Mechanism of Xing 9 ling tablet candy for alcoholic liver disease based on network pharmacology.

Xing 9 Ling tablet candy (X9LTC) effectively treats alcoholic liver disease (ALD), but its potential mechanism and molecular targets remain unstudied. We aimed to address this gap using network pharmacology. Furthermore, high-performance liquid chromatography (HPLC) and database analysis revealed a total of 35 active ingredients and 311 corresponding potential targets of X9LTC. Protein interaction analysis revealed PTGS2, JUN, and FOS as its core targets. Enrichment analysis indicated that chemical carcinogenesis-receptor activation, IL-17 and TNF signaling pathway were enriched by multiple core targets, which might be the main pathway of action. Further molecular docking validation showed that the core targets had good binding activities with the identified compounds. Animal experiments showed that X9LTC could reduce the high expression of ALT, AST and TG in the serum of ALD mice, alleviate the lesions in liver tissues, and reverse the high expression of PTGS2, JUN, and FOS proteins in the liver tissues. In this study, we established a method for the determination of X9LTC content for the first time, and predicted its active ingredient and mechanism of action in treating ALD, providing theoretical basis for further research.

[Extraction process optimization and link evaluation of Reyanning Mixture based on quality by design idea].

Reyanning Mixture is one of the superior Chinese patent medicine varieties of "Qin medicine". Based on the idea of quality by design(QbD), the extraction process of the Reyanning Mixture was optimized. The caffeic acid, polydatin, resveratrol, and emodin were used as critical quality attributes(CQAs). The material-liquid ratio, extraction temperature, and extraction time were taken as critical process parameters(CPPs) by the Plackett-Burman test. The mathematical model was established by the star design-effect surface method, and the design space was constructed and verified. The optimal extraction process of the Reyanning Mixture was obtained as follows: material-liquid ratio of 11.84 g·mL~(-1), extraction temperature at 81 ℃, and two extractions. A partial least-square(PLS) quantitative model for CQAs was established by using near-infrared spectroscopy(NIRS) combined with high-performance liquid chromatography(HPLC) under the optimal extraction process. The results showed that the correlation coefficients of the correction set(R_c) and validation set(R_p) of the quantitative models of four CQAs were more than 0.9. The root mean square error of the correction set(RMSEC) were 0.744, 6.71, 3.95, and 1.53 µg·mL~(-1), respectively, and the root mean square error of the validation set(RMSEP) were 0.709, 5.88, 2.92, and 1.59 µg·mL~(-1), respectively. Therefore, the optimized extraction process of the Reyanning Mixture is reasonable, feasible, stable, and reliable. The NIRS quantitative model has a good prediction, which can be used for the rapid content determination of CQAs during extraction. They can provide an experimental basis for the process research and quality control of Reyanning Mixture.

[Medicinal evolution and modern research progress on Mume Fructus].

Prunus mume is an edible and medicinal material, and Mume Fructus is its processed product, which was first recorded in Shennong's Classic of Materia Medica(Shen Nong Ben Cao Jing). It is an effective drug for stopping diarrhea with astringents and promoting fluid production to quiet ascaris. By consulting the ancient herbal works of the past dynasties, modern codes, and other rela-ted literature, this paper sorted out the medicinal evolution of Mume Fructus, examined the ancient efficacy of Mume Fructus and the main indications, and summarized the inclusion of Mume Fructus in national and provincial standards. It is recorded in the ancient herbal works of the past dynasties that Mume Fructus can be processed by various methods such as roasting, stir-frying or micro-frying, stir-frying with charcoal, single steaming, steaming with wine, and steaming after soaking in wine or vinegar, and prepared into pills, powders, and ointments, which are used in the treatment of fatigue, diabetes, malaria, dysentery, ascariasis, and other diseases. Mume Fructus has been included in nine editions of Chinese Pharmacopoeia and 19 provincial and municipal preparation specifications. The processing method of Mume Fructus is determined, namely, clean P. mume should be softened by moistening in water or steaming and pitted. By reviewing the effects of processing on its chemical composition, pharmacological effects, and its modern clinical application, this paper identified the following issues. The ancient application methods of Mume Fructus are diverse but less commonly used in modern times, there is a lack of standardized research on the processing, and the research on the changes caused by the difference in Mume Fructus before and after processing is not deep. Therefore, it is necessary to further investigate the change pattern of its chemical composition before and after processing and its correlation between its medicinal activity to standardize the processing technology and provide a solid basis for the use of Mume Fructus in parts and its quality control.

