Hepatoprotective Effect of Medicine Food Homology Flower Saffron against CCl4-Induced Liver Fibrosis in Mice via the Akt/HIF-1α/VEGF Signaling Pathway.

Liver fibrosis refers to a complex inflammatory response caused by multiple factors, which is a known cause of liver cirrhosis and even liver cancer. As a valuable medicine food homology herb, saffron has been widely used in the world. Saffron is commonly used in liver-related diseases and has rich therapeutic and health benefits. The therapeutic effect is satisfactory, but its mechanism is still unclear. In order to clarify these problems, we planned to determine the pharmacological effects and mechanisms of saffron extract in preventing and treating liver fibrosis through network pharmacology analysis combined with in vivo validation experiments. Through UPLC-Q-Exactive-MS analysis, a total of fifty-six nutrients and active ingredients were identified, and nine of them were screened to predict their therapeutic targets for liver fibrosis. Then, network pharmacology analysis was applied to identify 321 targets for saffron extract to alleviate liver fibrosis. Functional and pathway enrichment analysis showed that the putative targets of saffron for the treatment of hepatic fibrosis are mainly involved in the calcium signaling pathway, the HIF-1 signaling pathway, endocrine resistance, the PI3K/Akt signaling pathway, lipid and atherosclerosis, and the cAMP signaling pathway. Based on the CCl4-induced liver fibrosis mice model, we experimentally confirmed that saffron extract can alleviate the severity and pathological changes during the progression of liver fibrosis. RT-PCR and Western blotting analysis confirmed that saffron treatment can prevent the CCl4-induced upregulation of HIF-1α, VEGFA, AKT, and PI3K, suggesting that saffron may regulate AKT/HIF-1α/VEGF and alleviate liver fibrosis.

Identification and Characterization of CtUGT3 as the Key Player of Astragalin Biosynthesis in Carthamus tinctorius L.

Safflower (Carthamus tinctorius L.) is a multipurpose economic crop that is distributed worldwide. Flavonoid glycosides are the main bioactive components in safflower, but only a few UDP-glycosyltransferases (UGT) have been identified. Three differentially expressed UGT genes related with the accumulation of 9 flavonoid O-glycosides were screened from metabolomics and transcriptome analysis. Safflower corolla protoplasts were used to confirm the glycosylation ability of UGT candidates in vivo for the first time. The astragalin content was significantly increased only when CtUGT3 was overexpressed. CtUGT3 also showed flavonoid 3-OH and 7-OH glycosylation activities in vitro. Molecular modeling and site-directed mutagenesis revealed that G15, T136, S276, and E384 were critical catalytic residues for the glycosylation ability of CtUGT3. These results demonstrate that CtUGT3 has a flavonoid 3-OH glycosylation function and is involved in the biosynthesis of astragalin in safflower. This study provides a reference for flavonoid biosynthesis genes research in nonmodel plants.

Ghost cell odontogenic carcinoma: A rare case report and review of literature.

RATIONALE: Ghost cell odontogenic carcinoma is a rare malignant odontogenic carcinoma characterized by the presence of ghost cells. It has a nonspecific clinical and radiographic presentation and can be locally destructive and invasive, sometimes with distant metastases. However, no effective systemic therapy is currently recommended for such patients. PATIENT CONCERNS: The patient has been unable to undergo surgery or radiotherapy again. Therefore, he was referred to our department for a more aggressive, multimodal systematic treatment program. DIAGNOSES: The histopathological examination was morphologically suggestive of ghost cell odontogenic carcinomas. INTERVENTIONS: We report a case of locally invasive primary inoperable odontogenic shadow cell carcinoma in a 31-year-old Chinese man who achieved treatment with Toripalimab and chemotherapy, followed by Toripalimab maintenance therapy after 6 cycles. OUTCOMES: He achieved partial remission after treatment. The quality of life significantly improved after treatment. There were no grade 3/4 treatment-related adverse events during treatment. LESSONS: This case presented that Toripalimab and chemotherapy may be a safe and effective systemic therapy for ghost cell odontogenic carcinoma.

Exploring the mechanism of Taohong Siwu Decoction on the treatment of blood deficiency and blood stasis syndrome by gut microbiota combined with metabolomics.

