1. Ameliorative potential of Lavandula stoechas in metabolic syndrome via multitarget interactions
- Author
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Tugba Boyunegmez Tumer, Ibrahim Demirtas, Seda Savranoglu Kulabas, R. Ekren, Hande Ipek, Ali Rıza Tüfekçi, Sevki Arslan, and Ugur Sezerman
- Subjects
medicine.medical_treatment ,Peroxisome proliferator-activated receptor ,animal cell ,Pharmacology ,transcriptomics ,Mice ,0302 clinical medicine ,Drug Discovery ,Caffeic acid ,genetics ,cyclooxygenase 2 ,lavender ,C2C12 cell line ,chemistry.chemical_classification ,adipocyte cell line ,aerial plant part ,drug effect ,peroxisome proliferator activated receptor gamma ,gene expression regulation ,time of flight mass spectrometry ,3. Good health ,Lavandula ,030220 oncology & carcinogenesis ,Glucose-6-Phosphatase ,Lavandula stoechas ,antiinflammatory agent ,H4-II-E cell line ,glucose 6 phosphatase ,insulin ,in vitro study ,Glucose uptake ,Lipolysis ,lipoprotein lipase ,Nitric Oxide ,Article ,03 medical and health sciences ,protein serine threonine kinase ,Lavandula stoechas extract ,luteolin ,Protein kinase B ,mouse ,Animals ,Cell Line ,Cell Line, Tumor ,Cell Survival/drug effects ,Cyclooxygenase 2/genetics ,Gene Expression Regulation/drug effects ,Glucose/metabolism ,Glucose-6-Phosphatase/genetics ,Interleukin-1beta/genetics ,Lipolysis/drug effects ,Metabolic Syndrome/drug therapy ,Nitric Oxide/metabolism ,Nitric Oxide Synthase Type II/genetics ,PPAR gamma/metabolism ,Plant Components, Aerial ,Plant Extracts/*pharmacology ,Protein-Serine-Threonine Kinases/genetics ,Proto-Oncogene Proteins ,antiinflammatory activity ,medicine.disease ,030104 developmental biology ,chemistry ,phosphoenolpyruvate carboxylase kinase ,Metabolic syndrome ,metformin ,0301 basic medicine ,interleukin 1beta ,Interleukin-1beta ,Nitric Oxide Synthase Type II ,chemistry.chemical_compound ,4 hydroxybenzoic acid ,animal ,rat ,glucose ,isoprenaline ,Metabolic Syndrome ,biology ,messenger RNA ,cell line ,Protein-Serine-Threonine Kinases ,unclassified drug ,plant extract ,rosmarinic acid ,high performance liquid chromatography ,Cell Survival ,salicylic acid ,Protein Serine-Threonine Kinases ,Insulin resistance ,medicine ,drug mechanism ,controlled study ,apigenin ,nonhuman ,Plant Extracts ,Insulin ,Gluconeogenesis ,inducible nitric oxide synthase ,tumor cell line ,glucose transport ,RAW 264.7 cell line ,biology.organism_classification ,Rats ,PPAR gamma ,vanillic acid ,protein kinase B ,myotube ,metabolic syndrome X ,Transcriptome ,caffeic acid ,metabolism ,Proto-Oncogene Proteins c-akt ,ferulic acid - Abstract
Ethnopharmacological importance Decoction and infusion prepared from aerial parts of Lavandula stoechas L. (L. stoechas) have been traditionally used as remedy against several components of metabolic syndrome (MetS) and associated disorders including type II diabetes and cardiovascular diseases by Anatolian people. Aim of the study The aim is to elucidate the potential ameliorative effects of L. stoechas aqueous extracts on insulin resistance and inflammation models through multitarget in vitro approaches and also to elucidate mechanism of action by analyzing transcriptional and metabolic responses. Materials and methods An aqueous extract was prepared and fractionated to give rise to ethyl acetate (EE) and butanol (BE) extracts. The anti-insulin resistance effects of BE and EE were evaluated on palmitate induced insulin resistance model of H4IIE, C2C12 and 3T3L1 cells by using several metabolic parameters. Specifically, whole genome transcriptome analysis was performed by using microarray over 55.000 genes in control, insulin resistant and EE (25 µg/mL) treated insulin resistant H4IIE cells. Anti-inflammatory effects of both extracts were analyzed in LPS-stimulated RAW264.7 macrophages. Results Both EE and BE at low doses (25–50 µg/mL) significantly decreased hepatic gluconeogenesis in H4IIE cell line by suppressing the expression of PEPCK and G6Pase. In C2C12 myotubes, both extracts increased the insulin stimulated glucose uptake more effectively than metformin. Both extracts decreased the isoproterenol induced lipolysis in 3T3L1 cell line. Moreover, they also effectively increased the expression of lipoprotein lipase protein level in insulin resistant myotubes at low doses. EE increased the protein level of PPARγ and stimulated the activation AKT in insulin resistant H4IIE and C2C12 cell lines. The results obtained from biochemical assays, mRNA/protein studies and whole genome transcriptome analyses were found to be complementary and provided support for the hypothesis that EE might be biologically active against insulin resistance and act through the inhibition of liver gluconeogenesis and AKT activation. Besides, LPS induced inflammation in RAW264.7 macrophages was mainly inhibited by EE through suppression of iNOS/NO signaling, IL1β and COX-2 genes. HPLC-TOF/MS analysis of EE of L. stoechas mainly resulted in caffeic acid, apigenin, luteolin, rosmarinic acid and its methyl ester, 4-hydroxybenzoic acid, vanillic acid, ferrulic acid and salicylic acid. Conclusion Data suggest that EE of L. stoechas contains phytochemicals that can be effective in the treatment/prevention of insulin resistance and inflammation. These results validate the traditional use of L. stoechas in Anatolia against several metabolic disorders including metabolic syndrome.
- Published
- 2018