Alzheimer's disease (AD) and other aging-related diseases have become an important public health issue in China. However, current clinical drugs have failed to reverse the pathological process of AD. The holistic approach of traditional Chinese medicine offers advantages in improving cognitive function in AD through multiple molecular pathways, and may have potential for preventing AD. This paper summarizes the effects of classical traditional Chinese medicine and its active components in the improvement of AD-related cognitive dysfunction and describes the functional targets and related molecular mechanisms. This may have significance for the prevention and treatment of AD through multi-target intervention.

The COVID-19 outbreak has drawn attention to viral infectious diseases once again, and the development of antiviral drugs for both known and potentially emerging viruses is of great significance. In recent years, peptides and protein drugs are becoming a hot spot in the field of antiviral drug research and development. Phage display technology, as a powerful tool for screening peptides and protein drugs, has been increasingly concerned in the academic and industrial fields. The present review introduced the basic principle of phage display technology, summarized phage display libraries often used in antiviral drug discovery and their applications, discussed the challenges and future direction of antiviral drug research and development based on phage display technology.

Cell senescence is characterized by permanent cell cycle arrest, accompanied by the changes in cell metabolism and epigenetic regulation. Alzheimer's disease (AD) is a common neurodegenerative disease, with the main symptoms of memory loss and cognitive impairment. A large number of studies have shown that the senescence of central nervous system cells such as astrocytes and microglia is closely related to the occurrence of AD. Inhibition of brain cell senescence is expected to provide new ideas and therapeutic strategies for the prevention and treatment of AD. This paper reviews the potential roles and mechanisms of senescence of brain cells in AD, and interaction effects among brain cells. This review will provide a new direction for the study of pathological mechanism of AD and the development of anti-AD drugs.

With the acceleration of the aging process of our country's population, the impact of aging-related diseases - Alzheimer's disease (AD) on society and families has become increasingly prominent. AD is caused by multiple mechanisms, and the pathogenesis has not been fully elucidated. Most of the clinical treatments are single therapy, which mainly focuses on improving symptoms and are difficult to reverse the disease process. Therefore, the development of drugs that can both improve symptoms and reverse the disease process is extremely urgent in clinical. Increasing number of studies has shown that traditional Chinese medicine plays an important role in the prevention and treatment of AD. The natural products have many advantages, such as novel structures, multiple targets and diverse activities, which can be used as an important source of leading compounds for the treatment of AD. The review summarizes the main clinical treatment methods and the research progress of natural ingredients in traditional Chinese medicine, and provides a reference for the follow-up clinical treatment of AD combined with the advantages of traditional Chinese medicine treatment.

Asiatic acid (AA) is a ursane pentacyclic triterpenoids, which possesses a wide range of pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory, anti-bacterial. Due to poor solubility and low bioavailability, clinical application of asiatic acid is limited. To address these defects, the structural modifications of AA have been carried out, and large numbers of AA-based derivatives with novel structure and eximious biological activity have been developed. In this paper, the research progress of structural modifications, biological activity, structure-activity relationship and mechanism studies in recent twenty years are reviewed, which provides reference for development of AA-related drugs.

Coronavirus (CoVs) is a widespread pathogen that can infect humans and animals to cause serious acute and chronic respiratory diseases. Among them, SARS-CoV broke out in 2003, MERS-CoV was discovered and spread widely in 2012, and SARS-CoV-2 emerged at the end of 2019. They all belong to β-coronavirus. Peptidomimetic inhibitors targeting coronavirus main proteases (M^pro, 3CL^pro) have attracted much attention because of their broad spectrum and strong antiviral efficacy. In this review, peptidomimetic inhibitors of coronavirus main protease were classified and summarized according to the different "warheads" in design strategy. And also, the molecular structures, biological activity and design ideas of the inhibitors were analyzed and discussed, which is aimed to provide useful reference for further design and development of coronavirus inhibitors.

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

Coronary artery disease is the leading cause of death worldwide, the coronary artery stenosis or occlusion caused by atherosclerosis leads to myocardial ischemia, hypoxia, or necrosis, that is main histopathological features of coronary artery disease. Atherosclerosis relates closely to abnormal lipid regulation, chronic inflammation, and endothelial dysfunction. Cardiac enzymes and high, low-density lipoprotein are currently used to diagnose a variety of coronary artery diseases, but the evidence is inadequate. Thus, new cardioprotective therapies are required to explore sensitive molecular markers for the prediction of cardiovascular events. Lipids have an important role in maintaining the myocardial cell structure as well as cardiac function. Lipidomics is a newly emerged discipline that studies lipids on a large scale. Recent advancements in lipidomics on coronary artery disease have shown that certain lipids, such as ceramide, sphingosine, lysophosphatidic acid, oxidized lipids, and so on, are associated with the clinical classification and characteristics of coronary artery disease. In addition, recent studies of lipid profiles of the cardiac, fat, liver, and other tissue samples in animal models also have provided a novel viewpoint. Given the increasing application of lipidomics techniques for coronary artery disease, we provide a review of lipidomics technology, sensitive lipid markers, recent studies of therapeutic targets, and drug discovery for coronary artery disease.

