Triplinones A-H: Anti-Inflammatory Arylalkenyl α,β-Unsaturated-δ-Lactones Isolated from the Leaves of Australian Rainforest Plant (Lauraceae).

Our ongoing exploration of Australian rainforest plants for the biodiscovery of anti-inflammatory agents led to the isolation and structural elucidation of eight new arylalkenyl α,β-unsaturated-δ-lactones, triplinones A-H (), from the leaves of the Australian rainforest plant B. Hyland (Lauraceae). The chemical structures of these compounds were established by NMR spectroscopic data analysis, while their relative and absolute configurations were established using a combination of Mosher ester analysis utilizing both Riguera's and Kishi's methods, ECD experiments, and X-ray crystallography analysis.

Exploring the Anti-Inflammatory Potential of Australian Native Plants Based on their Ethnopharmacological Knowledge.

Inflammation represents the inherent protective reaction of the human body to various harmful agents and noxious stimuli. Standard anti-inflammatory therapy including nonsteroidal anti-inflammatory drugs are associated with several side effects. In the past decades, people rely on medicinal plants for the treatment of inflammation.

Insignoic acids A - E, unusual α, β-unsaturated keto fatty acids isolated from the exocarp of Australian rainforest tree Endiandra insignis (Lauraceae).

Anti-inflammatory bioassay-guided compound isolation from the exocarp of the Australian rainforest tree Endiandra insignis (family Lauraceae) has led to the discovery and structural elucidation of unusual α, β-unsaturated twenty-four carbon fatty acids and their positional isomers, insignoic acids A - E (1a - 5c). The stereochemistry and position of the double bond within the aliphatic chain were independently determined via NMR spectroscopy and Ozone-Induced Dissociation (OzID) Mass Spectrometry, respectively. Compounds (1a - 5c) displayed good to moderate anti-inflammatory activity in the range of 8-84 μM.

Polysciasoside B and C: new dammarane-type triterpene glycosides from the leaves of Australian rainforest plant (F.Muell.) Philipson (Araliaceae).

Phytochemical investigation of the leaves of (F.Muell.) Philipson (family Araliaceae) led to the isolation and identification of two new analogues belonging to the rare dammarane-type triterpene glycosides, polysciasosides B () and C ().

From the Bush to the Brain: Preclinical Stages of Ethnobotanical Anti-Inflammatory and Neuroprotective Drug Discovery-An Australian Example.

The Australian rainforest is a rich source of medicinal plants that have evolved in the face of dramatic environmental challenges over a million years due to its prolonged geographical isolation from other continents. The rainforest consists of an inherent richness of plant secondary metabolites that are the most intense in the rainforest. The search for more potent and more bioavailable compounds from other plant sources is ongoing, and our short review will outline the pathways from the discovery of bioactive plants to the structural identification of active compounds, testing for potency, and then neuroprotection in a triculture system, and finally, the validation in an appropriate neuro-inflammatory mouse model, using some examples from our current research.

A Method and Formula for the Quantitative Analysis of the Total Bioactivity of Natural Products.

Identification of bioactive natural products from plants starts with the screening of extracts for a desired bioactivity such as antimicrobial, antifungal, anti-cancer, anti-inflammatory, or neuroprotective. When the bioactivity shows sufficient potency, the plant material is subjected to bio-activity-guided fractionation, which involves, e.g.

Myrtinols A-F: New Anti-Inflammatory Peltogynoid Flavonoid Derivatives from the Leaves of Australian Indigenous Plant .

Our in-house ethnopharmacological knowledge directed our anti-inflammatory investigation into the leaves of . Bioassay guided isolation of the Australian indigenous plant led to the isolation of six new rare peltogynoid derivatives named myrtinols A-F (-) along with three known compounds 4--methylcedrusin (), 7--methylcedrusin () and 8-demethylsideroxylin (). The chemical structures of all the compounds were elucidated by detailed spectroscopic data analysis, and absolute configuration was established using X-ray crystallography analysis.

: A New Anti-Inflammatory Compound Isolated from the Australian Indigenous Plant .

Inspired by ethnopharmacological knowledge, we conducted a bioassay-guided fractionation of the leaves of which led to the discovery of a new anti-inflammatory compound, tristaenone A (). The structure was elucidated by detailed spectroscopic data analysis, and the absolute configuration was established using X-ray crystallography analysis. Tristaenone A () suppressed LPS and IFN-γ-induced NO, TNF-α and IL-6 production in RAW 264.

