Strictosamide ameliorates LPS-induced acute lung injury by targeting ERK2 and mediating NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) ranks among the deadliest pulmonary diseases, significantly impacting mortality and morbidity. Presently, the primary treatment for ALI involves supportive therapy; however, its efficacy remains unsatisfactory. Strictosamide (STR), an indole alkaloid found in the Chinese herbal medicine Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Wutan), has been found to exhibit numerous pharmacological properties, particularly anti-inflammatory effects. AIM OF THE STUDY: This study aimes to systematically identify and validate the specific binding proteins targeted by STR and elucidate its anti-inflammatory mechanism in lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Biotin chemical modification, protein microarray analysis and network pharmacology were conducted to screen for potential STR-binding proteins. The binding affinity was assessed through surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and molecular docking, and the anti-inflammatory mechanism of STR in ALI treatment was assessed through in vivo and in vitro experiments. RESULTS: Biotin chemical modification, protein microarray and network pharmacology identified extracellular-signal-regulated kinase 2 (ERK2) as the most important binding proteins among 276 candidate STR-interacting proteins and nuclear factor-kappaB (NF-κB) pathway was one of the main inflammatory signal transduction pathways. Using SPR, CETSA, and molecular docking, we confirmed STR's affinity for ERK2. In vitro and in vivo experiments demonstrated that STR mitigated inflammation by targeting ERK2 to modulate the NF-κB signaling pathway in LPS-induced ALI. CONCLUSIONS: Our findings indicate that STR can inhibit the NF-κB signaling pathway to attenuate LPS-induced inflammation by targeting ERK2 and decreasing phosphorylation of ERK2, which could be a novel strategy for treating ALI.

Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Neurodegenerative diseases (NDs) have posed significant challenges to public health, and it is crucial to understand their mechanisms in order to develop effective therapeutic strategies. Recent studies have highlighted the potential role of selenium in ND pathogenesis, as it plays a vital role in maintaining cellular homeostasis and preventing oxidative damage. However, a comprehensive analysis of the association between selenium and NDs is still lacking. METHOD: Five public databases, namely PubMed, Web of Science, EMBASE, Cochrane and Clinical Trials, were searched in our research. Random model effects were chosen, and Higgins inconsistency analyses (I2), Cochrane's Q test and Tau2 were calculated to evaluate the heterogeneity. RESULT: The association of selenium in ND patients with Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) was studied. A statistically significant relationship was only found for AD patients (SMD = -0.41, 95% CI (-0.64, -0.17), p < 0.001), especially for erythrocytes. However, no significant relationship was observed in the analysis of the other four diseases. CONCLUSION: Generally, this meta-analysis indicated that AD patients are strongly associated with lower selenium concentrations compared with healthy people, which may provide a clinical reference in the future. However, more studies are urgently needed for further study and treatment of neurodegenerative diseases.

Intestinal Escherichia coli and related dysfunction as potential targets of Traditional Chinese Medicine for respiratory infectious diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has saved countless lives and maintained human health over its long history, especially in respiratory infectious diseases. The relationship between the intestinal flora and the respiratory system has been a popular research topic in recent years. According to the theory of the "gut-lung axis" in modern medicine and the idea that "the lung stands in an interior-exterior relationship with the large intestine" in TCM, gut microbiota dysbiosis is a contributing factor to respiratory infectious diseases, and there is potential means for manipulation of the gut microbiota in the treatment of lung diseases. Emerging studies have indicated intestinal Escherichia coli (E. coli) overgrowth in multiple respiratory infectious diseases, which could exacerbate respiratory infectious diseases by disrupting immune homeostasis, the gut barrier and metabolic balance. TCM is an effective microecological regulator, that can regulate the intestinal flora including E. coli, and restore the balance of the immune system, gut barrier, and metabolism. AIM OF THE REVIEW: This review discusses the changes and effects of intestinal E. coli in respiratory infection, as well as the role of TCM in the intestinal flora, E. coli and related immunity, the gut barrier and the metabolism, thereby suggesting the possibility of TCM therapy regulating intestinal E. coli and related immunity, the gut barrier and the metabolism to alleviate respiratory infectious diseases. We aimed to make a modest contribution to the research and development of new therapies for intestinal flora in respiratory infectious diseases and the full utilization of TCM resources. Relevant information about the therapeutic potential of TCM to regulate intestinal E. coli against diseases was collected from PubMed, China National Knowledge Infrastructure (CNKI), and so on. The Plants of the World Online (https://wcsp.science.kew.org) and the Plant List (www.theplantlist.org) databases were used to provide the scientific names and species of plants. RESULTS: Intestinal E. coli is a very important bacterium in respiratory infectious diseases that affects the respiratory system through immunity, the gut barrier and the metabolism. Many TCMs can inhibit the abundance of E. coli and regulate related immunity, the gut barrier and the metabolism to promote lung health. CONCLUSION: TCM targeting intestinal E. coli and related immune, gut barrier, and metabolic dysfunction could be a potential therapy to promote the treatment and prognosis of respiratory infectious diseases.