Peptide drugs exhibit an irreplaceable role in clinics due to their high specificity, efficiency and low toxicity. At present, more than 80 peptide drugs have been approved for marketing with global sales exceeding $50 billion in 2019. However, with large molecular weights, high hydrophilicity and instability in digestive tract, oral peptide drugs encounter substantial physiological barriers leading to low oral bioavailability. Therefore, peptide drugs are mostly administered by parenteral routes. Although parenteral delivery of peptide drugs achieves high bioavailability, this is associated with inconvenience and discomfort, even causing severe side effects compared with the oral route possessing a high degree of patient compliance. Therefore, numerous studies concentrate on novel strategies to improve the oral bioavailability of peptide drugs. Some delivery technologies such as Eligen™ and Axcess™ have been successfully applied to the oral dosage form of therapeutic peptides and have accelerated relevant oral formulations for Food and Drug Administration (FDA) approval and clinical treatment. In this review, we focus on the oral peptide delivery, mainly summarizing the progress of recent strategies used to overcome oral barriers and the commercialization applications of related patents, which could facilitate the research and development (R & D) of clinical applications of oral delivery techniques for peptide drugs.

Cystic fibrosis (CF) is a common and life-threatening autosomal recessive disorder in Caucasians populations. The disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The absence of mature CFTR at the correct cellular location or dysfunction of CFTR proteins has been observed in CF patients. CF is frequently accompanied by a variety of complex complications, such as impairments in pulmonary functions, which may lead to successive infections and respiratory failure. Recently, with the understanding of the pathogenesis of CF, a wide array of therapeutic strategies for the treatment of CF has been designed. This review summarizes pathogenic mechanisms of CF, mechanisms of action of drugs, routes of administration, and new drug development as well as provides insights into the advanced treatment strategies for CF.

Nasal spray can treat local diseases such as rhinitis, it also plays an important role in the treatment of systemic diseases including vaccine immunity. As a drug-device combination product, spray pattern is often used as the quality indicator of nasal spray to ensure its quality, plume geometry can not only be combined with the spray pattern to evaluate the performance of the nasal spray, but also can predict the deposition of the nasal spray in the nasal cavity. This article systematically reviews the definition and measurement methods of the spray pattern and plume geometry of nasal spray and their correlation with nasal deposition behavior. The measurement parameters of spray pattern and plume geometry are defined. The influence of formulation, device and trigger parameters on spray pattern and plume geometry is clarified. The correlation between various parameters and nasal deposition is analyzed. The measurement parameters are classified according to the size and shape of the spray. Plume angle is closely related to the deposition of drugs in the nasal cavity. Jet-like plume with a smaller plume angle can increase the navigation ability of the nasal spray in the curved anatomical structure of the nasal cavity, which is conducive to increase drug deposition. This makes it possible to increase deposition of the nasal spray in the nasal cavity via appropriately increasing viscosity and thixotropy of the nasal spray formulation. This review provides the theoretical basis for the high quality nasal spray product development.

With the in-depth study on the gut microflora, the impact of intestinal bacteria on human health has attracted more and more attention. It has become a research hotspot in life science and medicine, and is considered as an important target of disease control. Prebiotics can regulate the composition and function of intestinal flora and then improve host health. Carbohydrate is the most basic prebiotic. Its unique physiochemical characteristics and gut microbiota-regulating ability make it a promising ingredient for achieving drug target delivery and intestinal health promotion. In this paper, different kinds of prebiotics and their regulation mechanism of intestinal bacteria were illuminated. Moreover, the research progress of carbohydrate prebiotics in drug delivery system was elucidated, and its application prospect is prospected, so as to provide reference for related research.

Obesity has become an important inducer of many public diseases such as diabetes, endocrine disorders, and so on. Anti-obesity treatment has become a hot topic. Inhibiting fat synthesis and promoting fat decomposition are important ways of drug anti-obesity treatment. With the in-depth study of the distribution, morphology and function of adipose tissue, brown adipose tissue containing multi-compartment fat drops and rich mitochondria have attracted people's attention. Beige adipocytes which are similar to brown adipocytes in morphology and function have aroused great interest, such cells can be transformed from white adipocytes by external stimulation or browning agents. This process is called "white fat browning". The expression of promoting energy consumption proteins in these cells increase, so that the function of adipocytes changes from energy storage to energy consumption to increase excessive energy consumption in the body and reduce lipid accumulation. The browning of white adipose tissue has brought new ideas for obesity treatment, but the systemic administration of browning agent has the risk of adverse reactions to non-target tissues such as heart and central nervous system, which limits its application in inducing white fat browning. Browning agents to white adipose tissue can reduce its adverse reactions and improve its bioavailability by constructing a drug delivery system targeting white adipose tissue. In this review, the mechanism on browning of white adipose tissue, the commonly used browning agents and the targeted delivery carriers that induce browning of white adipose tissue are summarized.

Anoectochilus roxburghii (Wall.) Lindl. is a medicinal species belonging to the Orchidaceae, whose whole plant can be used as a medicinal herb, known as "JinXianLian". It has antidiabetic, liver-protecting, anti-inflammatory, etc. A. roxburghii has long been used as food and medicine in Guangdong and Fujian provinces. With the wide recognition of the concept of "medicine and food homology" and the surge of market demand, wild A. roxburghii has been far from meeting the supply. It is important to establish an artificial propagation system. Resource characteristics are the key basis for optimizing germplasm and propagation systems. Therefore, this paper summarizes the germplasm resource characteristics and propagation technologies of A. roxburghii in China to provide a reference for sustainable development and subsequent mechanistic research.

