Confirmation of ethnopharmacological anti-inflammatory properties of Ocotea odorifera and determination of its main active compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Ocotea odorifera (Vell.) Rohwer has been used in traditional medicine in the south of Brazil for the treatment of inflammatory-related conditions, such as rheumatism. However, there is not any scientific evidence for popular use. AIMS OF THE STUDY: To investigate the O. odorifera anti-inflammatory potential and identification of the main active compounds through metabolomic approaches. MATERIALS AND METHODS: In order to in vivo evaluate the inhibition of the main inflammatory pathways, the leaf decoction, leaf extract, its fractions and the essential oils from leaves and branches were submitted to the ear oedema and the neutrophils recruitment assays. The samples were chemically investigated by UHPLC-HRMS or GC-MS. The multivariate statistical analysis (PLS-DA) was used to determine the substances correlated with the anti-inflammatory properties. RESULTS: The in vivo studies indicated a promissory anti-inflammatory effect on both oedema and neutrophil recruitment for some samples including the decoction; hydroethanolic, ethyl acetate, and chloroform fractions; and the essential oils. According to the PLS-DA, the S-(+)-reticuline was evidenced as one of the three compounds of the plant most correlated with both anti-inflammatory mechanisms. Thus, S-(+)-reticuline was isolated and the anti-inflammatory activity was confirmed. Moreover, for the first time, the dual inhibition of oedema and neutrophil recruitment was uncovered and reported. Another compound positively correlated with the anti-inflammatory activity is likely to be a new compound since zero hit on the comprehensive mass database were encountered. The compounds found in the essential oils also showed significant anti-inflammatory activity, and thus indeed the plant has different classes of active substances. CONCLUSIONS: The decoction of O. odorifera and different fractions from its ethanolic extract demonstrated anti-inflammatory activity through dual inhibition of oedema and neutrophil recruitment. Thus, corroborating the popular medicinal use of the decoction of leaves from O. odorifera as an anti-inflammatory medicine. Besides, reticuline, one of the main active compounds, was isolated and proved to display the dual mechanism of action, indicating the O. odorifera as a promising source of active compounds for the treatment of inflammatory conditions.

Chlorogenic acids from Tithonia diversifolia demonstrate better anti-inflammatory effect than indomethacin and its sesquiterpene lactones.

ETHNOPHARMACOLOGICAL RELEVANCE: T. diversifolia (Hemsl.) A. Gray (Asteraceae) has been used in the traditional medicine in several countries as anti-inflammatory and against other illnesses. It is important to evaluate the anti-inflammatory activity of extracts from the leaves of this species, including an infusion, to identify the main constituents of the extracts, observe their effects and correlate them with the anti-inflammatory activity. MATERIALS AND METHODS: An infusion, a leaf rinse extract (LRE) and a polar extract from the rinsed leaves (PE) were obtained and analysed by HPLC-UV-DAD and infrared spectroscopy. The major compounds of these extracts were quantified. The three obtained extracts were evaluated for their anti-inflammatory activities using the paw oedema and croton oil ear oedema assays in mice. Furthermore, neutrophil migration was measured by evaluating myeloperoxidase activity. RESULTS: The PE consists primarily of chlorogenic acids (CAs) and lacks sesquiterpene lactones (STLs). The LRE is rich in STLs and includes a few flavonoids. The infusion is chemically similar to the PE but also contains very low amounts of STLs. The PE and LRE have better mechanisms of action than non-steroidal anti-inflammatory drugs (NSAIDs). Unlike NSAIDs, both the PE and LRE inhibit oedema and neutrophil migration. The pool of CAs from the PE of T. diversifolia has an additional mechanism of action, and its anti-inflammatory effect was greater than what is described in the literature for this class of compounds using the same evaluation models. The similar chemical compositions observed for the infusion and the PE, contrasted with the different activities observed, suggests the presence of antagonist compounds produced during the extraction procedure (infusion); the infusion did not inhibit oedema, however it inhibited neutrophil migration. It suggests that although the great majority of plants present CAs, the category of anti-inflammatory effect of their extracts depends on a suitable pool of compounds and an absence of antagonists, among other factors. CONCLUSIONS: CAs from T. diversifolia comprise a good pool of anti-inflammatory compounds with better activity mechanisms than NSAIDs, other active compounds from the leaf extracts (STLs and flavonoids) and CAs from other plant sources. Thus, the PE of T. diversifolia has high potential for the development of new anti-inflammatory phytomedicines. The infusion probably contains antagonists, and therefore it can be useful to treat inflammation processes where neutrophil recruitment is involved and oedema is not.