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The phytochemical study of the Diaporthe species has revealed significant classes of mycotoxins and phomopsins. Dihydroanthracenone derivatives, chromanones and isochromophilones have also been isolated from Diaporthe sp. These findings led us to explore the Diaporthe perseae for phytochemical analysis that resulted in the isolation of four new compounds designated as isochromophilones H-K (1-4), alongside three previously identified metabolites. Using extensive spectroscopic investigations such as NMR, and Mass spectroscopy, their structures were elucidated. Furthermore, the antimicrobial and anti-diabetic potentials of all isolated compounds were assessed. Compounds 1-3 demonstrated significant antibacterial activity, while compounds 4-7 exhibited comparatively lower effectiveness than the reference antibiotics. Compounds 2-3 showed potent diabetic inhibition, displaying IC 50 values of 16.3 ± 0.3 and 25.4 ± 0.3, respectively. Compounds 1, 5, and 6 displayed mild anti-diabetic effects, with IC 50 values of 56.5 ± 0.8, 37.6 ± 0.4, and 48.2 ± 0.6. However, compounds 4 and 7 were found least active., Competing Interests: Declaration of competing interest The author has no conflict of interest exits in the submission of this manuscript and the authors have complied with journal ethical requirements. Moreover, manuscript is approved by all authors as well as all the authorities acknowledged for publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fulvic acids (FAs) have been commercially used in cosmetics and agronomy due to their unique biological activities, such as plant stimulation and anti-inflammatory effects. However, the extraction sources of FAs, such as peat, are currently limited. Consequently, new extraction methods using renewable resources need to be developed, while reproducing the biological functions. Here, ionic liquids (ILs) effectively extracted fulvic-like substances (FLSs) from wood sawdust. The overall molecular weight distributions of FLSs were similar to those of commercial FAs, and key organic groups (e.g., aromatic, phenolic, and methoxy groups) were also found to be shared between commercial FAs and FLSs. Detailed compositional analysis revealed by high-resolution mass spectrometry showed that the extracts contain both lignin-like and lipid-like molecules, while commercial FAs are biased toward lignin-like and carbohydrate-like molecules. FLSs generally showed better and similar performance in radical scavenging activity against ABTS +· and H 2 O 2 . Fibroblast proliferation and lettuce growth enhancements were also observed with the extract containing 1-ethyl-3-methylimidazolium acetate and triethylammonium hydrogen sulfate, respectively, which performed better than commercial FAs. Immunofluorescence staining of in vitro human follicle dermal papilla cells supports that coexpression of hair growth-related proteins can be accelerated with FLSs, and this effect was further evidenced by in vivo mouse model experiments. Finally, the reusability of ILs in the extraction process was confirmed by analyzing the structural features of FLSs from each recycling. Our findings indicate that ILs are useful for obtaining biologically functional fulvic analogs from renewable plant sources.

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 IC 50 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, β-unsaturated ketone carbonyl and Δ 12(13) double bond functionalities exhibited enhanced anti-inflammatory properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Decursin is a pyranocoumarin compounds which are rare secondary metabolic plant products, isolated from the roots of Angelica gigas (A. gigas) . The native Korean species Angelica gigas Nakai (AGN) is widely used as a remedy for a variety of medical conditions including hematopoiesis, improving women's circulation, as sedatives, analgesics and tonic. It is unique because of the presence of substantial amounts of pyranocoumarins including decursin, decursinol, and decursinol angelate. In this review, we provide a comprehensive insight into the distribution, morphology, and chemical composition of A. gigas . A detailed discussion regarding the biological applications of decursin based on the literature retrieved from PubMed, ScienceDirect, Scopus, and Google Scholar from 2000 to the present has been discussed. Both in vitro and in vivo studies have demonstrated that decursin has potential neuroprotective, anti-inflammatory, anti-melanogenic, anti-angiogenic, antioxidant, and anti-visceral properties. Mechanistic findings establish its significance in regulating important signalling pathways, triggering apoptosis, and preventing metastasis in different cancer types. The review additionally addressed the isolation methods, biosynthesis, physiochemical characteristics, toxicity and pharmacokinetic profile of decursin. The present state of clinical studies including A. gigas is investigated, emphasizing its advancements and possibilities in the field of translational medicine., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Muralikrishnan et al.)

