Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity.

Osteoporosis characterized by decreased bone density and mass, is a systemic bone disease with the destruction of microstructure and increase in fragility. Osteoporosis is attributed to multiple causes, including aging, inflammation, diabetes mellitus, and other factors induced by the adverse effects of medications. Without treatment, osteoporosis will further progress and bring great trouble to human life. Due to the various causes, the treatment of osteoporosis is mainly aimed at improving bone metabolism, inhibiting bone resorption, and promoting bone formation. Although the currently approved drugs can reduce the risk of fragility fractures in individuals, a single drug has limitations in terms of safety and effectiveness. By contrast, traditional Chinese medicine (TCM), a characteristic discipline in China, including syndrome differentiation, Chinese medicine prescription, and active ingredients, shows unique advantages in the treatment of osteoporosis and has received attention all over the world. Therefore, this review summarized the pathogenic factors, pathogenesis, therapy limitations, and advantages of TCM, aiming at providing new ideas for the prevention and treatment of OP.

Experimental Research on the Effect of Tounong San on the Immune Function of Rats with Superficial Suppurative Infection.

Purpose: This paper aims to investigate the effect of Tounong San (TNS), a well-known traditional Chinese medicine prescription for suppurative infections, on the immune function. Methods: A suppurative infection model was established by injecting Staphylococcus aureus into subcutaneous tissue on the backs of rats. The expressions of CD68, CD163, CD31 and MPO in abscess tissues, phagocytosis rate and reactive oxygen species (ROS) of neutrophils in blood, phagocytosis function of peritoneal macrophages, and proliferation of blood lymphocytes, expression of IL-1, IL-6, CH50, TNF-α, IFN-γ, IgG, IgM in serum were detected at different time points. Results: On the 3rd day of medication, fibrinogen wrapped around the abscesses was visible in TNS groups, with an increase in new blood vessels and the expression of a large number of macrophages and neutrophils. On the 6th day, the pus of TNS groups diminished, and the number of new blood vessels reached its peak. On the 9th day, the abscesses disappeared in TNS groups, fewer new blood vessels, macrophages, and neutrophils were expressed, and more fibrocytes appeared and filled the original pus cavities. On the 3rd and 9th day of medication, the phagocytic rates of neutrophils and macrophages were significantly improved in TNS group, and the ROS content of neutrophils was increased on the 9th day. TNS has no effect on lymphocyte proliferation in vitro, but it can regulate the secretion of IgG and IgM by lymphocytes. TNS increases the level of IL-1, decreases the levels of IL-6 and TNF-α, and regulates the expressions of IFN-γ and CH50 in two ways. Conclusion: TNS can form fibrinogen-wrapped pus to prevent bacterial infection from going deeper, and to improve the phagocytic function of phagocytes, the secretion of lymphocytes, and the defense function of the complement system. Therefore, it is a competitive drug for the treatment of suppurative diseases.

The Western and Chinese exercise training for blood pressure reduction among hypertensive patients: An overview of systematic reviews.

Hypertension remains the world's leading cause of premature death. Interventions such as exercise, diet modification, and pharmacological therapy remain the mainstay of hypertension treatment. Numerous systematic reviews and meta-analyses demonstrated the effectiveness of western exercises, such as aerobic exercise and resistance exercise, in reducing blood pressure in hypertensive patients. There is recently emerging evidence of blood pressure reduction with Chinese exercises, such as Tai Chi, Baduanjin, and Qigong. The current overview of systematic reviews aims to evaluate the quality and descriptively summarize the evidence for the effectiveness of western and Chinese exercises for hypertension management. Thirty-nine systematic reviews were included in this overview, with 15 of those being on Chinese exercise. Evidence suggests that exercise training, regardless of Western or Chinese exercise, generally reduced both systolic and diastolic blood pressure. High-intensity intermittent training did not further reduce blood pressure when compared to moderate-intensity continuous training. Conflicting results on the effectiveness of blood pressure reduction when comparing Chinese and Western exercise training were observed. This suggests the comparable effectiveness of Chinese exercise training, in particularly Tai Chi, to general or aerobic exercise training in terms of blood pressure reduction. The Chinese exercise modality and intensity may be more suitable for the middle-aged and elderly population.

