Recently, hepatic sinusoidal obstruction syndrome (HSOS) induced by misuse of Gynura japonica has increased and gained global attention. Large amounts of pyrrolizidine alkaloids (PAs) are present in G. japonica; these PAs are metabolically activated to generate pyrrole-protein adducts (PPAs). In this study, male SD rats were treated orally with a single dose of G. japonica extract (GJE) at 0.062 5, 0.25, 0.5, 1, and 2 g·kg^-1. Blood was collected from the orbital venous plexus at 2, 12, 24 and 48 h, and at 48 h after treatment the rats were anesthetized with isoflurane and livers were collected for hematoxylin & eosin staining. The kinetics of PPAs at different doses were studied at 10, 20, 30 min, 1, 2, 4, 6, 12, 24 h, and 48 h, after a single gavage of GJE. The experimental scheme was approved by the ethics committee of animal experiments of Shanghai University of Traditional Chinese Medicine (PZSHUTCM190912019). The concentration of PPAs in serum was determined by liquid chromatography-mass spectrometry (LC-MS). Kinetic data were processed by using the non-compartmental pharmacokinetics data analysis software program PK solutions 2^TM. The results demonstrate that the concentration of PPAs increased with the dose of GJE and positively correlated with the severity of liver injury. The elimination rate of PPAs in rats was significantly prolonged at higher doses. The level of PPAs and their clearance rate may serve as useful references for the detoxification of PAs-induced injuries.

"Kidney essence" is a profound concept in the theory of traditional Chinese medicine. But its biological basis is unknown until now, resulting in the therapeutic effects of traditional Chinese drugs on reinforcing kidney for supplementing essence hard to be evaluated. This study aimed, to explore the potential biological basis and mechanism of traditional Chinese drugs of reinforcing kidney for supplementing essence on diseases related to deficiency of kidney essence through network pharmacology analysis on the intersection of targets of drugs and diseases. The targets for ingredients in Rehmanniae radix praeparata (RRP), Polygoni multiflori radix praeparata (PMRP) and Polygonati rhizome (PR) were gathered from TCMSP and TCMID database. Osteoporosis, Alzheimer's disease, anemia, infertility and oligospermia targets were collected from OMIM and DisGeNET database. Drug-compound-target-disease (DCTD) network was established with Cytoscape 3.6.1 software, then Clue GO and DAVID database was used to acquire the annotation about GO terms and signaling pathways. Natural aging mice, an acknowledged syndrome model of deficiency of kidney essence, and RRP were used to verify the predictive targets by Western blot analysis. All animal experiments were conducted in accordance with the international guidelines and regulations for the care and use of animals. DCTD network showed that the intersection of drugs and diseases included 175 common targets. After topology analysis, 71 key were screened out targets which were associated with GO annotation exhibited that biological processes (including transcription regulation, RNA metabolism regulation, and DNA-dependent transcription regulation), cell composition (including nuclear lumen, organelle lumen, and membrane closure lumen), molecular function (including transcription regulation, transcription factor activity, and enzyme binding), and signaling pathway (including peroxisome proliferator-activated receptor alpha (PPARα), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (HIF-1), erythropoietin (EPO) and other signaling pathways. In natural aging mice, the expressions of HIF-1α, growth factor receptor-bound protein 2 (GRB2), MAPK3, signal transducer and activator of transcription 5A (STAT5A), transcription factor AP-1 (JUN) and proto-oncogene c-Fos (FOS) in EPO pathway were significantly decreased. RRP significantly reversed the decrease of the above targets. Above all, these results indicated that the therapeutic effects of traditional Chinese drugs of reinforcing kidney for supplementing essence on deficiency of kidney essence may be related to the regulation of nuclear transcriptional activity and EPO signaling pathway.