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 H 2 O 2 -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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jie Bao, Yan-Fen Zhao, Hua Zhang, Shan-Shan Huang, Long Wang, Chun-Ying Wang, Yu Zhang has patent #Penicillium fungus and application thereof in preparing antibacterial medicine (CN115806881) issued to Jie Bao. Lei Zhou, Wen-Min Hou, Mei-Hui Hou, Jie Bao, Peng-Wei Jing, Hao Li, Yong-Mei Wu has patent #Extraction of nitrogenophilic ketone compound and its application(CN115850231) issued to Jie Bao. Jie Bao, Yan-Fen Zhao, Kongkai Zhu, Hua Zhang, Xin-Xin Wang, Ze-Long Chen, Ruo-Ping Ma has patent #Azone compounds and their preparation methods and their application in preparation of neuroprotective drugs (CN115851454) issued to Jie Bao. Jie Bao, Yan-Fen Zhao, Hua Zhang, Xin-Xin Wang, Shan-Shan Huang, Xin-Ping Liu has patent #Azurophilic ketone compounds with effect of promoting peripheral nerve injury repair and preparation method thereof (CN115960729) issued to Jie Bao. Xin-Ping Liu, Jie Bao, Ruo-Ping Ma, Long Wang, Yan-Fen Zhao, Xin-Xin Wang, Xin-Hui Cheng, Jia-Hui Xu has patent #Preparation of benzopyran compound and its application in preparation of medicine for neurodegenerative diseases (CN116410185) issued to Jie Bao. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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 Aβ 25-35 -induced neurotoxicity in primary cultured cortical neurons at a concentration of 10 μM. Azaphilones 8 and 9 dramatically promoted axonal regrowth against Aβ 25-35 -induced axonal atrophy. Our study indicated that azaphilones could be promising lead compounds for neuroprotection.

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.

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.

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 IC 50 value of 23.9 μg/mL., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

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 (IC 50  = 1.21 ± 0.71 μM), compounds 1-16 with IC 50 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 EC 50 value ranging from 3.98 to 14.24 μM, while the EC 50 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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 LC 50 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.

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.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

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.

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., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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 IC 50 value of 360 µg/ml (DPPH). Soy lipoxygenase-1 (LOX-1) inhibitory activity of oxime was higher (IC 50  = 65.4 µM) than other compounds. Fluorescence studies showed that oxime had higher quenching capacity with a Q max of 76.3% and a binding constant of 0.9 × 10 5 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 .

Brazilein is among the main chemical constituents of Caesalpinia sappan . It has diverse pharmacological activities. Modern pharmacological studies have shown that the compound has antitumor, anti-inflammatory, antibacterial, antioxidant, immunomodulatory, and other pharmacological activities. Brazilein is often used as a stain in various industries. The separation of brazilein by traditional column chromatography will not only result in contamination of the chromatographic column materials, but also lead to loss of the active ingredient. Countercurrent chromatography is an advanced liquid-liquid chromatographic separation technique. It has been widely used for natural product separation and isolation as it offers several advantages, such as low solvent consumption, a highly selective solvent system, and high recoveries. Typical countercurrent chromatography techniques include centrifugal partition chromatography (CPC), high-speed countercurrent chromatography (HSCCC), and high performance countercurrent chromatography (HPCCC). It is well known that choosing a suitable solvent system is vital in countercurrent separation. Therefore, two methods were introduced for choosing a suitable solvent system. One is the generally useful estimation of solvent systems (GUESS) method, which employs thin-layer chromatography (TLC) to identify a suitable solvent system with minimal labor for the rapid purification of target compounds, and another is the Shake-Flash method. The solvent system could be determined by observing the distribution of the sample in the upper and lower phases. Two kinds of solvent systems were screened using the TLC-GUESS and Shake-Flash methods, and tested through the analysis mode of the HPCCC instrument. The results showed that chloroform-methanol-water (4:3:2, v/v/v) was the optimal solvent system for HPCCC separation. A total of 15.2 mg of brazilein and 5.7 mg of caesappanin C were obtained from an ethyl acetate extract with high purities (95.6% and 89.0%, analyzed by HPLC) in one step using the preparation mode of HPCCC, the reversed-phase liquid chromatography mode with the apparatus rotated at 1600 r/min, a flow rate of 10 mL/min, separation temperature of 25℃, and detection wavelength of 285 nm. Their structures were determined by spectroscopic and spectrometric analyses. Brazilein stained the solid packing material in the column and was difficult to elute. The results showed that the use of HPCCC for the separation of brazilein can not only prevent the loss of target active ingredients in Caesalpinia sappan , but also shorten the separation and purification times and improve the operating efficiency. Therefore, HPCCC can be used for the separation and preparation of other pigment compounds in Caesalpinia sappan and other dye plants.

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 GI 50 values ranging from 0.06 to 10.39 μM and IC 50 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The spineless cuttlefish Sepiella inermis encompasses a major share in the marine fisheries sector, and represents as a culinary delicacy in many cultures. Bioactivity-guided fractionation of methanol:ethyl acetate (MeOH:EtOAc, 1:1) extract of the edible parts of the species ensued in identification of two hexahydro chromenyl analogues namely, methyl 7-ethyl-hexahydro-8a-methyl-2 H -chromene-4-carboxylate ( 1 ) and methyl 1-acetoxy-hexahydro-3-methyl-3-propyl-1 H -isochromene-4-carboxylate ( 2 ). The isolated metabolites were checked for their radical scavenging and anti-inflammatory potentials by selective in vitro models. The isochromenyl derivative exhibited potential 2,2-diphenyl-1-picryl-hydrazil and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (IC 50  < 0.45 mg mL -1 ) radical-scavenging capacities along with pro-inflammatory cyclooxygenase-2 (COX-2) (IC 50 0.75 mg mL -1 ) and 5-lipoxygenase (5-LOX) (IC 50 0.77 mg mL -1 ) inhibitory activities. The titled compounds displayed the selectivity indices (IC 50 anti-COX-1/IC 50 anti-COX-2) greater than 1.25, in comparison with synthetic anti-inflammatory drug ibuprofen (0.44), which attributed to their greater selectivity towards inducible pro-inflammatory enzyme COX-2.

