Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Guì-Yào-Lüe" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). AIM OF THE STUDY: This study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. MATERIALS AND METHODS: A CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP ("HaiShi GuaLou" and "WanLou") by analyzing the main components and their effects. Network pharmacology, molecular docking-based studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. RESULTS: TP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKCα], protein kinase C beta type [PKCß], von Willebrand factor [vWF], and prostaglandin-endoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKCα, PKCß, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. CONCLUSION: Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways.

Unraveling the pharmacodynamic substances and possible mechanism of Trichosanthis Pericarpium in the treatment of coronary heart disease based on plasma pharmacochemistry, network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Coronary heart disease (CHD) is a chronic disease that seriously threatens people's health and even their lives. Currently, there is no ideal drug without side effects for the treatment of CHD. Trichosanthis Pericarpium (TP) has been used for several years in the treatment of diseases associated with CHD. However, there is still a need for systematic research to unravel the pharmacodynamic substances and possible mechanism of TP in the treatment of coronary heart. AIM OF THE STUDY: The purpose of current study was to explore the pharmacodynamic substances and potential mechanisms of TP in the treatment of CHD via integrating network pharmacology with plasma pharmacochemistry and experimental validation. MATERIALS AND METHODS: The effect of TP intervention in CHD was firstly assessed on high-fat diet combined with isoprenaline-induced CHD rats and H2O2-induced H9c2 cells, respectively. Then, the LC-MS was utilized to identify the absorbed components of TP in the plasma of CHD rats, and this was used to develop a network pharmacology prediction to obtain the possible active components and mechanisms of action. Molecular docking and immunohistochemistry were used to explore the interaction between TP and key targets. Subsequently, the efficacy of the active ingredients was investigated by in vitro cellular experiments, and their metabolic pathways in CHD rats were further analyzed. RESULTS: The effects of TP on amelioration of CHD were verified by in vivo and in vitro experiments. Plasma pharmacochemistry and network pharmacology screened six active components in plasma including apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin. The interaction of these compounds with potential key targets AKT1, IL-1ß, IL-6, TNF-α and VEGFA were preliminarily verified by molecular docking. And immunohistochemical results showed that TP reduced the expression of AKT1, IL-1ß, IL-6, TNF-α and VEGFA in CHD rat hearts. Then cellular experiments confirmed that apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin were able to reduce the ROS level in H2O2-induced HUVEC cells and promote the migration and tubule formation of HUVEC cells, indicating the pharmacodynamic effects of the active components. Meanwhile, the metabolites of TP in CHD rats suggested that the pharmacological effects of TP might be the result of the combined effects of the active ingredients and their metabolites. CONCLUSION: Our study found that TP intervention in CHD is characterized by multi-component and multi-target regulation. Apigenin, phenylalanine, linoleic acid, quercetin, luteolin, and tangeretin are the main active components of TP. TP could reduce inflammatory response and endothelial damage by regulating AKT1, IL-1ß, IL-6, TNF-α and VEGFA, reduce ROS level to alleviate the oxidative stress situation and improve heart disease by promoting angiogenesis to regulate endothelial function. This study also provides an experimental and scientific basis for the clinical application and rational development of TP.

Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3.

OBJECTIVE: This study aims to investigate the effect of red ginseng polysaccharide (RGP) on gastric cancer (GC) development and explore its mechanism. METHODS: GC cell lines AGS were treated with varying concentrations of RGP (50, 100, and 200 µg/mL). AGS cells treated with 200 µg/mL RGP were transfected with aquaporin 3 (AQP3) overexpression vector. Cell proliferation, viability, and apoptosis were evaluated by MTT, colony formation assay, and flow cytometry, respectively. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression of AQP3. The levels of Fe2+, malondialdehyde, and lactate dehydrogenase were measured using their respective detection kits, and the reactive oxygen species levels was determined by probe 2',7'-dichlorodihydrofluorescein diacetate. The expression of ferroptosis-related protein and PI3K/Akt pathway-related protein were assessed by western blot. In vivo experiments in nude mice were performed and the mice were divided into four groups (n = 5/group) which gavage administrated with 150 mg/kg normal saline, and 75, 150, 300 mg/kg RGP, respectively. Their tumor weight and volume were recorded. RESULTS: RGP treatment effectively inhibited the proliferation and viability of AGS cells in a dosage-dependent manner and induced apoptosis. It induced ferroptosis in AGS cells, as well as inhibiting the expression of PI3K/Akt-related proteins. AQP3 overexpression could reversed the effect of RGP treatment on ferroptosis. Confirmatory in vivo experiments showed that RGP could reduce the growth of implanted tumor, with increased RGP concentration resulting in greater tumor inhibitory effects. CONCLUSION: RGP might have therapeutic potential against GC, effectively inhibiting the proliferation and viability of AGS cells.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population.

