Use of bailing capsules (cordyceps sinensis) in the treatment of chronic kidney disease: a meta-analysis and network pharmacology.

The Bailing Capsule is a commonly used traditional Chinese medicine for the treatment of chronic kidney disease (CKD). However, its therapeutic effects and pharmacological mechanisms have not been fully explored. In this study, we integrated meta-analysis and network pharmacology to provide scientific evidence for the efficacy and pharmacological mechanism of Bailing Capsule in treating CKD. We conducted searches for randomized controlled studies matching the topic in PubMed, the Cochrane Library, Embase, Web of Science, and the Wanfang Database, and screened them according to predefined inclusion and exclusion criteria. Dates from the included studies were extracted for meta-analysis, including renal function indicators, such as 24-h urinary protein (24UP), blood urea nitrogen (BUN), and serum creatinine (Scr), as well as inflammatory indicators like high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Network pharmacology was employed to extract biological information, including active drug ingredients and potential targets of the drugs and diseases, for network construction and gene enrichment. Our findings indicated that 24UP, BUN, and Scr in the treatment group containing Bailing Capsule were lower than those in the control group. In terms of inflammatory indicators, hs-CRP, IL-6, and TNF-α, the treatment group containing Bailing Capsule also exhibited lower levels than the control group. Based on network pharmacology analysis, we identified 190 common targets of Bailing Capsule and CKD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that the pharmacological mechanism of Bailing Capsule might be related to immune response, inflammatory response, vascular endothelial damage, cell proliferation, and fibrosis. This demonstrates that Bailing Capsule can exert therapeutic effects through multiple targets and pathways, providing a theoretical basis for its use.

Energy preservation for skeletal muscles: Shenqi Fuzheng injection prevents tissue wasting and restores bioenergetic profiles in a mouse model of chemotherapy-induced cachexia.

BACKGROUND: Energy deficiency is the characteristic of chemotherapy-induced cachexia (CIC) which is manifested by muscle wasting. glycolysis, tricarboxylic acid (TCA) cycle, and lipid metabolism are central to muscle bioenergy production, which is vulnerable to chemotherapy during cancer treatment. Recent investigations have spotlighted the potential of Shenqi Fuzheng injection (SQ), a Chinese proprietary medicine comprising Radix Codonopsis and Radix Astragali, in alleviating CIC. However, the specific effects of SQ on muscle energy metabolism remains less explored. PURPOSE AND METHODS: Here, we integrated transcriptomics, spatial metabolomics, gas chromatography-mass spectrometry targeted quantitative analysis, and transmission electron microscopy techniques, combined with Seahorse live-cell metabolic analysis to reveal the changes in genes and pathways related to energy metabolism in the CIC model and SQ's protective effects at molecular and functional levels. RESULTS: Our data showed that chemotherapeutic agents caused glycolysis imbalance, which further leads to metabolic derangements of TCA cycle intermediates. SQ maintained glycolysis balance by facilitating pyruvate fluxing to mitochondria for more efficient bioenergy production, which involved a dual effect on promoting functions of mitochondrial pyruvate dehydrogenase complexes and inhibiting lactate dehydrogenase for lactate production. As a result of the sustained pyruvate level achieved by SQ administration, glycolysis balance was maintained, which further led to the preservation of mitochondrial integrity and function of electron transport chain, thereby, ensuring the normal operation of the TCA cycle and the proper synthesis of adenosine triphosphate (ATP). The above results were further validated using the Seahorse live-cell assay. CONCLUSION: In conclusion, our study highlights SQ as a promising strategy for CIC management, emphasizing its ability to harmonize the homeostasis of the muscle bioenergetic profile. Beyond its therapeutic implications, this study also offers a novel perspective for the development of innovative treatments in the realm of herbal medicine.

Dissecting chemical markers for controlling "Paozhi" method of traditional Chinese medicine with untargeted metabolomics: Vinegar-baked Euphorbia kansui as a case study.

