Evidence of synergistic mechanisms of hepatoprotective botanical herbal preparation of Pueraria montana var. lobata and Schisandra sphenanthera.

Background: Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI. Methods: High performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR. Results: Chemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI. Conclusion: Our study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.

Research progress of sorafenib drug delivery system in the treatment of hepatocellular carcinoma: An update.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in the contemporary era, representing a significant global health concern. Early HCC patients have mild symptoms or are asymptomatic, which promotes the onset and progression of the disease. Moreover, advanced HCC is insensitive to chemotherapy, making traditional clinical treatment unable to block cancer development. Sorafenib (SFB) is a first-line targeted drug for advanced HCC patients with anti-angiogenesis and anti-tumor cell proliferation effects. However, the efficacy of SFB is constrained by its off-target distribution, rapid metabolism, and multi-drug resistance. In recent years, nanoparticles based on a variety of materials have been demonstrated to enhance the targeting and therapeutic efficacy of SFB against HCC. Concurrently, the advent of joint drug delivery systems has furnished crucial empirical evidence for reversing SFB resistance. This review will summarize the application of nanotechnology in the field of HCC treatment over the past five years. It will focus on the research progress of SFB delivery systems combined with multiple therapeutic modalities in HCC treatment.

Study on the Underlying Mechanism of Yinhua Gout Granules in the Treatment of Gouty Arthritis by Integrating Transcriptomics and Network Pharmacology.

Purpose: Yinhua Gout Granules (YGG) is a traditional Chinese medicine preparation with a variety of pharmacological effects, and its clinical efficacy in the treatment of gouty arthritis (GA) has been fully confirmed. However, the pharmacodynamic basis of YGG and its anti-inflammatory mechanism of action in GA are unknown. The objective of this study was to identify the active components and molecular mechanisms of YGG in the treatment of GA. Methods: Ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) and network pharmacology were used to identify and predict the potential active ingredients and related signaling pathways. Then, we revealed the anti-GA effects of YGG based on pharmacodynamic experiments in GA rats. Finally, we integrated transcriptomics and network pharmacology to elucidate the potential mechanism of action and verified the putative mechanism by molecular docking, immunohistochemical (IHC) and Western blot. Results: We have identified 10 major active components of YGG that may have anti-GA effects, such as ferulic acid, rutin, luteolin, etc. Using molecular docking, we found that 10 major compounds could bind well to TNF, PTGS2, IL-6, IL1ß, NOS2 and PTGS1, and the binding energies were all less than -5 kcal/mol. Animal studies have shown that YGG can improve joint inflammation and inflammatory cell infiltration, reduce serum UA, BUN and Cr levels (p<0.01), and decrease IL-1ß, IL-6, TNF-α, COX-2 and PGE2 levels in synovial tissue (p<0.01), which are associated with the pathogenesis of GA. IHC and Western blot results showed that YGG could regulate TLR4/MYD88/NF-κB pathway to inhibit the inflammatory response induced by GA. Conclusion: This study found that YGG could not only improve the disease of GA by inhibiting the production of UA in the body, but also target the regulation of TLR4/MYD88/NF-κB signaling pathway through a variety of active components to achieve effective therapeutic effects on GA.

The investigation of thermal stability and GC-MS analysis of Acorus tatarinowii and Atractylodes lancea volatile oils treated by ß cyclodextrin inclusion and Pickering emulsion technologies.