Ethnobotany, phytochemistry and pharmacological properties of Fagopyri Dibotryis Rhizoma: A review.

Fagopyri Dibotryis Rhizoma (FDR) is an effective Chinese herbal medicine with a long history of use in China. FDR is effective in heat clearing and detoxifying, promotion of blood circulation, relieving carbuncles, dispelling wind, and removing dampness. Its seeds also have high nutritional value, are rich in protein, and contain a variety of mineral elements and vitamins. Therefore, FDR is considered a natural product with medical and economic benefits, and its chemical composition and pharmacological activity are of interest to scientists. The current review provides an overview of the available scientific information on FDR, particularly its botany, chemical constituents, and pharmacological activities. Various sources of valid and comprehensive relevant information were consulted, including the China National Knowledge Infrastructure, Web of Science, and PubMed. Among the keywords used were "Fagopyri Dibotryis Rhizoma", "botanical features", "chemical composition", and "pharmacological activity" in combination. Various ailments are treated with FDR, such as diabetes, tumor, sore throat, headache, indigestion, abdominal distension, dysentery, boils, carbuncles, and rheumatism. FDR is rich in organic acids, tannins, flavonoids, steroids, and triterpenoids. Experiments performed in vitro and in vivo showed that FDR extracts or fractions had a wide range of pharmacological activities, including antitumor, anti-inflammatory, immunomodulatory, antioxidant, antimicrobial, and antidiabetic. The current review provides an integrative perspective on the botany, phytochemistry and pharmacological activities of FDR. FDR may be used as a medicine and food. Based on its chemical composition and pharmacological effects, the main active ingredients of FDR are organic acids, tannins, and flavonoids, and it has obvious antitumor pharmacological activity against a variety of malignant tumors. Therefore, FDR is worthy of further study and application as a potential antitumor drug.

Synthesis and Characterization of a New Copolymer Consisting of Polyamide 1210 and Reactive Phosphorus-Nitrogen Flame-Retardant.

The thermal stability and reactivity of organophosphorus flame-retardants play a critical role in synthesizing copolymerized flame-retardant polyamides. Herein, this work successfully synthesizes a flame-retardant CEPPA-DDA salt (CDS) with both good thermal stability and high reactivity by reacting 2-carboxyethyl phenyl phosphonic acid (CEPPA) with 1,12-dodecanediamine (DDA). Flame-retardant polyamide 1210 (FRPA) is further prepared by copolymerizing the CDS, DDA, and sebacic acid (SEA). The test results show that the introduction of CDS can significantly improve the flame-retardant properties of FRPA. Specifically, the flame-retardant polyamide 1210 (FRPA-7) with 7 wt% CDS addition can reach V-0 grade according to UL-94 standard, accompanying limiting oxygen index value of 30.2% and tensile strength of 38.62 MPa. Compared with pure polyamide 1210, the peak heat release rate and total heat release rate of FRPA-7 reduce by 24.11% and 9.40%, respectively. This study provides a simple strategy to prepare flame-retardant polyamides with high flame retardancy and good mechanical properties, which are expected to show great potentials in future industrial applications.

Nauclea officinalis: A Chinese medicinal herb with phytochemical, biological, and pharmacological effects.

Nauclea officinalis (N. officinalis), a medicinal plant of the genus Nauclea in the family Rubiaceae, is used in the treatment of fever, pneumonia, pharyngolaryngitis, and enteritis in China. Extracts of N. officinalis include alkaloids, phenolic acids, pentacyclic triterpenoids, and flavonoids, which exert all kinds of pharmacological effects, for instance anti-inflammatory, anti-tumor, antibacterial, and antiviral and therefore show good effectiveness. To gain a comprehensive and deep understanding, the medicinal chemistry and chemical biology of N. officinalis are summarized in this review to provide a theoretical basis. The pharmacological effects were reviewed to provide evidence or insights into potential opportunities for further studies and medicinal exploitation of N. officinalis.

Clinical acupuncture therapy for femur head necrosis: A protocol for systematic review and meta analysis.

