Actinidia arguta Extract Containing Myo-Inositol Suppresses TNF-α-Induced VCAM-1 Expression and Monocyte Adhesion to Endothelial Cells via Inhibition of the PTEN/Akt/GSK-3ß and NF-κB Signaling Pathways.

The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. Actinidia arguta (kiwiberry) is an edible fruit that contains various bioactive components. While A. arguta extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified. We used tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs) for an in vitro model. AAE effectively hindered the attachment of THP-1 monocytes and reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Transcriptome analysis revealed that AAE treatment upregulated phosphatase and tensin homolog (PTEN), subsequently inhibiting phosphorylation of AKT and glycogen synthase kinase 3ß (GSK3ß) in HUVECs. AAE further hindered phosphorylation of AKT downstream of the nuclear factor kappa B (NF-κB) signaling pathway, leading to suppression of target gene expression. Oral administration of AAE suppressed TNF-α-stimulated VCAM-1 expression, monocyte-derived macrophage infiltration, and proinflammatory cytokine expression in C57BL/6 mouse aortas. Myo-inositol, identified as the major compound in AAE, played a key role in suppressing THP-1 monocyte adhesion in HUVECs. These findings suggest that AAE could serve as a nutraceutical for preventing atherosclerosis by inhibiting its initial pathogenesis.

Effect of Coenzyme Q10 Supplementation on Vascular Endothelial Function: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10 supplementation's effect on endothelial function. However, these studies have yielded conflicting results, therefore this systematic review and meta-analysis were conducted. AIM: This systematic review and meta-analysis were conducted to assess the effects of CoQ10 supplementation on endothelial factors. METHODS: A comprehensive search was done in numerous databases until July 19th, 2023. Quantitative data synthesis was performed using a random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis, and publication bias. RESULTS: 12 studies comprising 489 subjects were included in the meta-analysis. The results demonstrated significant increases in Flow Mediated Dilation (FMD) after CoQ10 supplementation (WMD: 1.45; 95% CI: 0.55 to 2.36; p < 0.02), but there is no increase in Vascular cell adhesion protein (VCAM), and Intercellular adhesion molecule (ICAM) following Q10 supplementation (VCAM: SMD: - 0.34; 95% CI: - 0.74 to - 0.06; p < 0.10) (ICAM: SMD: - 0.18; 95% CI: - 0.82 to 0.46; p < 0.57). The sensitivity analysis showed that the effect size was robust in FMD and VCAM. In meta-regression, changes in FMD percent were associated with the dose of supplementation (slope: 0.01; 95% CI: 0.004 to 0.03; p = 0.006). CONCLUSIONS: CoQ10 supplementation has a positive effect on FMD in a dose-dependent manner. Our findings show that CoQ10 has an effect on FMD after 8 weeks of consumption. Additional research is warranted to establish the relationship between CoQ10 supplementation and endothelial function.

Saponins from Allium macrostemon Bulbs Attenuate Endothelial Inflammation and Acute Lung Injury via the NF-κB/VCAM-1 Pathway.

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway's inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.

Muscone inhibits the progression of atherosclerotic plaques in mice aorta by inhibiting the NF-κB/p65 pathway.

Atherosclerosis (AS) is considered to be one of the main pathogenic factors of coronary heart disease, cerebral infarction and peripheral vascular disease. Oxidative stress and inflammation run through the occurrence and development of atherosclerosis and related cardiovascular events. Muscone is a natural extract of deer musk and also the main physiological active substance of musk. This study investigated the impact of muscone on atherosclerosis. ApoE-/- mice were used to establised AS model and injected with low-dose (4 mg/kg/day) or high-dose (8 mg/kg/day) of muscone intraperitoneally for 4 weeks. Then aortic tissues were collected, and pathological sections of the aorta were prepared for oil red staining, HE and masson staining. The changes of MDA, SOD, VCAM-1, NF-κB, and TNF-α were observed by Western blotting or immunofluorescence staining. The results showed that high-dose muscone could effectively reduce the plaque area/aortic root area and relative atherosclerotic area, reduce the collagen composition in plaque tissue. In addition, we also found that high-dose muscone can effectively increase MDA level, reduce the level of SOD, and inhibit the expression of VCAM-1, NF-κB/p65, TNF-α in arterial plaques. Our results indicate that the administration of muscone has the benefit of inhibiting atherosclerosis. The potential mechanisms may be associated with antioxidant effect and inhibition of inflammatory reaction in arterial plaques. With the increasing understanding of the relationship between muscone and atherosclerosis, muscone has high potential value as a new drug to treat atherosclerosis.

