Research and development practice of traditional Chinese medicine based on network target theory and technology / 中国中药杂志

Network targets theory and technology have transcended the limitations of the "single gene, single target" model, aiming to decipher the mechanisms of traditional Chinese medicine(TCM) based on biological network from the perspective of informatics and system. As the core of TCM network pharmacology, with the development of computer science and high-throughput experimental techniques, the network target theory and technology are beginning to exhibit a trend of organic integration with artificial intelligence technology and high-throughput multi-modal multi-omics experimental techniques. Taking the network target analysis of TCM like Yinqiao Qingre Tablets as a typical case, network target theory and technology have achieved the systematic construction, in-depth analysis, and high-throughput multi-modal multi-omics validation of multi-level biological networks spanning from traditional Chinese and Western phenotypes to tissues, cells, molecules, and traditional Chinese and Western medicines. This development helps to address critical issues in the analysis of mechanisms of TCM, including the discovery of key targets, identification of functional components, discovery of synergistic effects among compound ingredients, and elucidation of the regulatory mechanisms of formulae. It provides powerful theoretical and technological support for advancing clinical precision diagnosis and treatment, precise positioning of TCM, and precise research and development of TCM. Thus, a new paradigm of TCM research gradually emerges, combining big data and artificial intelligence(AI) with the integration of human experience and scientific evidence.

Platycodon grandiflorum extract attenuates lipopolysaccharide-induced acute lung injury via TLR4/NF-κBp65 pathway in rats.

The traditional Chinese medicine Platycodon grandiflorum (PG) is often used for the treatment of a number of chronic inflammatory diseases. In Chinese veterinary clinic, PG is always extracted by decoction and taken orally, however, the molecular mechanism of PG extract (PE) to reduce LPS-induced inflammation, especially acute lung injury (ALI) in vivo, are not known. Thus, we have studied the anti-inflammatory effects of PE on lipopolysaccharide (LPS)-induced acute lung injury via TLR4/NF-κBp65 pathway in rat. Sprague-Dawley rats were randomly divided into 4 groups: control group, LPS group, LPS±PE low dose group and LPS±PE high dose group. All rats were given corresponding PE solution or the same amount of normal saline by intragastric administration for 7 days. On the 7th day, 1 h after the last administration, 500 µg of LPS were introduced intratracheally to establish ALI rat model, and the same volume of normal saline was given to control group. The results showed that PE reduced the levels of LPS-induced pro-inflammatory mediators including IL-6, PGE2, and TNF-α, alleviated the lung injury histologically, and down-regulated LPS-induced mRNA and protein levels of TLR4/NF-κBp65 in lung tissue. This study demonstrated that PE has the anti-inflammatory effects on LPS-induced ALI in rats through TLR4/NF-κBp65 signaling pathway, indicating that PE is an effective suppressor for anti-inflammatory activities.

Clinical observation on moxibustion therapy plus tuina in treating children with recurrent respiratory tract infections due to qi deficiency of spleen and lung / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of moxibustion therapy plus Liu's pediatric massage (tuina) for children with recurrent respiratory tract infections due to qi deficiency of spleen and lung. Methods: A total of 60 children who met the inclusion criteria were divided into an observation group and a control group according to the visiting sequence, with 30 cases in each group. Children in the observation group were treated with moxibustion therapy plus Liu's pediatric massage, and those in the control group were treated with Liu's pediatric massage alone. The incidence of respiratory tract infections and traditional Chinese medicine (TCM) symptoms score were observed and recorded in both groups before and after treatment. And the clinical efficacy was compared between the two groups. Results: The total effective rate of the observation group was 93.3％, and that of the control group was 83.3％. The difference between the two groups was statistically significant (P<0.05). After treatment, the TCM symptoms score and total times of infections in both groups were all statistically different from those before treatment (all P<0.05). The differences in TCM symptoms score and infection frequency before and after treatment in the observation group were statistically different from those in the control group (both P<0.05). Conclusion: Moxibustion therapy plus Liu's pediatric massage has a better effect in improving the clinical symptoms and reducing the frequency of respiratory tract infections for children with recurrent respiratory tract infections due to qi deficiency of spleen and lung than the pediatric massage alone.