BACKGROUND: Taohong Siwu Decoction (THSWD) is a prescription which included in the "List of Ancient Classic Prescriptions (First Batch)" issued by the National Administration of Traditional Chinese Medicine (TCM) and the National Medical Products Administration of the People's Republic of China. THSWD is effective and widely applied clinically for many diseases caused by blood deficiency and stasis syndrome in TCM, such as primary dysmenorrhea, menopausal syndrome, coronary heart disease, angina pectoris, and diabetes. METHODS: The TCM model of blood deficiency and blood stasis syndrome was prepared by ice water bath combined with cyclophosphamide, and the rats were randomly divided into control group, blood deficiency, and blood stasis model group, positive group, and THSWD treatment group. Pharmacodynamics measured the blood routine, blood coagulation, and other related indexes in rats. UHPLC-MS technology was used to analyze the changes in the fingerprints of metabolites in the plasma of rats with blood deficiency and blood stasis syndrome, and combined with mass spectrometry information and public database retrieval, to find potential biomarkers for screening metabolites. At the same time, 16S rDNA sequencing technology was used to identify intestinal flora, and statistical analysis was used to find differences in strain diversity between groups. RESULTS: THSWD administration can significantly improve the physical signs, blood routine, and hematopoietic factors caused by the blood deficiency and blood stasis syndrome model, and improve the symptoms of blood deficiency. The results of the general pharmacological studies showed THSWD groups improved changes in blood plasma viscosity and coagulation-related factors caused by modeling, and improved coagulation function significantly. The metabolomic analysis found that compared to the model group, THSWD exerted better effects on ß-alanine, taurine, L-tyrosine, L-arginine, Eugenol, sodium deoxycholate, and deethylatrazine. Twenty-three potential differential metabolites showed intervention effects, mainly involved in eight metabolic pathways, including amino acid metabolism, taurine and hypotaurine metabolism, vitamin metabolism, and nucleotide metabolism. Gut microbiota data showed that, compared to the control group, the relative abundance and value of Firmicutes and Bacteroidota of the blood deficiency and blood stasis model group was significantly reduced, while the relative abundance of Actinobacteria, Spirochaetota, Proteobacteria, Campilobacterota, and other pathogenic bacteria was significantly increased. Following THSWD intervention, the abundance of beneficial bacteria increased, and the abundance of pathogenic bacteria decreased. Correlation analysis between the gut microbiota and differential metabolites showed that the two are closely related. THSWD affected the host blood system through mutual adjustment of these two factors, and improved blood deficiency and blood stasis syndrome in rats. CONCLUSION: The blood deficiency and blood stasis syndrome model of TCM disease caused by ice bath combined with cyclophosphamide lead to changes in the pharmacology, metabolomics, and gut microbiota. The intervention of THSWD can improve the symptoms caused by blood deficiency and blood stasis. The mechanism is mainly through the regulation of platelet function and amino acid metabolism.

Indistinct assessment of the quality of traditional Chinese medicine in precision medicine exampling as safflower.

The quality of traditional Chinese medicine (TCM) guarantees its clinical efficacy. Although advanced analytical techniques and methods can accurately determine the content of chemical components in TCM, it is difficult to accurately determine its clinical efficacy. In addition, the current analytical methods and technologies are complex and have difficulty meeting the requirements of a rapid, accurate and convenient determination of TCM quality. In this study, we first propose the concept of "indistinct" evaluation of the quality of TCM, that is, combining biological potency with character evaluation, quantifying the character evaluation, and preparing the safflower quality grade evaluation card based on the character analysis, which provides research ideas and methods for the rapid and accurate evaluation of the quality of TCM. We determined the biological potency of different batches of safflower based on the in vitro antiplatelet aggregation model and divided the safflower samples into two grades based on the biological potency. We further collected the color information of different grades of safflower samples, quantified the color information of different grades of safflower, drew a quality grade evaluation card for the rapid judgment of safflower quality grade and verified its accuracy by pharmacodynamic evaluation. To further analyze the differences in the material basis of different grades of safflower, the LC-MS method was used to simultaneously determine the contents of 19 chemical components, such as myricetin, in different grades of safflower samples to analyze the differences in the material basis of different grades of safflower. The result shows that the different grades of safflower exhibited significant differences in color. The pharmacodynamic results show that the quality evaluation card prepared based on color information can accurately evaluate quality, and the effect of first-class safflower is significantly better than that of second-class safflower. The chemical analysis results of different grades of safflower show that there are also significant differences between them, among which hypericin, 6-hydroxyapin-6-O-glucose-7-O-glucuronide, 6-hydroxykaempferol-3,6-O-diglucoside-7-O-glucuronic acid glycoside, 6-hydroxykaempferol-3,6,7-tri-O-glucoside and hydroxysafflower yellow A exhibit significant differences, which may be the main differentiating components of different grades of safflower. This study preliminarily confirmed that the "indistinct" evaluation of the quality of TCM based on character analysis is accurate and scientific, and the quality evaluation card prepared can accurately judge the quality of TCM, providing a reference for the rapid application of TCM character evaluation.

Mechanism of platelet activation and potential therapeutic effects of natural drugs.