BACKGROUND: The coronavirus disease 2019 (COVID-19) continues to spread worldwide. Integrated Chinese and Western medicine have had some successes in treating COVID-19. OBJECTIVE: This study aims to evaluate the efficacy and safety of three traditional Chinese medicine drugs and three herbal formulas (3-drugs-3-formulas) in patients with COVID-19. SEARCH STRATEGY: Relevant studies were identified from 12 electronic databases searched from their establishment to April 7, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs), non-RCTs and cohort studies that evaluated the effects of 3-drugs-3-formulas for COVID-19. The treatment group was treated with one of the 3-drugs-3-formulas plus conventional treatment. The control group was treated with conventional treatment. DATA EXTRACTION AND ANALYSIS: Two evaluators screened and selected literature independently, then extracted basic information and assessed risk of bias. The treatment outcome measures were duration of main symptoms, hospitalization time, aggravation rate and mortality. RevMan 5.4 was used to analyze the pooled results reported as mean difference (MD) with 95% confidence interval (CI) for continuous data and risk ratio (RR) with 95% CI for dichotomous data. RESULTS: Forty-one studies with a total of 13,260 participants were identified. Our analysis suggests that compared with conventional treatment, the combination of 3-drugs-3-formulas might shorten duration of fever (MD = -1.39; 95% CI: -2.19 to -0.59; P < 0.05), cough (MD = -1.57; 95% CI: -2.16 to -0.98; P < 0.05) and fatigue (MD = -1.36; 95% CI: -2.21 to -0.51; P < 0.05), decrease length of hospital stay (MD = -2.62; 95% CI -3.52 to -1.72; P < 0.05), the time for nucleic acid conversion (MD = -2.92; 95% CI: -4.26 to -1.59; P < 0.05), aggravation rate (RR = 0.49; 95% CI: 0.38 to 0.64; P < 0.05) and mortality (RR = 0.34; 95% CI: 0.19 to 0.62; P < 0.05), and increase the recovery rate of chest computerized tomography manifestations (RR = 1.22; 95% CI: 1.14 to 1.3; P < 0.05) and total effectiveness (RR = 1.24; 95% CI: 1.09 to 1.42; P < 0.05). CONCLUSION: The 3-drugs-3-formulas can play an active role in treating all stages of COVID-19. No severe adverse events related to 3-drugs-3-formulas were observed. Hence, 3-drugs-3-formulas combined with conventional therapies have effective therapeutic value for COVID-19 patients. Further long-term high-quality studies are essential to demonstrate the clinical benefits of each formula. Please cite this article as: You LZ, Dai QQ, Zhong XY, Yu DD, Cui HR, Kong YF, Zhao MZ, Zhang XY, Xu QQ, Guan ZY, Wei XX, Zhang XC, Han SJ, Liu WJ, Chen Z, Zhang XY, Zhao C, Jin YH, Shang HC. Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population. J Integr Med. 2023; 21(5): 441-454.

Antioxidative and Mitochondrial Protection in Retinal Pigment Epithelium: New Light Source in Action.