Effect of electroacupuncture on ventricular structure and function in rats with myocardial ischemia-reperfusion injury. / ç”µé’ˆå¯¹å¿ƒè‚Œç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ å¿ƒå®¤ç»“æž„å’ŒåŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on changes of ventricular structure and function in rats with myocardial ischemia-reperfusion injury (MIRI), so as to explore its potential mechanisms underlying improvement of ventricular remodeling after MIRI. METHODS: Forty male SD rats were randomly divided into 4 groups：sham operation group, model group, EA group and medication (sacubactril valsartan, LCZ696) group, with 10 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery and reperfusion. EA (2 Hz/100 Hz, 2 mA) was applied to bilateral "Neiguan" (PC6) for 20 min, once every other day for 21 d. Rats of the medication group received gavage of LCZ696 (60 mg·kg-1·d-1). After the intervention, echocardiography was used to detect the ejection fraction (EF) and fractional shortening (FS) of the left ventricle, and the contents of serum tumor necrosis factor-α(TNF-α), vascular cell adhesion molecule-1(VCAM-1) and intercellular cell adhesion molecule-1(ICAM-1) were assayed by enzyme-linked immunosorbent assay. The pathological changes of myocardial tissue were observed after HE staining. The Masson staining was used to evaluate the myocardial collagen deposition and myocardial fibrosis. The mRNA expression levels of collagen Ⅰ and Ⅲ and connective tissue growth factor (CTGF) in the myocardial tissue were detected by quantitative real-time PCR, and the expression levels of IL-1ß and IL-18 were detected by Western blot. RESULTS: In contrast to the sham operation group, the EF and FS levels of the left ventricle were ob-viously decreased (P<0.001), while the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, the expression levels of IL-1ß and IL-18 were significantly increased (P<0.001, P<0.000 1, P<0.05, P<0.01) in the model group. Compared with the model group, the EF and FS levels were remarkably increased (P<0.01), whereas the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, and the expression levels of IL-1ß and IL-18 were significantly down-regulated (P<0.001, P<0.01, P<0.05) in both the medication and EA groups. No significant differences were found between the EA and medication groups in all the indexes mentioned above. CONCLUSIONS: EA can improve the left-ventricular fibrosis and function, delay or reverse ventricular remodeling in MIRI rats, which may be related to its functions in down-regulating myocardial inflammatory response and mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF.

Effect of walnut consumption on markers of endothelial function in adults: A systematic review and meta-analysis of randomized controlled trials.

Findings on the effect of walnut consumption on endothelial function are conflicting. Therefore, the present systematic review and meta-analysis summarized available trials in this regard. A systematic search was performed in online databases including PubMed-Medline, Scopus, and ISI Web of Science up to October 2023. Articles that reported the effect of walnut intake on flow-mediated dilation (FMD), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and stimulus-adjusted response measure (SARM) were included. Random effects models for a weighted mean difference (WMD) or standardized mean difference (SMD) were used to test for the overall effect. Six eligible trials were analyzed (250 participants). Walnut intake significantly increased FMD (WMD: 0.94%, 95% CI: 0.12 to 1.75; p = 0.02). However, meta-analysis could not show any beneficial effect of walnut intake on ICAM-1 (SMD: -0.23, 95% CI: -0.68 to 0.22; p = 0.31), VCAM-1 (SMD: -0.02, 95% CI: -1.38 to 1.34; p = 0.97), and SARM (WMD: 0.01%, 95% CI: -0.01 to 0.04; p = 0.28). In conclusion, the present meta-analysis suggests that walnuts may reduce cardiovascular disease risk by improving FMD. However, further studies should be performed on adults to determine the effect of walnut intake on endothelial function.