Active ingredients screening and pharmacological mechanism research of curcumae rhizoma-sparganii rhizoma herb pair ameliorates liver fibrosis based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumae Rhizoma-Sparganii Rhizoma (CR-SR) is a classic herbal pair to promote blood circulation and remove blood stasis in ancient China. However, the molecular mechanism is still unclear. AIM OF STUDY: To screen out the anti-liver fibrosis active ingredients in CR-SR. Moreover, preliminary exploration the molecular mechanism of CR-SR to ameliorates liver fibrosis. MATERIALS AND METHODS: In this research, plant taxonomy has been confirmed in the "The Plant List" database (www.theplantlist.org). The chemical components of CR-SR were analysed by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). "Component-Target-Pathway-Disease" network of CR-SR components were built by network pharmacology. Then, the interaction between primary components and predicted protein targets based on network pharmacology were validated by molecular docking. The pharmacological actions of CR-SR were verified by blood biochemical indexes, histopathologic examination of CCL4 induced rats' model. The core protein targets were verified by Western blot. The effects of screened active components by molecular autodocking were verified by HSC-T6 cell experiment. RESULTS: The result shows that 57 chemical constituents in CR-SR herbal pair were identified by UPLC-Q/TOF-MS, in which, 27 compounds were closely connected with liver fibrosis related protein targets. 55 protein targets screened out by "component-target-pathway-disease network" maybe the underlying targets for CR-SR to cure liver fibrosis. Moreover, the 55 protein targets are mainly related to RNA transcription, apoptosis, and signal transduction. The molecular autodocking predicted that ten components can bond well with PTGS2 and RELA protein targets. The blood biochemical indexes, histopathologic examination of CCL4 induced rats experiment showed that CR-SR has well intervention effect of liver fibrosis. The Western blot analysis indicated that CR-SR could significantly inhibit RELA, PTGS2, IL-6, SRC, and AKT1 protein expression to exert the anti-fibrosis effect. The HSC-T6 cell experiment indicated that both formononetin (FNT) and curdione could significantly inhibit the activation of HSC and reduce the expression of PTGS2, and p-AKT1 which was accordance with the molecular autodocking results. CONCLUSION: This study proved the molecular mechanism of CR-SR multi-component and multi-target anti-liver fibrosis effect through mass spectrometry, network pharmacology, and western blotting technology. The research provides a theoretical evidence for the development and utilization of CR-SR herbal pair.

The most bioactive fraction of stir-fried Radix Paeoniae Alba regulating IL-6/STAT3 signaling pathway in allergic asthma mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Paeoniae Alba (RPA), a traditional Chinese medicine, has been used frequently in the treatment of asthma. Previous studies demonstrated the dichloromethane fraction of Stir-Frying RPA (FDCM) enhanced the effect of anti-allergic asthma compared with the dichloromethane fraction of RPA (DCM). AIM OF THE STUDY: The significant increasing of Paeoniflorin (PF), ethyl gallate (EG), 1,2,3,4,6-pentagalloylglucose (PGG) had been observed in FDCM. This study aimed to investigate the effects and mechanisms of these compounds from FDCM in ovalbumin (OVA)-induced allergic asthma mouse model. MATERIALS AND METHODS: The significant difference contents compounds fraction (FB-40) and other fractions in FDCM were enriched by Medium Pressure Liquid Chromatography (MPLC). The pharmacodynamics was verified among all fractions in OVA-induced allergic asthma mice. Moreover, the drug dose dependence of FB-40 (0.42 mg/kg, 0.21 mg/kg, and 0.07 mg/kg), which were the most active fraction from FDCM for anti-allergic asthma, was explored. The expression of IL-6, p-STAT3, and STAT3 was analyzed by Western blot analysis. In addition, the main components of FB-40 were identified by UPLC with standards. Finally, the anti-inflammatory effects of the main components from FB-40 were detected by LPS-stimulated BEAS-2B cells using an Elisa assay. RESULTS: The results showed that FB-40 was the most active fraction from FDCM, which could significantly improve the lung tissue pathological condition, and decrease the number of inflammatory cells in bronchoalveolar lavage fluid (BALF). It had greater pharmacological activity than its main component PF. FB-40 also showed dose dependence and regulated the IL-6/STAT3 signaling pathway in allergic asthma mice. Besides, PF, Albiflorin (AF), PGG, EG, and 1,2,3,6-Tetra-O-galloyl-ß-D-glucose (TGG) from FB-40 were identified by UPLC with the standard. At last, in the LPS-induced BEAS-2B cell experiments, EG, PGG, 1,2,3,6-Tetra-O-galloyl-ß-D-glucose (TGG) showed stronger inhibiting activities of cytokine than the monoterpenoid glycosides (PF and AF). CONCLUSION: The research proved that FB-40 was an active fraction in FDCM, which regulates IL-6/STAT3 Signaling Pathway to ameliorate allergic asthma. Gallic acids including TGG and PGG, and EG also play a role in the treatment of allergic asthma in FB-40.

