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Background: Telmisartan, a potent angiotensin II type-1 receptor blocker as well as partial PPAR–gamma agonist, has emerged as a versatile therapeutic agent with diverse pharmacological actions beyond its primary indication for essential hypertension. This review explores the complex mechanisms of action of telmisartan and clarifies its effectiveness in an inflammation, cancer, metabolic, and CNS disorders. Main body: Telmisartan inhibits many biochemical processes involved in the control of the cardiovascular system, such as vascular smooth muscle contraction, aldosterone production, and sympathetic tone modulation, by specifically targeting the angiotensin II type-1 receptor. Its distinct partial agonist action toward peroxisome proliferator-activated receptor gamma also imparts anti-inflammatory, antiproliferative, and antioxidant activities, making it a viable treatment for various diabetic patients who have atherosclerosis and myocardial infarction. Conclusion: Telmisartan's diverse pharmacological actions, encompassing anti-inflammatory, neuroprotective, nephroprotective, anticancer, and anti-anxiety properties, position it as a promising treatment option for a broad spectrum of medical conditions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the inhibitory effect of topically administered azithromycin (AZM), and moxifloxacin (MXF) against tumor necrosis factor-α (TNF-α) production in a rat model of endotoxin-induced uveitis (EIU). Methods: Thirty-six Wistar albino rats were divided into 6 equal groups. Groups 1, 2 and 3 were determined as sham, control group for topical AZM application and control group for topical MXF application, respectively. Sterile saline, topical AZM 1.5%, and topical MXF 0.5% were instilled 5 times daily for totally 6 days on both eyes of the rats in Group 4, Group 5, and Group 6, before and after inducing EIU by intravitreal injections of lipopolysaccharide, respectively. At 24 h after intravitreal injections, aqueous humor was collected from both eyes of each rat for the assessment of TNF-α concentration. Also, density of nuclear factor kappa B (NF-κB) in ciliary body, and the number of cells infiltrating the posterior segment of EIU rat eyes was assessed in one eye of each rat. Results: There was a significant reduction in mean aqueous humor concentration of TNF-α in EIU rats pretreated with topical AZM in comparison with those pretreated with sterile saline (139 ± 38.6 in Group 4 vs. 72 ± 12.6 in Group 5, p = 0.006). There was also a marked decrease in mean aqueous humor concentration of TNF-α in EIU rats pretreated with topical MXF (139 ± 38.6 in Group 4 vs.86.1 ± 35.5 in Group 6, p = 0.025). Also, evident suppressions were determined in mean density of NF-κB, and in mean number of cells in EIU rats pretreated either with topical AZM, or topical MXF. Conclusions: Topically applied AZM or MXF may be beneficial in the suppression of TNF-α production in aqueous humor. [ABSTRACT FROM AUTHOR]

To investigate protective effects of VVN001 on lipopolysaccharide (LPS)-induced inflammatory response in human retinal pigment epithelial (RPE) cells and in a mouse model of endotoxin-induced uveitis (EIU), and to explore the underlying mechanisms. Human primary RPE (hRPE) and ARPE-19 cells were pretreated with or without VVN001 for 1 h followed by 10 μg/mL LPS stimulation for 24 h. mRNA, and protein levels of inflammatory cytokines were analyzed with real-time PCR, western blotting, and ELISA. EIU was induced by intravitreal injection of 125 ng LPS in female BALB/c mice. VVN001 eye drops (1%) were locally administrated every 4 h for 24 h after LPS injection. Clinical scores were assessed with a slit lamp. mRNA and protein levels of inflammatory cytokines were investigated simultaneously. Compared with the LPS group, VVN001 pretreatment significantly reduced mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), IL-6, IL-8, TNF-α, IL-1β, IL-18, caspase-1 in hRPE, and ARPE-19 cells. Protein overproduction of ICAM-1, TNF-α, IL-1β, NLRP3, caspase-1 P20, and p-IκBα/IκBα stimulated by LPS was suppressed by VVN001 pretreatment. In vivo, VVN001 significantly reduced the average clinical score from 5.0 to 1.3 in EIU mice. Furthermore, overproduction of ICAM-1, IL-1β, NLRP3, caspase-1 P20, and p-IκBα/IκBα at mRNA and protein levels were remarkably suppressed by VVN001. VVN001 alleviated the inflammatory response induced by LPS both in vitro and in vivo. The effect of anti-inflammation is associated with inhibiting the overproduction of ICAM-1 and blocking the activation of NLRP3 inflammasome and the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: Calcium channel blockers (CCBs), widely used for hypertensive patients, have recently been shown to inhibit atherosclerosis by their antioxidative action. The aim of the present study was to examine whether the CCBs nilvadipine and diltiazem reduce ocular inflammation in endotoxin-induced uveitis (EIU). Methods: EIU was induced in male C57/B6 mice with a single intraperitoneal injection of lipopolysaccharide (LPS). The animals received intraperitoneal injections of either nilvadipine, diltiazem, or vehicle for 5 days before the LPS application. Twenty-four hours after EIU induction, adherent leukocytes to the retinal vasculature were counted with a concanavalin A lectin perfusion-labeling technique. The protein concentration in the aqueous humor was measured to assess blood-ocular barrier breakdown. Retinal levels of intercellular adhesion molecule (ICAM)-1 and monocyte chemotactic protein (MCP)-1 were analyzed by enzyme-linked immunosorbent assay. LPS-stimulated generation of superoxide in murine microvascular endothelial cells was examined with a nitroblue tetrazolium assay. Results: Compared to vehicle treatment, application of nilvadipine, but not diltiazem, led to significant suppression of EIU-associated retinal leukocyte adhesion, together with anterior-chamber protein leakage, retinal expression of ICAM-1 and MCP-1, and LPS-induced superoxide generation in vitro. Conclusions: The CCB nilvadipine exercises an inhibitory effect on the pathogenesis of ocular inflammation through the suppression of inflammation-related molecules. [ABSTRACT FROM AUTHOR]