Berberine alleviates contrast-induced nephropathy by activating Akt/Foxo3a/Nrf2 signalling pathway.

Contrast-induced nephropathy (CIN) is a condition that causes kidney damage in patients receiving angiography with iodine-based contrast agents. This study investigated the potential protective effects of berberine (BBR) against CIN and its underlying mechanisms. The researchers conducted both in vivo and in vitro experiments to explore BBR's renal protective effects. In the in vivo experiments, SD rats were used to create a CIN model, and different groups were established. The results showed that CIN model group exhibited impaired renal function, severe damage to renal tubular cells and increased apoptosis and ferroptosis. However, BBR treatment group demonstrated improved renal function, decreased apoptosis and ferroptosis. Similar results were observed in the in vitro experiments using HK-2 cells. BBR reduced ioversol-induced apoptosis and ferroptosis, and exerted its protective effects through Akt/Foxo3a/Nrf2 signalling pathway. BBR administration increased the expression of Foxo3a and Nrf2 while decreasing the levels of p-Akt and p-Foxo3a. In conclusion, this study revealed that BBR effectively inhibited ioversol-induced apoptosis and ferroptosis in vivo and in vitro. The protective effects of BBR were mediated through the modulation of Akt/Foxo3a/Nrf2 signalling pathway, leading to the alleviation of CIN. These findings suggest that BBR may have therapeutic potential for protecting against CIN in patients undergoing angiography with iodine-based contrast agents.

The formation of volatiles in fruit wine process and its impact on wine quality.

Fruit wine is one of the oldest fermented beverages made from non-grape fruits. Owing to the differences in fruit varieties, growing regions, climates, and harvesting seasons, the nutritional compositions of fruits (sugars, organic acids, etc.) are different. Therefore, the fermentation process and microorganisms involved are varied for a particular fruit selected for wine production, resulting in differences in volatile compound formation, which ultimately determine the quality of fruit wine. This article reviews the effects of various factors involved in fruit wine making, especially the particular modifications differing from the grape winemaking process and the selected strains suitable for the specific fruit wine fermentation, on the formation of volatile compounds, flavor and aroma profiles, and quality characteristics of the wine thus produced. KEY POINTS: • The volatile profile and fruit wine quality are affected by enological parameters. • The composition and content of nutrients in fruit must impact volatile profiles. • Yeast and LAB are the key determining factors of the volatile profiles of fruit wines.

Serum Dynamin-Related Protein 1 Concentrations Discriminate Phenotypes and Predict Prognosis of Heart Failure.

Background: Dynamin-related protein 1 (Drp1) has been demonstrated as a crucial role in mediating the programed cell death and cardiac metabolism through its regulatory of mitophagy in animal studies. However, the clinical values of Drp1 for human cardiac disease remain unknown. This study is aimed to evaluate the diagnostic and prognostic values of serum Drp1 in these patients with heart failure (HF). Methods: The enzyme linked immunosorbent assay (ELISA) was used for measuring serum Drp1 concentrations in 85 cases of HF with preserved ejection fraction (HFpEF) and 86 cases of HF with reduced ejection fraction (HFrEF). The diagnostic value of Drp1 was evaluated using the receiver operating characteristic (ROC) analysis. The composite endpoint was consisted of cardiac death and rehospitalization for HF, and the association between Drp1 and clinical outcomes were further determined. Results: Serum Drp1 concentrations were much higher in HFpEF than that in HFrEF (4.2 ± 3.7 ng/mL vs. 2.6 ± 2.2 ng/mL, p = 0.001) and the ROC analysis demonstrated it as a potential diagnostic biomarker for distinction of the HF phenotypes, with an optimal cutoff point of 3.5 ng/mL (area under the curve (AUC) = 0.659, sensitivity: 45.9%, specificity: 83.7%). Kaplan-Meier survival analysis indicated that a low serum concentration of Drp1 (cut-off value = 2.5 ng/mL, AUC = 0.738) was in relation to poor prognosis of HF. Moreover, binary logistic regression analysis identified the low serum concentration of Drp1 as an independent risk predictor for rehospitalization (odds ratio (OR) = 6.574, p = 0.001) and a composite endpoint (OR = 5.927, p = 0.001). Conclusions: Our findings suggested that low serum concentrations of Drp1 might serve as a predicting biomarker for distinction of HF phenotypes and overall prognosis of HF.