The processing of Traditional Chinese Medicine requires the appropriate parameters, while the specific chemical markers are still absent to obtain the optimized processing. In this study, we used vinegar-baked Euphorbia kansui as a case to dissect the chemical markers for the baking process using untargeted metabolomics. The robust chemical markers were selected based on the three rules, correlation, significant difference, and controllability. All the differential features were categorized based on their mass defects. After the differential analysis, 310 differential compounds were screened out and could be mainly divided into six categories: diacylglycerols and triacylglycerols demonstrated increasing trends with the baking time in the discriminant model, while ingenane-type diterpenes, jatrophane-type diterpenes, fatty acid esters, and fatty acids had decreasing trends. It was unexpected to find that the diterpenes did not correlate with the baking time. Only very few compounds meet the three rules. They were validated with a high-performance liquid chromatography method. Finally, only 13-Hydroxy-9,11-octadecadienoic acid and its isomer 9-Hydroxy-10,12-octadecadienoic acid could be used further to differentiate the commercial vinegar-baked Euphorbia kansui. It would be of interest to evaluate whether these two compounds could be utilized as markers to control more processing methods in future studies.

Determination of the intermediates in glycolysis and tricarboxylic acid cycle with an improved derivatization strategy using gas chromatography-mass spectrometry in complex samples.

Traditional Chinese medicine (TCM) is recognized as a complex matrix, and improved analytical methods are crucial to extract the key indicators and depict the interaction and alteration of the complex matrix. Shenqi Fuzheng Injection (SQ), a water extract of Radix Codonopsis and Radix Astragali, has demonstrated preventative effects on myotube atrophy induced by chemotherapeutic agents. To achieve the improved analytical capability of complex biological samples, we established a highly reproducible, sensitive, specific, and robust gas chromatography-tandem mass spectrometry (GC-MS) method to detect glycolysis and tricarboxylic acid (TCA) cycle intermediates with optimized factors in the extraction and derivatization process. Our method detected fifteen metabolites and covered most intermediate metabolites in glycolysis and TCA cycles, including glucose, glucose-6-phosphate, fructose-6-phosphate, dihydroxyacetone phosphate, 3-diphosphoglycerate, phosphoenolpyruvate, pyruvate, lactate, citrate, cis-aconitate, isocitrate, α-ketoglutarate, succinate, fumarate, and malate. Through methodological verification of the method, it was found that the linear correlation coefficients of each compound in the method were greater than 0.98, all of which had lower limits of quantification, the recovery rate was 84.94-104.45%, and the accuracy was 77.72-104.92%. The intraday precision was 3.72-15.37%, the interday precision was 5.00-18.02%, and the stability was 7.85-15.51%. Therefore, the method has good linearity, accuracy, precision, and stability. The method was further applied to study the attenuating effects of the SQ in a chemotherapeutic agents-induced C2C12 myotube atrophy model to evaluate the changes in the tricarboxylic acid cycle and glycolytic products under the action by the complex systems of TCM and disease model. Our study provided an improved method to explore TCM's pharmacodynamic constituents and action mechanisms.

An improved strategy for identification and annotation of easily in-sourced dissociation diterpene lactones from plant natural products: Taking Andrographis paniculata (Burm. f.) as an example.

RATIONALE: Diterpene lactones (DL) in Andrographis paniculata (AP) are known as "natural antibiotics" for their excellent antibacterial activity. During mass spectrometry (MS) analysis, the hydroxyl groups in the AP DL skeleton are prone to neutral loss of H2 O, producing high in-source fragment peaks and affecting the characterization of these components. METHODS: Mass tags were applied during the MS data acquisition step, and special adduct ion form was used to guide the data processing and characterization steps. Besides, the total number of characterized AP DLs significantly increased when combining the number of neutrally lost H2 O from AP DLs, incorporating information on the diagnostic ions, and adopting molecular networks generated with the Global Natural Products Social Molecular Networking database. RESULTS: Ninety-nine DLs, comprising 6 monohydroxyl groups, 20 dihydroxyl groups, 27 trihydroxy groups, and 46 DLs with more than 3 hydroxyl groups, were characterized from AP. In addition, based on the characteristic fragments in the product ions (C3 H4 , Δm/z = 40.03 Da), it could be assumed that 90 DLs had the C19-OH structure among the identified DLs. The current study provides a new approach for collecting, processing, and characterizing MS analysis of natural DLs prone to in-source fragmentation. CONCLUSIONS: MS characterization of AP DLs was significantly improved, and many potential new compounds were identified in AP. This characterization provides new methods for the purification and identification of AP DLs.

