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Tanshinone I from tanshen has been used in traditional Chinese medicine for treating cardiovascular diseases and inflammatory diseases. Given the link between inflammation and Type 2 diabetes mellitus (T2DM), we suspect that tanshinone I may have a beneficial effect on T2DM. This study was to investigate the potential effects of tanshinone I on T2DM and its underlying mechanism. T2DM was thus induced in Sprague-Dawley (SD) rats using streptozotocin (STZ) and high-fat diet. It was observed that T2DM rats had higher levels of total cholesterol (TC), nonesterified fatty acids (NEFAs), total triglyceride (TG) and total low density lipoprotein cholesterol (LDL-C) compared with normal, healthy SD rats. Treatment with tanshinone I decreased these levels and lowered blood glucose level in T2DM rats. In addition, enzyme-linked immunosorbent assay (ELISA) analysis showed that T2DM rats had elevated levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Furthermore, Western blot analysis revealed that T2DM rats had enhanced nuclear translocation of NF-κB as well as elevated phosphorylation of Ser307 in IRS-1(insulin receptor substrate 1). Treatment by tanshinone I lowered the levels of IL-6 and TNF-α, decreased nuclear translocation of NF-κB as well as phosphorylation of Ser307 in IRS-1. These results demonstrated that tanshinone I could alleviate T2DM syndrome in rats. [ABSTRACT FROM AUTHOR]

This study was aimed to explore the mechanism of rutaecarpine (RUT) on ethanol-induced gastric ulcer (GU) in mice by integrated approaches. At first, the efficacy was determined through the macroscopic and microscopic state of stomach tissue and the expression levels of GU-related factors. Then, the serum metabolomics method based on UPLC-Q-TOF/MS was used to explore the specific metabolites and metabolic pathways. Finally, the upstream key protein targets of these specific metabolites were analyzed by network pharmacology and verified by PCR to explore the potential mechanism. RUT alleviated the histological and pathological damage of gastric tissue caused by ethanol, and could remarkably ameliorate the level of GU-related factors. Subsequently, a total of 7 potential metabolites involved in 9 metabolic pathways were identified by metabolomics analysis. Then, a 'component-targets-metabolites' interaction network was constructed, and therefore 4 key target proteins (PLA2G1B, PDE5A, MIF and SRC) that may regulate the specific metabolites were obtained. This case was further verified by the results of PCR. ALL the above results strongly demonstrated that RUT exerted a gastroprotective effect against GU. And it is the first time to combine metabolomics combined with network pharmacology to elucidate the mechanism of RUT on GU, which may be related to the regulation of energy metabolism, oxidative stress, and inflammation, and these pathways may be regulated through the upstream protein PLA2G1B, PDE5A, MIF and SRC. [Display omitted] • RUT notably alleviated damage of gastric tissue triggered by ethanol. • RUT could remarkably ameliorate the level of GU-related factors. • potential metabolites involved in 9 metabolic pathways were identified. • 4 key target proteins that may regulate the specific metabolites were obtained. • The mechanism may be related to energy metabolism, oxidative stress, and inflammation. [ABSTRACT FROM AUTHOR]

