Sepsis is a life-threatening condition driven by a dysregulated host immune response to infection, with cytokine overproduction contributing to organ dysfunction and high mortality. Levosimendan, a calcium sensitizer used in acute heart failure, has been proposed to exert anti-inflammatory effects, but information on its immunomodulatory effects in early sepsis remains scarce. This study aimed to investigate the dose- and time-dependent effects of levosimendan on cytokine profiles in a rat model of lipopolysaccharide (LPS)-induced sepsis. Thirty-two male Wistar albino rats were randomly assigned to four groups: sham, sepsis control, low-dose levosimendan (1 mg/kg), and high-dose levosimendan (2 mg/kg). Cytokine levels (TNF-α, IL-1β, IL-6, IL-8, IL-17, MCP-1) were measured at 5 and 10 h post-LPS administration. High-dose levosimendan significantly reduced TNF-α, IL-1β, IL-6, and MCP-1 levels by the 10th hour, accompanied by improved Murine Sepsis Scores. IL-17 and IL-6 showed biphasic responses, increasing initially and decreasing significantly later, particularly with high-dose treatment. IL-8 reduction was observed only in the high-dose group. These findings support levosimendan’s dose and time-dependent anti-inflammatory effects and suggest it may modulate both early and late-phase cytokines in sepsis. Further studies are warranted to clarify its potential role in clinical sepsis management.

Sepsis is a major cause of morbidity and mortality, with cytokine dysregulation. Levosimendan, a calcium sensitizer with cardioprotective and anti-inflammatory properties. This study investigates the effects of levosimendan on early inflammatory cytokine levels and clinical outcomes in an experimental sepsis model. A murine sepsis model was established using lipopolysaccharide administration. Animals were divided into Sham, Sepsis Control, Low-Dose Levosimendan, and High-Dose Levosimendan groups. Serum cytokine levels (TNF-α, IL-1β, IL-6, IL-8, IL-17, and MCP-1) were measured at the 5th and 10th hours. Sepsis severity was assessed using Murine Sepsis Scores (MSS). TNF-α, IL-1β, IL-6, and MCP-1 levels were significantly elevated in the sepsis control group. Both low- and high-dose levosimendan groups exhibited an initial rise in IL-17 and IL-6, followed by a significant reduction at the 10th hour. High-dose levosimendan demonstrated the most pronounced anti-inflammatory effect, with significant reductions in TNF-α, IL-1β, and MCP-1 levels. MSS scores were significantly lower in levosimendan-treated groups, with high-dose treatment showing the greatest improvement. Levosimendan exerts a dose-dependent immunomodulatory effect in experimental sepsis, with high doses effectively suppressing pro-inflammatory cytokine levels and improving clinical outcomes. These findings highlight the potential therapeutic role of levosimendan in sepsis management, warranting further investigation in clinical settings.

Peripheral nerve injuries affect 13–23 out of 100,000 people annually, with Wallerian degeneration and subsequent inflammatory/oxidative responses critically impacting recovery. Aloperine, a natural alkaloid from Sophora alopecuroides L., exhibits potent anti-inflammatory and antioxidant properties but has never been studied for nerve repair. In this study, we aimed to investigate whether aloperine could enhance peripheral nerve regeneration by modulating inflammation and oxidative stress in a rat sciatic nerve injury model. Thirty male Wistar rats underwent sciatic nerve neurotmesis with epineural repair. Animals were divided into surgical controls (Group A), aloperine-treated rats (Group B; single 100 mg/kg intraperitoneal dose), and intact controls (Group C). After 8 weeks, outcomes were assessed via functional tests (pinprick, hot plate, extensor postural thrust), biochemical analyses (TNF-α, IL-6, IL-10, TOS/TAS), and histomorphometric evaluations (axon counts, diameter indices, immunohistochemistry). Aloperine treatment significantly improved functional recovery, with near-normal hot plate latency and motor performance. Biochemically, it reduced pro-inflammatory markers (TNF-α) while elevating IL-10. Oxidative stress was attenuated. Histologically, treated nerves showed better-preserved axonal architecture (reduced inflammation). This first investigation of aloperine for nerve repair demonstrates its therapeutic potential through dual anti-inflammatory and antioxidant mechanisms, significantly improving functional and structural outcomes. These findings support its development as a novel treatment for peripheral nerve injuries.