BACKGROUND: Femur Head Necrosis (FHN) is a common clinical joint orthopedic-related disease, and its incidence is increasing year by year. Symptoms include dull pain and dull pain in the affected hip joint or its surrounding joints. More severely, it can lead to limited joint movement and inability to walk autonomously. Surgical treatment has many sequelae. The high cost makes it unaffordable for patients, and the side effects of drug treatment are unknown. A large number of clinical studies have shown that acupuncture is effective in treating femoral head necrosis. Therefore, this systematic review aims to explore the safety and effectiveness of acupuncture in the treatment of femoral head necrosis. METHODS: We will conduct a comprehensive literature search in Medline, PubMed, Cochrane Database of Systematic Reviews, Embase, Chinese Biomedical Literatures Database (CBM), China National Knowledge Infrastructure (CNKI), Wang FangDatabase (WF), Chinese Scientific Journal Database (VIP) from inception to May 2021 without any language restriction. In addition, we will retrieve the unpublished studies and the references of initially included literature manually. The two reviewers will identify studies, extract data, and assess the quality independently. The outcomes of interest include: total effective rate; the total nasal symptom score; Hip function (Hip Harris joint score, WOMAC hip score, hip joint Lequesne index score, Merle D 'Aubigne and hip joint Postel score); Adverse events. Randomized clinical trials will be collected, methodological quality will be evaluated using the Cochrane risk-of-bias assessment tool, and the level of evidence will be rated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Meta-analysis will be performed using RevMan 5.4.0 software. The heterogeneity test will be conducted between the studies, P < .1 and I2 > 50% are the thresholds for the tests. We will utilize the fixed effects model or the random effects model according to the size of heterogeneity. RESULTS: The meta-analysis program will systematically evaluate the efficacy and safety of acupuncture in the treatment of FHN patients. CONCLUSION: This study will investigate whether acupuncture can be used as one of the non-surgical and non-pharmacological therapies for the prevention or treatment of FHN. TRIAL REGISTRATION NUMBER: INPLASY202150035.

The efficacy and safety of cupping therapy for treating of intractable peripheral facial paralysis: A protocol for systematic review and meta-analysis.

BACKGROUND: Peripheral facial paralysis (PFP) is a common clinical neurological disease and the incidence of intractable peripheral facial paralysis is on the rise. Symptoms include crooked mouth and eyes, tearing and shallow nasolabial folds. The disease seriously affects the physical and mental health of patients. At present, a large number of clinical studies have shown that cupping is effective in treating intractable peripheral facial paralysis (IPFP). Therefore, the purpose of this review is to evaluate the effectiveness and safety of cupping in the treatment of refractory peripheral facial paralysis. METHODS: We will conduct a comprehensive and systematic search of relevant documents in the following databases: Medline, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Chinese Biomedical Literatures Database, China National Knowledge Infrastructure (CNKI), Wang Fang Database, Chinese Scientific Journal Database from inception to February 2021 without any language restriction. The 2 reviewers will be independently completed select research, extract data, evaluate research quality and use the Cochrane risk of bias tool to assess methodological quality. Using revman5.4 software for statistical analysis. The degree of heterogeneity will be Determined through heterogeneity test, to definite whether to adopt a random effects model or a fixed-effects model. RESULTS: The protocol for the meta-analysis will systematically evaluate the efficacy and safety of cupping therapy for intractable peripheral facial paralysis patients. CONCLUSION: This study will explore whether or not cupping therapy can be used as one of the non-drug therapies to prevent or treat intractable peripheral facial paralysis.

Effectiveness and safety of massage in the treatment of obesity: A protocol for systematic review and meta-analysis.

BACKGROUND: Obesity has become one of the largest chronic diseases in the world. It is a chronic metabolic disease caused by various factors. In recent years, massage has been used more and more widely in the treatment of obesity diseases. However, the effectiveness and safety of massage in the treatment of adult obesity are still unclear. The purpose of this study is to evaluate the effectiveness and safety of massage in the treatment of adult obesity. METHODS: We will conduct a comprehensive review in Medline, PubMed, Cochrane System Evaluation Database, embbase, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wang Fang Database, Chinese Science Journal Database. There is no language restriction for the literature search from its establishment to February 2021. In addition, we will manually search for references to unpublished studies and originally included articles. Reviewers will identify the research, extract the data, and independently assess the quality. Results of interest include: total effective rate; total nasal symptom score; rhinitis quality-of-life questionnaire; visual analog scale; laboratory test indicators: IgE, IL6, IL10, or TNF-α levels; recurrence rate; adverse events. Randomized clinical trials will be collected, the Cochrane bias risk assessment tool will be used to assess methodological quality, and recommendations, evaluation, development, and evaluation methods will be used to assess the level of evidence. The meta-analysis will be performed using RevMan 5.4.0 software. A heterogeneity test will be conducted between studies, and P <.1 and I2> 50% are the thresholds for testing. According to the degree of heterogeneity, we will use a fixed effects model or a random effects model. RESULTS: The results of this study will provide sufficient evidence to judge whether massage is an effective and safe treatment for adult obesity. CONCLUSIONS: This study will provide evidence to determine whether massage is an effective intervention for Adult obesity. The research results will also be published in a peer-reviewed journal. INPLASY REGISTRATION NUMBER: INPLASY 202120061.