Objective: To investigate the stability of Acorus tatarinowii and Atractylodes lancea essential oils (ATaAL-EO) under a hot environment at 60 °C, and to analyze the differences in component, quantity, and quality changes, as well as variations in the main components, under different treatment methods of crude oil, ß-cyclodextrin inclusion of ATaAL-EO, and Pickering emulsion, to improve the stability and quality of ATaAL-EO. Methods: The stability of the ATaAL-EO group, the ß-cyclodextrin inclusion ATaAL-EO group, and the Pickering emulsion group were investigated under a 60 °C heat environment. Volatile oil retention rate and peroxide value were collected and measured. The volatile oil components of each group were determined by GC-MS, and t-tests were used to screen for differential components. PCA plots for each group were constructed using the OmicShare online platform. Line plots were generated using the Rmisc and reshape2 packages. Upset Venn diagrams under different hot environments were created using the OmicShare online platform to identify quantitative and qualitative changing components and heat map stack plots for newly generated compounds and connected line plots for disappearing compounds were produced for each group. Boxplots for the main component compounds under different hot environments were generated using the reshape2 and ggplot2 packages. Results: In a hot environment of 60 °C, the ß-cyclodextrin inclusion ATaAL-EO and Pickering emulsion group with 1, 3, and 8 h of placement showed higher retention and lower oxidation degree compared to the stability of the ATaAL-EO group. GC-MS analysis results showed that the stability of volatile components in the Pickering emulsion group and ß-cyclodextrin inclusion ATaAL-EO group was significantly improved compared to the crude oil group. Conclusion: ß-cyclodextrin inclusion complexes with ATaAL-EO, as well as Pickering emulsions, can significantly enhance the stability and quality of ATaAL-EO. Pickering emulsions have more advantages.

Development of curcumin-loaded galactosylated chitosan-coated nanoparticles for targeted delivery of hepatocellular carcinoma.

Curcumin (CUR) has good antitumor effects, but its poor aqueous solubility severely limits its clinical application and the systemic nonspecific distribution of the free drug in tumor patients is a key therapeutic challenge. In order to overcome the limitations of free drugs and improve the therapeutic efficacy, we developed novel galactosylated chitosan (GC)-modified nanoparticles (GC@NPs) based on poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PEG-PLGA), which can target asialoglycoprotein receptor (ASGPR) expressed on hepatocellular carcinoma cells and have excellent biocompatibility. The results showed that the drug loading (DL) of CUR was approximately 4.56 %. A favorable biosafety profile was maintained up to concentrations of 500 µg/mL. Furthermore, in vitro cellular assays showed that GC@NPs could be efficiently internalized by HepG2 cells via ASGPR-mediated endocytosis and successfully released CUR for chemotherapy. More importantly, in vivo anti-tumor experiments revealed that GC@NPs were able to accumulate effectively within tumor sites through EPR effect and ASGPR-mediated endocytosis, leading to superior inhibition of tumor growth compared to free CUR. Overall, GC@NPs are a promising CUR nanocarrier for enhanced tumor therapy with a good biosafety profile.

Targeted Drug Delivery Systems for Curcumin in Breast Cancer Therapy.

Breast cancer (BC) is the most prevalent type of cancer in the world and the main reason women die from cancer. Due to the significant side effects of conventional treatments such as chemotherapy and radiotherapy, the search for supplemental and alternative natural drugs with lower toxicity and side effects is of interest to researchers. Curcumin (CUR) is a natural polyphenol extracted from turmeric. Numerous studies have demonstrated that CUR is an effective anticancer drug that works by modifying different intracellular signaling pathways. CUR's therapeutic utility is severely constrained by its short half-life in vivo, low water solubility, poor stability, quick metabolism, low oral bioavailability, and potential for gastrointestinal discomfort with high oral doses. One of the most practical solutions to the aforementioned issues is the development of targeted drug delivery systems (TDDSs) based on nanomaterials. To improve drug targeting and efficacy and to serve as a reference for the development and use of CUR TDDSs in the clinical setting, this review describes the physicochemical properties and bioavailability of CUR and its mechanism of action on BC, with emphasis on recent studies on TDDSs for BC in combination with CUR, including passive TDDSs, active TDDSs and physicochemical TDDSs.

[Optimization of ethanol reflux extraction process of Ziziphi Spinosae Semen- Schisandrae Sphenantherae Fructus based on network pharmacology combined with response surface methodology].

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.

Review targeted drug delivery systems for norcantharidin in cancer therapy.

Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects.

Pickering emulsion technology based on the concept of "the combination of medicine and adjuvant" to enhance the oxidation stability of volatile oils in solid preparations-taking Lingzhu Pulvis as an example.