Comparison of microbial communities and volatile profiles of wines made from mulberry and grape.

In this study, three kinds of wines separately made from mulberry (MW), grape (GW), or mulberry/grape (MGW) were developed and their enological parameters, sensory scores, volatile components, and microbiota were investigated and compared. Contrary to the order of residual sugar and acidity of the three kinds of wines, the order of alcohol content from high to low is GW, MW, and MGW. A total of 60 volatile components (VCs), including esters (17), alcohols (12), acids (6), aldehydes (7), ketones (3), alkenes (3), amines (3), alkanes (4), pyrazines (2), benzene (1), sulfide (1), and thiazole (1), were identified by gas chromatography-ion mobility spectrometer (GC-IMS). The fingerprint of VCs and principal component analysis revealed that the volatile profiles of MGW and GW were more similar in comparison to that of MW and were significantly correlated with the mass ratio of mulberry to grape. Lactobacillus, Weissella, Pantoea, Leuconostoc, Lactococcus, Paenibacillus, Pediococcus, and Saccharomyces were identified as the main microflora at the genus level shared by the MW, MGW, and GW, suggesting that the heterolactic bacteria may contribute more to the high content of volatile acids in MW and MGW. The heatmap of core microbiota and main VCs of MW, MGW, and GW suggested the complicated and significant correlation between them. The above data implied that the volatile profiles were more closely related to the raw materials of winemaking and markedly affected by the fermentation microorganisms. This study provides references for evaluation and characterization of MGW and MW and improvement of MGW and MW winemaking process. KEY POINTS: • Fruit wine enological parameters, volatile profile, and microbiota were compared. • Sixty volatile compounds were identified by GC-IMS in three types of fruit wines. • Winemaking materials and microbiota affect volatile profiles of the fruit wines.

Vaspin Ameliorates Cardiac Remodeling by Suppressing Phosphoinositide 3-Kinase/Protein Kinase B Pathway to Improve Oxidative Stress in Heart Failure Rats.

ABSTRACT: This study aimed to explore whether vaspin could alleviate cardiac remodeling through attenuating oxidative stress in heart failure rats and to determine the associated signaling pathway. Cardiac remodeling was induced by myocardial infarction, transverse aortic constriction, or angiotensin (Ang) II infusion in vivo, and the neonatal rat cardiomyocytes (NRCMs) and neonatal rat cardiac fibroblasts (NRCFs) were treated with Ang II. Vaspin treatment alleviated fibrosis in myocardial infarction, transverse aortic constriction, and Ang II-treated rats. The Ang II-induced increases of atrial natriuretic peptide and brain natriuretic peptide in NRCMs and Ang II-induced increases of collagen I and collagen III in NRCFs were reduced after vaspin treatment. Vaspin administration inhibited the Ang II-induced increases of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, superoxide anions, malondialdehyde, and NADPH oxidases activity in NRCMs and NRCFs. The overexpression of PI3K, Akt, or NADPH oxidases 1 reversed the attenuating effects of vaspin on Ang II-induced elevation of atrial natriuretic peptide and brain natriuretic peptide in NRCMs, as well as Ang II-induced increases of collagen I and collagen III in NRCFs. The administration of wortmannin (PI3K inhibitor) or MK2206 (Akt inhibitor) inhibited the oxidative stress induced by Ang II in NRCMs and NRCFs. The above results suggest that vaspin can alleviate cardiac dysfunction and remodeling in heart failure rats. Vaspin attenuates Ang II-induced hypertrophy of NRCMs and fibrosis of NRCFs through suppressing PI3K/Akt pathway to alleviate oxidative stress.

Hypoglycemic effects of bioactive ingredients from medicine food homology and medicinal health food species used in China.