This study evaluated the regulatory effect of curcumin on memory follicular T cells (mTf) in obese mice with ulcerative colitis on the basis of determining its effective treatment of ulcerative colitis in obese mice. Forty male leptin mutant (ob/ob) mice were randomly divided into control group, control + curcumin group, dextran sodium sulfate (DSS) group and DSS + curcumin group, with 10 mice in each group. Mice in the DSS group and the DSS + curcumin group were induced by DSS to establish chronic ulcerative colitis model, and mice in the control + curcumin group and the DSS + curcumin group were given curcumin (200 mg·kg^-1·d^-1) by intragastric administration. Mice were sacrificed under anesthesia, and colon mass index, colon length and other conditions were observed in each group. Pathological injury of colonic was performed after HE staining. The levels of memory follicular helper T cells (mTfh) and memory follicular regulatory T cells (mTfr) in spleen of mice were detected by flow cytometry. The expression levels of interleukin-10 (IL-10) and interleukin-17A (IL-17A) in colon tissue were detected by ELISA. The results showed that curcumin significantly increased the body weight and colon length of obese mice with colitis, and decreased the colon weight, colon mass index and pathological score (P < 0.05). Curcumin significantly reduced the levels of central memory follicular T cells (cmTf), mTfh1, mTfh17 cells and the content of pro-inflammatory cytokine IL-17A (P < 0.01). The levels of effector memory follicular T cells (emTf) and mTfr and the content of anti-inflammatory cytokine IL-10 were increased (P < 0.05, P < 0.01). Therefore, curcumin may treat colitis in obese mice by regulating the balance of mTf cell subsets.

This study is to explore the mechanism of Xueshuantong improving cerebral microcirculation disorder through the combination of network pharmacology and experimental validation in vivo. Structural formulas of main Panax notoginseng saponins, including notoginsenoside R1, and ginsenoside Rg1, Re, Rb1 and Rd were obtained from Pubchem website and their potential targets were predicted by Swiss Target Prediction database. Potential molecular targets of brain microcirculation disorder were acquired from OMIM and GeneCards database. The overlapped molecular targets between the drug and disease were analyzed. Protein interaction analysis and topology maps were constructed through the STRING online analysis platform and Cytoscape software. Core action targets were selected. GO function and KEGG pathway were analyzed by DAVID database. Immunohistochemical method was used to examine the expression of platelet endothelial cell adhesion molecule-1 (CD31) in the ischemic cortex of middle cerebral artery occlusion and reperfusion (MCAO/R) rats. The levels of mRNA and protein expressions of core action targets in MCAO/R model rats′ brain microvessels were verified by RT-qPCR and Western blot. Based on network pharmacology, 242 targets of Xueshuantong, 425 targets of brain microcirculation disorder, and 35 overlapped targets were obtained. The potential key targets of Xueshuantong, protein kinase B (AKT1), vascular endothelial growth factor A (VEGFA), caspase 3 (CASP3), matrix metallopeptidase 9 (MMP-9), phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), signal transducer and activator of transcription 3 (STAT3) involved in the alleviation of cerebral microcirculation disorder were obtained by setting degree and betweenness centrality as screening parameters. Xueshuantong at the dose of 48 mg·kg^-1 was shown to significantly improve the injury of neurological behaviors, as well as the density and morphology of microvessels of MCAO/R model rats. Xueshuantong could down-regulate the mRNA levels of AKT1, MMP-9, and STAT3, increase the protein expression levels of CD31, phosphorylated AKT and phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K), and the ratio of B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/Bax), but decrease the protein expression levels of MMP-9, cleaved caspase-3 and phosphorylated STAT3. In summary, Xueshuantong could improve ischemic cerebral microcirculation disorder and thereby reduce nerve damage in ischemia-reperfusion rats by regulating signaling pathways related with PI3K, AKT, MMP-9, STAT3 and caspase-3 in microvessels. The study strictly adhered to all ethical protocols that experimental animals should follow in the course of medical research.

