Chromene meroterpenoids from Rhododendron dauricum L. and their anti-inflammatory effects.

Rhododendron dauricum L. is a perennial herb belonging to the genus Rhododendron, commonly utilized in formulations for treating coughs and bronchitis, as well as in herbal teas for enhancing immunity and preventing tracheitis. In this study, fifteen previously undescribed chromene meroterpenoids (1a/1b-4a/4b, 5-8, 9b, 10a, 11b), along with twenty-one known compounds were isolated from the dried twigs and leaves of Rhododendron dauricum L. Of these, (-)-rhodonoid E (9b), (+)-confluentin (10a), and (-)-rubiginosin D (11b) were separated for the first time by chiral HPLC separation. The elucidation of their structures, including absolute configurations, was achieved through a combination of techniques such as NMR, HRESIMS, modified Mosher's method and quantum-chemical calculation of electronic circular dichroism (ECD) spectra. Seven pairs of enantiomers, compounds 1a/1b-4a/4b and 9a/9b-11a/11b, were initially obtained in a racemic manner and were further separated by chiral HPLC preparation. The biological assessment of these compounds against NO production was conducted in the LPS-induced RAW264.7 macrophage cells model. Compounds 9a, 9b, and 11a displayed inhibitory rates exceeding 80%, with IC50 values ranging from 8.69 ± 0.94 to 13.01 ± 1.11 µM. A preliminary examination of the structure-activity relationship (SAR) for these isolates indicated that chromene meroterpenoids with α, ß-unsaturated ketone carbonyl and Δ12(13) double bond functionalities exhibited enhanced anti-inflammatory properties.

Proangiogenic Azaphilones from the Marine-Derived Fungus Neopestalotiopsis sp. HN-1-6.

Developing novel, safe, and efficient proangiogenic drugs is an important approach for the prevention and treatment of cardiovascular diseases. In this study, 4 new compounds, including 3 azaphilones (1-3) and 1 dihydroisocoumarin (4), as well as 13 known compounds (5-17), were isolated from the sea-mud-derived fungus Neopestalotiopsis sp. HN-1-6 from the Beibu Gulf of China. The structures of the new compounds were determined by NMR, MS, ECD, and NMR calculations. Compounds 3, 5, and 7 exhibited noteworthy proangiogenic activities in a zebrafish model at a concentration of 40 µM, without displaying cytotoxicity toward five human cell lines. In addition, some compounds demonstrated antibacterial effects against Staphylococcus aureus, Escherichia coli, and Candida albicans, with MIC values ranging from 64 µg/mL to 256 µg/mL.

Azaphilone pigments from the marine-derived Penicillium sclerotium UJNMF 0503 and their neuroprotective potential against H2O2-induced cell apoptosis through modulating PI3K/Akt pathway.

Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H2O2-induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway.

Neuroprotective azaphilones from a deep-sea derived fungus Penicillium sp. SCSIO41030.

Ten azaphilones including one pair of new epimers and three new ones, penineulones A-E (1-5) with the same structural core of angular deflectin, were obtained from a deep-sea derived Penicillium sp. SCSIO41030 fermented on a liquid medium. Their structures including absolute configurations were elucidated using chiral-phase HPLC analysis, extensive NMR spectroscopic and HRESIMS data, ECD and NMR calculations, and by comparing NMR data with literature data. Biological assays showed that the azaphilones possessed no antitumor and anti-viral (HSV-1/2) activities at concentrations of 5.0 µM and 20 µM, respectively. In addition, azaphilones 8 and 9 showed neuroprotective effects against Aß25-35-induced neurotoxicity in primary cultured cortical neurons at a concentration of 10 µM. Azaphilones 8 and 9 dramatically promoted axonal regrowth against Aß25-35-induced axonal atrophy. Our study indicated that azaphilones could be promising lead compounds for neuroprotection.

Efficacy of Precocene I from Desmosstachya bipinnata as an Effective Bioactive Molecules against the Spodoptera litura Fab. and Its Impact on Eisenia fetida Savigny.