The antioxidant properties of the volatile oil of Acorus calamus in Lingzhu Pulvis may be enhanced by the introduction of Pickering emulsion technology based on the concept of "the combination of medicine and adjuvant". The characterization of each drinking tablet of Lingzhu Pulvis was conducted to determine the stabilizer. The optimal stabilizer concentration, oil-water ratio and preparation method of the Pickering emulsion were then determined and analyzed using NIR. The contents of malondialdehyde and peroxide in the volatile oils of each group were compared at different AIBA concentrations. The trends of the components were then analyzed by GC-MS. The pearl powder was screened as the stabilizer of the Pickering emulsion; the pearl powder concentration of 0.065 g mL-1 and the oil-water ratio of 9 : 11 were found to be the optimal emulsion formation conditions, and the high-pressure homogenization method was the optimal preparation method. The NIR analysis showed that the volatile oil was wrapped by the pearl powder and no new chemical structure formed in the Pickering emulsion. The Pickering emulsions had lower oxidation levels than the crude oil groups at AIBA concentrations of 5, 10, and 15 mg mL-1. The results of the GC-MS analysis showed that the antioxidant properties of the volatile components were significantly higher in the Pickering emulsion group compared to the crude oil group. Pickering emulsions can be used to enhance the antioxidant properties of volatile components in oil-containing solid formulations based on the concept of "the combination of medicine and adjuvant".

Evaluation of the Clinical Efficacy of the Classic Prescription "Baihe Dihuang Decoction" Based on Meta-Analysis.

Purpose: To explore the clinical application of Baihe Dihuang Decoction. To provide certain data support and theoretical basis for the clinical application of Baihe Dihuang Decoction in the future. Methods: With "Baihe Rehmannia Tang" as the search term, the search was carried out on CNKI, VIP, Wanfang, PubMed and other databases. The statistical analysis of Baihe Dihuang decoction for treating diseases was obtained. Meta-analysis of the data was performed using RevMan 5.3 software to analyze the main therapeutic indicators of the disease. Results: According to the 83 valid literature that can be found, it is shown that 17 are used for the treatment of depression, 14 are used for the treatment of menopausal syndrome, 24 are used for the treatment of insomnia, and 28 are used for the treatment of other diseases. Conclusion: In the treatment of depression, menopausal syndrome, and insomnia combined with Baihe Dihuang Decoction can have a better therapeutic effect and diminish the incidence of adverse reactions. It provides a theoretical basis for the study and experimental study of its active components.

Oral Bioavailability-Enhancing and Anti-obesity Effects of Hydroxysafflor Yellow A in Natural Deep Eutectic Solvent.

Hydroxysafflor yellow A (HSYA), a primary active component in Carthami Flos, has been extensively applied in the treatment of cardiometabolic diseases. In this study, a natural deep eutectic solvent composed of glucose and choline chloride with 10% (v/v) of water (90% GCH) was evaluated to enhance the oral absorption of HSYA. Compared with HSYA in water, the relative oral bioavailability of HSYA in 90% GCH was increased to 326.08%. Furthermore, 90% GCH was demonstrated to decrease the mucus viscosity and increase the absorption rate constant of HSYA in the jejunum by 2.95 times. A pharmacodynamic study revealed that HSYA in 90% GCH was more effective in reducing body weight and correcting steatohepatitis and dyslipidemia in high-fat diet-induced obese rats. Serum metabolomics results showed that the correction of serum aromatic amino acid disorder may contribute to the anti-obesity effect of HSYA in 90% GCH. In conclusion, 90% GCH could be a delivery carrier for HSYA against obesity.

Exploring the Scientific Rationality of the Phenomenon of "Different Dosage Forms of the Same Prescription" of Chinese Proprietary Medicine Based on Biopharmaceutical Properties of Powder and Pill of Chuanxiong Chatiao Prescription.

