Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.@*METHODS@#A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.@*RESULTS@#FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).@*CONCLUSION@#FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Effect of Guizhi Fuling Capsule on Apoptosis of Myeloma Cells Through Mitochondrial Apoptosis Pathway / 中国结合医学杂志

OBJECTIVE@#To observe the effects of Guizhi Fuling Capsule (GZFLC) on myeloma cells and explore the mechanisms.@*METHODS@#MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative (10%, 20% and 40%) groups, GZFLC (10%, 20%, and 40%) groups and a control group. Cell counting kit-8 (CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie (ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cleaved caspase-3, -9, cytochrome C (Cytc) and apoptotic protease-activating factor 1 (Apaf-1). RPMI 8226 cells (2 × 107) were subcutaneously inoculated into 48 nude mice to study the in vivo antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design, the high-, medium-, or low-dose GZFLC (840, 420, or 210 mg/kg per day, respectively) or an equal volume of distilled water, administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry.@*RESULTS@#GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells (P<0.05). In addition, this drug increased the ROS levels and decreased the mitochondrial membrane potential (P<0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups, whereas the expression levels of cleaved caspase-3, -9, Cytc and Apaf-1 were increased (all P<0.01). Over time, the myeloma tumor volumes of the mice in the GZFLC-administered groups decreased, and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLC-administered groups revealed that the Cytc and Apaf-1 expression levels were increased (P<0.05).@*CONCLUSION@#GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma, which prolonged the survival times of the mice.

Exploration of medication rules and mechanisms of traditional Chinese medicine in the treatment of periodontal disease based on data mining, network pharmacology, and molecular docking / 口腔疾病防治

Objective @#To explore the medication law and mechanism of traditional Chinese medicine compounds in the treatment of periodontal disease through data mining, network pharmacology, and molecular docking. @* Methods@#First, data mining was used to search single medicinal materials for the treatment of periodontal disease, and the active components and their action targets were screened. Second, the disease target database was employed to download the targets related to the pathogenesis of periodontal disease, map them with the action targets of traditional Chinese medicine, and obtain the targets that are considered potential targets of traditional Chinese medicine in the treatment of periodontal disease. Potential targets were analyzed for gene ontology function and signaling pathway. They were then screened to obtain the key targets for the treatment of periodontal disease. Finally, the active components were docked with key targets.@* Results@# Among the traditional Chinese medicine prescriptions for the treatment of periodontal disease, Shudihuang, Mudanpi, Danggui, Fuling, Jinyinhua, Shanyao and Zhimu had the highest frequencies. Forty-three active components and 118 action targets were screened, and 52 potential targets were obtained by intersection with 856 disease targets. The molecular functions and biological processes in which potential targets may participate mainly focus on vitamin D biosynthesis and RNA polymerase Ⅱ regulation and involve 96 signaling pathways. Through the analysis of network topology parameters, 11 key targets were obtained. The results of molecular docking showed that the active components and RAC-alpha serine/threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53), and mitogen-activated protein kinase-1 (MAPK-1) have good binding activity. @* Conclusion @#Traditional Chinese medicine compounds may play a role in the treatment of periodontal disease by inhibiting alveolar bone absorption, have antibacterial and anti-inflammatory properties, and promote tissue repair. The effective treatment of periodontal disease by traditional Chinese medicine compounds provides a more scientific reference to the sustainable development of traditional Chinese medicine.

Study on Improvement Effects and Mechanism of Guizhi Fuling Pills on Phlegm-dampness Type PCOS Model Rats / 中国药房