Hepatoprotective Effect of Citrus aurantium L. Against APAP-induced Liver Injury by Regulating Liver Lipid Metabolism and Apoptosis.

Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms, but it always causes liver injury when overdosed. Zhishi, dried young fruit of Citrus aurantium L., is a famous Citrus herbal medicine in Asian countries which is rich in dietary phenolic substances. In this study, the mechanism of Zhishi protected against APAP-induced liver injury was studied more deeply by metabolomic strategy and pharmacological study. The metabolomics results demonstrated that Zhishi can prevent the APAP-induced liver injury model by regulating liver metabolic disorders in glycerophospholipid metabolism, fatty acid biosynthesis and glycerolipid metabolism. Moreover, it is confirmed that Zhishi blocked apoptosis of APAP-induced BRL-3A cell by simultaneously regulating p53 up-regulated apoptosis regulator (PUMA), AMPK-SIRT1 and JNK1 signaling pathways. Our findings indicated that Zhishi exhibited a hepaprotective effect against APAP-induced liver necrosis by inhibiting the PUMA and reversing disorder of liver lipid metabolism which could assist in improving the clinical outcomes of chemical-induced liver injury.

Vascular Protection of TPE-CA on Hyperhomocysteinemia-induced Vascular Endothelial Dysfunction through AA Metabolism Modulated CYPs Pathway.

A high concentration of homocysteine (Hcy) in plasma induces vascular endothelial dysfunction, and it may ultimately accelerate the development of cardiovascular diseases (CVDs). Although several B vitamins have been clinically applied for hyperhomocysteinemia (HHcy) treatment, the outcomes are not satisfied due to their limited therapeutic mechanism. Hence, in order to improve the curative effect, development of new effective therapeutic strategies should be put on the agenda. Total phenolic extracts of Citrus aurantium L. (TPE-CA) is a naturally obtained phenolic mixture, mainly containing flavones, flavanones and their glycosyl derivatives, flavonols, polymethoxyflavones and coumarins. Previous reports indicated that bioactive phenolic compounds possessed potent vascular protective effects and regarded as a protective agent against CVDs. Intriguingly, the exact mechanism underlying the suppressed effects of TPE-CA on HHcy could assist in revealing their therapy on CVDs. Here, the multi-targeted synergistic mechanism of TPE-CA on HHcy-induced vascular endothelial dysfunction was uncovered in a deduced manner. TPE-CA treatment exhibited an obvious superiority than that of B vitamins treatment. Network pharmacology was employed to identify the interrelationships among compounds, potential targets and putative pathways. Further experimental validation suggested that the treatment of TPE-CA for HHcy could not only effectively reduce the Hcy level in plasma through up-regulating transsulfuration pathway in Hcy metabolism, but also restore the HHcy-induced vascular endothelial dysfunction by activating cytochrome P450 enzymes (CYPs) epoxygenase signal cascades and inhibiting CYPs hydroxylase signal cascades in arachidonic acid (AA) metabolism.

Synergistic enhancement and hepatoprotective effect of combination of total phenolic extracts of Citrus aurantium L. and methotrexate for treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder characterized by joint destruction and bone damage. Methotrexate (MTX) is recommended as the first-line disease-modifying agent for the treatment of RA. However, the clinical efficacy of MTX is limited due to its low response and side effects, especially hepatotoxicity. Total phenolic extracts of Citrus aurantium L. (TPE-CA) are rich in dietary bioactive flavonoids, which show beneficial effects on liver health and are regarded as therapeutic tools against inflammatory diseases. In this study, the efficacy of MTX, alone or in combination with TPE-CA, for the treatment of collagen-induced arthritis and protection against hepatic injury in rats was investigated. TPE-CA and MTX combination effectively reduced the inflammatory symptoms and joint damage by inhibiting the NF-κB pathway. Moreover, TPE-CA significantly ameliorated MTX-induced chronic hepatic injury by enhancing antioxidant enzymes activities, suppressing hepatic cytochrome P450 2E1 expression, and modulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. This combination regimen not only provided synergistic enhancement but also exhibited hepatoprotective effect against chemically induced chronic hepatotoxicity. This could be an alternative strategy to improve the low response of MTX in RA treatment.