Three undescribed azaphilones, phomopsones A-C (1-3) and two known azaphilones (4-5) were isolated from the culture of endophytic fungus Phomopsis sp. CGMCC No.5416 from the stems of Achyranthes bidentata. Their structures were determined by spectroscopic analysis (HRESIMS, 1D and 2D NMR), and the absolute configurations were determined by CD spectroscopy. Compounds 2 and 3 showed significant inhibitory activities against HIV-1 with against HIV-1 with IC 50 values of 7.6 and 0.5 μmol/L, respectively. Compounds 2 and 3 also displayed moderate cytotoxicity with CC 50 values of 3.2-303 μmol/L against A549, MDA-MB-231 and PANC-1 cell lines. Moreover, compound 3 can induce the early apoptosis of PANC-1 cancer cells with the apoptosis rate of 28.54%., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

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 ( h MAO-B) with inhibition percentages of 89.98% and 95.26%, respectively. The inhibitory activity against human monoamine oxidase A ( h MAO-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 h MAO- 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 h MAO-B binging cavity.

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 IC 50 of 44.7 μM, and without cytotoxicity to RAW264.7 cells within 50 μM., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Chaetomium globosum is a filamentous fungus from which we have previously isolated a series of interesting natural products. Here, we isolated a previously unknown natural product from the culture of C. globosum. Through spectroscopic and crystallographic characterization, we determined the compound to be a new dimerized azaphilone-type product which we termed cochliodone J (1). Furthermore, our investigation into the biological activity of the natural product determined that 1 was cytotoxic to human cervix carcinoma HeLa cells with an IC 50 of 17.3 µM. Lastly, a plausible biosynthetic mechanism for 1 is suggested based on our previous study on the biosynthesis of a closely related compound, cochliodone A (2).

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 2 H -cyclopenta[ de ]chromene-2,5(4 H )-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 EC 50 values of 2.2-15.8 μM.

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.

A new azaphilone, chaephilone E, eight azaphilone derivatives, and three chaetoglobosins were isolated from endophytic fungi Chaetomium globosum. The structures of the compounds were elucidated by 1D and 2D NMR as well as HR-ESI-MS data, and the absolute configuration of chaephilone E was established on the basis of electronic circular dichroism and NOESY spectrum. The activity of chaephilone E was evaluated via the cytotoxic assay (human hepatoma cell lines HepG-2) and brine shrimp (Artemia salina) bioassay., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Increasing attention has recently been focused on complex symbiotic associations, for instance coral and its symbionts. Sea cucumber, harboring diverse fungi, has also attracted more and more attention for their functional diversity. Here, secondary metabolites produced by Chaetomium globosum associated with sea cucumber, Apostichopus japonicus, were investigated using gene mining with third-generation sequencing technology (PacBio SMRT). Nine compounds, including one new compound cytoglobosin X (1), were isolated from cultures of Chaetomium globosum. Compound 1 was identified based on NMR data, HRESIMS, and ECD, and the absolute configurations were identified as 3S, 4R, 7S, 8R, 9R, 16S, 19S, 20S, and 23S. In an antimicrobial assay, compound 4 showed moderate activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus with MICs of 47.3 and 94.6 μM, respectively. Our results suggest that the microbiomes associated with sea cucumber could be an important resource for biodiversity and structural novelty, and the bioactive compounds may protect the host from pathogen microbial.

Two new azaphilone derivatives, comazaphilones G and H (1 and 2), together with eight known analogues (3-10), were isolated from an endophytic fungus Penicillium variabile. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 1, 2 and 4-10 were tested their nitric oxide inhibitory activities in lipopolysaccharide-activated RAW 264.7 macrophage cells. Compounds 1, 2 and 4-9 showed significant nitric oxide inhibitory activities with IC 50 values ranged from 4.35 ± 0.05 to 40.52 ± 0.47 μM.

