Solidagenone from Solidago chilensis Meyen inhibits skin inflammation in experimental models.

Solidagenone (SOL) is a labdane-type diterpenoid found in Solidago chilensis, a plant traditionally used to treat skin diseases, kidney pain and ovarian inflammation. In this study, the topical anti-inflammatory activity of SOL was evaluated using in vivo and in silico assays. Croton oil-, arachidonic acid (AA)- and phenol-induced ear oedema mouse models were applied in the in vivo studies. Myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activities and tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) levels were determined, as well as histopathological analyses were conducted. Interaction profiles between SOL and cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glucocorticoid receptor, estradiol-17-ß-dehydrogenase and prostaglandin-E(2)-9-reductase were established using molecular docking. SOL significantly inhibited croton oil-, AA- and phenol-induced ear oedema (P < .001) at doses of 0.1, 0.5 and 1.0 mg/ear. The MPO and NAG activities and TNF-α, IL-6 and NO levels were decreased (P < .001). The histopathological data revealed that inflammatory parameters (oedema thickness, leucocyte infiltration and vasodilatation) were reduced by treatment with SOL at doses of 0.1, 0.5 and 1.0 mg/ear. The docking study showed that SOL interacts with COX-1 and prostaglandin-E(2)-9-reductase through hydrogen bonding, inhibiting these enzymes. These results indicate that SOL may be a promising compound for the treatment of cutaneous inflammatory disorders and has potential as a topical anti-inflammatory agent.

Brazilian medicinal plants with corroborated anti-inflammatory activities: a review.

CONTEXT: Inflammatory disorders are common in modern life, and medicinal plants provide an interesting source for new compounds bearing anti-inflammatory properties. In this regard, Brazilian medicinal plants are considered to be a promising supply of such compounds due to their great biodiversity. OBJECTIVES: To undertake a review on Brazilian medicinal plants with corroborated anti-inflammatory activities by selecting data from the literature reporting the efficacy of plants used in folk medicine as anti-inflammatory, including the mechanisms of action of their extracts and isolated compounds. METHODS: A search in the literature was undertaken by using the following Web tools: Web of Science, SciFinder, Pub-Med and Science Direct. The terms 'anti-inflammatory' and 'Brazilian medicinal plants' were used as keywords in search engine. Tropicos and Reflora websites were used to verify the origin of the plants, and only the native plants of Brazil were included in this review. The publications reporting the use of well-accepted scientific protocols to corroborate the anti-inflammatory activities of Brazilian medicinal plants with anti-inflammatory potential were considered. RESULTS: We selected 70 Brazilian medicinal plants with anti-inflammatory activity. The plants were grouped according to their anti-inflammatory mechanisms of action. The main mechanisms involved inflammatory mediators, such as interleukins (ILs), nuclear factor kappa B (NF-κB), prostaglandin E2 (PGE2), cyclooxygenase (COX) and reactive oxygen species (ROS). CONCLUSIONS: The collected data on Brazilian medicinal plants, in the form of crude extract and/or isolated compounds, showed significant anti-inflammatory activities involving different mechanisms of action, indicating Brazilian plants as an important source of anti-inflammatory compounds.

