Anti-inflammatory and protective effects of Pimpinella candolleana on ulcerative colitis in rats: a comprehensive study of quality, chemical composition, and molecular mechanisms.

Introduction: P. candolleana Wight et Arn. Is a traditional Chinese herbal medicine used by the Gelao nationality in southwest China, has been historically applied to treat various gastrointestinal disorders. Despite its traditional usage, scientific evidence elucidating its efficacy and mechanisms in treating ulcerative colitis (UC) remains sparse. This study aimed to determine the quality and chemical composition of Pimpinella candolleana and to identify its potential therapeutic targets and mechanisms in acetic acid-induced ulcerative colitis (UC) rats through integrated approaches. Methods: Morphological and microscopic characteristics, thin layer chromatography (TLC) identification, and quantitative analysis of P. candolleana were performed. UPLC-Q-TOF-MS, network pharmacology, and molecular docking were used to identify its chemical composition and predict its related targets in UC. Furthermore, a rat model was established to evaluate the therapeutic effect and potential mechanism of P. candolleana on UC. Results: Microscopic identification revealed irregular and radial arrangement of the xylem in P. candolleana, with a light green cross-section and large medullary cells. UPLC-Q-TOF-MS analysis detected and analyzed 570 metabolites, including flavonoids, coumarins, and terpenoids. Network pharmacology identified 12 effective components and 176 target genes, with 96 common targets for P. candolleana-UC, including quercetin, luteolin, and nobiletin as key anti-inflammatory components. GO and KEGG revealed the potential involvement of their targets in RELA, JUN, TNF, IKBKB, PTGS2, and CHUK, with action pathways such as PI3K-Akt, TNF, IL-17, and apoptosis. Molecular docking demonstrated strong affinity and binding between these key components (quercetin, luteolin, and nobiletin) and the key targets of the pathway, including JUN and TNF. Treatment with P. candolleana improved body weight loss, the disease activity index, and colonic histological damage in UC rats. Pimpinella candolleana also modulated the levels of IL-2 and IL-6 in UC rats, reduced the expression of pro-inflammatory cytokines such as IL-6, MAPK8, TNF-α, CHUK, and IKBKB mRNA, and decreased the expression of TNF, IKBKB, JUN, and CHUK proteins in the colon of UC rats, thereby reducing inflammation and alleviating UC symptoms. Conclusion: P. candolleana exerts its protective effect on UC by reducing the expression of proinflammatory cytokines and inhibiting inflammation, providing scientific evidence for its traditional use in treating gastrointestinal diseases. This study highlights the potential of P. candolleana as a natural therapeutic agent for UC and contributes to the development of novel medicines for UC treatment.

Effects of Dietary l-Glutamine Supplementation on the Intestinal Function and Muscle Growth of Piglets.

The aim of this study was to investigate the effects of dietary l-glutamine (Gln) supplementation on the morphology and function of the intestine and the growth of muscle in piglets. In this study, sixteen 21-day-old piglets were randomly divided into two groups: the Control group (fed a basal diet) and the Gln group (fed a basal diet supplemented with 0.81% Gln). Blood, gut, and muscle samples were collected from all piglets on Day 20 of the trial. Compared with the Control group, the supplementation of Gln increased (p < 0.05) the villus height, villus width, villus surface area, and villus height/crypt depth ratio of the small intestine. Furthermore, the supplementation of Gln increased (p < 0.05) total protein, total protein/DNA, and RNA/DNA in both the jejunum and ileum. It also increased (p < 0.05) the concentrations of carnosine and citrulline in the jejunal mucosa, as well as citrulline and cysteine concentrations in the ileum. Conversely, Gln supplementation decreased (p < 0.05) Gln concentrations in both the jejunum and ileum, along with ß-aminoisobutyric acid and 1-Methylhistidine concentrations, specifically in the ileum. Subsequent research revealed that Gln supplementation increased (p < 0.05) the mRNA levels for glutathione-S-transferase omega 2 and interferon-ß in the duodenum. In addition, Gln supplementation led to an increase (p < 0.05) in the number of Lactobacillus genus in the colon, but a decrease (p < 0.05) in the level of HSP70 in the jejunum and the activity of diamine oxidase in plasma. Also, Gln supplementation reduced (p < 0.05) the mRNA levels of glutathione-S-transferase omega 2 and interferon stimulated genes, such as MX1, OAS1, IFIT1, IFIT2, IFIT3, and IFIT5 in both the jejunum and ileum, and the numbers of Clostridium coccoides, Enterococcus genus, and Enterobacterium family in the colon. Moreover, Gln supplementation enhanced (p < 0.05) the concentrations of total protein, RNA/DNA, and total protein/DNA ratio in the longissimus dorsi muscle, the concentrations of citrulline, ornithine, arginine, and hydroxyproline, and the mRNA level of peptide transporter 1, while reducing the contents of hydrogen peroxide and malondialdehyde and the mRNA level of glutathione-S-transferase omega 2 in the longissimus dorsi muscle. In conclusion, dietary Gln supplementation can improve the intestinal function of piglets and promote the growth of the longissimus dorsi muscle.

