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.

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.

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.

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.

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.

Gnetum montanum extract induces apoptosis by inhibiting the activation of AKT in SW480 human colon cancer cells.

CONTEXT: Gnetum montanum Markgr. (Gnetaceae) is used to treat rheumatic arthralgia and bruises in the clinic. OBJECTIVE: To exam the activity and mechanism of G. montanum extract (GME) against colon cancer cells SW480. MATERIALS AND METHODS: The anti-proliferative activity of GME (0-120 µg/mL) on SW480 cells was determined using MTS assay at 24, 48, and 72 h. The in vitro activity of GME (0-120 µg/mL) on SW480 cells was investigated using flow cytometry and western blotting analysis. The in vivo activity of GME was evaluated using xenograft tumour model of zebrafish and nude mice. The chemical composition of GME was detected by using HPLC-MS/MS. RESULTS: The IC50 value SW480 cells viability by GME were 126.50, 78.25, and 50.77 µg/mL, respectively, for 24, 48, and 72 h. The experiments showed that apoptotic cells and G2/M phase cells increased from 20.81 to 61.53% (p < 0.01) and 25.76 to 34.93% with 120 µg/mL GME, respectively. GME also down-regulated the protein expression of P-AKT, P-GSK-3ß, P-PDK1, P-c-Raf, caspase-3, and Bcl-2, and up-regulated the expression cleaved caspase-3, cleaved PARP, and Bax. In vivo study found that GME can significantly inhibit the growth and migration of SW480 cells in xenograft zebrafish. GME reduced the nude mice tumour weight to approximately 32.19% at 28 mg/kg/day and to 53.17% (p < 0.01) at 56 mg/kg/day. Forty-two compounds were identified from the GME. DISCUSSION AND CONCLUSIONS: GME has a significant antitumor effect on colon cancer cells SW480, and it has the potential to be developed as an anticancer agent.

Proteome Analysis of Camellia nitidissima Chi Revealed Its Role in Colon Cancer Through the Apoptosis and Ferroptosis Pathway.

Colon cancer is the third most common cancer in the world with a high mortality rate. At present, surgery combined with radiotherapy and chemotherapy is the primary treatment, but patient prognosis remains poor. Traditional Chinese medicine (TCM) has become a complementary and alternative source of anti-cancer drugs. Camellia nitidissima Chi (CNC) is a TCM used to treat a variety of cancers. However, the role of CNC in cancer remains elusive, and its effect and mechanism on colon cancer have not been reported. Here, we show that CNC exerts an excellent inhibitory effect on colon cancer proliferation and apoptosis induction in vitro and in vivo. We performed label free-based quantitative proteomic analysis to evaluate the HCT116 cells treated with CNC. Our data revealed a total of 363 differentially expressed proteins, of which 157 were up-regulated and 206 down-regulated. Gene Ontology enrichment analysis showed that these proteins were involved in tumor occurrence and development through multiple biological processes such as cell proliferation, cell apoptosis, cell cycle, and cell death. Interestingly, we also found significant changes in ferroptosis pathways. The role of essential proteins glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HMOX1) were verified. CNC decreased the expression of GPX4 and increased the expression of HMOX1 at the mRNA and protein levels in vivo and in vitro. Collectively, these findings reveal that CNC regulates colon cancer progression via the ferroptosis pathway and could be an attractive treatment for colon cancer.

Antiproliferative activity of berberine in HepG2 cells via inducing apoptosis and arresting cell cycle.

