Unraveling the chemical constituents, absorption characteristics, and metabolic profile of Codonopsis Radix based on UPLC-Q- Orbitrap MS.

Codonopsis Radix (CR), a traditional tonic medicinal material in China, has been proven to possess a variety of bioactive functions. However, its chemical composition and in vivo metabolic pattern have not been fully elucidated. In this study, AB-8 macroporous resin column chromatography was employed for the enrichment of small molecular components in CR. Furthermore, a method combining ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry with Acquire X intelligent data acquisition technology software was developed for the preliminary screening and identification of the chemical composition of CR in vitro and their metabolites in vivo. As a result, a total of 116 components were preliminarily characterized in the CR extract, including 28 polyacetylenes, 33 organic acids, 4 amino acids, 23 alkaloids, 9 phenylpropanoids, 6 terpenoids, 2 nucleosides, and 11 others. Additionally, a total of 84 compounds, including 37 prototype components and 47 metabolites, were identified in the plasma, urine, and feces of rats after oral administration of CR. Specifically, 11, 24, 19, 32, and 25 constituents were identified in the heart, liver, spleen, lung, and kidney, respectively. Of note, the lung and spleen are the organs with the highest distribution of CR compounds. These findings will serve as valuable data for future research on the correlation between the chemical composition and pharmacological effects of CR.

Dietary Supplementation with Nervonic Acid Ameliorates Cerebral Ischemia-Reperfusion Injury by Modulating of Gut Microbiota Composition-Fecal Metabolites Interaction.

SCOPE: Cerebral ischemia-reperfusion (IR) injury stands as a prominent global contributor to disability and mortality. Nervonic acid (NA), a bioactive elongated monounsaturated fatty acid, holds pivotal significance in human physiological well-being. This research aims to explore the prophylactic effects and fundamental mechanisms of NA in a rat model of cerebral IR injury. METHODS AND RESULTS: Through the induction of middle cerebral artery occlusion, this study establishes a rat model of cerebral IR injury and comprehensively assesses the pharmacodynamic impacts of NA pretreatment. This evaluation involves behavioral analyses, histopathological examinations, and quantification of serum markers. Detailed mechanisms of nervonic acid's prophylactic effects are revealed through fecal metabolomics and 16S rRNA sequencing analyses. Our findings robustly support nervonic acid's capacity to ameliorate neurological impairments in rats afflicted with cerebral IR injury. Beyond its neurological benefits, NA demonstrates its potential by rectifying metabolic perturbations across diverse pathways, particularly those pertinent to unsaturated fatty acid metabolism. Additionally, NA emerges as a modulator of gut microbiota composition, notably by selectively enhancing vital genera like Lactobacillus. CONCLUSION: These comprehensive findings highlight the potential of incorporating NA as a functional component in dietary interventions aimed at targeting cerebral IR injury.

Exogenous Calcium Alleviates Oxidative Stress Caused by Salt Stress in Peanut Seedling Roots by Regulating the Antioxidant Enzyme System and Flavonoid Biosynthesis.

Soil salinity is one of the adversity stresses plants face, and antioxidant defense mechanisms play an essential role in plant resistance. We investigated the effects of exogenous calcium on the antioxidant defense system in peanut seedling roots that are under salt stress by using indices including the transcriptome and absolute quantitative metabolome of flavonoids. Under salt stress conditions, the antioxidant defense capacity of enzymatic systems was weakened and the antioxidant capacity of the linked AsA-GSH cycle was effectively inhibited. In contrast, the ascorbate biosynthesis pathway and its upstream glycolysis metabolism pathway became active, which stimulated shikimate biosynthesis and the downstream phenylpropanoid metabolism pathway, resulting in an increased accumulation of flavonoids, which, as one of the antioxidants in the non-enzymatic system, provide hydroxyl radicals to scavenge the excess reactive oxygen species and maintain the plant's vital activities. However, the addition of exogenous calcium caused changes in the antioxidant defense system in the peanut root system. The activity of antioxidant enzymes and the antioxidant capacity of the AsA-GSH cycle were enhanced. Therefore, glycolysis and phenylpropanoid metabolism do not exert antioxidant function, and flavonoids were no longer synthesized. In addition, antioxidant enzymes and the AsA-GSH cycle showed a trade-off relationship with sugars and flavonoids.