Local knowledge of homegarden plants in Miao ethnic communities in Laershan region, Xiangxi area, China.

BACKGROUND: Homegardens are small-scale land use systems with significant implications for local livelihoods, biodiversity conservation, and sustainable development due to their diverse flora and fauna. Conducting homegarden surveys enables researchers to gain insights into the traditional ecological knowledge of indigenous communities, preserve homegarden biodiversity, and promote sustainable livelihoods. This study has two objectives: first, to collect, record, and organize data on homegarden plants and related traditional knowledge from three communities in the Laershan Plateau, and second, to analyze the species and functional diversity of homegarden plants in the region while exploring the factors that contribute to the heterogeneous distribution of these plants among the communities of three townships. METHODS: This research employed field surveys in the Laershan Miao Autonomous Region in Xiangxi, China, from September 2021 to August 2023. Data were collected through observation and semi-structured interviews. The study utilized descriptive statistics and quantitative analysis, including the Relative Importance Value (RI), Use Value Index (UV), Jaccard Index (JI), and Comprehensive Index of Land Use Degree (La), to examine the diversity of local homegarden plants and related traditional knowledge, as well as community heterogeneity. RESULTS: The study area exhibited rich biodiversity, with 152 plant species recorded belonging to 62 families and 124 genera. These findings highlight the importance of homegarden plants in maintaining ecological balance and enhancing system resilience against disturbances. Homegarden plants serve multiple functions such as food, ornamental, medicinal, and fodder purposes, with edible and trade plants having the most abundant knowledge. Furthermore, this research revealed that communities with similar forest resource compositions may have similar homegarden plant compositions, demonstrating the connection between cultural exchange among different communities and patterns of plant species distribution. CONCLUSIONS: The Laershan region boasts diverse homegarden plant species crucial for ecological balance and resilience. Their multifunctionality reflects human impact. Plant diversity varies with residents' lifestyles, needs, and cultural exchanges. The close connection between plants and local life is clear. Factors like resource distribution, cultural exchange, and lifestyle influence plant distribution. Further research is needed for conservation and sustainable development. Future research should focus on culturally valuable plant species and traditional knowledge applications.

[Changes in Soil Nitrogen Components and Their Relationship with Environmental Factors with Different Tea Plantation Ages].

Changes in soil nitrogen components in tea gardens affect the soil nitrogen supply capacity and nitrogen cycle. In this study, soil samples were collected from forest land, cultivated land, and tea gardens with different plantation ages (30, 50, and 70 years) to explore the changes in soil nitrogen components and their relationship with physicochemical properties and enzyme activities. The results showed that:① with the increase in tea plantation age, the silt, total phosphorus, and urease and catalase activities gradually increased, whereas the sand, clay, pH, electrical conductivity, soil organic carbon, and the activities of invertase gradually decreased. The alkaline phosphatase activity increased first and then decreased with the increase in tea plantation age, and no significant differences were observed in soil water content and acid phosphatase activity. ② With the increase in tea plantation age, the contents of acid ammonia nitrogen, amino acid nitrogen, and nitrate nitrogen (NO3--N) increased significantly, and the contents of total nitrogen, acid ammonia nitrogen, hydrolyzable unknown nitrogen, and non-hydrolyzable nitrogen in tea gardens were significantly higher than those in forest land. ③ The total phosphorus, alkaline phosphatase, and urease were the main factors affecting soil nitrogen components. Among them, organic nitrogen components were significantly correlated with total phosphorus and alkaline phosphatase, and inorganic nitrogen components were significantly correlated with alkaline phosphatase, whereas total nitrogen had significant correlations with sand, silt, total phosphorus, urease, and alkaline phosphatase.