Strengthen the purification of eutrophic water and improve the characteristics of sediment by functional ecological floating bed suspended calcium peroxide and sponge iron jointly.

To overcome the shortcomings of conventional ecological floating bed (CEFB) in purifying landscape water, this study constructed a functional ecological floating bed (FEFB) through the suspension of calcium peroxide (CP) and sponge iron (SI) jointly below the CEFB. The purification effect of water quality and influence of sediment were compared in control check, CEFB, and FEFB systems, which were loaded the same sediment and reclaimed water in a field experiment. Results showed that the FEFB suspended with CP and SI had evident purification effect on the quality of landscape water supplied with reclaimed water and can maintain stably the nutrient status of the water body at mesotrophic levels and low turbidity. The FEFB promoted the degradation of humus, thus eliminating the chroma risk in water body caused by the decay of plants from the CEFB. Moreover, the FEFB can control the sediment mass produced, reduce the total nitrogen (TN) mass of sediment, and decrease the transformable TN (TTN) content in the sediment. The FEFB enhanced the stability of phosphorus (P) in the sediment, where the relative content of Ca-P and stable P reached 42.18% and 64.27%, respectively. To sum up, the FEFB suspended with SI and CP can not only effectively control the eutrophication and sensory index of landscape water but also change the TTN content and P forms in sediment, making the sediment more stable. Thus, the FEFB provides an innovative approach to reduce endogenous nutrient release for landscape water along with recharging with reclaimed water.

Integrated gut microbiota and serum metabolomics reveal the protective effect of oleanolic acid on liver and kidney-injured rats induced by Euphorbia pekinensis.

Euphorbia pekinensis (EP) is a commonly used Chinese medicine treating edema with potential hepatorenal toxicity. However, its toxic mechanism and prevention are remained to be explored. Oleanolic acid (OA) is a triterpene acid with potential hepatorenal protective activities. We investigated the protective effect and potential mechanism of OA on EP-induced hepatorenal toxicity. In this study, rats were given total diterpenes from EP (TDEP, 16 mg/kg) combined with OA (10, 20, 40 mg/kg) by gavage for 4 weeks. The results showed that TDEP administration could lead to a 3-4-fold increasement in hepatorenal biochemical parameters with histopathological injuries, while OA treatment could ameliorate them in a dose-dependent manner. At microbial and metabolic levels, intestinal flora and host metabolism were perturbed after TDEP administration. The disturbance of bile acid metabolism was the most significant metabolic pathway, with secondary bile acids increasing while conjugated bile acids decreased. OA treatment can improve the disorder of intestinal flora and metabolic bile acid spectrum. Further correlation analysis screened out that Escherichia-Shigella, Phascolarctobacterium, Acetatifactor, and Akkermansia were closely related to the bile acid metabolic disorder. In conclusion, oleanolic acid could prevent hepatorenal toxicity induced by EP by regulating bile acids metabolic disorder via intestinal flora improvement.

Molecular mechanisms of Biyu decoction as treatment for psoriasis: A network pharmacology and molecular docking study.

