UPLC-QTOF-MS based metabolomics unravels the modulatory effect of ginseng water extracts on rats with Qi-deficiency.

Ginseng is commonly used as a nutritional supplement and daily wellness product due to its ability to invigorate qi. As a result, individuals with Qi-deficiency often use ginseng as a health supplement. Ginsenosides and polysaccharides are the primary components of ginseng. However, the therapeutic effects and mechanisms of action of these components in Qi-deficiency remain unclear. This study aimed to determine the modulatory effects and mechanisms of ginseng water extract, ginsenosides, and ginseng polysaccharides in a rat model of Qi-deficiency using metabolomics and network analysis. The rat model of Qi-deficiency was established via swimming fatigue and a restricted diet. Oral administration of different ginseng water extracts for 30 days primarily alleviated oxidative stress and disrupted energy metabolism and immune response dysfunction caused by Qi-deficiency in rats. Ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for untargeted serum metabolomic analysis. Based on the analysis results, the active constituents of ginseng significantly reversed the changes in serum biomarkers related to Qi-deficiency in rats, particularly energy, amino acid, and unsaturated fatty acid metabolism. Furthermore, analysis of the metabolite-gene network suggested that the anti-Qi-deficiency effects of the ginseng components were mainly associated with toll-like receptor (TLR) signaling and inflammatory response. Additional verification revealed that treatment with the ginseng components effectively reduced the inflammatory response and activation of the myocardial TLR4/NF-κB pathway induced by Qi-deficiency, especially the ginseng water extracts. Therefore, ginseng could be an effective preventive measure against the progression of Qi-deficiency by regulating metabolic and inflammatory responses.

UPLC-Q-TOF/MS based serum and urine metabolomics strategy to analyze the mechanism of nervonic acid in treating Alzheimer's disease.

Nervonic acid is a natural component of breast milk and is frequently used as a food additive due to its excellent neuroprotective effects. Although it has been reported that nervonic acid may play a role in the recovery of human cognitive impairment, its specific mechanism of action is still unclear. In this study, the results of serum biochemical indexes showed that nervonic acid improved inflammation and reduced amyloid ß peptide (Aß) deposition and tau protein phosphorylation in Alzheimer's disease (AD) rats. Subsequently, we further used a metabolomics approach to investigate the potential mechanism of action of nervonic acid in the treatment of AD. The results of serum and urine metabolomics study showed that the intervention of nervonic acid significantly reversed the metabolic profile disorder in AD rats. A total of 52 metabolites were identified. They mainly involved linoleic acid metabolism, alpha-linolenic acid metabolism, phenylalanine metabolism and arachidonic acid metabolism, and all these metabolic pathways were associated with the emergence of inflammation in vivo. It suggests that the therapeutic effect of nervonic acid on AD is likely to be produced by ameliorating inflammation. The results obtained in this study provide new insights into the mechanism of nervonic acid treatment of AD and lay a foundation for the clinical application of nervonic acid in the treatment of Alzheimer's disease.

An integrated approach based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, network pharmacology, and molecular docking to study the key effective compounds and mechanism of action of Platycodi Radix in the treatment of chronic obstructive pulmonary disease.

Platycodi Radix (PR) is a valuable herb that is widely used in the treatment of chronic obstructive pulmonary disease in clinics. However, the mechanism of action for the treatment of chronic obstructive pulmonary disease remains unclear due to the lack of in vivo studies. Our study established a novel integrated strategy based on ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry, network pharmacology, and molecular docking to systematically analyze the tissue distribution and active compounds of PR in vivo and the therapeutic mechanism of chronic obstructive pulmonary disease. First, tissue distribution studies have shown that the lung is the organ with the highest distribution of PR compounds. Subsequently, network pharmacology results showed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and mitogen-activated protein kinase signaling pathway were the critical mechanisms of PR against chronic obstructive pulmonary disease. Ultimately, molecular docking results showed that the key targets were stably bound to the corresponding active compounds of PR. Our study is of great significance for the screening of the key effective compounds and the study of the mechanism of action in traditional Chinese medicine and provides data to support the further development and utilization of PR.

