A method was developed for the rapid and systematic identification of alkaloids in Chelidonium majus L. by HPLC-Q-TOF/MS. The separation was performed on an XCharge C18 column (5 μm, 4.6 mm×250 mm) with acetonitrile-0.1% formic acid in water by gradient elution. The flow rate was 0.7 mL·min^-1. The primary mass spectrometer molecular ion and the secondary mass spectrometry fragment ion were determined. The mass spectrometric cleavage of alkaloids was determined and the structures were used to systematically identify the alkaloids in Chelidonium majus L. To verify the accuracy of the qualitative results, three alkaloids were purified and identified by NMR. Twenty-one alkaloids were identified from Chelidonium majus L., including one aporphine-type alkaloid, three protopine-type alkaloids, 11 benzophenanthrine-type alkaloids and six protoberberine-type alkaloids. (S)-N-methylstylopine (8) was first reported in Chelidonium majus L. and dihydrocoptisine (11) and norchelidonine (12) were identified for the first time in Chelidonium majus L. using this technique. The chemical structures of the purified compounds are consistent with the qualitative results of the mass spectrometric analysis. The method is fast and accurate and can provide a basis for the identification and extraction of the chemical constituents of Chelidonium majus L.

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.

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.

Chloroquine is a quinine derivative which is synthesized by German scholars in 1934. In addition to its anti-malaria, treatment of systemic lupus erythematosus and immunomodulatory effects, chloroquine is also found valuable in broad-spectrum antiviral treatment. Clinical trials have confirmed that chloroquine has a good effect on acquired immunodeficiency syndrome. In 2019, there were many patients infected with novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). Preliminary clinical trials showed that chloroquine had obvious curative effect on patients with SARS-CoV-2. We summarize the effects of chloroquine to different viruses, explain its mechanism, and compare the results of its experiments in vitro and in vivo. The antiviral effect of chloroquine in vivo and in vitro are not consistent, which may be related to the model of animal, dosage and distribution of chloroquine in vivo, and the design of clinical research.

The benzaimides chidamide and entinostat are inhibitors of histone deacetylase and have been approved for clinic use. As drug resistance readily occurs in cancer chemotherapy, the characteristics of these drugs were studied in doxorubicin-sensitive and resistant human breast cancer MCF-7 cells. Using a CCK-8 assay for measuring cell proliferation, doxorubicin-resistant cells showed some resistance to chidamide and entinostat, with greater resistance to chidamide. Potentiation of cis-diamine-dichloroplatinum action by entinostat was observed in resistant cells. The accumulation of rhodomine 123, an indirect indicator of ATP-binding cassette B1 (ABCB1)-mediated resistance, was not affected by incubation with chidamide or entinostat, suggesting that neither drug is a substrate for ABCB1. However, ABCB1 expression was significantly increased in resistance cells incubated with a fixed concentration of entinostat. Slowing of the cell cycle at G1 phase and slightly increased cell numbers at G2/M phase was detected by flow cytometry when the cell lines were treated with chidamide or entinostat. Both drugs could induce spherical morphological changes and cleavage of PARP1, an indicater of apoptosis in doxorubicin-sensitive MCF-7 cells, whereas no apoptotic features were observed in resistant cells. These findings show that there is some resistance to chidamide and entinostat in doxorubicin-resistant MCF-7 cells and that this resistance may further oppose apoptosis.

