Machine Learning Exploration of the Relationship Between Drugs and the Blood-Brain Barrier: Guiding Molecular Modification.

OBJECTIVE: This study aimed to improve the efficiency of pharmacotherapy for CNS diseases by optimizing the ability of drug molecules to penetrate the Blood-Brain Barrier (BBB). METHODS: We established qualitative and quantitative databases of the ADME properties of drugs and derived characteristic features of compounds with efficient BBB penetration. Using these insights, we developed four machine learning models to predict a drug's BBB permeability by assessing ADME properties and molecular topology. We then validated the models using the B3DB database. For acyclovir and ceftriaxone, we modified the Hydrogen Bond Donors and Acceptors, and evaluated the BBB permeability using the predictive model. RESULTS: The machine learning models performed well in predicting BBB permeability on both internal and external validation sets. Reducing the number of Hydrogen Bond Donors and Acceptors generally improves BBB permeability. Modification only enhanced BBB penetration in the case of acyclovir and not ceftriaxone. CONCLUSIONS: The machine learning models developed can accurately predict BBB permeability, and many drug molecules are likely to have increased BBB penetration if the number of Hydrogen Bond Donors and Acceptors are reduced. These findings suggest that molecular modifications can enhance the efficacy of CNS drugs and provide practical strategies for drug design and development. This is particularly relevant for improving drug penetration of the BBB.

Construction of An Oral Bioavailability Prediction Model Based on Machine Learning for Evaluating Molecular Modifications.

OBJECTIVE: This study aims to explore the impact of ADME on the Oral Bioavailability (OB) of drugs and to construct a machine learning model for OB prediction. The model is then applied to predict the OB of modified berberine and atenolol molecules to obtain structures with higher OB. METHODS: Initially, a drug OB database was established, and corresponding ADME characteristics were obtained. The relationship between ADME and OB was analyzed using machine learning, with Morgan fingerprints serving as molecular descriptors. Compounds from the database were input into Random Forest, XGBoost, CatBoost, and LightGBM machine learning models to train the OB 7prediction model and evaluate its performance. Subsequently, berberine and atenolol were modified using Chemdraw software with ten different substituents for mono-substitution, and chlorine atoms for a full range of double substitutions. The modified molecular structures were converted into the same format as the training set for OB prediction. The predicted OB values of the modified structures of berberine and atenolol were compared. RESULTS: An OB database of 386 drugs was obtained. It was found that smaller molecular weight and a higher number of rotatable bonds (ten or less) could potentially lead to higher OB. The four machine learning models were evaluated using MSE, R2 score, MAE, and MFE as metrics, with Random Forest performing the best. The models' predictions for the test set were particularly accurate when OB ranged from 30% to 90%. After mono-substitution and double substitution of berberine and atenolol, the OB of both drugs was significantly improved. CONCLUSIONS: This study found that some ADME properties of molecules do not have an absolute impact on OB. The database played a decisive role in the process of the machine learning OB prediction model, and the performance of the model was evaluated based on predictions within a range of strong generalization ability. In most cases, mono-substitution and double substitution were beneficial for enhancing the OB of berberine and atenolol. In summary, this study successfully constructed a machine learning regression prediction model that can accurately predict drug OB, which can guide drug design to achieve higher OB to some extent.

Honokiol targeting ankyrin repeat domain of TRPV4 ameliorates endothelial permeability in mice inflammatory bowel disease induced by DSS.