A novel physical-biochemical treatment of refinery wastewater.

As of 2022, China has achieved a crude oil processing capacity of 918 million tons, leading to a notable escalation in the production of refinery wastewater. The composition of refinery wastewater is intricate and diverse, posing a substantial challenge to its treatment. In order to facilitate appropriate discharge or reuse, an exhaustive separation process is imperative for refinery wastewater. Conventional pre-treatment processes typically employ inclined plate separators and dissolved air flotation (DAF) for the removal of oil and suspended solids (SS), while sequencing batch reactor (SBR), oxidation ditch, or biological aerated filter (BAF) are employed for the biological treatment process. However, these approaches encounter challenges such as a large spatial footprint, suboptimal treatment efficiency, and high energy consumption. In response to these challenges, this study introduces a novel integrated apparatus consisting of a high-efficiency oil remover (HEOR), coalescence oil remover (COR), and an airlift-enhanced loop bioreactor (AELR). A pilot-scale test was conducted to evaluate the performance of this integrated system in practical field applications. The pilot-scale tests reveal that, without the addition of chemical agents, the petroleum removal efficiency of "HEOR + COR" system was 1.2 times that of DAF. Compared with the SBR system, AELR's volume loading was increased by 1.56 times. The effluent quality achieved in the pilot-scale tests attained parity with that the original process. The "HEOR + COR + AELR" system exhibited energy and carbon emissions reduction of 28% and 30% compared to the "DAF + SBR" system, respectively. Therefore, the operating costs was reduced by approximate 1 Chinese Yuan (CNY) per ton of treated water. This technological advancement serves as a valuable reference for the implementation of low-carbon treatment of refinery wastewater.

Rheological properties and microstructure of wheat flour dough systems with enzyme-hydrolyzed mashed potatoes.

The interest in incorporating potatoes into wheat dough is increasing. However, potatoes exhibit significant viscosity during thermal processing, affecting product processing and quality. This study aims to find an effective method to reduce the viscosity of mashed potatoes. We aimed to compare the effects of different enzymes (α-amylase, ß-amylase, and flavourzyme) and concentrations (0.01%, 0.05%, and 0.1%) on the micromorphology and rheological properties of mashed potatoes and potato-wheat dough. The impact of flavourzyme was the most significant (p<0.05). When enzyme concentration increased, viscosity decreased, and the degree of structural damage, indicated by increased porosity. Notably, the addition of flavourzyme can increase the content of sweet and umami free amino acids, improving the flavor of mashed potatoes. The scanning electron microscopy and confocal laser scanning microscopy images of potato-wheat dough revealed that enzyme-hydrolyzed mashed potatoes had improved homogeneity, reestablished the dough continuity, and strengthened the three-dimensional structure comprising proteins and starch. Notably, flavourzyme demonstrated the most significant effect on enhancing the protein-starch network structure. This was attributed to the exposure of functional groups resulting from protein hydrolysis, facilitating interaction with starch molecules. Our findings indicate that the addition of 0.1% flavourzyme (500 LAPU/g, pH 5.5, 55 ± 2°C, 30 min treated) was the most effective in reducing viscosity and reconstructing the gluten network. Enzymatic hydrolysis plays a vital role in the production of high-quality potato products, with particular importance in the baking industry, where flavourzyme exhibits significant potential. PRACTICAL APPLICATION: Enzymatic hydrolysis plays a vital role in the production of high-quality potato products, with particular importance in the baking industry, where flavourzyme exhibits significant potential.

Chitosan entrapping of sodium alginate / Lycium barbarum polysaccharide gels for the encapsulation, protection and delivery of Lactiplantibacillus plantarum with enhanced viability.