Low-color-temperature light-emitting diodes (LEDs) (called 1900 K LEDs for short) have the potential to become a healthy light source due to their blue-free property. Our previous research demonstrated that these LEDs posed no harm to retinal cells and even protected the ocular surface. Treatment targeting the retinal pigment epithelium (RPE) is a promising direction for age-related macular degeneration (AMD). Nevertheless, no study has evaluated the protective effects of these LEDs on RPE. Therefore, we used the ARPE-19 cell line and zebrafish to explore the protective effects of 1900 K LEDs. Our results showed that the 1900 K LEDs could increase the cell vitality of ARPE-19 cells at different irradiances, with the most pronounced effect at 10 W/m2. Moreover, the protective effect increased with time. Pretreatment with 1900 K LEDs could protect the RPE from death after hydrogen peroxide (H2O2) damage by reducing reactive oxygen species (ROS) generation and mitochondrial damage caused by H2O2. In addition, we preliminarily demonstrated that irradiation with 1900 K LEDs in zebrafish did not cause retinal damage. To sum up, we provide evidence for the protective effects of 1900 K LEDs on the RPE, laying the foundation for future light therapy using these LEDs.

Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration.

Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible mechanisms behind these effects. A549 cells were treated with TGF-[Formula: see text]1 and TFA to observe the potential effects of TFA on regulating alveolar epithelial cell proliferation, TGF-[Formula: see text]1-induced EMT, and the underlying mechanisms in vitro. Then, mouse pulmonary fibrosis was induced with a single intra-tracheal injection of bleomycin, and TFA was administrated by i.p. injection. Lung fibrosis was evaluated through histological and molecular analyses, and the possible mechanisms were explored using immunological methods. The results demonstrated that TFA could promote cell proliferation but inhibit TGF-[Formula: see text]1-induced EMT on A549 cells. TFA attenuated BLM-induced pulmonary fibrosis in mice by modulating inflammatory infiltration and M2 macrophage polarization; it furthermore modulated EMT through regulating the TGF-[Formula: see text]1/Smad pathway. In addition, TFA augmented the expression of the Wnt7b protein, which plays an important role in alveolar epithelium reparation. In conclusion, TFA alleviated bleomycin-induced mouse lung fibrosis by preventing the fibrotic response and increasing epithelium regeneration.

New compounds from the stems of Fissistigma acuminatissimum Merr. and their in vitro anti-inflammatory activity.

Three new compounds, 4,5,6,7-tetramethoxy-3-benzoylbenzofuran (1), 4-hydroxy-3,5,6-trimethoxydihydrochalcone-2-O-ß-D-glucopyranoside (2) and 2-hydroxy-3,4,5,6-tetramethoxyphenylethyl benzoate (3) along with five known flavonoids were isolated from the dichloromethane fraction of the stems of Fissistigma acuminatissimum Merr.'s ethanol extracts. The compounds were obtained by chromatographic methods and the structure elucidation was completed primarily on the basis of spectroscopic analyses, all of these compounds were isolated from F. acuminatissimum for the first time. All the fractions and compounds were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated tumor necrosis factor α (TNF-α) production in RAW264.7 cells in vitro. The dichloromethane fraction showed the most potent inhibition(38.2%) at 60 µg/mL, compound 1 (70.2%) and 3 (65.2%) showed significant inhibition at 10 µM.

[Concept and method of evidence-based toxicology of traditional Chinese medicine from origin and development of evidence-based toxicology].

Advances in science and technology promote the rapid development of toxicological detection technologies. However, there is still a lack of decision-making tools for toxicological risk assessment, such as the lack of transparent schemes to evaluate current toxicological research and practice and the lag of toxicological testing tools to evaluate toxicity, resulting in difficulties in toxicity verification and hindering the transformation of toxicological research paradigm. Some scholars have proposed to integrate the concept of evidence-based medicine with the toxicological practice to improve the technical methods of toxicological research concept and risk assessment decision-making. With the promotion of relevant scholars and academic organizations, the concept and connotation of evidence-based toxicology have gradually become clear and a framework for research and practice has been initially formed. Although there are still many challenges, it also provides a new idea for the toxicity risk assessment and safe medication decision-making of traditional Chinese medicine(TCM). The era of digital intelligence has brought new opportunities and broad space for the development of TCM evidence-based toxicology. The exploration of TCM evidence-based toxicology from concept to method is an important embodiment of the development of TCM evidence-based toxicology, and will also promote the continuous enrichment and improvement of the research and practice system of TCM evidence-based toxicology.

[Ovulatory disorders under "common therapeutic principle for different diseases": essence of "Tiangui" and relationship with ovulation disorders].