The therapeutic targets of berberine for hepatocellular carcinoma (HCC) and its detailed mechanisms remain unexplored. Here, an integration of network pharmacology, proteomic, bioinformatic and in vitro biochemical approach was proposed to reveal therapeutic targets and pathways underlying the antiproliferative activity of berberine against HepG2 cells. Results indicated that berberine caused the cytotoxicity and inhibited the growth of HepG2 cells with IC50 values ranging from 92 µM to 118 µM. Network pharmacology analysis revealed that targeting apoptosis and cell cycle pathways by berberine contributed to its antitumor efficacy against HCC. Proteomic analysis demonstrated that mitochondria-related apoptosis pathways were involved in the cytotoxic action of berberine, as evidenced by the expression of mitochondrial dysfunction-mediated proteins. Moreover, a total of 160 significantly altered proteins were screened, among which AKAP12 presented significantly increased levels under berberine treatment. Bioinformatic analysis of various public datasets showed that expression of AKAP12 in HCC liver tissues was downregulated, emphasizing its role as a tumor suppressor. Immunoblotting validated the increased levels of AKAP12, while co-immunoprecipitation identified its interaction with Cyclin D1. These data, together with flow cytometry analysis, suggested that AKAP12 mediated cell cycle arrest, thereby suppressing cell proliferation. Altogether, the antiproliferative action of berberine in HepG2 cells involves both apoptosis and cell cycle arrest. Regulating AKAP12 signalling by berberine might provide a promising strategy for HCC treatment.

Analysis on oral medication rules of traditional Chinese medicine prescriptions for prevention of COVID-19.

OBJECTIVE: To analyze the medication rules of traditional Chinese medicine (TCM) preventive oral prescriptions for COVID-19. METHODS: The preventive oral prescriptions for COVID-19 published by national and provincial health and wellness committees, administrations of TCM, medical institutions at all levels, medical masters and Chinese medicine experts were collected to establish a database, manual screening was carried out according to the inclusion and exclusion criteria, and frequency statistics, association rule analysis. The mutual information method, entropy hierarchical clustering and other methods were improved through Excel and the TCM inheritance auxiliary platform V2.5 to mine the rules and characteristics of medication. RESULTS: The selected 157 prescriptions contained a total of 130 TCMs. The top five TCMs with the highest use frequency were Glycyrrhizae Radix et Rhizoma (86), Astragali Radix (80), Lonicerea Japonicae Flos (70), Atractylodis Macrocephalae Rhizoma (62), Saposhnikoviae Radix (60). In accordance with TCM efficacy classification, most of them were medicines for qi-tonifying (279), followed by medicines for clearing heat and drying dampness (163), dispelling pathogenic wind-cold (126), resolving dampness (111), as well as dispelling pathogenic wind-heat (99). The characteristics of four-natures of the selected medicines are as follows: most of them were cold (59), followed by warm (38) and mild (21). In terms of five-taste, most of them were sweet (26) and acrid-and-bitter (24), followed by sweet-and-bitter (20), bitter (20) and acrid (15). For the meridian attribution, the five-zang organs and six-fu organs were all involved, most of them attributed to lung meridian (80), followed by stomach meridian (57) and spleen meridian (40). Based on association rule analysis, 12 commonly used medicine combinations with two or three TCMs were found. The commonly used medicinal pairs included Astragali Radix and Saposhnikoviae Radix (51), Astragali Radix and Atractylodis Macrocephalae Rhizoma (46), Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (43), Astragali Radix and Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (38), Forsythiae Fructus and Astragali Radix (37), and so on. In addition, 14 core combinations of medicines were obtained by complex system entropy cluster analysis, on this basis, six new prescriptions were screened out based on unsupervised entropy hierarchical clustering analysis. According to The Catalogue of Edible Traditional Chinese Medicinal Materials, Traditional Chinese Medicinal Materials for Health Food, and New Resources of Food published by National Health Commission of the People's Republic of China, there are 35 species belonging to the group of edible traditional Chinese medicinal materials, 20 species belonging to the group of new resources of food, 31 species belonging to the group of traditional Chinese medicinal materials for health food, 19.11% of the preventive oral prescriptions for COVID-19 were composed of the medicines belonging to the above three groups. Besides, there are 11 toxic species, and 24.84% of the preventive oral prescriptions for COVID-19 contained toxic TCMs. CONCLUSION: We found that invigorating qi and resolving dampness were the main treatment used to prevent for COVID-19, combined with the methods for strengthening vital energy and eliminating pathogenic factors. Most of the preventive oral prescriptions for COVID-19 were treated in lung, spleen and stomach meridians. In the process of selecting prescriptions and using TCMs to prevent for COVID-19, the safety of preventive medicines was also emphasized. And the theory of "Preventive Treatment of Disease" was embodied in these preventive oral prescriptions for COVID-19. For the prescriptions containing toxic TCMs, special attention should be paid to their safety in clinical application.