Tetraglochin andina Ciald.: A medicinal plant from the Argentinean highlands with potential use in vaginal candidiasis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Argentinean medicinal plant Tetraglochin andina Ciald, formerly classified as T. cristatum (Britton) Rothm is used in traditional medicine by inhabitants from Argentinean northwestern highlands (Puna) to treat candidiasis and as anti-inflammatory. AIM OF THE STUDY: To assess the potential of the crude drug as an anti-Candida agent with anti-inflammatory properties. The bioactivity and phytochemical composition of a dry extract of the plant was investigated. MATERIAL AND METHODS: The pharmacognostic description of the crude drug is carried out for the first time, including macroscopic and microscopic examinations of the different organs, physicochemical and extractive values (petroleum ether-, ethanol- and water-soluble). The dry extract from T. andina was evaluated as antifungal against pathogenic Candida sp. and Saccharomyces cerevisiae isolated from vaginal infections and reference strains, by the macrodilution and microdilution assays. The normal vaginal microbiome in women is characterized by the dominance of lactic acid-producing bacteria, mainly Lactobacillus spp. The effect of T. andina extract on Lactobacillus strains was also assayed. The inhibitory effect on proinflammatory enzymes (cyclooxygenase, lipoxygenase and phospholipase A2) and antioxidant capacity was studied. The chemical profile was analyzed by HPLC-ESI-MS. RESULTS: The hydroalcoholic extract inhibited the growth of all yeasts with Minimal Inhibitory Concentration (MIC) values between 12.5 and 400 µg GAE/mL and the MIC values on Lactobacillus were higher than the MIC values against Candida isolates ( > 400 µg GAE/mL). These results indicate that the hydroalcoholic extract could be used without affecting the normal microbiota of vaginal fluid. The extract showed antioxidant activity and could modulate the inflammatory process by three pathways (sPLA2, COX-2, LOX). The plant extract contained high total phenolic levels (386.9±1.7 mg GAE/g dry extract) and flavonoid levels (260.4±2.7 mg GAE/g dry extract). Fifty phenolic compounds were identified by HPLC-ESI-MS. They were mainly hydrolysable and condensed tannins. The dry extract was chemically and biologically stable during one year at room temperature or 4 °C. CONCLUSIONS: The presence of anti-Candida and anti-inflammatory activities in Tetraglochin andina extracts give support to their traditional use for treating conditions associated with microorganism infections and inflammatory process in humans. This plant preparation could be used to design phytopharmaceutical preparations to inhibit yeast growth and moderate the inflammatory and oxidative process.

In vitro COX-1 and COX-2 enzyme inhibitory activities of iridoids from Penstemon barbatus, Castilleja tenuiflora, Cresentia alata and Vitex mollis.

A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (36.0 ± 0.6%) and COX-2 (80.8 ± 4.0%) inhibition at 10 µM. Compound 10 shows a better inhibition against the COX-2 enzyme. Other iridoids tested in the present study showed weak or no inhibition against these enzymes. Furthermore, herein are presented key interactions of iridoid 10 with COX-1 and COX-2 enzymes through molecular docking studies. These studies suggest that 10 exhibits anti-inflammatory activity due to COX inhibition.

Cyclooxygenase inhibitory properties of nor-neolignans from Styrax pohlii.

Chemical investigation of the n-hexane and EtOAc fractions of the ethanolic extract from Styrax pohlii (Styracaceae) aerial parts resulted in the isolation of the benzofuran nor-neolignan derivatives egonol (1), homoegonol (2), homoegonol gentiobioside (3), homoegonol glucoside (4) and egonol gentiobioside (5). This is the first report of compounds 1-5 in S. pohlii. Compounds 1-5, the acetyl derivatives 1 a and 2 a, the ethanolic extract (EE), the n-hexane fraction (HF) and EtOAc fraction (EF) were tested for their inhibitory activities against COX-1 and COX-2. The results showed that EE, HF, EF and compounds 1-5 and 1 a-2 a shown weak to moderate inhibition of COX-1 and COX-2. Among the assayed nor-neolignans, 4 gave a COX-1 inhibition of 35.7% at 30 µM. Compound 5 displayed a COX-2 inhibition of 19.7% at 30 µM.

In vitro anti-inflammatory effects of naturally-occurring compounds from two Lauraceae plants

The in vitro anti-inflammatory effects of seven known lignans and one dihydrochalcone isolated from the leaves of two Lauraceae species (Pleurothyrium cinereum and Ocotea macrophylla), were evaluated through the inhibition of COX-1, COX-2, 5-LOX and the aggregation of rabbit platelets induced by PAF, AA and ADP. (+)-de-4"-O--methylmagnolin 4 was found to be a potent COX-2/5-LOX dual inhibitor and PAF-antagonist (COX-2 IC50 2.27 µM; 5-LOX IC50 5.05 µM; PAF IC50 2.51 µM). However, all compounds exhibited an activity at different levels, indicating good anti-inflammatory properties to be considered in further structural optimization studies.