The sustainability of agroecosystems are maintained with agro-chemicals. However, after more than 80 years of intensive use, many pests and pathogens have developed resistance to the currently used chemistries. Thus, we explored the isolation and bioactivity of a chemical compound, Precocene I, isolated from the perennial grass, Desmosstachya bipinnata (L.) Stapf. Fractions produced from chloroform extractions showed suppressive activity on larvae of Spodoptera litura (Lepidoptera: Noctuidae), the Oriental armyworm. Column chromatography analyses identified Precocene I confirmed using FTIR, HPLC and NMR techniques. The bioactivity of the plant-extracted Dp-Precocene I was compared to a commercially produced Precocene I standard. The percentage of mortality observed in insects fed on plant tissue treated with 60 ppm Db-Precocene I was 97, 87 and 81, respectively, for the second, third and fourth instar larvae. The LC50 value of third instars was 23.2 ppm. The percentages of survival, pupation, fecundity and egg hatch were altered at sub-lethal concentrations of Db-Precocene I (2, 4, 6 and 8 ppm, sprays on castor leaves). The observed effects were negatively correlated with concentration, with a decrease in effects as concentrations increased. Distinct changes in feeding activity and damage to gut tissues were observed upon histological examination of S. litura larvae after the ingestion of Db-Precocene I treatments. Comparative analyses of mortality on a non-target organism, the earthworm, Eisenia fetida, at equal concentrations of Precocene I and two chemical pesticides (cypermethrin and monocrotophos) produced mortality only with the chemical pesticide treatments. These results of Db-Precocene I as a highly active bioactive compound support further research to develop production from the grass D. bipinnata as an affordable resource for Precocene-I-based insecticides.

Chebulic acid derivatives from Balakata baccata and their antineuroinflammatory and antioxidant activities.

Sixteen chebulic acid derivatives, including nine new (1-9) and seven known (10-16) ones, were isolated from an ethanol extract of the branches and leaves of Balakata baccata. The structures of the new compounds were elucidated by their UV, IR, HRESIMS, NMR, electronic circular dichroism (ECD) and single-crystal X-ray diffraction data. The effects of all the isolates on antineuroinflammatory and antioxidant activities were evaluated. Compared with the positive control minocycline (IC50 = 1.21 ± 0.71 µM), compounds 1-16 with IC50 values being greater than 50 µM, displayed almost no effects on the inhibition of NO production in LPS-induced BV-2 microglial cells, however, the results of antioxidant activity for compounds 1-16 showed significant DPPH-radical scavenging abilities with EC50 value ranging from 3.98 to 14.24 µM, while the EC50 value of positive control vitamin C was 14.31 µM. At last, the results of PCR (qRT-PCR) analysis showed that compound 1 could enhance the expression of antioxidases (HO-1, GCLC, and NQO1) at the mRNA levels.

Azaphilones and Meroterpenoids from the Soft Coral-Derived Fungus Penicillium glabrum glmu003.

Two new azaphilone compounds, daldinins G (1) and H (2), together with nine known compounds daldinin D (3), sargassopenilline B (4), austalide V (5), austalide K (6), austalide P (7), austalide P acid (8), austalide H (9), 13-O-deacetyaustalide I (10), and 17-O-demethylaustalide B (11), were isolated from the soft coral-derived fungus Penicillium glabrum glmu003. The new structures of 1 and 2 were elucidated on the basis of 1D and 2D NMR, mass spectra, and electronic circular dichroism (ECD) data analysis. Compound 5 showed weak inhibitory activity against pancreatic lipase (PL) with IC50 value of 23.9 µg/mL.

HPLC-UV/HRMS methods for the unambiguous detection of adulterations of Ginkgo biloba leaves with Sophora japonica fruits on an extract level.

CONTEXT: Ginkgo biloba L. (Ginkgoaceae) leaf extract is one of the most frequently sold herbal extracts. There have been reports on poor quality and adulteration of ginkgo leaf extracts or the powdered plant material with extracts or powder of Styphnolobium japonicum (L.) Schott (Fabaceae) (syn. Sophora japonica L.) fruits, which is rich in flavone glycosides. OBJECTIVE: The study investigates whether ginkgo leaves genuinely contain genistein and sophoricoside and whether these two substances could be used as markers to detect adulterations with sophora fruits. MATERIALS AND METHODS: A total of 33 samples of dried ginkgo leaves were sourced from controlled plantations in China, the USA, and France. After extraction, the samples were analyzed using two high-performance liquid chromatography (HPLC) coupled with UV/HRMS methods for the detection of genistein and sophoricoside, respectively. Chromatograms were compared to standard reference materials. RESULTS: In none of the tested ginkgo samples, neither genistein nor sophoricoside could be detected. The applied method was designed to separate genistein from apigenin. The latter is a genuine compound of ginkgo leaves, and its peak may have been previously misidentified as genistein because of the same molecular mass. The method for the detection of sophoricoside allows identification of the adulteration with sophora fruit without prior hydrolysis. By both HPLC methods, it was possible to detect adulterations of ≥2% sophora fruits in the investigated ginkgo extract. CONCLUSION: The methods allow unambiguous detection of adulterations of ginkgo leaves with sophora fruits, using genistein and sophoricoside as marker compounds.

