A novel nonreversible heat-induced low-molecular-weight gel based on naturally-occurring self-assembled fupenzic acid for tumor therapy.

Herein, a nonreversible heat-induced supramolecular gel based on natural products was reported for the first time. This natural triterpenoid, fupenzic acid (FA), isolated from the roots of Rosa laevigata, was discovered to be capable of forming supramolecular gel spontaneously in 50 % ethanol-water solution induced by heating. Distinguished from the common thermosensitive gels, the FA-gel showed a distinctive nonreversible phase transition from the liquid to gel state upon heating. In this work, the entire gelation process of FA-gel induced by heating was recorded digitally by microrheology monitor. And a unique heat-induced gelation mechanism based on self-assembled FA has been proposed by using various experimental methods and molecular dynamics (MD) simulation. Its excellent injectability and stability were also demonstrated. Furthermore, the FA-gel had been evaluated to exhibit better anti-tumor activity and higher biosafety comparing with its equivalent free-drug, which opened up a new possibility to reinforce antitumor efficacy by using natural product gelator originated from traditional Chinese medicine (TCM) without any complicated chemical modifications.

The Biosynthesis Related Enzyme, Structure Diversity and Bioactivity Abundance of Indole-Diterpenes: A Review.

Indole diterpenes are a large class of secondary metabolites produced by fungi, possessing a cyclic diterpenoid backbone and an indole moiety. Novel structures and important biological activity have made indole diterpenes one of the focuses of synthetic chemists. Although the discovery, identification, structural diversity, biological activity and especially structure-activity relationship of indole diterpenes have been reported in some papers in recent years, they are absent of a systematic and comprehensive analysis, and there is no elucidation of enzymes related to this kind of natural product. Therefore, it is necessary to summarize the relevant reports to provide new perspectives for the following research. In this review, for the first time, the function of related synthases and the structure-activity relationship of indole diterpenes are expounded, and the recent research advances of them are emphasized.

Five New Polyoxypregnane Glycosides from the Vines of Aspidopterysobcordata and Their Antinephrolithiasis Activity.

From the dried vines of Aspidopterys obcordata Hemsl, five new polyoxypregnane glycosides, named obcordatas J-N (1-5), were obtained. Their structures were fully elucidated and characterized by HRESIMS and extensive spectroscopic data. In addition, all of the new compounds were screened for their antinephrolithiasis activity in vitro. The results showed that compounds 1-3 have prominent protective effects on calcium oxalate crystal-induced human kidney 2 (HK-2) cells, with EC50 values ranging from 6.72 to 14.00 µM, which is consistent with the application value of A. obcordata in folk medicine for kidney stones.

Abietane-Type Diterpenoids From Nepeta bracteata Benth. and Their Anti-Inflammatory Activity.

Terpenes possess a wide range of structural features and pharmaceutical activities and are promising for drug candidates. With the aim to find bioactive terpene molecules, eight new compounds were isolated from the medicinal plant Nepeta bracteata Benth., including seven new abietane-type diterpenoids (1-7), along with a new ursane-type triterpenoid (8). The structures of compounds 1-8 were elucidated through the detailed spectroscopic analyses of their 1D and 2D NMR and MS data, and the absolute configurations of compounds 1-7 were determined by comparing their experimental and calculated ECD spectra. Compound 1 was a novel degraded carbon diterpene with the disappearing of methyl signal at C-19, while compound 7 possessed a new norabietane-type diterpenoid carbon skeleton with the presence of five-membered lactone arising from ring rearrangement. The anti-inflammatory of all obtained isolates were evaluated on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the results of anti-inflammatory activity screening showed that compared with the LPS model group, all compounds were significantly down-regulation the TNF-α inflammatory factor at the specific concentration, except for compound 6.

Novel geranylhydroquinone derived meroterpenoids from the fungus Clitocybe clavipes and their cytotoxic activity.

