Latest ArticlesIn this study, licorice-derived vesicle-like particles (LVLPs) were used as carriers, and licochalcone-A (LCA), a signature active ingredient of the same source, was used as a model drug to construct a drug-loaded LVLP@LCA nanodelivery system, and to characterize and evaluate its in vitro properties and anti-inflammatory activity. Licochalcone-A (LCA), a signature active ingredient of traditional Chinese medicine from the same source, was used as a model drug to construct a drug-loaded exocyst-like nano-delivery system, LVLP@LCA, and its in vitro properties and anti-inflammatory activities were characterized and evaluated. The LVLP@LCA nanodelivery system was prepared by extracting the exocyst-like nanoparticles by gradient centrifugation and loading the anti-inflammatory drug LCA by ultrasonication. The LVLP@LCA nanoparticles were prepared with a particle size of about 160 nm and a tea saucershaped bilayer structure, with a high encapsulation rate and drug loading capacity. The in vitro results showed that LVLP@LCA further enhanced the ability of LCA to inhibit the proliferation of inflammatory cells and reduce the levels of ROS and NO in inflammatory cells. Meanwhile, ELISA and qRT-PCR results showed that LVLP@LCA significantly reduced the secretion and mRNA expression of IL-6, IL-1β, TNF-α, CCL5, CCL17 and other related inflammatory factors and chemokines. It was demonstrated by Western blot that LVLP@LCA reduced the expression of inflammation-inducing factor interleukin 6 (IL-6) through the JAK/STAT pathway, and then inhibited the activation of inflammatory response. The present study provides a theoretical basis for the comprehensive anti-inflammatory effect of LVLP@LCA and a new way of thinking for the application of Glycyrrhiza glabra as a traditional Chinese medicine against atopic dermatitis.
Vaccines are often administered by intramuscular or subcutaneous injection. Although these methods can effectively deliver vaccine antigens to the body and trigger the immune response. However, there are also some limitations, such as injection pain, complex operation, strict transportation conditions, poor immunogenicity and stability of the vaccine. With the development of technology, skin administration has become another new way to solve the above-mentioned problems of vaccine. Among the many ways of skin administration, microneedles show unique advantages and potential. This paper briefly describes the mechanism of microneedle transdermal immunity and its advantages over traditional injection. This paper briefly describes the mechanism and advantages of transdermal immunity of microneedles, enumerates the classification of microneedles, focuses on the design concept, structural advantages and preparation technology of bionic microneedles, and analyzes its application potential in vaccines. At the same time, this paper briefly describes the application of microneedle in vaccine, including bacterial infection, viral infection, cancer treatment and current clinical application progress. The challenges and prospects of microneedle vaccine are summarized from the aspects of safety, stability and acceptability of microneedle vaccine.
Conjugated estrogens (CE) are widely used in menopausal hormone therapy (MHT) for the relief of menopause-related symptoms (e.g., vasodilatory symptoms, neuropsychiatric symptoms, genitourinary atrophy symptoms, etc.) and the prevention of postmenopausal osteoporosis. This article reviews the characteristics, pharmacological effects, and practical applications of different dosage forms of CE (tablets, creams, and injections) in clinical practice. It has been shown that tablet CE effectively regulates the body's temperature center through systemic treatment, reduces hot flashes and night sweats, promotes bone formation, and increases bone density. Cream CE is used for local treatment to improve the genitourinary syndrome of menopause (GSM). Injectable CE is used for the treatment of abnormal uterine bleeding caused by hormonal imbalance without organ pathology. CE administered intravenously is indicated only for short-term use to rapidly and temporarily increase estrogen levels. Additionally, CE plays an important role in metabolism by improving insulin clearance and sensitivity and potentially protecting the nervous and cardiovascular systems, demonstrating a wide range of therapeutic potential. This paper provides new ideas for the design and development of drug dosage forms by exploring the formulation and application of CE.