BACKGROUND: Cardiovascular disease is one of the most concerning chronic diseases in the world. Many studies have shown that platelet overactivation is a very important factor in the occurrence and development of cardiovascular diseases. At present, the widely used antiplatelet drugs have some defects, such as drug resistance and adverse reactions. PURPOSE: The purpose of this article is to summarize the main mechanisms and pathways of platelet activation, the main targets of antiplatelet aggregation, and the antiplatelet aggregation components of natural drugs and their mechanisms of action to provide new research ideas for the development and application of antiplatelet drugs. STUDY DESIGN AND METHODS: In this review, we systematically searched the PubMed, Google Scholar, Web of Science, and CNKI databases and selected studies based on predefined eligibility criteria. We then assessed their quality and extracted data. RESULTS: ADP, AA, THR, AF, collagen, SDF-1α, and Ca2+ can induce platelet aggregation and trigger thrombosis. Natural drugs have a good inhibitory effect on platelet activation. More than 50 kinds of natural drugs and over 120 kinds of chemical compounds, including flavonoids, alkaloids, saponins, terpenoids, coumarins, and organic acids, have significantly inhibited platelet activation activity. The MAPK pathway, cGMP-PKG pathway, cAMP-PKA pathway, PI3K-AKT pathway, PTK pathway, PLC pathway, and AA pathway are the main mechanisms and pathways of platelet activation. CONCLUSION: Natural drugs and their active ingredients have shown good activity and application prospects in anti-platelet aggregation. We hope that this review provides new research ideas for the development and application of antiplatelet drugs.

Machine learning and bioinformatics-based insights into the potential targets of saponins in Paris polyphylla smith against non-small cell lung cancer.

Background: Lung cancer has the highest mortality rate among cancers worldwide, and non-small cell lung cancer (NSCLC) is the major lethal factor. Saponins in Paris polyphylla smith exhibit antitumor activity against non-small cell lung cancer, but their targets are not fully understood. Methods: In this study, we used differential gene analysis, lasso regression analysis and support vector machine recursive feature elimination (SVM-RFE) to screen potential key genes for NSCLC by using relevant datasets from the GEO database. The accuracy of the signature genes was verified by using ROC curves and gene expression values. Screening of potential active ingredients for the treatment of NSCLC by molecular docking of the reported active ingredients of saponins in Paris polyphylla Smith with the screened signature genes. The activity of the screened components and their effects on key genes expression were further validated by CCK-8, flow cytometry (apoptosis and cycling) and qPCR. Results: 204 differential genes and two key genes (RHEBL1, RNPC3) stood out in the bioinformatics analysis. Overall survival (OS), First-progression survival (FP) and post-progression survival (PPS) analysis revealed that low expression of RHEBL1 and high expression of RNPC3 indicated good prognosis. In addition, Polyphyllin VI(PPVI) and Protodioscin (Prot) effectively inhibited the proliferation of non-small cell lung cancer cell line with IC50 of 4.46 µM ± 0.69 µM and 8.09 µM ± 0.67µM, respectively. The number of apoptotic cells increased significantly with increasing concentrations of PPVI and Prot. Prot induces G1/G0 phase cell cycle arrest and PPVI induces G2/M phase cell cycle arrest. After PPVI and Prot acted on this cell line for 48 h, the expression of RHEBL1 and RNPC3 was found to be consistent with the results of bioinformatics analysis. Conclusion: This study identified two potential key genes (RHEBL1 and RNPC3) in NSCLC. Additionally, PPVI and Prot may act on RHEBL1 and RNPC3 to affect NSCLC. Our findings provide a reference for clinical treatment of NSCLC.

Comprehensive review of two groups of flavonoids in Carthamus tinctorius L.

Safflower (Carthamus tinctorius L.) is cultivated in various countries for the flavonoid compounds it contains. These flavonoids have been used in many industries as drugs and/or dyes. Over 60 flavonoids have been isolated from safflower. These flavonoids can be divided into two groups: special and common, both of which are active pharmaceutical ingredients efficacious in the treatment of cardiovascular and cerebrovascular diseases. Gene functions have been studied to figure out the biosynthesis of flavonoids in safflower. However, there is no comprehensive summary of the flavonoids in safflower. Research was recognised through systematic searches of ScienceDirect, PubMed, Web of Science, and CNKI databases by searching terms of "Carthamus tinctorius L.", "safflower", "flavonoid", "pharmacology", and "gene". More than 200 research reports were included after eligibility checks. This study summarizes the application of flavonoids in medicine and other industries. Comprehensively collects the chemical structure information of the two groups of flavonoids, and organic acids, alkaloids, spermidine, polyacetylene, and polysaccharides. The mechanism of two groups of flavonoids in treatment of cardiovascular and cerebrovascular diseases was describe in detail, and pharmacological mechanisms of protecting liver, lung and bone, and anti-cancer and anti-inflammatory were also summarised. Besides, the study updated the latest information on the molecular biology of safflower flavonoids. It is found that two groups of flavonoids in safflower have obvious differences in application, chemical structure, pharmacological mechanism, and biosynthetic pathway. It is hoped that this summative research will provide a new insight to flavonoids research in safflower.