OBJECTIVE：To stu dy the improvem ent effect and mechanism of Guizhi fuling pill （GZFLP） on rats with phlegm-dampness type polycystic ovary syndrome （PCOS）.METHODS：Totally fifty female SD rats with regular estrous cycle were randomly divided into blank control group （n＝10） and model group （n＝40）. The model group received letrozole intragastrically [1 mg/（kg·d），for 21 d ] to induce phlegm-damp PCOS rat model. Forty model rats were randomly divided into model group ，metformin group [positive control ，0.135 g/（kg·d）] and GZFLP low-dose ，high-dose groups [4.49，17.96 g/（kg· d）]，with 10 rats in each group. Each medicine group was given intragastric administration ，once a day ，for 30 consecutive days. Blank control and model group were given intragastric administration of equal volume normal saline.After last medication ，oral glucose tolerance test （OGTT）was used to detect the level of blood glucose in rats at 0，30，60 and 120 min. ELISA assay was used to detect the levels of follicle-stimulating hormone （FSH），luteinizing hormone （LH），estradiol（E2）and testosterone （T）； body weight ，the weight of uterus ，bilateral ovaries and paragonadal fat were weighed. HE staining was used to observe morphological changes of ovarian tissue sections. RT-PCR method and Western blotting assay were used to detect mRNA and protein expression of CYP 19a1 in ovary and Glut 4 in uterine. RESULTS ：Compared with blank control group ，the levels of blood glucose 30，60，120 min after intragastric administration of glucose solution as well as serum levels of LH ，E2 and T were increased significantly in model group （P＜0.05）；the body weight ，the weight of uterus ，bilateral ovaries and paragonadal fat were increased significantly （P＜0.05）；the volume of thecal cells increased significantly and showed spherical shape ；the mRNA and protein expression of CYP 19a1 in ovarian tissue and Glut 4 in uterine tissue were decreased significantly （P＜0.05 or P＜0.01）. Compared with model group ，above indexes of administration groups were improved significantly （P＜0.05 or P＜0.01）；the thickness of theca cell layer and the volume of theca cells in GZFLP low-dose and high-dose groups were also improved. CONCLUSIONS：GZFLP can up-regulate the expression of CYP19a1 in ovary and Glut4 in uterus ，so as to improve the abnormal glucose metabolism in phlegm-dampness type PCOS model rats ，reduce insulin resistance ，lower serum estrogen levels ，and reduce the degree of polycystic changes in ovary ，thereby playing a role in the treatment of PCOS.

Literature research and status analysis on clinical application of Guizhi Fuling Formula / 中国中药杂志

Guizhi Fuling Formula was first seen in Synopsis of Golden Chamber by ZHANG Zhongjing. It is composed of Cinnamomi Ramulus, Poria, Moutan Cortex, Persicae Semen, Peony and other drugs, commonly used in the treatment of gynecological diseases such as hysteromyoma, ovarian cyst, endometriosis, pelvic inflammation, dysmenorrhea, etc. In addition, it is also used in internal medicine and urology. This reflects the modern doctors' recognition of the famous prescriptions in ancient books. However, whether Guizhi Fuling Formula is really suitable for these diseases still needs further study for verification. The author systematically searched CNKI, Wanfang, SinoMed, PubMed, EMbase, Cochrane Library database: 2 304 papers on clinical research of Guizhi Fuling, covering 13 systems and 128 diseases. Combined with the questionnaire of experts, we investigated the knowledge of experts of traditional Chinese medicine, Western medicine and combination of Chinese and Western medicine on the applicable indications of Guizhi Fuling Formula in this paper, systematically elaborated the clinical applications of Guizhi Fuling Formula, and summarized the applicable indications of Guizhi Fuling Formula, in order to provide a reference for the clinical rational application of Guizhi Fuling Formula, and provide a reference also for clinical medication.

Effects of Guizhi Fuling Capsules and Its Main Components on Intestinal Flora of Primary Dysmenorrhea Model Rats / 中国药房

