Caveolin-1 (CAV-1) is related to inflammation, oxidative damage, and immunity. In order to obtain a series of dibenzoylmethane halophenols with strong anti-inflammatory and antioxidant effects targeting CAV-1, twenty-nine target compounds were therefore synthesized by Baker-Ventaraman rearrangement and demethylation reaction, starting from the substituted benzoyl chloride and o-hydroxyacetophenone, and their interactions with CAV-1 were investigated by BLI technique. Their in vitro anti-inflammatory and antioxidant properties were also evaluated. The results showed that compounds A6, A17, A18, and A29 not only specifically bind to CAV-1, but also present strong anti-inflammatory and antioxidant effects. These results suggest that this class of compounds can affect the signaling pathways related to inflammation and oxidative stress by directly acting on CAV-1. In particular, these compounds exhibit the most significantly inhibitory effects on IL-1β and COX-2 release. IL-1β plays a key regulatory role in the development of arthritis. Therefore, it is worth expecting for the application of such compounds in the prevention and treatment of arthritis.

Traditional Chinese medicine has a long history, unique system and perfect technology, which has been used to prevent or treat a variety of diseases in the form of compound medicine. Recently, some of the active ingredients from Chinese medicine were found to have self-assembly properties, mainly through non-covalent interactions, including π-π stacking, electrostatic interaction, hydrogen bond and coordination interactions, etc. Carrier-free nanoparticles based on self-assembly of active ingredients from Chinese medicine could not only improve the solubility of insoluble active ingredients, but also the bioavailability. As nanocarriers, the natural active ingredients could exert synergistic therapeutic effects. The strategy of self-assembly without carrier is safer and almost non-toxic compared to the commonly used nanocarriers. In addition, some ingredients from Chinese medicine could coordinate with metal ions to form stable nanoparticles, which could be applied to photothermal therapy. In this paper, we summarized and analyzed the recent achievements of carrier-free nanoparticles based on self-assembly of active ingredients from Chinese medicine, and briefly outlined the future development of this kind of nanomedicine.

Drug combination can effectively enhance the anti-tumor effect, reduce the drug dose, and improve medication safety. The use of nano-carrier for drug co-delivery can effectively avoid the differences in drug delivery behavior in vivo. Triptolide and celastrol are the main anti-tumor active components of Tripterygium wilfordii Hook f. Modern studies have shown that the combination of triptolide and celastrol can significantly enhance the antitumor effect, but they are limited by poor water solubility and low tumor tissue delivery rate. In this study, a biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol was prepared to characterize the morphology, particle size, potential, drug release, serum stability, and other properties. The immunogenicity, uptake behavior, and anti-cell proliferation ability of the biomimetic liposome was compared. All the animal experiments were carried out in accordance with protocol evaluated and approved by the Ethics Committee of Chengdu University of Traditional Chinese Medicine (Chengdu, China). The results showed that the biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol (C+T/RBCm@Lip) in this study had an average particle size of 119.12 ± 2.78 nm and a spherical "core-shell" structure. The zeta potential value was -16.9 ± 1.2 mV, and the drug release behavior in vitro was slow. In addition, the process of coating the cell membrane maintained the characteristics of erythrocyte membrane protein, had good stability in serum, and could effectively avoid the recognition and clearance of macrophages, without causing immunogenicity in vivo. The uptake effect of co-loaded biomimetic liposomes on HepG2 hepatocellular carcinoma cells was enhanced compared with that of uncoated cell membrane liposomes, and the inhibitory effect on proliferation of HepG2 cells was enhanced. In conclusion, the biomimetic liposomes coated with erythrocyte membrane prepared in this study is beneficial to the anti-tumor delivery of triptolide and celastrol, and could enhance the inhibitory effect on the growth of HepG2 liver cancer cells, providing a new idea for the anti-tumor application of Tripterygium wilfordii Hook f.