Therapeutic effect of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves on ischemic stroke via the microbiota-gut-brain axis.

Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) are widely used to treat ischemic stroke (IS); however, the specific mechanism remains unclear. The microbiota-gut-brain axis plays a critical role in IS and has become a potential therapeutic target. This study aimed to reveal and verify the therapeutic effect of ESL on IS through the microbiota-gut-brain axis. Ultra-high-performance liquid chromatography coupled with mass spectrometry-based untargeted/targeted metabolomics combined with 16S rRNA microbiota sequencing strategy were used to investigate the regulatory effect of ESL on the metabolism and intestinal microenvironment after IS. Lactobacillus reuteri and Clostridium butyricum were used to treat rats with IS to verify that elevated levels of probiotics are key factors in the therapeutic effect of ESL. The results showed that IS significantly altered the accumulation of 41 biomarkers, while ESL restored their concentrations back to normal. Moreover, ESL alleviated the dysbiosis of gut microbiota brought on by IS, by reducing the abundance of pathogens and increasing the abundance of probiotics (e.g., Lactobacillus reuteri and Clostridium butyricum); this could reduce post-stroke injury, thereby having a certain protective effect on IS. This study reveals that ESL plays an important role in treating IS through the microbiota-gut-brain axis, maintaining metabolic homeostasis in vivo.

Guanxin V attenuates myocardial ischaemia reperfusion injury through regulating iron homeostasis.

CONTEXT: Guanxin V (GX), a traditional Chinese medicine formula, is safe and effective in the treatment of coronary artery disease. However, its protective effect on myocardial ischaemia reperfusion injury (MIRI) is unclear. OBJECTIVE: To investigate the cardioprotective effect of GX on MIRI and explore the potential mechanism. MATERIALS AND METHODS: Sprague-Dawley male rats were divided into Sham, MIRI and MIRI + GX groups. GX (6 g/kg) was administered to rats via intragastric administration for seven days before ischaemia reperfusion (IR) surgery. The infarct size, histopathology, serum enzyme activities, ultrastructure of the cardiac mitochondria were assessed. H9c2 cells were pre-treated with GX (0.5 mg/mL), and then exposed to hypoxia/reoxygenation (HR). The cell viability and LDH levels were measured. Network pharmacology was conducted to predict the potential mechanism. The related targets of GX were predicted using the TCMSP database, DrugBank database, etc. Finally, pharmacological experiments were used to validate the predicted results. RESULTS: In vivo, GX significantly reduced the myocardial infarct size from 56.33% to 17.18%, decreased the levels of AST (239.32 vs. 369.18 U/L), CK-MB (1324.61 vs. 2066.47 U/L) and LDH (1245.26 vs. 1969.62 U/L), and reduced mitochondrial damage. In vitro, GX significantly increased H9c2 cell viability (IC50 = 3.913 mg/mL) and inhibited the release of LDH (207.35 vs. 314.33). In addition, GX could maintain iron homeostasis and reduce oxidative stress level by regulating iron metabolism-associated proteins. CONCLUSIONS: GX can attenuate MIRI via regulating iron homeostasis, indicating that GX may act as a potential candidate for the treatment of MIRI.

A multidimensional strategy to rapidly identify the chemical constituents in Shengxian Decoction by using ultra-performance liquid chromatography coupled with ion mobility spectrometry quadrupole time-of-flight mass spectrometry.

As a well-known traditional Chinese medicine formula, the chemical constituents of Shengxian Decoction still remain unclear due to its complexity. In this study, a multidimensional strategy based on ultra-performance liquid chromatography coupled with ion mobility spectrometry quadrupole time-of-flight mass spectrometry and informatics UNIFI platform was applied to achieve rapid and comprehensive identification of the complex composition of Shengxian Decoction. Data-independent acquisition, fast data-directed analysis, and high-definition MSE were used to obtain more and cleaner mass spectrum information. As a result, a total of 120 compounds including 74 saponins, 17 flavonoids, 7 cinnamic acid derivatives, 8 triterpenoids, and 14 others were identified or tentatively characterized by high-resolution molecular mass, fragment ions, and collision cross-section values. Furthermore, high-definition MSE was used to identify six pairs of co-eluting isomers that could not be detected from conventional data-independent acquisition and fast data-directed analysis. This research strategy has a certain potential for the analysis of other compound formulae and lays the foundation for the study of traditional Chinese medicine efficacy.