OBJECTIVE：To investigate the effects of Guizhi ful ing capsules and its principal components （paeoniflorin， paeonol and amygdalin ）on the intestinal flora of primary dysmenorrhea model rats. METHODS ：Female SD rats were randomly divided into normal group ，model group ，capsule group（Guizhi fuling capsule ，1 000 mg/kg），paeoniflorin group （15.0 mg/kg）， paeonol group （10.3 mg/kg）and amygdalin group （12.1 mg/kg），with 6 rats in each group. Except for normal group ，other groups were given estradiol benzoate subcutaneously on the back of rats and oxytocin intraperitoneally to induce primary dysmenorrhea model. From the 4th day after subcutaneous injection of estradiol benzoate ，normal group was given constant volume of normal saline intragastrically ；model group was given constant volume of 0.5％CMC-Na solution intragastrically ；administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. The writhing times and the contents of and MDA in uterus tissue of rats were determined ，and then com the contents of short-chain fatty acids （SCFAs）such as acetic acid，propionic acid ，butyric acid in colonic contents were detected by GC method. Using diver sity index as index ， Rep-PCR and Eric-PCR were used to evaluate the d iversity of intestinal flora in feces of rats. RESULTS ：Compared with normal group，the writhing times of rats were increased significantly in model group ；the contents of NO and MDA in uterus were increased significantly ，while the contents of acetic acid ，propionic acid and butyric acid in colonic contents and total content of SCFAs were decreased significantly （P＜0.05 or P＜0.01）；the number of DNA electrophoresis bands of intestinal flora was significantly reduced ，the brightness of most bands was significantly reduced ，and the diversity indexes （by Rep-PCR and Eric-PCR method ，hereinafter）1 h after administration were significantly reduced （P＜0.05 or P＜0.01）. Compared with model group，writhing times of rats were decreased significantly in capsule group ，paeoniflorin group and paeonol group ；the contents of NO in uterus of rats in capsule group and paeoniflorin group as well as the contents of MDA in capsule group ，paeoniflorin group and paeonol group were decreased significantly （P＜0.05 or P＜0.01）；the propionic acid content and total content of SCFAs in colon of rats in capsule group ，the contents of acetic acid ，propionic acid and butyric acid ，total content of SCFAs in paeoniflorin group as well as the contents of propionic acid and butyric acid ，total content of SCFAs in paeonol group were increased significantly；the content of isovaleric acid was decreased significantly in paeoniflorin group （P＜0.05 or P＜0.01）；DNA electrophoresis bands and its brightness of intestinal flora changed to different extents in administration groups ，and the diversity indexes of intestinal flora 1 h after administration were increased significantly in capsule group and paeoniflorin group ，while those indexes were decreased significantly in paeonol group and amygdalin group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Guizhi fuling capsules can significantly reduce writhing times and the contents of NO and MDA in uterus of primary dysmenorrhea model rats. At the same time ，the capsules also can regulate SCFAs content in colonic contents and intestinal flora diversity of rats. The above effects may be related to paeoniflorin and paeonol in the capsules.

Study of integrative evidence chain in clinical trial of Guizhi Fuling Capsules based on "Yibing Tongzhi" in clinical applications / 中国中药杂志

Guizhi Fuling Capsules is a new-type traditional Chinese medicine preparation made by modern process method. It was widely used to treat uterine fibroids, pelvic inflammation, dysmenorrhea, endometriosis, mammary gland hyperplasia and other gynecological diseases. Under the combination of disease and syndrome, the diagnosis and treatment model of "Yizheng Tongbing, Yibing Tongzhi" with Chinese patent medicine has been widely used in clinical practice. Meanwhile, the effectiveness and safety have been given more and more attention. Based on the effectiveness of Guizhi Fuling Capsules, this paper preliminarily summarized the dominant diseases in randomized controlled trials and systematic reviews of Guizhi Fuling Capsules. On the basis of the basic theory of traditional Chinese medicine and modern pharmacological mechanism, the clinical efficacy and mechanism of Guizhi Fuling Capsules were explored. Finally, according to the traditional Chinese medicine theory of "Yizheng Tongbing, Yibing Tongzhi", all the clinical evidences were integrated to form an integrated evidence chain, so as to provide guidance for the safe and rational use of Guizhi Fuling Capsules.