Curcumin/turmeric supplementation could improve blood pressure and endothelial function: A grade-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: A number of studies have examined the impact of curcumin/turmeric on blood pressure and the factors allegedly responsible for hypertension. In this systematic review and meta-analysis, we tried to sum up the existing literature on randomized controlled trials (RCTs) investigating this hypothesis. METHODS: Online databases (PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar) were searched from inception up to October 2022. We used the cochrane quality assessment tool to evaluate the risk of bias. Outcomes of interest included systolic blood pressure (SBP), diastolic blood pressure (DBP), blood levels of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), flow-mediated vasodilation (FMD), and pulse-wave velocity (PWV). Weighted mean differences (WMDs) were derived and reported. In case of significant between-study heterogeneity, subgroup analyses were carried out. Significance level was considered as P-values<0.05. RESULTS: Finally, 35 RCTs out of 4182 studies were included. Our findings suggested that curcumin/turmeric supplementation significantly improved SBP (WMD: -2.02 mmHg; 95 % CI: -2.85, -1.18), DBP (WMD: -0.82 mmHg; 95 % CI: -1.46, -0.18), VCAM-1 (WMD: -39.19 ng/mL; 95 % CI: -66.15, -12.23), and FMD (WMD: 2.00 %; 95 % CI: 1.07, 2.94). However, it did not significantly change levels of ICAM-1 (WMD: -17.05 ng/ml; 95 % CI: -80.79, 46.70), or PWV (WMD: -79.53 cm/s; 95 % CI: -210.38, 51.33). CONCLUSION: It seems that curcumin/turmeric supplementation could be regarded as a complementary method to improve blood pressure and endothelial function. However, further research is needed to clarify its impact on inflammatory adhesion molecules in the circulation.

Assessing Mailuoning injection in wound healing and thrombophlebitis management: A rat model study.

Thrombophlebitis is the inflammatory condition characterized by obstruction of one or more vessels, commonly in the legs, due to the formation of blood clots. It has been reported that traditional Chinese medicine, including Mailuoning injection, is advantageous for treating inflammatory and blood disorders. This research assessed the therapeutic efficacy of Mailuoning injection in the treatment of thrombophlebitis in rodents, as well as investigated its impact on fibrinolysis, inflammation, and coagulation. An experimental setup for thrombophlebitis was established in rodents via modified ligation technique. Five groups comprised the animals: sham operation group, model group, and three Mailuoning treatment groups (low, medium, and high dosages). The pain response, edema, coagulation parameters (PT, APTT, TT, FIB), serum inflammatory markers (IL-6, TNF-α, CRP), and expression levels of endothelial markers (ICAM-1, VCAM-1, NF-κB) were evaluated. Blood flow and vascular function were further assessed by measuring hemorheological parameters and the concentrations of TXB2, ET, and 6-k-PGF1α. In contrast to the sham group, model group demonstrated statistically significant increases in endothelial expression levels, coagulation latencies, and inflammatory markers (p < 0.05). The administration of mailing, specifically at high and medium dosages, resulted in a substantial reduction in inflammatory markers, enhancement of coagulation parameters, suppression of ICAM-1 and VCAM-1 expression, and restoration of hemorheological measurements to baseline (p < 0.05). Significantly higher concentrations of 6-k-PGF1α and lower levels of TXB2 and ET were observed in high-dose group, suggesting that pro- and anti-thrombotic factors were restored to equilibrium. Utilization of Mailuoning injection in rat model of thrombophlebitis exhibited significant therapeutic impact. This effect was manifested through pain alleviation, diminished inflammation, enhanced blood viscosity and facilitation of fibrinolysis. The study indicated that Mailuoning injection may serve as a viable therapeutic option for thrombophlebitis, potentially aiding in the improvement of wound healing by virtue of its anti-inflammatory and blood flow-enhancing characteristics.

[Effects of Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination on inflammatory responses in atherosclerotic mice].