ETHNOPHARMACOLOGICAL RELEVANCE: As a classic traditional Chinese medicine, Magnolia officinalis (M. officinalis) is widely used in digestive diseases. It has rich gastrointestinal activity including inflammatory bowel disease (IBD) treatment, but the mechanism is not clear. AIM OF THE STUDY: In recent years, there has been a growing interest in investigating the regulatory effects of herbal compounds on transient receptor potential (TRP) channel proteins. Transient receptor potential vanilloid 4 (TRPV4), a subtype involved in endothelial permeability regulation, was discussed as the target of M. officinalis in the treatment of IBD in the study. Based on the targeting effect of TRPV4, this study investigated the active ingredients and mechanism of M. officinalis extract in treating IBD. MATERIALS AND METHODS: To reveal the connection between the active ingredients in M. officinalis and TRPV4, a bioactivity-guided high performance liquid chromatography system coupled with mass spectrometry identification was utilized to screen for TRPV4 antagonists. TRPV4 siRNA knockdown experiment was employed to validate the significance of TRPV4 as a crucial target in regulating endothelial permeability by honokiol (HON). The interaction of the active ingredient representing HON with TRPV4 was confirmed by molecular docking, fluorescence-based thermal shift and live cell calcium imaging experiments. The potential binding sites and inhibitory mechanisms of HON in TRPV4 were analyzed by molecular dynamics simulation and microscale thermophoresis. The therapeutic effect of HON based on TRPV4 was discussed in DSS-IBD mice. RESULTS: Our finding elucidated that the inhibitory activity of M. officinalis against TRPV4 is primarily attributed to HON analogues. The knockdown of TRPV4 expression significantly impaired the calcium regulation and permeability protection in endothelial cells. The mechanism study revealed that HON specifically targets the Q239 residue located in the ankyrin repeat domain of TRPV4, and competitively inhibits channel opening with adenosine triphosphate (ATP) binding. The immunofluorescence assay demonstrated that the administration of HON enhances the expression and location of VE-Cadherin to protect the endothelial barrier and attenuates immune cell infiltration. CONCLUSIONS: The finding suggested that HON alleviates IBD by improving endothelial permeability through TRPV4. The discovery provides valuable insights into the potential therapeutic strategy of active natural products for alleviating IBD.

Mangiferin alleviates renal inflammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway.

Objective: Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys' inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs. Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis. Results: The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-α, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels. Conclusion: Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

Investigating the Underlying Mechanisms of Ardisia japonica Extract's Anti-Blood-Stasis Effect via Metabolomics and Network Pharmacology.

OBJECTIVE: Our study aims to assess Ardisia japonica (AJ)'s anti-blood-stasis effect and its underlying action mechanisms. METHODS: The primary components of AJ were determined using liquid chromatography-mass spectrometry (LC-MS). The blood stasis model was used to investigate the anti-blood-stasis effect of AJ extract. The underlying mechanisms of AJ against blood stasis were investigated via network pharmacology, molecular docking, and plasma non-targeted metabolomics. RESULTS: In total, 94 compounds were identified from an aqueous extract of AJ, including terpenoids, phenylpropanoids, alkaloids, and fatty acyl compounds. In rats with blood stasis, AJ reduced the area of stasis, decreased the inflammatory reaction in the liver and lungs of rats, lowered the plasma viscosity, increased the index of erythrocyte deformability, and decreased the index of erythrocyte aggregation, suggesting that AJ has an anti-blood-stasis effect. Different metabolites were identified via plasma untargeted metabolomics, and it was found that AJ exerts its anti-blood-stasis effect by reducing inflammatory responses through the cysteine and methionine metabolism, linolenic acid metabolism, and sphingolipid metabolism. For the effect of AJ on blood stasis syndrome, the main active ingredients predicted via network pharmacology include sinensetin, galanin, isorhamnetin, kaempferol, wogonin, quercetin, and bergenin, and their targets were TP53, HSP90AA1, VEGFA, AKT1, EGFR, and PIK3CA that were mainly enriched in the PI3K/AKT and MAPK signaling pathways, which modulate the inflammatory response. Molecular docking was also performed, and the binding energies of these seven compounds to six proteins were less than -5, indicating that the chemical components bind to the target proteins. CONCLUSIONS: This study suggests AJ effectively prevents blood stasis by reducing inflammation.

[Research progress in clinical application and pharmacological effect of Yiyi Fuzi Baijiang Powder].