Os efeitos anti-inflamatórios in vitro de sete conhecidos lignanos e uma dihidrocalcona isolados das folhas de duas espécies da família Lauraceae (Pleurothyrium cinereum e Ocotea macrophylla) foram avaliados por meio da inibição da COX1, COX-2, 5-LOX e agregação de plaquetas de coelhos induzida por PAF, AA e ADP. A (+)-4"-O-metilmagnolina-4 foi encontrada como mais potente inibidora tanto da COX-2 quanto de 5-LOX e antagonista de PAF (COX-2 IC50 2,27 µM; 5- LOX IC50 5,05 µM; PAF IC50 2,51 µM). Entretanto, todos compostos mostram uma atividade em intensidades diferentes, indicando boas propriedades anti-inflamátorias a serem consideradas para futuros estudos de modificações e otimização estruturais.

In vitro anti-inflammatory effects of naturally-occurring compounds from two Lauraceae plants.

The in vitro anti-inflammatory effects of seven known lignans and one dihydrochalcone isolated from the leaves of two Lauraceae species (Pleurothyrium cinereum and Ocotea macrophylla), were evaluated through the inhibition of COX-1, COX-2, 5-LOX and the aggregation of rabbit platelets induced by PAF, AA and ADP. (+)-de-4"-O-methylmagnolin 4 was found to be a potent COX-2/5-LOX dual inhibitor and PAF-antagonist (COX-2 IC(50) 2.27 µM; 5-LOX IC(50) 5.05 µM; PAF IC(50) 2.51 µM). However, all compounds exhibited an activity at different levels, indicating good anti-inflammatory properties to be considered in further structural optimization studies.

Stemodin-derived analogues with lipid peroxidation, cyclooxygenase enzymes and human tumour cell proliferation inhibitory activities.

A series of analogues, derived from the antiviral and cytotoxic diterpene stemodin, were prepared and evaluated for their lipid peroxidation (LPO), cyclooxygenase enzyme-1 (COX-1) and -2 (COX-2), and tumour cell proliferation inhibitory activities. Oxidation of stemodin produced stemodinone, which was then converted to stemod-12-en-2-one. Reaction of the latter under Petrow conditions (bromine; silver acetate/pyridine) yielded mainly dibrominated abeo-stachanes. Solvolysis of the dibromo compounds gave products of hydrolysis, some with rearranged skeleta. In the lipid peroxidation inhibitory assay three of the compounds exhibited prominent activity. Interestingly, all the analogues showed higher COX-1 enzyme inhibition than COX-2. Although a few of the diterpenes limited the growth of some human tumour cell lines, most compounds induced proliferation of such cells.

COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.

The anti-inflammatory potential of 26 neolignans (14 of the bicyclooctane-type and 12 of the benzofuran-type), isolated from three Lauraceae species (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), was evaluated in vitro through inhibition of COX-1, COX-2, 5-LOX and agonist-induced aggregation of rabbit platelets. Benzofuran neolignans were found to be selective COX-2 inhibitors, whereas bicyclooctane neolignans inhibit selectively the PAF-action as well as COX-1 and 5-LOX. The neolignan 9-nor-7,8-dehydro-isolicarin B 15 and cinerin C 7 were found to be the most potent COX-2 inhibitor and PAF-antagonist, respectively. Nectamazin C 10 exhibited dual 5-LOX/COX-2 inhibition.

Inhibition of cyclooxygenase activity by standardized hydroalcoholic extracts of four Asteraceae species from the Argentine Puna.