BACKGROUND: The therapeutic effects of a combination of Chinese medicines called Biyu decoction have been clinically verified, although its molecular targets in psoriasis remain unknown. AIM: To explore the molecular mechanisms of Biyu decoction for psoriasis treatment. METHODS: In this network pharmacology and molecular docking study, the Traditional Chinese Medicine Systems Pharmacology database was searched for Biyu decoction active ingredients. GeneCards, Online Mendelian Inheritance in Man, PharmGkb, Therapeutic Target Database, and DrugBank databases were searched for psoriasis-related genes. The genes targeted by the decoction's active ingredient and disease genes were intersected to obtain predictive targets of the drug during psoriasis treatment. Cytoscape 3.8.0 was used to construct a drug component/ target disease network. The The functional protein association networks database and Cytoscape were used to construct a protein-protein interaction network and streamline the core network. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for pathway enrichment analysis. Molecular docking technology was used to verify the drug component/target disease network. RESULTS: We screened 117 major active ingredients, including quercetin, kaempferol, naringenin, and acetyl-shikonin, and identified 213 gene targets, such as MAPK3, JUN, FOS, MYC, MAPK8, STAT3, and NFKBIA. Using a molecular docking analysis, the main active ingredients demonstrated good binding to the core targets. The Gene Ontology analysis showed that these ingredients were significantly associated with biological activities, such as transcription factor DNA binding, RNA polymerase II-specific DNA binding of transcription factors, and cytokine receptor binding; responses to lipopolysaccharides, molecules of bacterial origin, and oxidative stress; and were mainly distributed in membrane rafts, microdomains, and regions. The Kyoto Encyclopedia of Genes and Genomes analysis showed that decoction ingredients act on Th17 cell differentiation, tumor necrosis factor and mitogen-activated protein signaling pathways, the interleukin-17 signaling pathway, and the PI3K-Akt signaling pathway. CONCLUSION: Biyu decoction may be effective against psoriasis through multi-component, multi-target, and multi-channel synergy.

Revealing the mechanism of raw and vinegar-processed Curcuma aromatica Salisb. [Zingiberaceae] regulates primary dysmenorrhea in rats via integrated metabolomics.

Primary dysmenorrhea (PDM) is a common disorder among women around the world. Two processed products of Curcuma aromatica Salisb. [Zingiberaceae] (CAS) are traditional Chinese medicine (TCM) that have long been used to treat gynecological blood stasis syndrome such as primary dysmenorrhea. The mechanisms and active substances of CAS are still largely unknown. The study aimed to establish a rat model of primary dysmenorrhea which investigates the differences between the pharmacodynamics and mechanisms of raw CAS (RCAS) and vinegar-processed CAS (VCAS). Histopathology, cytokinetics, and metabolomics were adopted to evaluate the anti-blood stasis effect of RCAS and VCAS. In metabolomics, endogenous differential metabolites in plasma, urine, and feces are the essential steps to evaluate the effect of RCAS and VCAS. In this study, the rat model of primary dysmenorrhea was successfully established. After RCAS and VCAS intervention, the uterine tissue morphology of dysmenorrhea model rats was improved, and gland hypertrophy and myometrial hyperplasia were reduced as well as neutrophil content. Compared with the RCAS group, the VCAS group had better uterine morphology, few inflammatory factors, and significantly improved amino acid and lipid metabolism. The aforementioned results support the conclusion that VCAS performed better than RCAS in primary dysmenorrhea and that vinegar processing increases the efficacy of CAS.

Response mechanism of microorganisms to the inhibition of endogenous pollution release by calcium peroxide.

To further explore the response mechanism of microorganisms to the synchronous control of nitrogen and phosphorus release from sediments by CaO2, the spatiotemporal changes in the physical, chemical and biological indicators of the overlying water, interstitial water and sediments in each reactor were measured in the experiment. The experiment results showed that CaO2 could increase the ammonia monooxygenase activity, nitrite oxidase activity and Nitrospira abundance in the sediment near its dosing position, and enhanced the activities of nitrate reductase and nitrite reductase at a certain distance from the dosing position, thereby promoting nitrogen removal in sediments through the alternating process of nitrification and denitrification. At the same time, the increase of alkaline phosphatase activity and Saccharimonadales abundance in the test groups accelerated the hydrolysis of organic phosphorus, and the P immobilization in sediments was realized through the subsequent precipitation reaction of Ca2+ and PO43- under alkaline conditions. In addition, the enhanced activities of dehydrogenase and catalase ensured that CaO2 would not cause great killing effect on microorganisms when improving the hypoxic conditions and inhibiting endogenous release. As a result, the dissolved product of CaO2 such as Ca(OH)2 and H2O2 reduced the nutrients concentration and killed the algae, which kept the algae density and chlorophyll a concentration at a low level throughout the test groups. Therefore, this study systematically clarified the microbial mechanism of CaO2 synchronously controlling the release of nitrogen and phosphorus from sediments, which provided a new idea for the remediation of endogenous pollution in the water system.

Screening of Bioactive Fraction of Radix Paeoniae Alba and Enhancing Anti-Allergic Asthma by Stir-Frying Through Regulating PI3K/AKT Signaling Pathway.