Background: The 2020 edition of the Pharmacopoeia of the People's Republic of China (Chinese Pharmacopoeia 2020 edition) has 255 Chinese prescriptions with different dosage forms, accounting for 21.09% of the total prescriptions (1,209) in Chinese Pharmacopoeia 2020 edition. However, the scientific rationality of the phenomenon of "Different Dosage Forms of the Same Prescription" of Chinese proprietary medicine has been less explored. Based on the dosage form theory of "components in pills release slowly and take effect in slow-acting manner, while in powders release quickly and take effect in fast-acting way," we provided the in vitro dissolution experiment and in vivo pharmacokinetics of Chuanxiong Chatiao powders and pills in order to rationalize the phenomenon of "Different Dosage Forms of the Same Prescription" of Chuanxiong Chatiao prescription. Materials and Methods: Chuanxiong Chatiao powders and pills were prepared in the laboratory referring to the preparation methods in the Chinese Pharmacopoeia 2020 edition, and the contents of tetramethylpyrazine, ferulic acid, nodakenin, and isoimperatorin were determined by the external standard method. We measured the in vitro dissolution of four analytes of Chuanxiong Chatiao powders and pills according to the second method for dissolution determination (paddle method) in the Chinese Pharmacopoeia 2020 edition, and their corresponding contents in each sampling point were determined by LC-MS/MS. We also provided a pharmacokinetic study of Chuanxiong Chatiao powders and pills. Six female domestic rabbits were divided into two groups (powder and pill groups) and given Chuanxiong Chatiao powders and pills (9.85 g/kg) by surgical administration separately. Blood samples were collected at 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, 720, and 1,440 min after drug administration to measure the plasma concentration of the four analytes by LC-MS/MS. Results: The results of in vitro dissolution experiment showed that the dissolution rate of four analytes in the powder group was greater than that of the pill group. However, the solubilities of tetramethylpyrazine and isoimperatorin were very low in the powder and pill, which may be related to their low solubility properties. The results of the in vivo pharmacokinetic study of Chuanxiong Chatiao powders and pills showed that T max (h) of ferulic acid and nodakenin in the powder group was 0.420 and 0.053 times that of the pill group and t 1/2 (h) of ferulic acid, nodakenin, and isoimperatorin of the powder group was 0.910, 0.262, and 0.661 times that of the pill group, respectively. Conclusion: The in vitro dissolution rate and in vivo pharmacokinetic parameters of four analytes in CXCTF could partly explain the scientific rationality of the classic theory of ", " as in Chinese, which is helpful for providing a basis for the comparison of subsequent dosage forms. The results of our studies also suggest the complexity of the design of dosage forms of Chinese proprietary medicines and imply that we should pay more attention to the scientific rationality of the phenomenon of "Different Dosage Forms of the Same Prescription."

Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.

Urokinase-type plasminogen activator receptor (uPAR) is an attractive target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant tumours. uPAR is closely related to the invasion and metastasis of malignant tumours, plays important roles in the degradation of extracellular matrix (ECM), tumour angiogenesis, cell proliferation and apoptosis, and is associated with the multidrug resistance (MDR) of tumour cells, which has important guiding significance for the judgement of tumor malignancy and prognosis. Several uPAR-targeted antitumour therapeutic agents have been developed to suppress tumour growth, metastatic processes and drug resistance. Here, we review the recent advances in the development of uPAR-targeted antitumor therapeutic strategies, including nanoplatforms carrying therapeutic agents, photodynamic therapy (PDT)/photothermal therapy (PTT) platforms, oncolytic virotherapy, gene therapy technologies, monoclonal antibody therapy and tumour immunotherapy, to promote the translation of these therapeutic agents to clinical applications.

[Application of particle design technology in field of traditional Chinese medicine powder].

Solid preparations account for more than 50% of traditional Chinese medicines(TCM). TCM powder is an important raw material for solid preparations of TCM. Its powder properties directly affect the quality of solid preparations, and even clinical safety and effectiveness. Particle design technology based on the characteristics of powder in TCM is an important means to improve and enhance the quality of solid preparations. This study summarized the relevant principles, methods, characteristics, classification, equipment, and other elements of particle design technology in recent years, analyzed the difficulties in its application in the field of TCM powder, and proposed the strategies in conjunction with the development of computer data mining. The present study is expected to provide a reference for the suitability of particle design in the field of TCM powder.

[Particle design for improving content uniformity of Hewei Jiangni Capsules].

Targeting the poor powder characteristics of the contents in Hewei Jiangni Capsules, this study characterized the powder properties of the contents and employed particle design technique for improving the content quality. The content composite particles of Hewei Jiangni Capsules prepared by the particle design technique were evaluated by scanning electron microscopy(SEM), followed by infrared ray(IR), content uniformity, and in vitro dissolution detection. It was found that there was a good correlation between the crushed particle size of slices and the crushing time, and the calcined Haematitum was responsible for the poor content uniformity. After the fine powder of calcined Haematitum was super-finely ground for 8.5 min and those of the other contents in the capsule for 1 min, they were prepared into the composite particles, whose property characterizations were compared with those of the physical mixtures. The content uniformity of the prepared composite particles was significantly improved, and the preparation process was stable and reliable. The adoption of particle design technology to correct the poor uniformity of the physical mixture, solve the pharmaceutical defects of Hewei Jiangni Capsules, and improve the quality of prescriptions has provided important reference for the clinical application and development of Chinese medicinal preparations.