Three novel geranylhydroquinone derived meroterpenoids, named clavilactones J and K (1-2) and clavipol C (3), were isolated from the basidiomycete Clitocybe clavipes. Their structures were unambiguously identified by extensive spectroscopic data analysis, and the electronic circular dichroism (ECD) calculation, Gauge-Including Atomic Orbitals (GIAO) NMR calculations and Mo2(OAc)4-induced electronic circular dichroism experiments were used to establish their absolute configurations. Compound 1, with two epoxy groups located at the 10-membered carbocycle, is uncommon in the reported meroterpenoids from C. clavipes. All the obtained compounds (1-3) were tested for their cytotoxic activity against human tumor cell line HGC-27 by using the MTT assay. All the compounds exhibited moderate cytotoxic activities against HGC-27 cell with IC50 values ranging from 33.5 to 56.6 µM.

Supramolecular assemblies based on natural small molecules: Union would be effective.

Natural products have been used to prevent and treat human diseases for thousands of years, especially the extensive natural small molecules (NSMs) such as terpenoids, steroids and glycosides. A quantity of studies are confined to concern about their chemical structures and pharmacological activities at the monomolecular level, whereas the spontaneous assemblies of them in liquids yielding supramolecular structures have not been clearly understood deeply. Compared to the macromolecules or synthetic small molecular compounds, NSMs have the inherent advantages of lower toxicity, better biocompatibility, biodegradability and biological activity. Self-assembly of single component and multicomponent co-assembly are unique techniques for designing supramolecular entities. Assemblies are of special significance due to their range of applications in the areas of drug delivery systems, pollutants capture, materials synthesis, etc. The assembled mechanism of supramolecular NSMs which are mainly driven by multiple non-covalent interactions are summarized. Furthermore, a new hypothesis aimed to interpret the integration effects of multi-components of traditional Chinese medicines (TCMs) inspired on the theory of supramolecular assembly is proposed. Generally, this review can enlighten us to achieve the qualitative leap for understanding natural products from monomolecule to supramolecular structures and multi-component interactions, which is valuable for the intensive research and application.

A novel DPP-4 inhibitor Gramcyclin A attenuates cognitive deficits in APP/PS1/tau triple transgenic mice via enhancing brain GLP-1-dependent glucose uptake.

Enhancing glucagon-like peptide 1 (GLP-1) signaling with a dipeptidyl peptidase IV (DPP-4) inhibitor might exert protective effects on Alzheimer's disease (AD). We found that intragastric administration of Gramcyclin A (10, 20 and 40 mg/kg), a novel DPP-4 inhibitor, for 3 months significantly reversed cognitive decline in APP/PS1/tau triple transgenic mice in a dose-dependent manner. Gramcyclin A treatment markedly reduced Aß plaques as well as the insoluble and soluble forms of Aß40 and Aß42 in the hippocampus of APP/PS1/tau mice. Treatment with Gramcyclin A remarkedly decreased the level of microglia and suppressed neuroinflammation in the hippocampus of APP/PS1/tau mice. Moreover, Gramcyclin A treatment could increase brain glucose uptake in APP/PS1/tau mice, as detected by 18-fluoro-2-deoxyglucose (18 F-FDG) micro-positron emission tomography (micro-PET) imaging. Furthermore, Gramcyclin A significantly increased expression of glucagon-like peptide-1 (GLP-1), GLP-1R, proliferator-activated receptor gamma coactivator (PGC)-1α and glucose transporter 4 (GLUT4), and inhibited insulin receptor (IRS)-1 phosphorylation and tau hyperphosphorylation in the hippocampus of APP/PS1/tau mice. Collectively, Gramcyclin A conferred protective effects against AD via enhancing brain GLP-1-dependent glucose uptake. The DPP-4 inhibitor Gramcyclin A might be a potential therapeutic drug for AD.