The study aims to observe the effects and explore the mechanisms of Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination in the treatment of the inflammatory response of mice with atherosclerosis(AS) via the Toll-like receptor 4(TLR4)/myeloid differentiation primary response protein 88(MyD88)/nuclear factor-κB(NF-κB) signaling pathway. Male ApoE~(-/-) mice were randomly assigned into a model group, a Buyang Huanwu Decoction group, an Astragali Radix-Angelicae Sinensis Radix combination group, and an atorvastatin group, and male C57BL/6J mice of the same weeks old were used as the control group. Other groups except the control group were given high-fat diets for 12 weeks to establish the AS model, and drugs were administrated by gavage. Aortic intimal hyperplasia thickness, blood lipid level, plasma inflammatory cytokine levels, M1/M2 macrophage markers, and expression levels of proteins in TLR4/MyD88/NF-κB pathway in the vessel wall were measured to evaluate the effects of drugs on AS lesions and inflammatory responses. The results showed that the AS model was successfully established with the ApoE~(-/-) mice fed with high-fat diets. Compared with the control group, the model group showed elevated plasma total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c) levels(P<0.05), thickened intima(P<0.01), and increased plasma tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) levels(P<0.01). Moreover, the model group showed increased expression of vascular cell adhesion molecule-1(VCAM-1) and inducible nitric oxide synthase(iNOS)(P<0.01), inhibited expression of endothelial nitric oxide synthase(eNOS) and cluster of differentiation 206(CD206)(P<0.01), and up-regulated mRNA and protein levels of TLR4, MyD88, NF-κB inhibitor alpha(IκBα), and NF-κB in the vessel wall(P<0.05). Compared with the model group, Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination lowered the plasma TC and LDL-c levels(P<0.01), alleviated the intimal hyperplasia(P<0.01), and reduced the plasma TNF-α and IL-6 levels(P<0.05). Moreover, the two interventions promoted the expression of eNOS and CD206(P<0.05), inhibited the expression of VCAM-1 and iNOS(P<0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, IκBα, and NF-κB(P<0.05) in the vessel wall. This study indicated that Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination could delay the progression of AS, inhibit the polarization of vascular wall macrophages toward M1 type, and attenuate vascular inflammatory response by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway in the vascular wall. Astragali Radix and Angelicae Sinensis Radix were the main pharmacological substances in Buyang Huanwu Decoction for alleviating the AS vascular inflammatory response.

Effects of marine-derived n-3 PUFA supplementation on soluble adhesion molecules: A systematic review and dose-response meta-analysis of randomized controlled trials.

Long-chain n-3 poly unsaturated fatty acids have anti-inflammatory effects but their effects on serum levels of adhesion molecules are inconsistent and contradictory. In this updated systematic review and meta-analysis, marine sources of omega-3 fatty acids were pooled up to determine the effects of omega-3 supplementation on adhesion molecules. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to April 2023) were searched and all RCTs investigating the effects of marine sources of omega-3, on blood concentrations of adhesion molecules were included and a meta-analysis undertaken. Forty-two RCTs were included involving 3555 participants aged from 18 to 75 years. Meta-analysis of 38 arms from 30 RCTs reporting serum concentrations of vascular cell adhesion molecule-1 (VCAM-1) showed a significant reduction after omega-3 supplementation (WMD: -1.26, 95% CI: -1.88 to -0.64 ng/mL, P < 0.001). Meta-analysis of 40 arms from 30 RCTs reporting serum concentrations of intercellular adhesion molecule-1 (ICAM-1) revealed a reduction following omega-3 supplementation, although it was not significant (WMD: -1.76, 95%CI: -3.68 to 0.16 ng/mL, P = 0.07). Meta-analysis of 27 arms from 21 trials showed no effect on E-selectin (WMD: 0.01, 95%CI: -0.02 to 0.04 ng/mL, P = 0.62). Pooling 15 arms from 11 RCTs showed a marginally significant reducing effect on P-selectin concentrations (WMD: -2.67, 95%CI: -5.53 to 0.19 ng/mL, P = 0.06). A considerable decrease in VCAM concentration was observed after omega-3 supplementation in this meta-analysis with a trend to decreases in both ICAM and P-selectin levels, with effects that may be significant depending on study design, and there was no effect on E-selectin.

[Effect of mild moxibustion at 45 ℃ with different durations at "Zusanli" （ST36） on the inflammatory factors in the abdominal aorta of hyperlipidemia rats].