Integrated ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry-based components analysis and network pharmacology strategy of Gancao Xiexin Decoction in treating gastric ulcer.

Gancao Xiexin Decoction (GCXXD) is a traditional Chinese decoction that is often used in treating gastric ulcers. However, the substance basis and mechanism of action remain unclear. In this study, in vivo and in vitro components of GCXXD were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry. The compound Discover platform was used to ultimately enable rapid identification of compounds. Acquire X intelligent data acquisition technology software was innovatively adopted. In the process of collecting drug-containing plasma, all components detected in blank plasma samples were excluded to eliminate the interference and influence of endogenous components in plasma, making the analysis results more accurate and reliable. At the same time, the possibility of selecting precursor parent ions with low concentration levels within the chromatographic peak can be increased, improving the coverage and integrality of the detection of components in vivo. Also, the targeted network pharmacology strategy combined with molecular docking was established to explore the mechanism of GCXXD in treating gastric ulcers. As a result, 113 components were identified, 41 of which could enter the bloodstream and exert therapeutic effects in vivo. The main effective components are glycyrrhizic acid, 6-gingerol, jatrorrhizine, wogonin, palmatine, and liquiritigenin, main targets in vivo were related to ALB, IL6, and VEGF, which play an important role in anti-inflammatory and promoting angiogenesis. In summary, this study adopted a comprehensive analysis strategy to reveal the pharmacodynamic material basis and mechanism of GCXXD against gastric ulcers, providing a scientific basis for its clinical application.

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.

Multi-Omics Revealed Peanut Root Metabolism Regulated by Exogenous Calcium under Salt Stress.

High salinity severely inhibits plant seedling root development and metabolism. Although plant salt tolerance can be improved by exogenous calcium supplementation, the metabolism molecular mechanisms involved remain unclear. In this study, we integrated three types of omics data (transcriptome, metabolome, and phytohormone absolute quantification) to analyze the metabolic profiles of peanut seedling roots as regulated by exogenous calcium under salt stress. (1) exogenous calcium supplementation enhanced the allocation of carbohydrates to the TCA cycle and plant cell wall biosynthesis rather than the shikimate pathway influenced by up-regulating the gene expression of antioxidant enzymes under salt stress; (2) exogenous calcium induced further ABA accumulation under salt stress by up-regulating the gene expression of ABA biosynthesis key enzymes AAO2 and AAO3 while down-regulating ABA glycosylation enzyme UGT71C5 expression; (3) exogenous calcium supplementation under salt stress restored the trans-zeatin absolute content to unstressed levels while inhibiting the root cis-zeatin biosynthesis.

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.

Mass spectrometry-based serum lipidomics strategy to explore the mechanism of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves in the treatment of ischemic stroke.

Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) were reported to have neuroprotective function and are also used to treat cranial and cerebral traumas as a traditional Chinese medicine and food herbage plant. However, there has been no previous study on ESL treatment for stroke at the level of lipid disorders. To clarify the mechanism of ESL in treating ischemic stroke, this study was carried out from 3 aspects, namely, the regulation of lipid disorders, protection of the nervous system, as well as anti-inflammatory and antioxidant actions. This study established a lipidomics research strategy that was developed by UPLC-Q-TOF/MS analysis. The quantification of neurotransmitters in the serum and brain tissue of rats was performed using UPLC-TQ/MS. Also, we quantified the oxidative stress and inflammatory reaction by measuring the contents of SOD, MDA, TNF-α, IL-6, and IL-10 via the ELISA kits for serum and brain tissue. According to UPLC-Q-TOF/MS-based lipidomics analysis, 27 lipidomics biomarkers were identified in this study, including PC, PE, SM, and TG, which were distributed in various lipid metabolic pathways, including glycerophospholipid, linoleic acid, alpha-linolenic acid, glycerolipid, sphingolipid, and arachidonic acid metabolism pathways. By reversing the changes in the lipid content caused by the disease, ESL has a therapeutic effect on ischemic stroke. Furthermore, quantitative results of neurotransmitters indicated that they can be regulated by ESL. Finally, the results of ELISA showed that ESL can treat ischemic stroke to a certain extent by reducing the oxidative and inflammatory damage. Therefore, ESL may play a therapeutic role in the treatment of ischemic stroke in different ways. This research preliminarily revealed the mechanism of ESL in the treatment of ischemic stroke and provided support for the further application of ESL.