Large-scale preparative isolation of bergenin standard substance from Saxifraga atrata using polyamide coupled with MCI GEL® CHP20P as stationary phases in medium pressure chromatography.

In this study, polyamide and MCI GEL® CHP20P were employed as stationary phases in medium pressure chromatography (MPC) for the efficient preparative separation of bergenin from Saxifraga atrata. Ethanol-water, methanol-water, and acetonitrile-water mobile phases all showed good enrichment capacity for bergenin fraction when polyamide was used as a stationary phase. After 5 cycles of polyamide MPC using acetonitrile/water, 1.2 g of bergenin fraction was isolated from 180 g Saxifraga atrata herb. Further purification of this fraction was conducted using MCI GEL® CHP20P styrene-divinylbenzene beads. The bergenin fraction was separated into two fractions, and after three runs of MPC, 714.2 mg of bergenin with purity above 99% was obtained. The results demonstrate that the combination of polyamide and styrene-divinylbenzene MPC can be utilized for preparative isolation of compounds from natural products with high yield and purity.

A new epimer of azaphilone derivative pinophilin B from the gorgonian-derived fungus Aspergillus fumigatus 14-27.

A new epimer of azaphilone derivative pinophilin B, epi-pinophilin B (1), and three known analogues (2-4) were obtained from the culture of the gorgonian-derived fungus Aspergillus fumigatus 14-27. The structures of 1-4, including their relative configurations were determined by extensive spectroscopic analysis and comparing with literature data. The absolute configuration of 1 was determined by electronic circular dichroism (ECD) and optical rotatory (OR) calculations methods. Compounds 1-4 were isolated from A. fumigatus for the first time. Their antibacterial and cytotoxic activities were also evaluated.

Secundiflorol G isolated from Aeschynomene fascicularis, a Mayan medicinal plant, induces apoptosis in cervical cancer cells.

Secundiflorol G (SG) is an isoflavan isolated from the root bark of Aeschynomene fascicularis, a Mayan medicinal plant used to treat cancer-like symptoms. SG has been shown to have cytotoxic effects on cervical cancer cells (HeLa). Assays were done to identify the mechanisms of SG's cytotoxic effect.HeLa cells treated with SG exhibited early and late apoptosis, and caspase-9, -8 and -3 activities. It also induces generation of reactive oxygen species and disrupted mitochondrial membrane potential.SG isolated from A. fascicularis induces apoptosis through extrinsic and intrinsic pathways on HeLa cells. SG could be a candidate for in vivo studies and a promising natural compound in cervical cancer treatment.

Rhusflavanone and mesuaferrone B: tyrosinase and elastase inhibitory biflavonoids extracted from the stamens of Mesua ferrea L.

Chemical isolation and bioactivity studies were conducted on the stamens of Mesua ferrea L., which are being used in a traditional skincare formulation in Myanmar. Rhusflavanone and mesuaferrone B were obtained as the main biflavonoids together with lupeol, five common flavonoids, and five phenolic compounds. After being identified by NMR and other spectroscopic analyses, these compounds were evaluated for their 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical scavenging, human leukocyte elastase inhibitory, and mushroom tyrosinase inhibitory activities. The two biflavonoids exhibited strong inhibitory activities against elastase and tyrosinase, but low DPPH-radical scavenging activities. The contents of rhusflavanone and mesuaferrone B in the stamens were 0.35 ± 0.04% and 0.55 ± 0.06%, respectively. Moreover, lupeol was considered to be a cosmetically important component of the stamens because of its high content and strong elastase inhibitory activity. Rhusflavanone was reported to be isolated from M. ferrea for the first time.

Sophoricoside from Sophora japonica ameliorates allergic asthma by preventing mast cell activation and CD4+ T cell differentiation in ovalbumin-induced mice.

Asthma is a chronic inflammatory lung disorder with continuously increasing prevalence worldwide. Novel strategies are needed to prevent or improve asthma. The aim of this study was to investigate the effects of sophoricoside from Sophora japonica on allergic asthma. The mature seeds of S. japonica contain a large amount of sophoricoside. Sophoricoside reduced allergic and asthmatic symptoms by suppressing airway inflammation and antibody-antigen reaction in mouse models. In particular, sophoricoside suppressed immune cell recruitment into the airway lumens of the lungs and production of pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of ovalbumin (OVA)-induced mice. It also decreased the amounts of histamine and arachidonic acid metabolites released in OVA-induced mice and antibody-antigen stimulated mast cells. In addition, sophoricoside decreased differentiation of naïve CD4+ T cells into T helper type 1 (Th1), Th2, and Th17 cells. Overall, we demonstrated that sophoricoside improved allergic asthma by suppressing mast cell activation and CD4+ T cell differentiation.