Diabetes mellitus (DM) is a chronic progressive systemic disease caused by a metabolic disorder. In recent years, a large number of studies have shown that certain traditional Chinese medicines and their bioactive ingredients have obvious hypoglycemic effects. This literature review focuses on medicine food homology (MFH) and medicinal health food (MHF) species used in China with a hypoglycemic function and emphasizes the bioactive ingredients and their pharmacological effects. The bioactive ingredients of MFH and MHF have been divided into six categories: saponins, flavonoids, terpenoids, alkaloids, polysaccharides, and others; and their sources, models, efficacy, and mechanisms of action have been described. It is noteworthy that the mechanisms of the bioactive ingredients of MFH and MHF with hypoglycemic effects have been summarized as follows: a) insulin-mimetic effects and restoration of the damaged pancreas; b) effect on glucose metabolism; c) increased insulin sensitivity and improved insulin resistance; and d) regulation of intestinal flora. We conclude that this review provides useful data and information to support the further investigation and application of MFH and MHF to treat DM.

Advanced Research on the Antioxidant Activity and Mechanism of Polyphenols from Hippophae Species-A Review.

Oxidation is a normal consequence of metabolism in biological organisms. The result is the formation of detrimental reactive oxygen species (ROS) and reactive nitrogen species (RNS). A large number of studies have shown that polyphenolic compounds have good antioxidant properties. Hippophae species plants have high polyphenolic content and are widely used in food, medicinal, or the cosmetic field. The main polyphenols in Hippophae species are flavonoids, phenolic acids and tannins, which have multiple effects. However, there is a limited number of studies on polyphenols in Hippophae species plants. This review systematically summarizes the polyphenols compounds and antioxidant activity of Hippophae species plants, and it is noteworthy that the main mechanisms of the polyphenols of Hippophae with antioxidant activity have been summarized as follows: regulating enzyme activity, affect the antioxidant reaction of cells, and others. This review provides useful information for the further study and application of Hippophae species polyphenols and their antioxidant activity.

Cache-Aided General Linear Function Retrieval.

Coded Caching, proposed by Maddah-Ali and Niesen (MAN), has the potential to reduce network traffic by pre-storing content in the users' local memories when the network is underutilized and transmitting coded multicast messages that simultaneously benefit many users at once during peak-hour times. This paper considers the linear function retrieval version of the original coded caching setting, where users are interested in retrieving a number of linear combinations of the data points stored at the server, as opposed to a single file. This extends the scope of the authors' past work that only considered the class of linear functions that operate element-wise over the files. On observing that the existing cache-aided scalar linear function retrieval scheme does not work in the proposed setting, this paper designs a novel coded caching scheme that outperforms uncoded caching schemes that either use unicast transmissions or let each user recover all files in the library.

[Analysis on formula of Mongolian medicine for prevention of COVID-19].

The epidemic situation of coronavirus disease 2019(COVID-19) is developing rapidly in the world, and the influence is serious. In this study, the prescription of Mongolian medicine to prevent new type of COVID-19 was investigated. Based on the second edition and the third edition of COVID-19 Mongolian Medicine Prevention and Treatment Guidance Program issued by the Inner Mongolia Autonomous Region Health Commission, using Excel 2007, SPSS Modeler 18, SPSS Statistics 25, Cytoscape 3.7.1 statistical software as a tool, the association rules analysis and cluster analysis of Mongolian medicine included in the standard were carried out. Among the 45 prophylactic prescriptions included in the standard, a total of 34 high-frequency drugs using frequency ≥5 were used, of which Carthami Flos(21 times, 4.46%), Chebulae Fructus(20 times, 4.26%), Moschus(13 times, 2.77%), Myristicae Semen(12 times, 2.55%), Santali Albi Lignum(12 times, 2.55%), and Bovis Calculus(12 times, 2.55%) were the most common. The main drugs for the prevention of COVID-19 were Liang(13 times, 38.23%), Wen(9 times, 26.47%), the flavor was Ku(20 times, 34.48%), Xin(13 times, 22.41%), Gan(11 times, 18.97%), the most used drugs treating hot evil(99 times, 32.46%), treatment of "Heyi" drugs(51 times, 16.72%), treatment of "Badagan" drugs(40 times, 13.11%), treatment of "sticky" drugs(37 times, 12.13%), and a cough, eliminating phlegm and antiasthmatic(31 times, 10.16%), the association rule analysis found that the highest association intensity of the drug pair combination of 11. Clustering analysis using the cluster analysis of inter-group join method found a total of 8 categories. In this study, 45 prescriptions of Mongolian medicine for the prevention of COVID-19 were collec-ted and further analyzed, hoping to provide new ideas for clinical diagnosis and treatment.

