7, but not MMP-2 or MMP-9. The andrographolide-inhibited MMP-7 expression or activity appeared to occur via activator protein-1 (AP-1) because of its DNA binding activity was suppressed by andrographolide. Additionally, the transfection of Akt overexpression vector (Akt1 cDNA) to A549 cells could result in an increase expression of MMP-7 concomitantly with a marked induction on cell invasion. These findings suggested the inhibition on MMP-7 expression by andrographolide may be through suppression on PI3K/Akt/AP-1 signaling pathway, which in turn led to the reduced invasiveness of the cancer cells. Copyright © 2009. Published by Elsevier B.V.

PMID: 20097193 [PubMed - as supplied by publisher]

Chennai-based RRF launches Ayurveda remedy for swine flu 'Ayusrem'

The Food & Drug Administration (FDA) in the Union Territory of Pondicherry has granted licence to Chennai-based Ramoni Research Foundation (RRF), an institute conducting research in Ayurveda medicines, to manufacture and market an Ayurvedic antiviral medication Ayusrem, which is a potential drug to prevent and treat H1N1.

The scientists at the foundation claimed that the drug is a potential choice to prevent and treat H1N1 flu and will prove to be a boon to the people as it is being launched at a time when the entire world is stepping up efforts to tackle the H1N1 pandemic. According to the scientists, the drug is made of extracts from anti-viral plants and antipyretic plants like Andrographis paniculata, Curcuma Longa and Vetiveria zizanioides. Extracts of Immunomodulant plants like Zingiber officinale and Piper nigrum have also been included. The Analgesic ingredients in the formulation are from Andrographis paniculata, Zingiber officinale and Cyperus rotundus.

Read more at pharmabiz.com

Anti-inflammatory Activity of New Compounds from Andrographis paniculata by NF-kappaB Transactivation Inhibition

J Agric Food Chem. 2010 Jan 19. [Epub ahead of print]

Anti-inflammatory Activity of New Compounds from Andrographis paniculata by NF-kappaB Transactivation Inhibition.

Chao WW, Kuo YH, Lin BF.

Department of Biochemical Science and Technology.

Previous studies showed that the ethyl acetate (EtOAc) fraction of Andrographis paniculata (AP) possessed anti-inflammatory activity. This study further isolated these active compounds from bioactivity-guided chromatographic fractionation and identified eight pure compounds. Reporter gene assay indicated that 5-hydroxy-7,8-dimethoxyflavone (1), 5-hydroxy-7,8-dimethoxyflavanone (2), a mix of beta-sitosterol (3a) and stigmasterol (3b), ergosterol peroxide (4), 14-deoxy-14,15-dehydroandrographolide (5), and a new compound, 19-O-acetyl-14-deoxy-11,12-didehydroandrographolide (6a), significantly inhibited the transcriptional activity of NF-kappaB in LPS/IFN-gamma stimulated RAW 264.7 macrophages (P < 0.05). The two most abundant compounds, 14-deoxy-11,12-didehydroandrographolide (7) and andrographolide (8), had less inhibitory activity but exerted greater inhibitory activity by hydrogenation, oxidation, or acetylation to become four derived compounds, 9, 10, 11, and 12. All of the compounds significantly decreased TNF-alpha, IL-6, macrophage inflammatory protein-2 (MIP-2), and nitric oxide (NO) secretions from LPS/IFN-gamma stimulated RAW 264.7 cells. Compounds 5, 11, and 12 exerted the strongest inhibitory effect on NF-kappaB-dependent transactivation in the RAW 264.7 cell, with IC(50) values of 2, 2.2, and 2.4 mug/mL, respectively, providing encouraging results for bioactive compound development.

PMID: 20085279 [PubMed - as supplied by publisher]

Clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection

Phytomedicine. 2010 Jan 19. [Epub ahead of print]

A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection.

Saxena RC, Singh R, Kumar P, Yadav SC, Negi MP, Saxena VS, Joshua AJ, Vijayabalaji V, Goudar KS, Venkateshwarlu K, Amit A.