Yiyi Fuzi Baijiang Powder(YFBP), originating from Synopsis of the Golden Chamber, is a classic prescription composed of Coicis Semen, Aconiti Lateralis Radix Praeparata, and Patriniae Herba for the treatment of abscesses and pus discharge. This article presented a systematic analysis of the clinical application of YFBP, including the indicated diseases, the number of cases, efficacy, dosage, administration methods, and compatibility with other drugs. The analysis reveals that YFBP has a wide range of clinical applications. It is commonly used, often with modifications or in combination with western medicine, for diseases in the fields of gastroente-rology, gynecology, urology, dermatology, and others. And most of the Traditional Chinese Medicine(TCM) evidence involved in these diseases are damp-heat evudence. The prescription shows rich variations in clinical administration methods, and most of which are the treatment of aqueous decoction of it. The therapeutic effect is also significant, and the total effective rate of clinical treatment is re-latively high. Additionally, this article summarized the pharmacological research on YFBP and found that it possessed various pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and immune-modulating properties. Finally, correlation analysis was conducted on the main diseases, TCM types, prescription doses, pharmacological effects and action targets of YFBP, which to show the relationship between these five aspects in a visual form, reflecting the relationship between its clinical application and modern pharmacological effects. These findings provide a reference basis for further development and research on YFBP.

Exploring the potential use of Chinese herbs in regulating the inflammatory microenvironment of tumours based on the concept of 'state-target identification and treatment': a scooping review.

Tumours do not exist in isolation from the organism; their growth, proliferation, motility, and immunosuppressive response are intricately connected to the tumour's microenvironment. As tumour cells and the microenvironment coevolve, an inflammatory microenvironment ensues, propelling the phenomenon of inflammation-cancer transformation-an idea proposed by modern medicine. This review aims to encapsulate the array of representative factors within the tumour's inflammatory microenvironment, such as interleukins (IL-6, IL-10, IL-17, IL-1ß), transforming growth factor-beta (TGF-ß), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Moreover, drawing upon research in traditional Chinese medicine (TCM) and pharmacology, we explore the delicate interplay between these factors and tumour-associated inflammatory cells: tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (TANs) and dendritic cells (DCs). By analyzing the tumour-promoting effects of these entities, we delve into the connotations of Academician Tong Xiao-lin's novel model of "state-target differentiation" and its application in the diagnosis and treatment of tumours. Our aim is to enhance the precision and targeting of tumour treatment in clinical practice. Delving deeper into our understanding of tumour pathogenesis through the lens of modern medicine, we discern the key etiology and pathogenesis throughout the entire developmental stage of tumours, unveiling the evolutionary patterns of Chinese Medicine (CM) states: heat state → phlegm state → stagnation state → deficiency state. Building upon this foundation, we devised a state-regulating formula. Simultaneously, drawing on pharmacological research in traditional Chinese medicine (TCM), we meticulously identified a range of targeted drugs that effectively modulate the aforementioned tumour-related mediators. This comprehensive strategy-a harmonious integration of state identification, target recognition, and simultaneous regulation-aims to elevate clinical efficacy. The fusion of TCM with Western medicine in tumour treatment introduces novel dimensions to the precise and refined application of TCM in clinical practice.

A new perspective on Alzheimer's disease: m6A modification.

As a neurodegenerative disease, Alzheimer's disease (AD) is characterized by synaptic loss, extracellular plaques of amyloid accumulation, hyperphosphorylation of tau, and neuroinflammation. Various biological processes are affected by epitranscriptomic modifications, which regulate the metabolism of mRNA in cells and regulate the expression of genes. In response to changes in m6A modification levels, the nervous system becomes dysfunctional and plays a significant role in the development of Alzheimer's disease. As a result of recent research, this paper reviews advances in the understanding of the regulatory mechanisms of m6A modification in the occurrence and development of AD. In addition, the article discusses recent research techniques related to animal models of m6A and AD. Furthermore, it discusses the possibility of studying the pathogenesis of AD at the level of the epitranscriptome, identifying early diagnostic markers, and screening for effective treatment options.

Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants.