Allergic asthma is a common respiratory inflammation disease. The crude Radix Paeoniae Alba (RPA) and its processed products have been used frequently as antipyretic and anti-inflammatory agents in traditional medicine. To evaluate the effect of honey and bran processing, different fractions of RPA were used for treating anti-allergic asthma in the ovalbumin (OVA)-induced mice model, and then, the most effective fraction of RPA and stir-frying Radix Paeoniae Alba with honey and bran (FRPA) for treating anti-allergic asthma were compared mutually for pharmacological effects. The results showed that the treatment of the dichloromethane fraction of RPA significantly improved the pathological condition of lung tissues, decreased the number of eosinophils and other cells in bronchoalveolar lavage fluid (BALF), and the increased the expression of various inflammatory factors. Furthermore, the study discovered that the lung pathological conditions, compared with the high dose of dichloromethane RPA fraction, could be ameliorated by high dose of dichloromethane FRPA fraction treatment. Moreover, the expression of inflammatory factors and the phosphorylation of the PI3K/AKT signaling pathway could be diminished by FRPA. Finally, the contents of compounds with a significant difference in the FRPA dichloromethane fraction were paeoniflorin, ethyl gallate, pentagalloylglucose, galloylpaeoniflorin, and others by UPLC/Q-TOF-MS analysis. These findings suggest that the dichloromethane fraction of FRPA has an enhancement effect on anti-allergic asthma and provide the experimental basis for exploring the processed mechanism of RPA.

Toxicity of Tetradium ruticarpum: Subacute Toxicity Assessment and Metabolomic Identification of Relevant Biomarkers.

Tetradium ruticarpum (TR) is widely used in Asia to treat gastrointestinal disorders and pain. Stir-frying with licorice aqueous extract is a traditional processing procedure of TR formed in a long-term practice and performed before clinical application, and believed to reduce TR's toxicity. However, its toxicity and possible toxicity attenuation approach are yet to be well investigated. Subacute toxicity and metabolomics studies were conducted to help understand the toxicity of TR. The subacute toxicity assessment indicated that 3 fold of the recommended therapeutic dose of TR did not show obvious subacute toxicity in rats. Although an extremely high dose (i.e., 60 fold of the recommended dose) may cause toxicity in rats, it reversed to normal after 2 weeks of recovery. Hepatocellular injury was the major toxic phenotype of TR-induced liver damage, indicating as aspartate aminotransferase (AST) and liver index increasing, with histopathologic findings as local hepatocyte necrosis, focal inflammatory cell infiltration, slightly bile duct hyperplasia, and partial hepatocyte vacuolation. Moreover, we evaluated the impact of processing in toxicity. TR processed with licorice could effectively reduce drug-induced toxicity, which is a valuable step in TR pretreatment before clinical application. Metabolomics profiling revealed that primary bile acid biosynthesis, steroid biosynthesis, and arachidonic acid metabolism were mainly involved in profiling the toxicity metabolic regulatory network. The processing procedure could back-regulate these three pathways, and may be in an Aryl hydrocarbon Receptor (AhR) dependent manner to alleviate the metabolic perturbations induced by TR. 7α-hydroxycholesterol, calcitriol, and taurocholic acid were screened and validated as the toxicity biomarkers of TR for potential clinical translation. Overall, the extensive subacute toxicity evaluation and metabolomic analysis would not only expand knowledge of the toxicity mechanisms of TR, but also provide scientific insight of traditional processing theory, and support clinical rational use of TR.

Developing a competency-based framework for resident-as-teacher.

BACKGROUND/PURPOSE: Residents play an important role as teachers of junior colleagues and medical students. Clinical teaching also helps residents in clinical learning. However, the skills required for residents to be competent teachers are rarely described systemically. Beyond the widely adopted six core competencies for postgraduate training by the Accreditation Council for Graduate Medical Education (ACGME), the teaching competencies should be further developed, and the milestones should be clearly defined to serve as better references for resident training programs. METHODS: Twenty members, including five experts from major teaching hospitals across Taiwan and 15 from a public medical center, were invited to a workgroup to collaboratively develop a competency-based framework. The development process was similar to that suggested by the ACGME. The teaching competencies framework were drafted by an experienced physician educator. The draft was sent to each group member, and feedback was collected. Two workgroup meetings were held for consensus formation. The contents of the teaching competencies of residents were confirmed after two rounds of revision. The outline of the framework was also reported at an international meeting in September 2019. RESULTS: Two core competencies, instruction and assessment, with three sub-competencies and 37 milestones, were adopted in the final edition of resident-as-teacher competencies. The sub-competencies were "dissemination of knowledge" and "teaching of procedural skills" for instruction, and "direct observation and feedback" for assessment. CONCLUSION: A competency-based framework for resident-as-teacher was developed. The framework can be applied in combination with other existing competencies for holistic postgraduate training programs.