To preserve the viability of probiotics during digestion and storage, encapsulation techniques are necessary to withstand the challenges posed by adverse environments. A core-shell structure has been developed to provide protection for probiotics. By utilizing sodium alginate (SA) / Lycium barbarum polysaccharide (LBP) as the core material and chitosan (CS) as the shell, the probiotic load reached 9.676 log CFU/mL. This formulation not only facilitated continuous release in the gastrointestinal tract but also enhanced thermal stability and storage stability. The results obtained from Fourier transform infrared spectroscopy and thermogravimetric analysis confirmed that the addition of LBP and CS affected the microstructure of the gel by enhancing the hydrogen bond force, so as to achieve controlled release. Following the digestion of the gel within the gastrointestinal tract, the released amount was determined to be 9.657 log CFU/mL. The moisture content and storage stability tests confirmed that the encapsulated Lactiplantibacillus plantarum maintained good activity for an extended period at 4 °C, with an encapsulated count of 8.469 log CFU/mL on the 28th day. In conclusion, the newly developed core-shell gel in this study exhibits excellent probiotic protection and delivery capabilities.

Banxia Baizhu Tianma Tang decoction and modified Taohong Siwu combined with Western medicine to treat a patient with severe stenosis of the middle cerebral artery: A case report.

RATIONALE: Intracranial artery stenosis is an important cause of ischemic stroke, and MCA is one of the most common vessels causing intracranial artery stenosis. At present, there are 3 main treatments for MCA stenosis: medical drug therapy, surgery, and endovascular interventional therapy. PATIENT CONCERNS: We report a patient with severe middle cerebral artery stenosis, including his imaging and clinical manifestations. DIAGNOSIS: Severe stenosis of middle cerebral artery. INTERVENTIONS: Banxia Baizhu Tianma decoction combined with Taohong Siwu decoction combined with western medicine. OUTCOMES: The stenosis of M1 segment of middle cerebral artery was significantly improved, the stenosis rate was reduced from 70% to 30%, and the clinical symptoms of the patients basically disappeared. LESSONS: Banxia Baizhu Tianma decoction combined with Taohong Siwu plus subtraction combined with western medicine is effective in the treatment of middle cerebral artery stenosis.

Fucoxanthin extract ameliorates obesity associated with modulation of bile acid metabolism and gut microbiota in high-fat-diet fed mice.

PURPOSE: Fucoxanthin extract (FX) is a type of carotenoid with a beneficial effect against obesity. The purpose of this study was to explore its precise action mechanism of losing weight. METHODS: A high-fat diet induced obesity mouse model was established to study the effects of different doses of FX on C57BL/6J male mice for 12 weeks. Following intervention, serum indices, tissue sections, liver gene expression, and intestinal microorganisms were analyzed. RESULTS: FX at low, medium, and high dosages (80, 160, and 320 mg/kg/day, respectively) for 12 weeks was associated with the lower body weight of mice when compared to that of high-fat-diet fed mice. It also improved glucose tolerance as well as serum lipid levels, and reduced fat accumulation. Significant regulation of bile acid metabolism and intestinal microbiota may contribute to the above effects. The bile acids in the FXH group were significantly increased. A low-dose and a medium-dose FX increased the level of transmembrane G protein-coupled receptor 5 (TGR5); a low-dose and high-dose FX increased the farnesoid X receptor (FXR) expression, and a medium-dose had no effect. 16S rRNA sequencing indicated that the Lachnospiraceae and Oscillospiraceae contributed to the beneficial effects of FX. CONCLUSION: Our study sheds light on mechanisms behind the weight-lowering of FX, and manifested that bile acid metabolism and gut microbiota may be potential therapies. These results support that FX is a valuable candidate for promoting health and alleviating obesity.

Bacillus coagulans prevents the decline in average daily feed intake in young piglets infected with enterotoxigenic Escherichia coli K88 by reducing intestinal injury and regulating the gut microbiota.