Based on the research system of computer-aided drug design combined with complex network analysis, the potential mechanism of Dunhuang Dabupi Decoction in preventing and treating gastric cancer (GC) is analyzed, and the scientific connotation of its prescription rules is explored through the efficacy grouping. To study the effect of Dabupi Decoction freeze-dried powder solution on the proliferation activity of gastric cancer cells through cell experiments; the TCMSP and TCMID databases were used to collect the compound components of Dabupi Decoction. Swiss Target Prediction is used to predict potential targets of compounds. DrugBank, GeneCards, TTD, and DisGeNET were used to collect potential targets for gastric cancer. Analyze protein interactions of potential targets through the STRING database. DAVID database was used for KEGG enrichment analysis; Dabupi Decoction was divided into Wenzhong group (dried ginger), Yiqi group (ginseng, licorice, Atractylodes macrocephala), nourishing Yin group (Ophiopogon japonicus, Schisandra) and Jiangni group according to its efficacy characteristics. The inverse group (inula) has 4 functional compatibility groups. Cytoscape was used to construct a network of "medicinal flavor-potential active ingredient-key target" respectively, and the network was used to analyze the scientific connotation of the compatibility of efficacy groups. The Schrödinger software was used to verify the molecular docking of the core components and the core targets. The material basis of the Dabupi Decoction to prevent and treat gastric cancer was discovered through the combination of pattern analysis and combined free energy calculation. The core drug was analyzed from the perspective of dynamics through molecular dynamics simulation. Potential targets and representative potential compounds interact with each other. Cell experiments confirmed that Dabupitang freeze-dried powder solution can down-regulate the mitochondrial membrane potential of AGS gastric cancer cells, block the cell cycle in the G₀/G₁ phase (P < 0.05), and inhibit its proliferation (P < 0.05). The pathways enriched by the four functional groups contained in Dabupi Decoction are mainly distributed in the body's energy metabolism, inflammation-immune system regulation, and cycle-apoptotic functions. Each module is connected by a common target gene and has its own focus. The results of molecular docking showed that the compounds liquiritigenin, quercetin, kaempferol, isorhamnetin, methylophiopogonanone A, etc. may be the effective multi-target components of Dabupi Decoction. Estrogen receptor 1, androgen receptor, ATP-binding cassette superfamily G member 2, epidermal growth factor receptor, glycogen synthase kinase-3 beta and other targets have good affinity with each potential active compound, which may be a potential target of Dabupi Decoction for preventing and treating gastric cancer. Among them, kaempferol and the drug target EGFR not only have good binding ability, but also have good binding stability. This study is based on computer-aided drug design combined with complex network analysis strategies to initially reveal the material basis and molecular mechanism of Dabupi Decoction in the prevention and treatment of gastric cancer. It also explores the scientific connotation of Dabupi Decoction in the prevention and treatment of gastric cancer with different efficacy groups, and its clinical application provide chemical bioinformatics basis.

This manuscript aims to investigate the effects of resibufogenin on the proliferation, migration and invasion of human hepatocellular carcinoma cells and its related mechanisms. MTT assay was used to determine the inhibitory effect of resibufogenin on the growth of four hepatocellular carcinoma cells in vitro. Wound-healing assay and Transwell assay were used to evaluate the migration and invasion ability of resibufogenin on MHCC-97H cells. Western blot assay was used to detect the expression of migration and invasion related proteins in MHCC-97H cells treated with different concentrations of resibufogenin. The results showed that resibufogenin significantly inhibited the proliferation of hepatocellular carcinoma cells in vitro. The half maximal inhibitory concentration (IC₅₀) values on MHCC-97H, HepG2, SK-Hep-1 and Huh-7 cells were 0.55 ± 0.06, 2.83 ± 0.24, 5.25 ± 0.49, 14.89 ± 2.28 μmol·L^-1, respectively. Resibufogenin also suppressed the migration and invasion of MHCC-97H cells in a concentration-dependent manner. The protein expression of integrin α2, integrin α6, integrin β1, N-cadherin, matrix metalloproteinase 2 (MMP2) and transcription factor Twist in MHCC-97H cells were decreased significantly with the increase of the concentration of resibufogenin, while the protein expression of E-cadherin increased. In addition, we found that p-PI3K/PI3K and p-AKT/AKT ratios were significantly reduced after treatment with resibufogenin. In conclusion, resibufogenin can inhibit the proliferation, migration and invasion of hepatocellular carcinoma MHCC-97H cells in vitro, which is related to the regulation of intracellular migration and invasion protein expression and PI3K/AKT signaling pathway.

The purpose of this study was to investigate how Zuogui pills from the Kidney-tonifying and Nourishing Yin formula, in combination with the gonadotrophin-releasing hormone antagonist cetrorelix, affected the ovarian local oxidative stress response in decreasing ovarian reserve (DOR) mice. All animal experiments were carried out in accordance with the guidelines and standards established by Jinan University's Experimental Animal Management Committee. Cyclophosphamide (CTX)-treated DOR mice were given Zuogui pills, cetrorelix, or a combination of the two drugs intragastrically. After treatment, there were changes in the estrous cycle, serum sex hormone levels, oxidative stress-related indexes, growth biochemical factor levels, and SIRT1/P53/P21 expression. In comparison to the model group, the Zuogui pills and the cetrorelix+Zuogui pills group had significantly prolonged estrous periods and shortened interestrous periods, and the cetrorelix+Zuogui pills group had a significantly shortened cycle length. Follicle-stimulating hormone (FSH) decreased and estradiol (E₂) increased in all treatment groups compared to the model group, oxidative stress indexes nitric oxide synthase (NOS), nitric oxide (NO), and reactive oxygen species (ROS) decreased, growth biochemical factors brain derived neurotrophic factor (BDNF) and growth differentiation factor 9 (GDF-9) concentrations increased significantly, and leukemia inhibitory factor (LIF) showed no significant change. SIRT1/P53/P21 immunohistochemical results revealed that, when compared to the model group, the expression of SIRT1 increased while the expression of P53 and P21 proteins decreased in all treatment groups, with the cetrorelix+Zuogui pills group having the largest decrease, with significant differences in all indicators. We conclude that cetrorelix combined with Zuogui pills for kidney nourishing and Yin recipe improved the oxidative stress response in the follicle by regulating the SIRT1/P53/P21 pathway, reducing peroxide product production, protecting ovarian function, and regulating ovarian hormone secretion, and its efficacy is superior to that of cetrorelix or Zuogui pills alone.

