Latest ArticlesIt aimed to research the chemical constituents of Solidago canadensis Lour. A new sucrose derivative was isolated from the the methanol extract of Solidago canadensis Lour. with the technologies of silica gel, microporous resin, Rp-18, and Sephadex LH-20 column chromatography. It was identified as 2, 4, 6, 1′, 3′, 6′-O-hexaisovaleryl sucrose by 1D NMR, 2D NMR, high-resolution mass spectrometry, and acid hydrolysis method. Its mass spectrometry fragmentation behaviors were analyzed using high-resolution mass spectrometry and found that compound 1 was easy to break the glycosidic bond to produce the fragment at m/z 415. The ion at m/z 415 continued to eliminate the isovaleryl group as neutral or non-neutral form to generate a series of daughter ions. Compound 1 could inhibit NO production on LPS-induced neuroinflammatory responses in BV2 microglial cells at the concentrations of 5, 10, and 20 μmol·L-1 to exhibit neuroprotective effect. Its half maximal inhibition rate of NO was measured to be 13.96 ± 0.78 μmol·L-1.
Based on the genome and transcriptome data of Salvia miltiorrhiza, a cytochrome P450 gene annotated as SmCYP72A395, which was highly expressed in the periderm of S. miltiorrhiza root was cloned. The total length of the cDNA sequence of SmCYP72A395 was 1 578 base pairs, encoding 525 amino acids. The predicted molecular weight of the protein was 59.9 kDa. The physicochemical properties, subcellular localization, protein structure, and conserved domains were predicted by online bioinformatic tools. The theoretical isoelectric point of SmCYP72A395 was 8.68, with a transmembrane domain in the protein. This gene was highly expressed in the flower, leaf, and root periderm tissues of S. miltiorrhiza. To further identify the biological function of SmCYP72A395, the transgenic hairy roots with SmCYP72A395 overexpressed (SmCYP72A395-OE) and RNA interference (SmCYP72A395-RNAi) were constructed, and the content of tanshinone compounds was detected by UPLC between these transgenic lines and control line (haboring the vector plasmid in the transgenic line). Compared with the control line of transgenic hairy roots, the content of dihydrotanshinone Ⅰ, cryptotanshinone, tanshinone Ⅰ and tanshinone ⅡA in the SmCYP72A395-OE lines was significantly less than those in the control line. On the contrary, the content of dihydrotanshinone Ⅰ, cryptotanshinone, and tanshinone Ⅰ was higher in the SmCYP72A395-RNAi lines than those in the control line. These results demonstrated that SmCYP72A395 played a negative role in the regulation of tanshinone accumulation in S. miltiorrhiza. This study lays the foundation for further elucidating the biosynthesis and regulatory pathways of tanshinone compounds in S. miltiorrhiza.
Human cytomegalovirus (HCMV) infection poses significant morbidity and/or mortality risks for individuals with compromised immune systems, rendering it one of the most prevalent congenital infections worldwide. The pursuit of HCMV vaccines has spanned over five decades, with clinical trials primarily focusing on various vaccine candidates, including live attenuated vaccines, viral vectored vaccines, subunit vaccines, peptide vaccines, DNA vaccines, RNA vaccines, and viral-like particle vaccines, usually accompanied by the use of adjuvants. Although the development of vaccines against HCMV is being actively promoted, there are still numerous obstacles and challenges persisting in the research process, due to unique pathogenic characteristics and infection mechanisms of HCMV. Based on the summarized research progress, this article analyzes and discusses the faced challenges and potential approaches to provide valuable insights and guidance for the exploration and development of new vaccines candidates, and ultimately achieve prevention and control of HCMV infection.
Gliomas are the most common primary tumors in the central nervous system. However, the efficacy of first-line treatments for glioma is hindered by the blood brain barrier (BBB), making it difficult to reach an effective dose at the tumor site. The volatile oil from traditional Chinese medicine have the advantages of high fat solubility and ability to penetrate the blood brain barrier, has demonstrated promising inhibitory effects on glioma. The volatile oil components of traditional Chinese medicine can improve the anti-glioma efficacy by promoting the entry of chemotherapeutic drugs into the brain, inhibiting the exocytosis of drugs within the brain and synergizing with chemical drug therapy. However, the stability of volatile oil is poor, nano-formulations including liposomes, nanoparticles, and self-assembled prodrug delivery systems, can improve their stability and exert the therapeutic efficacy. As an effective drug for the treatment of glioma, volatile oil from traditional Chinese medicine shows good prospects for application. This review summarizes the mechanisms of action of volatile oil from traditional Chinese medicine and their main components against glioma, and the research progress of volatile oil combined with chemotherapeutic drugs or designed as nano-drug delivery systems for glioma therapy, with a view to providing reference for the application of volatile oil from traditional Chinese medicine in the treatment of glioma.