Background: Enterotoxigenic Escherichia coli (ETEC), an important intestinal pathogen, poses a significant threat to the intestinal health of piglets. Bacillus coagulans (BC), a potential feed additive, can improve the intestinal function of piglets. However, the effects of BC on growth performance and intestinal function in ETEC-infected piglets are still unclear. In this study, 24 7-day-old piglets were randomly assigned to three treatment groups: control group (fed a basal diet), ETEC group (fed a basal diet and challenged with ETEC K88) and BC+ETEC group (fed a basal diet, orally administered BC, challenged with ETEC K88). During Days 1-6 of the trial, piglets in the BC+ETEC group were orally administered BC (1×108CFU/kg). On Day 5 of the trial, piglets in the ETEC and BC+ETEC groups were orally administered ETEC K88 (5×109CFU/piglet). Blood, intestinal tissue, and content samples were collected from the piglets on Day 7 of the trial. Results: The average daily feed intake in the ETEC group was significantly reduced compared to that of the control group. Further research revealed that ETEC infection significantly damaged the structure of the small intestine. Compared to the control group, the villus height and surface area of the jejunum, the ratio of villus height to crypt depth in the duodenum and jejunum, and the activities of catalase and total superoxide dismutase in the jejunum were significantly reduced. Additionally, the levels of myeloperoxidase in the jejunum, malondialdehyde in the plasma and jejunum, and intestinal epithelial apoptosis were significantly increased in the ETEC group. However, BC supplementation had significantly mitigated these negative effects in the BC+ETEC group by Day 7 of the trial. Moreover, BC supplementation improved the gut microbiota imbalance by reversing the decreased numbers of Enterococcus, Clostridium and Lactobacillus in jejunum and Escherichia coli, Bifidobacterium and Lactobacillus in the colon, as well as the increased number of Escherichia coli in the jejunum induced by ETEC K88. Conclusions: Overall, BC supplementation reduced the decline in average daily feed intake in ETEC K88-infected piglets by attenuating intestinal epithelial apoptosis and oxidative stress and regulating the gut microbiota. This suggests that BC may be used to prevent intestinal infections caused by ETEC in piglets.

Screening and identification of neuraminidase inhibitors from Baphicacanthus cusia by a combination of affinity ultrafiltration, HPLC-MS/MS, molecular docking, and fluorescent techniques.

Natural products provide a new opportunity for the discovery of neuraminidase (NA)inhibitors. In this study, an affinity ultrafiltration (AUF) coupled with HPLC-MS/MS method was firstly developed and optimized for screening of NA inhibitors from natural products. The critical factors influencing the interaction of enzyme-ligand (including sample concentration, enzyme concentration, incubation time and temperature, pH of the buffer, and dissociation solvents and time) were investigated and optimized by a one-factor-at-a-time design. The method was then applied to discover NA inhibitory compounds in stems and leaves of Baphicacanthus cusia. As a result, five active alkaloids were screened out and identifiedas 2,4(1H,3H)-quinazolinedione (1), 4(3H)-quinazolinone (2), 2(3H)-benzoxazolone (3), tryptanthrin (4), and indirubin (5) through analysis of their DAD profiles, MS/MS fragments, and comparison with reference substances. These active compounds were further evaluated for their NA inhibitory activity using a fluorescence-based NA inhibition assay. The result from the fluorescent assay revealed that all the five compounds(1-5) showed pronounced NA inhibitory activities with IC50values of 98.98, 64.69, 40.16, 69.44, and 144.73 µM, respectively. Finally, molecular docking of these five alkaloids with NA showed that hydrogen bond and π-cation interactions dominated within the binding sites with binding energies ranging between -5.7 to -7.9 kcal/mol, which was supported by the results of the AUF and the fluorescence-based enzyme assay. The developed AUF method is simple and efficient for screening potential NA inhibitors from stems and leaves of B. cusia.

Construction of hierarchical SiO2 microcapsule towards flame retardation, low toxicity and mechanical enhancement of epoxy resins.

A novel approach for improving the flame retardancy, smoke suppression and mechanical properties of epoxy resins (EPs) has been proposed by incorporating functionalized hollow mesoporous silica microcapsules (SHP) loaded with phosphorous silane flame retardants (SCA) and coated with polydopamine (PDA) and transition metals. The proposed approach involves a multi-level structure that combines several mechanisms to enhance the flame-retardant properties of EP. The physical barrier provided by silica serves to impede heat and mass transfer during combustion, while the catalytic carbonization effect of phosphorus and transition metals promotes the formation of a protective char layer, which acts as a barrier to further flame propagation. Incorporating a low loading amount of 3 wt% SHP into the epoxy matrix resulted in EP/SHP-3 composites with significantly improved flame retardancy, as evidenced by a limiting oxygen index of 31.5% and a V-1 rating, in contrast to the values obtained for unmodified EP, which were 23.8% and no rating, respectively. In addition, cone calorimeter test (CCT) results indicated that the total heat release, peak heat release rate and total smoke production of EP/SHP-3 decreased by 18.2%, 25.2% and 18.4%, respectively. Moreover, the improved interfacial compatibility facilitated by polydopamine assists in the dispersion and compatibility of the SHP with the epoxy matrix, leading to better mechanical properties. Herein, the addition of 1 wt% SHP to EP significantly improved its mechanical performance, with a 16.7% increase in tensile strength and a 19.2% increase in impact strength. The design of the multi-level structural approach has the potential to provide new ideas for the simultaneous improvement of fire safety as well as mechanical properties of polymers.