An integrated strategy for evaluation of sulfur-fumigated edible herb Astragali Radix based on UPLC-MS/MS platforms and pharmacological analysis.

Astragali Radix is an edible herb that has been employed in Traditional Chinese medicine (TCM) and has recently been recognized by various countries; however, it is also one of the most extensively sulfur-fumigated TCM components. This study designed a UPLC-QTOF-MS/MS-guided isolation approach to generate sulfur-containing derivatives, and a novel sulfur-containing marker, namely, astragaloside sulfate, was characterized based on 1D and 2D NMR, which were derived from the main component of Astragali Radix, namely, astragaloside. Pharmacological experiments also showed that the activity of astragaloside decreased after it was converted into sulfate. Moreover, a rapid assay for the determination of astragaloside sulfate content by UPLC-QTRAP-MS/MS was established to evaluate samples that were non-fumigated and sulfur-fumigated at different levels. The method was applied to determine the content of JGS in the different batches of commercial samples. This research reveals that the practical procedure-based typical sulfur-containing indicator can be utilized for quality assurance of sulfur-fumigated and non-fumigated Astragali Radix.

Central-collapsed structure of CoFeAl layered double hydroxides and its photocatalytic performance.

Layered double hydroxides (LDHs) has been regarded as one of the most potential photocatalysts for degradation of the pollutants, due to the tunable elements in the laminates, high surface area and exposed active sites. Developing a photocatalyst with a visible light activity and fast charge separation efficiency is a main research focus. In this work, a central-collapsed CoFeAl-LDHs was formed via the selective etching Al3+ in the laminates, which relied on the function of OH- produced by urea hydrolysis. The Central-collapsed structure of CoFeAl-LDHs exhibited enhanced adsorption activity and photocatalytic efficiency. The results show that the pseudo-second-order kinetic model and the Langmuir model are suitable for adsorption behavior. This etching cavity is beneficial to the adsorption of MB and provides a better platform for the direct interaction between MB and CoFeAl-LDHs. The morphology and photoelectrochemical properties of the central-collapsed structure of LDHs were characterized and used to explore the relationship between the etching degree and photocatalytic activity. The photocatalytic properties of all the samples under visible light irradiation were evaluated, and LDH-6 has the best photocatalytic activity. This work provides a novel approach for the fabrication of central-collapsed structure of layered double hydroxides photocatalysts to meet environmental and energy requirements.

Construction of PDDA functionalized black phosphorus nanosheets/BiOI Z-scheme photocatalyst with enhanced visible light photocatalytic activity.

The use of black phosphorus (BP) nanosheets has attracted much attention in the area of photocatalysis owing to the thickness-tunable bandgap and high carrier mobility. In order to improve the stability of BP nanosheets, poly dimethyldiallyl ammonium chloride (PDDA) is used to passivate the BP nanosheets and change its surface properties. The present study concerns the development of a facile electrostatic assembly method for the construction of a Z-scheme system consisting of PDDA-functionalized BP nanosheets and layered BiOI in order to enhance visible light adsorption and promote electron-hole separation. The morphology, structure and photoelectrochemical properties of the composites are thoroughly characterized and the photocatalytic performances of all the samples were assessed under visible light irradiation. The 5-F-BP/BiOI exhibits excellent photocatalytic activity with removal efficiencies of 97.6% and 90.0% for methylene blue (MB) and tetracycline (TC), respectively. Superoxide radicals (·O2-) were found to be the main organic decomposition products according to species trapping experiments. The photocatalyst presents favorable stability after three catalytic cycles. This study provides new insights into the design of highly efficient Z-scheme photocatalysts based on functionalized BP nanosheets in order to meet environmental demands.

Natural Nitrogenous Sesquiterpenoids and Their Bioactivity: A Review.

