Biologically active compounds isolated from Centipeda and their biological activity as antioxidant and antiinflammatory agents

Compounds having useful biological activity, particularly antioxidant and anti-​inflammatory activity, derived from Centipeda cunninghamii, and biol. active derivatives thereof, pharmaceutical compns. comprising these compounds, and prophylactic and therapeutic use of the compounds

Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory Activity

Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson's and Alzheimer's disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factoror nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae) were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC 50 5.57 ± 1.4 g/mL), whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminali

Type III secretion inhibitors for the management of bacterial plant diseases

Altres ajuts: COST Action SUSTAIN (FA1208) from the European Union.The identification of chemical compounds that prevent and combat bacterial diseases is fundamental for crop production. Bacterial virulence inhibitors are a promising alternative to classical control treatments, because they have a low environmental impact and are less likely to generate bacterial resistance. The major virulence determinant of most animal and plant bacterial pathogens is the type III secretion system (T3SS). In this work, we screened nine plant extracts and 12 isolated compounds-including molecules effective against human pathogens-for their capacity to inhibit the T3SS of plant pathogens and for their applicability as virulence inhibitors for crop protection. The screen was performed using a luminescent reporter system developed in the model pathogenic bacterium Ralstonia solanacearum. Five synthetic molecules, one natural product and two plant extracts were found to down-regulate T3SS transcription, most through the inhibition of the regulator hrpB. In addition, for three of the molecules, corresponding to salicylidene acylhydrazide derivatives, the inhibitory effect caused a dramatic decrease in the secretion capacity, which was translated into impaired plant responses. These candidate virulence inhibitors were then tested for their ability to protect plants. We demonstrated that salicylidene acylhydrazides can limit R. solanacearum multiplication in planta and protect tomato plants from bacterial speck caused by Pseudomonas syringae pv. tomato. Our work validates the efficiency of transcription reporters to discover compounds or natural product extracts that can be potentially applied to prevent bacterial plant disease

(3R,4S,5S,8S,10R,13R)-3-Hy­droxy­kaura-9(11),16-dien-18-oic acid

The title compound, C20H28O3, was isolated during our investigation into the chemical composition and pharmacological activity of Centipeda cunninghamii (DC.) A. Braun & Asch. (Asteraceae). The enanti­opure compound, a diterpene with a carbon skeleton, is composed of three six- and one five-membered rings in chair, twist-boat, half-chair and envelope conformations, respectively. Each mol­ecule makes one intra- and one inter­molecular O—H⋯O hydrogen bond in the crystal lattice, forming hydrogen-bonded chains along [010]. The absolute configuration of the compound was assigned on the basis of optical rotation measurements

De quelques catéchismes créoles anciens: oublis, pertes, disparitions, réapparitions, découvertes

Il existe, dans le très vaste domaine des études postcoloniales, des territoires contigus ou semblables qui connaissent des phénomènes communs mais aux histoires très différentes, sinon radicalement opposées : tels les catéchismes - en langues romanes - fruit de la colonisation. Plus précisément, à l’histoire des catéchismes issus de la colonisation hispano-américaine, s’oppose l’histoire des catéchismes issus de la colonisation française, de l’Amérique et d’ailleurs. Ces derniers arrivent un siècle et demi environ après les espagnols et se manifestent de tout autre manière ; différents en sont l’époque, la scène et les acteurs : les destinateurs mais surtout les destinataires. Ce travail se propose de retracer l’histoire souvent aventureuse des plus anciens catéchismes des colonies ou ex-colonies françaises de la Caraïbe et de l’Océan Indien ; écrits en créole ou, parfois, en d’autres langues autochtones, ils constituent aussi des témoignages linguistiques absolument précieux. Rédigés généralement sur place, mais non toujours publiés, leur histoire est faite d’oublis, pertes, disparitions, réapparitions et découvertes. - - - In the wide field of postcolonial studies, there exist related or similar areas whose stories are nevertheless very different, if not indeed opposed. This is the case of catechisms in Romance languages (or of Romance origin), outcomes of European colonization. In particular, contradictions between the history of catechisms from Hispanic-American colonization and the catechisms produced by French colonization, in America and elsewhere. The latter appear a century and a half after the Spanish texts, and exhibit completely distinct characteristics: different periods, settings, actors, and especially recipients. I set out to recount the often adventurous history of the oldest catechisms in the French colonies, or ex-colonies, of the Caribbean and the Indian Ocean. Written in Creole or sometimes other indigenous languages, they are precious linguistic records. Compiled in the colonies, but not always published, these texts are often forgotten, lost, misplaced, resurfaced, discovered

The natural stilbenoid (-)-hopeaphenol inhibits cellular entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7, and B.1.351 variants