Application of metabolomics in irritable bowel syndrome in recent 5 years.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders worldwide, characterized by chronic abdominal pain or discomfort and altered bowel habits. To date, the exact pathogenesis of IBS remains elusive, but is clearly multifactorial, including environmental and host factors. However, the management of patients with IBS is challenging and the current diagnostic and therapeutic modalities have unsatisfactory outcomes. Therefore, it is important to develop more effective methods to diagnose IBS early. Metabolomics studies the metabolites most closely related to patient characteristics, which can provide useful clinical biomarkers that can be applied to IBS and may open up new diagnostic approaches. Traditional Chinese medicine (TCM) can play a role in improving symptoms and protecting target organs, but its mechanism needs to be studied in depth. In this review, based on PubMed/MEDLINE and other databases, we searched metabolomics studies related to IBS in the past 5 years, including those related to clinical studies and animal studies, as well as literatures on TCM interventions in IBS, to provide an updated overview of the application of metabolomics to the diagnosis and treatment of IBS and the improvement of IBS by TCM.

Sodium alginate-sodium hyaluronate-hydrolyzed silk for microencapsulation and sustained release of kidney tea saponin: The regulation of human intestinal flora in vitro.

Kidney tea saponin (KTS) exhibits considerable efficacy in lowering glucose levels; however, it does not have widespread applications owing to its low intestinal utilization. Therefore, in the present study, we prepared sodium alginate (SA)/sodium hyaluronate (HA)/hydrolyzed silk (SF) gel beads for the effective encapsulation and targeted intestinal release of KTS. The gel beads exhibited an encapsulation rate of 90.67 % ± 0.27 % and a loading capacity of 3.11 ± 0.21 mg/mL; furthermore, the release rate of KTS was 95.46 % ± 0.02 % after 8 h of simulated digestion. Fourier transform infrared spectroscopy revealed that the hydroxyl in SA/HA/SF-KTS was shifted toward the strong peak; this was related to KTS encapsulation. Furthermore, scanning electron microscopy revealed that the gel bead space network facilitates KTS encapsulation. In addition, the ability of KTS and the gel beads to inhibit α-amylase (IC50 = 0.93 and 1.37 mg/mL, respectively) and α-glucosidase enzymes (IC50 = 1.17 and 0.93 mg/mL, respectively) was investigated. In vitro colonic fermentation experiments revealed that KTS increased the abundance of Firmicutes/Bacteroidetes and butyric acid-producing bacteria. The study showed that the developed gel-loading system plays a vital role in delivering bioactive substances, achieving slow release, and increasing the abundance and diversity of intestinal flora.

Aikeqing, a kidney- and spleen-tonifying compound Chinese medicine granule, prevented ovariectomy-induced bone loss in rats via the suppression of osteoclastogenesis.

