METHODS: Male Sprague Dawley rats weighing 200-250 g were grouped into normal rats (N) and diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg body weight) whereas N similarly received citrate buffer. STZ-injected rats with blood glucose of more than 20 mmol/L were considered diabetic and were divided into vehicle-treated (DV) and TRF-treated (DT) groups. N and DV received vehicle, whereas DT received TRF (100 mg/kg body weight) via oral gavage once daily for 12 weeks. Fundus images were captured at week 0 (baseline), week 6 and week 12 post-STZ induction to estimate vascular diameters. At the end of experimental period, rats were euthanized, and retinal tissues were collected for morphometric analysis and measurement of NFκB, phospho-NFκB (Ser536), HIF-1α using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Retinal inflammatory and angiogenic cytokines expression were measured by ELISA and real-time quantitative PCR.
RESULTS: TRF preserved the retinal layer thickness (GCL, IPL, INL and OR; p
METHODS: We performed a systematic search using PubMed, Scopus, Cochrane Library, Web of Science for randomised controlled trials (RCTs), published until March 17, 2021. The quality assessment was carried out using the Cochrane Collaboration risk of bias tool. The Q-test and I 2 tests were used for the determination of heterogeneity of the included studies. Data were pooled using a random-effects model, and weighted mean difference (WMD) was used for the overall effect size.
RESULTS: Pooled findings of the five RCTs demonstrated that ginger supplementations had significantly reduced hs-CRP (WMD -0.42 mg/L; 95% CI, -0.78, -0.05, P = 0.03), TNF-α (-2.13 pg/mL; 95% CI: -3.41, -0.86, P = 0.001), and IL-6 (WMD: -0.61 pg/mL; 95% CI: -0.92, -0.30, P = 0.001) levels in patients with T2DM. The quality assessment of the studies showed that all of the included studies were at high risk of bias.
CONCLUSIONS: The meta-analysis shows that ginger supplementations reduced inflammatory parameters in patients with T2DM. Nonetheless, the reduction is relatively small, and its meaningful clinical effects are unknown. Future high-quality RCTs are needed to confirm the beneficial effects of ginger supplementation in patients with T2DM.
METHODS: The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively.
RESULTS: LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation.
CONCLUSION: There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.
DATA SYNTHESIS: We searched the following international databases from inception to January 2022: PubMed, Scopus, Web of Science and Embase, and Google Scholar. Our findings of eleven meta-analyses showed that cinnamon consumption can significantly improve total cholesterol (TC) (WMD = -1.01 mg/dL; 95% CI: -2.02, -0.00, p = 0.049), low-density lipoprotein-cholesterol (LDL-C) (WMD = -0.82 mg/dL; 95% CI: -1.57, -0.07, p = 0.032), and high-density lipoprotein-cholesterol (HDL-C) (WMD = 0.47 mg/dL; 95% CI: 0.17, 0.77, p = 0.002) levels but not triglyceride (TG) levels (WMD = -0.13 mg/dL; 95% CI: -0.58, 0.32, p = 0.570). Our results did not show any significant effect of cinnamon on malondialdehyde (MDA) levels (WMD = -0.47; 95% CI: -0.99, 0.05, p = 0.078) and C-reactive protein (CRP) levels (WMD = -1.33; 95% CI: -2.66, 0.00, p = 0.051) but there was enhanced total antioxidant capacity (TAC) in patients with type 2 diabetes (T2DM) and polycystic ovary syndrome (PCOS) (WMD = 0.34; 95% CI: 0.04, 0.64, p = 0.026) and increased levels of interleukin-6 (WMD = -1.48; 95% CI: -2.96, -0.01, p = 0.049).
CONCLUSIONS: Our results support the usefulness of cinnamon intake in modulating an imbalanced lipid profile in some metabolic disorders, particularly PCOS, as well as in improving TAC and interleukin-6. The review protocol was registered on PROSPERO as CRD42022358827.
SUMMARY: To treat BC, small-molecule inhibitors, phytomedicines, and nanoparticles are conjugated to attenuate BC signaling pathways. Due to their numerous target mechanisms and strong safety records, phytomedicines and nanomedicines have received much attention in studies examining their prospects as anti-BC agents by such unfulfilled demands.
KEY MESSAGES: The processes involved in the affiliation across the progression of tumors and the spread of inflammation are highlighted in this review. Furthermore, we included many drugs now undergoing clinical trials that target cancer-mediated inflammatory pathways, cutting-edge nanotechnology-derived delivery systems, and a variety of phytomedicines that presently address BC.
PURPOSE: The study was carried out to investigate the molecular mechanisms underlying the anti-inflammatory properties of the standardized 80% ethanol extract of Z. zerumbet through its effect on mitogen-activated protein kinase (MyD88)-dependent nuclear factor-kappa B (NF-кB), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Akt (PI3K-Akt) signaling pathways in lipopolysaccharide (LPS)-induced U937 human macrophages.
METHODS: Standardization of the 80% ethanol extract of Z. zerumbet was performed by using a validated reversed-phase HPLC method, while LC-MS/MS was used to profile the secondary metabolites. The release of pro-inflammatory markers, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and prostaglandin E2 (PGE2) was evaluated by enzyme-linked immunosorbent assay (ELISA), while the Western blot technique was executed to elucidate the expression of mediators linked to MyD88-dependent respective signaling pathways. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was carried out to quantify the relative gene expression of cyclooxygenase (COX)-2 and pro-inflammatory mediators at the transcriptional level.
RESULTS: The quantitative and qualitative analyses of Z. zerumbet extract showed the presence of several compounds including the major chemical marker zerumbone. Z. zerumbet extract suppressed the release of pro-inflammatory mediators, COX-2 protein expression and downregulated the mRNA expression of pro-inflammatory markers. Z. zerumbet-treatment also blocked NF-κB activation by preventing the phosphorylation of IKKα/β and NF-κB (p65) as well as the phosphorylation and degradation of IκBα. Z. zerumbet extract concentration-dependently inhibited the phosphorylation of respective MAPKs (JNK, ERK, and p38) as well as Akt. Correspondingly, Z. zerumbet extract suppressed the upstream signaling adaptor molecules, TLR4 and MyD88 prerequisite for the NF-κB, MAPKs, and PI3K-Akt activation.
CONCLUSION: The findings suggest that Z. zerumbet has impressive role in suppressing inflammation and related immune disorders by inhibition of various pro-inflammatory markers through the imperative MyD88-dependent NF-κB, MAPKs, and PI3K-Akt activation.