Asparagus cochinchinensis is a commonly used traditional Chinese medicine with steroidal saponins as its main active ingredients. Due to the structural similarity and size of the steroidal saponins, these compounds cannot always be effectively separated by a combination of normal phase silica gel column chromatography and reversed phase ODS column chromatography. In this experiment, chromatographic columns with different separation mechanisms were systematically screened, and it was found that a chiral chromatographic cellulose column could effectively separate these components. This column was used to separate 3 mixtures to obtain 6 single compounds (1-6). Structural identification showed that the singular structural difference between these poorly separated components resides in a terminal glycosyl group (xylose or rhamnose) in the C-3 glycosyl chain, and compounds 4 and 6 are two new steroidal saponins. Since the structures of compounds are often unknown during the isolation and purification of natural products, chiral columns are rarely used. This study suggests that chiral chromatographic columns are a valuable option for natural products that are difficult to separate by conventional means.

The structural modification of nano-micellar polymer carriers can not only increase the solubilization of insoluble drugs, but also make drug-loaded carriers aggregate in tumor tissues. In this paper, paclitaxel (PTX) was used as a model drug, D-α-tocopherol polyethyleneglycol 1 000 succinate (TPGS) modified by disulfide bond (-S-S-) and oleic acid (OA) was synthesized and mixed micelles were prepared with different molar ratios of sodium deoxycholate (NADC), and TPGS and NADC mixed micelles modified by thioether bond were synthesized for comparative study. The effects of the critical micelle concentration (CMC) of the modified polymer and the molar ratio of TPGS-OA and NADC on the physical and chemical properties of the micelle were investigated. Finally, the redox drug release ability of disulfide bond and thioether bond was compared. The results showed that when the molar ratio of TPGS-OA to NADC decreased, the drug loading increased, but the stability decreased. When the molar ratio was 3:1, the particle size, potential and entrapment efficiency of TPGS-S-S-OA/NADC were 96.24 ±0.14 nm, -24.4 mV and (98.7 ±0.08)%, respectively, hemolysis rate of mixed micelles is less than 2%. The disulfide modified mixed micelles released PTX completely within 5 h in 10 mmol·L^-1 H₂O₂ environment (pH 7.4), which was similar to that of thioether modified micelles. It was also found that the stability of micelles decreased when the pH value was low. All animal experiments were in accordance with ethical standards and were approved by the Animal Experimental Center of Shenyang Pharmaceutical University (No.211002300032403). In this study, we mainly developed stable nano-micelle carriers which can target drug release in tumor heterogeneous environment.

The adenosine triphosphate (ATP) liposome, prepared with the methods of film dispersion and ion-pairing was evaluated for its therapeutic effect on hypoxic brain damage. The appropriate formulation is adenosine disodium triphosphate, hexadecyl trimethyl ammonium bromide, soybean phospholipid, cholesterol with mass ratio of 1:1.98:8:3. The encapsulation efficiency of ATP liposome was (81.50 ±0.82) % and the loading efficiency was (6.79 ±0.07) %. In vitro release test and rheology test were conducted to investigate the physicochemical properties of ATP liposomes and empty gels respectively. The blank methylcellulose gel, followed with ATP liposome and ATP aqueous solution added to the methycellulose gel, were used for nasal administration in mice respectively. All experiments were approved by the Ethics Committee for Experimental Research in Academy of Military Medical Sciences. After 9 days of continuous administration, ATP liposome hydrogel increased the values of red blood cells and hemoglobin (P < 0.01) compared to ATP hydrogel and blank gel. And the ATP liposome hydrogel significantly increased the standard hypoxia tolerance time in mice compared to ATP hydrogel and blank gel after 13 days of nasal administration (P < 0.05). The immunohistochemical staining of mice hippocampus for the proapoptotic gene p53 showed that ATP liposome hydrogel was capable of protecting brain tissue in hypoxia. It is indicated that the prophylactic administration of ATP liposome nasal gel can significantly improve the hypoxia tolerance of mice, and the ATP liposome nasal gel was proved to be a promising anti-hypoxia preparation.

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus (SARS-CoV-2) is treated in accordance with symptoms, which is feasible and effective. However, current therapeutic drugs are ineffective against this virus. The development of targeted therapeutic drugs that are based on key proteins in SARS-CoV-2 replication and pathogenesis will provide a more effective means for clinical treatment. In addition, because SARS-CoV-2 is an RNA virus, which typically mutate readily, new drug development against COVID-19 will be a long-term and arduous task. New approaches to drug discovery for COVID-19 treatment using molecular simulation and machine learning algorithms, and based on the key proteins in the process of SARS-CoV-2 adsorption, entry into the host cell and viral replication are discussed herein, and we briefly introduce related work in our laboratory that can provide strategies to promote the discovery of drugs with different mechanisms of action.

Heart failure is a serious public health problem with tens of millions of people suffering from its poor prognosis. Epidemiological studies indicate that its morbidity is rising year by year and its mortality has dramatically increased in recent years, with a trend towards younger people. Although great progress has been achieved in the development of medicine in recent years, finding effective agents against heart failure remains an unconquered area in medicine development. A large number of natural medicines and their bioactive compounds, possessing mild and low toxicity as well as multiple target comprehensive effects, have been implicated in a wide range of pharmacological properties in recovering heart function, reducing energy barriers, and improving the life quality of patients. In recent years, they have been widely applied in clinical treatment for heart failure. Hence, summarizing and elucidating the convincing mechanisms for these natural medicines and their bioactive compounds would provide therapeutic targets and benefits for the treatment against heart failure.