Study on the potential mechanism, therapeutic drugs and prescriptions of insomnia based on bioinformatics and molecular docking.

Insomnia is a very common disease worldwide. It seriously affects the quality of human life and even endangers health. Traditional Chinese medicine (TCM) has unique advantages in the intervention and treatment of insomnia. However, its underlying mechanism has yet to be elucidated. This study was performed to explore the potential biomarkers and mechanisms of insomnia, and treatment TCM and classical prescriptions. The gene microarray data of insomnia is downloaded and preprocessed. Differentially expressed genes (DEGs) and GO and KEGG enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed. Small molecule drugs for curing insomnia were identified using cMap and CTD databases. We searched the TCM corresponding to small molecule drugs and the classic prescriptions corresponding to TCM by the TCMSP database. We constructed a network of "ingredient-TCM-classic prescriptions". The molecular docking was performed to validate the screening results. We obtained a total of 124 DEGs, including 78 up-regulated genes, 46 down-regulated genes, 10 Hub genes and 3 key modules. A total of 125 significant GO entries and 15 significant KEGG were enriched (P < 0.05). The main biological processes involve neuronal apoptosis, autophagy, cell growth and apoptosis, etc. These signaling pathways may be involved in molecular regulatory mechanisms of insomnia, such as autophagy regulation, Alzheimer's disease, pathways to neurodegenerative diseases and neurotrophic factor signaling pathways. We identified 10 traditional Chinese medicines and 2 classical prescriptions of potential value. In addition, the molecular docking results indicated that small molecule ligands were nicely bound to the Hub gene, and the binding affinity ranged from -7.6 to -9.7 kcal/mol. This study provides a foundation for the clinical treatment of insomnia, explains the molecular mechanisms, and efficiently develops TCM and classical prescriptions.

In Silico Identification and Validation of Cuproptosis-Related LncRNA Signature as a Novel Prognostic Model and Immune Function Analysis in Colon Adenocarcinoma.

Background: Colon adenocarcinoma (COAD) is the most common subtype of colon cancer, and cuproptosis is a recently newly defined form of cell death that plays an important role in the development of several malignant cancers. However, studies of cuproptosis-related lncRNAs (CRLs) involved in regulating colon adenocarcinoma are limited. The purpose of this study is to develop a new prognostic CRLs signature of colon adenocarcinoma and explore its underlying biological mechanism. Methods: In this study, we downloaded RNA-seq profiles, clinical data and tumor mutational burden (TMB) data from the TCGA database, identified cuproptosis-associated lncRNAs using univariate Cox, lasso regression analysis and multivariate Cox analysis, and constructed a prognostic model with risk score based on these lncRNAs. COAD patients were divided into high- and low-risk subgroups based on the risk score. Cox regression was also used to test whether they were independent prognostic factors. The accuracy of this prognostic model was further validated by receiver operating characteristic curve (ROC), C-index and Nomogram. In addition, the lncRNA/miRNA/mRNA competing endogenous RNA (ceRNA) network and protein−protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). Results: We constructed a prognostic model based on 15 cuproptosis-associated lncRNAs. The validation results showed that the risk score of the model (HR = 1.003, 95% CI = 1.001−1.004; p < 0.001) could serve as an independent prognostic factor with accurate and credible predictive power. The risk score had the highest AUC (0.793) among various factors such as risk score, stage, gender and age, also indicating that the model we constructed to predict patient survival was better than other clinical characteristics. Meanwhile, the possible biological mechanisms of colon adenocarcinoma were explored based on the lncRNA/miRNA/mRNA ceRNA network and PPI network constructed by WGCNA. Conclusion: The prognostic model based on 15 cuproptosis-related lncRNAs has accurate and reliable predictive power to effectively predict clinical outcomes in colon adenocarcinoma patients.

[UPLC fingerprint and determination of five components of substance benchmark of classical prescription Shentong Zhuyu Decoction].

