Fangji Huangqi Decoction alleviates rheumatoid arthritis through regulating HIF-1α mediated the angiogenesis and the balance between autophagy and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Fangji Huangqi Decoction (FHD) is frequently prescribed for the clinical treatment of wind-cold and wind-dampness pathogenic superficial deficiency syndrome. It also has a notable curative effect on rheumatoid arthritis (RA). AIM OF THE STUDY: The study aimed to explore the possible mechanism of FHD against RA and provided a theoretical basis for alternative therapies for RA. MATERIALS AND METHODS: We used UPLC-Q-TOF-MS to analysis the ingredients and absorbed blood components of FHD. At the same time, the collagen-induced arthritis (CIA) rat model was established to estimate the therapeutic effects on FHD by considering body weight, arthritis score, paw swelling, autonomous movement ability, and synovial microvessel counts. Subsequently, immunofluorescence, immunohistochemistry, and Western blot were employed to detect the anti-angiogenic capacity of FHD in vivo, as well as the levels of apoptosis and autophagy in the synovial tissue. In addition, flow cytometry and Western blot were used to assess the effects of FHD on apoptosis and autophagy in MH7A cells. The effects of FHD on the proliferation and migration of MH7A cells were measured by CCK8 assay, cell migration and, invasion experiments. Finally, a tube formation assay was performed to evaluate the angiogenic capacity of FHD in co-cultures of MH7A cells and HUVEC cells. RESULTS: Through testing of FHD's original formula, a total of 26 active ingredients have been identified, with 17 of them being absorbed into the bloodstream. FHD significantly improved the pathological symptoms and synovial hyperplasia of CIA rats. FHD could suppress the expression of HIF-1α, promote apoptosis in CIA rat synovial tissue, and suppress autophagy and angiogenesis. In vitro experiments showed that serum containing FHD inhibited the proliferation, migration, and invasion of MH7A cells, and also suppressed the expression of autophagy-related proteins while promoting apoptosis. FHD markedly repressed the expression of HIF-1α protein in TNF-α-stimulated MH7A cells and inhibited the tube formation capacity induced by MH7A cells in HUVEC cells. CONCLUSIONS: The study had proven that FHD played an excellent anti-RA role, which may be attributed to its potential mechanism of regulating the balance between autophagy and apoptosis in RA FLS by suppressing the HIF-1α, thus contributing to its anti-angiogenic activities.

Effects of endogenous DHA milk and exogenous DHA milk on oxidative stress and cognition in SAMP8 mice.

In this study, Senescence Accelerated Mice (SAMP8) were supplemented with exogenous DHA milk, endogenous DHA milk, normal milk, or 0.9 % saline solution. Enzyme-linked immunosorbent assay (ELISA), gas chromatography (GC), ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI MS/MS), and Morris water maze were used to characterize the effects of diet on oxidative stress and cognition in SAMP8 mice. Supplementation endogenous DHA milk or exogenous DHA milk can enhance the antioxidant capacity of mice organs. Endogenous DHA milk increased the superoxide dismutase (SOD) activity of mice brain and serum than normal milk and 0.9 % saline solution (P ≤ 0.05), as well as increased SOD activity of mice liver and glutathione peroxidase (GSH-Px) activity of mice brain than normal milk (P ≤ 0.05). Exogenous DHA milk increased SOD activity of mice brain than normal milk and 0.9 % saline solution, as well as increased SOD activity of mice serum than 0.9 % saline solution (P ≤ 0.05). Several polar lipid relative content, such as 18:0/18:2 PS, 17:0 Ceramide, and 20:4 LPC in mice brain was affected by dietary supplementation with DHA-containing milk. Lipid oxidation metabolites in mice brain were not affected by DHA-containing milk. Endogenous DHA milk increased the number of platform location crossing times of mice in the Morris water maze test, compared with Exogenous DHA milk, normal milk, and 0.9 % saline solution (P ≤ 0.05).

A comprehensive quality evaluation strategy of Shensong Yangxin capsules based on qualitative, fingerprint and quantitative analyses.