Medium chain triglycerides improve the growth performance, immune and antioxidant functions, and intestinal health of weaned rabbits.

The purpose is to study the effects of different doses of medium chain triglyceride (MCT) on growth performance, immune and oxidative functions, and intestinal health of weaned rabbits. A total of 600 weaned rabbits weighing about 993.26 g and at 35 d of age were randomly divided into five groups. The control group was fed a basal diet containing 2400 mg/kg soybean oil, and the experimental group was substituted with 600, 1200, 1800, and 2400 mg/kg MCT. The whole trial period lasted for 48 d. The results showed that treatment with 2400 mg/kg MCT significantly increased the weaning survival rate and crude fat digestibility (p < 0.05) and dramatically raised the levels of serum immunoglobulin (Ig)A, IgG, IgM, catalase, superoxide dismutase, and total antioxidant capability (p < 0.05). The villus height and crypt depth in 1800 mg/kg MCT group were observably enhanced (p < 0.05). The abundance of Bacteroidetes was significantly increased in 1800 and 2400 mg/kg MCT groups (p < 0.05). In conclusion, 1800 and 2400 mg/kg MCT substituting soybean oil in the diet of weaned rabbits can improve the growth performance and intestinal barrier function of weaned rabbits.

Mass spectrometry imaging: new eyes on natural products for drug research and development.

Natural products (NPs) and their structural analogs represent a major source of novel drug development for disease prevention and treatment. The development of new drugs from NPs includes two crucial aspects. One is the discovery of NPs from medicinal plants/microorganisms, and the other is the evaluation of the NPs in vivo at various physiological and pathological states. The heterogeneous spatial distribution of NPs in medicinal plants/microorganisms or in vivo can provide valuable information for drug development. However, few molecular imaging technologies can detect thousands of compounds simultaneously on a label-free basis. Over the last two decades, mass spectrometry imaging (MSI) methods have progressively improved and diversified, thereby allowing for the development of various applications of NPs in plants/microorganisms and in vivo NP research. Because MSI allows for the spatial mapping of the production and distribution of numerous molecules in situ without labeling, it provides a visualization tool for NP research. Therefore, we have focused this mini-review on summarizing the applications of MSI technology in discovering NPs from medicinal plants and evaluating NPs in preclinical studies from the perspective of new drug research and development (R&D). Additionally, we briefly reviewed the factors that should be carefully considered to obtain the desired MSI results. Finally, the future development of MSI in new drug R&D is proposed.

Authentication of Shenqi Fuzheng Injection via UPLC-Coupled Ion Mobility-Mass Spectrometry and Chemometrics with Kendrick Mass Defect Filter Data Mining.

Nearly 5% of the Shenqi Fuzheng Injection's dry weight comes from the secondary metabolites of Radix codonopsis and Radix astragali. However, the chemical composition of these metabolites is still vague, which hinders the authentication of Shenqi Fuzheng Injection (SFI). Ultra-high performance liquid chromatography with a charged aerosol detector was used to achieve the profiling of these secondary metabolites in SFI in a single chromatogram. The chemical information in the chromatographic profile was characterized by ion mobility and high-resolution mass spectrometry. Polygonal mass defect filtering (PMDF) combined with Kendrick mass defect filtering (KMDF) was performed to screen potential secondary metabolites. A total of 223 secondary metabolites were characterized from the SFI fingerprints, including 58 flavonoids, 71 saponins, 50 alkaloids, 30 polyene and polycynes, and 14 other compounds. Among them, 106 components, mainly flavonoids and saponins, are contributed by Radix astragali, while 54 components, mainly alkaloids and polyene and polycynes, are contributed by Radix codonopsis, with 33 components coming from both herbs. There were 64 components characterized using the KMDF method, which increased the number of characterized components in SFI by 28.70%. This study provides a solid foundation for the authentification of SFIs and the analysis of its chemical composition.