Evaluating Teaching Effectiveness of Medical Humanities in an Integrated Clerkship Program by a Novel Prospective Propensity Score Matching Framework.

BACKGROUND: This study aims to rigorously compare the effectiveness of the educational programs of a new integrated clinical clerkship in medicine (3 months) and surgery (3 months) at a cancer center with the conventional subspecialty-based rotations at a tertiary teaching hospital, by this prospective, pre-post comparative method. METHODS: Between 2013-2016, we compared 69 students who had selected the integrated clerkship that emphasized clinical competency and medical humanities training with 138 matched peers who had completed conventional clerkships during the same period. Outcome measures for medical humanities included empathy, patient-centeredness, and other values and skills related to holistic health care professionalism by introducing prospective propensity score matching (PSM). RESULTS: At baseline, no significant between-group differences existed. At the completion of the core clerkships, students receiving the integrative clerkship had significantly higher scores on the Patient-Practitioner Orientation Scale (PPOS) and the Professionalism Climate in Clinical Teaching Environment (PCI), and similar Jefferson Scale of Physician Empathy Student Version (JSPE) scores, as compared with the comparison group. We also found that the students in this program did not perform worse than those in the traditional internship group in the comprehensive and formative OSCE medical clinical skills test. CONCLUSIONS: Our study develops an empirical basis for rigorous evaluation to design medical education to improve the medical humanities values and skills of interns. Features of the new integrated clerkship program that we developed include substantial participation by the students in patient-centered in-hospital culture, as well as reflection, discussion, and feedback on actual clinical cases.

Screening of blood-activating active components from Curcuma wenyujin Y.H. Chen et C. Ling rhizome based on spectrum-effect relationship analysis and network pharmacology.

Curcuma wenyujin Y.H. Chen et C. Ling rhizome (also called EZhu in China) has long been used as plant medicine for its traditional effect on promoting blood circulation and remove blood stasis. However, the active components of EZhu are still unclear at present. This research is managed to investigate the pharmacodynamics material basis on removing blood stasis of EZhu by exploring the spectrum-effect relationship between UPLC-Q/TOF-MS fingerprints and pharmacologic actions. Hemorheology and related functional parameters were detected to evaluate the pharmacologic actions of EZhu. Relative content Changes of components in rat plasma were detected by UPLC-Q/TOF-MS. A compound-target-pathway network was built to predict the pharmacological activity of components in plasma. Then, bivariate correlation analysis (BCA) was used to explore the correlation degree between components in plasma and pharmacologic actions of EZhu. In UPLC-Q/TOF-MS fingerprints of rat plasma, 10 prototype components were identified. BCA results show that 8 components were concerned with the pharmacological activity for treating blood stasis syndrome (BSS) in varying degrees (R > 0.5, P < 0.05). Among them, zedoarofuran and curzerenone have shown correlation with more pharmacological indicators. The network predicted that 80 targets were closely related to 10 components, in which 48 targets were connected with 159 metabolic pathways including arachidonic acid metabolism, sphingolipid signaling pathway, and linoleic acid metabolism. Overall, this study provided a scientific basis for TCM quality control to ensure its safety and efficacy.

Gut microbiota disorder caused by diterpenoids extracted from Euphorbia pekinensis aggravates intestinal mucosal damage.