We determined the anti-inflammatory activity of standardized extracts of four medicinal plant species (Baccharis incarum, B. boliviensis, Chuquiraga atacamensis, Parastrephia lucida) that grow in the Argentine Puna (3800 m above sea level) and that are used to reduce oxidative stress and alleviate gout and arthritic pain. The extracts of plant aerial parts were standardized in terms of total phenolic compounds and flavone/flavanone content and free radical scavenging activity. All extracts showed high phenolic compound concentration (0.5-1.6 mg/mL), mainly flavones and flavonols (0.1-0.8 mg/mL). The extracts showed hydrogen donating ability (DPPH and ABTS) and reactive oxygen species scavenging activity (O2-, OH-, H2O2). The ability of the extracts to inhibit cyclooxygenase enzymes (COX-1 and COX-2) was determined by calculating percent inhibition of PGE2 production measured by enzyme immunoassay. All extracts inhibited both enzymes with IC50 values of 2.0 to 16.7 microg/mL. The anti-inflammatory activity of B. incarum and C. atacamensis extracts was higher than that of B. boliviensis and P. lucida. The IC50 values obtained for indomethacin were 0.11 and 0.78 microM for COX-1 and COX-2, respectively. The present results are consistent with the anecdotal use of these species in phytotherapic preparations.

Inhibition of cyclooxygenase activity by standardized hydroalcoholic extracts of four Asteraceae species from the Argentine Puna

We determined the anti-inflammatory activity of standardized extracts of four medicinal plant species (Baccharis incarum, B. boliviensis, Chuquiraga atacamensis, Parastrephia lucida) that grow in the Argentine Puna (3800 m above sea level) and that are used to reduce oxidative stress and alleviate gout and arthritic pain. The extracts of plant aerial parts were standardized in terms of total phenolic compounds and flavone/flavanone content and free radical scavenging activity. All extracts showed high phenolic compound concentration (0.5-1.6 mg/mL), mainly flavones and flavonols (0.1-0.8 mg/mL). The extracts showed hydrogen donating ability (DPPH and ABTS) and reactive oxygen species scavenging activity (O2●-, OH-, H2O2). The ability of the extracts to inhibit cyclooxygenase enzymes (COX-1 and COX-2) was determined by calculating percent inhibition of PGE2 production measured by enzyme immunoassay. All extracts inhibited both enzymes with IC50 values of 2.0 to 16.7 µg/mL. The anti-inflammatory activity of B. incarum and C. atacamensis extracts was higher than that of B. boliviensis and P. lucida. The IC50 values obtained for indomethacin were 0.11 and 0.78 µM for COX-1 and COX-2, respectively. The present results are consistent with the anecdotal use of these species in phytotherapic preparations.

Lipoperoxidation and cyclooxygenase enzyme inhibitory piperidine alkaloids from Cassia spectabilis green fruits.

Phytochemical work in the search for bioactive metabolites from the methanolic extract of Senna spectabilis green fruits led to the isolation of a new piperidine alkaloid, (+)-3- O-feruloylcassine ( 1), in addition to the known (-)-spectaline ( 2) and (-)-3- O-acetylspectaline ( 3). The isolates were submitted to in vitro evaluation of lipoperoxidation (LPO) and cyclooxygenase enzymes (COX-1 and -2) inhibitory properties and showed moderate antioxidant activities (40-70%) at 100 ppm when compared to commercial standards BHT and vitamin E and moderate inhibition of COX-1 (ca . 40%) and marginal inhibition of COX-2 enzymes (<10%) at 100 ppm when compared to nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin, rofecoxib, and celecoxib, respectively.

Antiplatelet activity of geranylgeraniol isolated from Pterodon pubescens fruit oil is mediated by inhibition of cyclooxygenase-1.

Geranylgeraniol is a natural isoprenoid with anti-inflammatory properties extracted from the Pterodon pubescens Benth. fruit oil (PpO). In this work, the antiplatelet effect of both PpO and geranylgeraniol is investigated. ADP-, thrombin- and arachidonic acid (AA)-induced aggregation in human and rabbit platelets showed a prime involvement of PpO and geranylgeraniol in the arachidonic acid cascade. The lack of any significant inhibition of platelet aggregation induced by U-46 619 and thrombin, associated with PpO and geranylgeraniol suppression of prostaglandin E(2) and thromboxane A(2) formation demonstrate, for the first time, the involvement of geranylgeraniol in the AA metabolisation by inhibiting the cyclooxygenase enzyme.