Cryptocaryoic acids A - C: New phenyl alkyl acids isolated from the leaves of Australian rainforest plant Cryptocarya mackinnoniana.

Phytochemical investigation of the leaves of the Australian rainforest tree Cryptocarya mackinnoniana led to the discovery of three new oxygenated phenyl alkyl acids, cryptocaryoic acids A - C and two known compounds, cryptocaryone and 2',6'-dihydroxy-4'-methoxychalcone. The structures of all the compounds were determined by detailed spectroscopic analysis. Mosher's analysis was used for absolute stereochemistry determination at C-11, while the remaining stereochemistry determination of the one remaining stereocenter C-13 was based on NOESY correlations.

Identification of Nrf2 Activators from the Roots of Valeriana officinalis.

Various age-related chronic diseases have been linked to oxidative stress. The cellular antioxidant response pathway is regulated by the transcription factor nuclear erythroid factor 2. Therefore, plant-derived nuclear erythroid factor 2 activators might be useful therapeutics to stimulate the body's defense mechanisms.

Pharmacological considerations for treating neuroinflammation with curcumin in Alzheimer's disease.

Prof. Dr. Peter Riederer, the former Head of the Neurochemistry Department of the Psychiatry and Psychotherapy Clinic at the University of Würzburg (Germany), has been one of the pioneers of research into oxidative stress in Parkinson's and Alzheimer's disease (AD).

Ternstroenol F: a new pentacyclic triterpenoid saponin isolated from the Australian rainforest plant .

A detailed close phytochemical investigation of the fruits of led to the isolation and identification of the minor metabolite, ternstroenol F, which possessed the usual barrigenol-like terpenoid backbone. The notable difference was that this minor metabolite had the 2(4()-6(decatrienoic acid forming an ester bond at C-22 of the oleanane backbone. Ternstroenol F was evaluated for its inhibitory effects on NO inhibition, cell viability and TNF- α release in RAW 264.

Acronyols A and B, new anti-inflammatory prenylated phloroglucinols from the fruits of .

Two new phloroglucinols, acronyols A () and B () along with the four known () pholoroglucinols were identified following anti-inflammatory activity guided fractionation from the fruits of (family Rutaceae). The pholoroglucinols () were evaluated for their inhibitory effects on NO production and downregulation of TNF-α in RAW 264.7 macrophage cell lines.

Eupomatenes A - E: Neolignans isolated from the leaves of Australian rainforest plant Eupomatia laurina.

A detailed phytochemical investigation of the leaves of the Australian rainforest tree Eupomatia laurina, led to the discovery of five new neolignans, eupomatenes A - E and eight known compounds, eupomatenoid-2, trans-(2'S)-2-[1'-(4-methoxyphenyl)prop-2'-yl]anethol, chlorogenic acid, chlorogenic acid-methyl ester, tyrosol-1-O-β-xylopyranosyl-1(1 → 6)-O-β-glucopyranoside, leucoside, kaempferol-3-O-neohesperidoside, and pachypodol. The structures of all the compounds were determined by detailed spectroscopic analysis. All compounds were also evaluated for their anti-inflammatory properties by assessing their inhibitory effects on nitric oxide (NO) production and TNF- α release in RAW 264.

Identification of tetragocarbone C and sideroxylin as the most potent anti-inflammatory components of Syncarpia glomulifera.

In contrast to ancient Western and Asian cultures, medicinal plants of the Aboriginal and Torres Strait Islanders in Australia have not been as intensively studied for their molecular composition and molecular bioactivity. Syncarpia glomulifera subsp. glomulifera is a species in the plant family Myrtaceae.

Potential anti-neuroinflammatory compounds from Australian plants - A review.

Neuroinflammation is a complex response to brain injury involving the activation of glia, release of inflammatory mediators, such as cytokines and chemokines, and generation of reactive oxygen and nitrogen species. Even though it is considered an event secondary to neuronal death or dysfunction, neuro-inflammation comprises a majority of the non-neuronal contributors to the cause and progression of neurodegenerative diseases like Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), Chronic Traumatic Encephalopathy (CTE) and others. As a result of the lack of effectiveness of current treatments for neurodegenerative diseases, neuroinflammation has become a legitimate therapeutic target for drug discovery, leading to the study of various in vivo and in vitro models of neuroinflammation.