Predictive model for hygroscopicity of contents in Guizhi Fuling Capsules / 中国中药杂志

To control the risks of powder caking and capsule shell embrittlement of Guizhi Fuling Capsules, a predictive model for hygroscopicity of contents in Guizhi Fuling Capsules was built. A total of 90 batches of samples, including raw materials, intermediate powders and capsules, were collected during the manufacturing of Guizhi Fuling Capsules. According to the production sequence, 47 batches were used as the calibration set, and the properties of raw materials and the four intermediate powders were comprehensively characterized by the physical fingerprint. Then, the partial least squares(PLS) model was developed with the content hygroscopicity as the response variable. The variable importance in projection(VIP), variance inflation factor(VIF) and regression coefficients were used to screen out potential critical material attributes(pCMAs). As a result, five pCMAs from 54 physical parameters were screened out. Furthermore, different models were built by different combinations of pCMAs, and their predictive robustness of 43 batches was evaluated on the basis of the validation set. Finally, the tap density(D_c) of wet granules obtained from wet granulation and the angle of repose(α) of raw materials were identified as the critical material attributes(CMAs) affecting the hygroscopicity of the contents of Guizhi Fuling Capsules. The prediction model established with the two CMAs as independent variables had an average relative prediction error of 2.68% for samples in the validation set, indicating a good accuracy of prediction. This paper proved the feasibility of predictive modeling toward the control of critical quality attributes of Chinese medicine oral solid dosage(OSD). The combination of the continuous quality improvement, the industrial big data and the process modeling technique paved the way for the intelligent manufacturing of Chinese medicine oral solid preparations.

Identification of chemical constituents in Guizhi Fuling Capsules by UPLC-Q-TOF-MS/MS / 中国中药杂志

To qualitatively characterize the chemical composition of Guizhi Fuling Capsules using UPLC-ESI-Q-TOF-MS/MS. The analysis was performed on Agilent ZORBAX RRHD Eclipes Plus C_(18)(2.1 mm×100 mm, 1.8 μm) column,that was eluted with mobile phase consisting of acetonitrile and 0.1% formic acid in a gradient mode. The flow rate was 0.4 mL·min~(-1), and column temperature was 30 ℃. Tandem mass spectrometry was acquired in both negative and positive ESI modes. These components were further analyzed based on high-resolution mass-to-charge ratios, fragment ion species, reference substances and literature data. In conclusion, a total of 200 compounds were identified, in which 40 were verified with reference substances. The current study laid a foundation for in-depth studies of its mass balance and pharmacodynamics.

Studies on chemical constituents in Guizhi Fuling Capsule (VII) / 中草药

Objective To study the chemical constituents from the n-butanol extract of Guizhi Fuling Capsule. Methods The chemical constituents were isolated and purified by multiple chromatographic methods. Their structures were identified on the basis of the spectral data and physicochemical properties. Results Five compounds were identified as 3'-O-galloylsucrose (1), 4'-O-galloylsucrose (2), 6'-O-galloylsucrose (3), 1'-O-galloylsucrose (4), and 1,2,3,4,6-pentagalloylglucose (5). Conclusion Compounds 1-5 are isolated from Guizhi Fuling Capsule for the first time, and compound 1 is a new compound. Compounds 1-5 inhibited calcium influx in uterine smooth muscle cells of primary mice.

Analysis on 1 500 adverse reactions of Guizhi Fuling Capsules based on spontaneous response system / 中国中药杂志

To understand the characteristics of adverse reactions and find early warning signs after intake of Guizhi Fuling Capsules. The 1 500 adverse reaction(ADR) cases of Guizhi Fuling Capsules obtained by spontaneous reporting system(SRS) from 2008 to 2017 were analyzed by proportional reporting ratios method(PRR), Bayesian confidence propagation neural network method(BCPNN) and propensity score method. The number of ADR reports increased year by year, and reached the peak in the fourth quarter of 2014. A total of 1 500 ADR cases were monitored, including 10 severe ADR cases. There were a total of 934 cases aged between 18-44 years old, accounting for 62.27%. All patients were orally administered. Among them, 1 398 patients received a single dose according to the package insert, and 57.4% had ADR within 24 h. The top five clinical manifestations of ADR were gastric dysfunction, abdominal pain, nausea, vomiting and rash, which mainly damaged the digestive system. The ADR signals were analyzed. PRR suggested that "gastric dysfunction" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. BCPNN suggested that "nausea" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. After the propensity score weighting method was used to control the confounding factors, the warning signals remained unchanged. The results show that Guizhi Fuling Capsules has fewer adverse reactions and is relatively safe. This study provides a basis for studying ADR of Guizhi Fuling Capsules, and guidance for drug vigilance and risk management of Guizhi Fuling Capsules.