Dissecting the Regulation of Arachidonic Acid Metabolites by Uncaria rhynchophylla (Miq). Miq. in Spontaneously Hypertensive Rats and the Predictive Target sEH in the Anti-Hypertensive Effect Based on Metabolomics and Molecular Docking.

Uncaria rhynchophylla (Miq). Miq. (UR), as a traditional Chinese medicine, was employed in treating hypertension as a safe and effective therapy. The pharmacological properties of UR have characteristics of multiple biological targets and multiple functional pathways. Hypertension is related to impaired metabolic homeostasis and is especially associated with the abnormal regulation of arachidonic acid metabolites, the classical cardiovascular active compounds. This study aimed to examine the anti-hypertensive effect of UR extract (URE) and its regulating role in differential metabolic pathways. The results showed that daily administration of URE at a dose of 4 g crude drug/kg orally could exert hypotensive effects on spontaneously hypertensive rats (SHRs) for 8 weeks. Non-targeted metabolomics analysis of the plasma samples suggested that the anti-hypertension effect of URE in SHRs was associated with the reorganization of the perturbed metabolic network, such as the pathways of glycerophospholipid metabolism, linoleic acid metabolism, and arachidonic acid metabolism. For the targeted metabolomics, twenty-eight arachidonic acid metabolites in SHRs were quantitatively analyzed for the first time based on ultra-high performance liquid chromatography-tandem mass spectrometry method after URE administration. URE restored the functions of these cardiovascular active compounds and rebalanced the dynamics of arachidonic acid metabolic flux. Among them, the inhibition of soluble epoxide hydrolase (sEH) enzyme activity and up-regulation of vasodilators epoxyeicosatrienoic acids (EETs) were identified as contributors to the anti-hypertension effect of URE on SHRs, and sEH represented an attractive and promising drug-binding target of URE. With the molecular docking approach, 13 potential anti-hypertension ingredients as well as sEH inhibitors were discovered, which were worthy of further investigation and verification in future studies.

Introducing Zirconium Organic Gels for Efficient Radioiodine Gas Removal.

Iodine radioisotope, as one of the most important fission products of uranium, may cause severe damage to human health when it is accidentally discharged into the environment. Hence, efficient removal of radioactive iodine is one of the most critical issues for both used nuclear fuel (UNF) reprocessing and environmental remediation. In this work, three metal-organic gels (MOGs) were introduced for iodine removal. The presented zirconium-based MOGs, namely, CWNU, CWNU-NH2, and CWNU-2NH2, were prepared via moderate solvothermal reactions. These MOGs all exhibit excellent chemical stability and reusability, marked iodine sorption capability, and favorable machinability, which can even rival commercial ones. The sorption capacities are determined to be 3.36, 4.10, and 4.20 g/g, respectively. The increased amount of amino group is considered to be responsible for the elevated iodine sorption capacity and kinetics, as confirmed by combined sorption studies and XPS analysis. The presented work sheds light on the utilization of MOGs for radioiodine capture.

In-depth exploration and comparison of chemical constituents from two Lilium species through offline two-dimensional liquid chromatography combined with multimode acquisition of high-resolution mass spectrometry.

Lilium lancifolium and Lilium brownii viridulum were two common cultivars of Lilium in China, which have been used as a source of food in ancient China, and as a traditional herbal medicine in most northern hemispheres countries continues today. However, only a few secondary metabolites in Lilium closely related to human health have been reported. In this research, an offline two-dimensional (HILIC and RP C18) separation system combined with multimode high-resolution mass spectrometry data acquisition was established for in-depth exploration and comparison of the chemical components in Lilium. In total, 331 components were identified, among which phenylpropanoid derivatives and steroidal saponins were the most abundant components. Furthermore, sulfur derivatives and steroidal alkaloids were systematically characterized in Lilium for the first time. These results provided valuable information for in-depth differentiating types of components characterization, which may be applied to assess and improve the edible and medicinal values of Lilium.

A simple and effective method for identification of Fraxini Cortex from different sources by multi-mode fingerprint combined with chemometrics.

