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Australian native plants have a long history of therapeutic use in indigenous cultures, however, they have been poorly studied scientifically. We analysed the effects of 14 plant derived compounds from the species Pilidiostigma glabrum, Myoporum montanum, Geijera parviflora, and Rhodomyrtus psidioides for their potential wound healing properties by assessing their ability to induce or suppress Collagen I and Collagen III expression in human skin fibroblasts in culture. The compound 7-geranyloxycoumarin was able to significantly increase Collagen I (23.7%, p < 0.0002) expression in comparison to control. Significant suppression of Collagen III was observed for the compounds flindersine (11.1%, p < 0.02), and (N-acetoxymethyl) flindersine (27%, p < 0.00005). The implications of these finding is that these compounds could potentially alter the expression of different collagens in the skin allowing for the potential development of new wound healing therapies and new approaches for treating various skin diseases as well as photo (sun) damaged, and aged skin. Refereed/Peer-reviewed

Ethnopharmacological relevance Australian Aboriginal people used crushed leaves of Geijera parviflora Lindl. both internally and externally for pain relief, including for toothache ( Cribb and Cribb, 1981 ). This study tested the hypothesis that this traditional use might be at least in part explained by the presence of compounds with anti-inflammatory activity. Materials and methods A crude extract (95% EtOH) was prepared from powdered dried leaves. From the CH 3 Cl fraction of this extract compounds were isolated by bioassay-guided fractionation and tested for: (1) cytotoxicity in RAW 264.7 murine leukemic monocyte–macrophages, (2) prostaglandin E 2 (PGE 2 ) inhibitory activity in 3T3 Swiss albino mouse embryonic fibroblast cells, as well as (3) nitric oxide (NO) and (4) tumour necrosis factor alpha (TNFα) inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Isolated compounds were also tested for (5) antibacterial activity against a panel of Gram-positive ( Staphylococcus aureus ATCC 29213 and ATCC 25923, Staphylococcu s epidermidis ATCC 35984, biofilm-forming) and Gram-negative ( Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) strains by broth microdilution. Results Eleven compounds were isolated, including one new flavone and one new natural product, with a further four compounds reported from this species for the first time. Some of the compounds showed good anti-inflammatory activity in vitro . In particular, flindersine ( 1 ) and N-(acetoxymethyl) flindersine ( 3 ) inhibited PGE 2 release with IC 50 values of 5.0 μM and 4.9 μM, respectively, without any significant cytotoxicity. Several other compounds showed moderate inhibition of NO ( 5 , 6 , 7 ) and TNF-α ( 6) , with IC 50 in the low micromolar range; however much of this apparent activity could be accounted for by the cytotoxicity of these compounds. None of the compounds showed anti-bacterial activity. Conclusions The inhibition of PGE 2 , an important mediator of inflammation and pain, by flindersine and a derivative thereof, along with the moderate anti-inflammatory activity shown by several other compounds isolated from Geijera parviflora leaf extract, support the traditional use of this plant for pain relief by Australian Aboriginal people.

In an effort to identify natural compounds with immunosuppressive activity, nine new flavonoids, including one isoflav-3-ene derivative ( 1 ), one coumaronochromone ( 2 ), two isoflavanones ( 3 , 4 ), one isoflavone derivative ( 6 ), one isoflavone ( 7 ), three flavonols ( 8 , 9 , 10 ), as well as one known compound, hydroisoflavone C ( 5 ), were isolated from the roots of Campylotropis hirtella . The structures of these compounds were elucidated by extensive spectroscopic measurements. All of the compounds were assessed for immunosuppressive activity. Among the isolates, compound 2 showed good inhibitory activity against mitogen-induced splenocyte proliferation with an IC 50 of 0.28 μM and relatively low cytotoxicity.