Febuxostat, as a xanthine oxidase inhibitor, is a classic anti-gout drug with significant therapeutic effects and good tolerability. The structures of febuxostat and its derivatives can be divided into two parts: a substituted phenyl ring and a five-membered or six-membered heterocyclic ring with a carboxyl substitution. This paper reviewed the research progress of febuxostat derivatives in recent ten years and classified the structure-activity relationships of various febuxostat derivatives. Exploring the action mechanisms and structure-activity relationships of xanthine oxidase inhibitors might be significant for the rational design and development of new anti-gout chemical entities.

Tripterygium wilfordii Hook. f. is a valuable medicinal plant, with anti-tumor, anti-inflammatory, immunosuppressive and other pharmacological activities. Triterpenoids are one of the main active components that exert pharmacological effects. However, the content of triterpenoids dominated by triptolide is very low in Tripterygium wilfordii, and the analysis of the biosynthetic pathway of triterpenoids in Tripterygium wilfordii provides an effective new idea for obtaining these compounds. 2, 3-Oxidosqualene cyclases (OSCs) are the key enzyme that catalyzes the formation of triterpene skeleton diversity. Based on the genome and transcriptome data of Tripterygium wilfordii, 16 OSC genes were identified and analyzed. Phylogenetic analysis showed that 16 TwOSC proteins could be mainly classified as four groups. They are β-amyrin synthase group, friedelin synthase group, multifunctional amyrin synthase and cycloartenol synthase group. TwOSC6 was successfully cloned. Functional characterization analysis revealed that TwOSC6 can catalyze the formation of α-amyrin and β-amyrin. This indicates that TwOSC6 is a multifunctional amyrin synthase. This provides new gene resources for the diversity of Tripterygium wilfordii triterpenoids, as well as new gene elements for biosynthesis triterpenoids.

Dendrobium officinale Kimura et Migo is a rare Chinese herbal medicine, while Dendrobium crepidatum Lindl is a local medicine in Yunnan, both of which have the function of nourishing yin and stomach. To reveal the differences in chemical composition between the two species, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to analyze the chemical composition of stems and leaves of D. officinale and D. crepidatum. Principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA) were used to determine the differences in metabolites between species and parts of Dendrobium. Fifty-eight chemical compounds were identified in the two species. Analysis indicated that the side ring of alkaloids connected with nitrogen was readily cleaved during analysis. The results of PCA analysis showed that the stems and leaves of D. officinale and D. crepidatum could be easily differentiated, and the chemical constituents of D. officinale and D. crepidatum were significantly different. OPLS-DA analysis showed that there were 16 metabolite differences between the stems and 22 differences in metabolites between the leaves of D. officinale and D. crepidatum. The main metabolite differences in components between the two Dendrobium species were dendrocrepidine B, dendrocrepidine C and dendrocrepine. There were 14 differences in metabolites between the stems and leaves of D. crepidatum. In conclusion, the chemical compositions of D. officinale and D. crepidatum are quite different; the small molecular compounds of D. officinale are mainly terpenoids and flavonoids, and the content of alkaloids is low. There is no significant difference between stem and leaf. In contrast, D. crepidatum is mainly composed of alkaloids and terpenoids, with crepidamine and dendrocrepine as its unique components, and there are great differences in the components between stems and leaves. This study provides a theoretical basis for the development and utilization of Dendrobium resources.

This research aimed at the key issue that chemical drugs and Chinese medicine hydrophilic small molecule anti-tumor drugs were difficult to break through the dense interstitial permeability barrier of pancreatic cancer to achieve the key problem of drug efficacy in the deep part of tumor tissue. To solve this problem, the lipophilic molecule squalene (SQ) and the hydrophilic anti-tumor drug chidamide (CHI) were linked by a trypsin responsive bond to form a prodrug (SQ-CHI) and a folic acid modified prodrug self-assembled nanoparticles (FA-SQ-CHI NPs) were further developed. The feature of prodrug molecules and nanoparticles were characterized. The in vitro release characteristics and cytotoxicity of blank vector were investigated. The efficacy and permeability of the prodrug nanoparticles in the PSN-1 monolayer cell and PSN-1/HSPC co-cultured tumor spheroids model was evaluated. The results showed that SQ-CHI prodrug molecules and FA-SQ-CHI NPs were successfully developed. The nanoparticles were regular spherical, well-dispersed, with a particle size of (173.3 ± 1.5) nm, a drug load of (59.02 ± 0.8) % and showed trypsin responsive release ability. The prodrug nanoparticles can significantly enhance the penetration and anti-proliferation effects of CHI in the PSN-1/HSPC tumor spheroids. In conclusion, the construction of folic acid-modified SQ-CHI prodrug self-assembled nanoparticles can significantly enhance the penetration of CHI in the pancreatic cancer microenvironment in vitro. This research would provide a new idea for the construction of targeted drug delivery system for chemical drugs and Chinese medicine hydrophilic small molecule drugs in the application of anti-pancreatic cancer.