The essence of the "common therapeutic principle for different diseases"(Yibing Tongzhi in Chinese for short) is the disease-syndrome combination, which is the classic mode of understanding and treating diseases in traditional Chinese medicine(TCM). This study holds the view that Yibing Tongzhi is the optimal treatment mode of ovulation disorders since ovulation disorders have the common pathogenesis, i.e., "kidney-Tiangui(reproduction-stimulating essence)-Chongren(thoroughfare and conception vessels)-uterus axis" disorder. Kidney is an important basis of the reproductive axis, where kidney essence, kidney yang, and kidney Qi are the key substances and driving forces promoting the operation of the reproductive axis. Chongren is an important transmission path. "Tiangui", the upstream substance related to the heart, brain and kidney with a connecting effect, plays a key role in the ovulation mechanism and is a representative of the reproductive axis function. There are four common Tiangui abnormalities in ovulatory disorders, including hypomenorrhea, yin and yang deficiency, abnormal exuberance of extreme yin, and abnormal phase. The dynamic changes of "Tiangui" can induce different diseases, such as polycystic ovary syndrome and hyperprolactinemia, which ultimately lead to anovulatory infertility. Therefore, with "Tiangui" as the entry point, it is the treatment trend for ovulatory disorders under Yibing Tongzhi.

[Establishment of multiple evidence-integrated evaluation and prediction method for "toxic" Chinese medicines].

Traditional Chinese medicine(TCM) carries the experience and theoretical knowledge of the ancients, and the use of "toxic" Chinese medicines is a major feature and advantage of TCM. "Toxic" Chinese medicines have unique clinical value and certain medication risk under the guidance of TCM theories such as compatibility for detoxification and treatment based on syndrome differentiation. In recent years, the safety events of Chinese medicines have occurred frequently, which has made the safety of Chinese medicine a public concern in China and abroad. However, limited by conventional cognitive laws and technical methods, basic research on toxicity of Chinese medicines fails to be combined with the clinical application. As a result, it is difficult to identify the clinical characteristics of, predict toxic and side effects of, or form a universal precise medication regimen for "toxic" Chinese medicines, which restricts the clinical application of them. In view of the problem that the toxicity of "toxic" Chinese medicines is difficult to be predicted and restricts the clinical application, the evidence-based research concept will provide new ideas for safe applcation of them in clinical practice. The integrated development of multiple disciplines and techniques in the field of big data and artificial intelligence will also promote the renewal and development of the research models for "toxic" Chinese medicines. Our team tried to propose the academic concept of evidence-based Chinese medicine toxicology and establish the data-intelligence research mode for "toxic" Chinese medicines and the intelligent risk prediction method for medicinal combination in the early stage, which provided methodological supports for solving the above problem. Thus, on the basis of summarizing the research status and problems of the clinical medication regimen of "toxic" Chinese medicines, our team took the evidence-based toxicology of TCM as the core concept, and tried to construct the multiple-evidence integrated evaluation and prediction method for "toxic" Chinese medicine, so as to guide the establishment of the non-toxic medication regimen of "toxic" Chinese medicines. Specifically, through the analysis of multivariate data obtained from the basic research, the evidence-based toxicology database of Chinese medicines and the individualized "toxicity-effect" intelligent prediction platform were built based on the disease-syndrome virtual patients, so as to identify the clinical characteristics and risks of "toxic" Chinese medicines and develop individualized medication regime. This study is expected to provide a methodological reference for the establishment of medication regimen and risk prevention strategy for "toxic" Chinese medicines. The method established in this study will bridge clinical research and basic research, enhance the transformation of the scientific connotation of attenuated compatibility, promote the development of evidence-based Chinese medicine toxicology, and ensure the clinical safety of "toxic" Chinese medicines.

[Guiding significance of "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology (FU Qing-zhu Nyu Ke) for dealing with ovulation disorder infertility caused by hyperprolactinemia].

