Anti-Inflammatory Properties of Oxygenated Isocoumarins and Xanthone from Thai Mangrove-Associated Endophytic Fungus Setosphaeria rostrata.

Chronic inflammation plays a crucial role in the development and progression of numerous chronic diseases. To search for anti-inflammatory metabolites from endophytic fungi isolated from plants growing in Thai mangrove areas, a chemical investigation of those fungi was performed. Five new oxygenated isocoumarins, setosphamarins A-E (1-5) were isolated from the EtOAc extract of an endophytic fungus Setosphaeria rostrata, along with four known isocoumarins and one xanthone. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of the undescribed compounds were established by comparative analysis between experimental and calculated circular dichroism (ECD) spectroscopy. All the compounds were evaluated for their anti-inflammatory activity by monitoring nitric oxide inhibition in lipopolysaccharide-induced macrophage J774A.1 cells. Only a xanthone, ravenelin (9), showed potent activity, with an IC50 value of 6.27 µM, and detailed mechanistic study showed that it suppressed iNOS and COX-2 expression.

Tocotrienol monomers and dimers from the roots of Litchi chinensis with tyrosinase inhibition activity.

Four undescribed modified tocotrienols, including two monomers, litchinols A (1) and B (2), and two walsurol dimers, δ,δ-walsurol (3) and γ,δ-bi-O-walsurol (4), as well as seven known compounds (5-11) were isolated from the roots of Litchi chinensis. The structures of the undescribed compounds were elucidated based on analyses of spectroscopic data and ECD spectra. All tocotrienol derivatives (1-6) were evaluated for their tyrosinase inhibition activity. Only monomers 1-2 and 5-6 displayed potent inhibitory activity and greater than kojic acid. Kinetic analysis revealed that the representative compound 2 was uncompetitive inhibitor with the inhibition constant value of 5.70 µM.

Synergistic impact of arbutin and kaempferol-7-O-α-L-rhamnopyranoside from Nephelium lappaceum L. on whitening efficacy and stability of cosmetic formulations.

Four flavonoid glycosides, namely quercetin-3-O-rhamnoside (1), kaempferol-3-O-ß-D-glucopyranosyl (2), kaempferol-7-O-α-L-rhamnopyranoside (3), and kaempferol-3-O-ß-D-glucopyranosyl-7-O-α-L-rhamnopyranoside (4), from Nephelium lappaceum L. seeds were evaluated for their efficacy against melanin inhibition in B16F10 melanoma cells and tyrosinase inhibition. Among them, kaempferol-7-O-α-L-rhamnopyranoside (3) displayed the highest potency in both activities without any significant cytotoxicity. The combination of compound 3 and arbutin in specific proportions demonstrated a synergistic effect (CI < 1) in inhibiting melanin production in B16F10 cells and tyrosinase inhibition. Additionally, a cosmetic formulation containing compound 3 and arbutin as active ingredients exhibited favorable stability under accelerated storage conditions. Quantitative analysis indicated that compound 3 and arbutin levels in the formulation were above 90% after one month of storage. Determination of the formulation's shelf life using the Q10 method, estimating it to be around 5.2 months from the date of manufacture. The synergy between arbutin and kaempferol-7-O-α-L-rhamnopyranoside (3) extracted from N. lappaceum substantially enhances both the whitening effectiveness and the stability of cosmetic formulations.

Acrotrione B, a Prenylated and Highly Oxidized Xanthenoid with Antibacterial and Anti-proliferative Activities from the Roots of Acronychia pedunculata.