Synthesis, characterization and anti-inflammatory properties of karanjin (Pongamia pinnata seed) and its derivatives.

Karanja (Pongamia pinnata) is a medicinal tree used in the Indian traditional ayurvedic system for treating several ailments. The seeds contain a unique furano-flavonoid karanjin, which has shown to possess many medicinal properties. Its usage at the clinical level is affected due to poor solubility and absorption. In the present investigation, molecular modifications of karanjin were attempted and evaluated their effect on anti-inflammatory activity. Firstly, Karanja ketone was obtained from karanjin by hydrolysis, and it was converted into karanja ketone oxime. The oxime undergoes Beckmann rearrangement and cyclized to yield furano benzoxazole (karanja oxazole). The new derivatives were purified with >95% purity (HPLC) and spectrally characterized (HR-MS, FTIR, and NMR). Among the test compounds, karanja ketone oxime exhibited higher antioxidant activity with an IC50 value of 360 µg/ml (DPPH). Soy lipoxygenase-1 (LOX-1) inhibitory activity of oxime was higher (IC50 = 65.4 µM) than other compounds. Fluorescence studies showed that oxime had higher quenching capacity with a Qmax of 76.3% and a binding constant of 0.9 × 105 M-1 for soy LOX-1. In-silico interaction studies showed that karanja ketone oxime had the least binding energy of -5.76 kcal/mol with LOX-1 by forming two hydrogen bonds with hydrophobic amino acids Leu 390 and Gly 392. The compounds were evaluated for their acute anti-inflammatory activity by the paw and ear edema in the rat model. Karanjin inhibits paw edema and ear edema by 34.13% and 51.13%, respectively, whereas the derivatives inhibited by 45-57 % and 70-76.8%. This study reports a rational approach to synthesize karanjin derivatives with considerable anti-inflammatory properties, both in-vitro and in-vivo.

Antimicrobial Constituents from Machaerium Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Permeabilized Gram-Negative Pathogens.

Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium Pers. This plant was previously assigned as Machaerium multiflorum Spruce, from which machaeriols A-D (6-9) and machaeridiols A-C (10-12) were reported, and all were then re-isolated, except the minor compound 9, for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture 10 + 11 was the most active with an MIC value of 1.25 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA) strains BAA 1696, -1708, -1717, -33591, and vancomycin-resistant Enterococcus faecium (VRE 700221) and E. faecalis (VRE 51299) and vancomycin-sensitive E. faecalis (VSE 29212). Compounds 6-8 and 10-12 were found to be more potent against MRSA 1708, and 6, 11, and 12 against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols (7 or 8) and machaeridiols (11 or 12), which exhibited a strong synergistic activity of 12 + 8 (MIC 0.156 and 0.625 µg/mL), with >32- and >8-fold reduction of MIC's, compared to 12, against MRSA 1708 and -1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds 10 + 11, 11, 12, and 8 showed activity in the range of 0.5-8 µg/mL for two strains of Acinetobacter baumannii, 2-16 µg/mL against Pseudomonas aeruginosa PAO1, and 2 µg/mL against Escherichia coli NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of Klebsiella pneumoniae.

Enantiomeric chromene derivatives with anticancer effects from Mallotus apelta.

Mallotusapelta(Lour.) Müll.Arg has been used in traditional medicine for the treatment of chronic hepatitis. Six new chromene derivatives, malloapeltas C-H (1-6) and one known compound, malloapelta B (7) were isolated and structured from the leaves of M.apelta. Two pairs of enantiomers (1a/1b and 2a/2b) were successfully separated by chiral high-pressure liquid chromatography (HPLC). The structures and absolute configurations of compounds were determined using spectroscopic methods, including 1D, 2D NMR, and MS and quantum chemical calculation methods. All compounds were evaluated for cytotoxic activity using cell counting kit-8 (CCK-8) assay against ovariancancer cell line (TOV-21G). Compounds 1-5 and 7 exhibited significant growth and viability inhibitory effects with GI50 values ranging from 0.06 to 10.39 µM and IC50 values ranging from 1.62 to 10.42 µM on ovarian cancer cell line, TOV-21G. The most cytotoxic compounds 2, 3, and 7 were chosen for studying in apoptosis mechanism. Compounds 2, 3, and 7-induced apoptosis as evidenced by activated caspase 8, caspase 9, and PARP, increased Bak and Bax, and decreased Bcl-xL and survivin. Moreover, compounds 2, 3, and 7 significantly inhibited the NF-κB signaling pathway. Taken together, our findings propose the potential application of compounds 2, 3, and 7 for treating cancer via modulating NF-κB activity.