Shensong Yangxin capsule (SSYXC), an effective Chinese patent medicine, has been recorded in the Chinese Pharmacopeia, mainly for the treatment of coronary heart disease and ventricular premature beat. To further complete the quality evaluation of SSYXC, a comprehensive analysis strategy was established. Firstly, the components of SSYXC were qualitatively analysed using ultra-high- performance liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. A total of 134 compounds were identified or tentatively characterized. Additionally, the fingerprint of SSYXC was established by HPLC, and the similarity of 10 batches of SSYXC was elucidated by similarity analysis. The result indicated that the consistency of chemical composition is good. Finally, to enhance the quality control of SSYXC, according to the results of the fingerprint analysis, the contents of the seven active components was determined, comprising morroniside, loganin, paeoniflorin, salvianolic acid B, palmatine hydrochloride, berberine hydrochloride and tanshinone IIA. In conclusion, the established method, comprising identification of components, fingerprint analysis and quantification of multicomponents, can be sensitively and comprehensively applied to the quality evaluation of SSYXC, which can provide chemical ingredients bases for quality control and the pharmacodynamic mechanism of SSYXC, which could serve as a benchmark for controlling the quality of other Chinese patent medicines.

Deciphering the enigma between low bioavailability and high anti-hepatic fibrosis efficacy of Yinchen Wuling powder based on drug metabolism and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Yinchen Wuling powder (YCWLP) is a famous traditional Chinese medicine formula with the effect of "removing jaundice and eliminating dampness", which has the potential to prevent and treat hepatic fibrosis (HF). However, the mechanism of the active ingredients of YCWLP in treating HF remains to be clarified. AIM OF THE STUDY: This study aims to investigate the in vivo metabolic profile of YCWLP and the mechanism of its gut microbiota-mediated therapeutic effect on HF via network pharmacology. MATERIALS AND METHODS: In this comprehensive study, the UHPLC-FT-ICR-MS platform was used for the systematic characterization of the in vivo metabolic profile of YCWLP, and the mediating effect of gut microbiota was elucidated by comparing the differences of metabolites between the normal rats and pseudo germ-free rats administrated with YCWLP. Then, the identified active ingredients of YCWLP metabolized by gut microbiota and their targets associated with HF were used for further network pharmacological analysis, including the construction of PPI network, GO and KEGG enrichment and compound-target-pathway-disease network. RESULTS: Overall, 41 prototype compounds and 138 metabolites were identified in the biosamples after YCWLP administration. Among them, 15 drug prototypes are clearly metabolized by gut microbiota, and 91 metabolites showed significant differences between the N-YCWLP group and the PGF-YCWLP group, which might be attributed to the mediation of gut microbiota. Network pharmacology studies on the aforementioned 15 prototype components indicated crucial roles of arginine biosynthesis and complement and coagulation cascades-related genes such as PLG, NOS3, GC and F2 in the treatment of HF by YCWLP mediated by gut microbiota. CONCLUSIONS: The therapeutic effects of multiple active ingredients in YCWLP on HF depend on the metabolism of gut microbiota. This study offers novel insights into the relationship between bioactive chemical constituents and the action mechanism of YCWLP against HF.

Bile acids metabolism involved in the beneficial effects of Danggui Shaoyao San via gut microbiota in the treatment of CCl4 induced hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Shaoyao San (DSS) is a traditional Chinese medicine (TCM) first recorded in the Synopsis of the Golden Chamber. DSS has proven efficacy in treating hepatic fibrosis (HF). However, the effects and mechanisms of DSS on HF are not clear. AIM OF THE STUDY: To investigate the effect of DSS on HF via gut microbiota and its metabolites (SCFAs, BAs). MATERIALS AND METHODS: HF rats were induced with CCl4 and treated with DSS. Firstly, the therapeutic efficacy of DSS in HF rats and the protection of gut barrier were assessed. Then, 16S rRNA gene sequencing and untargeted fecal metabolomics preliminarily explored the mechanism of DSS in treating HF, and identified different microbiota and metabolic pathways. Finally, targeted metabolomics and RT-qPCR were used to further validate the mechanism of DSS for HF based on the metabolism of SCFAs and BAs. RESULTS: After 8 weeks of administration, DSS significantly reduced the degree of HF. In addition, DSS alleviated inflammation in the ileum and reduced the levels of LPS and D-lactate. Furthermore, DSS altered the structure of gut microbiota, especially Veillonella, Romboutsia, Monoglobus, Parabacteroides, norank_f_Coriobacteriales_Incertae_Sedis. These bacteria have been linked to the production of SCFAs and the metabolism of BAs. Untargeted metabolomics suggested that DSS may play a role via BAs metabolism. Subsequently, targeted metabolomics and RT-qPCR further confirmed the key role of DSS in increasing SCFAs levels and regulating BAs metabolism. CONCLUSIONS: DSS can alleviate CCl4-induced HF and protect the gut barrier. DSS may exert its beneficial effects on HF by affecting the gut microbiota and its metabolites (SCFAs, BAs).