Six undescribed azaphilones, deflectins C1-C3, deflectins D1-D2, and deflectin E, along with five known azaphilones were obtained from a solid culture of the wild fungus Aspergillus deflectus NCC0415. Their structures were determined by HRESIMS, NMR and ECD analyses, together with the GIAO 13 C NMR calculation method. All compounds displayed strong or moderate inhibitory activity against protein tyrosine phosphatases SHP2 and PTP1B. Structure-activity relationship analysis of these azaphilones suggested that the length of the ketone aliphatic side chain would affect their SHP2 and PTP1B inhibitory activity. In addition, the presence of a Δ 8(12) double bond on γ-lactone ring and the presence of CH 3 -2' in fatty chains may increase their inhibitory activity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The rhizomes of Bergenia ciliata ( B. ciliata , Family: Saxifragaceae ) are widely used for treating gastric ulcers in folk medicine in Asia. It was hypothesized that anti-ulcer activity of B. ciliata is due to its anti-Helicobacter pylori ( H. pylori) activity. The anti-H. pylori activity was investigated on six clinical bacterial isolates using agar well-diffusion and broth micro-dilution methods. The anti-H. pylori activity of amoxicillin (standard) was the highest (Zone of inhibition; ZI = 25 mm, minimum inhibitory concentration; MIC=0.125 µg/µL) whereas among all the extracts of the rhizomes, methanol extract showed the highest activity (ZI = 16 mm, MIC = 12.50 µg/µL). Bioassay guided isolation of methanol extract using chromatographic and crystallization techniques isolated bergenin (ZI = 21mm, MIC = 0.391µg/µL) as constituent responsible for anti-H. pylori activity. The present study describes for the first time anti-H. pylori activity and possible mechanism of anti-ulcer properties of rhizomes of B. ciliata.

Ethnopharmacological Relevance: Bergenin is a well-known active compound that exhibits antioxidant, antiarrhythmic, hepatoprotective, and anti-inflammatory activities. However, the resource reserve of Rodgersia sambucifolia, one of the main raw materials for extracting bergenin, have sharply declined, and the bergenin content in different germplasms differs vastly, resulting in a serious shortage of the market supply of bergenin., Aim of the Study: To investigate the influence of genetic diversity and environmental factors on bergenin content in Rodgersia sambucifolia., Materials and Methods: Fifty Rodgersia sambucifolia samples with a growth period of 2-3 years were collected from different areas across China and the bergenin content was determined via HPLC. Meanwhile the total genomic DNA was extracted and ISSR was performed. The bergenin content as measured using HPLC and the environmental data gathered from the meteorological stations and field work were combined and analyzed using correlation tests in XLSTAT 2018 to detect the key factors affecting bergenin content. The genetic UPGMA tree constructed based on genetic distances of the 50 samples and the chemical dendrogram constructed according to the distance between the bergenin content were compared to determine the correlation between genetic and chemical differentiation., Results: Among the 50 individuals, bergenin content varied from 2.83 to 12.54%, with the highest content being 4.43-fold that of the lowest content. The survey of the 50 individuals produced a total of 193 amplified bands, 187 of which were polymorphic (96.89%). In the study, bergenin content was positively correlated with annual mean temperature (AMT) (r = 0.583, P < 0.0001) and 1-12 month monthly mean temperature (MMT) (P < 0.0001). A comparison of the genetic dendrogram with the AHC dendrogram found no corresponding relationship between them. Mantel correlation analyses also showed that there was no significant correlation between them (r = 0.144)., Conclusions: There were large differences in bergenin content among different germplasms that were not correlated with the high genetic variation in Rodgersia sambucifolia but were significantly correlated with environmental factors, such as temperature. This study lays the foundation for subsequent superior germplasm selection and artificial breeding of Rodgersia sambucifolia to improve the bergenin content and meet market demands., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The phytochemical investigation of Fraxinus hupehensis led to the isolation and characterization of ten compounds which were identified as fraxin ( 1 ), fraxetin ( 2 ), esculetin ( 3 ), cichoriin ( 4 ), euphorbetin ( 5 ), kaempferol-3- O - β -rutinoside ( 6 ), oleuropein ( 7 ), linoleic acid ( 8 ), methyl linoleate ( 9 ), and β -sitosterol ( 10 ). Structures of the isolated constituents were characterized by 1 H NMR, 13 C NMR and HRMS. All the compounds, except compounds 3 and 4, were isolated for the first time from this plant. Further, this was the first report for the occurrence of compound 5 in the Fraxinus species. Antifungal activity evaluation showed that compound 2 exhibited significant inhibitory effects against Bipolaris maydis, Sclerotium rolfsii, and Alternaria solani with EC 50 values of 0.31 ± 0.01 mmol/L, 10.50 ± 0.02 mmol/L, and 0.40 ± 0.02 mmol/L respectively, compared to the positive control, Carbendazim, with its EC 50 values of 0.74 ± 0.01 mmol/L, 1.78 ± 0.01 mmol/L and 1.41 ± 0.00 mmol/L. Herbicidal activity tests showed that compounds 8 - 10 had strong inhibitory effects against the roots of Echinochloa crus-galli with EC 50 values of 1.16 ± 0.23 mmol/L, 1.28 ± 0.58 mmol/L and 1.33 ± 0.35 mmol/L respectively, more potently active than that of the positive control, Cyanazine, with its EC 50 values of 1.56 ± 0.44 mmol/L. However, none of the compounds proved to be active against the tested bacteria ( Erwinia carotovora, Pseudomonas syringae, and Ralstonia solanacearum ).