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID- 19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host angiotensin-converting enzyme II (ACE2) receptor may be effective inhibitors of SARS-CoV-2 cell entry. Here, we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 binding assay and identified (-)-hopeaphenol, a resveratrol tetramer, in addition to vatalbinoside A and vaticanol B, as potent and selective inhibitors of RBD/ACE2 binding and viral entry. For example, (-)-hopeaphenol disrupted RBD/ACE2 binding with a 50% inhibitory concentration (IC50) of 0.11 mM, in contrast to an IC50 of 28.3 mM against the unrelated host ligand/receptor binding pair PD-1/PD-L1 (selectivity index, 257.3). When assessed against the USA-WA1/2020 variant, (-)-hopeaphenol also inhibited entry of a VSVDG-GFP reporter pseudovirus expressing SARS-CoV-2 spike into ACE2-expressing Vero-E6 cells and in vitro replication of infectious virus in cytopathic effect and yield reduction assays (50% effective concentrations [EC50s], 10.2 to 23.4 mM) without cytotoxicity and approaching the activities of the control antiviral remdesivir (EC50s, 1.0 to 7.3 mM). Notably, (-)-hopeaphenol also inhibited two emerging variants of concern, B.1.1.7/Alpha and B.1.351/Beta in both viral and spike-containing pseudovirus assays with similar or improved activities over the USA-WA1/2020 variant. These results identify (-)-hopeaphenol and related stilbenoid analogues as potent and selective inhibitors of viral entry across multiple SARS-CoV-2 variants of concern

Phytochemical studies and bioactivity of Centipeda and Eremophila species

The aim of this study was to isolate and characterise biologically active compounds from endemic Australian plants. A total of 6 novel, and 26 known compounds have been isolated throughout the course of this work. A comprehensive investigation of the GC-MS chemical profile of C. cunninghamii leaf essential oil found that thymol (1) cis-chrysanthenyl acetate (4), myrtenyl acetate (2), myrtenol (3) and cis-chrsanthenol (5) were the major constituents. The essential oil and crude solvent extracts of C. cunninghamii possessed significant antioxidant and antiinflammatory activity. A 50% aqueous ethanol extract was demonstrated to possess multiple modes of anti-inflammatory action. The crude extract was found to significantly inhibit both COX-1 and COX-2 cyclooxygenases and was comparable to the positive controls; Ibuprofen and Celebrex respectively. The crude extract also exhibited anti-inflammatory activity in the nitric oxide (NO) and tumor necrosis factoralpha (TNF-α) assays, but did not show inhibition in the lipoxygenase (LO) assay. A total of seventeen compounds, of which 10, 6, 7, 8 and 9 are novel, have been identified from the aqueous-ethanolic extract of C. cunninghamii. Five flavonoids; axillarin (16), isokaempferide (17), 4’,5,7-trihydroxy-3,6-dimethoxyflavone (18), jaceidin (19), and 2’,4’,5,7-tetrahydroxy-6-methoxyflavone-3-O-β-glucopyranoside (10) were isolated from the flowers of C. cunninghamii. A series of caffeic acids were isolated as the major component of the stems, these included; chlorogenic acid (12) and its methyl ester (13), caffeic acid ethyl ester (11), isochlorogenic acid A (14) macroantoin G (15) and the novel 4ξ,5ξ-di-O-caffeoyl-2,6ξ-dihydroxyhept-2-ene-1,7- dioic acid (6) and its 1-methyl ester (7), 7-methyl ester (8) and 1,7-dimethylester (9) derivatives. Lastly, arnicolide C (20) a sesquiterpene lactone, 3-hydroxykaura-9(11),16- diene-18-oic acid (21) and 8-hydroxy-9,10-diisobutyryloxythymol (23) were characterised by spectroscopic methods. All of the compounds were evaluated for anti-inflammatory activity, as determined by the inhibition of prostaglandin E2 in 3T3 fibroblast cells. All compounds, inhibited PGE2 production to some extent, at a concentration of 31.25 μg/mL. The flavonoids 10 and 16-19 were the most active compounds. The caffeic acids 6-9, 12-14 and the thymol derivative 23 also significantly inhibited PGE2 production. The IC50 values were determined for the novel compounds; 10, 6, 7, 8 and 9, as 1.47, 2.48, 4.73, 5.54 and 1.26 μM, respectively. These novel compounds were more potent than the positive control, aspirin, which was found to inhibit PGE2 production by 42% at a concentration of 18 μM. Antioxidant activity, as determined by oxygen radical absorbance capacity (ORAC) has also been attributed to both the flavonoids; 10, 16-19 and caffeic acid compounds; 6-9 and 12-14. The antioxidant capacity of these compounds was found to be comparable to epicatechin, a major antioxidant constituent of green tea. A detailed analysis of the wood, leaf, branch and root oil of E. mitchellii was carried out by a combination of GC-FID, GC-MS, LC/MS and NMR spectroscopy. The wood, root, leaf and branch oils were found to be predominantly composed of sesquiterpenes. The three major compounds identified in the leaf oil, which accounted for 44% of the oil, were α-pinene (40), (+) spathulenol (15) and an unidentified sesquiterpene alcohol. The composition of the leaf oil was complex and chemically distinct from the wood and root oils, whereas the branch oil was found to exhibit a chemical composition that was intermediate between the leaf and the wood oil. After fractionation by preparative HPLC six components of the wood oil were characterized and accounted for 80% of the oil. The major constituents of the wood oil were; eremophilone (30), 9-hydroxy-7(11),9-eremophiladien-8-one (36), santalcamphor (35) and the novel 9-hydroxy-1,7(11),9-eremophilatrien-8-one (42). Two minor constituents, 8-hydroxy-10,11-eremophiladien-9-one (32) and 8-hydroxy-1,11- eremophiladien-9-one (33) were also isolated in this study. The two major constituents of the root oil of E. mitchellii were found to be eremophilone (30) and the zizaene, sesquithuriferone (43). These, together with the minor constituents 32, 33, 42, 35 and 36 accounted for 92% of the root oil. The insecticidal properties of E. mitchellii were evaluated against several species of termites Nasutitermes walkeri (Hill), Nasutitermes exitiosus (Hill) and Coptotermes acinaciformis (Froggatt). Bioassay-guided fractionation of E. mitchellii wood oil was undertaken to investigate the termiticidal metabolites. Of the major components, it has been determined that eremophilone (30) was the most active constituent of the wood oil followed by 8-hydroxy-1,11-eremophiladien-9-one (33), 9-hydroxy-7(11),9- eremophiladien-8-one (36) and santalcamphor (35). The methanolic extracts from a total of 36 species have been evaluated for cytotoxicity against P388D1 mouse lymphoblast cells. A collection of fifteen species of Eremophila from Western Australia and a further twenty from the Northern Territory were surveyed. Cytotoxicity was found to be largely non-selective across a range of human cancer cell lines, including MCF7 (mammary adenocarcinoma), Hep G2 (hepatocellular carcinoma), A2780 (ovarian carcinoma), A-375 (malignant melanoma) and PC-3 (prostate cancer). Fractionation of the leaf material of E. racemosa afforded the six major metabolites. Isolation and structural elucidation of these polar compounds revealed the cyanogenetic glycoside prunasin (65), the flavonoid luteolin (74), the furofuran lignans, phillygenin (75), its 4-O-β-D-glucoside phillyrin (76), pinoresinol-4-O-β-D-glucoside (77) and epipinoresinol-4-O-β-D-glucoside (78). Fractionation of the leaf material of E. maculata var. brevifolia afforded piceine (81) and epipinoresinol-4-O-β-D-glucoside (78). Quercetin (79) and nepetin (80) were isolated from the methanolic extracts of E. bignoniflora