The secondary metabolites from the dandelion-derived Epicoccum sorghinum 1-2 were isolated by silica gel and Sephadex gel column chromatography, and semi-preparative high performance liquid chromatography (HPLC). Their structures were identified by comprehensive NMR and MS methods. Their antibacterial activities were determined by filter paper method. Finally, seven compounds were isolated and identified from the fermentation product of E. sorghinum 1-2, including (4R*, 5R*, 6S*)-4, 5-dihydroxy-6-(6'-methylsalicyloxy)-2-methoxymethyl-2-cyclohexen-l-one (1), (4R*, 5R*, 6S*)-4, 5-dihydroxy-6-(6'-methylsalicyloxy)-2-methyl-2-cyclohexen-1-one (2), (4R, 5R, 6S)-4, 5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydroxymethyl-2-cyclohexen-1-one (3), (-)-gabosine E (4), theobroxide (5), 3-chlorogentisyl alcohol (6), and 3-hydroxybenzyl alcohol (7), of which 1-5 are epoxydons, and 6 and 7 are phenolics. Compounds 1 and 2 are new structures reported for the first time. Compound 6 showed significant antibacterial activity against Staphylococcus aureus.

To study the chemical constituents from the the deep-sea fungus Alternaria sp. F49. Seven compounds were isolated from the EtOAc extract by using silica gel, Sephadex LH-20, ODS and HPLC methods. Based on the spectroscopic analysis, their structures were identified as (8R)-5-O-methyl-orcinotriol (1), orcinotriol (2), α-acetylorcinol (3), 3'-hydroxyalternariol 5-O-methyl ether (4), altenusiol (5), altenusin (6), and 5'-methoxy-6-methyl-biphenyl-3, 4, 3'-triol (7). (8R)-5-O-Methyl-orcinotriol (1) is a new phenolic compound which has never been reported in the literature. Compounds 4-7 showed strong DPPH free radical scavenging activity; whereas compounds 1-7 showed strong ABTS free radical scavenging activity.

Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL^-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.

Ten compounds were isolated from the water extract of Eriocaulon buergerianum by HP20, ODS, Sephadex LH-20 and MCI Gel CHP-20 column chromatographic methods. Their structures were identified by spectroscopic and chemical approaches as 6-methoxyquercetin-3-O-(2'''-vanilloyl)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (1), syringaresinol-4'-O-β-D-glucopyranoside (2), rutin (3), 1-O-feruloylglycerol (4), 1, 2-benzenediol (5), vomifoliol (6), β-D-(6-O-trans-feruloyl) fructofuranosyl-α-D-O-glucopyranosied (7), dihydroferulic acid (8), guanosine (9) and quercetin-3-O-β-gentiobioside (10). The compound 1 is a new compound, the compounds 2 and 4-10 were obtained from Eriocaulon genus for the first time, and the compound 3 was isolated from this plant for the first time. Molecular docking study showed that 1 is a potential inhibitor of TNF-α. The compound 1 was evaluated for their anti-inflammatory activities in vitro, and 1 showed significant inhibitory activity against TNF-α production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells at the concentrations of 1, 10 and 100 μmol·L^-1.

The quality control and evaluation methods of Schizonepeta tenuifolia were established by HPLC fingerprint, multi index component content determination and chemical pattern recognition to provide basis for the quality control of medicinal materials. The chemical components of 25 batches of Schizonepeta tenuifolia panicle medicinal materials and decoction pieces collected were analyzed by high performance liquid chromatography, and the common pattern of fingerprint was established. A total of 22 common chromatographic peaks were calibrated, and their similarity was more than 0.9. The samples were divided into three categories according to different producing areas by cluster analysis. The results of principal component analysis and cluster analysis were consistent. Finally, five differential markers of different batches of Schizonepeta tenuifolia were selected by orthogonal partial least squares discriminant analysis. Through the identification of the reference substance, it was determined that peak 9 was hesperidin, peak 10 was rosmarinic acid, peak 13 was tilianin, peak 14 was quercetin, and peak 20 was pulegone. The quality evaluation method established in this study is stable and reliable, and is suitable for the quality control of Schizonepeta tenuifolia.

This study is to establish and validation in vivo models of moxifloxacin based on the theory of physiologically based pharmacokinetics (PBPK), and then to predict the distribution of moxifloxacin in human venous return and organ such as lung, spleen and so on. The efficacy of moxifloxacin and its pharmaceutical preparations were quantified by comparing the pharmacokinetic parameters with the minimum inhibitory concentration of related pathogenic bacterium. The results showed that the anti-infection efficacy of pharmaceutical moxifloxacin preparation in the corresponding organs was basically the same. The PBPK model of moxifloxacin preparations can be more accurately described the pharmacokinetic of anti-infective drugs in human, it is suitable for the efficacy evaluation of anti-infective drugs and provides a strong basis for the corresponding scientific research and scientific supervision.