OBJECTIVE: To investigate the effects of mild moxibustion at 45°C on the chronic inflammatory response of the abdominal aorta in rats with hyperlipidemia and the effects of different moxibustion durations. METHODS: Thirty-six SD rats were randomly divided into the following groups： blank control group (2 weeks), model group (2 weeks), moxibustion group (2 weeks), blank group (4 weeks), model group (4 weeks), and moxibustion group (4 weeks). A model of hyperlipidemia with chronic inflammation was established through high-fat diet feeding for 8 weeks. Rats in the moxibustion groups received mild moxibustion treatment at bilateral "Zusanli"(ST36) at 45 °C, 10 min every time, once a day, for consecutive 2 or 4 weeks. The morphology of the abdominal aorta in each group was observed by using HE staining. Contents of serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), endothelin-1 (ET-1) and the contents of nitric oxide (NO), ox-LDL, and ET-1 in the abdominal aorta were measured by using ELISA. Protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta of rats in each group were detected by using Western blot and real-time fluorescence quantitative PCR respectively. The positive expression of IL-6 in the abdominal aorta of rats was detected by Immunofluorescence. RESULTS: Compared to the blank control group, rats in the model group had increased contents of LDL, TC, TG, ox-LDL, VCAM-1, ICAM-1, IL-6, TNF-α, and ET-1 in the serum, increased contents of ox-LDL and ET-1 in the abdominal aorta, increased protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta(P<0.01, P<0.05, P<0.001), with decreased HDL content in the serum, decreased NO content in the abdominal aorta (P<0.01, P<0.05), as well as dark pink abdominal aorta, rough textures in the adventitia, media, and intima, and rough endothelial layer. Compared to the model group(2 weeks), LDL, ICAM-1, ET-1 contents in the serum, ox-LDL content in the abdominal aorta were decreased(P<0.05), while serum IL-6 and TNF-α contents, and NO content in the abdominal aorta were significantly increased(P<0.01, P<0.05), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(2 weeks). Compared to the model group(4 weeks), contents of LDL, TC, TG, VCAM-1, ICAM-1, IL-6, TNF-α, ox-LDL, and ET-1 in the serum, ox-LDL and ET-1 contents in abdominal aorta, protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta were significantly decreased(P<0.05, P<0.01), while HDL content in the serum and NO content in the abdominal aorta were significantly increased(P<0.05, P<0.01), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks). In addition, content of HDL in the serum were significantly increased(P<0.05), while TNF-α content in the serum, protein expression of IL-6 in the abdominal aorta were significantly decreased (P<0.001, P<0.05), with smoother vascular walls, and clearer nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks), in comparison with the moxibustion group(2 weeks). CONCLUSION: Mild moxibustion of 45 °C at ST36 can improve vascular endothelial damage and inflammatory response induced by high-fat diet by regulating serum lipids, vascular tone, adhesion molecules, and inflammatory factors, of which the effect of moxibustion intervention for 4 weeks is more significant.

[Effect of Isodon ternifolius-medicated serum on hepatic stellate cells based on TLR4/NF-κB/NLRP3 signaling pathway].

The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-ß1(TGF-ß1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-ß1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.

Effect of Black Garlic Consumption on Endothelial Function and Lipid Profile: A Before-and-After Study in Hypercholesterolemic and Non-Hypercholesterolemic Subjects.

BACKGROUND: Black garlic is obtained from raw garlic (Allium sativum L.), by a fermentation process, under humidity and heat treatment, showing a high concentration of organosulfur compounds, which have been related to benefits in the prevention or delay of cardiovascular diseases (CVDs). The objective of the research was to evaluate whether long-term consumption of black garlic improves endothelial function and lipid profile in subjects with hypercholesterolemia. METHODS: Single center, controlled clinical trial with two branches: Hypercholesterolemia vs. Healthy condition. Sixty-two subjects of both sexes were distributed in two groups, the hypercholesterolemia group (n = 31) (total cholesterol (TC) range 200-300 mg/dL and low-density lipoprotein (LDL)-cholesterol range 135-175 mg/dL) and the healthy group (n = 31). The intervention consisted of the ingestion of 4 cloves of black garlic (12 g) daily for 12 weeks. RESULTS: significant increases in Apolipoprotein (Apo)A1 occurred in both groups: Hypercholesterolemia (Δ 11.8 mg/dL p < 0.001) vs Healthy (Δ 11.1 mg/dL p < 0.001). Besides, significant reductions for endothelial adhesion molecules monocyte chemoattractant protein-1 (MCP-1) (Δ -121.5 pg/mL p = 0.007 vs. Δ -56.3 pg/mL p = 0.015), intracellular adhesion molecule-1 (ICAM-1) (Δ -39.3 ng/mL p < 0.001 vs. Δ 63.5 ng/mL p < 0.001), and vascular cyto-adhesion molecule-1 (VCAM-1) (Δ -144.4 ng/mL p < 0.001 vs. Δ -83.4 ng/mL p = 0.061) were observed, for hypercholesterolemic and healthy subjects, respectively. CONCLUSIONS: These data show that black garlic consumption could improve some parameters related to endothelial function and lipid profile, which may have a favorable impact on the risk of CVDs, although more long-term studies are necessary to confirm.