Comparable efficacy of 100 mg aspirin twice daily and rivaroxaban for venous thromboembolism prophylaxis following primary total hip arthroplasty: a randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Aspirin has demonstrated safety and efficacy for venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA); however, inconsistent dose regimens have been reported in the literature. This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA.@*METHODS@#Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin (100 mg twice daily) or rivaroxaban (10 mg once daily). Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence, deep vein thrombosis (DVT) on Doppler ultrasonography, total blood loss (TBL), laboratory bloodwork, Harris hip score (HHS), post-operative recovery, and the incidence of other complications.@*RESULTS@#We included 70 patients in this study; 34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis, respectively. No cases of symptomatic VTE occurred in this study. The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group (8.8% vs. 8.3%, χ2 = 0.01, P = 0.91), confirming the non-inferiority of aspirin for DVT prophylaxis (χ2 = 2.29, P = 0.01). The calculated TBL in the aspirin group (944.9 mL [658.5-1137.8 mL]) was similar to that in the rivaroxaban group (978.3 mL [747.4-1740.6mL]) (χ2 = 1.55, P = 0.12). However, there were no significant inter-group differences in HHS at post-operative day (POD) 30 (Aspirin: 81.0 [78.8-83.0], Rivaroxaban: 81.0 [79.3-83.0], χ2 = 0.43, P = 0.67) and POD 90 (Aspirin: 90.0 [89.0-92.0], Rivaroxaban: 91.5 [88.3-92.8], χ2 = 0.77, P = 0.44), the incidence of bleeding events (2.9% vs. 8.3%, χ2 = 0.96, P = 0.33), or gastrointestinal complications (2.9% vs. 5.6%, χ2 = 1.13, P = 0.29).@*CONCLUSION@#In terms of safety and efficacy, the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA. This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR18000202894; http://www.chictr.org.cn/showproj.aspx?proj=33284.

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.

Akebia trifoliata (Thunb.) Koidz Seed Extract inhibits human hepatocellular carcinoma cell migration and invasion in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: The high recurrence rate postoperative and extensive metastases have become the obstacle of Hepatocellular Carcinoma (HCC) efficacy improvements, which contribute to most of the patient mortality. Akebia trifoliata (Thunb.) Koidz has been shown pharmacological activities in clinical and anti-HCC biological activity in previous research, but its potential function of anti-metastasis remains unknown. AIM OF THIS STUDY: To make sure whether ATKSE inhibits migration and invasion in HCC cell lines in vitro and the potential mechanism. MATERIALS AND METHODS: A UHPLC-HRMS analysis was adopted to identify and control the quality of the ethanol extract of Akebia trifoliata (Thunb.) Koidz Seed (abbreviated ATKSE). Cell viability of three kinds of HCC cell lines (HEPG2, HUH7, and SMMC7721) was detected using MTT assay and Flow cytometry. Adhesion capacity was measured by cell-matrigel adhesion assay. Wounded healing and Matrigel-transwell invasion assays were performed to assess cell migration and invasion, respectively. Western blot assay was used to detect several metastasis-related protein molecules, including FAK adhesion signaling, cadherin molecules, and MMPs. ELISA assay was used to evaluate the secreted MMP9 level. RESULTS: ATKSE significantly suppressed HCC cells viability and proliferation (from 0.9 up to 3.0 mg/ml); then under sub-lethal concentration (from 0.25 up to 1.0 mg/ml), ATKSE inhibited cell adhesion, migration, and invasion in a way of dose-dependent. Several metastatic-related molecules or pathway, including FAK adhesion signaling, cadherin molecules, and MMPs, took part in this process. There are both differences and commonalities in various cell lines: typically such as p-FAK was down-regulated by ATKSE in both HEPG2 and SMMC7721, while was raised in HUH7; Further attempts on the combination of ATKSE and FAK inhibitors, provide us with the enhanced inhibitory effects of invasion and migration in HEPG2 and HUH7 cells, as well as antagonistic effects in SMMC7721. As a target or potential mechanism, it may be more valuable to concern FAK inhibition by ATKSE in HEPG2 cells than in the other two cells. CONCLUSIONS: These results suggest that ATKSE has anti-metastasis potency in HCC cells.