The method of homogeneity evaluation for active pharmaceutical ingredient (API) spatial distribution in lyophilized product was investigated for the first time with confocal micro-Raman spectroscopy mapping, using pemetrexed disodium for injection as a model drug. Certain areas of the lyophilized product were scanned to obtain Raman spectra. The classical method ("peak clipping" method) was employed for mapping with characteristic Raman peaks of the API and the excipient. Due to the API being finely dispersed in the excipient in lyophilized products, the classical method cannot discriminate between the two ingredients making the distribution homogeneity difficult to evaluate. The "ratio of characteristic peak intensities" method was then utilized. Using this method, the relative intensity of the characteristic Raman peaks of the API to the excipient was applied for mapping and the relative content of API to excipient was calculated for a homogeneity evaluation of the drug distribution. The validation of this method showed a good linear relationship between the relative intensity and the relative content of API to excipient (r² > 0.99), and the precision and recovery were adequate for homogeneity evaluation of API by Raman spectroscopy mapping. Five products of pemetrexed disodium for injection from different manufacturers were tested through Raman maps applying this method and the histograms of relative Raman intensity were also plotted by frequency to help the homogeneity evaluation of drug distribution. The results showed that there were obvious differences in the drug distribution homogeneity from different products, where a more homogeneous API distribution was found in the brand product. This research provides a reliable method for the homogeneity evaluation of API distribution, which facilitates quality evaluation and process optimization of lyophilized products.

A randomized, open, fasting, single dose, two sequence, two cycle and double cross administration trial design was adopted. Took the test or reference efavirenz tablets of 200 mg orally in a single time. The plasma concentration of efavirenz in healthy subjects was determined by LC-MS/MS. WinNonLin8.1 software was used to calculate the main pharmacokinetic parameters of efavirenz and to evaluate the bioequivalence. The main pharmacokinetic parameters within 72 h: t_max were 2.574 ± 0.871 and 2.808 ± 0.912 h; C_max were 1 586.732 ± 424.538 and 1 549.518 ± 366.086 ng·mL^-1; AUC_{0-72 h} were 28 464.672 ± 5 682.518 and 27 828.826 ± 5 082.487 h·ng·mL^-1; t_1/2 were 63.524 ± 26.037 and 58.748 ± 20.950 h; λ_z were 0.013 ± 0.006 and 0.013 ± 0.005 h^-1. The main bioequivalence indicators were as follows: The 90% confidence interval of C_max was 95.62%-107.15%, and the geometric mean ratio was 101.22%; The 90% confidence interval of AUC_{0-72 h} was 100.43%-104.38%, and the geometric mean ratio was 102.38%. The results showed that the main pharmacokinetic parameters of the test drug and the reference drug were similar, and the two preparations had bioequivalence. This human bioequivalence clinical study was approved by the drug clinical trials ethics committee of the Second Hospital of Anhui Medical University (ethics approval No.: YW2021-110).

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

For quantitative analysis of related substances in TSD-1 active pharmaceutical ingredient, structures of prepared impurities were confirmed by NMR and UHPLC-MS, and a high performance liquid chromatographic method was established to determine the related substances in TSD-1. The analytical column was an Agilent ZORBAX Eclipe XDB-C8 (250 mm × 4.6 mm, 5 µm). The mobile phase A was 50 mmol·L^-1 ammonium acetate solution (adjusted pH to 5.8 with acetic acid) and the mobile phase B was acetonitrile. The whole run was carried out by gradient elution at a flow rate of 1.0 mL·min^-1. The detection wavelength was set at 240 nm and the column temperature was 30 ℃. The resolutions among peaks of TSD-1, impurity A, impurity B, TSD-D, and TSD-F were good. The calibration curves (n = 7) of TSD-1, impurity A, impurity B, TSD-D and TSD-F were linear in their respective weight ranges of 0.242-48.4 µg·mL^-1 (r = 1.000 0), 0.244-9.75 µg·mL^-1 (r = 0.999 9), 0.244-4.80 µg·mL^-1 (r = 0.999 9), 0.254-1.02 µg·mL^-1 (r = 0.999 9), and 0.247-0.987 µg·mL^-1 (r = 0.999 9). The lower limits of quantitation were 0.244, 0.244, 0.254, and 0.247 µg·mL^-1 for impurity A, impurity B, TSD-D, and TSD-F, respectively, and the average recovery of each impurity ranged from 99.08% to 103.00% with high accuracy. TSD-D and TSD-F were not detected in the three batches of TSD-1 active pharmaceutical ingredients, and impurity A and impurity B were not detected beyond the limit. The established HPLC method is simple, accurate, and suitable for determination of related substances of TSD-1, which can provide a valuable reference for the subsequent development of TSD-1.