Jinqi Jiangtang Capsule (JQJTC) is one of the commonly used dosage forms of Jinqi Jiangtang formula, derived from the classic Qianjin Huanglian Pill, which is widely used in the treatment of diabetes mellitus. However, its pharmacokinetics is not still unclear. In this study, a stable and reliable method for the quantitative analysis of multiple components from JQJTC in mouse plasma and liver was established by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Then, the concentration changes of 16 components from JQJTC in plasma and liver of type 2 diabetic mice were determined and the kinetics was analyzed. The results demonstrated that the established UPLC-MS/MS method met the requirements for the determination of biological samples. The alkaloids, organic acids, flavonoids, and saponins were absorbed into mouse blood after JQJTC was administered by gavage, and there were significant differences in the rates of absorption, transport into liver and elimination and exposure levels of 16 components in plasma and liver. And the exposure of alkaloids, calycosin-7-glucoside and its glycosides, formononetin, and cycloastragenol in the liver were significantly higher than that in the plasma. The results provided a basis for further research on the pharmacodynamic substances of JQJTC. The use of all experimental animals has been approved by the Ethics Committee of Laboratory Animal of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM2401310001).
Through several chromatographic methods, such as silica gel, Sephadex LH-20 and high performance liquid chromatography (HPLC), six iridoids were isolated from the roots and rhizomes of Patrinia scabiosaefolia. By means of nuclear magnetic resonance (NMR) spectroscopy, 13C NMR calculation and mass spectrometry (MS), their structures were identified as patrinin A (1), patrinin B (2), loganin aglycone (3), isovillosol (4), 1, 3-dimethoxy-4, 7-dimethyl-octahyhro-cyclopenta[c]pyran-6, 7-diol (5) and viburnshosin A (6). Among them, compounds 1 and 2 were new compounds. Furthermore, the anti-influenza virus and anti-inflammatory activities of the isolates were evaluated.
This study investigates the anti-fatigue effects and mechanisms of Lycium barbarum and Ginseng combination using network pharmacology and in vivo validation. The effective components and their action targets of Lycium barbarum and Ginseng were explored through TCMSP, ETCM and other databases combined with literature. The fatigue targets were obtained through OMIM and Gene Cards databases. The intersection targets of drug targets and disease targets were screened out and imported into String database and Cytoscape 3.10.0 to construct PPI network. GO and KEGG enrichment analysis of the core targets were performed by David database. A mouse exercise-induced fatigue model was established to evaluate the anti-fatigue effects and mechanisms of the Lycium barbarum-Ginseng combination. The results showed that 55 active ingredients of Lycium barbarum and Ginseng were obtained, corresponding to 573 targets. The number of fatigue targets was 1 137, 115 total targets and 26 core targets were screened. KEGG enrichment pathways mainly included PI3K-AKT, HIF-1α, AGE-RAGE and other signaling pathways. All animal experiments were approved by the Experimental Animal Ethics Committee of Nanjing University of Chinese Medicine (approval number: 202308A018). The results showed that the low, middle and high dose groups of Lycium barbarum and Ginseng (1∶1) could prolong the exhaustive swimming time of mice, and the middle dose group had a more significant effect than Ginseng group and Lycium barbarum group. The middle and high dose groups of Lycium barbarum combined with Ginseng significantly reduced blood urea nitrogen (BUN) in mice. Compared with Ginseng group and Lycium barbarum group, the high dose group had a more significant effect. Lactic acid (LD) levels were significantly decreased in Ginseng group, Lycium barbarum group and combination group. Compared with the Ginseng group, the levels of liver glycogen (Lgly) and muscle glycogen (Mgly) were significantly increased in the middle dose group of Lycium barbarum combined with Ginseng. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were significantly decreased in Ginseng group and Lycium barbarum combined with Ginseng high dose group. The content of glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) in the high dose group of Lycium barbarum combined with Ginseng can be significantly decreased. The results of Western blot showed that the low dose group of Lycium barbarum combined with Ginseng could significantly up-regulate the expression of P-PI3K and AKT proteins in the muscle tissue of fatigue mice, and the middle dose group could significantly down-regulate the expression of P-AKT and HIF-1α proteins. Compared with Ginseng group and Lycium barbarum group, the expression of PI3K protein in the high dose group was significantly increased. The expression of AKT protein in the low-dose group was significantly increased. In conclusion, Lycium barbarum combined with Ginseng has more positive effects on improving exercise endurance, reducing the accumulation of metabolites and improving glycogen storage levels in mice than Ginseng group and Lycium barbarum group, and its mechanism may be the regulation of AKT, PI3K, HIF-1α and other core targets and PI3K/AKT/HIF-1α signaling pathway to exert anti-fatigue effect.