The COVID-19 pandemic has brought about unprecedented medical and healthcare challenges worldwide. With the continual emergence and spread of new COVID-19 variants, four drug compound libraries were interrogated for their antiviral activities against SARS-CoV-2. Here, we show that the drug screen has resulted in 121 promising anti-SARS-CoV-2 compounds, of which seven were further shortlisted for hit validation: citicoline, pravastatin sodium, tenofovir alafenamide, imatinib mesylate, calcitriol, dexlansoprazole, and prochlorperazine dimaleate. In particular, the active form of vitamin D, calcitriol, exhibits strong potency against SARS-CoV-2 on cell-based assays and is shown to work by modulating the vitamin D receptor pathway to increase antimicrobial peptide cathelicidin expression. However, the weight, survival rate, physiological conditions, histological scoring, and virus titre between SARS-CoV-2 infected K18-hACE2 mice pre-treated or post-treated with calcitriol were negligible, indicating that the differential effects of calcitriol may be due to differences in vitamin D metabolism in mice and warrants future investigation using other animal models.

Uncovering the effective substances and mechanism of Ipomoea pes-caprae against rheumatoid arthritis using liquid chromatography-mass spectrometry and targeted network pharmacology.

Ipomoea pes-caprae (L.) R. Br (Convolvulaceae) is a commonly used marine traditional Chinese medicine in the southern coastal areas of China. It has been widely used to treat rheumatoid arthritis, but its effective substances and anti-rheumatoid arthritis mechanism remain ambiguous. Hence, in this study, the chemical profile and absorbed ingredients of Ipomoea pes-caprae were elucidated by ultra-performance liquid chromatography-mass spectrometry. Moreover, targeted network pharmacology was used to clarify the mechanism of action of Ipomoea pes-caprae in treating rheumatoid arthritis. Finally, 23 compounds were identified in the aqueous extracts of Ipomoea pes-caprae and 12 absorbed ingredients were detected in rats' plasma. These 12 absorbed ingredients might be the essential effective substances of Ipomoea pes-caprae. The tissue distributions of 3 absorbed ingredients in rats were successfully analyzed. The targeted network pharmacological analysis results indicated that the regulation of inflammatory reaction, immune response, cell proliferation, and apoptosis were the critical mechanism of Ipomoea pes-caprae against rheumatoid arthritis. This study successfully clarified the effective substances and potential mechanisms of Ipomoea pes-caprae in treating rheumatoid arthritis. The results of this research could provide a valuable reference for further scientific research and clinical application.

Aquaporins: A new target for traditional Chinese medicine in the treatment of digestive system diseases.

Aquaporins (AQPs) are a family of transmembrane proteins expressed in various organ systems. Many studies have shown that the abnormal expression of AQPs is associated with gastrointestinal, skin, liver, kidneys, edema, cancer, and other diseases. The majority of AQPs are expressed in the digestive system and have important implications for the physiopathology of the gastrointestinal tract as well as other tissues and organs. AQP regulators can prevent and treat most gastrointestinal-related diseases, such as colorectal cancer, gastric ulcer, and gastric cancer. Although recent studies have proposed clinically relevant AQP-targeted therapies, such as the development of AQP inhibitors, clinical trials are still lacking and there are many difficulties. Traditional Chinese medicine (TCM) has been used in China for thousands of years to prevent, treat and diagnose diseases, and is under the guidance of Chinese medicine (CM) theory. Herein, we review the latest research on the regulation of AQPs by TCMs and their active components, including Rhei Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Salviae miltiorrhizae Radix et Rhizoma, Poria, Astragali radix, and another 26 TCMs, as well as active components, which include the active components include anthraquinones, saponins, polysaccharides, and flavonoid glycosides. Through our review and discussion of numerous studies, we attempt to explore the regulatory effects of TCMs and their active components on AQP expression in the corresponding parts of the body in terms of the Triple Energizer concept in Chinese medicine defined as "upper energizer, middle energizer, and lower energizer,"so as to offer unique opportunities for the development of AQP-related therapeutic drugs for digestive system diseases.

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups.

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, ß-elemene, can act on multi-target and multi-channel to play an antihepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an antihepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".

Regulation of transient receptor potential channels by traditional Chinese medicines and their active ingredients.

