Elucidating the therapeutic mechanism of Hengqing II decoction in Alzheimer's disease using network pharmacology and molecular docking techniques.

PURPOSE: The aim of our research was to investigate the mechanism of the Hengqing II decoction in treating Alzheimer's disease (AD) through network pharmacology and experimental validation methods. METHODS: Firstly, the major chemical compounds of Hengqing II decoction were characterized by ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-Q-TOF-MS/MS), and the gene sets related to AD treatment by Hengqing II decoction were collected through the database of PubChem, Swiss TargetPrediction, and DisGeNET. Secondly, a multi-level molecular network of "Traditional Chinese medicine (TCM)-compound-target-disease" was constructed and visualized using the STRING platform and Cytoscape 3.9.1 software, and the enrichment analysis based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases was performed to predict the potential active compounds and targets of Hengqing II decoction for treating AD. Finally, molecular docking simulation was applied to investigate the binding interactions between potential active compounds and key targets, and the western blotting technique was employed to examine the expression levels of AKT1, TNF-α, and NOS2 proteins affected by active compounds. RESULTS: Totally 120 compounds in Hengqing II decoction were characterized by UHPLC-Q-TOF-MS/MS. Network pharmacology results showed that potential active compounds in Hengqing II decoction in treating AD included catalpol, gastrodin, and rehmannioside D, etc., and the main target proteins were TNF-α, NOS2, and AKT1. Further functional enrichment analysis revealed that Hengqing II decoction mainly exerted its therapeutic effects on AD by regulating lipid and atherosclerosis signaling pathways, AD signaling pathways, AKT1 signaling pathways, and PTGS2 signaling pathways. CONCLUSION: Hengqing II decoction exerted therapeutic effects on AD through multi-component, multi-target, and multi-pathway regulation, and its action mechanisms were related to oxidative stress, neuroinflammation, autophagy, and other pathways. Our research laid the data foundation for further exploration of action mechanism and clarification of clinical positioning and provided new ideas and clues in TCM formula research.

The infusion of Baccharis spicata (Lam. ) Baill (Asteraceae) has antiviral activity against hepatitis B virus without cytotoxic effects against several cell lines / La infusión de Baccharis spicata (Lam. ) Baill (Asteraceae) posee actividad antiviral contra el virus de la hepatitis B sin efectos citotóxicos contra varias líneas celulares

Medicinal plants are used to cure diseases, and their replacement is frequent and affects public health. The genus Baccharis has representatives within the medicinal flora of Argentina, although the replacement of the species of this genus known under the vulgar name of "carqueja" by Baccharis spicata has been detected i n herbalists or markets of herbal products. The genotoxic safety of this species has been established in previous work of our group. The aim of this study was to evaluate the antiviral activity of an infusion made from B. spicata leaves against hepatitis B virus with the HepG2.2.15 cellular system and to determine cytotoxicity in HepG2.2,15, A549 and Vero cell lines. Infusion of B. spicata was active to inhibit HBV replication with an EC 50 of 22.54 µg/mL and a CC 50 of 190 µg/mL.

Las plantas medicinales son empleadas para la cura de enfermedades, y su sustituc ión es frecuente y afecta a la salud pública. El género Baccharis posee representantes dentro de la flora medicinal de Argentina, aunque se ha detectado la sustitución de las especies de dicho género conocidas bajo el nombre vulgar de "carqueja" por Baccha ris spicata en herboristerías o mercados de productos herb arios . Se ha establecido la seguridad genotóxica de esta especie en trabajos previos de nuestro grupo. Este estudio buscó evaluar la actividad antiviral de una infusión elaborada a partir de hojas de B. spicata frente al virus de la hepatitis B con el sistema celular HepG2.2.15 y determinar la citotoxicidad en las líneas celulares HepG2.2.15, A549 y Vero. La infusión de B. spicata fue activa para inhibir la replicación del virus con un EC 50 de 22.54 µg/mL y un CC 50 de 190 µg/mL.

Potential anti-gout properties of Wuwei Shexiang pills based on network pharmacology and pharmacological verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuwei Shexiang Pills (WWSX), a classic Tibetan medicine, consists of Chebulae Fructus (removed pit), Aucklandiae Radix, Moschus, Aconiti Fiavi Radix, and Acori Calami Rhizoma. It is used clinically in China to treat joint pain, swelling and other symptoms, and has the function of dispelling wind and relieving pain. However, to date, the mechanism of how it works against gout is still unclear. AIMS OF THE STUDY: Using network pharmacology, molecular docking and pharmacological verification to explore the potential anti-gout properties of WWSX. MATERIALS AND METHODS: With the use of UPLC-Q/TOF-MS, the main components of WWSX were obtained and screened for potential anti-inflammatory components by network pharmacology and molecular docking. The anti-inflammatory activity of the components screened from WWSX was also tested by in vitro assays. The anti-gout mechanism of WWSX was predicted by network pharmacology, and the pharmacological validation experiments using gouty arthritis model and mouse air pouch model were used to explore the multifaceted mechanism of WWSX to modify gout. RESULT: Thirty-eight active ingredients were obtained from the UPLC-Q/TOF-MS detection. The network pharmacology and molecular docking analysis showed that 104 co-targets were participated in the treatment of gout, and the main signaling pathways involved were NOD-like receptor pathway, NF-κB pathway and MAPK pathway. Pharmacological evaluation showed that WWSX could significantly improve gout in gouty arthritis models and mouse air pouch models by modulating the above pathways. CONCLUSION: This work has predicted and validated the anti-inflammatory material basis and predicted the anti-gout mechanism of WWSX which was verified by network pharmacology, molecular docking and in vitro cellular studies. The results reveal the mechanism of WWSX in the treatment of gout and provide a theoretical basis for its clinical application.