In an effort to identify new anti-inflammatory and antibacterial agents with potential application in wound healing, five new dibenzofurans, 1,3,7,9-tetrahydroxy-2,8- dimethyl-4,6-di(2-methylbutanoyl)dibenzofuran (1), 1,3,7,9- tetrahydroxy-2,8-dimethyl-4-(2-methylbutanoyl)-6-(2- methylpropionyl)dibenzofuran (2), 1,3,7,9-tetrahydroxy-2,8- dimethyl-4,6-di(2-methylpropionyl)dibenzofuran (3), 1,3,7,9- tetrahydroxy-4,6-dimethyl-2-(2-methylbutanoyl)-8-(2- methylpropionyl)dibenzofuran (4), and 1,3,7,9-tetrahydroxy- 4,6-dimethyl-2,8-di(2-methylpropionyl)dibenzofuran (5), were isolated from the leaves of Pilidiostigma glabrum together with one previously described dibenzofuran. Structure elucidation was achieved by way of spectroscopic measurements including 2D-NMR spectroscopy. Compounds with 2,8-acyl substitutions had potent antibacterial activity against several Gram-positive strains (MIC in the low micromolar range), while compounds with 4,6- acyl substitutions were less active. All compounds except 3 inhibited the synthesis of nitric oxide in RAW264 macrophages with IC50 values in the low micromolar range. Compounds with 2,8-acyl substitutions also inhibited the synthesis of PGE2 in 3T3 cells, whereas 4,6-acyl-substituted compounds were inactive. None of the compounds inhibited the synthesis of TNF-α in RAW264 cells. The compounds showed variable but modest antioxidant activity in the oxygen radical absorbance capacity assay. These findings highlight that much of the Australian flora remains unexplored and may yet yield many new compounds of interest. Initial clues are provided on structure/activity relationships for this class of bioactives, which may enable the design and synthesis of compounds with higher activity and/or selectivity. Refereed/Peer-reviewed

Seven new oleanane-type triterpenoid saponins (glabasaponin A-G) were isolated from the roots of Glycyrrhiza glabra together with a known compound macedonoside A. The structures of compounds 1-7 were determined on the basis of 1D and 2D NMR as well as the MS data analyses. The sugar moieties of compound 5 were confirmed by gas chromatography after hydrolysis.

Phytochemical investigation of the fresh bulbs of Fritillaria anhuiensis S. C. Chen et S. E. Yin, resulted in the isolation of a known steroidal alkaloid solanidine of (22S,25S)-solanid-5-en-3beta-ol (1), which has never yet been found as a natural substance, and of a new steroidal alkaloid (22S,25S)-solanid-5,20(21)-dien-3beta-ol. Compounds 1 and 2 were the first solanidine-type alkaloids with 22-S configuration discovered from nature. Their structures were elucidated based on spectroscopic analysis, including 1D and 2D NMR experiments.

From the dried roots of Campylotropis hirtella (Franch.) Schindl., five novel isoflavonoids, 3( S)-7,2',4'-trihydroxy-5,5'-dimethoxy-6-(3-methylbut-2-enyl)-isoflavan ( 1), 3( S)-2',4'-dihydroxy-5,5'-dimethoxy-(6'',6''-dimethylpyrano)-(2'',3'':7,6)-isoflavan ( 2), 3( R)-5,4'-dihydroxy-2'-methoxy-3'-(3-methylbut-2-enyl)-(6'',6''-dimethylpyrano)-(7,6 : 2'',3'')-isoflavanone ( 3), 3( R)-5,4'-dihydroxy-2'-methoxy-(6'',6''-dimethylpyrano)-(7,6: 2'',3'')-isoflavanone ( 4), and 3( R)-5,4'-dihydroxy-7,2'-dimethoxy-6-geranylisoflavanone ( 5) were isolated. The structures of the compounds were elucidated on the basis of spectroscopic analysis. All isolates exhibited good immunosuppressive activities on mitogen-induced splenocyte proliferation, and their cytotoxicity on splenic lymphocytes was also tested.