Mediating effects of working memory on the relationship between chronic pain and overgeneral autobiographical memory.

This study is to explore the function of working memory (WM) and autobiographical memory (AM) in patients with chronic pain. Totally, 331 patients with chronic pain and 333 healthy controls were recruited. These subjects were subjected to assessment with Pain Assessment Protocol (PAP), Visual Analogue Scale (VAS), Working Memory Index (WMI) and Autobiographical Memory Test (AMT). Patients with chronic pain scored significantly lower in WMI and higher in overgeneral autobiographical memory (OGM) of AMT. Chronic pain was significantly negatively related with WM and positively related with OGM. The structural equation model indicated that WM mediated the relationship of chronic pain and OGM. These findings suggest that WM and AM are impaired in the patients with chronic pain,,chronic pain is closely related with OGM, and WM acts an important mediating role between chronic pain and OGM.

A review of botany, ethnomedicine, phytochemistry, pharmacology and toxicology of Sarcandra species.

BACKGROUND: Sarcandra is one of the five genera of Chloranthaceae, which has a long history of medicinal use and high medicinal value, with excellent therapeutic effects on liver cancer, pneumonia, colitis, bone fractures, and dysentery. Among its species, Sarcandra glabra (Thunb.) Nakai has been extensively utilized in diverse compound formulations, toothpaste, tea, daily commodities, as well as health supplements. Therefore, in terms of its medicinal properties and effectiveness, the genus has considerable potential for development and utilization. PURPOSE: This paper presents a systematic review of the botany, ethnomedicine, phytochemistry, pharmacology, and toxicology of Sarcandra plants, aiming to deepen our understanding of Sarcandra properties further, to provide a reference for the rational utilization of Sarcandra plant resources, and at the same time laying a foundation for the development of new medicines and the study of natural products. METHODS: In this paper, we collected information about Sarcandra species through PubMed, Science Direct, Web of Science, Baidu Scholar, Google Scholar, CNKI, and other databases using the keywords Sarcandra, botany, traditional uses, chemical compounds, pharmacology and toxicology. Its botanical-related information was obtained through the Flora of China (www.iplant.cn). RESULTS: Three species of Sarcandra plants worldwide are distributed from eastern Asia to India. This genus has a long history of medicinal uses, high medicinal value, and a wide range of applications. At present, 462 compounds have been isolated and identified from Sarcandra plants, and their diversity contributes to the diversity of the pharmacological effects of Sarcandra plants. Numerous studies have shown that Sarcandra plants exhibit significant antitumor, antibacterial, anti-inflammatory, antimalarial, antiviral, antithrombocytopenia, immunomodulatory, antioxidant, hepatoprotective, hypoglycemic and hypolipidemic effects, with low toxicity and side effects. However, most studies have focused on Sarcandra glabra (Thunb.) Nakai and studies on other plants of the genus have yet to be explored. CONCLUSIONS: Sarcandra plants have a wide range of clinical uses and diverse chemical compounds. However, the main research has been concentrated on Sarcandra glabra (Thunb.) Nakai, and future research should explore the medicinal properties of other Sarcandra plants to expand their potential clinical applications. Meanwhile, the pharmacological activities of compounds from Sarcandra species need to be studied in greater depth and detail to provide an appropriate scientific basis for developing new drugs and natural product research.

Polygonum ciliinerve (Nakai) Ohwi: a review of its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology.