In recent years, activation of thermal transient receptor potential (TRP) ion channels at a range of temperatures has received widespread attention as a target for traditional Chinese medicine (TCM) to regulate body temperature and relieve pain. Discovery of transient receptor potential vanilloid 1 (TRPV1) was awarded a Nobel Prize, reflecting the importance of these channels. Here, the regulatory effects of TCMs and their active ingredients on TRP ion channels are reviewed, and future directions for research on the cold, hot, warm, cool, and neutral natures of TCMs are considered. In herbs with cold, hot, warm, cool, and neutral natures, we found 29 TCMs with regulatory effects on TRP ion channels, including Cinnamomi Cortex, Capsici Fructus, Rhei Radix et Rhizoma, Macleayae cordatae Herba, Menthae Haplocalycis Herba, and Rhodiolae Crenulatae Radix et Rhizoma. Although some progress has been made in understanding the regulation of TRP ion channels by TCMs and their ingredients, the molecular mechanism by which TCMs have this effect remains to be further studied. We hope this review will provide a reference for further research on the cold, hot, warm, cool, and neutral natures of TCMs.

Progress on structural modification of Tetrandrine with wide range of pharmacological activities.

Tetrandrine (Tet), derived from the traditional Chinese herb Fangji, is a class of natural alkaloids with the structure of bisbenzylisoquinoline, which has a wide range of physiological activities and significant pharmacfological effects. However, studies and clinical applications have revealed a series of drawbacks such as its poor water solubility, low bioavailability, and the fact that it can be toxic to humans. The results of many researchers have confirmed that chemical structural modifications and nanocarrier delivery can address the limited application of Tet and improve its efficacy. In this paper, we summarize the anti-tumor efficacy and mechanism of action, anti-inflammatory efficacy and mechanism of action, and clinical applications of Tet, and describe the progress of Tet based on chemical structure modification and nanocarrier delivery, aiming to explore more diverse structures to improve the pharmacological activity of Tet and provide ideas to meet clinical needs.

Anti-inflammatory/anti-oxidant properties and the UPLC-QTOF/MS-based metabolomics discrimination of three yellow camellia species.

The species of Camellia nitidissima Chi (CC) and C. euphlebia Merr. ex Sealy (CE) are two most important plant sources for commercialized herbal tea (Jinhuacha) worldwide. However, some other species of camellia genus are also sold as alternatives in market due to the great commercial value. In this study, the similarity and difference of CC and CE as well as C.insularis (CI) are comprehensively compared both in chemistry and pharmacology. Based on the ultraperformance liquid chromatography coupled with a hybrid quadrupole orthogonal time-of-flight mass spectrometer(UPLC-QTOF-MS) analysis, a sequential-optimization based new statistical model has been developed by combining the untargeted metabolomics and fingerprint analyses, and successfully applied for chemical pattern recognition and discrimination of three yellow camellias species. The results indicated that CC, CE and CI could be well discriminated with the optimized chemical combination including quercetin-3-O-rhamnoside (C2), okicamelliaside (C4), Kaempferol 7-O-rhamnoside (C6), Corymboside (C9), asiatic acid-glc-rha-xyl (C11) and 3'-methy-4'-glucoside-ellagic acid (C14). Moreover, the 30 % ethanolic extracts of yellow camellias species presented the optimal activities on anti-inflammation/anti-oxidation in LPS-stimulated Raw264.7 macrophages dose-dependently. The averaged 50 % inhibitory concentrations (IC50) on NO production were 754.68 ± 50.96, 1182.39 ± 22.10, 1527.83 ± 106.24 µg(herb)/mL, and ROS production were 311.70 ± 26.57, 332.64 ± 25.46, 917.60 ± 41.36 µg(herb)/mL for CC, CE and CI, respectively. The results indicated a certain similarity of CC and CE, as well as their significant difference from CI.

[Medication law and mechanism of traditional Chinese medicine in prevention and treatment of epidemic diseases: based on traditional Chinese medicine theory of cold pestilence].