Mfat-1 ameliorates cachexia after hypoxic-ischemic brain damage in mice by protecting the hypothalamus-pituitary-adrenal axis.

AIMS: Cachexia, a metabolic syndrome, affects 21 % of patients suffering from ischemic encephalopathy. However, the specific mechanism and prevention measures are still unclear. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been proven to reduce inflammatory cytokine levels during ischemic events, but whether they have a protective effect against cachexia after hypoxic-ischemic brain damage (HIBD) remains unclear. MAIN METHODS: C57BL/6J wild-type and mfat-1 transgenic male mice were treated with and without HIBD. One day after HIBD, the epididymal white fat, gastrocnemius muscle and hypothalamus were weighed and analyzed the phenotypic changes. RNA sequencing was applied to gastrocnemius muscle to identify differential genes and pathways in HIBD groups. The effect of HPA axis on cachexia post-HIBD was examined via adrenalectomy, dexamethasone (0.1 mg/kg), and corticosterone injection (100 mg/kg). KEY FINDINGS: The results showed that the incidence of cachexia in mfat-1 mice, which produce high proportion of n-3 PUFAs, was significantly lower than that in wild-type mice post-HIBD. Cachexia-related factors, such as inflammation, muscle atrophy and lipid metabolism were significantly improved in mfat-1 HIBD. RNA sequencing revealed that catabolic and proteasome pathways were significantly downregulated. In hypothalamus, inflammatory cytokines, lipid peroxidation levels were reduced. Corticosterone, glucocorticoid receptor, and dexamethasone suppression test all showed that mfat-1 improved the dysfunction of the HPA axis post-HIBD. The present study elucidated for the first time that mfat-1 reduced HIBD-induced hyperactivation of the HPA axis in mice by reducing inflammation and oxidative stress and contributed to the reduction of metabolic imbalance in peripheral tissues. SIGNIFICANCE: Our study provides mechanistic information for the development of intervention strategies to prevent cachexia.

The effect of vegetable oil pre-emulsified with whey protein and pectin on physicochemical properties and microstructure of low-fat yogurt.

The effects of whey protein isolate (WPI)-pectin pre-emulsified vegetable oil on the physicochemical properties and microstructure of low-fat yogurt (LFY) were investigated by particle size distribution, water-holding capacity (WHC), texture, rheology, electron microscopy, storage stability, and sensory analysis. The vegetable oil was pre-emulsified into two types of emulsions, a mixed emulsion (ME: WPI-pectin complexes were adsorbed directly at the interface) and a bilayer emulsion (BE: Pectin was added to a previously established WPI-stabilized interface). The results showed that yogurts added with pre-emulsified vegetable oil (ME-Y, BE-Y) had significantly better quality than LFY, with better WHC, textural properties, rheological properties, and storage stability. The average particle size of ME (11.96 µm) was larger than that of BE (10.23 µm). The consistency of yogurt added with ME (ME-Y) was significantly higher than that of yogurt added with BE (BE-Y), at 2359.10 and 2181.12 g s, respectively. Meanwhile, ME-Y exhibited storage stability similar to full-fat control (FFY) and higher sensory scores. Interestingly, the WHC of BE-Y (49.03%) was higher than that of ME-Y (45.63%). In addition, WPI + Pectin-Y exhibited higher WHC (53.81%) and consistency (2518.73 g s) compared to ME-Y and BE-Y, but the particle size distribution was not uniform, and the direct addition of WPI, pectin, and oil had no positive effect on improving the rheological properties of yogurt. Overall, the addition of WPI-pectin pre-emulsified vegetable oil improved the quality of LFY. These findings are particularly relevant for the production of higher quality LFY.