Nitrogenous sesquiterpenoids fromnatural sourcesare rare, so unsurprisingly neither the potentially valuable bioactivity nor thebroad structural diversity of nitrogenous sesquiterpenoids has been reviewed before. This report covers the progressduring the decade from 2010 to February 2020 on the isolation, identification, and bioactivity of 391 nitrogen-containing natural sesquiterpenes from terrestrial plant, marine organisms, and microorganisms. This complete and in-depth reviewshouldbe helpful for discovering and developing new drugs of medicinal valuerelated to natural nitrogenous sesquiterpenoids.

Eleucanainones A and B: Two Dimeric Structures from the Bulbs of Eleutherine americana with Anti-MRSA Activity.

Two naphthoquinone-derived heterodimers with unprecedented carbon skeletons, eleucanainones A (1) and B (2), were isolated from the bulbs of Eleutherine americana. Their structures were elucidated by comprehensive spectroscopic methods. The structures of 1 and 2 were determined to be the first examples of dibenzofuran- and naphthalenone-containing naphthoquinone dimers. Compound 1 exhibited significant anti-MRSA activity in vitro with minimum inhibitory concentration (MIC) values of 0.78 µg/mL by downregulation of basal expression of agrA, cidA, icaA and sarA in methicillin-resistant S. aureus (MRSA).

Study on chemical constituents of an edible mushroom Volvariella volvacea and their antitumor activity in vitro.

Phytochemical investigation of the fruiting body of Volvariella volvacea led to the isolation of a new furanone, 2(5H)-furanone-4-propionic acid named volvafuranone A (1), together with twelve known compounds (2-13). Compounds 2-7, 9-11 were isolated from this mushroom for the first time. The isolated compounds were assessed for their cytotoxicity against four human tumour lines (SGC-7901, PC-3M, MCF-7, HepG-2), and the results showed that compound 2, 3, 12, 13 have significant cytotoxicity with IC50 values of 5.90 µM (HepG-2), 20.72 µM (HepG-2), 27.98 µM (PC-3M) and 23.15 µM (PC-3M), respectively.

Bioactive triterpenoid saponins from the tubers of Hemsleya amabilis Diels.

Five new cucurbitane-type triterpenoid saponins Xuedanosides A-E (1-5) were isolated from the medicinal plant Hemsleya amabilis Diels by silica gel column, octadecylsilyl (ODS) column, and pre-HPLC techniques. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Separated compounds were evaluated for their cytotoxic activity in HeLa, HCT-8, MCF-7 and HepG2 human cancer cell lines, and compounds 1 and 2 showed significant effects against HeLa cells with IC50 values of 3.21 and 8.57 µM, respectively.

Polyhydroxy cucurbitane triterpenes from Hemsleya penxianensis tubers.

Ten new cucurbitane triterpenoids, hemsleyacins A-J (1-10), together with three known cucurbitane triterpenoids, dihydrocucurbitacin F (11), scandenogenin D (12), and jinfushanencin F (13), were separated from ethanolic tuber extracts of Hemsleya penxianensis. The absolute configurations of the new compounds were established based on NMR, HRESIMS, and CD spectra. Compounds 7 and 10-12 were evaluated in terms of their antifeedant activity against Plutella xylostella larvae. The result showed that compound 10 exhibited potent antifeedant activity against P. xylostella larvae after 48 h of treatment. Furthermore, the MTT test showed that compound 11 exhibited potent inhibition toward the UMUC-3 and T24 cell lines with IC50 values of 29.12 and 35.62 µM, respectively, compared to the positive control cisplatin IC50 values of 8.27 and 13.72 µM. Western blot analysis revealed that compound 11 treatments substantially inhibited the phosphorylation of IκBα.

New naphtoquinones derivatives from the edible bulbs of Eleutherine americana and their protective effect on the injury of human umbilical vein endothelial cells.