Efficient Algorithms for Coded Multicasting in Heterogeneous Caching Networks.

Coded multicasting has been shown to be a promising approach to significantly improve the performance of content delivery networks with multiple caches downstream of a common multicast link. However, the schemes that have been shown to achieve order-optimal performance require content items to be partitioned into several packets that grows exponentially with the number of caches, leading to codes of exponential complexity that jeopardize their promising performance benefits. In this paper, we address this crucial performance-complexity tradeoff in a heterogeneous caching network setting, where edge caches with possibly different storage capacity collect multiple content requests that may follow distinct demand distributions. We extend the asymptotic (in the number of packets per file) analysis of shared link caching networks to heterogeneous network settings, and present novel coded multicast schemes, based on local graph coloring, that exhibit polynomial-time complexity in all the system parameters, while preserving the asymptotically proven multiplicative caching gain even for finite file packetization. We further demonstrate that the packetization order (the number of packets each file is split into) can be traded-off with the number of requests collected by each cache, while preserving the same multiplicative caching gain. Simulation results confirm the superiority of the proposed schemes and illustrate the interesting request aggregation vs. packetization order tradeoff within several practical settings. Our results provide a compelling step towards the practical achievability of the promising multiplicative caching gain in next generation access networks.

Prognostic significance of serum dynamin­related protein 1 in patients with heart failure: Findings from a prospective observational study.

Mitochondrial dysfunction plays a critical role in the development and exacerbation of heart failure (HF). Dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fission, influences cardiac energy metabolism. The present study investigated the relationship between serum Drp1 levels and the prognosis of patients with HF across a broad spectrum. Serum Drp1 concentrations were measured using ELISA. The primary outcome was the risk of composite major adverse cardiac events (MACEs), which included instances of cardiac death and HF-related readmissions. To assess the prognostic significance of serum Drp1, a receiver operating characteristic curve was constructed to predict MACE-free survival. Additionally, an optimal threshold value for Drp1 was determined and was used to stratify patients into different risk categories. A total of 256 HF patients were finally included and categorized into two groups based on their serum Drp1 levels, labeled as the low (Drp1 ≤2.66 ng/ml, n=101) and high group (Drp1 >2.66 ng/ml, n=155). Patients with low serum Drp1 concentrations showed impaired heart structure and function, as assessed by echocardiography. The 6-month follow-up results indicated that patients with reduced Drp1 concentrations faced a substantially increased risk of MACEs (21.1% vs. 2.8%; P<0.001). The present study revealed that diminished serum Drp1 concentrations could potentially act as a predictive marker for the prognosis of HF in a broad patient population.

The Molecular Mechanism of Radix Paeoniae Rubra.-Cortex Moutan. Herb Pair in the Treatment of Atherosclerosis: A Work Based on Network Pharmacology and In Vitro Experiments.

