title: Anti-inflammatory, gastroprotective, and cytotoxic effects of Sideritis scardica extracts.
abstract: Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and N-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in extracts. Apoptotic and necrotic cell death were analyzed by double staining with fluoresceinisothiocyanate (FITC)-conjugated annexin V and PI. The developed HPLC method enabled qualitative fingerprint analysis of phenolic compounds in the investigated extracts. Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4 mg/kg), which produced a 50 % decrease in inflammation, diethyl ether and N-butanol extracts exhibited about the same effect in doses of 200 and 100 mg/kg (53.6 and 48.7 %; 48.4 and 49.9 %, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine. The diethyl ether extract showed significant dose-dependent cytotoxicity on B16 cells and HL-60 cells, decreasing cell growth to 51.3 % and 77.5 % of control, respectively, when used at 100 µg/mL. It seems that phenolic compounds (apigenin, luteolin, and their corresponding glycosides) are responsible for the diethyl ether extract cytotoxic effect. It also appears that induction of oxidative stress might be involved in its cytotoxicity, since B16 and HL-60 cells increased their ROS production in response to treatment with diethyl ether extract. Neither of the tested extracts nor any phenolic compounds showed significant cytotoxic effect to human PBMC. These results demonstrated the potent anti-inflammatory and gastroprotective activities, as well as the promising cytotoxicity.
authors.affiliation: Institute for Medicinal Plant Research "Dr Josif Pančić", Belgrade, Serbia.
authors.forename: Vanja M
authors.initials: VM
authors.lastname: Tadić
authors.forename: Ivica
authors.initials: I
authors.lastname: Jeremic
authors.forename: Silva
authors.initials: S
authors.lastname: Dobric
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Isakovic
authors.forename: Ivanka
authors.initials: I
authors.lastname: Markovic
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trajkovic
authors.forename: Dragica
authors.initials: D
authors.lastname: Bojovic
authors.forename: Ivana
authors.initials: I
authors.lastname: Arsic
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000302:isolation & purification; D047310:Apigenin / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D002351:Carrageenan / Q000494:pharmacology; D016923:Cell Death; D045744:Cell Line, Tumor; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005419:Flavonoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D016166:Free Radical Scavengers / Q000032:analysis / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D047311:Luteolin / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D015394:Molecular Structure; D010936:Plant Extracts / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000302:isolation & purification; D059808:Polyphenols / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D031365:Sideritis / Q000737:chemistry*; D013634:Tannins / Q000032:analysis / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D016166:Free Radical Scavengers; D005765:Gastrointestinal Agents; D010936:Plant Extracts; D059808:Polyphenols; D017382:Reactive Oxygen Species; D013634:Tannins; D047310:Apigenin; D002351:Carrageenan; D047311:Luteolin