Anthocyanin supplementation improves obesity-related inflammatory characteristics: A systematic review and meta-analysis of randomized controlled trials.

The relationship between anthocyanin intake and obesity-related inflammatory markers remains unclear in existing research. To investigate this, we hypothesized that anthocyanin supplementation could reduce plasma concentrations of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1, and other cytokines in obesity. We conducted a systematic search of PubMed, Web of Science, Scopus, SinoMed, and other related literature and identified 16 randomized controlled trials that met our inclusion criteria. Our findings showed that anthocyanin intake was significantly associated with a reduction in vascular cell adhesion molecule-1 mean plasma concentrations (-53.56 ng/mL; 95% confidence interval [CI], -82.10 to -25.03). We also observed a modest decrease in CRP (-0.27 ng/mL; 95% CI, -0.58 to 0.05), TNF-α (-0.20 ng/mL; 95% CI, -0.54 to 0.15), and IL-6 (-0.53 ng/mL; 95% CI, -1.16 to 0.10) mean plasma concentrations. Subgroup analysis revealed that anthocyanin intake tended to decrease CRP and IL-6 concentrations in overweight or dyslipidemic individuals. Additionally, the intervention duration subgroup analysis showed that anthocyanin supplementation had a stronger effect on plasma IL-6 and TNF-α in participants after 8 to 12 weeks of intervention. In conclusion, our meta-analysis indicated that anthocyanin supplementation can effectively reduce obesity-related inflammatory markers associated with chronic low-grade inflammation.

Effects of quercetin supplementation on endothelial dysfunction biomarkers and depression in post-myocardial infarction patients: A double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Endothelial dysfunction and depression are highly prevalent in patients who have experienced a myocardial infarction (MI). Epidemiological studies have pointed out that a diet rich in flavonoids, e.g., quercetin, can prevent the development of these biological phenomena. Therefore, we aimed to investigate the effects of quercetin supplementation on the levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and on depression in post-MI subjects. METHODS: Eighty-eight post-MI patients who had experienced their first MI (body mass index ≤35 kg/m2, age 30-65 years) were recruited from the Rasool-e-Akram and Afshar Hospitals, Iran, and included in this randomized, placebo-controlled, double-blind parallel study. The participants were randomly assigned to receive a daily dose of 500 mg quercetin (n = 44) or placebo (n = 44) for 8 weeks. Serum concentrations of ICAM-1 and VCAM-1 were quantified by ELISA and depression levels were assessed using the Beck's Depression Inventory (BDI-II) questionnaire at baseline and at 8-week follow-up. RESULTS: Seventy-six participants completed the study, but the intention-to-treat (ITT) analysis was conducted for all 88 participants who were randomized into the intervention groups. No significant changes in serum concentrations of ICAM-1 or VCAM-1 (P = 0.21 and P = 0.80, respectively) were observed after 8 weeks of quercetin supplementation versus placebo. In addition, depression levels did not differ significantly between the quercetin and placebo groups. CONCLUSION: Our findings demonstrated that in post-MI patients, daily supplementation with quercetin (500 mg/day) for 8 weeks did not affect endothelial dysfunction biomarkers and depression levels. This trial was registered at IRCT.ir as IRCT20190428043405N1.

In Vitro Anti-Inflammatory and Vasculoprotective Effects of Red Cell Extract from the Black Sea Urchin Arbacia lixula.

Sea urchins have emerged as an important source of bioactive compounds with anti-inflammatory and antioxidant properties relevant to human health. Since inflammation is a crucial pathogenic process in the development and progression of atherosclerosis, we here assessed the potential anti-inflammatory and vasculoprotective effects of coelomic red-cell methanolic extract of the black sea urchin Arbacia lixula in an in vitro model of endothelial cell dysfunction. Human microvascular endothelial cells (HMEC-1) were pretreated with A. lixula red-cell extract (10 and 100 µg/mL) before exposure to the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The extract was non-toxic after 24 h cell treatment and was characterized by antioxidant power and phenol content. The TNF-α-stimulated expression of adhesion molecules (VCAM-1, ICAM-1) and cytokines/chemokines (MCP-1, CCL-5, IL-6, IL-8, M-CSF) was significantly attenuated by A. lixula red-cell extract. This was functionally accompanied by a reduction in monocyte adhesion and chemotaxis towards activated endothelial cells. At the molecular level, the tested extract significantly counteracted the TNF-α-stimulated activation of the pro-inflammatory transcription factor NF-κB. These results provide evidence of potential anti-atherosclerotic properties of A. lixula red-cell extract, and open avenues in the discovery and development of dietary supplements and/or drugs for the prevention or treatment of cardiovascular diseases.