Fingerprints of 18 batches of substance benchmark of Shentong Zhuyu Decoction(SZD) were established by UPLC under the following conditions: Waters Sun Fire C_(18) column(3.0 mm×150 mm, 3.5 µm), column temperature of 35 ℃, gradient elution with mobile phase of acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) at the flow rate of 0.4 mL·min~(-1), and detection by wavelength switching. A total of 16 common peaks were identified. The similarities among the fingerprints were calculated by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) and the result showed they were in the range of 0.911-0.988. Based on the 16 common peaks, cluster analysis(CA), principal component analysis(PCA), and partial least square discriminant analysis(PLS-DA) all categorized the 18 batches of samples into two groups(S1, S2, S5-S8, S14, and S17 in one group, and S1, S2, S5-S8, S14, and S17 in another), and 11 most influential components were screened. Five known components with great difference among samples(hydroxysafflor yellow A, ferulic acid, benzoic acid, ecdysone, and ammonium glycyrrhizinate) were determined. The combination of multi-component content determination and fingerprints can reflect the overall cha-racteristics of the primary standards of SZD, which is simple, feasible, reproducible, and stable. This study can serve as a reference for the quality control of the primary standards of SZD.

A comparative study on the traditional versus modern yellow rice wine processing methods using Taohong Siwu Decoction for pharmaceutical production.

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (THSWD) is based on the "First Recipe of Gynecology." It is widely used in various blood stasis and deficiency syndromes, mainly in gynecological blood stasis, irregular menstruation, and dysmenorrhea. THSWD has great demand in traditional Chinese medicine (TCM), gynecology, orthopedics, and internal medicine. According to classical records, three medicinal materials, namely Rehmanniae radix, Angelica sinensis, and Carthamus tinctorius, used in THSWD need to be "washed with yellow rice wine." In the study of TCM prescriptions, the processing methods of medicinal materials not only needed to follow traditional records but also should consider modern technical conditions. Many medicinal materials in the repertoire of classical prescriptions involve yellow rice wine processing. Determining the processing method for medicinal materials is a key and difficult problem in the research and development of classical prescriptions. AIM OF THE STUDY: With THSWD as the representative, this study analyzed differences between no processing method, the modern processing method of "stir-frying the materials with yellow rice wine," and the traditional processing method of "washing with yellow rice wine." We focused on three aspects: composition, efficacy, and endogenous metabolism. This study aimed to provide a reference for research on the processing methods of medicinal materials used in classical prescriptions. MATERIALS AND METHODS: UPLC-Q-Orbitrap HRMS was used to quickly identify and classify the main chemical compounds of THSWD. A model of primary dysmenorrhea (PD) was established using estradiol benzoate combined with oxytocin. The latent period and writhing time; the levels of serum PGF2α, PGE2, ET-1, and ß-EP; and the pathological sections of the uterus were observed to determine their pharmacodynamic differences. GC-TOF/MS was used to analyze the differences in serum metabolites in rats. RESULTS: A total of 54 active compounds were identified, and the results showed that catalpol and rehmapicroside disappeared following yellow rice wine processing. Compared with materials processed by the traditional method, the relative contents of 15 components, such as 5-hydroxymethylfurfural and digitalis C, increased in materials processed by the modern method. However, the relative contents of 16 components, such as hydroxysafflor yellow A, verbascoside, and ferulic acid, decreased in the modern processing method. The modern and classic processing methods acted on PD through different metabolic pathways. THSWD obtained by classical processing methods mainly treated PD through anti-inflammatory and estrogen metabolism pathways, whereas THSWD obtained by modern processing methods mainly treated PD through anti-inflammatory metabolic pathways. CONCLUSION: The study revealed the differences in different yellow rice wine processing methods in terms of chemical composition of the THSWD obtained, as well as the mechanisms of action for the treatment of PD. This study provides a reference for the clinical application of THSWD and development of classical prescription preparations.

A systematic review on botany, processing, application, phytochemistry and pharmacological action of Radix Rehmnniae.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Rehmanniae (RR) is the tuber root of Rehmannia glutionsa Libosch, which was firstly recorded in Shennong's Classic of Materia Medica (⟪⟫). RR is a non-toxic and wide used traditional Chinese medicine. RR has the effect of clearing heat, generating essence, cooling blood, stopping bleeding, nourishing yin and blood, and filling marrow. It is used in clinic in the form of processed decoction pieces, including Dry Radix Rehmnniae (DRR) and Rehmanniae Radix Praeparata (RRP). The application of RR in traditional Chinese medicine (TCM) prescriptions can treat various diseases, such as anemia, irregular menstruation, deficiency of liver yin, renal failure and so on. AIM OF REVIEW: This paper aims to provide a comprehensive and productive review of RR, which mainly contains botanical characteristics, processing methods, traditional application, chemical composition, quality control and pharmacological action. MATERIALS AND METHODS: Literature search was conducted through the Web of Science, Baidu Scholar, ScienceDirect, PubMed, CNKI, and WanFang DATA using the keywords "Radix Rehmnniae", "Rehmanniae Radix Praeparata", "processing", "clinical application", "chemical composition", "quality control", and "pharmacological action". In addition, information was collected from relevant textbooks, reviews, and documents. RESULTS: RR is a traditional Chinese herbal medicine with clinical value and rich resources. More than 100 components have been isolated and identified from RR. It has multiple pharmacological actions, such as hemostasis, antioxidation, anti-osteoporosis, lowering blood sugar, improving renal function, anti-inflammation, protecting neuronal function, antidepression and anti-anxiety. DRR and RRP are two different processed products of RR. After processing, there are great changes in property, taste, efficacy, clinical application, chemical composition and pharmacological action. At present, identifying chemical constituents of RR and its medicinal value has been deeply studied. However, there is a lack of research on the reasons for the differences in pharmacological effects between DRR and RRP. The reasons for these differences need to be further verified. Catalpol, the active component of RR, has been studied extensively in the literature, but the pharmacological effects of catalpol cannot represent the pharmacological effects of the whole RR. In the future, effective components such as rehmannioside D, polysaccharide, total glycosides, and effective parts in RR need to be further studied and developed. The pharmacodynamic material basis and mechanism of RR need to be further discussed. The scientific connotation and processing methods of RRP need to be studied and standardized.