Postmenopausal women are prone to osteoporosis due to increased osteoclast activation and bone resorption caused by oestrogen deficiency. In Traditional Chinese Medicine theory, medicines with spleen- and kidney-nourishing effects are commonly used in postmenopausal osteoporosis (PMOP) treatment. Aikeqing (AKQ) is a compound Chinese medicinal granule with spleen- and kidney-nourishing effects. Herein, we investigate the in vitro and in vivo anti-osteoporotic effects of AKQ, its underlying mechanisms and pharmacodynamic basis. In vitro antiosteoporotic effects of AKQ were assessed by its ability to promote osteoblastogenesis in MC3T3-E1 and/or inhibit RANKL-induced osteoclastogenesis in murine bone marrow monocytes (BMMs). The protective effect of AKQ on bone loss induced by oestrogen deficiency was evaluated in ovariectomized rats. The underlying mechanisms were studied in BMMs by detecting the effects of AKQ on the RANKL-induced expression of genes and proteins involved in the regulation of osteoclastogenesis. The main chemical constituents of AKQ in the granule were analyzed by UPLC-QTOF-MS. Our findings show that AKQ did not affect osteoblastogenesis, but it inhibited RANKL-induced osteoclastogenesis. In the ovariectomized rats, oral administration of AKQ (4 g/kg/d) for 90 d effectively prevented oestrogen deficiency-induced bone loss. Mechanistic studies in BMMs revealed that AKQ inhibited RNAKL-induced activation of NF-κB (p65) and MAPKs (p38 and JNK) via blocking the RANK-TRAF6 interaction, subsequently suppressing the translocation and expression of NFATc1 and c-Fos. UPLC-QTOF-MS analysis quantified the 123 main components of AKQ. Taken together, AKQ was demonstrated for the first time as a novel alternative therapy for osteoclast-associated bone diseases.

Rapid identification of chemical components in Xuelian granule by UHPLC-Q-orbitrap-HRMS based on enzyme activity in vitro.

BACKGROUND: Xuelian granule (XL), a traditional Chinese medicine (TCM) formula, has been used for the treatment of diabetic nephropathy for a long time as a hospital preparation. Because the active ingredients in the XL that can help to treat diabetic nephropathy are still unclear, which limits the interpretation for its pharmacological mechanism, further development and subsequent study on the material basis of its efficacy. METHODS: In this study, a screening method based on inhibition activity against aldose reductase (AR) was employed for activity-directed chemical analysis of XL using ultra-high performance liquid chromatography combined with quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-orbitrap-HRMS) technique. RESULTS: A total of 178 compounds, including 46 terpenes, 47 organic acids, 25 flavonoids, 29 phenylethanoid glycosides, and 31 other types, were tentatively identified from XL which might responsible for its AR inhibition activity. CONCLUSION: This is the first study for a systematic, rapid, and accurate qualitative analysis of XL. This research provides a scientific and experimental basis for further researches on pharmacodynamics material basis and quality control of XL.

Unveiling differential mechanisms of chuanxiong cortex and pith in the treatment of coronary heart disease using SPME-GC×GC-MS and network pharmacology.

Ligusticum chuanxiong Hort (LCH) is a well-known traditional Chinese medicinal herb for treating coronary heart disease (CHD). This study investigated the differential preventive mechanisms of Rhizome Cortex (RC) and Rhizome Pith (RP) of LCH. Solid-phase microextraction combined with comprehensive two-dimensional gas chromatography-tandem mass spectrometry analysis identified 32 differential components, and network pharmacology revealed 11 active ingredients and 191 gene targets in RC, along with 12 active ingredients and 318 gene targets in RP. Primary active ingredients in RC were carotol, epicubenol, fenipentol, and methylisoeugenol acetate, while 3-undecanone, (E)- 5-decen-1-ol acetate, linalyl acetate, and (E)- 2-Methoxy-4-(prop-1-enyl) phenol were dominant in RP. KEGG mapping analysis associated 27 pathways with RC targets and 116 pathways with RP targets. Molecular docking confirmed the efficient activation of corresponding targets by these active ingredients. This study provides valuable insights into the preventive and therapeutic effects of RC and RP in CHD.