Ferroptosis, an iron-dependent form of regulated cell death, was recently demonstrated to be closely associated with the immune system. Regulators of ferroptosis may be the cells and secretions of the immune system. Ferroptosis has contributed to the progression of various diseases, namely, cancer, ischemia, and degenerative diseases. However, research on the relationship between ferroptosis and asthma remains fragmented. Non-immune cells associated with asthma are also closely associated with ferroptosis. Further studies on cross-linking asthma inflammation with ferroptosis signaling pathways could help identify several key molecules, known as ferroptosis regulators, that regulate asthma. Ferroptosis provides a new perspective to interpret and understand the manifestations of asthma, potential drug discovery targets, and new therapeutic options to effectively intervene in the imbalance caused by abnormal inflammation in asthma. Thus, the pathogenesis of ferroptosis and its contribution to the pathogenesis of asthma is essential in deepening the understanding and improving the prognosis and cure rate of the patients. Herein, we introduce the main molecular mechanisms of ferroptosis and asthma, describe the relationship between ferroptosis and asthma based on their common regulatory cells or molecules, and discuss potential drug discovery targets and therapeutic applications of ferroptosis in the context of immunomodulation and symptom alleviation. [Display omitted] • Ferroptosis provides potential drug discovery targets for asthma. • A systemic relationship between ferroptosis and asthma is aimed at comprehensively explaining the mechanism of asthma occurrence and development. • The crosslinked pathway of ferroptosis and autophagy also contributes to explore the regulation of ferroptosis beneficial for patients with asthma. [ABSTRACT FROM AUTHOR]

Although considerable advance has been made in diagnosing and treating, asthma is still a serious public health challenge. Traditional Chinese medicine (TCM) is an effective therapy of complementary and alternative medicine. More and more scientific evidences support the use of TCM for asthma treatment, and active ingredients from Chinese medicine plants are becoming a hot issue. To summarize the frontier knowledge on the function and underlying mechanisms of the active ingredients in asthma treatments and provide a fully integrated, reliable reference for exploring innovative treatments for asthma. The cited literature was obtained from the PubMed and CNIK databases (up to September 2020). Experimental studies on the active ingredients of Chinese medicine and their therapeutic mechanisms were identified. The key words used in the literature retrieval were "asthma" and "traditional Chinese medicine" or "Chinese herbal medicine". The literature on the active ingredients was then screened manually. We summarized the effect of these active ingredients on asthma, primarily including the effect through which these ingredients can regulate the immunologic equilibrium mechanism by acting on a number of signalling pathways, such as Notch, JAK-STAT-MAPK, adiponectin-iNOS-NF-κB, PGD2-CRTH2, PI3K/AKT, Keap1-Nrf2/HO-1, T-bet/Gata-3 and Foxp3-RORγt, thereby regulating the progression of asthma. The active ingredients from Chinese medicine have multilevel effects on asthma by regulating the immunologic equilibrium mechanism or signalling pathways, giving them great clinical value. However, the safety and functional mechanism of these ingredients still must be further determined. [Display omitted] ● Active ingredients of TCM are natural products with low toxicity. ● TCM origin from a variety of sources and have potential in anti-inflammatory. ● Biological effects of TCM are mediated by modulation on multiple signaling pathways. ● TCM related anti-inflammatory effect without instigating systemic immunosuppression. [ABSTRACT FROM AUTHOR]