Polygonum ciliinerve (Nakai) Ohwi is a perennial twining vine plant from the Polygonaceae family, which is a Chinese herbal medicine with great value for development and utilization. The purpose of this paper is to provide a systematic review of the botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicology of Polygonum ciliinerve (Nakai) Ohwi, as well as an outlook on the future research directions and development prospects of the plant. Data on Polygonum ciliinerve (Nakai) Ohwi were obtained from different databases, including China National Knowledge Infrastructure, Baidu Academic, Wanfang Database, Google Academic, PubMed, Web of Science, SpringerLink, Wiley; books; standards; and Ph.D. and MSc theses. So far, 86 compounds have been identified from Polygonum ciliinerve (Nakai) Ohwi, including anthraquinones, stilbenes, flavonoids, tannins, chromogenic ketones, organic acids and esters, lignans, isobenzofurans, alkaloids, naphthols, and others. Studies have found that Polygonum ciliinerve (Nakai) Ohwi has a wide range of pharmacological effects, including antiviral, antibacterial, anti-inflammatory and analgesic, antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. Clinically, Polygonum ciliinerve (Nakai) Ohwi is very effective in the treatment of gastritis and chronic gastritis. Based on its traditional use, chemical composition, and pharmacological activity, Polygonum ciliinerve (Nakai) Ohwi is a promising source of natural medicine in drug development.

Research Progress of Eucommia ulmoides Oliv and Predictive Analysis of Quality Markers Based on Network Pharmacology.

Du Zhong is a valuable Chinese medicinal herb unique to China. It is a national second- class precious protected tree, known as "plant gold", which has been used to treat various diseases since ancient times. The main active ingredients are lignans, phenylprophetons, flavonoids, iridoids and steroids and terpenoids, which have pharmacological effects such as lowering blood pressure, enhancing immunity, regulating bone metabolism, protecting nerve cells, protecting liver and gallbladder and regulating blood lipids. In this paper, a comprehensive review of Eucommia ulmoides Oliv. was summarized from the processing and its compositional changes, applications, chemical components, pharmacological effects, and pharmacokinetics, and the Q-marker of Eucommia ulmoides Oliv. is preliminarily predicted from the aspects of traditional efficacy, medicinal properties and measurability of chemical composition, and the pharmacodynamic substance basis and potential Q-marker of Eucommia ulmoides Oliv. are further analyzed through network pharmacology. It is speculated that quercetin, kaempferol, ß-sitosterol, chlorogenic acid and pinoresinol diglucoside components are selected as quality markers of Eucommia ulmoides Oliv., which provide a basis for the quality control evaluation and follow-up research and development of Eucommia ulmoides Oliv.

Sambucus williamsii Hance: A comprehensive review of traditional uses, processing specifications, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics.

OBJECTIVE: Sambucus williamsii Hance, belonging to the Sambucus L. family (Viburnaceae), possesses medicinal properties in its roots, stems, leaves, flowers, and fruits. It is recognized for its ability to facilitate bone reunion, enhance blood circulation, remove stasis, and dispel wind and dampness. This traditional Chinese medicine holds significant potential for development and practical use. Hence, this paper offers an in-depth review of S. williamsii, covering traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics, aiming to serve as a reference for its further development and utilization. MATERIALS AND METHODS: Information for this study was gathered from various books, bibliographic databases, and literature sources such as Google Scholar, Web of Science, PubMed, Chinese National Knowledge Infrastructure, Baidu Scholar, VIP Database for Chinese Technical Periodicals, and Wanfang Data. RESULTS: Phytochemical investigations have identified approximately 238 compounds within the root bark, stem branches, leaves, and fruits of S. williamsii. These compounds encompass flavonoids, sugars, glycosides, terpenoids, phenylpropanoids, alkaloids, phenols, phenolic glycosides, and other chemical constituents, with phenylpropanoids being the most prevalent. S. williamsii exhibits a wide range of pharmacological effects, particularly in promoting osteogenesis and fracture healing. CONCLUSION: This comprehensive review delves into the traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of S. williamsii. It provides valuable insights into this plant, which will prove beneficial for future research involving S. williamsii.

Quality markers of Guchang Zhixie pills based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