Ginkgolide C attenuates cerebral ischemia/reperfusion-induced inflammatory impairments by suppressing CD40/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. (Ginkgoaceae), a traditional Chinese medicine, has been applied for thousands of years for the treatment of cardio-cerebral vascular diseases in China. It is written in Compendium of Materia Medica that Ginkgo has the property of "dispersing poison", which is now referred to as anti-inflammatory and antioxidant. Ginkgolides are important active ingredients in Ginkgo biloba leaves and ginkgolide injection has been frequently applied in clinical practice for the treatment of ischemic stroke. However, few studies have explored the effect and mechanism of ginkgolide C (GC) with anti-inflammatory activity in cerebral ischemia/reperfusion injury (CI/RI). AIM OF THE STUDY: The present study aimed to demonstrate whether GC was capable of attenuating CI/RI. Furthermore, the anti-inflammatory effect of GC in CI/RI was explored around the CD40/NF-κB pathway. MATERIALS AND METHODS: In vivo, middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in rats. The neuroprotective effect of GC was assessed by neurological scores, cerebral infarct rate, microvessel ultrastructure, blood-brain barrier (BBB) integrity, brain edema, neutrophil infiltration, and levels of TNF-α, IL-1ß, IL-6, ICAM-1, VCAM-1, and iNOS. In vitro, rat brain microvessel endothelial cells (rBMECs) were preincubated in GC before hypoxia/reoxygenation (H/R) culture. The cell viability, levels of CD40, ICAM-1, MMP-9, TNF-α, IL-1ß, and IL-6, and activation of NF-κB pathway were examined. In addition, the anti-inflammatory effect of GC was also investigated by silencing CD40 gene in rBMECs. RESULTS: GC attenuated CI/RI as demonstrated by decreasing neurological scores, reducing cerebral infarct rate, improving microvessel ultrastructural features, ameliorating BBB disruption, attenuating brain edema, inhibiting MPO activity, and downregulating levels of TNF-α, IL-1ß, IL-6, ICAM-1, VCAM-1, and iNOS. Coherently, in rBMECs exposed to H/R GC enhanced cell viability and downregulated levels of ICAM-1, MMP-9, TNF-α, IL-1ß, and IL-6. Furthermore, GC suppressed CD40 overexpression and hindered translocation of NF-κB p65 from the cytosol to the nucleus, phosphorylation of IκB-α, and activation of IKK-ß in H/R rBMECs. However, GC failed to protect rBMECs from H/R-induced inflammatory impairments and suppress activation of NF-κB pathway when CD40 gene was silenced. CONCLUSIONS: GC attenuates cerebral ischemia/reperfusion-induced inflammatory impairments by suppressing CD40/NF-κB pathway, which may provide an available therapeutic drug for CI/RI.

Total flavone of flowers of Abelmoschus manihot (L.) Medic inhibits the expression of adhesion molecules in primary mesenteric arterial endothelial cells and ameliorates dextran sodium sulphate-induced ulcerative colitis in mice.