Angelica dahurica Extracts Attenuate CFA-Induced Inflammatory Pain via TRPV1 in Mice.

Angelica dahurica, belonging to the family Apiaceae, is a well-known herbal medicine. The roots of Angelica dahurica are commonly used for the treatment of headache, toothache, abscess, furunculosis, and acne. However, little is known about their analgesic molecular mechanism underlying pain relief. In this study, we used behavioral tests to assess the analgesic effect of the ADE (Angelica dahurica extracts) on CFA (complete Freund's adjuvant)-induced inflammatory pain mice models. TRPV1 (Transient Receptor Potential Cation Channel Subfamily V Member 1) protein activity in dorsal root ganglion (DRG) was assessed with a calcium imaging assay. TRPV1 expression was detected with western blot and immunohistochemistry. Then, we examined the constituents of ADE using combined ultra-performance liquid chromatography-quadrupole time-of-light mass spectrometry (UPLC/Q-TOF-MS). Our results showed that ADE effectively attenuated mechanical and thermal hypersensitivities in CFA-induced inflammatory pain model in mice. ADE also significantly reduced the activity and the protein expression of TRPV1 in DRG from CFA mice. Therefore, ADE might be an attractive and suitable analgesic agent for the management of chronic inflammatory pain.

Synthesis, characterization, in vitro antioxidant and hypoglycemic activities of selenium nanoparticles decorated with polysaccharides of Gracilaria lemaneiformis.

Under a simple redox system of selenite and ascorbic acid, we used Gracilaria lemaneiformis polysaccharides (GLPs) as a stabilizer and dispersing agent to generate well-dispersed and stable selenium nanoparticles (SeNPs). The size, stability, morphology and physicochemical properties of GLPs-SeNPs were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FT-IR) spectra, energy dispersive X-ray (EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Thermogravimetric (TG). The results showed that orange-red, amorphous, zero-valent and spherical GLPs-SeNPs with mean diameter of approximately 92.5 nm were successfully prepared, which exhibited good storage stability at 4 °C and remaining highly stable at different ion strengths and pH. The 2,2-diphenyl-1-pycrylhydrazyl (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and superoxide anion radical (O2•-) radical scavenging ability of GLPs-SeNPs were higher than those of bare SeNPs, GLPs and sodium selenite (Na2SeO3), and could reach 103.41%, 94.23%, 86% at a concentration of 1.5 mg/mL, respectively. Besides, GLPs-SeNPs also showed higher inhibitory effects on α-amylase and α-glucosidase. In vitro cytotoxicity assay and hemolysis activity examinations indicated that GLPs-SeNPs have excellent biocompatibility. Therefore, the GLPs-SeNPs might be used as a potential antioxidant agent and antidiabetic agent for food and medical applications.

The efficacy and safety of fire needle for the treatment of lumbar disc herniation: A protocol for systematic review and meta-analysis.

BACKGROUND: A very large acceleration in clinical studies on the efficacy of fire needle to treat lumbar disc herniation (LDH) are increasing, while studies on the assessment of its efficacy are still lacking. Therefore, this study will demonstrate the efficacy of fire needle in the treatment of LDH combining with the meta-analysis. METHODS: The studies on randomized controlled trials (RCTs) will be searched at the databases of China National Knowledge Infrastructure (CNKI), WANFANG database (Chinese Medicine Premier), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature database (CBM), PubMed, EMBASE, and Cochrane Library from their inception to May 1, 2020. RESULTS: This authentic and multi-dimensional study will shed light on the referable information for the treatment of LDH with fire needle. CONCLUSION: This study will evaluate the efficacy of fire needle in the treatment of LDH. REGISTRATION: PROSPERO (registration number CRD42020158596).