Increasingly researches suggested that intermittent fasting (IF) can be part of a healthy lifestyle, which can improve risk factors associated with obesity and diabetes. Based on LC-MS metabolomics technology, this study preliminarily discussed the effect of IF on the metabolism of mice under normal physiological conditions by detecting the fecal metabolites. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. The mice were subjected to intermittent fasting for 10 weeks by fasting for 24 hours on alternate days, and their feces at 5 and 10 weeks were collected. The results show that the weight, food and water intake was not significant altered in mice with IF, but fasting blood glucose level was decreased. We found that fecal metabolites change was present at 5-week, being more prominent in 10-week. Relative to the control mice, we detected 17 and 108 metabolites in two time points, respectively. These metabolites were mainly enriched in the pathways of linoleic acid metabolism and bile acid biosynthesis. We further found that 10 metabolites may be a close correlation with IF, which had the same change trend at two time points. In conclusion, the present study provides a new approach to study the metabolism mechanism in IF treatment of related diseases.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine the plasma concentration of progesterone in Beagle dogs, and apply it to the study of the pharmacokinetics of progesterone sustained-release formulation in Beagle dogs. The plasma samples were processed by protein precipitation method and megestrol acetate was used as an internal standard (IS). The quantitation analysis was performed using multiple-reaction monitoring (MRM) mode at the specific ion transitions of m/z 315.2→97.0 for progesterone and m/z 385.2→267.1 for megestrol acetate (IS) under the positive ion condition. Male Beagle dogs were injected intramuscularly with progesterone sustained-release microspheres and the plasma samples were collected at different time points after administration. The relevant pharmacokinetic parameters were calculated by WinNonlin 8.1 software. A good linearity over the range of 0.1-500.0 ng·mL^-1 was yielded by this method. The intra- and inter-day precision (RSD) were all less than 13.25% and the accuracy (RE) was within 8.92%. Stability test showed that progesterone in dog plasma was stable at room temperature for 12 h, up to 60 days at -20 ℃ and after three cycles of freeze-thaw. The recovery of it ranged from 71.43%-77.97%. After intramuscular injection of progesterone sustained-release microspheres in Beagle dogs, t_max was 19.00 ± 25.36 h, C_max was 137.72 ± 11.59 ng·mL^-1, t_1/2 was 83.83 ± 26.43 h. The drug was released continuously in vivo and in a continuous absorption process for many times with good sustained-release effect. The method developed in this study is sensitive, rapid and stable. It is suitable for the determination of progesterone plasma concentration in Beagle dogs, and can be applied to the preclinical pharmacokinetic study of progesterone-related formulations. The animal experiment scheme of this study was approved by the Animal Ethics Committee of the Academy of Military Medical Sciences.

Local drug delivery is a new strategy to prevent postoperative recurrence of cancer, thermosensitive gel is a typical topical drug delivery system. In this study, a novel paclitaxel thermosensitive gel (PTG) was prepared to prevent recurrence after chemotherapy for cancer, the effects of drug particle size on release and absorption rate in vivo were investigated. Paclitaxel suspensions with different particle sizes were prepared by medium grinding, high pressure homogenization, air crushing and screening. Using poloxamer as the gel matrix and carbomer as the biological adhesive, Box-Behnen was used to optimize the formulation of PTG. The morphology, viscosity, rheological properties and biological adhesion of thermosensitive gel were characterized. The relationship between dissolution and release of thermosensitive gel was investigated by weight loss method, pharmacokinetics was studied in rats. The paclitaxel suspensions with the particle sizes of 350 nm, 800 nm, 3 μm and 9 μm were prepared, 19% poloxamer 407, 4% poloxamer 188 and 0.1% carbomer were used to prepare PTG. The phase transition temperature of thermosensitive gel was 30 to 35 ℃, there was a good linear relationship between in vitro release and gel dissolution. In the pharmacokinetic study, area under the curve (AUC_0-t) increased with the decrease of particle size. In general, the PTG prepared in this study can rapidly change into gel under human body temperature, provided with good adhesion. The release rate in vitro is closely related to the particle size, the release rate increased with the decrease of particle size. This study provides data support for preventing postoperative recurrence of cancer. The animal welfare and experimental process in this paper follow the regulations of the Animal Ethics Committee of the Academy of Military Medical Sciences.

We intend to study the structural characteristics of Lycopus europaeus Linn. chloroplast genome and compare the evolutionary relationship of species from Lamiaceae with similar medicinal effects. The total DNA of Lycopus europaeus was sequenced using the Illumina Hiseq 4000 Sequencing platform and was assembled using NOVOplasty software. And then we annotated and analyzed the genome using the CPGAVAS2 online tool. We constructed the phylogenetic tree using the Stellera chamaejasme and Potentilla chinensis as the outgroup. The whole length of Lycopus europaeus chloroplast genome was 152 085 bp. A total of 132 genes were annotated including 88 protein-coding genes, 8 rRNA genes and 36 tRNA genes. Among them, 8 protein-coding genes (ndhB, rps7, rps12, rps19, rpl2, rpl23, ycf2, ycf15), 7 tRNA coding genes (trnM-CAU, trnL CAA, trnN-GUU, trnE-UUC, trnV-GAC, trnA-UGC, trnR-ACG) and 4 rRNA coding genes (rrn16s, rrn23s, rrn4.5s, rrn5s) are located in the IR region. There are 13 protein coding genes [rps16, rps19 (×2), atpF, rpoC1, rpl2 (×2), petB, petD, rpl16, ndhB (×2), ndhA] each contains one intron, two protein-coding genes (ycf3, clpP) each contain two introns, and 8 tRNA coding genes each contain one intron. A total of 34 SSRs were detected in the chloroplast genome of Lycopus europaeus. Phylogenetic analysis revealed that two species in the Lycopus genus, four species in the Dracocephalum genus, Glechoma longituba, two species in the Mentha genus and Prunella vulgari, in total 10 species are most related. The complete genome sequence of Lycopus europaeus was obtained and analyzed, which clarified the evolutional relationship between the species of Lycopus europaeus and in the Lamiaceae family.