Traditional Chinese medicine Guchang Zhixie pills(GCZX) is one of the famous varieties of "Qin medicine" that has been extensively applied to treating irritable bowel syndrome(IBS). However, despite the acknowledged clinical advantages of GCZX there are significant constraints on its quality control and evaluation. The present study utilized UHPLC-Q-Exactive-Orbitrap-MS to analyze the chemical composition of GCZX. Additionally, network pharmacology approaches were utilized to explore the underlying mechanism by which blood components exert therapeutic effects in the treatment of IBS. Furthermore, the GCZX samples were evaluated for their quality on the basis of the qualitative results obtained from 25 batches of GCZX samples using fingerprinting; subsequently, multivariate statistical analysis methods were employed for further analysis. The results indicated the presence of 198 individual components. Among them, 17 prototype compounds were detected in the serum of rats that were administered with GCZX. The potential therapeutic mechanism of GCZX in the treatment of IBS may be associated with the modulation of the neurological system, the immunological system, and the inflammatory response. Moreover, a total of seven prominent peaks were identified after fingerprint analysis. The range of fingerprint similarity among the 25 batches of samples varied from 0.843 to 1.000. The application of chemometrics analysis successfully facilitated the categorical classification of 25 batches of GCZX into three distinct groups. Seven components hold significant importance and should be duly considered during the quality control process of GCZX. The present study can establish the Q-Markers of GCZX for IBS, thereby providing a foundation for investigating the theoretical underpinnings and elucidating the mechanisms underlying the therapeutic effects of GCZX in the treatment of IBS.

Involvement of CYP2 and mitochondrial clan P450s of Helicoverpa armigera in xenobiotic metabolism.

Insect CYP2 and mitochondrial clan P450s are relatively conserved genes encoding enzymes generally thought to be involved in biosynthesis or metabolism of endobiotics. However, emerging evidence argues they have potential roles in chemical defense as well, but their actual detoxification functions remain largely unknown. Here, we focused on the full complement of 8 CYP2 and 10 mitochondrial P450s in the generalist herbivore, Helicoverpa armigera. Their varied spatiotemporal expression profiles were analyzed and reflected their specific functions. For functional study of the mitochondrial clan P450s, the redox partners, adrenodoxin reductase (AdR) and adrenodoxin (Adx), were identified from genomes of eight insects and an efficient in vitro electron transfer system of mitochondrial P450 was established by co-expression with Adx and AdR of H. armigera. All CYP2 clan P450s and 8 mitochondrial P450s were successfully expressed in Sf9 cells and compared functionally. In vitro metabolism assays showed that two CYP2 clan P450s (CYP305B1 and CYP18A1) and CYP333B3 (mito clan) could epoxidize aldrin to dieldrin, while CYP305B1 and CYP339A1 (mito clan) have limited but significant hydroxylation capacities to esfenvalerate. CYP303A1 of the CYP2 clan exhibits high metabolic efficiency to 2-tridecanone. Screening the xenobiotic metabolism competence of CYP2 and mitochondrial clan P450s not only provides new insights on insect chemical defense but also can give indications on their physiological functions in H. armigera and other insects.

Roles of the variable P450 substrate recognition sites SRS1 and SRS6 in esfenvalerate metabolism by CYP6AE subfamily enzymes in Helicoverpa armigera.

The cotton bollworm P450s of the clustered CYP6AE subfamily share high sequence identities but differ dramatically in their capacity to metabolize xenobiotics, especially esfenvalerate. Among them, CYP6AE17 has the highest sequence identity with CYP6AE18 but shows ~7-fold higher metabolic efficiency. CYP6AE11 is most active towards esfenvalerate but CYP6AE20 is inactive even though the enzymes share 54.8% sequence identity. Sequence analysis revealed the SRS1 (Substrate Recognition Site) and SRS6 between CYP6AE17 and CYP6AE18, and SRS1 between CYP6AE11 and CYP6AE20 are the most variable among all six SRSs. In order to identify the key factors that underlie the observed catalytic difference, we exchanged these SRS sequences between two pairs of P450s and studied the activity of the resulting hybrid mutants or chimeras. In vitro metabolism showed that the CYP6AE17/18 chimeras had 2- and 14-fold decreased activities and the CYP6AE18/17 chimeras had 6- and 10-fold increased activities to esfenvalerate. Meanwhile, after exchanging SRS1 with each other, the CYP6AE11/20 chimera folded incorrectly but the CYP6AE20/11 chimera gained moderate activity to esfenvalerate. Molecular modelling showed that amino acids variants within SRS1 or SRS6 change the shape and chemical environment of the active sites, which may affect the ligand-binding interactions. These results indicate that the protein structure variation resulting from the sequence diversity of SRSs promotes the evolution of insect chemical defense and contributes to the development of insect resistance to pesticides.