A new series of azaphilone pigments named atrorosins have been isolated from the filamentous fungus Talaromyces atroroseus. Atrorosins have a similar azaphilone scaffold as the orange Monascus pigment PP-O, with a carboxylic acid group at C-1, but are unique by their incorporation of amino acids into the isochromene system. Despite that the atrorosin precursor PP-O, during fermentation, was initially produced as two isomers (3:2, cis:trans ratio), the atrorosins were surprisingly almost exclusively (99.5%) produced as the cis-form, possibly due to steric interactions with the incorporated amino acid. When grown on complex media, a whole range of atrorosins is produced, whereas individual atrorosins can be produced selectively during fermentation by supplementing with the desired primary amine-containing compound.

Phytochemical investigation of the EtOAc-soluble fraction of the ethanolic extract of a yellow mutant of the fungus Monascus purpureus BCRC 38110 (Eurotiaceae) grown on rice resulted in the isolation of one new azaphilone derivative, monapurpureusone ( 1 ), one acetophenone metabolite isolated for the first time from natural source, monapurpureusin ( 2 ), along with four known compounds, TW94a ( 3 ), ergosterol ( 4 ), monascin ( 5 ), and ankaflavin ( 6 ). The structures and relative configurations of these compounds were elucidated by spectroscopic analyses, including 1D- and 2D-NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds. Some phytochemicals were evaluated for both anti-inflammatory activity through the measurement of nitric oxide (NO) production levels in lipopolysaccharide (LPS)-stimulated murine-derived macrophages RAW264.7 cell lines and antioxidant activities.

Tambulin, a flavonol isolated from Zanthoxylum armatum, showed potent insulin secretory activity in our preliminary anti-diabetic screening. Here, we explored the insulin secretory mechanism(s) of tambulin focusing in glucose-dependent, K ATP ‒ and Ca 2+ ‒channels dependent, and cAMP-PKA pathways. Mice islets and MIN6 cells were incubated with tambulin in the presence of pharmacological agonists/antagonists and the secreted insulin was measured using mouse insulin ELISA kit. The intracellular cAMP was measured by an acetylation cAMP ELISA kit. Tambulin (200 μM) showed potent insulin secretory activity only at stimulatory glucose (11-25 mM) concentrations; however, no change in insulin release was observed at basal glucose both in mice islets and MIN6 cells. Notably, in the presence of diazoxide, a K ATP channel opener; the incomplete inhibition of tambulin-induced insulin secretion was observed whereas, complete inhibition was found using verapamil, an L-type Ca 2+ channel blocker. Furthermore, the insulinotropic potential of tambulin was amplified in tolbutamide treated, and depolarized islets suggest tambulin's target other than tolbutamide. Tambulin showed no additive effect in the IBMX-induced intracellular cAMP; whereas, exerted an additive effect in the IBMX-induced insulin secretion. Furthermore, tambulin-induced insulin secretion was dramatically inhibited by PKA inhibitor (H-89), while moderate inhibition was found by using PKC inhibitor (calphostin C). Molecular docking studies also showed the best binding affinities of tambulin with PKA suggest the PKA dependent signaling cascade is involved more in tambulin-induced insulin secretion. Based on these findings, it is concluded that tambulin stimulates insulin secretion in a Ca 2+ channel-dependent but K ATP channel-independent manner, most likely by activating the cAMP-PKA pathway., (Copyright © 2019. Published by Elsevier Masson SAS.)

In view of limited information, a laboratory experiment was conducted to study the stability of organo-arsenic complexes as affected by competing anions i.e. phosphate, nitrate and sulphate. For this purpose, humic acid (HA) and fulvic acid (FA) were extracted from farmyard manure (FYM), vermicompost (VC), sugarcane bagasse (SB) and soil. A pot experiment was also conducted with 4 levels each of arsenic (As) (10, 20, 30 and 40  mg  kg -1 ) and amendments (no amendment, FYM, VC and SB at the rate of 10  t  ha -1 each). Results indicate that stability of FA extracted from sugarcane bagasse have the highest stability constant (log K) as 9.77 and the corresponding mole ratio (x) value of 1.51. The phosphate was the most effective in replacing As from organo-As complexes followed by sulphate and nitrate. Under pot culture study, As content in wheat grain was the lowest in sugarcane bagasse amended soil followed by FYM and VC at all levels of As application. Solubility-free ion activity model was most effective in predicting As uptake by wheat grain based on Olsen extractable As, pH and Walkley & Black organic C. Efficacy of organic amendments in reducing health hazard for intake of As through consumption of wheat grain grown on contaminated soil was also reflected in the values of hazard quotient (HQ)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A new isoflavone, 4'-prenyloxyvigvexin A ( 1 ) and a new pterocarpan, (6a R ,11a R )-3,8-dimethoxybitucarpin B ( 2 ) were isolated from the leaves of Lonchocarpus bussei and the stem bark of Lonchocarpus eriocalyx , respectively. The extract of L. bussei also gave four known isoflavones, maximaisoflavone H, 7,2'-dimethoxy-3',4'-methylenedioxyisoflavone, 6,7,3'-trimethoxy-4',5'-methylenedioxyisoflavone, durmillone; a chalcone, 4-hydroxylonchocarpin; a geranylated phenylpropanol, colenemol; and two known pterocarpans, (6a R ,11a R )-maackiain and (6a R ,11a R )-edunol. (6a R ,11a R )-Edunol was also isolated from the stem bark of L. eriocalyx . The structures of the isolated compounds were elucidated by spectroscopy. The cytotoxicity of the compounds was tested by resazurin assay using drug-sensitive and multidrug-resistant cancer cell lines. Significant antiproliferative effects with IC 50 values below 10 μM were observed for the isoflavones 6,7,3'-trimethoxy-4',5'-methylenedioxyisoflavone and durmillone against leukemia CCRF-CEM cells; for the chalcone, 4-hydroxylonchocarpin and durmillone against its resistant counterpart CEM/ADR5000 cells; as well as for durmillone against the resistant breast adenocarcinoma MDA-MB231/ BCRP cells and resistant gliobastoma U87MG . Δ EGFR cells.