Ternstroenols A - E: Undescribed pentacyclic triterpenoids from the Australian rainforest plant Ternstroemia cherryi.

Chromatographic separation of the extracts of the Australian rainforest plant Ternstroemia cherryi led to the isolation of five undescribed barrigenol-like triterpenoids, ternstroenols A - E, from the fruits and three known ones from the leaves. Ternstroenols A - E represent a new form of structural diversity, being the first in its kind to incorporate a trans- 2, 4, 6- decatrienoyl moiety at C-22. The structures of the ternstroenols were assigned by detailed spectroscopic analysis, degradation and chemical derivatization.

Mulgravanols A and B, rare oxidized xanthenes and a new phloroglucinol isolated from the Australian rainforest plant Waterhousea mulgraveana (Myrtaceae).

Phytochemical investigation of the Australian rainforest plant leaves Waterhousia mulgraveana, yielded two rare oxidized xanthenes, mulgravanols A (1) and B (2) along with a new phloroglucinol, mulgravanol C (3). Mulgravanol A (1) is the first reported example of a complex xanthene flanked by a methine bridged phloroglucinol unit. All the compounds displayed moderate inhibitory effects on nitric oxide production and TNF-α release in RAW 264.

The reciprocal EC value as a convenient measure of the potency of a compound in bioactivity-guided purification of natural products.

Identification of potent natural products is a challenging task in which sophisticated separation processes including HPLC are employed. The bioactivity of HPLC fractions is determined with a bioassay, and the most potent compounds are progressed to structural elucidation. In pharmacology, the potency of a compound is expressed as the half-maximal effective concentration (EC), which refers to the concentration of a drug that induces a response halfway between the baseline and maximum.

Hydrogen peroxide mediates pro-inflammatory cell-to-cell signaling: a new therapeutic target for inflammation?

Nitric oxide is now universally recognized as an extracellular signaling molecule. Nitric oxide, produced in one cell, diffuses across the extracellular space and acts with targets in an adjoining cell. In this study, we present proof that hydrogen peroxide - like nitric oxide - acts as a true first (intercellular) messenger for a multitude of pro-inflammatory ligands.

Determination of glyoxal and methylglyoxal in serum by UHPLC coupled with fluorescence detection.

Glyoxal (GO) and methylglyoxal (MGO) are two important biomarkers in diabetes. Analytical methods for determination of GO and MGO in serum samples are either HPLC with UV-Vis (low sensitivity) or MS/MS (expensive) detection. These disadvantages have hampered the introduction of these biomarkers as a routine analyte for diabetes diagnostics into the clinical laboratory.

Costatamins A - C, new 4-phenylcoumarins with anti-inflammatory activity from the Australian woodland tree Angophora costata (Myrtaceae).

The bioassay-guided isolation of new anti-inflammatory metabolites from the Australian Indigenous plant Angophora costata led to the discovery of three new 4-phenylcoumarins, costatamins A - C (1-3). The structures were determined by detailed spectroscopic analysis. Costatamins A - C were evaluated for their inhibitory effects on (a) NO production and (b) TNF-α release in RAW 264.

Cytochalasins from an Australian Marine Sediment-Derived Phomopsis sp. (CMB-M0042F): Acid-Mediated Intramolecular Cycloadditions Enhance Chemical Diversity.

Chemical analysis of an Australian coastal marine sediment-derived fungus, Phomopsis sp. (CMB-M0042F), yielded the known cytochalasins J (1) and H (2), together with five new analogues, cytochalasins J-J (3-5) and H and H (6 and 7). Structures of 1-7 were assigned on the basis of detailed spectroscopic analysis, chemical interconversion, and biosynthetic and mechanistic considerations.

Pyxipyrrolones: Structure Elucidation and Biosynthesis of Cytotoxic Myxobacterial Metabolites.

In the search for new secondary metabolites from myxobacteria, a strain from the genus Pyxidicoccus was investigated. This led to the identification of a new class of natural products showing structural novelty and interesting biological activity. Isolation and structure elucidation of two analogues led to the identification of pyxipyrrolone A and B, harboring the novel 3-methylene-2,3,4,5,6,7,8,9-octahydro-1H-benzo[e]isoindol-1-one scaffold.

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 factor- or nitric oxide.