Fraxini Cortex has a long history of being used as a medicinal plant in traditional Chinese medicine. However, it is challenging to differentiate and make quality evaluations for Fraxini Cortex from different origins due to their similarities in morphological features, as well as general chemical composition using traditional chemical analytical methods. In this study, a simple and effective method was developed to identify Fraxini Cortex from different origins by multi-mode fingerprint combined with chemometrics. Digital images of the high-performance thin-layer chromatography profiles were converted to grayscale intensity, and the common patterns of high-performance thin-layer chromatography fingerprints were generated with ChemPattern software. Authentication and quality assessment were analyzed by similarity analysis, hierarchical cluster analysis, principal component analysis, and multivariate analysis of variance. The ultra-high-performance liquid chromatography fingerprints were analyzed by similarity analysis, principal component analysis, and orthogonal partial least square-discriminant analysis. When combined with chemometrics, high-performance thin-layer chromatography and ultra-high-performance liquid chromatography fingerprint provided a simple and effective method to evaluate the comprehensive quality of Fraxini Cortex, and to distinguish its two original medicinal materials (Fraxinus chinensis Roxb. and Fraxinus rhynchophylla Hance.) recorded in the Chinese Pharmacopeia and its three adulterants (Fraxinus mandschurica Rupr., Fraxinus pennsylvanica Marsh., and Juglans mandshurica Maxim.). A similar workflow may be applied to establish a differentiation method for other medicinal and economic plants.

Characterization of chemical constituents in Shuanghuanglian oral dosage forms by ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry.

Shuanghuanglian is a common traditional Chinese medicine prescription. It is an herbal formula composed of Lonicerae Japonicae Flos, Scutellariae Radix, and Forsythiae Fructus. A comprehensive understanding of Shuanghuanglian oral dosage forms components was obtained using a method based on ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry for the separation and characterization of Shuanghuanglian oral liquids, granules, soft capsules, and effervescent tablets. A total of 358 components were chemically defined or tentatively identified, including flavonoids, caffeic acid derivatives, lignans, coumarins, iridoids, triterpenes, and anthraquinones. The results will provide a basis for the general study of Shuanghuanglian and be meaningful for the composition identification of traditional Chinese medicine prescriptions.

Untargeted metabolomics coupled with chemometric analysis deducing robust markers for discrimination of processing procedures: Wine-processed Angelica sinensis as a case study.

Wine-processed Angelica Sinensis is a widely used Chinese medicinal decoction piece in China. However, there are hardly any robust markers indicating the processing procedure of wine-processed Angelica Sinensis, including the amount of rice wine and processing degree. A strategy integrating untargeted metabolomics and chemometric analysis for deducing robust markers was provided and applied to the discrimination of processing procedure. First, 86 compounds were tentatively identified in wine-processed Angelica Sinensis by ultra-high-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry. Second, 93 potential chemical markers were selected using multivariate analysis, among which nine robust chemical markers were selected by verification with commercial samples. Finally, the effects of processing temperature, time, and amount of rice wine on the three selected chemical markers were investigated through a rapid analytical method. It was demonstrated that both m/z 258.1097 and 238.1189 were positively correlated with the amount of rice wine and processing degree. In summary, this study introduced two candidate processing markers as robust markers for discriminating the processing procedures of wine-processed Angelica sinensis. It also proposed a strategy to provide the reference for the research of other decoction pieces.

Structural Characterization of a Polysaccharide from Gastrodia elata and Its Bioactivity on Gut Microbiota.

A novel homogeneous polysaccharide named GEP-1 was isolated and purified from Gastrodia elata (G. elata) by hot-water extraction, ethanol precipitation, and membrane separator. GEP-1, which has a molecular weight of 20.1 kDa, contains a polysaccharide framework comprised of only glucose. Methylation and NMR analysis showed that GEP-1 contained 1,3,6-linked-α-Glcp, 1,4-linked-α-Glcp, 1,4-linked-ß-Glcp and 1,4,6-linked-α-Glcp. Interestingly, GEP-1 contained citric acid and repeating p-hydroxybenzyl alcohol as one branch. Furthermore, a bioactivity test showed that GEP-1 could significantly promote the growth of Akkermansia muciniphila (A. muciniphila) and Lacticaseibacillus paracasei (L.paracasei) strains. These results implied that GEP-1 might be useful for human by modulating gut microbiota.