Epidemic diseases have caused huge harm to the society. Traditional Chinese medicine(TCM) has made great contributions to the prevention and treatment of them. It is of great reference value for fighting diseases and developing drugs to explore the medication law and mechanism of TCM under TCM theory. In this study, the relationship between the TCM theory of cold pestilence and modern epidemic diseases was investigated. Particularly, the the relationship of coronavirus disease 2019(COVID-19), severe acute respiratory syndrome(SARS), and influenza A(H1 N1) with the cold pestilence was identified and analyzed. The roles of TCM theory of cold pestilence in preventing and treating modern epidemic diseases were discussed. Then, through data mining and textual research, prescriptions for the treatment of cold pestilence were collected from major databases and relevant ancient books, and their medication laws were examined through analysis of high-frequency medicinals and medicinal pairs, association rules analysis, and cluster analysis. For example, the prescriptions with high confidence levels were identified: "Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Paeoniae Radix Alba" "Glycyrrhizae Radix et Rhizoma-Pinelliae Rhizoma-Bupleuri Radix", and TCM treatment methods with them were analyzed by clustering analysis to yield the medicinal combinations: "Zingiberis Rhizoma-Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma" "Poria-Atractylodis Macrocephalae Rhizoma" "Cinnamomi Ramulus-Asari Radix et Rhizoma" "Citri Reticulatae Pericarpium-Perillae Folium" "Pinelliae Rhizoma-Magnoliae Officinalis Cortex-Atractylodis Rhizoma" "Paeoniae Radix Alba-Angelicae Sinensis Radix-Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Scutellariae Radix-Rhizoma Zingiberis Recens" "Ephedrae Herba-Armeniacae Semen Amarum-Gypsum Fibrosum" "Chuanxiong Rhizoma-Notopterygii Rhizoma et Radix-Angelicae Dahuricae Radix-Platycodonis Radix-Saposhnikoviae Radix". Then, according to the medication law for cold pestilence, the antiviral active components of medium-frequency and high-frequency medicinals were retrieved. It was found that these components exerted the antiviral effect by inhibiting virus replication, regulating virus proteins and antiviral signals, and suppressing protease activity. Based on network pharmacology, the mechanisms of the medicinals against severe acute respiratory syndrome coronavirus(SARS-CoV), 2019 novel coronavirus(2019-nCoV), and H1 N1 virus were explored. It was determined that the key targets were tumor necrosis factor(TNF), endothelial growth factor A(VEGFA), serum creatinine(SRC), epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), mitogen-activated protein kinase 14(MAPK14), and prostaglandin-endoperoxide synthase 2(PTGS2), which were involved the mitogen-activated protein kinase(MAPK) pathway, advanced glycation end-products(AGE)-receptor for AGE(RAGE) pathway, COVID-19 pathway, and mTOR pathway. This paper elucidated the medication law and mechanism of TCM for the prevention and treatment of epidemic diseases under the guidance of TCM theory of cold pestilence, in order to build a bridge between the theory and modern epidemic diseases and provide reference TCM methods for the prevention and treatment of modern epidemic diseases and ideas for the application of data mining to TCM treatment of modern diseases.

Rapid Chemical Profiling of Compound Huanggen Granules and Absorbed Prototypes in Cynomolgus Monkey Plasma by Integrating UHPLC-Q-TOF-MSE Method and Data Post-Processing Strategy.