Molecular mechanism of Epimedii Folium in treatment of osteoporosis based on network pharmacology / 中国中药杂志

Osteoporosis is a systematic bone disease,characterized by deterioration in bone mass or micro-architecture,and increasing risk of fragility and fractures. With the development of aging problems,osteoporosis has been a global health problem. At present,due to the undesirable side effects of synthetic osteoporosis inhibitors,more efforts are made in treatment of osteoporosis by traditional Chinese medicine and its prescriptions. Epimedii Folium,one of the most common herbs for osteoporosis,has attracted great attentions worldwide.In this study,network pharmacology was employed to analyze the active components and potential molecular mechanism of Epimedii Folium on osteoporosis. Component-target network analysis showed that those with higher molecular network degree were flavonoids,with estrogen-like activity,antioxidation and free radical-scavenging activities,playing certain roles in preventing and treating osteoporosis. On the other hand,the targets with high degree were mostly related with sex hormone,osteoclast differentiation,bone matrix degradation,and reactive oxygen species in drug-target network. Multiple components of Epimedii Folium could be interacted with these targets. This study shows that Epimedium could prevent and treat osteoporosis through multiple active ingredients acting on multiple targets.

Clinical observation of warm acupuncture combined with yoga posture method in the treatment of periarthritis with frozen period / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of warm acupuncture combined with yoga posture method in the treatment of periarthritis with frozen period.@*METHODS@#Ninety patients with periarthritis who met the inclusion criteria were randomly divided into a control group 1, a control group 2 and an observation group, 30 cases in each group. Warm acupuncture was applied in the control group 1 (Jianzhen (SI 9), Jianyu (LI 15), Jianliao (TE 14), etc were selected), yoga posture method was applied in the control group 2, warm acupuncture combined with yoga posture method were given in the observation group, the treatment was given once a day, 10 times as a course with 2 days between courses and continuous for 2 courses. After 2 courses of treatment, the shoulder joint pain score and shoulder function grading were used to evaluate the clinical efficacy, and the clinical efficacy was observed.@*RESULTS@#①The pain scores of the three groups were significantly lower after treatment (all 0.05). ②After treatment, the functional classification of shoulder joints were significantly improved in the three groups (all 0.05). ③After 2 courses of treatment, the effective rate of the observation group was 86.7% (26/30), which was better than 70.0% (21/30) in the control group 1 and 76.7% (23/30) in the control group 2 (both <0.05).@*CONCLUSION@#Warm acupuncture combined with yoga posture method can effectively relieve shoulder pain and improve dysfunction. The clinical comprehensive effect is better than simple acupuncture and yoga posture method.

Rapid identification of chemical components in compound Nanxing acesodyne plaster by UPLC-Q-TOF-MS/MS / 中国中药杂志

The study aims to qualitatively analyze the chemical composition of compound Nanxing acesodyne plaster by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). The analysis was performed on Agilent Zorbax SB-C_(18)( 4. 6 mm×250 mm,5 μm) column. The mobile phase consisted of methanol and 0. 2% formic acid-water was used as gradient elution. The flow rate was 1 mL·min~(-1) and column temperature was 30 ℃. The Mass spectrometry was acquired in both positive and negative ion modes using ESI. The components were identified by the precise mass-to-charge ratio,secondary fragmentation and other information combined with reference substance and literature data. As a result,58 compounds were identified and predicted,including alkaloids,flavonoids,coumarins,organic acids and lactone compounds,of which 12 compounds were verified by the reference substances. The results provide reference for the quality control of compound Nanxing acesodyne plaster,and lay the foundation for elucidating the active components mechanism.

New situation and new strategies——research and development and internationalization of new drugs and health products of traditional Chinese medicine / 中国药理学与毒理学杂志

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

Network-assisted mechanism investigation of Yaobitong Capsules on lumbar intervertebral discs / 中成药

AIM To explore analgesic mechanism of Yaobitong Capsules (Notoginseng Radix et Rhizoma,Chuanxiong Rhizoma,Corydalis Rhizoma,etc.) on lumbar intervertebral discs.METHODS An array of data mining,molecular docking and network analysis were employed to investigate the active compounds and key target protein.RESULTS Among the forty-six active hits identified by virtual screening,most compounds displayed good oral bioavailability and might confer an optimal CNS exposure.And eleven molecules (coptisine,diligustilide,corypalmine,chuanxiongterpene,etc.) were further confirmed to alleviate lumbar intervertebral discs through their targeting at nineteen proteins (such as p38,CGRP,MMPs,TNFα) to inhibit the inflammatory response and the infiltration of microvasculature,to reduce the nociceptors sensitivity,and to modulate the balance of Collagen and proteoglycans in catabolic and anabolic responses.CONCLUSION Yaobitong Capsules' clear molecular working mechanism and the key active compounds are revealed by this network-assisted investigation highlight the subsequent experiments on targets and active compounds.