A new prenylated xanthenoid with a highly oxidized core, acrotrione B (1: ), together with six previously reported acetophenones (2:  - 7: ), were isolated from the roots of Acronychia pedunculata. The structures of the isolated compounds were elucidated by thorough analysis of their 1D and 2D NMR spectroscopic data. The relative and absolute configurations of acrotrione B were determined by electronic circular dichroism (ECD) calculations. Acrotrione B is an unusual, oxidized xanthenoid with a cyclohexadienone core that has not been previously reported. It thus represents a new skeletal type within the xanthenoid class. Acrotrione B (1: ) exhibited anti-proliferative activity against Hela (IC50 = 16.0 µM) and A549 (IC50 = 16.3 µM) cell lines. 5'-Prenylacrovestone (4: ) and acrovestone (5: ) were even more potent with IC50 values of 5.1 µM and 0.77 µM, respectively, against Hela cells and 11.8 µM and 1.13 µM, respectively, against A549 cells. Moreover, acrotrione B (1: ) displayed moderate antibacterial activities against Staphylococcus aureus, Bacillus cereus, and Bacillus subtilis, with MIC values in the range of 16 - 64 µg/mL. Finally, acropyrone (6: ) showed a significant suppression of lipopolysaccharide (LPS) induced NO production in murine macrophage J774.A1 cells (IC50 = 8.9 µM).

Fatty acid acylated flavonol glycosides from the seeds of Nephelium lappaceum and their nitric oxide suppression activity.

Five undescribed fatty acid esters of flavonol glycosides, nephelosides A-E, along with eight known compounds, were isolated from the seeds of Nephelium lappaceum L. The structures were elucidated by extensive analysis of spectroscopic data in combination with GC-MS analysis. Potency of compounds toward nitric oxide suppression was assessed by monitoring the inhibition of lipopolysaccharide-stimulated nitric oxide production in J744.A1 macrophage cells. Nepheloside D, kaempferol and kaempferol 7-O-α-L-rhamnopyranoside showed significant activity with IC50 values of 26.5, 11.6 and 12.0 µM, respectively.

Bioactive xanthones, benzophenones and biphenyls from mangosteen root with potential anti-migration against hepatocellular carcinoma cells.

Liver cancer refers primarily to hepatocellular carcinoma (HCC) accounting for over 90% of cases and is the highest incidence in men in Thailand. Over the past decades, the incidence of HCC dramatically increased with a strong rise of mortality rates. Garcinia mangostana, "Queen of Fruit" of Thailand, is known as a rich source of xanthones with potent cytotoxic properties against various cancer cells. Study on xanthones is provoking not only due to the structural diversity but also a wide variety of pharmacological activities. Hence the aim of the current study is to determine the effects of metabolites from G. mangostana root on cell proliferation and migration of hepatocellular carcinoma cells. Twenty-two metabolites, including two new benzophenones and one new biphenyl, were isolated and characterized. Five xanthones with a prenyl moiety showed significant cytotoxicity against both HCC cells tested; however, only dulxanthone D displayed the most promising activity on the migration of Huh7 HCC cells, comparable to sorafenib, a standard drug. Moreover, the compound dose-dependently induced apoptosis in Huh7 cells via mitochondrial pathway. Accordingly, dulxanthone D held a great potential for development as a novel migration inhibitor for effective HCC treatment.

Cassane-type diterpenes from roots of Pterolobium macropterum and their anti-inflammatory activity.

Eight undescribed cassane diterpenes, pterolobirins C-J, together with two known analogs, were isolated from the roots of Pterolobium macropterum. Their structures were characterized by extensive spectroscopic techniques including NMR, MS, ECD and X-ray crystallographic spectroscopy. The absolute configuration of pterolobirin J was confirmed by single-crystal X-ray diffraction data. The compounds were screened for their anti-inflammatory activity on the lipopolysaccharide (LPS) induced nitric oxide (NO) production in J774. A1 macrophage cells. Pterolobirin E and sucutinirane C displayed good NO inhibition with IC50 values of 24.44 ± 1.34 and 19.16 ± 1.22 µM, respectively.

Picrotoxane sesquiterpene and α-pyrone derivative from Dendrobium signatum and their free radical scavenging potency.