AIMS: In this study, we aim to establish an integrated research strategy for the rapid chemical profiling of Compound Huanggen Granules (CHG) and absorbed prototypes in plasma by integrating the UHPLC-Q-TOF-MSE method and data post-processing strategy, to provide some valuable research basis for the further studies on the quality control, pharmacokinetics and pharmacodynamics of CHG. BACKGROUND: Compound Huanggen Granules (CHG), a traditional Chinese medicine (TCM) hospital preparation, has long been used in clinical practice for the prevention and treatment of liver fibrosis. However, due to the lack of in vitro chemical and in vivo metabolism studies, its pharmacodynamic material basis is still unrevealed. OBJECTIVE: To simplify the mass data post-processing process and enhance the structural identification efficiency by reducing the possibility of false positive, and rapidly identify the absorbed prototypes in plasma after oral administration of CHG. METHODS: An analytical strategy integrating ultra high-performance liquid chromatography coupled with quadrupletime- of-flight mass spectrometry (UHPLC-Q-TOF-MSE, E represents collision energy) method and data postprocessing strategy based on a self-built in-house components database was established and utilized for the rapid characterization of the multi-constituents of CHG and prototypes in cynomolgus monkey plasma after oral administration. RESULTS: As a result, a total of 81 compounds, including 14 phenolic acids, 6 coumarins, 25 flavonoids, 5 anthraquinones, 5 phenylpropanoids, 15 triterpenoid saponins, and 11 others, were plausibly or unambiguously identified based on their accurate masses, and MS/MS fragment pathways analysis, and also by comparison of retention time and MS data with reference standards. In the in vivo study, according to the extracted ion chromatograms (EICs) of identified components, 34 absorbed prototypical components were rapidly identified in cynomolgus monkey plasma after oral administration. CONCLUSION: It was demonstrated that the data post-processing strategy applied in this study could greatly simplify the data post-processing process and enhance the structural identification efficiency by reducing the possibility of false positives, and the results obtained might be helpful for further studies on the quality control, pharmacokinetics and pharmacodynamics of CHG.

Targeted discovery and characterization of secoiridoid glycosides from Jasminum pentaneurum Hand.-Mazz by ultra-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry based on diagnostic ion and neutral loss filtering strategy.

In this study, we proposed an integrated analytical strategy for the rapid and comprehensive discovery of a specific class of secoiridoid glycosides from a Yao medicine, Jasminum pentaneurum Hand.-Mazz. The strategy fully took advantage of the accuracy of ultra-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry, and the efficiency of diagnostic ion filtering and neutral loss filtering. Twenty-four secoiridoid glycosides, including three known ones and 21 unreported ones, were rapidly discovered and characterized based on the detail analysis of their mass spectrometry data. Particularly, 10-syringicoyl-ligustroside (18) was isolated under the guidance of mass spectrometry analysis. Its chemical structure was elucidated on the basis of extensive spectroscopic data analysis, and absolute configuration was further elucidated by comparison of its experimental and electronic circular dichroism spectra. Furthermore, the mass spectrometry data of 18 was analyzed and the corresponding results indicated that its fragment pathway was fully consistent with the applied diagnostic ion filtering and neutral loss filtering rules, and thus the precision and efficiency of the integrated strategy were validated. The result demonstrated that the proposed integrated strategy could serve as a rapid, accurate, and comprehensive targeted components discovery method to effectively screen out those ingredients of interest from the complex herbal medicines.

[Research progress of Curcuma kwangsiensis root tubers and analysis of liver protection and anti-tumor mechanisms based on Q-markers].

Curcuma kwangsiensis root tuber is a widely used genuine medicinal material in Guangxi, with the main active components of terpenoids and curcumins. It has the effects of promoting blood circulation to relieve pain, moving Qi to relieve depression, clearing heart and cooling blood, promoting gallbladder function and anti-icterus. Modern research has proved its functions in liver protection, anti-tumor, anti-oxidation, blood lipid reduction and immunosuppression. Considering the research progress of C. kwangsiensis root tubers and the core concept of quality marker(Q-marker), we predicted the Q-markers of C. kwangsiensis root tubers from plant phylogeny, chemical component specificity, traditional pharmacodynamic properties, new pharmacodynamic uses, chemical component measurability, processing methods, compatibility, and components migrating to blood. Curcumin, curcumol, curcumadiol, curcumenol, curdione, germacrone, and ß-elemene may be the possible Q-markers. Based on the predicted Q-markers, the mechanisms of the liver-protecting and anti-tumor activities of C. kwangsiensis root tubers were analyzed. AKT1, IL6, EGFR, and STAT3 were identified as the key targets, and neuroactive ligand-receptor interaction signaling pathway, nitrogen metabolism pathway, cancer pathway, and hepatitis B pathway were the major involved pathways. This review provides a basis for the quality evaluation and product development of C. kwangsiensis root tubers and gives insights into the research on Chinese medicinal materials.