Expression of G-protein coupled estrogen receptor in the testis of the male mouse with kidney yin or kidney yang deficiency and its impact on the reproductive function of the mouse / 中华男科学杂志

Objective@#To investigate the expression of the G-protein coupled estrogen receptor (GPER) in the testis of the male mouse with kidney yin or kidney yang deficiency and its influence on the reproductive function of the mouse.@*METHODS@#We randomized 30 six-week-old male Kunming mice into three groups of equal number: kidney yang deficiency, kidney yin deficiency, and normal control, and established the models of kidney yang deficiency and kidney yin deficiency by peritoneal injection of hydrocortisone at 50 mg/kg for 5 days and 25 mg/kg for 10 days, respectively. We observed the behavioral changes of the mice using the elevated plus-maze, exhaustive swimming and field experiment, examined the semen quality with the automatic sperm quality analyzer, calculated the average number of the offspring, measured the serum testosterone (T) and estradiol (E2) levels and T/E2 ratio by Roche electrochemiluminescence assay, and determined the localization and expression of GPER in the testis by immunohistochemistry and immunofluorescence staining.@*RESULTS@#Compared with the mice with kidney yin deficiency, those with kidney yang deficiency showed remarkably fewer entries into the open arm and central area (P 0.05); the latter group also exhibited significant decreases in the epididymal sperm count (［7.27 ± 1.30］ vs ［3.05 ± 1.06］ ×108/g, P 0.05), and markedly reduced serum T (［24.96 ± 6.18］ vs ［16.72 ± 5.92］ ng/dl,P <0.05), E2 (［19.81 ± 4.01］ vs ［15.24 ± 1.11］ pg/ml,P <0.05) and T/E2 ratio (1.41 vs 1.25, P <0.05). The expression of GPER was found in the cytoplasm of the Leydig cells, negative in the nuclei and cell membrane, significantly higher in the kidney yang than in the kidney yin deficiency group (P <0.05).@*CONCLUSIONS@#The numbers of sperm and offspring decreased while the percentage of morphologically abnormal sperm increased in both the kidney yang and kidney yin deficiency mice, even more significantly in the former, which might be associated with the up-regulated expression of GPER in the testis of the mouse with kidney yang deficiency and consequently the reduced serum T level and T/E2 ratio.

Mechanism of Tongsaimai tablet for atherosclerosis based on network pharmacology / 中国中药杂志

Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis, 97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein (docking score ≥ 7), and 37 molecules of them could act on more than 2 targets (≥ 2) with higher betweenness, suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore, the predicted active compounds contained more flavonoids and saponins, reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that, the active compounds of Tongsaimai tablets could regulate inflammation, stabilize plaque, protect vascular endothelial cell, regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins, such as Toll-like receptors (TLR1, TLR2), matrix metalloproteinase (MMP1, MMP2, MMP3, MMP9), angiotensin converting enzyme (ACE), leukotriene A4 hydrolase (LTA4-H), 5-lipoxidase (5-LOX), peroxisome proliferators-activated receptors (PPARα, PPARγ). These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile, verified the characteristics of multi-components, multi-targets and integral regulation for Tongsaimai tablets, providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet.

HTRF-based high-throughput PGE2 release prohibition model and application in discovering traditional Chinese medicine active ingredients / 中国中药杂志