Radix Paeoniae Rubra. (Chishao, RPR) and Cortex Moutan. (Mudanpi, CM) are a pair of traditional Chinese medicines that play an important role in the treatment of atherosclerosis (AS). The main objective of this study was to identify potential synergetic function and underlying mechanisms of RPR-CM in the treatment of AS. The main active ingredients, targets of RPR-CM and AS-related genes were obtained from public databases. A Venn diagram was utilized to screen the common targets of RPR-CM in treating AS. The protein-protein interaction network was established based on STRING database. Biological functions and pathways of potential targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Cytoscape was used to construct the drug-compound-target-signal pathway network. Molecular docking was performed to verify the binding ability of the bioactive ingredients and the target proteins. The endothelial inflammation model was constructed with human umbilical vein endothelial cells stimulated with ox-LDL, and the function of RPR-CM in treating AS was verified by CCK-8 assay, enzyme-linked immunosorbent assay, and qPCR. In this study, 12 active components and 401 potential target genes of RPR-CM were identified, among which quercetin, kaempferol and baicalein were considered to be the main active components. A total of 1903 AS-related genes were identified through public databases and four GEO datasets (GSE57691, GSE72633, GSE6088 and GSE199819). There are 113 common target genes of RPR-CM in treating AS. PPI network analysis identified 17 genes in cluster 1 as the core targets. Bioinformatics analysis showed that RPR-CM in AS treatment was associated with multiple downstream biological processes and signal pathways. PTGS2, JUN, CASP3, TNF, IL1B, IL6, FOS, STAT1 were identified as the core targets of RPR-CM, and molecular docking showed that the main bioactive components of RPR-CM had good binding ability with the core targets. RPR-CM extract significantly inhibited the levels of inflammatory factors TNF-α, IL-6, IL-1ß, MCP-1, VCAM-1 and ICAM-1 in HUVECs, and inhibited endothelial inflammation. This study revealed the active ingredients of RPR-CM, and identified the key downstream targets and signaling pathways in the treatment of AS, providing theoretical basis for the application of RPR-CM in prevention and treatment of AS.

Applied Analytical Methods for Detecting Heavy Metals in Medicinal Plants.

For thousands of years, medicinal plants (MPs) have been one of the main sources of drugs worldwide. However, recently, heavy metal pollution has seriously affected the quality and safety of MPs. Consuming MPs polluted by heavy metals such as Pb, Hg, and Cu significantly threaten the health of consumers. To manage this situation, the levels of heavy metals in MPs must be controlled. In recent years, this field has attracted significant attention, but few researchers have systematically summarized various analytical methods. Therefore, it is necessary to investigate methods that can accurately and effectively detect the amount of heavy metals in MPs. Herein, some important analytical methods used to detect heavy metals in MPs and their applications have been introduced and summarized in detail. These include atomic absorption spectrometry, atomic fluorescence spectrometry, inductively coupled plasma mass spectrometry, inductively coupled plasma atomic emission spectrometry, X-ray fluorescence spectrometry, neutron activation analysis, and anodic stripping voltammetry. The characteristics of these methods were subsequently compared and analyzed. In addition, high-performance liquid chromatography, ultraviolet spectrophotometry, and disposable electrochemical sensors have also been used for heavy metal detection in MPs. To elucidate the systematic and comprehensive information, these methods have also been briefly introduced in this review.

Osteocrin alleviates cardiac hypertrophy via attenuating oxidative stress.

Osteocrin (OSTN) is a secretory peptide mainly derived from the skeletal muscles and bones. The present study aims to explore the role of OSTN in cardiac hypertrophy and its underlying mechanism. Experiments were carried out in mice receiving angiotensin (Ang) II to induce cardiac hypertrophy, and in neonatal rat cardiomyocytes (NRCMs) or human cardiac AC16 cells with Ang II-induced cardiomyocytes hypertrophy. The expression of OSTN was lower in Ang II-treated mouse heart of mice, NRCMs and AC16 cells. OSTN overexpression attenuated the hypertrophy and fibrosis of heart in mice induced by Ang II. Overexpression of OSTN inhibited hypertrophy of NRCMs and AC16 cells induced by Ang II. Increased oxidative stress was observed in the heart of mice, NRCMs and AC16 cells treated with Ang II. Overexpression of NADPH oxidase 1 (Nox1) reversed the attenuating effects of OSTN on the Ang II-induced hypertrophic cardiomyocytes. Treatment with NADPH oxidase inhibitor apocynin (APO) suppressed the hypertrophy of NRCMs and AC16 cells induced by Ang II. The above findings suggested OSTN upregulation could attenuate cardiac hypertrophy and fibrosis. The upregulation of OSTN could alleviate hypertrophy of cardiomyocytes via suppressing oxidative stress.

Appropriate Dose of Dapagliflozin Improves Cardiac Outcomes by Normalizing Mitochondrial Fission and Reducing Cardiomyocyte Apoptosis After Acute Myocardial Infarction.

