Hawthorn leaf flavonoids alleviate the deterioration of atherosclerosis by inhibiting SCAP-SREBP2-LDLR pathway through sPLA2-â ¡A signaling in macrophages in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Hawthorn leaves are a combination of the dried leaves of the Rosaceae plants, i.e., Crataegus pinnatifida Bge. or Crataegus pinnatifida Bge. var. major N. E. Br., is primarily cultivated in East Asia, North America, and Europe. hawthorn leaf flavonoids (HLF) are the main part of extraction. The HLF have demonstrated potential in preventing hypertension, inflammation, hyperlipidemia, and atherosclerosis. However, the potential pharmacological mechanism behind its anti-atherosclerotic effect has yet to be explored. AIM OF THE STUDY: The in vivo and in vitro effects of HLF on lipid-mediated foam cell formation were investigated, with a specific focus on the levels of secreted phospholipase A2 type IIA (sPLA2-II A) in macrophage cells. MATERIALS AND METHODS: The primary constituents of HLF were analyzed using ultra-high performance liquid chromatography and liquid chromatography-tandem mass spectrometry. In vivo, HLF, at concentrations of 5 mg/kg, 20 mg/kg, and 40 mg/kg, were administered to apolipoprotein E knockout mice (ApoE-/-) fed by high-fat diet (HFD) for 16 weeks. Aorta and serum samples were collected to identify lesion areas and lipids through mass spectrometry analysis to dissect the pathological process. RAW264.7 cells were incubated with oxidized low-density lipoprotein (ox-LDL) alone, or ox-LDL combined with different doses of HLF (100, 50, and 25 µg/ml), or ox-LDL plus 24-h sPLA2-IIA inhibitors, for cell biology analysis. Lipids and inflammatory cytokines were detected using biochemical analyzers and ELISA, while plaque size and collagen content of plaque were assessed by HE and the Masson staining of the aorta. The lipid deposition in macrophages was observed by Oil Red O staining. The expression of sPLA2-IIA and SCAP-SREBP2-LDLR was determined by RT-qPCR and Western blot analysis. RESULTS: The chemical profile of HLF was studied using UPLC-Q-TOF-MS/MS, allowing the tentative identification of 20 compounds, comprising 1 phenolic acid, 9 flavonols and 10 flavones, including isovitexin, vitexin-4″-O-glucoside, quercetin-3-O-robibioside, rutin, vitexin-2″-O-rhamnoside, quercetin, etc. HLF decreased total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) levels in ApoE-/- mice (P < 0.05), reduced ox-LDL uptake, inhibited level of inflammatory factors, such as IL-6, IL-8, TNF-α, and IL-1ꞵ (P < 0.001), and alleviated aortic plaques with a thicker fibrous cap. HLF effectively attenuated foam cell formation in ox-LDL-treated RAW264.7 macrophages, and reduced levels of intracellular TC, free cholesterol (FC), cholesteryl ester (CE), IL-6, TNF-α, and IL-1ß (P < 0.001). In both in vivo and in vitro experiments, HLF significantly downregulated the expression of sPLA2-IIA, SCAP, SREBP2, LDLR, HMGCR, and LOX-1 (P < 0.05). Furthermore, sPLA2-IIA inhibitor effectively mitigated inflammatory release in RAW264.7 macrophages and regulated SCAP-SREBP2-LDLR signaling pathway by inhibiting sPLA2-IIA secretion (P < 0.05). CONCLUSION: HLF exerted a protective effect against atherosclerosis through inhibiting sPLA2-IIA to diminish SCAP-SREBP2-LDLR signaling pathway, to reduce LDL uptake caused foam cell formation, and to slow down the progression of atherosclerosis in mice.

Effects of different interventions on insomnia in adults: Systematic review and network meta-analysis.