Centipeda cunninghamii: an Australian traditional medicinal plant

Centipeda cunninghamii (DC.) A.Braun & Asch. is an endemic Australian Asteraceae with a long history of traditional use as a medicinal plant for treating wounds, infections and inflammation. Whilst its essential oil composition, principally chrysanthenyl and sabinyl acetates, has been known for some time, there was little scientific information regarding its phytochemistry and biological activity. Investigations on aqueous ethanolic extracts confirmed its anti-inflammatory and antioxidant (ORAC) activity. Detailed investigations suggest the extract acts against a range of inflammatory markers including COX-1, COX-2, NO and TNF

Pharmacognosy of Centipeda cunninghamii, an endemic Australian traditional medicinal plant

Centipeda is a genus in the family Asteraceae comprising 12 taxa in 10 species. All but one species occur in Australia. There are documented traditional medicinal uses of five species across Australia, India and China. Investigations of the aqueous ethanolic extract of C. cunninghamii (DC) A. Braun & Asch, have confirmed its antiinflammatory and antioxidant (ORAC) activity. Detailed investigations suggest that the extract acts against a range of inflammatory markers including; PGE2 COX, NO and TNF-α, but not through the lipoxygenase pathway. Seventeen compounds were isolated and subsequent bioassays indicated that the anti-inflammatory activity was linked to flavonoids and terpenoids, whilst the antioxidant activity was attributed to both flavonoids and a group of novel heptenedioic acid caffeoyl esters. Quality control for medicinal plant production of this species has utilised the levels of phenolics, flavonoids and sequiterpenes to optimise growing and extraction parameters