Delivering water-soluble drugs via carriers often causes problems such as low loading and rapid releasing, so it is an urgent need to construct a high-load sustained-release drug delivery system for the clinical application of water-soluble drugs. Two-dimensional layered nanomaterials exhibit great potential in drug delivery due to their high specific surface area. In this study, bulk graphitic carbon nitride (b-g-C₃N₄) was obtained by calcination of urea. Graphitic carbon nitride nanosheets (g-C₃N₄-NS) were made from an alkali chemical-ultrasonic-assisted stripping process. Scanning electron microscopy, transmission electron microscopy and atomic force microscopy were adopted to observe the morphological characteristics of g-C₃N₄-NS, while the structural characteristics of g-C₃N₄-NS were analyzed by X-ray diffractometer and Fourier transform infrared spectroscopy. Ultraviolet spectrometry and fluorescence spectrometry were used to investigate the optical properties of g-C₃N₄-NS, and scanning electron microscopy and X-ray diffractometer were employed to investigate the stability of g-C₃N₄-NS. Polyethyleneimine (PEI) was applied in the study to functionally modify g-C₃N₄-NS, and salvianolic acid B (Sal B) was used as a water-soluble drug model to investigate the loading capacity and drug releasing behavior of g-C₃N₄-NS. The results showed that g-C₃N₄-NS had a sheet structure, and it is easy to self-assemble in layers in the ionic environment to create flocculating settling. PEI modification can lead to the switching in the surface charge of g-C₃N₄-NS and significantly improve its stability. The results of cytotoxicity test and zebrafish embryo toxicity test showed that the toxicity was low when the concentration of PEI-g-C₃N₄-NS was less than 800 μg·mL^-1. The large specific surface area and surface charge of PEI-g-C₃N₄-NS allow the maximum load factor over Sal B to reach 327.4%. In addition, PEI-g-C₃N₄-NS can continuously release drugs slowly, with a cumulative release rate of 79.2% in seven straight days. The release process conforms to the Higuchi equation. In summary, g-C₃N₄-NS modified by PEI exhibits good biocompatibility and high stability, and shows great potential in high-load and sustained-release applications of water-soluble drugs.

Fifteen 9-substituted palmatine (1) derivatives were synthesized and evaluated for their anti-Helicobacter pylori (Hp) activities in vitro. Structure-activity relationship studies revealed that introducing appropriate substituted secondary amino group at position 9 of lead 1 might be beneficial for potency. Among them, compound 5a showed the most potential activity against metronidazole (Met) resistant Hp isolates with minimal inhibitory concentrations (MICs) of 4 μg·mL^-1, much better than that of lead 1. Compound 5a displayed satisfactory safety profile in acute toxicity assay. Molecular docking suggested that 5a might act on Hp urease. The results provided key scientific evidence for the development of 1 derivatives into a new class of anti-Hp component.

In recent years, cancer immunotherapy has become an important field of basic and applied researches of cancer immunology. Cancer immunotherapy mainly includes cancer vaccine, oncolytic virus therapy, chimeric antigen receptor T cells (CAR-T cells), immune checkpoint blocks, monoclonal antibodies, and other strategies. Among them, monoclonal antibody-based cancer immunotherapy has the fastest development. In the past 20 years, monoclonal antibody has become one of the drugs with remarkable curative effect and novel type for human malignant tumors, especially the monoclonal antibody targeting immune checkpoints, play an important role in immunotherapy. In this review, we will summarize the current situation of monoclonal antibody-based cancer immunotherapy, potential immune modulatory mechanism, antibody targeting molecules and its immunotherapeutic agents, and explore the trend of monoclonal antibody-based agents in cancer immunotherapy.

The paper aims to study and compare the effects of Scutellaria baicalensis leaves (SLE) and Scutellaria baicalensis tea (STE) water extracts on the lifespan of Drosophila melanogaster, and explore their anti-aging mechanism through metabolomics. Lifespan, food intake and fertility were measured after administering different doses of SLE and STE to a Drosophila natural aging model, and the metabolic profile of Drosophila was analyzed by metabolomics and multivariate statistical methods. The results showed that SLE and STE (1, 3 g·L^-1) could significantly prolong the average lifespan, median life and maximum lifespan of male Drosophila, improve the fertility of Drosophila, and had no effect on the food intake. Through metabolomics technology, 14 differential metabolites related to aging were found, involving a total of five metabolic pathways. All differential metabolites were reversed after STE intervention, while 13 differential metabolites were reversed after SLE intervention. The results suggest that SLE and STE can delay aging of Drosophila, and the anti-aging mechanism is related to energy metabolism.

Small molecular drugs with large ring structure have recently attracted the attention in medicinal chemistry, the reason is their advantages in improving pharmacological activity and selectivity, and in satisfying drug-like properties. The macrocyclic structure takes into account both the microscopic structure for binding to targets and the macroscopic properties required by the pharmacokinetics. Although macrocyclic drugs historically originated from natural products, in recent years, they have been successfully designed, expanded the chemical space of traditional small molecules, and, to some extent, broken through the well-known the Role of Five in drug innovation. In addition, macrocyclic molecules also pave the path for developing drugs for non-druggability targets and for interfering with protein-protein interaction. This article focuses on the molecular design of macrocyclic drugs with some successful examples, concisely discusses structural optimization of a few macrocyclic natural drugs, and briefly describes stapled peptides in medicinal chemistry.