Determination of the components of danyikangtai powder into the plasma and its pharmacodynamic study.

Danyikangtai powder has a definite therapeutic effect on pancreatitis. However, the internal mechanism is unclear. The purpose of this experiment is to quickly identify the blood components of danyikangtai powder and evaluate its efficacy. 25 blood components were identified by comparing the components with the same mass spectrometry information from in vivo and in vitro samples. The AR42J cells of the pancreatitis model were treated with drug-containing plasma, and the drug efficacy was evaluated by investigating the amylase release rate. This study provides a scientific reference for its pharmacological research and rational clinical application.

Dual process model of farmers' mindfulness and sustainable economic behavior: Mediating role of mental health and emotional labor.

Mindful awareness of our interconnection with the natural environment could help to redeem our lost environmentally entrenched identity and help us to act more sustainably, concluding the predictable gaps between mindfulness and sustainable behavior. We propose more precisely that mindful attentiveness may be essential to establishing sustainable economic behavior through understanding emotional labor and enhanced mental health. Likewise, with an ever-rising concern related to mental health and emotional labor, recent industrialization and commoditization of agricultural products have stressed the need for mindfulness, and causing sustainable economic behavior of farmers that is imminent. Hence, the study will not only explore the connection between mindfulness and sustainable economic behavior, but there is a need to examine the mediating role of emotional labor and the mental health of farmers in China. The study selected the farmers because mindful awareness, emotional labor, and mental health of a farmer can significantly contribute to sustainable economic behavior and bring a connection with the natural environment. The data of 358 responses were analyzed using SPSS-AMOS. The results revealed that mindfulness, mental health, and emotional labor have a significant connection with the sustainable economic behavior of farmers in China. The results also indicated that mental health and emotional labor mediate between mindfulness and sustainable economic behavior. The results set the tone for the policy-makers to create awareness among all the stakeholders about the importance of mindfulness to help farmers manage their emotional labor and mental health for better, sustainable performance outcomes.

Decarboxylative Selective Phosphorylation of Aliphatic Acids: A Transition-Metal- and Photocatalyst-Free Avenue to Dialkyl and Trialkyl Phosphine Oxides from White Phosphorus.

Developing practical and mild strategies for the direct functionalization of white phosphorus (P4 ) without chlorination is an appealing but formidable challenge. To this end, we report a breakthrough in the preparation of structurally diverse dialkylphosphines and trialkylphosphines that rely on the successive generation of carbon-centered radicals from N-hydroxyphthalimide (NHPI) esters and the controllable alkylation of the P4 molecule under transition-metal- and photocatalyst-free conditions. To facilitate separation and prevent product losses during purification, the corresponding oxidation products dialkylphosphine oxides (DAPOs) and trialkylphosphine oxides (TAPOs) were isolated. This photoinduced phosphorylation reaction features one-pot operation, high product selectivity, and tolerates a broad range of alkyl NHPI esters, including derivatives of complex natural products and pharmaceuticals. Further diversified transformation of DAPOs to construct P-F, P-C, P-N, and P-O bonds was also demonstrated.

Dietary Schizochytrium Microalgae Affect the Fatty Acid Profile of Goat Milk: Quantification of Docosahexaenoic Acid (DHA) and Its Distribution at Sn-2 Position.

The objective of this study was to detect the influence of dietary Schizochytrium microalgae on milk composition, milk fatty acids, and milk sn-2 fatty acids in goat's milk. Firstly, we could see that the fat content increased in low microalgae supplementation goat's milk (LM, 15 g/day) and the lactose content decreased in medium microalgae supplementation goat's milk (MM, 25 g/day) compared with control goat's milk (C, 0 g/day). Moreover, the absolute concentration of the docosahexaenoic acid (DHA) of LM, MM, and high microalgae supplementation (HM, 35 g/day) goat's milk was 29.485, 32.351, and 24.817 mg/100 g raw milk, respectively, which were all higher than that in the control goat's milk with 4.668 mg/100 g raw milk. In addition, the sn-2 DHA content increased in MM and HM goat's milk. However, the decreasing trend of the sn-2 DHA content was observed in LM goat's milk. As for other fatty acids, the oleic acid (C18:1n9c) and linolenic acid (C18:3n3) content decreased and increased, respectively, in all experimental goat milk. Finally, an interesting phenomenon was found, which was that docosanoic acid (C22:0) and tetracosenic acid (C24:1) were only detected in test goat's milk. Consequently, the phenomena of this study demonstrated that dietary Schizochytrium microalgae have an obvious effect on the fatty acid and sn-2 fatty acid profile of goat's milk, and they provide an effective method to improve the content of goat's milk DHA in practical production.