OBJECTIVE: Insomnia is a common sleep disorder. There are many clinical-intervention methods for treating this condition, but thus far, the most effective method has not been determined. METHODS: We conducted a network meta-analysis by including random evidence of insomnia improvement in people over 18 years old, without other physical diseases. From January 1, 1990 to June 15, 2022, we searched multiple electronic databases for randomized controlled trials of different insomnia-related, clinical-intervention methods. R software was used to analyze 10 indices, in order to evaluate the effect of sleep improvement. Primary outcomes comprised Pittsburgh sleep quality-index (PSQI) scores and insomnia severity-index (ISI) scores. RESULTS: Finally, 122 randomized controlled trials were included in our study. For the PSQI scores, we found the sequence of intervention measures by effect to be as follows: electroacupuncture, acupuncture, repetitive transcranial magnetic stimulation (rTMS), essential oils, herbal medicine, traditional Western medicine, Tai Chi and Baduanjin, music, supplements, cognitive behavioral therapy for insomnia (CBT-I), and exercise. The results for ISI were similar to those for PSQI, but with slight differences. CONCLUSION: Our research results indicate that various measures have a certain effect on improving sleep, among which the effect of instruments is more prominent. The curative effect of placebo groups was better than that of blank control groups. There is essentially no statistical difference in detailed classification within the same intervention category.

The role of the chloroplast localised phosphate transporter GmPHT4;10 gene in plant growth, photosynthesis and drought resistance.

In view of the importance of inorganic phosphate to plant growth and development, the role of phosphate transporters responsible for absorption and transportation in crops has attracted increasing attention. In this study, bioinformatics analysis and subcellular localisation experiment showed that GmPHT4;10 is a member of PHT4 subfamily of phosphate transporters and located in chloroplasts. The gene was induced by phosphate deficiency and drought, and was the highest in leaves. After GmPHT4;10 gene was replenished to AtPHT4;5 gene deletion mutant lines (atpht4;5 ), the phenotype of the transgenic lines was basically recovered to the level of wild-type, but there were significant differences in phosphate content and photosynthetic indicators between wild-type and revertant lines. Meanwhile, the difference of proline content and catalase activity between the two lines also indicated that GmPHT4;10 gene and its orthologous gene AtPHT4;5 were different in drought resistance and drought resistance mechanism. After overexpression of GmPHT4;10 gene in Arabidopsis thaliana , more phosphate and proline were accumulated in chloroplasts and catalase activity was increased, thus improving photosynthesis and drought resistance of plants. The results further supplement the cognition of PHT4 subfamily function, and provides new ideas and ways to improve photosynthesis by revealing the function of chloroplast phosphate transporter.

Phenolic compound profile and gastrointestinal action of Solanaceae fruits: Species-specific differences.

In this study, the presence of phenolic compounds derived from four Solanaceae fruits (tomato, pepino, tamarillo, and goldenberry) during gastrointestinal digestion and the effect of these compounds on human gut microbiota was investigated. The results indicated that the total phenolic content of all Solanaceae fruits were increased during digestion. Furthermore, the targeted metabolic analysis identified 296 compounds, of which 71 were changed after gastrointestinal digestion in all Solanaceae fruits. Among these changed phenolic compounds, 51.3% phenolic acids and 91% flavonoids presented higher bioaccessibility in pepino and tamarillo, respectively. Moreover, higher levels of glycoside-formed phenolic acids, including dihydroferulic acid glucoside and coumaric acid glucoside, were found in tomato fruits. In addition, tachioside showed the highest bioaccessibility in goldenberry fruits. The intake of Solanaceae fruits during the in vitro fermentation decreased the Firmicutes/Bacteroidetes ratio (F/B) compared with the control (∼15-fold change on average), and goldenberry fruits showed the best effect (F/B = 2.1). Furthermore, tamarillo significantly promoted the growth of Bifidobacterium and short-chain fatty acids production. Overall, this study revealed that Solanaceae fruits had different phenolic compound profiles and health-promoting effects on the gut microbiota. It also provided relevant information to improve the consumption of Solanaceae fruits, mainly tamarillo and goldenberry fruits, due to their gut health-promoting properties, as functional foods.

Total saponins from Panax japonicus reduce inflammation in adipocytes through the miR155/SOCS1/NFκB signaling pathway.