Objective: Dapagliflozin (DAPA) has been reported to have significant cardiac protective effects on heart failure (HF). However, the dose and time, as well as the underlying mechanisms, for DAPA treatment in acute myocardial infarction (AMI) remain controversial. The aim of this study aimed to assess the efficacy and safety of DAPA treatment along with an increased concentration gradient for AMI and explore the potential mechanisms. Methods: Non-diabetic Sprague-Dawley rats were used for establishing AMI models and then were treated with three different concentrations of DAPA [0.5 mg/kg, 1 mg/kg and 1.5 mg/kg, described as AMI+DAPA Low, AMI+DAPA Medium (Med) and AMI+DAPA High, respectively] for six weeks from the onsetting of AMI. Echocardiography, histological staining and Western blot were performed to assess the relevant cardiac protective effects. Mitochondrial biogenesis and myocardial apoptosis were evaluated via the electron microscopy and TUNEL assay, respectively, as well as the Immunoblotting. In vitro, H9c2 cells were subjected to hypoxic treatment to assess the efficacy of DAPA on mitochondrial biogenesis and apoptosis. Results: The medium dose of DAPA treatment could significantly reduce the infarct size (P < 0.01) and the echocardiography results showed that the MI-induced damage in cardiac function got partly repaired, showing no significant difference in left ventricle ejection fraction (LVEF) versus the Sham group (Sham vs AMI+DAPA Med group: 70.47% vs 61.73%). The Western blotting results confirmed the relevant benefits and the underlying mechanisms might be through the activation of PGAM5/Drp1 signaling pathway to normalize the mitochondrial fission and reduce cardiomyocyte apoptosis. Moreover, a medium dose of DAPA treatment could avoid increased damage to the bladder endothelium following higher treatment doses. Conclusion: Appropriate dose of DAPA treatment could improve the cardiac remodeling and reduce the cardiomyocyte apoptosis after AMI, without increased damage to bladder endothelium, which might be more preferred for MI patients without diabetes.

Downregulation of amphiregulin improves cardiac hypertrophy via attenuating oxidative stress and apoptosis.

Amphiregulin (AREG) is a ligand of epidermal growth factor receptor and participates in the fibrosis of multiple organs. However, whether AREG can regulate hypertrophic cardiomyopathy is not well known. This research aims to explore the effect of AREG on cardiac hypertrophy, and whether the oxidative stress and apoptosis was involved in the influence of AREG on cardiac hypertrophy. Angiotensin (Ang) II induced cardiac hypertrophy in mice and neonatal rat cardiomyocytes (NRCMs) or HL-1 cells in vitro. AREG expressions raised in the heart of mice. After AREG downregulation, the increases of Ang II induced cardiac weight and cardiomyocytes area were inhibited. Down-regulation of AREG could inhibit Ang II induced the increases of atrial natriuretic peptide, brain natriuretic peptide, beta-myosin heavy chain in the heart of mice, and NRCMs and HL-1 cells. The enhancement of oxidative stress in mice heart with Ang II treatment was alleviated by AREG knockdown. The raises of Ang II induced Bax and cleaved caspase3 in mice heart were inhibited by AREG downregulation. AREG downregulation reduced myocardial hypertrophy via inhibition of oxidative and apoptosis. AREG may be a target for future cardiac hypertrophy treatment.

Tumstatin (69-88) alleviates heart failure via attenuating oxidative stress in rats with myocardial infarction.

Background: This study aimed to elucidate the effects of tumstatin (69-88) on heart failure and the underlying mechanism. Materials and methods: Myocardial infarction (MI) was induced by ligating the left coronary artery in rats to trigger heart failure. Results: Tumstatin (69-88) can reduce cardiac insufficiency in rats with heart failure. The increased cardiac fibrosis in MI rat was attenuated by tumstatin (69-88). Increase of cardiac atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in rats with myocardial infarction, and Ang II-treated NRCMs or H9C2 cells was inhibited by tumstatin (69-88). In the heart of MI rats, and Ang II-treated NRCMs or H9C2 cells, the superoxide anions and NADPH oxidase (Nox) activity rose and the superoxide dismutase (SOD) activity was reduced, which was inhibited by tumstatin (69-88). Diethyldithiocarbamate, an SOD inhibitor, increased the ANP and BNP in NRCMs or H9C2 cells. Tumstatin (69-88) inhibited the Ang II-induced raises of ANP and BNP in NRCMs or H9C2 cells, which was reversed by DETC. Conclusions: These results indicate that tumstatin (69-88) alleviates cardiac dysfunction of heart failure. Tumstatin (69-88) improves the hypertrophy of cardiomyocytes via attenuation of oxidative stress. Tumstatin (69-88) may be a potential drug for heart failure in the future.