A five-dimensional data collection strategy for multicomponent discovery and characterization in Traditional Chinese Medicine: Gastrodia Rhizoma as a case study.

Establishing the identity of bioactive compounds to control the quality of Traditional Chinese Medicines is made more challenging by the complexity of the metabolite matrix, the existence of isomers, and the range of compound concentration and polarity observed between individual samples of the same plant in a multicomponent preparation. In addition, LC-MS analysis has limited capability for the separation and analysis of potentially important trace compounds and isomers, which hinders the comprehensive metabolite characterization of functional foods and Traditional Natural Medicine. To facilitate and improve the chemical composition characterization and enhance metabolite discernment, a comprehensive strategy was developed which integrates ion mobility mass spectrometry (IMS) with offline two-dimensional liquid chromatography based on hydrophilic interaction chromatography (HILIC) and conventional reversed phase (RP) C18 chromatography. Through application of the HILIC × RP offline 2D-LC approach, trace compounds were enriched and separated promoting a more efficient and detailed analysis of the matrix complexity. Comprehensive non-targeted multidimensional data (Rt1D, Rt2D, MS, CCS and MS/MS) and data-independent-acquisition (DIA) mass data of the metabolites in complex food and drug samples were obtained in the IMS-DIA-MS/MS mode on a Waters-SYNAPT G2-Si mass spectrometer with an ESI source. Through the application of high-efficiency neutral loss (NLs) and diagnostic product ions (DPIs) filter strategies, information from DIA mass data permitted the rapid detection and identification of compounds. The identification coverage of metabolites with low-quality MS/MS data was also improved. In the absence of analytical standards, Collision Cross Section (CCS) prediction and matching strategies based on theoretical chemical structures provided a method to distingish isomers. To demonstrate the efficacy of the technique this comprehensive strategy was applied to the compound characterization of Gastrodia Rhizoma (GR). Characterization of 272 compounds was achieved, including 146 unreported compounds. The results affirm that this comprehensive five-dimensional data collection strategy has the capacity to support the in-depth study of the high level of chemical diversity in Traditional Chinese Medicines.

Fast determination of 16 circulating neurotransmitters and their metabolites in plasma samples of spontaneously hypertensive rats intervened with five different Uncaria.

This study aimed to establish a sensitive, reproducible, and rapid liquid chromatography method with tandem mass spectrometry detection to perform simultaneous quantitative analysis of 16 neurotransmitters and their metabolites in rat plasma, including levodopa, dopamine, norepinephrine, epinephrine, L-tryptophan, kynurenic acid, serotonin, melatonin, choline, acetylcholine, histamine, phenylethylamine, as well as excitatory (L-glutamic acid and L-aspartic acid) and inhibitory (γ-aminobutyric acid and L-glycine) neurotransmitters. These analytes were measured by ultra-high performance chromatography coupled with triple quadrupole mass spectrometry using a hydrophilic interaction chromatographic column (ethylene-bridged hybrid amide column). The internal standards of stable isotope labeling were used to improve the reliability of the results. Our method provided high linearity for all neurotransmitters (for all coefficients measured > 0.99), with inter- and intra-day accuracy from -14.82% to 17.49% and precision was between 0.89% and 17.70%. The method was subsequently verified in an animal study, where the intervention of five different Uncarias, the traditional Chinese medicine with hypotensive effects, was applied to the spontaneously hypertensive rats (SHRs). SHRs showed dysregulated plasma kynurenic acid, acetylcholine, and norepinephrine levels, and these neuroactive analytes were significantly restored by Uncaria treatment compared with the model group (SHR group). Compared with captopril, included as a positive control for its hypotensive effect, Uncaria had more effects on perturbing the levels of plasma neurotransmitters, which might indicate Uncaria's potential in treating symptoms related to the nervous system. These results suggested that the changes in the neurotransmitters and their metabolites in plasma may be related to the pathogenesis of hypertension. It also provided valuable information about the action mechanisms of Uncaria on its hypotensive effects.