One new picrotoxane sesquiterpene (1) and one new α-pyrone derivative (4), together with nine known compounds, were isolated from the aerial parts of Dendrobium signatum. The structures of the new compounds were elucidated based on the interpretation of 1D and 2D NMR, HRESIMS and electronic circular dichroism (ECD) data. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction data. The new α-pyrone 4 exhibited promising ABTS scavenging activity with IC50 value of 0.7 µM.

Two new rearranged clerodane diterpenes from Thai Tinospora baenzigeri.

A new rearranged clerodane-type diterpene (1), tinobaenzigeride, and a new rearranged clerodane glucoside (2) were isolated from the stems of Tinospora baenzigeri, along with four known compounds (3‒6). Their structures were elucidated by spectroscopic data analysis. In addition, the structure and configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 1 are a rare example of rearranged clerodanes, since it contains a fully oxygenated tetrahydrofuran moiety. The isolated compounds were evaluated for their cytotoxicity against Hep-G2 and MCF-7 cancer cells, none of them did show any significant activity at 25 µM.

Diterpenoids from the aerial parts of Euphorbia antiquorum and their efficacy on nitric oxide inhibition.

Eight previously undescribed diterpenoids of different types were isolated from ethyl acetate extract of the aerial parts of Euphorbia antiquorum L., along with fifteen known diterpenoids. Their structures and configurations were determined by 1D and 2D NMR, MS, and electronic circular dichroism (ECD). Additionally, the absolute configuration of ent-12-oxo-2,3-secobeyer-15-en-2,3-dioic acid-3-methyl ester was confirmed through single-crystal X-ray diffraction. Efficacy of the compounds on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in murine macrophage J774.A1 cells was evaluated. ent-15-Acetoxylabda-8(17),13E-diene-3-one, ent-15-oxolabda-8(17),13E-diene-3-one and rhizophorin B was significantly suppressed NO production with IC50 values of 11.7, 12.5 and 16.1 µM, respectively.

Rearranged Clerodane Diterpenoids from the Stems of Tinospora baenzigeri.

Four new rearranged clerodane-type diterpenoids (1-4), a new glucoside (5), and six known compounds (6-11) were obtained from the EtOAc crude extract of Tinospora baenzigeri stem. The structures of the new compounds were elucidated by interpreting their spectroscopic data, particularly 1D and 2D NMR. Single-crystal X-ray diffraction analysis was subsequently performed to confirm the structures and relative configurations of compounds 1-4. These compounds are rare examples of rearranged clerodanes, particularly compound 4, possessing a fully oxidized tetrahydrofuranyl ring. The isolated compounds were assayed for their protective effect against N-acetyl- p-aminophenol (APAP)-induced HepG2 cell damage. Compounds 8, 9, and 11 showed hepatoprotective activity at 10 µM with 17.0, 19.2, and 39.0% inhibition, respectively, whereas rearranged clerodanes (1-3 and 5) were weakly active.

Inhibition of TNF-α-Induced Inflammation by Sesquiterpene Lactones from Saussurea lappa and Semi-Synthetic Analogues.

We investigated the tumor necrosis factor-alpha (TNF-α) inhibitory activity of sesquiterpenes from Saussurea lappa root extracts. According to the hexane and EtOAc extracts showing significant activity with IC50 values of 0.5 and 1.0 µg/mL, respectively, chromatographic fractionation of the extracts was performed and led to the isolation of 10 sesquiterpenes (1: -10: ). Costunolide (1: ), a major compound, and dehydrocostus lactone (4: ) exhibited high efficiency in decreasing TNF-α levels, with IC50 values of 2.05 and 2.06 µM, respectively. In addition, sesquiterpene analogues were synthesized to establish their structure-activity relationship (SAR) profile. Among the semi-synthetic analogues, compounds 6A: and 16: showed the most potent activity with IC50 values of 1.84 and 1.97 µM, respectively. More importantly, compound 6A: showed less toxicity than costunolide and 16: . These results provided the first SAR profile of sesquiterpene lactones and indicated that the α-methylene-γ-lactone moiety plays a crucial role in TNF-α inhibition. Additionally, the epoxide derivative 6A: might represent a lead compound for further anti-TNF-α therapies, owing to its potent activity and reduced toxicity.