Depression is a highly debilitating and life-threatening psychiatric disorder. The classical antidepressants are still not adequate due to undesirable side effects. Therefore, the development of new drugs for depression treatment is an urgent strategic to achieving clinical needs. Licorisoflavan A is a bioactive ingredient isolated from Glycyrrhizae Radix and has been recently reported for neuroprotective effects. In this study, the antidepressant-like effect and neural mechanism of licorisoflavan A were explored. In the mice behavioral despair test, we observed that licorisoflavan A exhibited powerful antidepressant-like effect in forced swimming test (FST), tail suspension test (TST), without affecting locomotor activity in open field test (OFT). Additionally, licorisoflavan A administration significantly restored Chronic mild stress (CMS)-induced changes in sucrose preference test (SPT), FST, and TST, without altering the locomotion in OFT. In chronical-stimulated mice, the licorisoflavan A treatment effectively attenuated the expressions of Brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), the phosphorylations of cAMP response element binding protein (CREB), extracellular signal-regulated kinase (ERK)-1/2, eukaryotic elongation factor 2 (eEF2), mammalian target of rapamycin (mTOR), initiation factor 4E-binding protein 1 (4E-BP-1), and p70 ribosomal protein S6 kinase (p70S6K) in hippocampus of CMS-induced mice. Additionally, licorisoflavan A could reverse the decreases in synaptic proteins post-synaptic density protein 95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) caused by CMS, and its antidepressant-like effect was blocked by the AMPA receptor antagonist NBQX. These findings served as preclinical evidence that licorisoflavan A exerted potent antidepressant-like effects involving BDNF-TrkB pathway and AMPA receptors. Licorisoflavan A might be used as a potential medicine against depression-like disorder.

Objective: The objective of the work was to optimize the extraction conditions of Caesalpinia sappan L. heartwood in order to maximize the brazilin content and antibacterial activity of the extract., Methods: Two independent factors were studied: extraction temperature (45-95 °C) and extraction time (30-60 min). In addition, five dependent factors were monitored, including extraction yield, brazilin content, and clear zones against Staphylococcus aureus TISTR 1466, Staphylococcus epidermidis TISTR 518 and Propionibacterium acnes DMST 14961. The brazilin content was quantified by high-performance liquid chromatography and antibacterial activity was determined by disk diffusion assay., Results: The high temperature provided high total extract yield as well as brazilin content, while extraction time had little effect on yield or brazilin content. Extraction time had a positive effect, while extraction temperature had little effect on clear zone against S. aureus. The largest clear zone against S. epidermidis was achieved at low extraction temperature and long extraction time. Conversely, short extraction time and high extraction temperature provided the largest clear zone against P. acnes. The optimal conditions providing the highest brazilin content was an extraction temperature and extraction time of 95 °C and 30 min, respectively. The same optimal conditions also provided the simultaneous greatest antibacterial activity against the three bacteria. Modeled optimal conditions were validated be conducting extraction using these values. Yield and antibacterial activity of the resulting extract demonstrated that the model had a low percentage error., Conclusion: The optimal condition will be used as a standard condition for extraction of C. sappan heartwood to maximize brazilin content and antibacterial activity., (Copyright © 2019 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Two azaphilone pigments (1 and 2), two dihydrobenzofurans (3 and 4), two macrodiolides (5 and 6), and a dimeric alkyl aromatic constituent (7) were isolated from the goose dung-derived fungus Coniella fragariae. Compounds 1-3 proved to be new natural products. Coniellins H and I (1 and 2) feature a tetracyclic core and an aldehyde group at C-5, which is unusual for azaphilone derivatives. The X-ray structure of pyrenophorin (5) is reported for the first time. Pyrenophorin (5) showed strong cytotoxicity against several cancer cell lines with IC 50 values ranging from 0.07 to 7.8 μM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The fungus Penicillium canescens was isolated from the inner tissue of the Mediterranian sponge Agelas oroides . Fermentation of the fungus on solid rice medium yielded one new chlorinated diphenyl ether ( 1 ) and 13 known compounds ( 2 - 14 ). Addition of 5% NaBr to the rice medium increased the amounts of 4 - 6 , while lowering the amounts of 8 , 12 , and 14 . Furthermore, it induced the accumulation of 17 and two new brominated azaphilones, bromophilones A and B ( 15 and 16 ). Compounds 15 and 16 are the first example of azaphilones with the connection of a benzene moiety and the pyranoquinone core through a methylene group. The structures of the new compounds were elucidated based on the 1D and 2D NMR spectra as well as on HRESIMS data. The absolute configuration of the condensed bicyclic moiety of 15 and 16 was determined by sTDA ECD calculations. Compound 16 exhibited moderate cytotoxicity against the mouse lymphoma cell line L5178Y (IC 50 8.9 μM), as well as against the human ovarian cancer cell line A2780 (IC 50 2.7 μM), whereas the stereoisomer 15 was considerably less active.