Analysis on application law of dampness-removing traditional Chinese medicines in treatment of coronavirus disease 2019.

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) has been diagnosed as an epidemic disease characterized by cold and dampness pathogens in TCM clinic. Due to many Chinese medicines with different functions were used in the treatment of COVID-19, it is very important to find the law of application of damp-removing traditional Chinese medicine with high frequency application, with view to providing a reference for the use and research of Chinese medicine to further control the pandemic. METHODS: The publicly released diagnosis and treatment programs issued by the National Health Commission and Health Commission of provinces, autonomous regions and municipalities, and Chinese herbs prescription information in these were collected, a database was established, and Excel and Graphpad 8.0 software were used to analyze the frequency of use of various Chinese medicines, the frequency and property characters including five flavors (bitter, pungent, sweet, sour, and salty) and four natures (warm, hot, cool, and cold) and channel tropisms of Chinese medicine for removing dampness. RESULTS: A total of 137 prescriptions of Chinese medicine for treating COVID-19 were collected, including 178 TCMs showing functions of resolving phlegm, relieving cough and asthma, resolving dampness, clearing damp and inducing dieresis, clearing heat, tonifying deficiency, and relieving exterior syndrome, in which the TCMs with the first four functions that we called the dampness-removing TCMs, accounted for 35.78%. Also a number of TCMs in the rest functions showed removing-dampness. The first four functions were divided into subfunctions including aromatic resolving dampness, clearing heat and drying dampness, drying dampness and tonifying spleen qi, drying dampness and removing phlegm, inducing diuresis and relieving swelling, inducing diuresis and relieving exterior syndrome. Among them, the most frequently used TCMs was Ephedrae Herba, followed by Citri Reticulatae Pericarpium, Pogostemonis Herba, Pinelliae Rhizoma, Poria, Scutellariae Radix, and Atractylodis Rhizoma. The property character analysis in the dampness-removing TCMs showed that bitter and pungent were largely present and sour and astringent were absent, warm and hot were dominant; And the lung, spleen, stomach, large intestine, bladder were main channel tropisms. CONCLUSION: Dampness-removing TCMs are the first important type of traditional Chinese medicine to be considered in the treatment of COVID-19 in Chinese medicine. The application of dampness-removing TCMs in the treatment of COVID-19 needs to be combined with its application law. This study may provide meaningful and useful information on further research to investigate the effective compounds from the dampness-removing Chinese medicine with high frequency application, and also provide a reference for the clinical treatment of COVID-19 accurately against dampness evil with dampness-removing traditional Chinese medicines.

Identifying Active Compounds and Mechanism of Camellia nitidissima Chi on Anti-Colon Cancer by Network Pharmacology and Experimental Validation.

Camellia nitidissima Chi (CNC) is a traditional Chinese medicine (TCM) with anticancer property. However, its underlying mechanisms of anti-colon cancer (CC) remain unknown. Therefore, a systematic approach is proposed in the present study to elucidate the anticancer mechanisms of CNC based on network pharmacology and experimental validation. Initially, the potential active ingredients of CNC were verified via the TCMSP database based on the oral bioavailability (OB) and drug-likeness (DL) terms. Hub targets of CNC were acquired from SwissTarget prediction and TCMSP databases, and target genes related to CC were gathered from GeneCards and OMIM databases. Cytoscape was used to establish the compound-target networks. Next, the hub target genes collected from the CNC and CC were parsed via GO and KEGG analysis. Results of GO and KEGG analysis reveal that quercetin and luteolin in CNC, VEGFA and AKT1 targets, and PI3K-Akt pathway were associated with the suppression of CC. Besides, the result of molecular docking unveils that VEGFA demonstrates the most powerful binding affinity among the binding outcomes. This finding was successfully validated using in vitro HCT116 cell model experiment. In conclusion, this study proved the usefulness of integrating network pharmacology with in vitro experiments in the elucidation of underlying molecular mechanisms of TCM.