Prostaglandin (PG) E2 is an active substance in pathological and physiological mechanisms, such as inflammation and pain. The in vitro high-throughput assay for screening the inhibitors of reducing PEG2 production is a useful method for finding out antiphlogistic and analgesic candidates. The assay was based on LPS-induced PGE2 production model using a homogeneous time-resolved fluorescence(HTRF) PGE2 testing kit combined with liquid handling automation and detection instruments. The critical steps, including the cell density optimization and IC50 values determination of a positive compound, were taken to verify the stability and sensibility of the assay. Low intra-plate, inter-plate and day-to-day variability were observed in this 384-well, high-throughput format assay. Totally 5 121 samples were selected from the company's traditional Chinese medicine(TCM) material base library and used to screen PGE2 inhibitors. In this model, the cell plating density was 2 000 cells for each well; the average IC₅₀ value for positive compounds was (7.3±0.1) μmol; the Z' factor for test plates was more than 0.5 and averaged at 0.7. Among the 5 121 samples, 228 components exhibited a PGE2 production prohibition rate of more than 50%, and 23 components exhibited more than 80%. This model reached the expected standards in data stability and accuracy, indicating the reliability and authenticity of the screening results. The automated screening system was introduced to make the model fast and efficient, with a average daily screening amount exceeding 14 000 data points and provide a new model for discovering new anti-inflammatory and analgesic drug and quickly screening effective constituents of TCM in the early stage.

Research on immune-modulation effects and its mechanisms of Guizhi Fuling capsule and its active ingredient combination / 中国中药杂志

The effects of Guizhi Fuling capsule and its active ingredient combination within different concentration on SPL proliferate were observed by MTT method. The ratio of CD80/86, CD3CD25 and CD3CD69 was used to evaluate cell activation effects of Guizhi Fuling capsule and its active ingredient combination by FCM. Guizhi Fuling capsule with concentration of 400 mg · L(-1)can promote spleen lymphocyte proliferation, as well as the active ingredient combination, which showed the obvious dose-effect relationship. Compared with control group, the difference has statistical significance (P≤0.01). The result of FCM showed that Guizhi Fuling capsule and its active ingredient combination can promote CD80 and CD86 expression on spleen lymphocyte, and also can increase CD25 and CD69 ratio between spleen CD3+ cells. Compared with control group, the difference has statistical significance (P≤0.01). Thus, Guizhi Fuling capsule and its active ingredient combination may have immune-modulate effects, and the mechanism may have a close relationship with the lymphocyte activation.

Study on effective substance basis and molecular mechanism of Qigui Tongfeng tablet using network pharmacology method / 中国中药杂志

Qigui Tongfeng tablet (QLTFT) is a traditional Chinese medicine with good effect for treating gout. Here, network pharmacology method and molecular similarity analysis were utilized to study the effective substance basis and molecular mechanism of the QLTFT on the gout. The similarity to the medicinal compounds is reflected in the Tanimoto coefficient that gives the structural similarity of two compounds. Operationally, similar modifiers were described as pairs of concepts with a similarity score of 0. 500. The results of the molecular similarity analysis suggested that the flavonoids in QLTFT could be new leads for gout. Furthermore, complex biological systems may be represented and analyzed as computable networks. Two important properties of a network were degree and betweenness. Nodes with high degree or high betweenness may play important roles in the overall composition of a network. And the results of network analysis showed that dongbeinine, verticinone-N-oxide, verticine N-oxide, peimine, peiminine, isobaimonidine, dongbeirine, peimisine and simi-arenol which with high degree acted on xanthine dehydrogenase/oxidase, matrix metalloproteinase-9, an arachidonate 5-lipoxygenase-activating protein, tyrosine-protein kinase and etc. Inhibition of these targets can prevent the formation of uric acid, reduce inflammation by uric acid and regulate the body's immune response. Thus, these compounds may be the main effective substance basis. The research results not only reveals its molecular mechanism, but also provide a theoretical basis for the quality control of drugs and clinical application.

Monitor on influence of quality standard improvement upon Guizhi Fuling capsules efficacy / 中国中药杂志

In 2012, the preparation process and quality standard for Guizhi Fuling capsule were improved. To compare the effects and differences of capsules before (2011) and after(2012-2014) the improvement, evaluation models for intrinsic dysmenorrhea, pelvic inflammation and hysteromyoma were applied in rats. Models were induced by oxytocin, liqiud bacteria mixture and estrogen loading, respectively. The capsules (12 batchs/year, 48 bathcs in all), sampled randomly in 2011-2014, the effects were assessed using the three models. In anti-dysmenorrhea models, remarked reduction of writhing frequency, ET-1 and PGF2α content in uterus could be detected, as well as extension of writhing latency. In pelvic inflammation rats, depression of TNF-α and raise of IL-2 were induced by earh batch of capsules. In hysteromyoma model, uterine weight and smooth muscle proliferation, including E2 and P level in plasma, were lowered obviously by all batchs of capsules. Secondly, Guizhi Fuling capsules produced in 2012-2014 revealed better effectiveness than the ones manufactured in 2011. Moreover, pharmacodynamics indexes of the samples made in 2011 differed significantly between groups, which could not be observed in the ones ot 2012-2014. After tne preparation process and quality standard improvement, the effectiveness and homogeneity of Guizhi Fuling capsules were enhanced.

