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.

Severe alcoholic hepatitis (SAH) represents the most extreme form of alcoholic liver disease (ALD), accompanied by an extremely high mortality rate. Currently, there is a dearth of appropriate animal models for related research. The objective of this study is to establish a mouse model of SAH, thereby providing a preclinical animal model for subsequent research on SAH. This study is based on the NIAAA (National Institute on Alcohol Abuse and Alcoholism) model and constructs a mouse model by combining bacterial endotoxins. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-102). The model emulates the pathological processes of clinical SAH in terms of mouse mortality, liver tissue damage, and inflammatory markers, thereby establishing the model. Ultimately, it is ascertained that the optimal conditions for SAH mouse modeling based on the NIAAA model are the last intragastric administration of alcohol at a concentration of 7.5 g·kg^-1 in combination with intraperitoneal injection of lipopolysaccharide at a dose of 5 mg·kg^-1 for a period of 12 h. Under these conditions, the mouse model effectively simulates the high mortality and liver dysfunction seen in clinical SAH, with pathological staining results closely mirroring clinical findings. Additionally, it demonstrates a significant infiltration of neutrophils in the liver, indicative of an excessive inflammatory response. This model provides an ideal platform for preclinical research on SAH.

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 K_m 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).

Respiratory infections, as common diseases, along with other respiratory system diseases such as asthma, rare diseases including cystic fibrosis, chronic obstructive pulmonary disease, and lung cancer, can be prevented using vaccines. Taking respiratory infections as an example, vaccines are mostly administered via intramuscular injection, inducing the production of serum IgG, thereby neutralizing viral infectivity and alleviating COVID-19 symptoms. However, due to the lack of secretory IgA and IgG in muscle tissues, intramuscular vaccines cannot quickly provide protection to the respiratory tract. To overcome the shortcomings of intramuscular injection, some vaccine candidates for nasal or nebulized inhalation are under development or have been approved. Clinical studies show that inhaled vaccines can induce antibody responses similar to those of intramuscular vaccines at much lower doses. Inhaled vaccines can simultaneously induce humoral, cellular, and mucosal immunity, providing triple protection. With the application of new vaccines (e.g. mRNA vaccines and DNA vaccines) in inhalable formulations for COVID-19, inhaled vaccines have been proven to have broad application prospects in the prevention of lung diseases. Given this background and the known abundance of immune cells in the lungs, increasing research efforts are devoted to developing single-dose inhalable nano dry powder vaccines. This article discusses the roles and advantages of inhaled vaccines in mucosal immunity, their potentials for treating different diseases, and prospects for the future development of inhaled vaccines based on nanotechnology.

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.

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 PeakView^TM 1.2 software and Molecule Profiler^TM 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 Ⅱ_A, 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.

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.

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.

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.