Three new benzaldehyde derivatives, sporulosaldeins A - C (1: -3: ), and 3 new benzopyran derivatives, sporulosaldeins D - F (4: -6: ), were discovered from an endophytic fungus, Paraphaeosphaeria sp. F03, which was isolated from Paepalanthus planifolius leaves. Compounds 1: -6: were elucidated by 1- and 2-dimensional nuclear magnetic resonance experiments and high-resolution mass spectrometry analysis. The absolute configuration of compound 5: was determined through the comparison of experimental and calculated electronic circular dichroism data. Compounds 1: -6: were found to exhibit antifungal activity with minimum inhibitory concentration (MIC) values of 7.8 - 250 µg/mL and racemic mixture of compound 6: exhibited weak cytotoxicity against MCF-7 and LM3 with IC 50 values of 34.4 and 39.2 µM, respectively., Competing Interests: The authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Aegle marmelos is a plant species native to India. Commercially available food products such as jam, jelly, candy, squash etc. are prepared from ripe fruit pulp of A. marmelos . Ripe fruit processing accounts for 60% of whole fruit mass while 40% remains unutilized and generates waste (hard shell, pomace, fiber and seeds) on a massive scale which do not have high value applications. A new flavone 3,5,7-trihydroxy-2-(4'-hydroxy-3'-isopentyloxyphenyl-4 H -chromen-4-one ( 5 ) in addition to the known compounds 1-4 , has been isolated from seeds of A. marmelos . Also, compound 7-(3'-methylbut-2'-enyloxy)-2 H -chromen-2-one ( 2) has been isolated for the first time from A. marmelos . The structure of compounds 1-5 was determined by spectral analysis (UV, IR, NMR, etc.). Additionally, the non-edible oil obtained from seeds was investigated for waste to wealth recovery of 6- O -ascorbyl esters in high regioselectivity via one step semi-synthetic approach in the presence of ascorbic acid and H 2 SO 4 at ambient temperature.

Six hundred forty natural compounds were tested for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Of those, sargachromanol I (SCI) and G (SCG) isolated from the brown alga Sargassum siliquastrum, dihydroberberine (DB) isolated from Coptis chinensis, and macelignan (ML) isolated from Myristica fragrans, potently and effectively inhibited AChE with IC 50 values of 0.79, 1.81, 1.18, and 4.16 µM, respectively. SCI, DB, and ML reversibly inhibited AChE and showed mixed, competitive, and noncompetitive inhibition, respectively, with K i values of 0.63, 0.77, and 4.46 µM, respectively. Broussonin A most potently inhibited BChE (IC 50  = 4.16 µM), followed by ML, SCG, and SCI (9.69, 10.79, and 13.69 µM, respectively). In dual-targeting experiments, ML effectively inhibited monoamine oxidase B with the greatest potency (IC 50  = 7.42 µM). Molecular docking simulation suggested the binding affinity of SCI (-8.6 kcal/mol) with AChE was greater than those of SCG (-7.9 kcal/mol) and DB (-8.2 kcal/mol). Docking simulation indicated SCI interacts with AChE at Trp81, and that SCG interacts at Ser119. No hydrogen bond was predicted for the interaction between AChE and DB. This study suggests SCI, SCG, DB, and ML be viewed as new reversible AChE inhibitors and useful lead compounds for the development for the treatment of Alzheimer's disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Natural 2H-chromenes were isolated from the crude extract of Piper aduncum (Piperaceae) and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) applying collision-induced dissociation. Density functional theory (DFT) calculations were used to explain the preferred protonation sites of the 2H-chromenes based on thermochemical parameters, including atomic charges, proton affinity, and gas-phase basicity. After identifying the nucleophilic sites, the pathways were proposed to justify the formation of the diagnostic ions under ESI-MS/MS conditions. The calculated relative energy for each pathway was in good agreement with the energy-resolved plot obtained from ESI-MS/MS data. Moreover, the 2H-chromene underwent proton attachment on the prenyl moiety via a six-membered transition state. This behavior resulted in the formation of a diagnostic ion due to 2-methylpropene loss. These studies provide novel insights into gas-phase dissociation for natural benzopyran compounds, indicating how reactivity is correlated to the intrinsic acid-base equilibrium and structural aspects, including the substitution pattern on the aromatic moiety. Therefore, these results can be applied in the identification of benzopyran derivatives in a variety of biological samples., (© 2019 John Wiley & Sons, Ltd.)