Department of Pharmacology and Clinical Pharmacology, King George Medical University, Lucknow, India.

A randomized, double blind placebo controlled clinical study was conducted to evaluate the efficacy of KalmCold, an extract of Andrographis paniculata, in patients with uncomplicated upper respiratory tract infection (URTI). The assessment involved quantification of symptom scores by Visual Analogue Scale. Nine self evaluated symptoms of cough, expectoration, nasal discharge, headache, fever, sore throat, earache, malaise/fatigue and sleep disturbance were scored. A total of 223 patients of both sexes were randomized in two groups which received either KalmCold (200 mg/day) or placebo in a double blind manner. In both the treatments, mean scores of all symptoms showed a decreasing trend from day 1 to day 3 but from day 3 to day 5 most of the symptoms in placebo treated group either remained unchanged (cough, headache and earache) or got aggravated (sore throat and sleep disturbance) whereas in KalmCold treated group all symptoms showed a decreasing trend. Within groups, mean scores of symptoms in both the groups decreased significantly (p </= 0.05) from day 1 to day 3 and day 5 while from day 3 to day 5 all symptoms except expectoration in placebo group did not improve significantly whereas in KalmCold treated group all symptoms improved significantly (p </= 0.05) except earache. Comparing mean between both groups, all symptoms at day 1 and day 3 were found to be the same while at day 5 all symptoms except earache in KalmCold treated group improved significantly (p </= 0.05) than placebo group. Similarly, within groups, overall scores of all symptoms in both the groups decreased significantly (p </= 0.05) from day 1 to day 3 and day 5 while from day 3 to day 5 placebo group did not improve significantly whereas KalmCold treated group showed significant improvement (p </= 0.05). On between groups analysis, KalmCold group showed significant reduction (p </= 0.05) in overall symptom scores as compared to placebo group. In both placebo and KalmCold treated groups, there were only a few minor adverse effects with no significant difference in occurrence (Z = 0.63; p > 0.05). The comparison of overall efficacy of KalmCold over placebo was found to be significant (p </= 0.05) and it was 2.1 times (52.7%) higher than placebo. The findings of this study revealed that KalmCold was effective in reducing symptoms of upper respiratory tract infection. Copyright © 2010 Elsevier GmbH. All rights reserved.

PMID: 20092985 [PubMed - as supplied by publisher]

Activation of the cAMP/CREB/Inducible cAMP Early Repressor Pathway Suppresses Andrographolide-Induced Gene Expression

J Agric Food Chem. 2010 Jan 11. [Epub ahead of print]

Activation of the cAMP/CREB/Inducible cAMP Early Repressor Pathway Suppresses Andrographolide-Induced Gene Expression of the pi Class of Glutathione S-Transferase in Rat Primary Hepatocytes.

Yang AJ, Li CC, Lu CY, Liu KL, Tsai CW, Lii CK, Chen HW.

Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan.

Andrographolide (Ap) is a bioactive compound in Andrographis paniculata that is a Chinese herb. The pi class of glutathione S-transferase (GSTP) is one kind of phase II detoxification enzyme. Here we show that induction of GSTP protein and mRNA expression in rat primary hepatocytes by Ap was inhibited by forskolin and a variety of cAMP analogues. The inhibitory effect of the cAMP analogues was partially blocked by pretreatment with H89. In the presence of Ap, forskolin, or both, the expression of phospho-cAMP response element-binding protein (CREB) was increased. Ap alone had no effect on inducible cAMP early repressor (ICER) mRNA expression; however, Ap played a potentiating role in forskolin-induced ICER mRNA expression. An EMSA and immunoprecipitation assay showed that ICER binding to cAMP-response element (CRE) was increased in cells cotreated with Ap and forskolin for 3 and 8 h. Taken together, these results suggest that ICER is likely to be involved in the suppression of Ap-induced GSTP expression caused by the increase of cAMP in rat primary hepatocytes.

PMID: 20063885 [PubMed - as supplied by publisher]