Anti-inflammatory activity of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas L.
BACKGROUND
Plants from genus Lavandula have been used as anti-inflammatory drugs in Mediterranean traditional medicine. Nowadays, there is a growing interest for complementary medicine, including herbal remedies, to treat inflammatory bowel disease (IBD).


OBJECTIVE
To test the anti-inflammatory properties of Lavandula dentata and Lavandula stoechas extracts in two inflammatory experimental models: TNBS model of rat colitis and the carrageenan-induced paw edema in mice, in order to mimic the intestinal conditions and the extra-intestinal manifestations of human IBD, respectively.


METHODS
The extracts were characterized through the qualitative HPLC analysis. Then, they were assayed in vitro and in vivo. In vitro studies were performed in BMDMs and CMT-93 epithelial cells with different concentrations of the extracts (ranging from 0.1 to 100µg/ml). The extracts were tested in vivo in the TNBS model of rat colitis (10 and 25mg/kg) and in the carrageenan-induced paw edema in mice (10, 25 and 100mg/kg).


RESULTS
L. dentata and L. stoechas extracts displayed immunomodulatory properties in vitro down-regulating different mediators of inflammation like cytokines and nitric oxide. They also showed anti-inflammatory effects in the TNBS model of colitis as evidenced by reduced myeloperoxidase activity and increased total glutathione content, indicating a decrease of neutrophil infiltration and an improvement of the oxidative state. Besides, both extracts modulated the expression of pro-inflammatory cytokines and chemokines, and ameliorated the altered epithelial barrier function. They also displayed anti-inflammatory effects in the carrageenan-induced paw edema in mice, since a significant reduction of the paw thickness was observed. This was associated with a down-regulation of the expression of different inducible enzymes like MMP-9, iNOS and COX-2 and pro-inflammatory cytokines, all involved in the maintenance of the inflammatory condition.


CONCLUSIONS
L. dentata and L. stoechas extracts showed intestinal anti-inflammatory effect, confirming their potential use as herbal remedies in gastrointestinal disorders. In addition, their anti-inflammatory effect was also observed in other locations, thus suggesting a possible use for the treatment of the extra-intestinal symptoms of IBD.
CIBER-EHD, Department of Pharmacology, IBS.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
Francesca
F
Algieri
CIBER-EHD, Department of Pharmacology, IBS.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
Alba
A
Rodriguez-Nogales
CIBER-EHD, Department of Pharmacology, IBS.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
Teresa
T
Vezza
CIBER-EHD, Department of Pharmacology, IBS.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
Jose
J
Garrido-Mesa
CIBER-EHD, Department of Pharmacology, IBS.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
Natividad
N
Garrido-Mesa
CIBER-EHD, Department of Pharmacology, IBS.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
M Pilar
MP
Utrilla
Department of Botany, University of Granada, Granada, Spain.
M Reyes
MR
González-Tejero
Department of Botany, University of Granada, Granada, Spain.
Manuel
M
Casares-Porcel
Department of Botany, University of Granada, Granada, Spain.
Joaquin
J
Molero-Mesa
Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avenida Fuentenueva s/n, 18071 Granada, Spain; Research and Development Centre for Functional Food (CIDAF), Health-Science Technological Park, Avenida del Conocimiento 37, 18016 Granada, Spain.
Maria
M
Del Mar Contreras
Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avenida Fuentenueva s/n, 18071 Granada, Spain; Research and Development Centre for Functional Food (CIDAF), Health-Science Technological Park, Avenida del Conocimiento 37, 18016 Granada, Spain.
Antonio
A
Segura-Carretero
Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores de Andalucía (MEDINA), Granada, Spain.
José
J
Pérez-Palacio
Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores de Andalucía (MEDINA), Granada, Spain.
Caridad
C
Diaz
Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores de Andalucía (MEDINA), Granada, Spain.
Noemí
N
Vergara
Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores de Andalucía (MEDINA), Granada, Spain.
Francisca
F
Vicente
CIBER-EHD, Department of Pharmacology, IBS.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
M Elena
ME
Rodriguez-Cabezas
CIBER-EHD, Department of Pharmacology, IBS.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain. Electronic address: jgalvez@ugr.es.
Julio
J
Galvez
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002351:Carrageenan; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004487:Edema / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D027523:Lavandula / Q000737:chemistry* / Q000145:classification; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D000432:Methanol / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D017208:Rats, Wistar; D012997:Solvents / Q000737:chemistry*; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D010936:Plant Extracts; D012997:Solvents; D009569:Nitric Oxide; D014302:Trinitrobenzenesulfonic Acid; D002351:Carrageenan; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D005978:Glutathione; D000432:Methanol
Antioxidant activity; Carrageenan-induced paw edema; Lavandula dentata L.; Lavandula stoechas L.; Polyphenols; TNBS colitis