Plant extracts from central Asia showing antiinflammatory activities in gene expression assays

Plant natural products remain a good resource for the discovery of novel pharmaceuticals. A mouse macrophage‐based quantitative, reverse transcription polymerase chain reaction (qRT‐PCR) system was optimized to screen plant extracts for antiinflammatory activities using three well known genetic markers of inflammation. Plants used for extraction were taxonomically identified and vouchered species from two Central Asian countries, Uzbekistan and Kyrgyzstan, collected through the International Cooperative Biodiversity Groups (ICBG) program. The mRNA expression of cyclooxygenase‐2, interleukin 1β and inducible nitric oxide synthase genes in RAW macrophages was determined quantitatively in response to treatment with plant extracts applied at 100 µg/mL. The screening of 1000 extracts from 449 plant species belonging to 68 plant families resulted in 75 extracts (7.5%) showing strong (75% or higher inhibition) activity against at least one target gene. Many extracts showed qualitative and quantitative differences in the levels of activities against each target gene. Extracts identified from this screen were able to reduce inflammatory symptoms in vivo, thereby validating the screening approach. Copyright © 2008 John Wiley & Sons, Ltd.

[1]  Michael J. Balick,et al.  The value of undiscovered pharmaceuticals in tropical forests , 1995, Economic Botany.

[2]  I. Raskin,et al.  In Vitro and in Vivo Anti-Inflammatory Activity of a Seed Preparation Containing Phenethylisothiocyanate , 2006, Journal of Pharmacology and Experimental Therapeutics.

[3]  M. Egger,et al.  COX 2 inhibitors, traditional NSAIDs, and the heart , 2005, BMJ : British Medical Journal.

[4]  M. Whiteman,et al.  β-Phenylethyl and 8-methylsulphinyloctyl isothiocyanates, constituents of watercress, suppress LPS induced production of nitric oxide and prostaglandin E2 in RAW 264.7 macrophages , 2005 .

[5]  I. Verma,et al.  Inflammation-associated cancer: NF-κB is the lynchpin , 2005 .

[6]  Ricky A. Sharma,et al.  Oxidative stress and cyclooxygenase activity in prostate carcinogenesis: targets for chemopreventive strategies. , 2005, European journal of cancer.

[7]  D. Giugliano,et al.  The metabolic syndrome and inflammation: association or causation? , 2004, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[8]  I. Raskin,et al.  Can an apple a day keep the doctor away? , 2004, Current pharmaceutical design.

[9]  T. Krakauer.  Molecular therapeutic targets in inflammation: cyclooxygenase and NF-kappaB. , 2004, Current drug targets. Inflammation and allergy.

[10]  J. van der Greef,et al.  Screening of Natural Products Extracts for the Presence of Phosphodiesterase Inhibitors Using Liquid Chromatography Coupled Online to Parallel Biochemical Detection and Chemical Characterization , 2003, Journal of biomolecular screening.

[11]  E. Heiss,et al.  Mechanism-based in vitro screening of potential cancer chemopreventive agents. , 2003, Mutation research.

[12]  I. Raskin,et al.  Plants and human health in the twenty-first century. , 2002, Trends in biotechnology.

[13]  P. Hermkens,et al.  The contribution of combinatorial chemistry to lead generation: an interim analysis. , 2001, Current medicinal chemistry.

[14]  M Elofsson,et al.  The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. , 2001, Chemistry & biology.

[15]  S. Schreiber,et al.  Target-oriented and diversity-oriented organic synthesis in drug discovery. , 2000, Science.

[16]  Pickett,et al.  Computational methods for the prediction of 'drug-likeness' , 2000, Drug discovery today.

[17]  D J Newman,et al.  The influence of natural products upon drug discovery. , 2000, Natural product reports.

[18]  J. Winer,et al.  Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. , 1999, Analytical biochemistry.

[19]  Carl Nathan,et al.  Nitric oxide synthases: Roles, tolls, and controls , 1994, Cell.

[20]  H. Bartsch,et al.  Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. , 1994, Mutation research.

[21]  A. Gentry.  Tropical forest biodiversity and the potential for new medicinal plants , 1993 .

[22]  A. K. Picman.  Biological activities of sesquiterpene lactones , 1986 .