Traditional Chinese Medicine for adjuvant treatment of breast cancer: Taohong Siwu Decoction.

The high incidence of breast cancer is the greastest threat to women' health all over the world. Among them, HER-2 positive breast cancer has the characteristics of high malignancy, easy recurrence and metastasis, and poor prognosis. Traditional Chinese medicine (TCM) has a rich theoretical basis and clinical application for breast cancer. TCM believes that blood stasis syndrome is one of the important pathogenesis of breast formation and development. Taohong Siwu Decoction (TSHWD) is based on the "First Prescription of Gynecology" Siwu Decoction. It is widely used in various blood stasis and blood deficiency syndromes, mainly in gynecological blood stasis. Clinical studies have found that THSWD can treat breast cancer by reducing blood vessel and lymphangiogenesis with auxiliary chemotherapy. In this study, we aim to explore the material basis and mechanism of THSWD in the treatment of HER-2 positive breast cancer through literature review and network pharmacology studies. Through a literature review of the traditional application, chemical composition of Chinese herbal medicine of THSWD, as well as its clinical reports and pharmacological research on breast cancer treatment. Meanwhile, we conducted "component-pathway-target" network through network pharmacology reveals the main material basis, possible targets and pathways of THSWD in inhibiting HER-2 positive breast cancer. Literature review and network pharmacology research results had predicted that, baicalein, kaempferol, caffeic acid, amygdalin, quercetin, ferulic acid, gallic acid, catalpol, hydroxysafflor yellow A, paeoniflorin in THSWD are the main effective chemical composition. THSWD regulates 386 protein targets and 166 pathways related to breast cancer. The molecular mechanism is mainly to improve the microenvironment of tumor cells, regulate the process of tumor cell EMT, and inhibit tumor cell proliferation and metastasis. This study revealed the mechanism of action of THSWD in the treatment of HER-2 positive breast cancer through literature review and network pharmacology studies, providing a scientific basis for clinical application.

Integrated serum pharmacochemistry and network pharmacological analysis used to explore possible anti-rheumatoid arthritis mechanisms of the Shentong-Zhuyu decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Shentong-Zhuyu decoction (STZYD) has been recognized by the Chinese National Administration of Traditional Chinese Medicine (TCM) as a classic TCM formula. Use of STZYD has shown a satisfactory clinical therapeutic outcome for rheumatoid arthritis (RA); despite this, its bioactive chemical composition and relevant mechanism(s) of this action have not been clearly elucidated. AIM OF THE STUDY: To explore the bioactive chemical composition of STZYD used for RA treatment and its possible mechanism(s) of action. MATERIALS AND METHODS: Serum pharmacochemistry mediated by the UPLC-Q-Exactive MS/MS method was employed to identify the absorbed phytochemical compounds in serum derived from STZYD, which were commonly considered as the potential bioactive compounds. And then, these components were used to construct a compound-target network for RA using a network pharmacology approach, to predict the possible biological targets of STZYD along with potential signaling pathways. Afterwards, we established a Complete Freund's adjuvant (CFA)-induced RA rat model, and observed the anti-RA effect of STZYD by a series of indexes, including foot swelling, ankle diameter, arthritis score, morphological and radiographic analysis, serum inflammatory factors, and histopathological analysis of synovial tissues. Particularly, the predicted pathway by the combination of serum pharmacochemistry and network pharmacology was further validated using RT-qPCR, Western blot, and immunohistochemical analyses in animal experiment. RESULTS: Totally, 38 compounds derived from STZYD have been identified by serum sample analysis. Based on it, 387 genes related to these identified compounds in STZYD and 3807 genes related to RA were collected by network pharmacology. Critically, KEGG analysis indicated that the PI3K/AKT signaling pathway was recommended as one of the main pathway related to anti-RA effect of STZYD. Experimentally, STZYD significantly alleviated CFA-induced arthritis without any visible side-effects. Compared to the RA model group without any treatment, the treatment of STZYD significantly reduced the expression of both mRNA and protein targets in the PI3K/AKT signaling pathway. Furthermore, this result was also corroborated by immunohistochemistry analysis. All these studies could effectively corroborate the predicted result as above, suggested that the feasibility of this integrated strategy. CONCLUSION: This study provided a useful strategy to identify bioactive compounds and the potential mechanisms for TCM formula by integrating serum pharmacochemistry and network pharmacology.