This paper discussed the guiding significance of "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) for dealing with ovulation disorder infertility caused by hyperprolactinemia(HPRL). FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) concentrates on the disease entities, main symptoms, pathogenesis, and syndrome differentiation, based on which the prescriptions are prescribed. This reflects the "disease-syndrome-symptom" mode, with the core lying in the "combination of disease with syndrome". The contained Discussion on Menstruation Regulation(Tiao Jing Pian) and Discussion on Getting Pregnant(Zhong Zi Pian) have important reference significance for later doctors in the diagnosis and treatment of inferti-lity, and many prescriptions are still in use due to good effects. It is believed in traditional Chinese medicine(TCM) that HPRL results from kidney deficiency and liver depression, among which kidney deficiency is the main cause. Liver depression accelerates the onset of HPRL, so the kidney-tonifying and liver-soothing herbs were mainly selected. The "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) sheds enlightenment on the diagnosis and treatment of ovulation infertility caused by HPRL, in that it is not confined to disease entity and syndrome type. The integration of "disease-syndrome-symptom" highlights the main complaint of patients and emphasizes the main pathogenesis, thus giving full play to the overall advantage of syndrome differentiation. For multiple diseases in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) such as infertility due to liver depression, infertility due to obesity, delayed menstruation, and irregular menstruation, although the typical lactation symptom of HPRL is not mentioned, the medication can still be determined according to the chief complaint, syndrome type, and symptoms and signs, making up for the defects of excessive reliance on serum biochemical indicators in modern Chinese medicine. We should learn its diagnosis and treatment thoughts of paying attention to liver, spleen, kidney, and heart, holism, and strengthening body resistance to eliminate pathogenic factors.

The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against renal injury and inflammation in mice with diabetic kidney disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown. AIM OF THE STUDY: To clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms. MATERIALS AND METHODS: We used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined. RESULTS: FTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80+ macrophage cell infiltration and Ly-6G+ neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ. CONCLUSION: FTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ.

The multifaceted mechanisms of Paeoniflorin in the treatment of tumors: State-of-the-Art.

Paeoniflorin is a water-soluble monoterpenoid glycoside that can be derived from multiple herbaceous plants, such as Radix Paeoniae Rubra, Radix Paeoniae Alba, Paeonia suffruticosa and Cimicifugae Foetidae. Multiple studies have suggested that Paeoniflorin possesses an excellent anti-tumor effect in variety of tumors, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer and bladder cancer. It can induce cell apoptosis, inhibit proliferation, invasion and metastasis via different molecular mechanisms, which are mainly involved in nuclear transcription factor kappα (NF-κB), B-cell lymphoma-2(Bcl-2) family, MicroRNA, neural precursor cell expressed developmentally down-regulated protein 4(NEDD4) signaling pathway, transcription activating factor (STAT3), p21, p53/14-3-3 signaling pathway, transforming growth factor-ß1(TGF-ß1)/Smads signaling pathway, Mitogen-activated protein kinase (MAPK) signaling pathway and Notch-1. Current studies on anti-tumor effect and mechanism of action of Paeoniflorin remain unclear. Therefore, this study reviews the research progress in the anti-tumor effect and mechanism of Paeoniflorin in an attempt to provide a new thought and theoretical basis for further development and clinical application of Paeoniflorin.

In the presence of TGF-ß1, Asperosaponin VI promotes human mesenchymal stem cell differentiation into nucleus pulposus like- cells.

BACKGROUND: The regeneration of nucleus pulposus (NP) cells is an effective method to prevent intervertebral disc degeneration (IVDD). In this study, we investigated the role of Asperosaponin VI (ASA VI), isolated from a traditional Chinese medicine (TCM), the root of Dipsacus asper Wall, in promoting human mesenchymal stem cell (HMSC) proliferation and differentiation into NP-like cells and explored the possible mechanism of action. METHODS: The effects of ASA VI on HMSC viability and proliferation were determined by the XTT method and EDU staining. Then, Real-time qPCR, immunocytochemistry and immunofluorescence assays were used to measure the effect of ASA VI on the expression of extracellular matrix (ECM) components, such as COL2A1, aggrecan, SOX9, KRT19, PAX1, and glycosaminoglycans (GAGs), in NP cells. In addition, Western blot assay was used to measure the expression of p-ERK1/2 and p-smad2/3. RESULTS: ASA VI was able to promote the proliferation and differentiation of HMSCs into NP-like cells, and the optimum concentration was 1 mg/L. Western blot assay indicated that the possible mechanism might be related to the activation of p-ERK1 / 2 and p-Smad2 / 3. CONCLUSIONS: ASA VI can promote the proliferation and differentiation of HMSCs into NP-like cells, which can potentially be used as a treatment for IVDD.