Pupillary function test in rat: Establishment of imaging setup and pharmacological validation within modified Irwin test.

INTRODUCTION: Pupillary function is a sensitive pharmacological readout in humans, but drug effects are not well characterized in rodents. Hence improved methods are needed for quantifying pupillary responses in conscious albino rodents. METHODS: A novel camera-based pupillary imaging method was developed for conscious rats under red-light settings to investigate the effect of various reference compounds on pupil and iris diameter and light reflex. The chosen compounds (pilocarpine, tropicamide, phenylephrine, clonidine, cocaine, morphine) possess well characterized effects in humans. In rats, the compounds were administered topically as eye drops and/or systemically by intraperitoneal injection. RESULTS: Red-light was utilized in order to induce intermediate pupillary width at baseline conditions in conscious albino and pigmented rats, thereby enabling detection of light-induced constriction (miosis) and dilation (mydriasis) of the pupil. Pupil diameter and light reflex were affected by both topical and systemic administration of pilocarpine, tropicamide, phenylephrine, clonidine, cocaine, morphine. However only pharmacologically induced mydriasis was found in albino rats, whereas pigmented rats displayed both mydriasis and miosis albeit with differential responses. The pupillary imaging system is suitable for stand-alone studies as well as for pupil function assessment within the frame of a typical CNS study evaluating behavior (modified Irwin test), locomotor activity and body temperature. DISCUSSION: Strain-specific pharmacological responses were detected for pupillary function, with slightly more human-like responses in pigmented rats than albino rats, illustrating that effects on the rat pupil/iris cannot be directly translated to humans. Nevertheless, changes in pupillary diameter and/or pupillary light reflex in rats is a functional endpoint that can be quantified during early testing, and may trigger more detailed mechanistic characterization beyond the safety pharmacology core CNS battery.

Ethnomedicinal plants of Sarigöl district (Manisa), Turkey.

ETHNOPHARMACOLOGICAL RELEVANCE: This paper provides new and significant ethnopharmacological information on medicinal plants used by native people who live in Sarigöl and its surroundings in Turkey. AIM OF THE STUDY: To compile herbal remedies from the area of Sarigöl with their traditional uses, parts of the plant used and form of administration as well as to calculate ethnobotanical indices and validate its therapeutic use. MATERIALS AND METHODS: Plant samples that have been collected by herbalists or informants from Sarigöl and its surroundings for medical purposes were studied by visiting the villages during the study period, and then brought to the laboratory to identify the species. The relative frequency citation (RFC), use value (UV), informant consensus factor (ICF) and fidelity level (FL) were computed for the plants included in the study as well as a pharmacological validation from International Official sources by using WHO, ESCOP and EMA monographs. RESULTS: In this research conducted between 2010 and 2013, 141 taxa affiliated with 55 families, including 3 Gymnosperms, were determined as they used for medical purposes. The study was carried out by visiting 15 villages and 4 herbalist shops identified in Sarigöl and its surroundings. Asteraceae, Lamiaceae, Fabaceae, Rosaceae and Apiaceae have been detected as the most consumed families for medical purposes. The research showed that most of the informants agreed on the use of Vitis vinifera fruits to cure gastrointestinal diseases that demonstrated the highest fidelity level (0.62). Only 31, out of 141, of the species recorded in this study, currently have a monograph with a validated use. CONCLUSION: During the survey, it was observed that local people consumed plants in the form of the infusion, whereas when using hard organs such as bark or branches, decoctions were preferred. It was identified that most of the medicinal plants have been used for gastrointestinal and respiratory disorders, and they are mainly utilized in the form of infusion or decoction. Vitis vinifera has a different traditional use compared to therapeutic indication proposed by monographs from Official sources like ESCOP or EMA.

An automated system for the recognition of various specific rat behaviours.

The automated measurement of rodent behaviour is crucial to advance research in neuroscience and pharmacology. Rats and mice are used as models for human diseases; their behaviour is studied to discover and develop new drugs for psychiatric and neurological disorders and to establish the effect of genetic variation on behavioural changes. Such behaviour is primarily labelled by humans. Manual annotation is labour intensive, error-prone and subject to individual interpretation. We present a system for automated behaviour recognition (ABR) that recognises the rat behaviours 'drink', 'eat', 'sniff', 'groom', 'jump', 'rear unsupported', 'rear wall', 'rest', 'twitch' and 'walk'. The ABR system needs no on-site training; the only inputs needed are the sizes of the cage and the animal. This is a major advantage over other systems that need to be trained with hand-labelled data before they can be used in a new experimental setup. Furthermore, ABR uses an overhead camera view, which is more practical in lab situations and facilitates high-throughput testing more easily than a side-view setup. ABR has been validated by comparison with manual behavioural scoring by an expert. For this, animals were treated with two types of psychopharmaca: a stimulant drug (Amphetamine) and a sedative drug (Diazepam). The effects of drug treatment on certain behavioural categories were measured and compared for both analysis methods. Statistical analysis showed that ABR found similar behavioural effects as the human observer. We conclude that our ABR system represents a significant step forward in the automated observation of rodent behaviour.