Lu Dangshen is the geoherb in Shanxi Province. The content of Codonopsis pilosula polysaccharides (CPP) in Lu Dangshen is more than that in other Codonopsis Radix from other regions. Glycosyltransferase is the key enzyme for the synthesis of bioactive components, such as CPP and tangshenoside I. Based on the transcriptome data of C. pilosula [Codonopsis pilosula (Franch.) Nannf.] from different producing areas, this study carried out functional annotation of GO and KEGG, conservative domain analysis, phylogenetic tree analysis and expression pattern analysis of glycosyltransferase genes in C. pilosula to provides a theoretical basis for exploring the mechanism of genuineness formation in Lu Dangshen. In this study, 98 glycosyltransferase genes were screened and identified, which belonged to GT family 1, GT family 2, GT family 90 and other families. By GO functional annotation, it was found that most of the glycosyltransferase genes had catalytic activity. Analysis of KEGG functional annotation showed that C. pilosula glycosyltransferase was mainly involved in glycan organism and terpenoid and polyketone metabolism. Among them, conserved domain of 42 glycosyltransferase genes in GT family 1 was [X]-W-[2X]-Q-[3X]-[LH]-[5X]-[FLTHCGWNS]-[2X]-E-[4X]-[GVP]-[4X]-P-[4X]-Q-[2X]-[NAK]. Phylogenetic tree analysis based on the glycosyltransferase sequence in Arabidopsis thaliana showed that C. pilosula glycosyltransferases were mainly located in Arabidopsis thaliana UGT73, 72 and 85 branches. Gene expression pattern analysis showed that expression of CpUGT73AH2 was higher in Lu Dangshen than that in Baitiaodang and could respond to drought and low temperature stress. In conclusion, a glycosyltransferase gene CpUGT73AH2, which is involved in the metabolism of terpenoids and polyketides and can respond to environmental stress, was screened from the C. pilosula glycosyltransferase family 1, which was used to further study the role of C. pilosula glycosyltransferase in Lu Dangshen. It laid a theoretical foundation for further study on the role of C. pilosula glycosyltransferase in the formation of Lu Dangshen.

Cirsium souliei (Asteraceae) is a perennial medicinal herb of Cirsium with important medicinal and ecological values. Here, we sequenced the complete chloroplast (cp) genome of C. souliei based on high-throughput sequencing technology, then assembled and annotated it, and analysed the structure and characteristics of the cp genome. The result indicated that the cp genome of C. souliei was a typical quadripartite circular structure of 152 470 bp in length, and GC content was 37.7%. The cp genome of C. souliei encoded 134 genes, including 89 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Meanwhile, we detected 188 simple sequence repeats (SSR) loci in the cp genome, which were mainly composed of mononucleotide repeats. Codon bias analysis showed that leucine (Leu) was the highest amino acids with frequency (10.51%), and there were 30 codons with the value of relative synonymous codon usage (RSCU) above one, of which mostly ended with A/U. Additionally, the result from phylogenetic analysis based on 46 cp genomes of Carduoideae showed that C. souliei and C. vulgare were sister species, and had the closest relationship with 100% bootstrap within Cirsium. This study provides theoretical basis for future studying genetic diversity, population genetic structure, systematics and evolution, and speciation mechanism.

In the process of evolution, pathogenic Streptococcus pyogenes secretes an immunoglobulin G-degrading enzyme IdeS which can specifically cleave the hinge region of immunoglobulin G in order to escape the immune response against the host. On the one hand, IdeS can be used for IgG fingerprinting as a tool enzyme combined with mass spectrometry technology. On the other hand, IdeS can be used to treat the antibody-responsive diseases produced by autoimmunity as a therapeutic protein. In this study, the backbone of plasmid pCold was used to construct two expression vectors of recombinant protein IdeS, which were heterologously expressed in Escherichia coli Shuffle T7. After purification by affinity chromatography, the recombinant IdeS activity was detected and their activity differences between the two were compared. Among them, the yield of the recombinant IdeS containing the His6-tag at the N-terminus was 4 mg·L^-1, and the cleavage reaction with antibody IgG1 at 1∶200 (m/m) at 37 ℃ for 30 min could complete. However, the yield of the recombinant IdeS containing both the N-terminal His6 tag and the C-terminal silica affinity tag (silica bing peptide, SiBP) is 1.5 mg·L^-1, and the degradation reaction with antibody IgG1 at 1∶20 (m/m) at 37 ℃ for 30 min could reach the end. The C-terminal fusion peptide has a great influence on the yield and activity of IdeS, which is not conducive to subsequent application in drug development. Above all, the recombinant IdeS containing the His6-tag at the N-terminus expressed by this system has high activity and can fully meet the needs of antibody drug development and mapping analysis of IgG.