Restoring perturbed oxylipins with Danqi Tongmai Tablet attenuates acute myocardial infarction.

Salvianolic acids have a special synergic effect on panax notoginsenosides in acute myocardial infarction (AMI) and have been developed into a new drug as Danqi Tongmai Tablet (DQTT). To explore candidate targets and mechanisms of DQTT on AMI, a network pharmacology-based analysis was performed on absorbed prototype compounds of DQTT in rat plasma. Target prediction from network analysis indicated that the arachidonic acid pathway might contribute to the therapeutic effects of DQTT on AMI, and the regulatory effects on cyclooxygenase (COX) and lipoxygenase (LOX) were validated using an oxygen-glucose deprivation/reoxygenation model established on H9c2 cardiomyocytes. To further explore the action mechanisms of DQTT, 38 oxylipins were quantitatively analyzed among high, medium, and low doses of DQTT using a rat AMI model with an ultra high performance liquid chromatograph coupled with a triple quadrupole mass spectrometry (UHPLC-QqQ/MS) detection system. As attenuation was observed in AMI with DQTT treatment, the perturbed arachidonic acid metabolome was partly restored in a dose-dependent fashion with a significant elevation of anti-inflammatory metabolites, while pro-inflammatory lipids were decreased. Cytokine array analysis also supported the anti-inflammatory effects of DQTT, as significant down-regulation of pro-inflammatory cytokines was observed. The analysis of ischemic heart tissues demonstrated that COX and LOX, the inflammation-induced catalytic enzymes of arachidonic acid metabolism, were inhibited on both gene expression and protein level. These results confirmed that DQTT could restore the arachidonic acid metabolome to maintain an anti-inflammatory profile against the ischemic tissue injury and support that DQTT can be a promising medicinal therapy against AMI.

Structural characterization of two novel polysaccharides from Gastrodia elata and their effects on Akkermansia muciniphila.

Two homogeneous polysaccharides, GEP-3 and GEP-4, were purified from Gastrodia elata, a precious traditional Chinese medicine. Their structural characteristics were obtained using HPGPC, PMP-HPLC, LC/MS, FT-IR, NMR, and SEM methods. GEP-3 was 1,4-glucan with molecular weight of 20 kDa. Interestingly, GEP-4 comprised of a backbone of →[4)-α-Glcp-(1]10→[4)-α-Glcp-(1→]5[6)-ß-Glcp-(1]11→6)-α-Glcp-(3→ and two branches of ß-Glcp and p-hydroxybenzyl alcohol citrate, with repeating p-hydroxybenzyl alcohol attached to the backbone chain at O-6 position of →4,6)-α-Glcp-(1→ and O-1 position of →3,6)-α-Glcp-(1→. GEP-4 is a novel polysaccharide obtained and characterized for the first time. Bioactivity test indicated that both of them significantly promote the growth of Akkermansia muciniphila (Akk. muciniphila). Furthermore, GEP-3 and GEP-4 promoted the growth of Akk. muciniphila from high-fat diet (HFD) fecal microbiota. These results indicated that GEP-3 and GEP-4 were potential Akk. muciniphila growth promoters.

Anti-neuroinflammatory activity of Shenqi Fuzheng Injection and its main active constituents.

Enhancement of alternative activation (M2) in microglia is a promising therapeutic target for microglia-mediated neuroinflammation. Shenqi Fuzheng Injection (SFI) is a clinical adjuvant treatment for cancer to reduce the side effects during cancer treatment, including boosting mood and improving appetite. However, the mechanism of SFI's effects on central symptoms is not clear. Therefore, using arginase 1 (Arg1) and transforming growth beta-1 (Tgfb1) as markers for M2 microglia activation, we found that compounds 1, 5, 12, 14, and 15 are the major M2-promoting constituents in SFI, which significantly upregulated Arg1 or Tgfb1 gene expression. Our results suggested that these compounds in SFI may promote M2 microglial activation and have potential uses in modulating microglial activation and alleviating neuroinflammation.