Exploring the mechanism of Jianpi Huatan recipe in protecting hepatocellular carcinoma based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Huatan Recipe (JPHTR) is an effective prescription for delaying progression of hepatocellular carcinoma (HCC) provided by Longhua Hospital affiliated to Shanghai University of traditional Chinese Medicine, and it is consisted of nine traditional Chinese drugs, but the protective mechanism of JPHTR against HCC progression is unclear. AIM OF THE STUDY: To study the mechanism of JPHTR preventing the progression of HCC based on the network pharmacology. MATERIALS AND METHODS: The chemical component and potential gene targets of JPHTR and the important gene targets of HCC were obtained by retrieving traditional Chinese medicine network pharmacology analysis system (TCMNPAS) database. The data obtained from the database are used to construct the drugs-chemical component-targets network and protein-protein interaction network by using Cytoscape software and STRING database. The potential targets of JPHTR and HCC targets were imported into TCMNPAS-related modules in order to obtain the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Finally, we used HCC rat model to verify the vital signaling pathways predicted by network pharmacology. RESULTS: A total of 197 potential compounds and 721 potential targets of JPHTR and 611 important gene targets of HCC were obtained. Through the experiment in vivo, it was found that JPHTR can reduce the serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, reduce the lipid droplets and inflammatory injury of liver tissue, and reduce the mRNA expression of Interleukin-6 (Il-6), Janus tyrosine Kinase2 (Jak2) and Forkhead box O3 (Foxo3) in FOXO pathway in the liver, thus delaying the development of HCC. CONCLUSION: Through network pharmacology and rat experiments, it is preliminarily confirmed that JPHTR may delay the progression of HCC by regulating the expression of Il-6/Jak2/Foxo3 in FOXO signal pathway, which is expected to be a new therapeutic target for the protection of HCC.

[Effects of electroacupuncture on neurological function and expressions of p-JNK and Beclin-1 in traumatic brain injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on neurological function, the expressions of phosphorylated c-Jun amino terminal kinase (p-JNK) and Beclin-1 in rats with traumatic brain injury (TBI), so as to explore the underlying mechanism of EA in the treatment of TBI. METHODS: A total of 64 SD rats were randomly divided into blank, sham, modeling groups, with 8 rats in the blank group and the sham group and 48 rats in the modeling group. The modified Feeney free-fall impact method was used to establish the TBI rat model. After modeling, rats of the modeling group were randomly divided into model and EA groups, which were further divided into 3 d, 7 d and 14 d subgroups with 8 rats in each group. Rats in the EA group were treated with acupuncture at "Baihui" (GV20, retained for 15 min), "Shuigou" (GV26, stabbed for 20 s), "Neiguan" (PC6) and "Zusanli" (ST36) of the right side. EA (2 Hz, 1 mA) was applied to PC6 and ST36 for 15 min. The above treatments were performed once a day, and different subgroups were continuously stimulated for 3, 7 and 14 days, respectively. The neurological impairment was evaluated by modified neurological severity score(mNSS). The pathological morphological changes and the protein expressions of p-JNK and Beclin-1 in the injured area of the brain were detected by Nissl staining and immunohistochemistry, separately. RESULTS: After modeling, the mNSS and the protein expressions of p-JNK and Beclin-1 were increased (P< 0.05) on day 3, 7 and 14 in the model group relative to the sham group. The Nissl bodies were reduced or even dissolved and neurons were seriously damaged in the model group on the 3rd day, which were mildly repaired on day 7 and 14. Following acupuncture interventions, compared with the model group, the mNSS on day 7 and 14 and the protein expressions of p-JNK and Beclin-1 on day 3, 7 and 14 were decreased (P< 0.05)in the EA group. The status of Nissl bodies and neurons in the EA group was better at all time points than that in the model group. There were no significant differences in the above indicators between the blank group and the sham group. CONCLUSION: EA can significantly improve the neurological function of TBI model rats, which may be related to its effects in down-regulating the protein expressions of p-JNK and Beclin-1 in the injured area of the brain.

Preventive effect and mechanism of Tibetan tea extract on thrombosis in arachidonic acid-induced zebrafish determined via RNA-seq transcriptome profiles.

Thrombosis is a key pathological event in cardiovascular diseases and is also the most important targeting process for their clinical management. In this study, arachidonic acid (AA) was used to induce thrombus formation in zebrafish larvae. Blood flow, red blood cell (RBCs) aggregation and cellular oxidative stress were measured to evaluate the antithrombotic effect of Tibetan tea (TT). Meanwhile, the potential molecular mechanism was further explored by transcriptome sequencing (RNA-seq). The results indicated that TT could significantly restore heart RBCs intensity of thrombotic zebrafish, whilst decreasing RBCs accumulation in the caudal vein. The transcriptome analysis revealed that the preventive effect of TT on thrombosis could be mostly attributed to changes in lipid metabolism related signaling pathways, such as fatty acid metabolism, glycerollipid metabolism, ECM-receptor interaction and steroid biosynthesis signaling pathway. This study demonstrated that Tibetan tea could alleviate thrombosis by reducing oxidative stress levels and regulating lipid metabolism.