Gut microbiota disorder will lead to intestinal damage. This study evaluated the influence of total diterpenoids extracted from Euphorbia pekinensis (TDEP) on gut microbiota and intestinal mucosal barrier after long-term administration, and the correlations between gut microbiota and intestinal mucosal barrier were analysed by Spearman correlation analysis. Mice were randomly divided to control group, TDEP groups (4, 8, 16 mg/kg), TDEP (16 mg/kg) + antibiotic group. Two weeks after intragastric administration, inflammatory factors (TNF-α, IL-6, IL-1ß) and LPS in serum, short chain fatty acids (SCFAs) in feces were tested by Enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. The expression of tight junction (TJ) protein in colon was measured by western blotting. Furthermore, the effects of TDEP on gut microbiota community in mice have been investigated by 16SrDNA high-throughput sequencing. The results showed TDEP significantly increased the levels of inflammatory factors in dose-dependent manners, and decreased the expression of TJ protein and SCFAs, and the composition of gut microbiota of mice in TDEP group was significantly different from that of control group. When antibiotics were added, the diversity of gut microbiota was significantly reduced, and the colon injury was more serious. Finally, through correlation analysis, we have found nine key bacteria (Barnesiella, Muribaculaceae_unclassified, Alloprevotella, Candidatus_Arthromitus, Enterorhabdus, Alistipes, Bilophila, Mucispirillum, Ruminiclostridium) that may be related to colon injury caused by TDEP. Taken together, the disturbance of gut microbiota caused by TDEP may aggravate the colon injury, and its possible mechanism may be related to the decrease of SCFAs in feces, disrupted the expression of TJ protein in colon and increasing the contents of inflammatory factors.

Evaluation of Peroxidase in Herbal Medicines Based on an Electrochemical Sensor.

Peroxidases are species-specific. Differences in peroxidase can objectively reflect the genetics among species. The use of peroxidase to assist in species identification is relatively simple and effective. In this work, we proposed a graphene-modified electrode. This electrode can amplify the signal of electrocatalytic reduction of hydrogen peroxide. Since peroxidase can catalyze the reduction of hydrogen peroxide, this signal can be used as an indicator to demonstrate the content of peroxidase in different plant tissues. Twelve herbal medicines were selected for our study. The results show that this electrochemical-based detection technique was comparable to colorimetric method in terms of accuracy.

Bioactive constituents and the molecular mechanism of Curcumae Rhizoma in the treatment of primary dysmenorrhea based on network pharmacology and molecular docking.

BACKGROUND: Curcumae Rhizoma (CR) has a clinical efficacy in activating blood circulation to dissipate blood stasis and has been used for the clinical treatment of qi stagnation and blood stasis (QSBS) primary dysmenorrhea for many years. However, its molecular mechanism is unknown. OBJECTIVE: The present study aimed to demonstrate the multicomponent, multitarget and multipathway regulatory molecular mechanisms of CR in the treatment of QSBS primary dysmenorrhea. METHODS: Observations of pathological changes in uterine tissues and biochemical assays were used to confirm that a rat model was successfully established and that CR was effective in the treatment of QSBS primary dysmenorrhea. The main active components of CR in rat plasma were identified and screened by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The component-target-disease network and protein-protein interaction (PPI) network of CR were constructed by a network pharmacology approach. Then, we performed Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was adopted to verify the interactions between the core components and targets of CR to confirm the accuracy of the network pharmacology prediction results. Furthermore, we evaluated the bioactive constituents of CR and molecular mechanism of by which CR promote blood circulation and remove blood stasis via platelet tests in vivo and in vitro and Western blot analysis. RESULTS: The results of HE staining and biochemical assays of PGF2α, TXB2 and Ca2+ showed that CR was effective in the treatment of QSBS primary dysmenorrhea. A total of 36 active components were identified in CR, and 329 common targets were obtained and used to construct the networks. Of these, 14 core components and 10 core targets of CR in the treatment of primary dysmenorrhea were identified. The GO and KEGG enrichment analyses revealed that the common targets were involved in multiple signaling pathways, including the calcium, cAMP, MAPK, and PI3K-Akt signaling pathways, as well as platelet activation, which is closely related to platelet aggregation. The molecular docking results showed that the 14 core components and 10 core targets could bind spontaneously. Two core targets (MAPK1 and CCR5) and 7 core components (Isoprocurcumenol, Curcumadione, Epiprocurcumenol, (+)-Curdione, Neocurdione, Procurcumenol, and 13-Hydroxygermacrone) were closely related to CR in the treatment of primary dysmenorrhea. Furthermore, the in vivo platelet test showed that CR clearly inhibited platelet aggregation. Five core components ((+)-Curdione, Neocurdione, Isoprocurcumenol, Curcumadione and Procurcumenol) obviously inhibited platelet aggregation in vitro. In addition, based on the relationships among the signaling pathways, we confirmed that CR can effectively inhibit the expression of MAPK and PI3K-Akt signaling pathway-related proteins and decrease the protein expression levels of ERK, JNK, MAPK, PI3K, AKT and CCR5, thereby inhibiting platelet aggregation. CONCLUSION: This study demonstrated the bioactive constituents and mechanisms of CR in promoting blood circulation and removing blood stasis and its multicomponent, multitarget and multipathway treatment characteristics in primary dysmenorrhea. The results provide theoretical evidence for the development and utilization of CR.