Ionic liquids (ILs) have gained much attention as alternative solvents to volatile organic solvents due to their attractive properties. This study aimed to develop an efficient method for the selective separation of decursin (D) and decursinol angelate (DA) from Angelica gigas Nakai ( A. gigas ) using ILs and crystallization. The IL 1-butyl-3-methylimidazolium tetrafluoroborate ((BMIm)BF 4 ) was the most efficient at extracting D and DA. Parameters including solid-to-liquid ratio, time, and temperature were optimized by response surface methodology (RSM). Under optimal extraction conditions (1 g/6.5 mL solid-to-liquid ratio, 60 °C temperature, and 120 min time), the extraction yields of D and DA were 43.32 mg/g (97.06%) and 17.87 mg/g (97.12%), respectively. Moreover, drowning out crystallization using deionized water (DW) as an anti-solvent offered an excellent ability to recover D and DA from the A. gigas -(BMIm)BF 4 extraction solution. The rates of recovery and the total purity of D and DA were found to be greater than 97%. Therefore, a rapid and efficient method of combining ILs with crystallization was effectively achieved for the selective separation of D and DA. This approach is assumed to be beneficial in the pharmaceutical industry for the effective obtention of D- and DA-enriched products.

The methanol extract of Abronia nana suspension cultures were subjected to column chromatography to identify potential inhibitors of β-secretase, which is a major factor in Alzheimer's disease development. Two new C -methylisoflavones boeravinone T ( 1 ) and U ( 4 ) were isolated with three knowns boeravinone B ( 2 ), J ( 3 ) and X ( 5 ). The half-maximal inhibitory concentration (IC 50 ) values of compounds 1 - 5 were 18.29, 8.57, 7.87, 12.02 and 5.30 μM, respectively. The most potent 5 , non-competitively inhibited β-secretase [inhibition constant (K i ) = 3.79 μM]. Compounds 1 - 5 did not inhibit other proteases such as chymotrypsin, trypsin and elastase at concentrations up to 1 mM, indicating that they were relatively specific inhibitors of β-secretase. A free hydroxyl group at C-3 position of the C -methylisoflavone skeleton appeared to be responsible for the stronger inhibitory activity against β-secretase.

Background: Glycyrrhiza (licorice) species are rich in bioactive secondary metabolites and their roots are used traditionally for the treatment of several diseases. In recent years, secondary metabolites of licorice are gaining popularity, especially due to their significant cytotoxic and antitumor effects. However, Glycyrrhiza iconica, an endemic species to Turkey, was not investigated in terms of its anticancer secondary metabolites previously., Purpose: This study aimed to isolate the cytotoxic compounds from G. iconica through bioactivity-guided fractionation and to elucidate mechanisms of action of the most potent compounds., Methods: Total MeOH extract and CHCl 3 , EtOAc, n-buOH and rH 2 O subextracts were prepared from G. iconica roots. Sequential chromatographic techniques were conducted for the isolation studies. The chemical structures of the isolates were established based on NMR and HR-MS analysis. Sulforhodamine B assay was used to evaluate the cytotoxic activity of extracts, main fractions as well as isolates against hepatocellular (Huh7), breast (MCF7) and colorectal (HCT116) cancer cell lines. The mechanisms underlying the cytotoxicity of the most active compounds in Huh7 cells were elucidated by using Hoechst staining, Fluorescence-activated cell sorting and Western blot assays., Results: A new dihydrochalcone, iconichalcone (1) along with 15 known phenolic compounds were isolated from the active CHCl 3 , EtOAc and n-buOH subextracts. Compounds 2-5, 7-16 were found to be responsible for the in vitro cytotoxic activity of G. iconica against all tested cancer cell lines with IC 50 values ranging from 2.4 to 33 µM. Amongst these compounds, licoricidin (10), dehydroglyasperin C (12), iconisoflaven (13) and 1-methoxyficifolinol (15) were found to be the most active compounds according to SRB and real time bioactivity assays and submitted to further mechanistic investigations in Huh7 cells. Compounds 10, 12, 13 and 15 caused accumulation of cells in different phases of cell cycle. Moreover, 10, 12, 13 and 15 induced apoptosis through caspase activation. Besides, 12 showed activation of p53 expression and thus G 2 /M arrest as well as a condensed nuclei, established very promising results., Conclusion: The results demonstrated that the aforementioned compounds, particularly 12 could be potential lead molecules for anticancer drug development that deserve further in vivo and clinical investigations., (Copyright © 2019 Elsevier GmbH. All rights reserved.)