Lipoperoxidation and cyclooxygenases 1 and 2 inhibitory compounds from Iryanthera juruensis.

Plants from Iryanthera genus have been traditionally used as food supplements by South American Indians. The MeOH extract of leaves of Iryanthera juruensis, one of the plants endemic to the Amazon region and consumed in Brazil, and the hexane extract from its seeds inhibited lipid peroxidation (LPO) and cyclooxygenase (COX-1 and -2)) enzymes in in vitro assays. Further analyses of these extracts yielded 5-deoxyflavones (1-5) from the leaf extract and sargachromenol (6), sargaquinoic acid (7), a novel juruenolic acid (8), omega-arylalkanoic acids (9a-c), and the lignan guaiacin (10) from the seed extract. Compounds 3-5 inhibited LPO by 86%, 77%, and 88% at 10 ppm, respectively, and compounds 6 and 9a-c showed inhibition at 76% and 78% at 100 ppm, respectively. However, compounds 7 and 8 were inactive and lignan 10 exhibited LPO inhibitory activity by 99% at 100 ppm compared to commercial antioxidants butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and vitamin E. The flavones 1-5 also inhibited COX-1 and -2 enzymes by 50-65% at 100 ppm. Compound 6 showed high but nonselective inhibition of COX-1 and COX-2 enzymes, when compared to aspirin and Celebrex, a nonsteroidal anti-inflammatory drug (NSAID). Compounds 7 and 10 inhibited COX-1 by 60% and 65% and COX-2 by 37% and 18%, respectively, whereas compounds 8 and 9a-c showed little or no activity against these enzymes.

New acetylenes isolated from the bark of Heisteria acuminata.

Five new linear acetylenic compounds, namely, pentadeca-6,8,10-triynoic acid (1), octadeca-8,10,12-triynoic acid (2), trans-pentadec-10-en-6,8-diynoic acid (3), cis-hexadec-11-en-7,9-diynoic acid (4), and cis-octadec-12-en-7,9-diynoic acid (5), were isolated from the bark of Heisteria acuminata by bioassay-guided fractionation, using cyclooxygenase (COX) and 5-lipoxygenase (5-LO) assays as models for antiinflammatory activity. The structures of compounds 1-5 were established by NMR, MS, IR, and Raman spectroscopy. These isolated compounds were found to be potent inhibitors of COX. Compounds 4 and 5 were the most potent inhibitors of 5-LO, whereas the other compounds only showed a weak inhibition at the same concentration.

Evaluation of some Samoan and Peruvian medicinal plants by prostaglandin biosynthesis and rat ear oedema assays.

In our ongoing program to find new anti-inflammatory compounds, 58 extracts from 46 different medicinal plant species, used in treatment of inflammatory disorders-38 plants from the traditional medicine of Western Samoa and eight originating from the indigenous medicine of the Shipibo-Conibo tribe of Peruvian Amazonia-ere evaluated. The ability of all extracts to inhibit cyclooxygenase-1 catalysed prostaglandin biosynthesis in vitro was examined. Of the plant species tested 14 showed moderate to strong inhibition; including 11 Samoan and three Peruvian species. Further, 12 Samoan and all eight Peruvian species were investigated on their inhibitory activity of ethyl phenylpropiolate induced rat ear oedema in vivo. Significant activity was shown by 10 of the Samoan and by all eight Peruvian species. An additional evaluation of the most active species was provided through a compilation of existing literature documenting traditional medicinal uses, pharmacological activity and chemical constituents. Several known cyclooxygenase-1 inhibitors were reported to which the observed pharmacological activity can be attributed at least partly. The combination of chemical and pharmacological literature data and our experimental data may help to explain the anti-inflammatory use of these species in indigenous medicine.