Synthetic cannabinoid N-(1-carbamoyl-2, 2-dimethylpropyl)-1-butylazole-3-formamide (ADB-BUTINACA), as a new psychoactive substance, shows strong stimulant and hallucinogenic effects. It can cause cardiovascular, renal and gastrointestinal diseases, and in severe cases, it can lead to death. However, there are few reports on toxicology studies of the ADB-BUTINACA metabolic pathway and its long-term effects on the organism and the molecular mechanisms behind it. In this study, the metabolic profile of rat serum after low, medium and high doses of ADB-BUTINACA (0.1, 1, and 5 mg·kg-1) intervention were analyzed using UHPLC coupled with a Q-Orbitrap-MS (UHPLC-Q-Orbitrap-HRMS). The results showed that the intervention of ADB-BUTINACA could cause significant changes of 50 metabolites such as L-glutamate and 3-hydroxybutyrate, and nine metabolic pathways including alanine, aspartate and glutamate metabolism, retinol metabolism, and TCA cycle were disturbed. These findings provide a novel experimental and theoretical framework for further investigation of the toxicological mechanisms underlying ADB-BUTINACA-induced dysregulation of lipid and energy metabolism. Furthermore, they offer valuable insights that could facilitate the diagnosis and prevention of ADB-BUTINACA toxicity, thereby underscoring their significant implications for public health. The study was conducted in adherence to both the Declaration of Helsinki and the National Institutes of Health's Guidelines for the Care and Use of Laboratory Animals, and received approval from the animal experimental center at the Zhejiang Chinese Medical University (Ethical number: 20220718-11).
The study aims to establish HPLC fingerprint and multi-index content determination method of Guanxin Qiwei tablets and provide scientific basis for its quality control. The fingerprints of 18 batches of Guanxin Qiwei tablets were established by Shim-pack GGIST HP C18 chromatographic column, and analyzed comprehensively in combination with the Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition). Cluster analysis (CA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for stoichiometric study. HPLC-MS/MS method was established for simultaneous determination of 9 components. A total of 22 common peaks were identified in 18 batches of Guanxin Qiwei tablets fingerprint, and the similarity was 0.952-0.998, 9 common peaks were identified. They were No. 1 gallic acid, No. 3 protocatechuic acid, No. 8 ellagic acid, No. 9 salvianolic acid B, No. 12 luteolin, No. 13 apigenin, No. 19 dehydrodiisoeugenol, No. 20 cryptotanshinone and No. 21 tanshinone ⅡA. CA and PCA analysis grouped 18 batches of Guanxin Qiwei tablets into 3 categories: S1-S4 (manufacturer A) was grouped into one category, S5-S8 (manufacturer B) was grouped into one category, and S9-S18 (manufacturer C and D) was grouped into one category. Under OPLS-DA analysis mode, 14 quality differentiators were selected with the variable important projection (VIP) greater than 1 as the standard, and all of them had significant differences. The linear relationship of the 9 components was good in their respective ranges, and the linear correlation coefficient r was greater than or equal to 0.099 9. Precision RSDS were all lower than 3.00%. The stability and repeatability were good, RSD lower than 5.00%; The average recoveries were 96.58%-106.28%, RSD was 2.68%-6.45%. This method is efficient and stable, and can be used for quality control of Guanxin Qiwei tablets.
There are abundant resources of traditional Chinese medicine in China, and it is found that the effective components of traditional Chinese medicine contain functional groups that are easy to coordinate with metal ions, such as amino, carboxyl and hydroxyl, which can complex with transition metal ions to derive new compounds. These traditional Chinese medicine metal complexes often exhibit unique properties and functions compared with their corresponding monomers, providing a new path for new drug development. Based on the formation principle of metal complexes with traditional Chinese medicine and the common coordination metal ions, in this review, the effective components in traditional Chinese medicine are roughly divided into anthraquinone, alkaloid, flavone, coumarin, amino acids and polysaccharide compounds, so as to provide new ideas for the discovery of new traditional Chinese medicine, and provide scientific basis for the modernization and internationalization of traditional Chinese medicine.
