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Cardiovascular disease (CVD) is a serious public health problem, and among non-communicable diseases, CVD is now the leading cause of mortality and morbidity worldwide. CVD involves multiple organs throughout the body, especially the intestinal tract is the first to be involved. The impairment of the intestinal mucosal barrier is considered a significant pathological alteration in CVD and also contributes to the accelerated progression of the disease, thereby offering novel insights for CVD prevention and treatment. The treatment of Chinese medicine is characterized by multi-metabolites, multi-pathways, and multi-targets. In recent years, the studies of Traditional Chinese Medicine (TCM) in treating CVD by repairing the intestinal mucosal barrier have gradually increased, showing great therapeutic potential. This review summarizes the studies related to the treatment of CVD by TCM (metabolites of Chinese botanical drugs, TCM formulas, and Chinese patent medicine) targeting the repair of the intestinal mucosal barrier, as well as the potential mechanisms. We have observed that TCM exerts regulatory effects on the structure and metabolites of gut microbiota, enhances intestinal tight junctions, improves intestinal dyskinesia, repairs intestinal tissue morphology, and preserves the integrity of the intestinal vascular barrier through its anti-inflammatory, antioxidant, and anti-apoptotic properties. These multifaceted attributes position TCM as a pivotal modulator of inhibiting myocardial fibrosis, and hypertrophy, and promoting vascular repairment. Moreover, there exists a close association between cardiovascular risk factors such as hyperlipidemia, obesity, and diabetes mellitus with CVD. We also explore the mechanisms through which Chinese botanical drugs impact the intestinal mucosal barrier and regulate glucose and lipid metabolism. Consequently, these findings present novel insights and methodologies for treating CVD.

Enterovirus 71 (EV71) is the major pathogen causing fatal neurological complications of hand, foot, and mouth disease (HFMD) in young children. Currently no effective antiviral therapy is available. In the present study, we found that natural compound Berberine (BBR) displayed potent inhibitory effects on EV71 replication in various neural cells (IC50 of 2.79–4.03 μM). In a newborn mouse model of lethal EV71 infection, Berberine at 2–5 mg/kg markedly reduced mortality and clinical scores. Consistently, the replication of EV71 and pathological changes were attenuated in various infected organs including brain and lung with BBR treatment. Interestingly, EV71 infection in the brain mainly localized in the peripheral zone of brainstem and largely in astrocytes. Primary culture of astrocytes from newborn mouse brain confirmed the efficient EV71 replication that was mostly inhibited by BBR treatment at 5 μM. Further investigations revealed remarkably elevated cellular reactive oxygen species (ROS) levels that coincided with EV71 replication in primary cultured astrocytes and various cell lines. BBR largely abolished the virus-elevated ROS production and greatly diminished EV71 replication by up-regulating NFE2 like bZIP transcription factor 2 (Nrf2) via the kelch like ECH associated protein 1 (Keap)-Nrf2 axis. The nuclear localization of Nrf2 and expression of downstream antioxidant enzymes heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were increased significantly by BBR treatment. Collectively, our findings revealed that BBR prevents lethal EV71 neurological infection via inhibiting virus replication through regulating Keap-Nrf2 axis and ROS generation in astrocytes of brainstem, thus providing a potential antiviral treatment for severe EV71 infection associated with neurological complications.

Purpose: To assess the functional and anatomical consequences of single-dose dexamethasone (DEX) implants for the treatment of refractory macular edema (ME) secondary to retinal vein occlusion (RVO) after anti-vascular endothelial growth factor agents.Methods: A literature search of studies on switching therapy to DEX implants from anti-VEGF agents in refractory RVO patients was performed with five electronic databases (PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library) prior to January 2022. The main outcomes included best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes at different follow-up endpoints from baseline. All analyses were performed using Stata version 15.0.Results: The final analysis included four eligible studies with a total of 99 patients. After single-dose DEX implant application, BCVA improved significantly at 2, 3, and 6 months with an average gain of −0.23 logarithm of the minimum angle of resolution (logMAR) (p = 0.004), −0.20 logMAR (p = 0.027), and -0.09 logMAR (p = 0.021), respectively. Mean CMT reduction was also significant from baseline to 2 months (-241.89 μm, p < 0.001), 3 months (−222.61 μm, p < 0.001), and 6 months (−90.49 μm, p < 0.001). No serious adverse events were observed in any of the included studies.Conclusion: This meta-analysis showed that RVO patients with refractory ME could benefit significantly from switching therapy to DEX implantation, with efficacy lasting 6 months after a single-dose application. Intravitreal DEX implantation is a safe and effective option for refractory cases.

