Advanced Chemophenetic Analysis of Essential Oil from Leaves of Piper gaudichaudianum Kunth (Piperaceae) Using a New Reduction-Oxidation Index to Explore Seasonal and Circadian Rhythms.

The aromatic species Piper gaudichaudianum Kunth (Piperaceae) is widely used in Brazil for medicinal and ritualistic applications. In the current study, chemophenetic patterns were realized across season and circadian rhythm based on the chemical profile of essential oils (EOs) from leaves. Hydrodistilled essential oils were analyzed by GC-MS and GC-FID, and a new calculation of metabolite oxidation level, averaged for each individual molecule component of the EO, was used to explore the patterns of metabolism/biosynthesis. This new index used an intermediate calculation, the 'weighted average redox standard' (SRO), to enable a value for mixtures of metabolites to be generated, the 'general mixture redox index' (GMOR). The indices were subjected to a proof-of-concept approach by making comparison to outcomes from multivariate analyses, i.e., PCA and HCA. Chemical analysis demonstrated that the essential oils were dominated by sesquiterpenes, constructed of 15 classes of compound (C-skeletons), and 4 C-skeletons were recognized in the monoterpene group, giving a total of 19. The variation of chemical profiles was distinct at different phenological stages, but stronger chemical variation was evident between day and night as compared to season. Furthermore, due to comprehensive sampling across different regions, nine chemotypes were recognized, including those previously reported. The SRO and GMRO indices demonstrate that phenological variation of chemistry is mainly an outcome of redox fluctuations in terpene biosynthesis, changing from day to night. These indices also corroborate that chemical diversity is increased with oxidative metabolism. Lastly, the current study demonstrates pronounced phenotypic plasticity in P. gaudichaudianum, which makes it a suitable candidate to help further our understanding of chemophenetics and chemical ecology.

Pharmacological study of anti-inflammatory activity of aqueous extracts of Mikania glomerata (Spreng.) and Mikania laevigata (Sch. Bip. ex Baker).

ETHNOPHARMACOLOGICAL RELEVANCE: Mikania glomerata Spreng. (MG) and Mikania laevigata Sch. Bip. ex Baker (ML), popularly known as guaco, are medicinal plants similar in morphology, chemical composition and medicinal uses. Both species are often used and sold without distinction; however, it is believed that their chemical composition is different. AIM: Thus, the aim of this study is to investigate if the aqueous extract of MG and ML present similar anti-inflammatory activity to the point of being used interchangeably. MATERIAL AND METHODS: Different doses of both extracts and coumarin were given to rats in different experimental models to assess the anti-inflammatory activity between these two species. For this, the animals were submitted to paw edema, pleurisy and degranulation of peritoneal mast cell and the extracts were also characterized by Ultra High Efficiency Liquid Chromatography coupled to Mass Spectrometry (UHPLC-MS). RESULTS: The chromatographic method showed that ML presents ten times more coumarin than MG. Oral administration of MG, ML and coumarin inhibited paw edema induced by carrageenan (400 mg/kg, 55% inhibition; 400 mg/kg, 57% inhibition; 75 mg/kg, 38% inhibition; p < 0.05, respectively). MG, ML and coumarin treatment also inhibited the edema induced by compound 48/80 (400 mg/kg, 56% inhibition; 400 mg/kg, 69% inhibition; 75 mg/kg, 40% inhibition; p < 0.05, respectively). MG, ML and coumarin did not prevent mast cell degranulation and the consequent histamine release in Wistar rat peritoneal mast cells induced by compound 48/80. MG did not inhibit cell infiltration in pleurisy nor the highest dose tested, while ML decreased the leukocyte migration (200 and 400 mg/kg, 23% and 30% inhibition; p < 0.001, respectively) and, to a lesser extent, coumarin also reduced cell infiltration (10, 50 and 75 mg/kg; 15%, 16% and 17% inhibition; p < 0.001, respectively). CONCLUSION: The variation of the results of the anti-inflammatory activity found in M. glomerata and M. laevigata demonstrates that these two species should not be used interchangeably. Coumarin, as already proven, has anti-inflammatory action however, we have suggested that it probably is not the only component responsible for this therapeutic effect in the extracts.

Effects of different protocol doses of low power gallium-aluminum-arsenate (Ga-Al-As) laser radiation (650 nm) on carrageenan induced rat paw ooedema.