BACKGROUND: Flowers of Abelmoschus manihot (L.) medic (AM) is a traditional Chinese medicine used to treat chronic nephritis, nephrotic syndrome, diabetic nephropathy, and colonic inflammation. PURPOSE: This study aimed to explore the influence of the total flavone of AM flowers (TFA) on acute ulcerative colitis (UC) and the potential underlying mechanism. METHODS: Efficacy of TFA (30, 60, 120 mg/kg) on UC was evaluated in a dextran sodium sulphate (DSS)-induced colonic inflammatory mouse model by analyzing disease activity index (DAI), histopathological score, colon length, and cytokine expression. Expression levels of critical adhesion molecules and nuclear factor kappa B (NF-κB) were examined by qRT-PCR, Western blotting, or immunofluorescence labeling. Myeloperoxidase activity was examined using ELISA. In vitro THP-1 adhesion assay was used to evaluate monocyte adhesion. RESULTS: TFA significantly reduced DAI score, prevented colon shortening, and ameliorated histological injuries of colons in DSS-treated mice. TFA inhibited the expression of cytokines (IL-1ß and TNF-α) and adhesion molecules (ICAM-1, VCAM-1, and MAdCAM-1) in colon tissues of DSS mice. In vitro studies on mesenteric arterial endothelial cells (MAECs) showed that TFA attenuated TNF-α-induced upregulation of ICAM-1, VCAM-1, and MAdCAM-1, as well as THP-1 cell adhesion to MAECs. TFA also suppressed the phosphorylation and nuclear translocation of NF-κB in MAECs. CONCLUSION: TFA efficaciously ameliorates UC possibly by inhibiting monocyte adhesion through blocking TNF-α-induced NF-κB activation, which in turn suppresses the upregulation of adhesive molecules in colon endothelial cells. Inhibiting the expression of adhesion molecule in MAECs may represent a useful strategy for therapeutic development to treat UC, with TFA being a safe and efficacious therapeutic agent.

Highly pathogenic porcine reproductive and respiratory syndrome virus-induced inflammatory response in porcine pulmonary microvascular endothelial cells and effects of herbal ingredients on main inflammatory molecules.

The role of microvascular endothelial cells (MVECs) in viral infection has received increasing attention. Our previous study demonstrated the susceptibility of porcine pulmonary MVECs to highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV), while their responses to the viral infection remain unclear. This study aimed to understand effects of the HP-PRRSV infection on functions of porcine pulmonary MVECs and the intervention effects of Chinese herbal ingredients on them. Highly purified porcine pulmonary MVECs were separated using CD31-immunomagnetic beads and infected with HP-PRRSV JXA1 and HN strain. The virus particles in cells and the ultrastructural pathological changes of cells were revealed by transmission electron microscopy. High-throughput transcriptome sequencing indicated that 104 and 228 genes were differentially expressed at 36 h post-infection, respectively, including many inflammatory molecules such as interleukins, chemokines, and adhesion molecules. The expression kinetics of HP-PRRSV-induced IL-1α, IL-6, IL-8, and VCAM-1 were characterized at the mRNA and protein levels. Luteolin significantly down-regulated HP-PRRSV-induced increase of the four molecules at both levels, and glycyrrhetinic acid and baicalin reduced that of IL-6 and VCAM-1. Our results suggest that porcine pulmonary MVECs play important roles in the inflammatory lung injury caused by HP-PRRSV infection and that herbal ingredients have potential regulatory effects on the HP-PRRSV-induced dysfunction of MVECs.

The effects of probiotics on VCAM-1 and ICAM-1: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: We performed the present systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of probiotics on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels in adults. METHODS: A systematic search current to April 2022 was performed in MEDLINE, EMBASE, and Cochrane Database using relevant keywords to detect eligible articles. A random-effects model was used to estimate the standardized mean difference (SMD) and 95% confidence interval (95% CI). RESULTS: Six eligible trials were included in the final analysis. The pooled analysis revealed that there was a significant reduction in VCAM-1 from baseline to post-probiotic course with standardized mean difference [SMD: -0.66 ng/ml; 95% CI: -1.09, -0.23 ng/ml; P = 0.003]. The effects of probiotic intake on VCAM-1 were more pronounced when it was received via supplements [SMD: -0.61 ng/ml; 95% CI: -1.08, -0.14 ng/ml; P = 0.010], for 12 weeks [SMD: -0.60 ng/ml; 95% CI: -1.09, -0.12 ng/ml; P = 0.014] and when it was prescribed for individuals with metabolic syndrome [SMD: -0.79 ng/ml; 95% CI: -1.40, -0.19 ng/ml; P = 0.010]. Moreover, VCAM-1 levels were decreased in the subgroup of multispecies probiotic regiments [SMD: -0.71 ng/ml; 95% CI: -1.38, -0.04 ng/ml; P = 0.039]. CONCLUSION: Our study demonstrates potential beneficial effects of probiotics on VCAM-1 in adults. However, more larger-scale, long-time RCTs are needed to confirm the accurate effect of probiotics on endothelial dysfunction biomarkers.