Identification of Constituents and Exploring the Mechanism for Toutongning Capsule in the Treatment of Migraine

Toutongning capsule (TTNC) is an effective and safe traditional Chinese medicine used in the treatment of migraine. In this present study, a multiscale strategy was used to systematically investigate the mechanism of TTNC in treating migraine, which contained UPLC-UESI-Q Exactive Focus network pharmacology and experimental verification. First, 88 compounds were identified by the UPLC-UESI-Q Exactive Focus method for TTNC. Then, the target fishing for these compounds was performed by means of an efficient drug similarity search tool. Third, a series of network pharmacology experiments were performed to predict the key compounds, targets, and pathways. They were protein-protein interaction (PPI), KEGG pathway enrichment analysis, and herbs-compounds-targets-pathways (H-C-T-P) network construction. As a result, 18 potential key compounds, 20 potential key targets, and 6 potential signaling pathways were obtained for TTNC in treatment with migraine. Finally, molecular docking and experimental were carried out to verify the key targets. In short, the results showed that TTNC is able to treat migraine through multiple components, multiple targets, and multiple pathways. This work may provide a theoretical basis for further research on the molecular mechanism of TTNC in the treatment of migraine.

Biological Activities of Extracts from Ageratum fastigiatum: Phytochemical Study and In Silico Target Fishing Approach

In the present study, the ethanolic extract from aerial parts of Ageratum fastigiatum was evaluated in vitro against epimastigote forms of Trypanosoma cruzi (Y strain), promastigote forms of Leishmania amazonensis (PH8 strain), and L. chagasi (BH400 strain). The extract was also evaluated against Staphylococcus aureus (ATCC 25 923), Escherichia coli (ATCC 11 775), Pseudomonas aeruginosa (ATCC 10 145), and Candida albicans (ATCC 36 802). The phytochemical screening was performed by thin-layer chromatography and high-performance liquid chromatography. The extract was fractionated using flash preparative chromatography. The ethanolic extract showed activity against T. cruzi, L. chagasi, and L. amazonensis and antimicrobial activity against S. aureus, E. coli, P. aeruginosa, and C. albicans. The phytochemical screening revealed coumarins, terpenes/sterols, and flavonoids in the ethanolic extract. In addition, the coumarin identified as ayapin was isolated from this extract. We also performed in silico prediction of potential biological activities and targets for compounds previously found in A. fastigiatum. Several predictions were confirmed both retrospectively and prospectively by experimental results described here or elsewhere. Some activities described in the in silico target fishing approach were validated by the ethnopharmacological use and known biological properties. Some new activities and/or targets were predicted and could guide future studies. These results suggest that A. fastigiatum can be an interesting source of substances with antiparasitic and antimicrobial activities.

Recent Advances in In Silico Target Fishing

In silico target fishing, whose aim is to identify possible protein targets for a query molecule, is an emerging approach used in drug discovery due its wide variety of applications. This strategy allows the clarification of mechanism of action and biological activities of compounds whose target is still unknown. Moreover, target fishing can be employed for the identification of off targets of drug candidates, thus recognizing and preventing their possible adverse effects. For these reasons, target fishing has increasingly become a key approach for polypharmacology, drug repurposing, and the identification of new drug targets. While experimental target fishing can be lengthy and difficult to implement, due to the plethora of interactions that may occur for a single small-molecule with different protein targets, an in silico approach can be quicker, less expensive, more efficient for specific protein structures, and thus easier to employ. Moreover, the possibility to use it in combination with docking and virtual screening studies, as well as the increasing number of web-based tools that have been recently developed, make target fishing a more appealing method for drug discovery. It is especially worth underlining the increasing implementation of machine learning in this field, both as a main target fishing approach and as a further development of already applied strategies. This review reports on the main in silico target fishing strategies, belonging to both ligand-based and receptor-based approaches, developed and applied in the last years, with a particular attention to the different web tools freely accessible by the scientific community for performing target fishing studies.