Poly (β-amino ester)s (PβAEs) contain tertiary amine backbones and biodegradable ester bonds, making them highly biocompatible and pH-responsive. Meanwhile, originated from combinatorial libraries, PβAEs are simple to synthesize, easy to obtain raw materials and can be easily adapted to meet the different performance needs of gene carriers by adjusting the monomer type, monomer ratio and reaction time. Therefore, PβAEs are promising material for non-viral gene carriers. This paper provides a comprehensive overview of the properties and synthesis of PβAEs gene carriers and summarizes the progress of research on the gene delivery of each type of PβAEs.

NAC transcription factor genes play an important role in regulating plant adversity stress tolerance and secondary metabolism. To explore DaNAC transcription factor participation in the synthesis of asperosaponin Ⅵ in Dipsacus asper, we analyzed the expression of DaNAC genes based on full-length transcriptome data from different tissues (root, stem, leaf, flower, seed) to provide a theoretical foundation for regulating the metabolism of D. asper. RNA-seq data was used to identify open reading frames. Bioinformatic methods were used to identify the conserved domain motifs and construct an evolutionary tree. qRT-PCR was carried out to analyze tissue-specific and adversity-stressed expression. Twenty-nine DaNAC sequences were identified, all of which contain the conserved NAM domain and conserved motif 1 and motif 2 at the N terminal. Five DaNAC genes are closely related to the NAC genes in Arabidopsis thaliana and rice that are involved in adversity stress and are clustered in the Group Ⅰ subfamily. qRT-PCR revealed that DaNAC genes are differentially expressed between tissues. The expression levels were highest in leaves, followed by roots, stems and petioles, and the lowest in flowers and seeds. Compared with normal growth conditions, the expression of four NAC genes was up-regulated by treatment with low temperature (15 ℃). The expression of three genes (34564NAC2, 33883NAC48, 6727NAC14) was up-regulated and one gene (34480NAC22) was down-regulated by 150 μmol·L^-1 MeJA. The results illustrate that the expression of NAC genes is induced by adversity stress, which provides a foundation for further study on the role of NAC family members in adversity stress in D. asper.

We identified and analyzed the components and chemical constituents of hawthorn leaves of Crataegus pinnatifida Bge. (wild) and C. pinnatifida Bge. var major N. E. Br (cultivated) by using ultra high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS^E) combined with UNIFI data analysis platform and multivariate statistics. Fifty-eight chemical compounds were identified, including organic acids, flavonoids, triterpenoic acids, monoterpenes and sesquiterpenoids; among them, terpenoid content was the most abundant. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to identify the differential components of hawthorn leaves from two sources. The results show that there are differences in the chemical compositions of the two sources, including 24 flavonoids and terpenoids (including monoterpenoids, sesquiterpenoids and triterpenoid acids). The types of flavonoids (such as rutin, vitexin-2''-O-rhamnoside, isovitexin-2''-O-rhamnoside, hyperoside, quercetin-3-O-β-D-glucoside) and terpenoids (crataegolic acid, corosolic acid and ursolic acid) in C. pinnatifida were more varied than those found in C. pinnatifida Bge. var major N. E. Br, and their contents were relatively higher. This study provides a comprehensively analysis of the different chemical components of hawthorn leaves from two sources listed in the Chinese Pharmacopoeia, and provides a basis for the selection of raw materials and the potential development and utilization of hawthorn leaves.