Predictors of caring ability and its dimensions among nurses in China: A cross-sectional study.

BACKGROUND: Caring is an essential component of professional nursing practice, which directly affects the quality of patient care. Nurses' caring ability may not meet patients' demands for high-quality care. There are challenges in designing and implementing interventions to improve nurses' caring ability, especially in China. Understanding Chinese nurses' caring ability and related influential factors serves as the basis for effective interventions to improve their ability to care for patients. AIM: To describe the caring ability of nurses and its potential predictors in China. METHODS: From January to February 2018, a cross-sectional survey was conducted among 2304 Registered Nurses working at different levels of hospitals across 29 provinces in China. The structured online survey included socio-demographic information, Caring Ability Inventory, Caring Efficacy Scale and Professional Quality of Life. Descriptive statistics, univariate analyses and multivariate analyses were conducted. RESULTS: Overall caring ability and its three dimensions of the participants were all significantly lower than the Nkongho' norm, an international scoring standard of nurse's caring ability. Age, employment type, workplace, caring efficacy, compassion satisfaction, burnout and secondary traumatic stress were predictors of knowing, explaining 41.8% of the variance. Predictors of courage were educational level, bereavement experience, caring efficacy, compassion satisfaction and burnout (31.7% of the variance). Educational level, workplace, exposure to critically ill patients, caring efficacy, compassion satisfaction, burnout and secondary traumatic stress were influencing factors of patience, accounting for 19.5% of the variance. CONCLUSIONS: Chinese nurses' caring ability, with patience, knowing, and courage in descending order. Particular attention needs to be paid to the courage dimension of the nurses' caring ability. Further, the predictors of overall caring ability and each dimension were diverse. These results indicate that nurse educators and administrators need to identify training priorities and design targeted interventions based on the influencing factors.

Caring in community nursing practice: Inductive content analysis reveals an inter-dynamic system between patients and nurses.

AIMS AND OBJECTIVES: To examine the understanding of caring in the practice of community nursing from the perspectives of patients and nurses. BACKGROUND: An increasing population of patients with chronic disease has produced a need for humanistic caring in communities. As a result, caring has become a core value of community nursing professionals. However, community nurses meet many difficulties in trying to practice person-centred care with their clients. Furthermore, most community nurses-especially in China-lack systematic education and training about caring because the practical meaning of caring in community practice is unknown. DESIGN: The qualitative study described herein employed inductive content analysis. METHODS: Eleven community patients with chronic disease and fifteen community nurses who were nominated as a caring nurse from different community clinics in Beijing, China, participated in thirty-one interviews during January to August in 2018. Nine documents from the interviewed nurses were collected. Both interview data and documents were analysed using strategies of inductive content analysis. The COREQ checklist was used. RESULTS: Patients and their corresponding nurses described a wide range of caring experiences that were generalised into 28 concepts. Caring emerged as an inter-dynamic system that comprised the foundation and quality of a caring relationship, the caring philosophy and behaviours of interactions, and positive feedback from caring interactions. A relationship-based framework of caring in community nursing practice was constructed. CONCLUSIONS: Identifying this systematic concept of caring provides insights that are applicable to the creation of targeted management, education and practice interventions to ultimately enhance the quality of community health care-in China or elsewhere. RELEVANCE TO CLINICAL PRACTICE: The systematic understanding of caring in community nursing practice will inform nurses in community health clinics, their educators and their managers on how to provide care to community patients and how to develop caring competence for community nurses.

A rapid protocol to distinguish between Citri Exocarpium Rubrum and Citri Reticulatae Pericarpium based on the characteristic fingerprint and UHPLC-Q-TOF MS methods.