Chamigrane Sesquiterpenes from a Basidiomycetous Endophytic Fungus XG8D Associated with Thai Mangrove Xylocarpus granatum.

Six new chamigrane sesquiterpenes, merulinols A‒F (1‒6), and four known metabolites (7‒10) were isolated from the culture of the basidiomycetous fungus XG8D, a mangrove-derived endophyte. Their structures were elucidated mainly by 1D and 2D NMR, while the structures of 1 and 2 were further confirmed by single-crystal X-ray diffraction analysis. The in vitro cytotoxicity of all compounds was evaluated against three human cancer cell lines, MCF-7, Hep-G2, and KATO-3. Compounds 3 and 4 selectively displayed cytotoxicity against KATO-3 cells with IC50 values of 35.0 and 25.3 µM, respectively.

Highly oxygenated chromones from mangrove-derived endophytic fungus Rhytidhysteron rufulum.

Five highly oxygenated chromones, rhytidchromones A-E, were isolated from the culture broth of a mangrove-derived endophytic fungus, Rhytidhysteron rufulum, isolated from Thai Bruguiera gymnorrhiza. Their structures were determined by analysis of 1D and 2D NMR spectroscopic data. The structure of rhytidchromone A was further confirmed by single-crystal X-ray diffraction analysis. These compounds were evaluated for cytotoxicity against four cancer cell lines (MCF-7, Hep-G2, Kato-3 and CaSki). All compounds, except for rhytidchromone D, displayed cytotoxicity against Kato-3 cell lines with IC50 values ranging from 16.0 to 23.3µM, while rhytidchromones A and C were active against MCF-7 cells with IC50 values of 19.3 and 17.7µM, respectively.

Inhibitory effects of flavonoids from stem bark of Derris indica on the formation of advanced glycation end products.

ETHNOPHARMACOLOGICAL RELEVANCE: Derris indica (Lamk.) Bennet has been used in traditional medicine in many countries for the treatment of bronchitis, whooping cough, rheumatic joints and dipsia in diabetes. In addition, several studies have revealed that this plant displayed various pharmacological activities including anti-diabetic. The present study was designed to isolate the active compounds from its stem bark and evaluate their inhibitory activity on the formation of advanced glycation end products. MATERIAL AND METHODS: The EtOAc extract of the stem bark of Derris indica was isolated by column chromatographic techniques. The structures of isolated compounds were established on the basis of extensive spectroscopic methods. All compounds were assayed for their inhibitory effects on advanced glycation end products formation using BSA-methylglyoxal assay. RESULTS: Chromatographic fractionation of the EtOAc extract of Derris indica stem bark led to the isolation of two new pyranoflavonoids, derrisins A and B (1-2), along with 11 known flavonoids (3-13). The inhibitory activities of the compounds on the formation of advanced glycation end products were evaluated. Derrisin B (2) was the most active compound with IC50 value of 18.0µM, and displayed stronger inhibitory activity compared with positive control aminoguanidine. CONCLUSIONS: This study provided the possibility that a pyranoflavonoid (2) found in Derris indica might have therapeutic potential as an inhibitor against the formation of advanced glycation end products.

Rearranged limonoids and chromones from Harrisonia perforata and their anti-inflammatory activity.

Two new rearranged limonoids, harperforatin (1) and harperfolide (2), and a new chromone, harperamone (3), were isolated from fruits and roots of Harrisonia perforata, together with eight known compounds. Their structures were elucidated on the basis of spectroscopic data. Harperfolide (2) exhibited potent anti-inflammatory activity by suppressing nitric oxide (NO) production from activated macrophages with IC50 value of 6.51 µM. Furthermore, its effect is mediated by reduction of iNOS protein expression, attributable to the inhibitory action of LPS-induced NO production.