Descurainia sophia seeds (DS), Astragalus mongholicus (AM), and their formulas are widely used to treat heart failure caused by various cardiac diseases in traditional Chinese medicine practice. However, the molecular mechanism of action of DS and AM has not been completely understood. Herein, we first used mass spectrometry coupled to UPLC to characterize the chemical components of DS and AM decoctions, then applied MS-based quantitative proteomic analysis to profile protein expression in the heart of rats with isoproterenol-induced cardiomyopathy (ISO-iCM) before and after treated with DS alone or combined with AM, astragaloside IV (AS4), calycosin-7-glucoside (C7G), and Astragalus polysaccharides (APS) from AM. We demonstrated for the first time that DS decoction alone could reverse the most of differentially expressed proteins in the heart of the rats with ISO-iCM, including the commonly recognized biomarkers natriuretic peptides (NPPA) of cardiomyopathy and sarcomeric myosin light chain 4 (MYL4), relieving ISO-iCM in rats, but AM did not pronouncedly improve the pharmacological efficiency of DS. Significantly, we revealed that AS4 remarkably promoted the pharmacological potency of DS by complementarily reversing myosin motor MYH6/7, and further downregulating NPPA and MYL4. In contrast, APS reduced the efficiency of DS due to upregulating NPPA and MYL4. These findings not only provide novel insights to better understanding in the combination principle of traditional Chinese medicine but also highlight the power of mass spectrometric proteomics strategy combined with conventional pathological approaches for the traditional medicine research.

Curcumin exhibits anti-tumor effects in several cancers, including colorectal carcinoma (CRC), but the detailed mechanisms are still unclear. Here we studied the mechanisms underlying the anti-tumor effect of curcumin in colon cancer cells. SW480 cells were injected into mice to establish the xenograft tumor model, followed by evaluation of survival rate with the treatment of curcumin. The expression levels of β-catenin, Axin and TCF4 were measured in the SW480 cells in the absence or presence of curcumin. Moreover, miRNAs related to the curcumin treatment were also detected in vitro. Curcumin could suppress the growth of colon cancer cells in the mouse model. This anti-tumor activity of curcumin was exerted by inhibiting cell proliferation rather than promoting cell apoptosis. Further study suggested that curcumin inhibited cell proliferation by suppressing the Wnt/β-catenin pathway. MiR-130a was down-regulated by curcumin treatment, and overexpressing miR-130a could abolish the anti-tumor activity of curcumin. Our study confirms that curcumin is able to inhibit colon cancer by suppressing the Wnt/β-catenin pathways via miR-130a. MiR-130a may serve as a new target of curcumin for CRC treatment.

As a kind of potent stimulus, lipopolysaccharide (LPS) has the ability to cause cell damage by activating toll-like receptor(TLR)4, then nuclear factor kappa B (NF-κB) translocates into the nucleus and changes the expression of related inflammatory genes. Baicalin is extracted from Radix Scutellariae, which possesses anti-inflammation, antioxidant and antibacterial properties. However, the effects of it on LPS-induced liver inflammation have not been fully elucidated. This study aims to investigate the anti-inflammatory effects of Baicalin on the LPS-induced liver inflammation and its underlying molecular mechanisms in chicken. The results of histopathological changes, serum biochemical analysis, NO levels and myeloperoxidase activity showed that Baicalin pretreatment ameliorated LPS-induced liver inflammation. ELISA and qPCR assays showed that Baicalin dose-dependently suppressed the production of IL-1β, IL-6, and TNF-α. Furthermore, the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were significantly decreased by Baicalin. TLR4 is an important sensor in LPS infection. Molecular studies showed that the expression of TLR4 was inhibited by Baicalin pretreatment. In addition, Baicalin pretreatment inhibited NF-kB signaling pathway activation. All results demonstrated the protective effects of Baicalin pretreatment against LPS-induced liver inflammation in chicken via negative regulation of inflammatory mediators through the down-regulation of TLR4 expression and the inhibition of NF-kB activation.

Paeoniflorin-6'-O-benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug. [ABSTRACT FROM AUTHOR]

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2.