Emerging Applications of Metabolomics to Assess the Efficacy of Traditional Chinese Medicines for Treating Type 2 Diabetes Mellitus.

Diabetes is a common and complex disease that can exacerbate the complications related to cardiovascular disease, and this is especially true for type 2 diabetes mellitus (T2DM). In addition to the standard pharmacological therapies, T2DM has also been treated with nonconventional regimens such as traditional Chinese medicine (TCM), e.g., herbal medicines and TCM prescriptions, although the mechanisms underlying the therapeutic benefits remain unclear. In this regard, many studies have used metabolomics technology to elucidate the basis for the efficacy of TCM for T2DM. Metabolomics has recently attracted much attention with regard to drug discovery and pharmacologically relevant natural products. In this review, we summarize the application of metabolomics to the assessment of TCM efficacy for treating T2DM. Increasing evidence suggests that the metabolic profile of an individual patient may reflect a specific type of T2DM syndrome, which may provide a new perspective for disease diagnosis. In addition, TCM has proved effective for countering the metabolic disorders related to T2DM, and this may constitute the basis for TCM efficacy. Therefore, further determining how TCM contributes to the reversal of metabolic disorders, such as using network pharmacology or by assessing the contribution of host-gut microbiota interactions, will also provide researchers with new potential targets for pharmacologic-based therapies.

Comprehensive Analysis of Fecal Microbiome and Metabolomics in Hepatic Fibrosis Rats Reveal Hepatoprotective Effects of Yinchen Wuling Powder From the Host-Microbial Metabolic Axis.

Hepatic fibrosis (HF) is a typical consequence in the development of multiple chronic liver diseases, which is intimately related to the composition and metabolic status of gut microbiota. A myriad of evidence has indicated that traditional Chinese medicine can treat HF by regulating gut microbiota. Yinchen Wuling powder (YCWLP) is a famous traditional Chinese medicine prescription, which has been used to relieve liver diseases for thousands of years. YCWLP has demonstrated protective function on HF, but its effect on the alterations of gut microbiota is still unclear, and its explicit therapeutic mechanism also needs to be further elucidated. In this study, 16S rRNA gene sequencing and fecal metabolomics analysis were combined to investigate the influence of YCWLP on gut microbiota in HF rats and the interactions between gut microbiota and host metabolism. The results showed that YCWLP treatment significantly improved the disorder of multiple organ indices, HF-related cytokines and plasma LPS induced by HF. Masson's trichrome stainings also showed that YCWLP treatment could significantly alleviate the severity of HF in rats. Additionally, YCWLP could reverse the significant changes in the abundance of certain genera closely related to HF phenotype, including Barnesiella [Ruminococcus] and Christensenella. Meanwhile, YCWLP significantly increased the abundance of Bifidobacterium, Coprococcus and Anaerostipes, which are closely related to butyrate production. Metabolomics and Spearman's correlation analysis showed that YCWLP could regulate the disorder of arginine biosynthesis, sphingolipid metabolism and alanine, aspartate and glutamate metabolism in HF rats, and these regulations were intimately related to Barnesiella, [Ruminococcus], Christensenella, Coprococcus and Anaerostipes. By explaining the biological significance of the above results, we concluded that YCWLP might ameliorate HF by regulating the imbalance of gut microbiota, increasing the abundance of butyrate-producing bacteria to reduce ammonia production, promote ammonia degradation, and regulate pro-inflammatory cytokines and immune function.

Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes.