Study on anti-inflammation and immunoloregulation effect of Guizhi Fuling capsule ingredients using high content screening / 中国中药杂志

The present study sought to investigate the anti-inflammation and immunoloregulation effect of 17 Guizhi Fuling capsule ingredients. The anti-inflammatory ingredients on LPS-induced RAW264. 7 cell injury were assessed with ELISA and immunofluorescence. The release of IL-1β, TNF-α, PGE2 were detected with ELISA and the expression of COX-2 was detected with immunofluorescence. The effects of them on promoting splenic lymphocyte proliferation were assessed with MTT and Hoechst 33342 staining method. The results showed that 15 ingredients had obviously anti-inflammatory activity on LPS- induced injury and play the immunoloregulation roles. This study suggested that the 15 ingredients may be the active ingredients on pelvic infection.

Study of effective components and molecular mechanism for Guizhi Fuling formula treatment of dysmenorrhea, pelvic inflammatory disease and uterine fibroids / 中国中药杂志

In this study, the active components and potential molecular .mechanism of Guizhi Fuling formula in treatment on dysmenorrhea, pelvic inflammation, and hysteromyoma were investigated using network pharmacological methods. Sterols and pentacyclic triterpenes, with high moleculal network degree, revealed promising effects on anti-inflammatory, analgesic, anti-tumor, and immune-regulation, according to D-T network analysis. On the other hand, the targets with high degree were involved in inflammatory, coagulation, angiopoiesis, smooth muscle contraction, and cell reproduction, which showed the novel function in anti-dysmenorrhea, pelvic inflammation, and hysteromyoma. Furthermore, the formula was indicated to play a key role in smooth muscle proliferation, inhibition of new vessels, circulation improvement, reduction of hormone secretion, alleviation of smooth muscle, block of arachidonic acid metabolism, and inflammation in uterus. Thus, the main mechanism of Guizhi Fuling formula was summarized. In conclusion, Guizhi Fuling formula was proven to alleviated dysmenorrhea, pelvic inflammation, and hysteromyoma by acting on multiple targets through several bioactive compounds, regulating 21 biological pathways.

Study on anti-inflammation effect and involved mechanism of Guizhi Fuling capsule and its active complex / 中国中药杂志

The aim of this study was to investigate the anti-inflammatory effect of Guizhi Fuling capsule and its active complex (consistent of 15 active compounds) on LPS-induced RAW264. 7 cells. The effect of Guizhi Fuling capsule and its active complex on cell viability in RAW264. 7 cells were determined by MTT assay. The inhibitory effect of Guizhi Fuling capsule and active complex on the releasing of IL-1β, TNF-α and PGE2 induced by LPS in RAW264. 7 cells was detected by ELISA assay. The expression of IL-1β and mPGES-1 in Guizhi Fuling capsule or active complex treated RAW264. 7 cells was examined by Western blot assay. Guizhi Fuling capsule and active complex showed no significant effect on the cell viability in RAW264. 7 cells at doses range from 12.5 to 400 mg x L(-1). Compared with LPS treated group, Guizhi Fuling capsule and active complex dose dependently reduced the releasing of IL-1β, TNF-α and PGE2 induced by LPS in RAW264. 7 cells. Moreover, the expression of IL-1β and mPGES-1 was decreased after Guizhi Fuling capsule and active complex treatment, which might contribute to the inhibitory effect of Guizhi Fuling capsule in the releasing of IL-1β, TNF-α and PGE2. This study provided the evidence that Guizhi Fuling capsule and active complex remarkably inhibited the releasing of IL-1β, TNF-α and PGE2induced by LPS in RAW264. 7 cells by reducing the expression IL-1β and mPGES-1. This study provided an experimental basis of Guizhi Fuling capsule for the treatment of inflammation and a theoretical basis for the development of effective compounds of Guizhi Fuling capsule.