New evidence for tamoxifen as an antischistosomal agent: in vitro, in vivo and target fishing studies

Background: Praziquantel is the only drug available to treat schistosomiasis, and there is an urgent demand for new anthelmintic agents. Methodology & results: We conducted in-depth in vitro and in vivo studies and report a target fishing investigation. In vitro, tamoxifen was active against adult and immature worms at low concentrations (<5 μM). Tamoxifen at a single dose (400 mg/kg) or once daily for five consecutive days (100 mg/kg/day) in mice harboring either adult (patent infection) or juvenile (prepatent infection) significantly reduced worm burden (30–70%) and egg production (70–90%). Target fishing studies revealed propionyl-CoA carboxylase as a potential target for tamoxifen in Schistosoma mansoni and glucose uptake by S. mansoni was also significantly reduced. Conclusion: Our results provide news evidence of antiparasitic effect of tamoxifen and reveal propionyl-CoA carboxylase as a potential target.

Fisheries discard as an alternative for agricultural feed in the state of Campeche, Mexico

Objective: To determine the incidence of non-target fishing species, in riparianfishing, as a dietary alternative for the agricultural sector in the state of Campeche,Mexico.Design / methodology / approach: The ports surveyed in the state of Campeche:Champotón, Seybaplaya and Campeche. A total of 89 questionnaires were appliedat random and at the free will to participate to coastal fishermen. The obtained datawere analyzed with the R vr 3.4.4 statistical software.Results: The results showed that the coastal fishing catch is 760.1 kg onaverage/week, and fishing discards of 30.42 kg/week. Of the bycatch, 68.8% isdiscarded and the rest sold at a low price (US $ 0.2). Among the waste products,234 species stand out, but seven represent the 58.7% of maximum incidence,mainly Bosh Ariopsis felis, Chac-chi Haemulon plumierii, Cojinuda Caranx crysos,Ixpil Upeneus sp., Macabi Elops saurus, Postà Bairdiella chrysoura and SardinaHerengula jaguana.Delimitations / implications: There is a wide variety of species of which theirpotential as a protein source is unknown, which can be used as input in feed.Findings / conclusions: Registered fishing discards are made up of more than 30non-target species and according to their incidence can be considered as inputs infeed manufacturing for the agricultural sector.

Systems Pharmacology-Based Strategy to Explore the Pharmacological Mechanisms of Citrus Peel (Chenpi) for Treating Complicated Diseases

Citri Reticulatae Pericarpium (CRP), also known as Chenpi in Chinese, is the dry mature peel of Citrus reticulata Blanco or its cultivated varieties. CRP as the health-care food and dietary supplement has been widely used in various diseases. However, the potential pharmacological mechanisms of CRP to predict and treat various diseases have not yet been fully elucidated. A systems pharmacology-based approach is developed by integrating absorption, distribution, metabolism, and excretion screening, multiple target fishing, network pharmacology, as well as pathway analysis to comprehensively dissect the potential mechanism of CRP for therapy of various diseases. The results showed that 39 bioactive components and 121 potential protein targets were identified from CRP. The 121 targets are closely related to various diseases of the cardiovascular system, respiratory system, gastrointestinal system, etc. These targets are further mapped to compound-target, target-disease, and target-pathway networks to clarify the therapeutic mechanism of CRP at the system level. The current study sheds light on a promising way for promoting the discovery of new botanical drugs.

Comprehensive computational target fishing approach to identify Xanthorrhizol putative targets

Xanthorrhizol (XNT), is a bioactive compound found in Curcuma xanthorrhiza Roxb. This study aimed to determine the potential targets of the XNT via computational target fishing method. This compound obeyed Lipinski’s and Veber’s rules where it has a molecular weight (MW) of 218.37 gmol-1, TPSA of 20.23, rotatable bonds (RBN) of 4, hydrogen acceptor and donor ability is 1 respectively. Besides, it also has half-life (HL) values 3.5 h, drug-likeness (DL) value of 0.07, oral bioavailability (OB) of 32.10, and blood–brain barrier permeability (BBB) value of 1.64 indicating its potential as therapeutic drug. Further, 20 potential targets were screened out through PharmMapper and DRAR-CPI servers. Co-expression results derived from GeneMANIA revealed that these targets made connection with a total of 40 genes and have 744 different links. Four genes which were RXRA, RBP4, HSD11B1 and AKR1C1 showed remarkable co-expression and predominantly involved in steroid metabolic process. Furthermore, among these 20 genes, 13 highly expressed genes associated with xenobiotics by cytochrome P450, chemical carcinogenesis and steroid metabolic pathways were identified through gene ontology (GO) and KEGG pathway analysis. In conclusion, XNT is targeting multiple proteins and pathways which may be exploited to shape a network that exerts systematic pharmacological effects.