Status Quo and Analysis of the Cardiovascular Clinical Practice Guidelines/Expert Consensuses of Chinese and Integrative Medicine: A Systematic Review.

OBJECTIVE: To describe and analyze the status quo of cardiovascular clinical practice guidelines or expert consensuses including both Chinese medicine (CM) and integrative medicine, through systematic literatures searching and quality assessment. METHODS: Data bases including Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database were searched for published CM or integrative cardiovascular clinical practice guidelines or expert consensuses. The website www. medlive.cn was also retrieved as supplementary. The clinical practice evaluation tool AGREE II was used to assess the quality of included guidelines or consensuses. RESULTS: A total of 31 relevant clinical practice guidelines or expert consensuses were included, covering diagnosis, treatment, Chinese patent and patient fields. Common cardiovascular diseases like coronary heart diseases, heart failure and arrhythmia were also involved. Through analysis it was found that both the quantity and quality of included guidelines have been improved year by year. A total of 4 evidence-based clinical practice guideline has been found, one of which was a guideline project plan. Except that, the remaining 27 reports were all consensus-based guidelines. The scores of each field, from highest to lowest, were clarity of presentation (58%), scope and purpose (54%), stakeholder involvement (28%), rigor of development (21%), applicability (13%) and editorial independence (8%). CONCLUSIONS: Although clinical practice guidelines in cardiovascular domain of Chinese have gained increasing concern, with both quantity and quality improved, there is still huge gap in methodology and reporting standards between CM guidelines and international ones. On the one hand, it is essential to improve and standardize the methodology of developing CM guidelines. On the other hands, the evaluation system of evidence and recommendation with CM characters should be developed urgently.

Phlorizin ameliorates obesity-associated endotoxemia and insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity.

Phlorizin (PHZ) is one of phytonutrients in apples that contributes to the health-promoting effect implicated by the saying, 'an apple a day keeps the doctor away'. PHZ was firstly identified as a competitive inhibitor of sodium-glucose co-transporters-2 (SGLT2); however, its low bioavailability makes it hard to fully explain its pharmacological mechanisms. This study aimed to investigate the ameliorating effect of PHZ on high-fat diet (HFD)-induced obesity via modulating the "gut microbiota-barrier axis". Firstly, C57BL/6 J mice were fed a normal chow diet (NCD) or HFD coadministered with or without PHZ for 12 weeks. Our results showed that PHZ supplementation significantly reduced HFD-induced body weight gain (P < .001), alleviated metabolic disorders (MDs) like insulin resistance (P < .001) and elevation of serum lipopolysaccharides (LPS) (P < .001), attenuated HFD-induced gut microbiota alterations, enhanced short-chain fatty acids (SCFAs) production (P < .001), and inhibited fecal LPS production (P < .001). To investigate the role of the fecal microbiota in the observed beneficial effects, a fecal microbiota transplantation (FMT) experiment was performed by transplanting the feces of the four groups of mice (as donor mice) daily collected from the fourth week to a new batch of acclimatized HFD-fed mice. Our results confirmed that feeding the gut contents of the PHZ-modulated mice could attenuate HFD-induced MDs, accompanied by enhanced glucagon-like peptide 2 (GLP-2) secretion (P < .001) and restoration of HFD-induced damage in the gut epithelial barrier. This study has provided evidence that the "gut microbiota-barrier axis" was an alternative target for the anti-obesity effect of PHZ. This work has also provided an explanation for the high efficacy of PHZ despite the low bioavailability, and PHZ holds great potential to be developed as a functional food ingredient.

A Novel Streptomyces sp. Strain PBSH9 for Controlling Potato Common Scab Caused by Streptomyces galilaeus.