Two novel diterpenoids were isolated from the bulbs of Fritillaria anhuiensis S. C. Chen and S. E. Yin. Compound 1 was the first diterpenoid containing a sulfonyl group isolated from nature. Compound 2 was a novel kaurane-type diterpenoid. Their structures were determined by extensive spectroscopic analysis (IR, MS, NMR, and X-ray diffraction). Compound 1 significantly attenuated nitric oxide (NO) production of a macrophage cell line of Raw 264.7 cells stimulated with IFN-γ.

Five anthranilic acid derivatives, a mixture I of three new compounds 11′-hexadecenoylanthranilic acid ( 1 ), 9′-hexadecenoylanthranilic acid ( 2 ), and 7′-hexadecenoylanthranilic acid ( 3 ), as well as a new compound 9,12,15-octadecatrienoylanthranilic acid ( 4 ) together with a new natural product, hexadecanoylanthranilic acid ( 5 ), were isolated from Geijera parviflora Lindl. (Rutaceae). Their structures were elucidated by extensive spectroscopic measurements, and the positions of the double bonds in compounds 1 – 3 of the mixture I were determined by tandem mass spectrometry employing ozone-induced dissociation. The mixture I and compound 5 showed good antibacterial activity against several Gram-positive strains.

Two novel alkaloids (parvifloranines A and B), possessing an unusual 11-carbon skeleton linked with amino acids, were isolated from Geijera parviflora , an endemic Australian Rutaceae. Their structures were elucidated by extensive spectroscopic measurements including 2D NMR analyses. Parvifloranine A was found to be a mixture of two enantiomers, (S)-1 and (R)-1 , in a ratio of 1:4, based on their separation using a chiral column. Parvifloranine B is also believed to be a mixture of enantiomers. Proposed biosynthetic pathways are discussed. Parvifloranine A inhibited the synthesis of nitric oxide in LPS-stimulated RAW 264.7 macrophages with an IC 50 value of 23.4 μM. Refereed/Peer-reviewed

Pilidiostigmin, a novel dimeric acylphloroglucinol derivative, was isolated from the leaves of the Australian plant species Pilidiostigma glabrum (Myrtaceae). Pilidiostigmin exists in the plant in the form of a sodium salt, which is rare in natural products. The elucidation of the structure and relative configuration was achieved by spectroscopic measurements with special emphasis on 1D and 2D NMR techniques. Pilidiostigmin was found to display biological activity; it significantly and dose-dependently inhibited the synthesis of nitric oxide in LPS-stimulated RAW 264.7 macrophages at low micromolar concentrations. (C) 2013 Elsevier Ltd. All rights reserved.

A pair of isomeric isoflavonoid derivatives, Hirtellanines A ( 1 ) and B ( 2 ), has been isolated from the roots of Campylotropis hirtella (Franch.) Schindl. and their structures were elucidated on the basis of spectroscopic methods, with special emphasis on 1D and 2D NMR techniques. The in vitro assay showed that Hirtellanine A had strong B lymphocyte suppression activity (IC 50 : 0.06 μM) and T lymphocyte suppression activity (IC 50 : 0.92 μM). Hirtellanine B showed moderate B lymphocyte suppression activity (IC 50 : 3.00 μM) and T lymphocyte suppression activity (IC 50 : 9.55 μM). Due to the potent immunosuppressive activities and lower cytotoxicity, Hirtellanine A could be a promising lead towards novel immunosuppressive agents.

In an effort to identify hemostatic components from Liparis nervosa (Thunb.) Lindl. using a bioactivity-guided fractionation approach, the n-BuOH extract was found to promote ADP-induced platelet aggregation and two compounds were isolated from the active extract. Compound 1 was a new nervogenic acid glycoside and the structure was elucidated as 3,5-bis(3-methyl-but-2-enyl)-4- O-[β-D-xylopyranosyl-(1→2)-β-D-glucopyranosyl]-benzoic acid by extensive spectroscopic measurements. Adenosine (2) was isolated from this plant for the first time. Compound 1 also showed good pro-coagulant activity in vitro.