An LC-MS/MS method was developed for the simultaneous determination prednisone acetate, prednisone and active metabolite prednisolone in dog plasma, and applied to a bioavailability and pharmacokinetics study of oral dose of prednisone acetate (2.0 mg·kg^-1) and prednisone (1.8 mg·kg^-1) given to Beagle dogs in a randomized, two-way crossover study. This experiment scheme was approved by the Experimental Animal Ethics Committee of Shanghai Institute of Medicine, Chinese Academy of Sciences. Dexamethason was used as internal standard. After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on an HSS T₃ (50 mm×2.1 mm, 1.8 μm) column using a gradient elution procedure. The mobile phase consisted of methanol and 5 mmol·L^-1 ammonium acetate aqueous solution (0.1% formic acid). Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 401.2→295.2 for prednisone acetate, m/z 359.2→313.2 for prednisone, m/z 361.2→325.1 for prednisolone, m/z 393.2→373.0 for dexamethason. After prednisone acetate was administered, the C_max of prednisone was (25.1 ±3.61) ng·mL^-1 and AUC_0-t was (115 ±27.2) h·ng·mL^-1, while the C_max of prednisolone was (207 ±38.5) ng·mL^-1 and AUC_0-t was (760 ±218) h·ng·mL^-1. After prednisone was administered, the C_max of prednisone was (67.9 ±22.6) ng·mL^-1 and AUC_0-t was (160 ±19.3) h·ng·mL^-1, while the C_max of prednisolone was (582 ±81.4) ng·mL^-1 and AUC_0-t was (1 310 ±140) h·ng·mL^-1. The relative bioavailability of prednisone acetate to prednisone was only 57.1%.

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.

Our previous report demonstrated puerarin protected β cells by up-regulating the expression of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R). However, whether the anti-diabetic effects of puerarin in vivo depend on GLP-1R activation has not been clarified. In this study, the GLP-1R agonist exendin-4 (Ex4) and the GLP-1R antagonist exendin 9-39 (Ex9-30) were used. Type 2 diabetes was induced in C57BL/6J mice by a high fat diet (HFD) and divided into the following groups: control, HFD, HFD/puerarin (300 mg·kg^-1·d^-1), HFD/puerarin/exendin 9-39 (Ex9-39: 10 nmol·kg^-1·d^-1), and HFD/puerarin/exendin-4 group (Ex4: 10 nmol·kg^-1·d^-1). Animal experiments were approved by the Research Animal Care Committee of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine (AEWC-025). Puerarin was administered orally, Ex9-39 and Ex4 were administered by intraperitoneal injection for 10 days. Compared with HFD group, after 10-day treatment, the fasting blood glucose and oral glucose tolerance test (OGTT) of diabetic mice were effectively improved by puerarin (P < 0.05). Meanwhile, serum insulin levels were increased by puerarin, and levels of glucagon, triglycerides, and total cholesterol were significantly reduced (P < 0.05). Importantly, Ex4 significantly enhanced the anti-diabetic effects of puerarin in HFD mice, while Ex9-39 markedly inhibited the effects of puerarin (P < 0.05), which indicates that the effects of puerarin depend on GLP-1R activation. Furthermore, results of Western blotting of liver tissue showed puerarin effectively activated AKT and inhibited FOXO1, which relied on GLP-1R activation as well. Taken together, our findings demonstrate that puerarin ameliorates glucose homeostasis in HFD mice and is dependent on GLP-1R activation. This study provides experimental support for the potential application of puerarin.

More and more clinical evidence shows that patients with Coronavirus Disease 2019 (COVID-19) died due to severe complications such as acute respiratory distress syndrome and multiple organ failure due to the aggravation of the disease in the later period, and the main cause of the aggravation is "cytokine storm". There is no specific drug for the treatment of severe COVID-19 patients. Although western medicine can improve some symptoms, it leaves a large sequela, while traditional Chinese medicine plays an important role in this outbreak. In this paper, based on the clinical reported cytokines storm-related indicators, the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) was used to mine and screen the traditional Chinese medicines acting on these cytokines based on the theory of "damp toxin invading the lung". It was found that 19 cytokines, including interleukin-6 (IL-6), tumor necrosis factor α (TNFα), granulocyte-macrophage colony stimulating factor (GM-CSF) and so on, were closely related to COVID-19, and 22 traditional Chinese medicines such as Ephedrae Herba, Glycyrrhizae Radix Et Rhizoma and Lonicerae Japonicae Flos acted on these cytokines, so as to provide certain reference for the reasonable choice of prescription and addition or modification of drugs for COVID-19 patients in the middle and late stage of Chinese medicine clinical treatment.