Effects of Koumiss on Intestinal Immune Modulation in Immunosuppressed Rats.

Koumiss is a traditional fermented dairy product with health and medicinal benefits. It is very popular in the Inner Mongolia Autonomous Region of China. The results of relevant studies have shown that koumiss can regulate the gastrointestinal environment, improve the absorption of nutrients, improve the body's intolerance to lactose, enhance the body's immunity, prevent scurvy and atherosclerosis, and aid in the treatment of tuberculosis. However, there are no systematic reports on the effects of koumiss on immunity. In this study, we aimed to decipher the effects of koumiss on intestinal immune modulation. We used liquid chromatography-tandem mass spectrometry (LC-MS) analysis to determine the composition of Koumiss. Using Compound Discoverer software, we compared the mass spectrometry data with the compound information in the online databases ChemSpider and mzCloud to intelligently identify the main chemical components of koumiss. Additionally, we used Mass Frontier small molecule fragmentation libraryTM to determine the structure of fragment ions. A total of 21 components were identified, which clarified the chemical basis of koumiss. These 21 compounds were then used to perform molecular docking with immune-related targets, such as TNF, IL2, IL10, etc. The results indicated good docking activity between most of the compounds and the targets. Then, an immunosuppressive rat model was used to determine the therapeutic effect of koumiss. The results of this study showed that koumiss could, to a certain extent, correct the atrophy of the thymus and spleen in immunosuppressed model rats. The number of leukocytes, lymphocytes, and the CD4+/CD8+ ratio of peripheral blood lymphocytes was also increased. In addition, it could effectively improve the structure of the small intestinal mucosa, which shows that koumiss has a positive effect on the intestinal immune function of immunosuppressed rats. These findings provide an experimental basis for the development and utilization of koumiss as a therapeutic product.

Integrated Phytochemical Analysis Based on UPLC-MS/MS and Network Pharmacology Approaches to Explore the Effect of Odontites vulgaris Moench on Rheumatoid Arthritis.

Odontites vulgaris Moench has the effect of clearing away heat, detoxification, dispelling wind, and clearing dampness. In this study, the potential anti-inflammatory compounds of O. vulgaris were investigated using ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) combined with the network pharmacology approach and further confirmed on an LPS-activated RAW 264.7 macrophage model. Monomer compounds were prepared from the active fraction using modern advanced separation and purification methods. UPLC-Q-Exactive HRMS was used to identify the chemical compounds in the active fractions of O. vulgaris. D-mannitol, geniposidic acid, salidroside, shanzhiside methyl ester, eleutheroside B, geniposide, 7,8-dihydroxycoumarin, gardoside methyl ester, arenarioside, vanillic acid, p-hydroxy-cinnamic acid, melampyroside, syringaresinol, tricin, and diosmetin were isolated from O. vulgaris for the first time. A compound database of O. vulgaris was established based on the existing literature to predict the mechanism of O. vulgaris in the treatment of rheumatoid arthritis. The results suggest that the PI3K-Akt pathway mediates O. vulgaris and deserves more attention in the treatment of RA. Finally, the anti-rheumatoid arthritis effects of the four target compounds were validated with the decreased levels of NO, TNF-α, IL-6 and IL-1ß in RAW 264.7 macrophage cells treated with LPS. The present study explored the potential targets and signaling pathways of O. vulgaris in the treatment of RA, which may help to illustrate the mechanisms involved in the action of O. vulgaris and may provide a better understanding of the relationship between O. vulgaris and RA. This study provides novel insights into the development of new drugs and utilization of Mongolian traditional Chinese medicine resources.

Ethnopharmacology, Phytochemistry, Pharmacology, Toxicology and Clinical Applications of Radix Astragali.

Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.