Traditional Chinese medicine (TCM) network pharmacology and molecular docking technology were applied to explore the mechanism of anti-coronavirus pneumonia (coronavirus disease 2019, COVID-19) of Qingfei Paidu decoction. The Chinese Pharmacopoeia (2015 edition) and Traditional Chinese Medicine Systems Pharmacology (TCMSP), OMIM (Online Mendelian Inheritance in Man), GeneCard, STRING, and others online databases are used for building a series of network, and selecting the core target and analyzing the signal pathway. Finally, we make molecular docking predictions for the important compounds. The results showed that the Qingfei Paidu decoction compound-pneumonia target network contained 292 compounds and 214 corresponding targets, and the core targets involved AKT1 (AKT serine/threonine kinase 1), IL6 (interleukin 6), MAPK8 (mitogen-activated protein kinase 8), MAPK1 (mitogen-activated protein kinase 1), and JUN (jun proto-oncogene). GO (Gene Ontology) function enrichment analysis yielded 858 GO entries, and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment screening yielded 122 related pathways, including hypoxia inducible factor-1 (HIF-1) and Toll-like receptor (TLRs) signaling pathways related to pneumonia, as well as T-cell receptor (TCR) signaling pathway related to lung injury protection. The molecular docking results showed that some core compounds of the Chinese herbal medicine of Qingfei Paidu decoction have a certain degree of affinity for 2019-novel coronavirus (2019-nCoV) main protease (3C-like protease, 3CLpro) and angiotensin-converting enzyme 2 (ACE2). In this paper, we preliminarily explored the potential therapeutic mechanism for Qingfei Paidu decoction to against COVID-19 and predicted the active ingredients. We hope that the results will help to the further study on the active ingredients and mechanism of Qingfei Paidu decoction to COVID-19.

The chemical constituents of Zingiber officinale peel were isolated and purified by various chromatographic separation techniques such as Diaion HP-20, MCI Gel CHP-20, Sephadex LH-20, ODS, silica gel and semi-preparative HPLC. Seven terpenoids were identified by physicochemical properties and spectral data:(4R, 6S)-1-(hydroxymethyl)-5, 5-dimethylbicyclo[3.1.1]hept-2-en-4-ol (1), 4-(hydroxymethyl)-1-isopropylcyclohex-2-ene-3, 4-diol (2), 3, 5, 6-trihydroxy-7-megastigmen-9-one (3), 3-(3-hydroxybutyl)-2, 4, 4-trimethyl-2, 5-cyclohexadien-1-one (4), angelicoidenol (5), grasshopper ketone (6), and dihydrophaseic acid (7), in which compounds 1, 2 are new compounds, named:(4R, 6S)-1-(hydroxymethyl)-5, 5-dimethylbicyclo[3.1.1]hept-2-en-4-ol and 4-(hydroxymethyl)-1-isopropylcyclohex-2-ene-3, 4-diol, and compounds 3-7 were obtained from this plant for the first time.

The protein proteolysis-targeting chimeras (PROTAC) are a kind of bifunctional compound that can recruit target proteins and degrade the enzyme of target proteins. The mechanism of PROTAC is using the ubiquitin-proteasome pathway to degrade target protein specifically. Because of its potential to target non-proprietary proteins and to play roles in drug resistance, PROTAC has attracted wide attention. This review summarizes the application of small molecule PROTAC in previous studies of different targets, such as nuclear proteins, membrane proteins and cytoplasmic proteins.

The ethyl acetate fraction of 80% ethanol extract from Bidens parviflora Willd.was isolated and purified by silica, polyamide, Sephadex LH-20 and HPLC. A total of eleven compounds were isolated and identified by physicochemical properties and spectral data as (2S)-11E-tetradecene-3, 5, 7, 9-tetrayne-1, 2, 13-triol (1), pyridine-4-formyl-O-β-D-glucopyranoside (2), maritimein (3), trichocarpine (4), okanin-4-methyl ether-3'-O-β-D-glucopyranoside (5), okanin-4-methyl ether-4'-O-β-D-(6″-acetyl)-glucopyranoside (6), (Z)-6-O-(4″-acetyl-6″-O-p-coumaroyl-β-D-glucopyranosyl)-6, 7, 3', 4'-tetrahydroxyaurone (7), quercetin-3-O-α-L-arabinoside (8), hyperoside (9), (3S)-(6E, 12E)-tetradecadiene-8, 10-diyne-1, 14-diol-3-O-β-D-glucopyranoside (10), bipinnata polyacetyloside B (11). Compounds 1 and 2 are new compounds, compounds 4 and 8 were isolated from the genus Bidens for the first time, compounds 5-7, 10 and 11 were isolated from this plant for the first time.