BACKGROUND: The rising incidence of metabolic diseases due to chronic inflammation in the adipose tissue has been attributed to factors such as high fat diet (HFD). Previous studies have demonstrated that the total saponins from Panax japonicus (TSPJ) can reduce HFD-induced adipocyte inflammation, but the underlying mechanism remains unclear. In this work, we explored the molecular mechanism by which TSPJ reduces inflammation response in adipocytes. METHODS: We first established C57BL/6 mouse and 3T3-L1 adipocyte models. Lentiviruses packaged with the plasmids were injected into mice through the tail vein or into adipocytes to generate the in vivo and in vitro models with miR155 knockdown and overexpression. The mice were fed with HFD to trigger inflammation and administered TSPJ (25 mg/kg∙d and 75 mg/kg∙d) by gavage. The adipocytes were treated with palmitic acid (PA) to trigger inflammation response, then treated with TSPJ (25 µg/ml and 50 µg/ml). Finally, the expression of miR155, inflammatory factors, SOCS1, and NFκB pathway-related proteins was explored. RESULTS: TSPJ significantly inhibited the expression of inflammation-related genes and the miR155 expression in adipocytes both in vitro and in vivo. The dual luciferase reporter gene assay revealed that miR155 mediated the downregulation of SOCS1. TSPJ significantly inhibited and upregulated the phosphorylation of the NFκB protein and the SOCS1 proteins, respectively. CONCLUSION: TSPJ inhibits miR155 to upregulate the SOCS1 expression, which subsequently inhibits the NFκB signaling pathway, thereby mitigating the inflammatory response in the adipocytes of HFD mice.

Different Chinese herbal medicine therapy for idiopathic thrombocytopenic purpura: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is a common immune system and blood system disease in clinical practice, and it is a hemorrhagic disease caused by immune factors causing platelet destruction and decreasing number of platelets. There is currently no effective treatment plan for ITP. At this stage, glucocorticoid and gamma globulin are mostly used in the treatment of ITP, and some patients use splenectomy to achieve therapeutic purposes, but the various treatment methods are inadequate. At this stage, a large number of randomized controlled studies have reported that Chinese herbal medicine has achieved good curative effect in the treatment of ITP. However, due to the variety of Chinese herbal medicine, there has been no evidence of the effectiveness and safety of Chinese herbal medicine in the treatment of ITP. Because of the above reasons, this study uses the network meta-analysis method based on Bayesian method to compare the clinical efficacy and safety of different kinds of Chinese herbal medicine in the treatment of ITP through direct and indirect comparison, in order to provide evidence-based medical support for the treatment of ITP with Chinese herbal medicine. METHODS: This study uses the method of combining free words with theme words, and using computer to retrieve PubMed, EMbase, The Cochrane Library, WANFANG Database, CNKI, and VIP Database, etc, to collect the randomized control studies on Chinese herbal medicine in the treatment of ITP. The retrieval time is from the establishment of each database to January 2021, and the retrieval languages are Chinese and English. Two researchers independently read the title, abstract and full text of the article to determine whether it is included in the literature; In the event of a disagreement, a third researcher will join the discussion to resolve the disagreement; For the literature that lacks information, trying to contact the original author of the document to supplement it. The literature quality evaluation carried out by using the Stata 14.0 software to draw network and funnel plots, in accordance with the quality evaluation criteria of version 5.1.0 of the Cochrane System Evaluation Manual. Statistical analysis is performed by using ADDIS 1.16.8 software based on the Bayesian model. RESULTS: This study will compare the clinical efficacy and safety of different types of Chinese herbal medicine in the treatment of idiopathic thrombocytopenic purpura through the method of network meta-analysis, and rank the different types of Chinese herbal medicine according to their effectiveness, and the results will be published in a peer-reviewed, high-quality academic journal. CONCLUSION: This study will find effective and safe Chinese herbal medicine for clinical treatment of ITP from the perspective of evidence-based medicine, and benefit more ITP patients.