Study on Improvement Effects of Fuling Gancao Decoction on Functional Dyspepsia Model Rats / 中国药房

OBJECTIVE： To study improvement effects of Fuling gancao decoction on functional dyspepsia （FD） model rats. METHODS： Sixty SD rats were randomly divided into normal group， model group， Fuling gancao decoction high-dose group （20 g/kg）， Fuling gancao decoction low-dose group （10 g/kg）， drug combination group （Fuling gancao decoction 10 g/kg+domperidone 0.004 g/kg）， domperidone group （0.004 g/kg）， with 10 rats in each group. Except for normal group， other groups were givenicy dilute hydrochloric acid intragastrically to establish FD model.  After modeling， normal group and model group were given constant volume of distilled water at room temperature intragastrically， and other groups were given relevant drug solution （1 mL/100 g） intragastrically， once a day， for consecutive 7 d. The amount of gastric residue was measured to evaluate the gastric emptying function. Immunohistochemistry SP method was used to detect the protein expression of AQP3， Ghrelin and Substance P in gastric mucosa tissue. The protein expression of Claudin-1， Occludin and VIP were detected by Western blot assay. RESULTS： Compared with normal group， the amount of gastric residue was increased significantly in model group （P＜0.01）； positive expression of AQP3 and Ghrelin protein in gastric mucosa tissue was decreased significantly， while the positive expression of Substance P protein tended to increase； the protein expression levels of AQP3， Ghrelin， Claudin-1 and Occludin were decreased significantly， while those of Substance P and VIP were increased significantly （P＜0.05 or P＜0.01）. Compared with model group， the amount of gastric residue was decreased significantly in administration groups （P＜0.05 or P＜0.01）； the positive expression of AQP3 and Ghrelin protein tended to increase， while less positive expression of Substance P was found； the protein expression levels of AQP3 and Occludin in gastric mucosa tissue were increased significantly in administration groups， while those of VIP were decreased significantly  （P＜0.05 or P＜0.01）； the protein expression levels of Ghrelin and Claudin-1 in gastric mucosa tissue were increased significantly in Fuling gancao decoction high-dose group， Fuling gancao decoction low-dose group and drug combination group， while those of Substance P were decreased significantly （P＜0.05）. CONCLUSIONS： Fuling gancao decoction may improve the symptom of fluid retention in FD model rats by up-regulating the protein expression of AQP3， Ghrelin， Claudin-1 and Occludin and down-regulating the protein expression of Substance P and VIP in gastric mucosa tissue of rats.

Current situation and consideration of patent protection in classical representative famous prescriptions in China / 中国中药杂志

Classical Representative Famous Prescription is the valuable cultural heritage of Chinese medicine. In November 2018,the State Council issued the " Intensive Implementation of the National Intellectual Property Strategy in 2018 to Accelerate the Construction of IP Strong Country",explicitly proposing to strengthen the intellectual property protection of Classical Representative Famous Prescription.How about the current situation of intellectual property protection of lassical Representative Famous Prescription in China? We selected Liuwei Dihuang Pills,Shengmai Powder and Guizhi Fuling Pills( three representative drugs on market) from Chinese Pharmacopoeia2015 Volume I issued by Chinese Pharmacopoeia Commission to analyze their patent layout,reflecting its status quo of patent protection as follows: first,in recent years,the number of related patent applications for Classical Representative Famous Prescriptions has declined,which was positively correlated with the drug registration and approval policies in recent years,but the policy dividend has not been reflected in the patent application,which may be related to the long period of pharmaceutical R&D; secondly,the patent applicant in the field of Chinese medicine is mainly based on individuals,but the applicant of Classical Representative Famous Prescription is mainly of enterprises,and in addition,the company applicants have the highest authorization rate; thirdly,the main technologies are to improve preparation method and the dosage form in the research and development of Classical Representative Famous Prescription,but these two types of authorized patents have much difficulty in further application on the market. Therefore,the innovative entities shall look for a new breakthrough in secondary development and utilization of Classical Representative Famous Prescriptions.