BACKGROUND: A crosstalk exists between diabetes and Alzheimer's disease (AD), and diabetic encephalopathy displays AD-like disorders. Sarsasapogenin (Sar) has strong anti-inflammatory efficacy, showing neuroprotection and memory-enhancement effects. PURPOSE: This study aims to verify the ameliorative effects of Sar on diabetic encephalopathy in vivo and in vitro, and to clarify the mechanisms from attenuation of AD-like pathology. METHODS: Streptozotocin-induced type 1 diabetic rats and high glucose-cultured SH-SY5Y cells were used in this study. After Sar treatment (20 and 60 mg/kg) for consecutive 9 weeks, Morris water maze and novel object recognition tasks were performed. Hematoxylin-eosin staining was used for examining loss of neurons in CA1 area and ki67 expression for reflecting neurogenesis in DG area of hippocampus. Aß production pathway and tau phosphorylation kinase cascade were examined in these two models. RESULTS: Sar improved learning and memory ability, loss of neurons and reduction of neurogenesis in the hippocampus of diabetic rats. Moreover, Sar suppressed Aß overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3ß cascade in the hippocampus and cerebral cortex of diabetic rats and high glucose-cultured SH-SY5Y cells, and PPARγ antagonism abolished the effects of Sar on key molecules in the two pathways. Additionally, it was found that high glucose-stimulated Aß overproduction was prior to tau hyperphosphorylation in neurons. CONCLUSION: Sar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aß overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders.

Activity Components from Gynostemma pentaphyllum for Preventing Hepatic Fibrosis and of Its Molecular Targets by Network Pharmacology Approach.

Hepatic fibrosis would develop into cirrhosis or cancer without treating. Hence, it is necessary to study the mechanism and prevention methods for hepatic fibrosis. Gynostemma pentaphyllum is a traditional medicinal material with a high medicinal and health value. In this study, nineteen compounds obtained from G. pentaphyllum were qualitative and quantitative by HPLC-FT-ICR MS and HPLC-UV, respectively. Among them, the total content of 19 gypenosides accurately quantified reaches 72.21 mg/g and their anti-proliferation against t-HSC/Cl-6 cells indicated compound 19 performed better activity (IC50: 28.1 ± 2.0 µM) than the other compounds. Further network pharmacology study demonstrated that compound 19 mainly plays an anti-fibrosis role by regulating the EGFR signaling pathway, and the PI3K-Akt signaling pathway. Overall, the verification result indicated that compound 19 appeared to be nontoxic to LO2, was able to modulate the PI3K/Akt signal, led to subG1 cells cycle arrest and the activation of mitochondrial-mediated apoptosis of t-HSC/Cl-6 cells for anti-hepatic fibrosis.

Transcutaneous electrical nerve stimulation and solifenacin succinate versus solifenacin succinate alone for treatment of overactive bladder syndrome: A double-blind randomized controlled study.

OBJECTIVE: We evaluated a combination of transcutaneous electrical nerve stimulation (TENS) and solifenacin succinate versus solifenacin alone in the treatment of overactive bladder (OAB). METHODS: Ninety-seven female outpatients with OAB were screened for this double-blind randomized controlled study. Eighty-six patients who met our inclusion criteria were divided randomly into two groups. In group A (43 patients), patients received oral solifenacin and "fake" TENS on the foot; in group B (43 patients), patients received oral solifenacin and effective TENS on the foot. Improvements in OAB symptoms were assessed by Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire (OAB-q), voiding diaries and urodynamic tests. 70 of 86 patients (36 in group A, 34 in group B) completed the 2 months of treatment and 3 months of follow-up. RESULTS: Statistically, the maximum bladder volume and OAB symptoms of both groups improved significantly after treatment. The improvement in group B was significantly better than that in group A, as indicated by the maximum bladder volume, OAB-q score and voiding diary. Some mild adverse effects were observed, including dry mouth, stomach upset, constipation, muscle pain and local paresthesia. CONCLUSION: The combination of TENS and solifenacin was more effective in improving OAB symptoms than solifenacin alone.

Investigation of the therapeutic effect of Yinchen Wuling Powder on CCl4-induced hepatic fibrosis in rats by 1H NMR and MS-based metabolomics analysis.