Seven new naphthoquinone derivatives, named eleutherins A-G (1-7), were isolated from the edible bulbs of Eleutherine americana (Hong-Cong), which belongs to the Iridaceae family. Their structures were elucidated on the basis of spectroscopic analysis including high-resolution-electron spray ionization-mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) techniques. The absolute configurations of compounds 1-4 were determined by experimental and calculated data. Additionally, a hypothetical biosynthetic pathway of 1-7 was postulated. All the isolates were evaluated for their protective effect against the injury of human umbilical vein endothelial cells (HUVECs) in vitro. Eleutherins A and B (1-2) showed a potential protective effect on microvessels.

Congmujingnosides B-G, triterpene saponins from the stem of Aralia chinensis and their protective effects against H2O2-induced myocardial cell injury.

Phytochemical investigation of the stem of Aralia chinensis yielded six new oleanane-type triterpene saponins named as congmujingnosides B-G (1-6). The new ones were elucidated on the basis of the chemical and spectroscopic analysis. Protective effects of compounds 1-6 were tested against H2O2-induced H9c2 cardiomyocyte injury, and the data showed that compounds 1 and 5 had significant cell-protective effects. No significant DPPH radical scavenging activity was observed for compounds 1-6.

[A new naphthalene derivative from bulbs of Eleutherine americana].

A new naphthalene derivative and three known compounds were isolated from the petroleum ether extract of the bulbs of Eleutherine americana by using various chromatographic techniques, such as column chromatography over silica gel and semi-preparative HPLC. Their structures were elucidated by spectroscopic date (MS, UV, IR, NMR), which were identified as eleutherol B (1), 4,8-dihydroxy-3-methoxy-1-methylanthraquinone-2-carboxylic acid methyl ester (2), 8-hydroxy-3,4-dimethoxy-1-methylanthraquinone-2-carboxylic acid methyl ester (3), and isoeleutherine (4). Compound 1 is a new compound. The diastolic blood vessels activity of compound 1 and 2 were potent, reaching 82.5% and 85.3% at the concentration of 10 µmol·L⁻¹, which were basically the same as that of the positive drug tanshinone ⅡA.

Quantitative Evaluation of Twelve Major Components of Sulfur-Fumigated Astragali Radix with Different Durations by UPLC-MS.

In this study, an improved UPLC-MS (Ultra-high performance liquid chromatography-tandem mass spectrometry) method for simultaneously quantifying twelve major components belonging to two chemical types was developed and validated, and was applied to quantitatively compare the quality of sulfur-fumigated Astragali Radix of different durations and of the fresh reference sample. The results showed that the contents of triterpenes astragaloside III and astragaloside IV decreased moderately, while the flavonoids calycosin, formononetin, and 7,2'-dihydroxy-3',4'-dimethoxyisoflavane decreased significantly. The corresponding flavonoid glycosides increased accordingly, which indicated the occurrence of chemical transformation of flavonoids and glycosides in the process of sulfur-fumigation. These transformations were further confirmed by the synthesis of flavonoid glycosides under simulated sulfur-fumigation circumstances. Furthermore, the sulfur-fumigated duration varied in proportion with the contents of compounds 7, 11, and 12. These results suggest that the established method was precise, accurate and sensitive enough for the global quality evaluation of sulfur-fumigated Astragali Radix. Further, sulfur-fumigation not only changes the proportions of bioactive components, but also causes chemical transformation in Astragali Radix.

Pyrrole Alkaloids from the Edible Mushroom Phlebopus portentosus with Their Bioactive Activities.

Seven pyrrole alkaloids, three of which are novel (phlebopines A⁻C (1⁻3)), were isolated from the fruiting bodies of the edible mushroom Phlebopus portentosus. Their structures were determined on the basis of spectroscopic data. All the isolated compounds were tested for their neuroprotective properties and acetylcholine esterase (AChE) inhibition activities. Compound 7 displayed remarkable neuroprotective effects against hydrogen peroxide (H2O2)-induced neuronal-cell damage in human neuroblastoma SH-SY5Y cells.