Ginsenoside Rb1 protects dopaminergic neurons from inflammatory injury induced by intranigral lipopolysaccharide injection.

Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson's disease. As such, inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson's disease. Ginsenoside Rb1, the most active ingredient of ginseng, reportedly exerts neuroprotective effects by suppressing inflammation in vitro. The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rb1 in a lipopolysaccharide-induced rat Parkinson's disease model. Rats were divided into four groups. In the control group, sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days. In the ginsenoside Rb1 group, ginsenoside Rb1 (20 mg/kg) was intraperitoneally injected for 14 consecutive days after sham surgery. In the lipopolysaccharide group, a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson's disease model. Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days. In the ginsenoside Rb1 + lipopolysaccharide group, lipopolysaccharide was unilaterally microinjected into the rat substantial nigra. Subsequently, ginsenoside Rb1 was intraperitoneally injected for 14 consecutive days. To investigate the therapeutic effects of ginsenoside Rb1, behavioral tests were performed on day 15 after lipopolysaccharide injection. We found that ginsenoside Rb1 treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group. To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rb1, contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography. Compared with the lipopolysaccharide group, ginsenoside Rb1 obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites in the striatum. To further explore the neuroprotective effect of ginsenoside Rb1 against lipopolysaccharide-induced neurotoxicity, immunohistochemistry and western blot assay of tyrosine hydroxylase were performed to evaluate dopaminergic neuron degeneration in the substantial nigra par compacta. The results showed that lipopolysaccharide injection caused a large loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra and a significant decrease in overall tyrosine hydroxylase expression. However, ginsenoside Rb1 noticeably reversed these changes. To investigate whether the neuroprotective effect of ginsenoside Rb1 was associated with inhibition of lipopolysaccharide-induced microglial activation, we examined expression of the microglia marker Iba-1. Our results confirmed that lipopolysaccharide injection induced a significant increase in Iba-1 expression in the substantia nigra; however, ginsenoside Rb1 effectively suppressed lipopolysaccharide-induced microglial overactivation. To elucidate the inhibitory mechanism of ginsenoside Rb1, we examined expression levels of inflammatory mediators (tumor necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and cyclooxygenase 2) and phosphorylation of nuclear factor kappa B signaling-related proteins (IκB, IKK) in the substantia nigra with enzyme-linked immunosorbent and western blot assays. Our results revealed that compared with the control group, phosphorylation and expression of inflammatory mediators IκB and IKK in the substantia nigra of lipopolysaccharide group rats were significantly increased; whereas, ginsenoside Rb1 obviously reduced lipopolysaccharide-induced changes on the lesioned side of the substantial nigra par compacta. These findings confirm that ginsenoside Rb1 can inhibit inflammation induced by lipopolysaccharide injection into the substantia nigra and protect dopaminergic neurons, which may be related to its inhibition of the nuclear factor kappa B signaling pathway. This study was approved by the Experimental Animal Ethics Committee of Shandong University of China in April 2016 (approval No. KYLL-2016-0148).

Effects of remote ischemic preconditioning on contrast induced nephropathy after percutaneous coronary intervention in patients with acute coronary syndrome.

OBJECTIVE: The aim of this study was to explore the clinical effects of remote ischemic preconditioning (RIPC) on contrast-induced nephropathy after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). PATIENTS AND METHODS: The study was a single-center, prospective, randomized, controlled study. A total of 161 patients with ACS and the rate of estimate glomerular filtration (eGFR) 15 to 70 mL/min/1.73 m2 undergoing PCI were randomly assigned to RIPC group (induced by 4 times of 5-minute inflations of a blood pressure cuff to 200 mmHg around the upper arm, followed by 5-min intervals of reperfusion at 1 hour before PCI therapy) or control group (an uninflated cuff around the arm). Successful completion of the PCI eventually included 107 cases of patients, including 50 cases in the RIPC group and 57 cases in the control group. The level of serum creatinine (Scr), CystatinC (CysC), blood neutrophil gelatinase-associated lipocalin (NGAL), eGFR were measured in all patients at 6 AM before the day of PCI, and 4-hour NGAL, 24-hour CysC, 72-hour Scr, and eGFR after PCI in the 2 groups. The incidence of major adverse events in the kidney (including the incidence of CIN, the need for dialysis, or renal replacement therapy after using contrast agent) and the composite endpoint of cardiovascular events were recorded at 6 months after PCI. RESULTS: There were no statistically significant differences in baseline indicators between the 2 groups. Scr, CysC, and blood NGAL levels and the incidence of CIN in patients with RIPC group were significantly lower than those form the control group after PCI (P < .05), but there were no significant differences between the average value of eGFR and occurrence of Major cardiovascular events in the postoperative 6 months (P > .05). CONCLUSIONS: RIPC can reduce PCI-related CIN and protect renal function in patients with ACS. The benefits of these patients by RIPC may be related to the reduction of the NGAL and CysC.