A new benzoic acid derivative, spinulacid (1), together with six known compounds ascomindone A (2), ascomindone C (3), monomethylsulochrin (4), barceloneic acid A (5), flufuran (6), and 5-hydroxymethyl-furaldehyde (7) were obtained from the rice fermentation extract of an endophytic fungus Penicillium spinulosum isolated from Emmenopterys henryi Oliv. by various chromatographic techniques. Their structures were elucidated by the analysis of NMR data, MS and comparison with literature. The biological activity results showed that compounds 1, 2, 5, and 6 exhibited significant proangiogenic activity in transgenic zebrafish at concentrations of 20 and 40 μmol·L-1 (the animal experiment was approved by the Animal Ethical and Welfare Committee of Biology Institute, Shandong Academy of Science, the approval number is SWS20240611). Compounds 1 and 4 displayed moderate or strong antifungal activity against phytopathogen Fusarium graminearum with minimum inhibitory concentration (MIC) values of 12.5, and 6.25 μg·mL-1, respectively. Besides, compound 4 was also found to show obvious antibacterial activity against Staphylococcus aureus and Erwinia carotovora with MIC values of 6.25 and 12.5 μg·mL-1, respectively.
JAZ proteins, as inhibitors in the jasmonic acid (JA) signaling pathway, play a crucial role in regulating plant growth and development, as well as the biosynthesis of secondary metabolites in plants. To explore the functions of the JAZ gene family in Tripterygium wilfordii, our study systematically identified the members of the JAZ gene family in T. wilfordii. We analyzed their physicochemical properties, chromosome localization, phylogenetic tree, and protein conserved motifs. Additionally, we investigated the expression patterns of TwJAZs in different tissues, constructed a gene regulatory network map, and ultimately cloned the full-length sequences of 18 JAZ genes. The results showed that the 18 TwJAZs were unevenly distributed across 12 chromosomes, encoding amino acid numbers ranging from 122 to 525, with molecular weights of 13.87 to 54.73 kDa, and isoelectric points ranging from 6.83 to 10.27. Subcellular localization prediction indicated that 13 TwJAZs were localized in the nucleus, while 5 TwJAZs were located in the cytoplasm and chloroplasts. The phylogenetic tree analysis revealed that the JAZ family proteins of T. wilfordii could be divided into five subfamilies, with members of the same subfamily sharing similar conserved motifs. Expression pattern analysis demonstrated that TwJAZs were predominantly expressed in flowers, leaves, and peeled stems, with most TwJAZs showing the highest expression levels after 4 hours of methyl jasmonate (MeJA) induction. The transcription factor regulatory network shows that TwJAZs are strongly correlated with transcription factor families such as AP2/ERF-ERF, NAC, and bHLH. This study comprehensively identified all the JAZ gene family sequences in T. wilfordii, initially clarifying the structural and functional characteristics of the TwJAZs, and laying an important foundation for further research on the functions and regulatory mechanisms of TwJAZs.
In 2024, drug discovery continues to develop on the basis of the achievement before. The number of approved first-in-class (FIC) drugs reach a higher level. The Center for Drug Evaluation and Research of U.S. Food and Drug Administration has totally approved 50 novel drugs, including 30 small molecule drugs and 20 macromolecule drugs. Comparing to the number of approved drugs in 2023, the total in 2024 falls slightly. But the proportion of FIC drugs increase obviously. There are 24 FIC drugs (48%) approved in 2024, which include 13 FIC small molecule drugs and 11 FIC macromolecule drugs and whose indications mainly focus on tumor, and endocrine and metabolic disease. Among 24 FIC drugs, many drugs have breakthrough clinical value, such as the first combination of muscarinic acetylcholine receptor M1/M4 agonist and peripheral muscarinic acetylcholine receptor antagonist, xanomeline and trospium chloride, the first thyroid hormone receptor beta agonist, resmetirom, the first dual antagonist of endothelin receptor type A and B to treat hypertension, aprocitentan. The huge value of FIC drugs in clinical therapy, academic research and commerce, is attracting wide attention from the patients, researchers and enterprises. This review will analyze the research background, development process and therapeutic application of three first-in-class small molecule drugs in this year from a medicinal chemistry perspective, expecting to provide more research directions and methods for the development and research of FIC drugs.