Hepatic fibrosis (HF) is a typical consequence of various chronic liver diseases, and there is still no ideal drug for its treatment. Yinchen Wuling Powder (YCWLP), a famous traditional Chinese medicine prescription, is effective for the treatment of icteric hepatitis, hepatic fibrosis, non-alcoholic fatty liver disease and other liver diseases in clinical practices, however, the underlying mechanisms of YCWLP on HF is still unclear. In this study, 1H NMR and MS-based metabolomics analysis along with body weight change, serum liver function indexes, serum liver fibrosis index and histopathological observations of liver were applied to evaluate the therapeutic effect of YCWLP on hepatic fibrosis and the mechanism associated with this. The results of the pharmacodynamics study show that YCWLP has a significant therapeutic effect on hepatic fibrosis. As for the metabolomics research, 7 metabolites in the plasma samples, 28 in the urine samples and 6 in the liver samples were significantly altered due to the protective effect of YCWLP on CCl4-induced hepatic fibrosis. These endogenous metabolites are involved in amino acid metabolism, carbohydrate metabolism, glycerophospholipid metabolism and gut bacteria metabolism. These findings suggest that YCWLP could treat hepatic fibrosis by promoting urea circulation and reducing blood ammonia accumulation, improving carbohydrate metabolism and reducing oxidative stress, improving glycerophospholipid metabolism and protecting cell membrane, and regulating intestinal flora metabolism.

Sarsasapogenin ameliorates diabetes-associated memory impairment and neuroinflammation through down-regulation of PAR-1 receptor.

Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition-enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes-associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes-associated memory impairment in streptozotocin-induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end-products and its receptor (AGEs/RAGE) axis and suppressed up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) in cerebral cortex. On the other hand, Sar mitigated high glucose-induced neuronal damages, NLRP1 inflammasome activation, and PAR-1 up-regulation in high glucose-cultured SH-SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR-1 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF-κB mediated the effect of PAR-1 up-regulation in high glucose condition by using PAR-1 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF-κB regulated by cerebral PAR-1. HIGHLIGHTS: Sarsasapogenin ameliorated memory impairment caused by diabetes in rats. Sarsasapogenin mitigated neuronal damages and neuroinflammation by down-regulating cerebral PAR-1. The NLRP1 inflammasome and NF-κB signaling mediated the pro-inflammatory effects of PAR-1. Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic rodents.

Rapid characterization of the chemical constituents of Yinchen Wuling Powder by UPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry.

Yinchen Wuling Powder (YCWLP) is a classic Chinese medicine prescription with a long history and has been commonly used for treating jaundice hepatitis, liver fibrosis, hyperlipidemia and early diabetes in clinical applications. However, the chemical composition of YCWLP is still unclear. In order to obtain the chemical profile of YCWLP, a systematic ultra-performance liquid chromatography coupled with fourier transform ion cyclotron resonance mass spectrometry (UPLC-FT-ICR-MS) method was developed in this study. As a result, a total of 138 compounds including terpenoid acids, organic acids, flavonoids, sesquiterpenes, coumarins and anthraquinones were identified by comparing the retention time, molecular ions and fragmentation behaviors with the reference compounds or the in-house database. This study comprehensively elucidated the chemical basis of YCWLP and provided a scientific basis for further quality control and pharmacology research.

Pharmacokinetic-pharmacodynamic modeling analysis and anti-inflammatory effect of Wangbi capsule in the treatment of adjuvant-induced arthritis.

Clinically, Wangbi Capsule (WBC) is widely used in the treatment of Rheumatoid arthritis (RA) because of its remarkable therapeutic effect. To reveal the mechanism, a pharmacokinetic-pharmacodynamic (PK-PD) model was developed for the first time to assess the relationship between time-concentration (dose)-effect. Freund's Complete Adjuvant was used to induce the adjuvant-induced arthritis model. Multi-indices were used to evaluate the therapeutic effect and an S-Imax PK-PD model was established based on the concentrations of osthole, 5-O-methylvisamminoside, cimifugin, albiflorin, paeoniflorin and icariin and the levels of interleukin-1ß and prostaglandin E2 using a two-compartment PK model together with a PD model with an effect-site compartment. The results suggest that WBC can treat RA by regulating the levels of prostaglandin E2 and interleukin-1ß. For the PK-PD model, the parameters indicated that WBC had a large safety margin and all six bioactive ingredients of WBC have therapeutic effects on RA. Among them icariin, osthole and 5-O-methylvisamminoside may be the main effective substances. This study provided a scientific basis for further study of population pharmacokinetics / population pharmacodynamics (PPK/PPD), to develop a reasonable administration plan and improve individualized drug therapy.