Citri Exocarpium Rubrum (CER) and Citri Reticulatae Pericarpium (CRP) are used as common functional foods and traditional Chinese medicine (TCM). As different parts of the same fruit, CER and CRP have different effects in clinical applications. However, they are commonly confused due to the similarity of the chemical compounds and a lack of scientific method to distinguish them in the finished product. In this study, an ultra-high performance liquid chromatography-diode array detector (UHPLC-DAD) technique and an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF MS) method were employed to generate the characteristic fingerprint under the optimum analytical conditions. Principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) were applied to represent different chemical markers for CER and CRP. 44 potential markers including 15 polymethoxylated flavanones (PMFs), 5 flavone-C-glycosides, 6 flavanone-O-glycosides, 3 flavonoid-O-glycosides, 8 organic acids, 5 limonoids and 2 alkaloids were successfully identified by using UNIFI software. The heat map showed that there were significant differences in the CER and CRP samples. Furthermore, 12 potential markers were screened out by characteristic fingerprint and UHPLC-Q-TOF MS methods and were analyzed by quantitative analysis of multicomponents by a single marker (QAMS) method. Finally, a prediction model based on the discovered chemical markers was established for discrimination between CER and CRP. Using these markers can significantly distinguish the unknown processed products of CER and CRP. In conclusion, an effective way to quickly and easily distinguish CER and CRP was successfully established based on the characteristic fingerprint and UHPLC-Q-TOF MS. It could also be a new strategy for analysis of different processed products of the same plant source.

Study on the therapeutic material basis and effect of Acanthopanax senticosus (Rupr. et Maxim.) Harms leaves in the treatment of ischemic stroke by PK-PD analysis based on online microdialysis-LC-MS/MS method.

Leaves of Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASL) have revealed significant biological activity in the treatment of ischemic stroke diseases. However, there was no in-depth study of the therapeutic material basis and effect of ASL from the pharmacokinetics-pharmacodynamics (PK-PD) analysis level. In this study, a method based on microdialysis coupled with ultra-performance liquid chromatography combined with triple quadruple mass spectrometry (MD-UPLC-QQQ-MS) was established to simultaneously and continuously collect and quantify the active compounds and endogenous neuroactive substances related to therapeutic effect in plasma and hippocampus of fully awake ischemic stroke rats. The acquired data were analyzed by the PK-PD analysis method. It was found that hyperoside, quercitrin, quercetin, and caffeic acid could pass through the blood-brain barrier, and quercetin needed a longer intake time than quercitrin and hyperoside, but the passage rate was higher. The exposure of the four compounds in the hippocampus affected the contents of seven neuroactive substances in different ways and was depicted graphically (concentration-time effect). In addition, the study found that the brain index and brain water content of ischemic stroke rats were significantly reduced after the oral administration of ASL. ASL observably regulated the content or activity of six important biochemical indexes in rats. On the one hand, this study verified that ASL could regulate ischemic stroke in many aspects. On the other hand, a visualized method to express the relationship between pharmacokinetics and pharmacodynamics in the hippocampus of cerebral ischemic areas was established. This research gives a hand to the study on the therapeutic material basis and effect of traditional Chinese medicine mechanism.

Mass spectrometry-based urinary metabolomics for the investigation on the mechanism of action of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves against ischemic stroke in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) can treat ischemic, neurasthenia, and hypertension diseases. However, only few studies have been conducted on the mechanism of action of ESL for ischemic disease treatment. AIM OF THE STUDY: This study aimed to discover the potential biomarkers in the rats caused by ischemic stroke and build a gene-enzyme-biomarker network to explore the mechanism of ESL treatment on ischemic stroke further. MATERIALS AND METHODS: The urinary metabolomics strategy was developed by combining UPLC-Q-TOF/MS with multivariate data analysis. The gene-enzyme-biomarker network was built by Cytoscape 3.6.0 on the basis of the potential biomarkers filtered out via urinary metabolomic analysis. Then, the potential target enzymes of ESL in the treatment of ischemic stroke were selected for further validation analysis via the ELISA kits. RESULTS: A total of 42 biomarkers associated with ischemic stroke have been identified, among which 38 species can be adjusted by ESL, including 5'-methylthioadenosine, prostaglandin A2, l-methionine, aldosterone, 11b-hydroxyprogesterone, prostaglandin E3, dehydroepiandrosterone, taurine, 5-methoxyindoleacetate, and p-cresol glucuronide. These biomarkers were involved in several metabolic pathways, including taurine and hypotaurine, arachidonic acid, cysteine and methionine, steroid hormone biosynthesis, tryptophan, and tyrosine metabolism pathways. The gene-enzyme-biomarker network was built, and three predicted target proteins, including cyclooxygenase-2 (COX-2), monoamine oxidase (MAO), and nitric oxide synthase (NOS), were selected as the potential target enzymes for ESL in ischemic stroke treatment. CONCLUSIONS: All results showed that ESL can play a therapeutic role in treating ischemic stroke through different pathways. This study will provide an overall view of the mechanism underlying the action of ESL against ischemic stroke.

