Abstract
Recently, our research group identified and reported 1,8-cineole (CIN), a monoterpene that naturally occur in many aromatic plants, as one of the major constituent of the essential oil from leaves of Hyptis martiusii (EOHM), as well as characterized the gastroprotective action of this oil. The aim of this study was to investigate the mechanisms of action involved in the antiulcer and healing activity of CIN, in order to confirm its correlation with the gastroprotective effect of EOHM. Wistar rats were exposed to different protocols (acute ulceration, gastrointestinal motility and antisecretory activity). In addition, were determinated the involvement of nitric oxide and sulphydryl groups; the levels of gastric mucus, lipid peroxidation, sulphydryl groups and myeloperoxidase activity. The healing ability was evaluated by acetic acid-induced chronic ulcer and histological and immunohistochemical analysis (PCNA, Ki-67 and BrdU). The treatment with CIN inhibited ethanol-, ethanol/HCl- and indomethacin-induced gastric lesions. The highest doses of CIN inhibited gastric emptying, but did not affect intestinal transit. CIN (100 mg/kg) reduced the volume of basal but not stimulated acid secretion. CIN increased levels of mucus (89.3%), prevented depletion of –SH groups (62.6%) and reduced the level of lipid peroxidation (55.3%) and myeloperoxidase activity (59.4%) in the gastric mucosa. In chronic ulcer model, CIN reduced in 43.1% the gastric area lesion, promoted significant regeneration and restoration of the levels of mucus in glandular cells as confirmed by histological analysis; and promoted increase in cell proliferation as evidenced by reactivity for PCNA, Ki-67 and BrdU. This findings demonstrate the role of 1,8-cineole as an important ulcer healing agent and indicate the involvement of antioxidant and cytoprotective mechanisms in the gastroprotective effect of compound. This study also provides evidence that 1,8-cineole is related to the gastroprotective effect of the essential oil of Hyptis martiusii.
Highlights
A wide variety of chemical substances, mixtures of herbs and plant extracts have been proved to possess therapeutic properties in experimental models of peptic ulcer
In the HCl/ethanol-induced gastric ulcer model, CIN caused a significant level of gastroprotection when compared to the control group (245.5 ± 43.0 mm2), corresponding to 88.5, 95.2 and 99.4% of inhibition of the lesion area for doses at 50, 100 and 200 mg/kg, respectively
Pantoprazole (40 mg/kg) significantly inhibited the gastric lesions induced by ethanol and HCl/ethanol in 53.7% and 91.5%, respectively, when compared to the control group
Summary
A wide variety of chemical substances, mixtures of herbs and plant extracts have been proved to possess therapeutic properties in experimental models of peptic ulcer. The gastroprotective effect of these compounds and extracts (combined or in isolation) has been attributed to three main functions, including antisecretory, cytoprotective and antioxidant properties [1]. 1.8-cineole, known as eucalyptol, is a monoterpene found naturally in many aromatic plants of the Eucalyptus, Croton, Hyptis, Pectis, Rosamarinus and Salvia genera [2, 3, 4]. In the specific case of the Hyptis genus, 1,8-cineole is reported to be the main compound in species such as H. fruticosa, H. goyazensis, H. suaveolens and H. martiusii [10]. (Lamiaceae), popularly known as cidreira-do-mato, is characterized as a potential source of essential oils, like other species of the genus. A study conducted by Araújo et al [2] showed that the essential oil of fresh leaves of H. martiusii consists of mono- and sesquiterpenes, and its major components are 1,8-cineole, δ-3-carene, bicyclogermacrene and β-caryophyllene
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