Rutamarin: Efficient Liquid-Liquid Chromatographic Isolation from Ruta graveolens L. and Evaluation of Its In Vitro and In Silico MAO-B Inhibitory Activity.

Naturally occurring coumarins are a group of compounds with many documented central nervous system (CNS) activities. However, dihydrofuranocoumarins have been infrequently investigated for their bioactivities at CNS level. Within the frame of this study, an efficient liquid-liquid chromatography method was developed to rapidly isolate rutamarin from Ruta graveolens L. (Rutaceae) dichloromethane extract (DCM). The crude DCM (9.78 mg/mL) and rutamarin (6.17 M) were found to be effective inhibitors of human monoamine oxidase B (hMAO-B) with inhibition percentages of 89.98% and 95.26%, respectively. The inhibitory activity against human monoamine oxidase A (hMAO-A) for the DCM extract was almost the same (88.22%). However, for rutamarin, it significantly dropped to 25.15%. To examine the molecular interaction of rutamarin with hMAO- B, an in silico evaluation was implemented. A docking study was performed for the two enantiomers (R)-rutamarin and (S)-rutamarin. The (S)-rutamarin was found to bind stronger to the hMAO-B binging cavity.

Benzopyran Derivatives and an Aliphatic Compound from a Mangrove Endophytic Fungus Penicillium citrinum QJF-22.

Two new benzopyran derivatives, (2R,4S)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol and (2S,4R,2'S,4'R)-4,4'-oxybis(5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran), and a new aliphatic compound, (3E,5Z,8S,10E)-8-hydroxytrideca-3,5,10,12-tetraen-2-one, together with three known benzopyran derivatives, were obtained from a mangrove endophytic fungus Penicillium citrinum QJF-22 collected in Hainan island. Their structures were determined by analysis of spectroscopic data and the relative configuration of (2R,4S)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol was also confirmed by single-crystal X-ray diffraction. The absolute configurations of four compounds were established by comparison of ECD spectra to calculations. The configuration of (3E,5Z,8S,10E)-8-hydroxytrideca-3,5,10,12-tetraen-2-one was confirmed by comparison of optical value to the similar compound. The configurations of the compounds (2S,4S)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol and (2R,4R)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol were first determined. (3R,4S)-3,4,8-Trihydroxy-3,4-dihydronaphthalen-1(2H)-one exhibited moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC50 of 44.7 µM, and without cytotoxicity to RAW264.7 cells within 50 µM.

Dipleosporalones A and B, Dimeric Azaphilones from a Marine-Derived Pleosporales sp. Fungus.

Dipleosporalones A and B (1 and 2), two new [2 + 2] azaphilone dimers, were obtained from a marine-derived Pleosporales sp. fungus. The absolute configurations of 1 and 2 were elucidated by calculations of their ECD spectra. Dipleosporalone A (1) possessed an unprecedented skeleton with an uncommon 6/4/6 ring system. Compounds 1 and 2 showed cytotoxicity about 30-90-fold more potent than that of their monomer pinophilin B.

Isolation, Absolute Configuration, and Biological Activities of Chebulic Acid and Brevifolincarboxylic Acid Derivatives from Euphorbia hirta.

Twenty new chebulic acid and brevifolincarboxylic acid derivatives, including eight optically pure or achiral compounds (1-7 and 14) and six pairs of enantiomers (8a/8b-13a/13b), along with nine known analogues (15-23), were isolated from an EtOH extract of the aerial parts of Euphorbia hirta. The absolute configurations of the new compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD data. Racemic or scalemic mixtures of 8-13 were isolated, and their enantiomers were analyzed by chiral-phase HPLC-ECD measurements. Compound 12 possesses an unprecedented 2H-cyclopenta[de]chromene-2,5(4H)-dione scaffold. Compounds 12, 20, and 23 displayed moderate inhibitory effects against lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, while all the isolates exhibited significant DPPH radical scavenging activities with EC50 values of 2.2-15.8 µM.