Chemical components and pharmacological effects for Guizhi Fuling Prescription and predictive analysis on quality marker (Q-marker) / 中草药

Guizhi Fuling Prescription is a classic prescription for promoting blood activation and resolving stasis. It has the functions of improving blood rheology, regulating endocrine, anti-inflammation, anti-cancer, and analgesia. In ancient times, it was used to treat women’s bleeding during pregnancy, abdominal pain, and postpartum lochia. It is also often used to treat gynecological diseases in modern clinics, such as uterine fibroids, ovarian cysts, dysmenorrhea, endometriosis and so on. This paper reviewed the research progress of chemical constituents, pharmacological activities, clinical application, and quality control of Guizhi Fuling Prescription in recent years. On the basis of this, the quality markers of Guizhi Fuling Prescription are predicted and analyzed based on the “five principles” of quality markers of Chinese materia medica in order to provide reference for the study of quality control of Guizhi Fuling Prescription.

Research progress on material basis of Guizhi Fuling Prescription in treating gynecological blood stasis syndrome / 中草药

Guizhi Fuling Prescription first appeared in “Synopsis of Golden Chamber” by Zhongjing Zhang, which is mainly used to treat the accumulation of the woman’s belly. It is the preferred base for the treatment of gynecological blood stasis. The prescription, single herbs and its anti-gynaecological blood stasis material basis of Guizhi Fuling Prescription were summarized in this thesis based on the ancient books and Chinese and foreign literatures mining with view to providing reference for its in-depth study.

Study on on-line near-infrared spectroscopic for moisture monitoring in a fluidized bed drying process of Guzhi Fuling Capsules / 中草药

Objective: To establish a real-time moisture monitoring model for the fluidized bed drying process of Guizhi Fuling Capsules (GFC) by using online near-infrared spectroscopy (NIRS). Methods: A total of 176 samples from 16 production batches were collected by NIRS diffuse reflection probe for modeling. The moving window average smoothing method was used for spectral preprocessing. The characteristic variables were 4 759.45—5 338.00 cm−1, 5 503.84—6 101.67 cm−1, and 8 512.25—8 809.24 cm−1, which were screened by the interval partial least squares method (siPLS) combined with the moving window partial least squares (mwPLS). The partial variable least squares (PLS) method was used to build a multivariate correction model for moisture. Results: The root mean square error of cross-validation (RMSECV) of predicted moisture was 0.243%, the ratio of predicton to deviation (RPD) was 13.384, and the relative standard error of prediction (RSEP ) was 0.270%. The reliability of the online monitoring method was continuously verified by eight production batches. The relative error of 40 samples was less than 4.7%, indicating that the PLS quantitative model prediction performance was robust and accurate. The real-time monitoring trend chart of the moisture in the drying process can accurately determine the drying end point, and the moisture content of the end sample was within the control limit. Conclusion: The quantitative model established by online NIRS combined with PLS can be applied to the on-line monitoring of moisture content in the fluidized bed drying process of production scale GFC and the prediction performance was robust and accurate.

Post-marketing surveillance on Guizhi Fuling Jiaonang based on literature review / 中国中药杂志

To systemically evaluate the post-marketing safety of Guizhi Fuling Jiaonang. Computer retrieval was conducted in Medline, EMbase, the Web of Science, Clinical Trials. Gov, the Cochrane Library, CNKI, VIP, WanFang Data and CBM to collect relevant information. The papers were then screened according to inclusion and exclusion criteria. A total of 234 papers were included in this study, including 164 randomized controlled trials, 7 quasi-randomized controlled trials, 8 non-randomized controls, 56 case series, and 1 cohort study. The patients were only treated with Guizhi Fuling Jiaonang in 56 studies, and Guizhi Fuling Jiaonang was combined with other drugs in 178 studies. The total ADRs/AEs incidence was 1.99% in single use of Guizhi Fuling Jiaonang, and 8.21% in combined use, but showing no severe adverse reactions. Gastrointestinal system damage was most common in mild ADRs. In this study, it was found that the overall safety of Guizhi Fuling Jiaonang was acceptable. The direct evidences of the drug's safety case reports were systematically analyzed in this study, but the mechanism study on the safety of the drug after marketing or the prospective long-term clinical observation study was not sufficient, so the further studies on the safety of drug use should be conducted in order to provide better guidance for clinical medication.