[Powder modificationfor improving content uniformity of Ziyin Yiwei Capsules].

Based on the defects in powder properties of the contents of Ziyin Yiwei Capsules, this study screened out the main medicinal slice powders causing the poor powdery properties, and introduced the powder modification process to improve the powdery properties of these slice powders, the pharmaceutical properties of the capsule contents, and the content uniformity of Ziyin Yiwei Capsules, so as to provide a demonstration for the application of powder modification technology to the preparation of Chinese medicinal solid preparations. Through the investigation on the powder properties of the contents of Ziyin Yiwei Capsules, it was clarified that the pulverized particle size of the capsule contents had a good correlation with the pulverization time. According to the measurement results of the powder fluidity and wettability, the quality defects of the capsule contents were caused by the fine powders of Taraxaci Herba and Lungwortlike Herba. "Core-shell" composite particles were prepared from medicinal excipients magnesium stearate and fine powders of Taraxaci Herba and Lungwortlike Herba slices after ultra-fine pulverization to improve the powder properties of the problematic fine powders. Powder characterization data including fluidity and wettability were measured, followed by scanning electron microscopy(SEM) and infrared ray(IR) detection. It was determined that the optimal dosage of magnesium stearate was 2%, and the compositing time was 3 min. The composite particles were then used as content components of the Ziyin Yiwei Capsules. The powder characteristics between the original capsule and the modified composite capsule including the particle size, fluidity, wettability, uniformity of bulk density, and uniformity of chromatism as well as the content uniformity and in vitro dissolution were compared. The results showed that the powder characteristics and content uniformity of the prepared composite capsule were significantly improved, while the material basis of the preparation was not changed before and after modification. The preparation process was proved to be stable and feasible. The powder modification technology solved the pharmaceutical defects that were easy to appear in the preparation of traditional capsules, which has provided experimental evidence for the use of powder modification technology for improving the quality of Chinese medicinal solid preparations and promoting the secondary development and upgrading of traditional Chinese medicinal dosage forms such as capsules.

[Quality evaluation of Aralia taibaiensis based on spectrum-activity relationship].

A spectrum-activity relationship is established with high performance liquid chromatography(HPLC) fingerprints and the in vitro antioxidant activity to improve the quality evaluation system of Aralia taibaiensis. The HPLC profiles of 12 batches of samples were collected, and the similarity evaluation, heat map analysis and principal component analysis were conducted for the chemometric study of the fingerprint data. Combined with grey correlation analysis, the contributions of the common peaks in the fingerprints to the antioxidant activity were clarified, and the important peaks reflecting the efficacy were identified. The results showed that 17 common peaks were found in 12 batches of A. taibaiensis samples, and 6 of them were identified as saponins. Similarity evaluation, heat map analysis and principal component analysis roughly classified the A. taibaiensis herbs into two categories, i.e.,(1) S1-S10, S12 and(2) S11. Twelve batches of samples showed different antioxidant activities in a dose-dependent manner. In particular, S9 had the strongest antioxidant activity, while S11 was the weakest in antioxidant capacity, which was basically consistent with the overall score results. The results of grey correlation analysis demonstrated that the 17 common peaks scavenged DPPH radicals in the following order: X_3>X_(17)>X_4>X_8>X_7>X_(13)>X_2>X_6>X_(11)>X_(10)>X_(16)>X_(12)>X_9>X_5>X_(14)>X_1>X_(15), and scavenged ABTS radicals in the order of X_4>X_3>X_7>X_8>X_2>X_(17)>X_(13)>X_6>X_(16)>X_(11)>X_5>X_(12)>X_(10)>X_9>X_(14)>X_1>X_(15). Among them, X_3, X_4, X_7(araloside C), X_8 and X_(17) were the important peaks reflecting the efficacy of A. taibaiensis, which were basically consistent with those contained in the principal component 1. In this study, the correlation between the HPLC fingerprints of 12 batches of A. taibaiensis and its antioxidant activity provides a reference for the Q-marker screening and quality control of A. taibaiensis.

Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology.

OBJECTIVE: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription that can be effective in treating febrile seizures (FS) and there are few research works conducted on its mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. MATERIALS AND METHODS: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS is obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software, the potential core compounds and targets of FS were obtained. The R language and ClusterProfiler software package are adopted to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets are also revealed. RESULTS: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened, which were involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS in regulating FS in the pathogenesis and the therapeutic mechanism of FS were discussed and clarified. CONCLUSION: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS were preliminarily screened through the analysis of network pharmacology data, which are consistent with the principle of multi-compounds' compatibility with TCM prescriptions and a unified treatment of diseases from multiple aspects, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

Analysis of Clinical Efficacy of Traditional Chinese Medicine in Recovery Stage of Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: We provide an updated meta-analysis with detailed information on a combination of TCM and routine treatment. METHODS: Retrieve appropriate articles with no language restrictions on keywords until 8 July 2019 in an electronic database. All trajectories are screened according to certain criteria. The quality of certified research was also evaluated. We made a detailed record of the results of the measurement. Meta-analysis was carried out by using the Revman 5.3 software. RESULTS: Sixty-seven RCTs were included, and 6594 subjects were analyzed. Compared with routine treatment, the total effective rate (TER) of TCM combined with routine treatment was improved, and the recovery of stroke was also significantly accelerated. Regulation of blood lipids by notably shrinking the contents of TC, TG, and LDL and enhancing the levels of HDL. The levels of serum hs-CRP, WHV, and WLV decreased significantly, indicating that the expression of thrombomodulin was decreased after the comprehensive treatment of traditional Chinese medicines (TCMs). The combination of TCM treatment could enhance the protection of neural function by decreasing the NIHSS scoring while increasing the BI scoring. Paeoniae Radix Rubra, Angeticae Sinensis Radix, etc., can effectively improve the clinical symptoms of stroke convalescent patients and promote the recovery of neurological function. ACU of Baihui, Renzhong, etc., can improve the clinical rehabilitation effect of patients. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results. CONCLUSION: A combination of TCM and routine treatment in the treatment of stroke could improve TER, and it is beneficial to the rehabilitation of patients in the recovery period of apoplexy. These effects can be mediated by a combination of several mechanisms. Nevertheless, due to the limitations of this study, these results should be handled with caution.

Studies on pharmacokinetic properties and absorption mechanism of phloretin: In vivo and in vitro.

Phloretin is a natural dihydrochalcone flavonoid that is mainly distributed in apple, pear and other juicy fruit peels or root peels. Phloretin exhibits several pharmacological properties, such as antidiabetic, antioxidant, anti-inflammatory, and antitumor activities. However, the poor water solubility of phloretin limits its application in the treatment of numerous diseases. To date, the underlying mechanisms of phloretin absorption have not been investigated. In this study, the pharmacokinetics of phloretin orally administered to Sprague-Dawley (SD) rats were examined, and the absorption mechanisms of phloretin were investigated in a Caco-2 cell monolayer and single-pass intestinal perfusion in SD rat. The effects measured by basic parameters, such as compound concentration, time, temperature, paracellular pathway, in different intestinal segments were analyzed, and various inhibitors, such as the P-glycoprotein (P-gp) inhibitor verapamil, the multidrug resistance protein 2 (MRP2) inhibitor indomethacin, the breast cancer resistance protein (BCRP) inhibitor reserpine, and the closely related regulator EDTA, were evaluated to determine their effects on the absorption of phloretin. The pharmacokinetics of phloretin was studied by oral and intravenous injection in rats. The bioavailability was 8.676 %.The SPIP experiments showed that P-gp, MRP2, BCRP protein inhibitor and closely related regulator, could significantly increase the apparent permeability coefficient (Papp) of phloretin. Monolayer transport experiments in Caco-2 cells showed that P-gp, MRP2 protein inhibitor and closely related regulator EDTA, significantly increased the Papp value of phloretin. In conclusion, phloretin is a substrate of P-gp and MRP2, and its modes of transport include active transport, efflux protein transport and cell bypass.