Potato common scab is an important soilborne disease worldwide that can significantly reduce the quality and economic values of potato. The disease is caused by multiple species of Streptomyces, which are not well controlled due to lack of effective strategies. Streptomyces galilaeus has been recently identified as a dominant species causing potato common scab in Inner Mongolia, China. This study was focused on screening and characterizing antagonists for biological control against pathogenic S. galilaeus. Bacterial strain PBSH9 was isolated from a potato tuber. PBSH9 was identified as a Streptomyces sp. on the basis of morphological, physiological, and biochemical characteristics, as well as DNA sequence analysis. PBSH9 inhibited S. galilaeus with a diameter of inhibitory zone of 19.8 mm on agar plates. The extracellular filtrate of PBSH9 also inhibited S. galilaeus growth with a diameter of inhibition zone of 10.0 mm. Furthermore, PBSH9 promoted potato sprouting and emergence. Disease control was up to 81.88% in greenhouse trials, and from 47.64 to 73.97% in 3-year field trials. Among the tested inoculation methods, seed treatment was more effective than soil drenching for PBSH9 application. PBSH9 not only effectively controlled potato common scab but also increased potato growth. Thus, it can be a potential candidate for biocontrol agent.

Effect of Chinese Medicine on No or Slow Reflow after Percutaneous Coronary Intervention in Myocardial Infarction Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematic review the effect of Chinese medicine (CM) on no or slow reflow after percutaneous coronary intervention (PCI) in myocardial infarction (MI) patients. METHODS: The PubMed, EMBASE databases, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wanfang Knowledge Service Platform (Wanfang Database) and Chinese Scientific Journal Database (VIP) were searched up to December 2017. Randomized controlled trials (RCTs) which evaluated the effect of CM therapies on no or slow reflow after PCI in MI patients were included. The primary outcome was the effect of reperfusion. Secondary outcomes were left ventricular ejection fraction, incidence of major adverse cardiovascular events and adverse effect. RESULTS: Ten RCTs covering 814 patients were included. Two studies revealed that the incidence of no or slow reflow was less in Shenmai Injection () group than in the control group measured by thrombolysis in myocardial infarction (TIMI) ⩽ 2 (risk ratio=0.55, 95% confidence interval 0.38 to 0.81, P=0.003, I2=37%). Two studies indicated that Salvianolate Injection showed no additional benefit on no or slow reflow measured by corrected TIMI frame count compared with the conventional treatment (mean difference -4.24, 95% confidence interval -13.03 to 4.54, P=0.34, I2=86%). In addition, Tongxinluo Capsules (), Danhong Injection () and Xuesaitong Injection () may have the potential to reduce no or slow reflow measured during or after PCI in individual studies. CONCLUSIONS: Current evidence from RCTs are not sufficient to evaluate the effect of CM adjuvant therapies on no or slow reflow after PCI for MI patients. The included studies are limited by small sample size and unclear baseline conditions. Further rigorously designed researches and verification studies with sufficient number of patients are warranted.

Canscora lucidissima, a Chinese folk medicine, exerts anti-inflammatory activities by inhibiting the phosphorylation of ERK1/2 in LPS-activated macrophages.

BACKGROUND: Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. However, the underlying mechanism of its anti-inflammatory effect is not fully understood. METHODS: In this study, we investigated the anti-inflammatory mechanism of ethanol extract of C. lucidissima (Cl-EE) in lipopolysaccharide (LPS)-induced inflammatory models. ELISA, real-time PCR, Western blot and luciferase reporter assay were used for the experiments in vitro, and ICR mouse endotoxemia model was used for in vivo test. RESULTS: Our data showed that Cl-EE reduced the production of NO by down-regulating the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 cells. Meanwhile, it potently decreased other proinflammatory mediators, such as TNF-α, IL-6, MCP-1 and IL-1ß at the transcriptional and translational levels. Further study indicated that Cl-EE did not affect NF-κB signaling pathway but significantly suppressed the phosphorylation of ERK1/2, rather than JNK or p38. In a LPS-induced endotoxemia mouse model, a single intraperitoneal injection of Cl-EE (75-300 mg/kg) could lower circulatory TNF-α, IL-6 and MCP-1 levels. CONCLUSIONS: Collectively, our results indicated that Cl-EE suppressed the phosphorylation level of ERK1/2 thus reducing the transcription and translation of inflammatory genes, thereby exerted anti-inflammatory activity. This study reveals the anti-inflammatory mechanism of C. lucidissima and may provide an effective treatment option for a variety of inflammatory diseases.