Non-pharmacological management of hypertension.

Hypertension is an insidious disease which predisposes to cardiovascular complications and if not treated properly can lead to various serious complications. Economic limitations, having additional benefits with few or almost no side effects have made non-pharmacological management of hypertension an attractive approach for dealing with hypertension, in developed and developing countries alike. A MEDLINE search was done for relevant references with emphasis on original studies, randomized controlled trials, and meta-analyses for this review paper. Lifestyle modifications including changes in the dietary pattern, adopting special diets with low sodium, saturated fat and high calcium, magnesium and potassium and trying the new methods like time restricted meal intake which work in tandem with the circadian rhythm are opening new vistas in the field of non-pharmacological management of hypertension. Lifestyle modifications that effectively lower blood pressure are increased physical activity, weight loss, limited alcohol consumption, relaxation techniques of Yoga, Acupuncture, Tai chi, mindfulness-based stress-reduction program, and Transcendental Meditation. Air pollution of the surrounding air is linked with poor health outcomes and is a major contributor to the global burden of disease. Fine particulate matter <2.5 µm in diameter (PM2.5) is strongly associated with cardiovascular morbidity and mortality. Short-term PM exposure (hours to weeks) increases the likelihood of adverse cardiovascular events including myocardial infarction, stroke, and heart failure, and longer-term exposure multiplies that risk. Non-pharmacological methods should be initiated early phase of disease and should be continued with medication.

Change in the active component of processed Tetradium ruticarpum extracts leads to improvement in efficacy and toxicity attenuation.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried and nearly ripe fruits of Tetradium ruticarpum (A. Juss.) T.G. Hartley (TR) have long been used in treating headache and gastrointestinal disorders in oriental medicine. TR is usually processed by stir-frying with licorice extract before use. Although processing procedure is considered as the way to relieve pungent smell, reduce toxicity, and improve efficacy, its effects on TR's toxicity and efficacy and bioactive compound profiles are largely unknown. AIM OF THE STUDY: The purposes of the study are to evaluate the acute toxicity, efficacy and variation of toxic and effective components of TR before and after processing, and to explore the possible mechanism of how the processing procedure affect the quality of TR as a herbal medicine. MATERIALS AND METHODS: Volatile oil, aqueous extract and ethanol extract of raw and processed TR were tested for their acute toxicity, analgesic, and anti-inflammatory effects in mouse models, respectively. To identify potential toxic and effective components, the extracts were analyzed with gas chromatography-mass spectrometry and ultra-performance liquid chromatography - quadrupole time-of-flight mass spectrometry, followed by fold-change-filtering analysis. RESULTS: LD50 and LD5 tests indicated that although the aqueous extract has higher toxicity than volatile oil and ethanol extract, the use of TR is safe under the recommended does. The processing procedure could effectively decrease the toxicity of all three extracts with the largest decrease in volatile oil, which is likely due to the loss of volatile compounds during processing. Analgesic and anti-inflammatory studies suggested that volatile oil and ethanol extract of TR have better efficacy than the aqueous extract and the processing procedure significantly enhanced the efficacy of these two former extracts, whereas processing showed no substantially effects on the bioactivities of aqueous extract. Integrated analysis of animal trial and chromatographic analyses indicated that indole and quinolone type alkaloids, limonoids, amides and 18ß-glycyrrhetinic acid were identified as the potential main contributors of TR's efficacy, whereas hydroxy or acetoxy limonoid derivates and coumarins could be the major causes of toxicity. Moreover, the reduced toxicity and improved efficacy of the processed TR are liked due to the licorice ingredients and altered alkaloids with better solubility. CONCLUSIONS: In summary, the integrated toxicity and efficacy analyses of volatile, aqueous and ethanol extracts of TR indicated that the processing procedure could effectively reduce its acute toxicity in all three extracts and enhance its analgesic and anti-inflammatory effects in volatile and ethanol extracts. The promising candidate compounds related to the toxicity and efficacy of TR were also identified. The results could expand our understanding of the value of the standard processing procedure of TR, be valuable to the quality control of TR manufacturing and administration, as well as support clinical rational and safety applications of this medicinal plant.