Oral Nano Drug Delivery Systems for the Treatment of Type 2 Diabetes Mellitus: An Available Administration Strategy for Antidiabetic Phytocompounds.

In view of the worldwide serious health threat of type 2 diabetes mellitus (T2DM), natural sources of chemotherapies have been corroborated as the promising alternatives, with the excellent antidiabetic activities, bio-safety, and more cost-effective properties. However, their clinical application is somewhat limited, because of the poor solubility, instability in the gastrointestinal tract (GIT), low bioavailability, and so on. Nowadays, to develop nanoscaled systems has become a prominent strategy to improve the drug delivery of phytochemicals. In this review, we primarily summarized the intervention mechanisms of phytocompounds against T2DM and presented the recent advances in various nanosystems of antidiabetic phytocompounds. Selected nanosystems were grouped depending on their classification and structures, including polymeric NPs, lipid-based nanosystems, vesicular systems, inorganic nanocarriers, and so on. Based on this review, the state-of-the-art nanosystems for phytocompounds in T2DM treatment have been presented, suggesting the preponderance and potential of nanotechnologies.

[Prescription compatibility connotation and action mechanism of Siwu Decoction in treating primary dysmenorrhea].

The aim of this paper was to study the prescription compatibility connotation in the treatment of primary dysmenorrhea(PD) and verify the mechanism as predicted by network pharmacology of Siwu Decoction(SWD). Mice PD model was constructed by using estradiol benzoate-oxytocin. PD mice were randomly divided into 8 groups, namely normal group, model group, positive group, complete formula group, Rehmanniae Radix Praeparata-free group, Paeoniae Radix Alba-free group, volatile oil-free group, Chuan-xiong Rhizoma and Angelicae Sinensis Radix-free group. Latent time, writhing times, inhibition rate, prostaglandin F_2_α(PGF_2_α) and prostaglandin E_2(PGE_2) levels in serum, endothelin-1, Ca~(2+), expression levels of prostaglandin synthase 2 G/H(PTGS2), estrogen receptor(ESR1), glucocorticoid receptor gene(NR3 C1) mRNA and protein expression levels in the uterus homogenate and pathological changes of uterine tissue were index to explore the prescription compatibility connotation and verify the mechanism of SWD in the treatment of PD. Compared with the extraction liquid of the whole recipe, the effect of Rehmanniae Radix Praeparata-free group and Paeoniae Radix Alba-free group with volatile oil were slightly lower, the effect of essential oil-free group was significantly lower, and the effect of Chuanxiong Rhizoma and Angelicae Sinensis Radix-free group was worse than that of the whole recipe. The relative expression levels of PTGS2 protein and mRNA were significantly reduced by the SWD. The relative expressions of protein and mRNA of ESR1, NR3 C1 were significantly increased. SWD treats PD by regulating the expression of key proteins PTGS2, ESR1 and NR3 C1.Its main medicinal herbs were Angelicae Sinensis Radix and Chuanxiong Rhizoma. Active components were mainly in volatile oil, but Paeo-niae Radix Alba and Rehmanniae Radix Praeparata also had some contributions.