Cocktail probe drug method was used to evaluate the effect of cold treatment drugs such as Gegen Decoction on cytochrome P450 (CYP450) enzyme activity in rat liver. The in vitro incubation system of rat liver microsomes was optimized. Based on LC tandem mass spectrometry (LC-MS/MS), an analytical method for simultaneous determination of the content of metabolites of each subenzyme probe in rat liver microsome CYP450 enzyme was established. Cocktail probe drug method was used to characterize the effects of Gegen Decoction, a classical prescription for the treatment of wind-cold cold, and acetaminophen, chlorpheniramine maleate, anhydrous caffeine and nacotine hydrochloride, which were commonly used in the treatment of cold, on the activity of CYP2D6, CYP2C9, CYP3A4 and other sub-enzymes in rat liver microsomes, so as to provide reference for the safety of clinical drug combination. The results showed that the established analysis method was stable and reliable, which met the requirements of biological sample determination. After optimization, the protein concentration of rat liver microsomes in the incubation system was 3.00 mg·mL-1, the incubation time was 240 min, and the terminator was acetonitrile. The Km values of three CYP subenzyme specific probe substrates dextromethorphan, testosterone and tolbutamide were 21.49, 87.33 and 354.7 μmol·L-1, respectively. The effectiveness of the established incubation system was verified by positive inhibitors. Compared with the blank control group, when the concentration of each Western medicine and the concentration of Gegen Decoction extract were within 100.00 μmol·L-1 and 3.00 mg·mL-1, respectively, Gegen Decoction extract, chlorpheniramine maleate and noscapine hydrochloride had inhibitory effects on CYP2C9 and CYP2D6 enzymes in rat liver microsomes; anhydrous caffeine had inhibitory effects on CYP2C9 and CYP3A4 enzymes in rat liver microsomes; no significant inhibitory effect on acetaminophen; the induction effect of narcotine hydrochloride on CYP3A4 enzyme in rat liver microsomes was greater than 40% of the activity of positive inducer, suggesting that there may be a certain risk of drug interaction when combined with narcotine hydrochloride, and attention should be paid to the dose of drug treatment. The experimental protocol strictly adhered to the guidelines of the Ethics Committee of Animal Research of Guangdong Pharmaceutical University (Approval: gdpulacspf2022137).
Five sesquiterpenoids were isolated from a 50% acetone extract of Cornus officinalis leaves, a traditional non-medicinal part of Cornus officinalis, using modern column chromatographic techniques such as macroporous adsorbent resins colum, silica gel colum, chromatography gel colum and semi-preparative liquid chromatography techniques. Their structures were identified by modern wave spectroscopy techniques and electronic circular dichroism (ECD) and assigned as cornurtone A (1), cornucadinoside B (2), lacinilene C (3), 3, 12-dihydroxycadalene (4), cornucadinoside C (5). Compound 1 was new compound and compounds 2-5 were first isolated from leaves of Cornus officinalis. Compounds 2 and 3 had potential neuroprotective activities.
This study investigated the material basis of Huoluoxiaolingdan in treating diabetic peripheral neuropathy (DPN) through ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and network pharmacology. UPLC-Q-TOF-MS/MS combined with PeakViewTM 1.2 software and Molecule ProfilerTM software were used to analyze the the chemical components of Huoluoxiaolingdan and blood-absorbed ingredients in normal rats and rats with DPN induced by high fat diet combined with low dose streptozotocin injection. Swiss Target Prediction database, GeneCards and other databases were used to search the corresponding targets of active ingredients and disease targets. The intersection targets were obtained using Venny 2.1 platform, which were then imported into the STRING platform and Cytoscape 3.10.1 software to construct the protein-protein interaction network and the "component-target" network relationship diagram, and the core components and core targets were analyzed. GO and KEGG pathway enrichment analysis of key targets were performed. All experiments were approved by the experimental Animal Ethics Committee from Nanjing University of Chinese Medicine (No. 202310A023). A total of 83 chemical components were identified, including 52 terpenoids such as tanshinone ⅡA, 11 phthalides such as Z-ligustilide, 15 organic acids such as ferulic acid, 4 coumarins and 1 phenol. Additionally, 15 prototype components and 29 metabolites were identified in normal rats' plasma, and 17 prototype components and 32 metabolites were identified in DPN rats' plasma. Network pharmacology results show that 5 core components such as 3-acetyl-11-keto-β-boswellic acid and 11-keto-β-boswellic acid may act through 27 core targets such as TNF and IL6 to regulate AGE-RAGE and PI3K/Akt and other signaling pathways so as to play a therapeutic role in treatment of DPN. The study efficiently analyzed the constituents in vitro and blood-absorbed ingredients of Huoluoxiaolingdan and the cracking regularity of the main compounds, and the core components of its treatment of DPN were analyzed in combination with network pharmacology, which can provide reference for further research of the pharmacodynamic substantial basis and mechanism of Huoluoxiaolingdan in the treatment of DPN.
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.