Guizhi Fuling Wan reverses drug resistance by regulating PTEN and MTDH in ovarian cancer SKOV3/DDP Cells / 中国药理学与毒理学杂志

OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog (PTEN) and metadherin (MTDH). METHODS Guizhi Fuling Wan (GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition, Wistar rats were given GFW viagavage at 4 g·kg-1·d-1,8 g·kg-1·d-1,16 g·kg-1·d-1,or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera, medium-dose sear, high-dose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells. Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells. RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera. RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli-taxel, the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold, respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec-tively; there was a significant difference between the groups (P<0.01). RT-qPCR results showed that, compared with the blank serum, the sera can up-regulate the expression of PTEN mRNA and down-regulate the expression of MTDH mRNA in a dose-dependent manner. Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement. CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH, up-regulation of PTEN and induction of apoptosis, providing with an experiment basis for the applica-tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.

An UPLC-MS/MS method for simultaneous determination of multiple constituents in Guizhi Fuling capsule with ultrafast positive/negative ionization switching / 中国天然药物

Guizhi Fuling capsule (GFC), a traditional Chinese medicine (TCM) with effects of promoting blood circulation and dissipating blood stasis, has been widely used in the clinic. Because of the complex matrix and various chemical structure types, quality control of GFC remains great challenge. In the present study, an ultra performance liquid chromatography hybrid triple-quadrupole mass spectrometry (UPLC-QQQ MS) method with ultrafast positive/negative ionization switching was developed for simultaneous determination of 18 bioactive components in GFC, including methyl gallate, ethyl gallate, oxypaeoniflorin, benzoic acid, albiflorin, paeonolide, paeoniflorin, 1, 2, 3, 4, 6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, pachymic acid, amygdalin, cinnamaldehyde, paeonol, cinnamic acid, 4-hydroxybenzoic acid, and gallic acid. Separation was performed on an Agilent Zorbax Extend-C18 column (2.1 mm × 50 mm, 1.8 μm), using a gradient elution with acetonitrile and water containing 0.1% formic acid. Cholic acid was selected as the internal standard. This newly developed method was fully validated for linearity, precision, accuracy, and stability, and then applied to quality assessment of GFC. Finally, the batch-to-batch reproducibility of GFC samples was evaluated by the cosine ration and Euclidean distance method, which showed high quality consistency. The results demonstrated that the developed method pro vided a reasonable and powerful manner for quality control of GFC.

Study on the Inhibitory Effect and Mechanism of Guizhi Fuling Pill on Angiogenesis in Rats with Endometriosis / 现代医院

Objective To analyze and discuss the specific effect and mechanism of Guizhi Fuling pill on angiogenesis in rats with endometriosis. Methods A rat model of endometriosis was established in 40 rats in the same batch, they were randomly divided into 4 groups. The model control group did not give any drugs; the low dose of Guizhi Fuling pill group was given 0. 5 g Guizhi Fuling pill every day; the high dose of Guizhi Fuling pill group was given 3. 0 g cinnamon Fuling pill every day; gestation three ketone group was given three ketene 2 g every day. After 4 weeks of continuous administration, the rats were killed and the expression of VEGF and HIF-1 alpha in the rats was determined. The mechanism of Guizhi Fuling pill in the treatment of endometriosis was determined through the expression of VEGF and HIF-1α. Results Guizhi Fuling pill significantly inhibited the level of intravascular VEGF in rat endometriosis and inhibited the level of mRNA expression of HIF-1α. Conclusion Guizhi Fuling pill can inhibit the angiogenesis of endometriosis, and its mechanism is related to the inhibition of VEGF and HIF-1 alpha.