Nitric oxide (NO) is widely present in peripheral and central nervous system and regulates many physiological functions. Sleep-arousal is an advanced physiological activity. Studies have shown that NO is involved in the regulation of sleep and arousal. Nitric oxide synthases (NOSs) are a family of enzymes that catalyze the production of NO from L-arginine. Through guanylate cyclase or S-nitrosation of protein, NO can affect the activity of the ascending reticular activating system to regulate the sleep-arousal process. This paper summarizes the production of NO, its effect on sleep-arousal and its mechanism in the ascending reticular activating system, and provides new ideas and directions for the study of sleep and arousal.

Butylphthalide and ferulic acid exhibit excellent therapeutic effects in ischemic stroke. In this research, twelve 3-n-butylphthalide derivatives were designed by molecular hybridization strategy. The target compounds were obtained by nucleophilic substitution, reduction reaction, esterification reaction and elimination reaction, and the structure was confirmed by ¹H NMR, ¹³C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The compounds with the best neuroprotective activity were biologically evaluated for their ability to inhibit platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) via the Bron method.The results indicate that 7b exhibited potent neurocyte protective activity as well as prominent anti-platelet aggregation activity. Compound 7b has potential to be developed as a drug for ischemic stroke.

Higenamine (HG) is an active cardiotonic component isolated from Aconite. Chinese and foreign scholars have done a lot of research on the metabolism and pharmacological effects of HG, which confirmed that it has cardiovascular pharmacological effects of cardiactonic action and vasodilation for the treatment of heart failure and bradycardia, anti-oxidative and anti-apoptotic effects which can be used to protect the heart and reduce heart ischemia and reperfusion injury. In addition, HG inhibits the expression of iNOS mRNA by inhibiting the activity of the transcription factor NF-κB, inhibits the lipopolysaccharide (LPS)-induced NO product, and inhibits platelet aggregation and thrombus formation, thereby improving the experimental septic shock in animals. This article reviews the recent progress in cardiovasular pharmacology of HG, which will contribute to the further development and clinical application of it in the future.

HPLC-RID and HPIC-CD methods were established for the determination of sucrose octasulfate content in irinotecan hydrochloride liposomes for injection. HPLC-RID:This method was performed on a Kromasil 100-5-NH₂ column (250 mm×4.6 mm, 5 μm) with a mobile phase of 0.8 mol·L^-1 ammonium sulfate buffer (pH 3.5)-acetonitrile (83:17). The flow rate, column temperature and detector temperature were maintained at 1 mL·min^-1, 30℃ and 30℃ respectively. HPIC-CD:This method was performed on an anion exchange column Dionex InPac^TM AS11-HC (250 mm×4 mm, 9 μm) with an eluent of 30 mmol·L^-1 sodium hydroxide solution. The flow rate was 1.5 mL·min^-1, the column temperature was 30℃ and the detector temperature was 35℃. The HPLC-RID method and HPIC-CD method were validated with respects to specificity, limit of detection, limit of quantitation, linearity, precision, accuracy, stability and robustness and met the validation requirements. There were no significant differences between the HPIC-CD and HPLC-RID methods according to T-test analysis, both of which were applicable for the measurement of sucrose octasulfate concentration in irinotecan hydrochloride liposomes for injection. However, the HPLC-CD was better at the following aspects:higher detection sensitivity, simpler sample pretreatment, lower time and money spent, better environmental protection.