Non-target metabonomic method provided new insights on the therapeutical mechanism of Gancao Fuzi decoction on rheumatoid arthritis rats.

Gancao Fuzi decoction (GFD) is a classic Chinese medicine formula for the treatment of rheumatic and rheumatoid arthritis. The main active components of GFD are alkaloids, flavonoids and saponins. This study aimed to clarify the pharmacodynamic effects of the active components in GFD and investigate the mechanism of them treating rheumatoid arthritis rats by the method of metabonomics. Seven groups were studied, named as the normal group (NG), the model group (MG), the Gancao Fuzi decoction treatment group (GFDe), the alkaloids group (ALK), the compatibility of alkaloids with flavonoids group (AF), the compatibility of alkaloids with saponins group (AS) and the compatibility of alkaloids with flavonoids and saponins group (AFS), respectively. Firstly, the anti-inflammatory and analgesic effects of these groups were studied. Besides, urinary metabonomics based on ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was employed for delineation of metabolic alterations in the rats. Based on our results, it is concluded that AFS showed better anti-inflammatory and analgesic activities in GFD. Urinary metabonomic study and multivariate statistical analyses were used to investigate the mechanism of different groups. 26 potential biomarkers have been identified. By the analysis of heat map combined with score plot, the AFS group was the closest group to the NG group after treatment in GFD. The changes of urinary endogenous metabolites showed that AFS exhibited better effect on regulating the taurine and hypotaurine metabolism, phenylalanine metabolism, TCA cycle, tryptophan metabolism, fatty acid metabolism, vitamin B6 metabolism, arginine and proline metabolism and purine metabolism pathways. The pharmacodynamics results showed that three components of flavonoids, saponins and alkaloids in GFD played an overall efficacy. Metabonomics studies showed that the compatibility of three components in GFD achieved the therapeutic effect by regulating the perturbations of multiple metabolic pathways.

Systematic studies on the in vivo substance basis and the pharmacological mechanism of Acanthopanax Senticosus Harms leaves by UPLC-Q-TOF-MS coupled with a target-network method.

The leaves of Acanthopanax Senticosus Harms (ASL) can be used as a food ingredient and also as raw materials for making tea and wine. As a traditional Chinese medicine (TCM), ASL has demonstrated significant effects in the treatment of ischemic stroke, but the substance basis and the pharmacological mechanism of ASL are unclear. In this study, a sensitive and rapid method was constructed for the separation and identification of the absorbed prototype components and metabolites from ASL in rat plasma and brain using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A database of ASL active ingredients was established, which comprised 27 prototype ingredients and 20 metabolites from the rat plasma and 10 prototype ingredients and 7 metabolites from the rat brain. A comprehensive and effective target-network pharmacological method for tracing co-related targets and pathways between ASL and ischemic stroke was also set up. As a result, 34 targets and 30 pathways were obtained. TNF, NF-κB, IL-6, IL-1B, ICAM, and MMP-9 targets are all critical factors related to ischemic stroke, while the NF-κB signaling pathway, MAPK signaling pathway, TNF signaling pathway, and arachidonic acid metabolism play significant roles in the development of ischemic stroke. The visualized relationship between ASL and ischemic stroke was demonstrated by compound-target networks and compound-target-pathway networks, which revealed the therapeutic targets around the signaling pathways of ASL in the treatment of ischemic stroke. This research method will open a window for the mechanistic studies of TCM in the treatment of diseases.