• Acupuncture was effective in attenuation of AHR, mucus secretion and airway inflammation in OVA-induced mouse asthma model. • Suppression of SLC3A2 and ATP1A3 expression contributes to the inhibitory role of acupuncture on airway inflammation. • Acupuncture induced reduction of MDA level and increase of GSH and SOD levels in the lung tissue of OVA-induced mouse asthma model. Asthma is a chronic airway inflammatory disease and acupuncture is frequently used in patients suffering from asthma in clinic. However, the regulatory mechanism of acupuncture treatment in asthma is not fully elucidated. We sought to investigate the effectiveness of acupuncture on asthma and the associated regulatory mechanism. An ovalbumin (OVA)-induced mouse asthma model was established and the effect of acupuncture on airway hyperresponsiveness (AHR), mucus hypersecretion and inflammation was assessed. Tandem mass tag (TMT)-based quantitative proteomics analysis of lung tissue and bioinformatics analysis were performed. Our results revealed that the OVA-induced mouse asthma model was successfully established with the significantly elevated AHR to methacholine (Mch), and acupuncture was effective in attenuation of AHR to Mch, peribronchial and perivascular inflammation and mucus production. The inflammatory cells around the airways, mucous secretion as well as levels of IgE, CCL5, CCL11, IL-17A in bronchoalveolar lavage fluid (BALF) and IL-4, IL-5 and IL-13 levels in serum were siginificantly inhibited by acupuncture. TMT-based quantitative proteomics analysis found that a total of 6078 quantifiable proteins were identified, and 564 (334 up-regulated and 230 down regulated) differentially expressed proteins (DEPs) were identified in OVA-induced asthma model group (A) versus normal control group (NC). Acupuncture treatment resulted in 667 DEPs (416 up-regulated and 251 down regulated) compared with A group, and 86 overlapping DEPs were identified in NC, A and AA groups. Among the 86 overlapping DEPs, we identified 41 DEPs regulated by acupuncture. Based on the above data, we performed a systematic bioinformatics analysis of the 41 DEPs, and results showed that these 41 DEPs were predominantly related to 4 KEGG pathways including SNARE interactions in vesicular transport, ferroptosis, endocrine and other factor-regulated calcium reabsorption, and protein digestion and absorption. DEPs of SLC3A2 and ATP1A3 expression levels were verified by immumohistochemical staining. Mice in OVA-induced asthma model group had elevated SLC3A2 and ATP1A3 expression and acupuncture had the ability to downregulate SLC3A2 and ATP1A3 protein expression. Furthermore, acupuncture reduced the MDA level and increased the GSH and SOD levels in the lung tissue. Taken together, our data suggested that acupuncture was effective in treating asthma by attenuation of AHR, mucus secretion and airway inflammation, and the mechanism was associated with regulation of ferroptosis, SLC3A2 and ATP1A3 protein expression as well as oxidative stress. Results from our experiments revealed the anti-inflammatory effect of acupuncture in OVA-induced mouse asthma model, leading to a more effective approach to be chosen by patients in clinic. [ABSTRACT FROM AUTHOR]

• Ang-II has been reported to be involved in key events of the inflammatory process and tissue damage. • Cell-based therapy has been proved to be effective in the treatment SAP. • Pretreatment is the adaptation of MSCs to Ang-II in advance to mitigate endogenous Ang-II damage. • Ang-II is a good trigger for pretreating MSCs to enhance the paracrine release of growth factors (GFs). • Ang-II-MSCs can increase paracrine production of VEGF, improved the anti-apoptosis capacity of endothelial cells. Mesenchymal stem cells (MSCs) pretreatment is an effective route for improving cell-based therapy of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that the application of human umbilical cord-MSCs (hUC-MSCs) pretreated with angiotensin-II (Ang-II) might be a potential therapeutic approach for severe acute pancreatitis (SAP). Therefore, the effect of Ang-II pretreated hUC-MSCs on SAP was investigated in vitro and in vivo. In the present study, human umbilical cord-derived MSCs pretreated with or without Ang-II were delivered through the tail vein of rats 12 h after induction of SAP. Pancreatitis severity scores and serum lipase levels, as well as the levels of VEGF and VEGFR2 were evaluated. We found that the administration of Ang-II-MSCs significantly inhibited pancreatic injury, as reflected by reductions of pancreatitis severity scores, serum amylase and serum lipase levels. Furthermore, the reduced apoptotic rate and increased tube formation in human umbilical vein endothelial Cells (HUVEC) were found resulting from the administration of Ang-II-MSC-CM. Moreover, knockdown of VEGFR2 can block the effect of Ang-II-MSC-CM on preventing HUVEC from apoptosis, as well as the capacity of tube formation was also suppressed. In addition, the expression of increased Bcl-2 and alleviated caspase-3 were observed in HUVEC and HUVEC transfectants exposure to Ang-II-MSC-CM. Collectively, these results elucidated that the pretreatment of hUC-MSCs with Ang-II improved the outcome of MSC-based therapy for SAP via enhancing angiogenesis and ameliorating endothelial cell dysfunction in a VEGFR2 dependent manner. [ABSTRACT FROM AUTHOR]