The purpose of the present study was to investigate the effect of the low power laser therapy on the acute inflammatory process. Male Wistar rats were used. The rat paw oedema was induced by sub-plantar injection of carrageenan, the paw volume was measured before and 1, 2, 3 and 4 h after the injection using a hydroplethysmometer. To investigate the mechanism action of the Ga-Al-As laser on inflammatory oedema, parallel studies were performed using adrenallectomized rats or rats treated with sodium diclofenac. Different laser irradiation protocols were employed for specific energy densities (EDs), exposure times and repetition rates. The rats were irradiated with the Ga-Al-As laser during 80 s each hour. The ED that produced an anti-inflammatory effect were 1 and 2.5 J/cm(2), reducing the oedema by 27% (P<0.05) and 45.4% (P<0.01), respectively. The ED of 2.5 J/cm(2) produced anti-inflammatory effects similar to those produced by the cyclooxigenase inhibitor sodium diclofenac at a dose of 1 mg/kg. In adrenalectomized animals, the laser irradiation failed to inhibit the oedema. Our results suggest that low power laser irradiation possibly exerts its anti-inflammatory effects by stimulating the release of adrenal corticosteroid hormones.

Synthesis of substituted benzamides as anti-inflammatory agents that inhibit preferentially cyclooxygenase 1 but do not cause gastric damage.

Parsalmide (5-amino-N-butyl-2-(2-propynyloxy) benzamide) (5a), is a non-steroidal anti-inflammatory drug (NSAID), commercialised in Italy until 1985 with the brand name of Synovial(R), that has been widely used to treat arthritic patient. In addition, it was shown to spare gastric mucosa. Here we have synthesised a series of novel substituted benzamides, related to Parsalmide, and have evaluated their activity in vitro on COX-1 and COX-2 as well as in vivo in the carrageenin-induced rat paw edema, a classical in vivo anti-inflammatory assay. Compounds 5b, 11a and 11b, which showed a favourable profile in vitro and in vivo, were screened in comparison with Parsalmide for gastrointestinal (GI) tolerability in vivo in the rat. Results obtained showed that Parsalmide and compound 11b inhibited both COX-1 and COX-2 in vitro as well as they were active in vivo. Both compounds were devoid of gastric effect at the efficacious dose. In addition, both prevented indomethacin-induced gastric damage. Thus, these compounds may guide the definition of a new leading structure with anti-inflammatory activity that may allow designing new safer NSAIDs.

The relaxation of isolated rabbit corpus cavernosum by the herbal medicine Catuama and its constituents.

The effects of the Brazilian herbal medicine Catuama and each of its plant constituents (Paullinia cupana, Trichilia catigua, Zingiber officinalis and Ptychopetalum olacoides) were investigated on rabbit corpus cavernosum (RbCC) using a bioassay cascade. Catuama caused short-lived and dose-dependent relaxations (11% +/- 7%, 26% +/- 5% and 82% +/- 9%, at doses of 1, 3 and 10 mg, respectively). Neither the nitric oxide synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 10 microM) nor the soluble guanylate cyclase inhibitor ODQ (10 microM) significantly affected the Catuama-induced relaxations. Similarly, the selective ATP-dependent K(+) channel (K(ATP)) blocker glibenclamide (10 microM), the muscarinic receptor antagonist atropine (1 microM) and the voltage-dependent Na(+) channel blocker tetrodotoxin (1 microM) all failed to affect significantly the Catuama-induced relaxations. These results indicate that the relaxations induced by Catuama involve neither nitric oxide release nor K(ATP) channel activation. The extracts of P. cupana, Z. officinalis and P. olacoides caused short-lived and dose-dependent RbCC relaxations, whereas T. catigua evoked long-lasting relaxations which were occasionally preceded by a brief contractile effect. The extract of P. cupana was the most active in relaxing RbCC strips. The relaxations induced by all extracts were not significantly affected by L-NAME (10 microM). The infusion of ODQ (10 microM) had no significant effect on the P. cupana- and Z. officinalis-induced relaxations but reduced by >50% (p < 0.05) those evoked by P. olacoides and T. catigua. Incubations of RbCC with Catuama(10 mg/mL for 0.25 to 5 min) caused increases of cAMP levels (143% increase at 5 min of incubation). Incubations of RbCC with P. cupana extract (1 mg/mL) increased the cAMP levels by 200% whereas higher doses (10 and 100 mg/mL) caused smaller increases in the nucleotide levels (150% and 89%, respectively). The extracts of Z. officinalis and P. olacoides (same doses) caused smaller increases of the cAMP levels compared with the P. cupana extract, whereas T. catigua (1-100 mg) did not increase the levels of this nucleotide above the basal values. Our results show that of the four extracts assayed, P. cupana was the most effective, indicating that it is the main extract responsible for the relaxing effect of Catuama on rabbit cavernosal tissue.