Total glucosides of paeony: A review of its phytochemistry, role in autoimmune diseases, and mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Radix Alba (PRA, called baishao in China), the root of Paeonia lactiflora Pall., has shown a rich medicinal value for more than 2000 years. PRA is used in local medicine and traditional medicine for autoimmune diseases associated with inflammation. At present, total glucosides of paeony (TGP), the main active ingredient of PRA, has been developed into a preparation for the treatment of autoimmune diseases, as TGP exhibits the effect of regulating immunity, anti-inflammatory, and analgesic effects. AIM OF THE REVIEW: TGP was developed and applied to inflammation-related autoimmune diseases in modern clinical practice. Based on its application in traditional prescriptions, this article reviews PRA's botany and phytochemistry (including its extraction process and quality control), and discusses the clinical application and pharmacological research of TGP as an anti-inflammatory drug from the perspective of ethnopharmacology. Additionally, we review modern pharmacological and molecular-target research on TGP and discuss the mechanisms of TGP in treating autoimmune diseases. Through a systematic literature review, we also highlight the clinical efficacy of TGP in the treatment of immune diseases, and provide a reference for the continued scientific development and quality control of TGP so that its wider application and clinical value can be fully realized. MATERIALS AND METHODS: Literature search was conducted through the Web of Science, Baidu Scholar, ScienceDirect, PubMed, CNKI, and WanFang DATA using the keywords "Total glucosides of paeony", "Paeonia lactiflora Pall. ", "Paeonia veitchii Lynch", "Paeoniae Radix Alba or white peony", "Paeoniae Radix Rubra or red peony", "Paeoniflorin", "Albiflorin", "Autoimmune diseases", and their combinations. In addition, information was collected from relevant textbooks, reviews, and documents. RESULTS: Approximately 15 compounds have been identified in TGP, of which paeoniflorin and albiflorin are the most common constituents. In recent years, studies have found that TGP and its main chemical components are effective in the treatment of autoimmune diseases, such as rheumatoid arthritis, psoriasis, oral lichen planus, and Sjogren's syndrome. TGP has a variety of pharmacological effects related to PRA traditional effects, including anti-organ-damage, anti-inflammatory, analgesic, antioxidant, cardiovascular, and nervous-system protection. Previously published reports on TGP treatment of autoimmune diseases have shown that TGP regulates intracellular pathways, such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways. However, there is no standardized preparation method for TGP, and there is insufficient quality control of formulations. Many related pharmacological studies have not tested TGP components, and the validity of such pharmacological results requires further verification. CONCLUSIONS: Modern pharmacological research on TGP is based on the traditional usage of PRA, and its folk medicinal value in the treatment of autoimmune diseases has now been verified. In particular, TGP has been developed into a formulation used clinically for the treatment of autoimmune diseases. The combination of TGP capsules and chemicals to treat autoimmune diseases has the effect of increasing efficacy and reducing toxicity. Based on further research on its preparation, quality control, and mechanisms of action, TGP is expected to eventually play a greater role in the treatment of autoimmune diseases.

[Pharmacodynamics of Siwu Decoction on blood supply based on factor analysis].

To evaluate the pharmacodynamic effect of Siwu Decoction in treating blood deficiency in mice under multidimensional pharmacodynamic indexes by factor analysis. The mouse blood deficiency model was established with cyclophosphamide combined with acetophenone; and mouse organ index,white blood cells,red blood cell,hemoglobin,platelet counts in whole blood,serum granulocyte-macrophage colony-stimulating factor,macrophagecolony-stimulating factor,promotion erythropoietin,interleukin-3 and interleukin-6 were used as indicators to characterize the blood-enriching effect of Siwu Decoction; the pharmacodynamic effect of Siwu Decoction on blood deficiency model was evaluated comprehensively by factor analysis. Four common factors were extracted from 14 pharmacodynamics indexes through the factor analysis,namely blood phase factor,viscera index,hematopoietic regulatory factor 1-spleen index and hematopoietic regulatory factor 2-viscera index. The cumulative contribution rate of variance reached 86. 581%. The comprehensive score of factor analysis showed that Siwu Decoction had the best effect on blood replenishment,and it is significant compared with the model group( P<0. 01). The effect of alcohol precipitation of Siwu Decoction was slightly decreased. The study showed that Siwu Decoction has the best blood-enriching effect,followed by water decoction and traditional decoction. Alcohol precipitation had the worst effect. Factor analysis can be used for the comprehensive evaluation of blood deficiency mice model,and is a suitable evaluation method for animal model for multi-dimensional multistage complex data analysis. It provides a new model to evaluate the efficacy of multidimensional data in the future.

[Network pharmacology-based study on mechanism of Siwu Decoction in treatment of primary dysmenorrhea].

This paper aimed to predict and explore the mechanism of multiple components, targets and pathways of Siwu decoction for treatment of primary dysmenorrhea, and to establish a network pharmacological model of "compound-target-pathway-disease". According to the active ingredients in Siwu Decoction, Swiss Target Prediction server was used to predict the active component targets based on the reverse pharmacodynamic group matching method, and the primary dysmenorrhea targets approved by FDA were selected by database including DrugBank, OMIM and TTD. According to the enrichment analysis of the target pathways by using KEGG, the Cytoscape software was used to construct the network of "compound-target-pathway-disease" of Siwu Decoction. Network analysis showed that there were 20 active components involved in 114 pathways. And 16 components, 16 target proteins and 24 pathways were related to primary dysmenorrhea. Siwu Decoction may play a role in treating primary dysmenorrhea by acting on protein targets and pathways related to hormone regulation, central analgesia, spasmolysis,inflammation and immunity. This study revealed the potential active compounds and possible mechanism of Siwu Decoction for treatment of primary dysmenorrhea, providing theoretical references for further systematic laboratory experiments on effective compounds and action mechanism of Siwu Decoction.