Triplinones A-H: Anti-Inflammatory Arylalkenyl α,ß-Unsaturated-δ-Lactones Isolated from the Leaves of Australian Rainforest Plant Cryptocarya triplinervis (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,ß-unsaturated-δ-lactones, triplinones A-H (1-8), from the leaves of the Australian rainforest plant Cryptocarya triplinervis 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. Compounds 1-8 exhibited good inhibitory activities toward nitric oxide (NO) production in lipopolysaccharide (LPS) and interferon (IFN)-γ induced RAW 264.7 macrophages, in particular compounds 1-3 and 5, with IC50 values of 7.3 ± 0.5, 6.0 ± 0.3, 5.6 ± 0.3, and 5.4 ± 2.5 µM, respectively.

Insignoic acids A - E, unusual α, ß-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, ß-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. The low therapeutic index observed when assessing the cell viability in the RAW macrophage cell lines, prompted us to investigate the anticancer potential of these unusual fatty acids. The anti-cancer activity was assessed in A-431 carinoma cell lines and MM649 melanoma cell lines. Insignoic acid C (3a-f) exhibited the highest level of potency with an IC50 value of 5-7 µM against both the cell lines. The insignoic acids are the first of their kind known for incorporating an alpha-beta unsaturated system flanked next to a keto group with an additional level of oxygenation at C-6 in a 24­carbon fatty acid backbone.

Neuroinflammation in Alzheimer's Disease: A Potential Role of Nose-Picking in Pathogen Entry via the Olfactory System?

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Many possible factors might contribute to the development of AD, including amyloid peptide and tau deposition, but more recent evidence suggests that neuroinflammation may also play an-at least partial-role in its pathogenesis. In recent years, emerging research has explored the possible involvement of external, invading pathogens in starting or accelerating the neuroinflammatory processes in AD. In this narrative review, we advance the hypothesis that neuroinflammation in AD might be partially caused by viral, bacterial, and fungal pathogens entering the brain through the nose and the olfactory system. The olfactory system represents a plausible route for pathogen entry, given its direct anatomical connection to the brain and its involvement in the early stages of AD. We discuss the potential mechanisms through which pathogens may exploit the olfactory pathway to initiate neuroinflammation, one of them being accidental exposure of the olfactory mucosa to hands contaminated with soil and feces when picking one's nose.

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

Phytochemical investigation of the leaves of Polyscias australiana (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 (1) and C (2). Also isolated in high yields from this plant was the known saponin, ß-hedrin (3). The two new polysciasoside analogues exhibited no anti-inflammatory activity (inhibitory effects on NO inhibition and cell viability in RAW 264.7 macrophages) or cytotoxic activity against AGS gastric adenocarcinoma or the MCF7 breast adenocarcinoma cell lines. In contrast, the known compound ß-hedrin exhibited potent anti-inflammatory and cytotoxicity in these biological assays.