Effect and mechanism of safranal in a mouse model of sepsis-related liver injury induced by lipopolysaccharide / 临床肝胆病杂志

‍ ObjectiveTo investigate the protective effect of safranal against sepsis-related liver injury （SRLI） induced by lipopolysaccharide （LPS） in mice and its mechanism. MethodsA total of 32 experimental male C57BL/6 mice were divided into control group， single drug group， model group， and treatment group using the simple random method， with 8 mice in each group. The mice in the single drug group and the treatment group were intraperitoneally injected with safranal （60 mg/kg） for 7 days of pretreatment， and the mice in the model group and the treatment group were intraperitoneally injected with LPS （10 mg/kg） to induce acute liver injury. The activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured； HE staining was used to observe liver tissue sections； immunohistochemistry was used to analyze the expression of the downstream protein heme oxygenase-1 （HO-1） in the signal pathway； TUNEL was used to analyze the apoptosis of hepatocytes； Western blot was used to measure the expression of total proteins （nuclear factor erythroid 2-related factor 2 ［Nrf-2］ and HO-1） in liver tissue. The human liver cell line L02 was pretreated with safranal （100 μmol/L）， followed by induction of acute hepatocellular injury with LPS （100 ng/mL）， and DCFH-DA fluorescent labeling was used to detect reactive oxygen species （ROS）. ResultsAfter safranal pretreatment， the treatment group had significantly lower levels of ALT and AST than the model group （both P<0.001）， with a relatively intact pseudolobular structure and a smaller necrotic area in the liver. Compared with the model group， the treatment group had significant increases in the expression levels of Nrf2 and HO-1 in liver tissue after safranal+LPS treatment （both P<0.001）， and immunohistochemistry showed that safranal pretreatment increased the number of HO-1-positive cells. In the cell model of LPS-induced acute liver injury， the treatment group had a significant reduction in the production of ROS compared with the model group. ConclusionSafranal can exert a protective effect against SRLI induced by LPS in mice through the Nrf2/HO-1 pathway.

The antiepileptic activity of Safranal in kindling model of epilepsy in male rats

Abstract Recent studies suggested that safranal exerts anticonvulsant properties. The present study aimed to investigate the effect of safranal on epileptic activities in the amygdala electrical kindling model in male rats. Animals were implanted with a recording electrode on the skull and a tripolar in the amygdala. After 10 days of recovery, the afterdischarge (AD) threshold of each animal was determined and stimulated once daily the AD threshold for full kindling development. Then, parameters including afterdischarge duration (ADD), stage 4 latency (S4L), stage 5 duration (S5D), and stimulation threshold were determined before and after injection of safranal (0.05, 0.1, 0.2 ml/ kg; i.p). While the dose of 0.05 ml/kg had no significant effect, the dose of 0.1 ml/kg increased the AD threshold as well as S4L and decreased the S5D (P<0.05). Injection of 0.2 ml/kg of the safranal significantly decreased the ADD and S5D (P<0.05) and 83.3% of animals had no stage 4 and stage 5 of kindling (P<0.001). Based on the obtained data safranal has anticonvulsant effects dosedependently. It seems that a dose of 0.2 ml/kg is the minimum effective dose. Further investigation is warranted to conduct the clinical implications for the treatment of epileptic disorders

Neuroprotective effects of safranal on a rat model of traumatic injury to the spinal cord by anti-apoptotic,anti-inflammatory and edema-attenuating actions / 西安交通大学学报(医学版)

Objective To investigate the effect of safranal on neurologic functions and histopathologic changes after spinal cord injury (SCI)and the related molecular mechanisms.Methods We randomly assigned 36 rats into six groups:control group,injury group and four treatment groups (namely,A,B,C,and D).The Basso Beattie Bresnahan locomotor rating scale (BBB)and HE staining were applied to evaluate the neuroprotective effect and determine the most effective dosage.Another 60 rats were randomly and evenly assigned to three groups:control group,injury group and treatment group.Nissl staining,TUNEL staining and electron microscopy were used to analyze histopathological changes;RT-PCR,immunohistopathological staining,ELISA,and Western blot were used to detect the expressions of apoptosis-related proteins (Bax and Bcl-2 ),inflammation-related factors (IL-1β, IL-10,TNF-αand P38MAPK),and edema-related factor (APQ-4).Results The optimal dosage for safranal was 100 mg/kg.Neurocyte structure was found more distinct in treatment group than in injury group.In addition,we detected a smaller number of apoptotic neurocyte (26.37±1.54 vs.35.94±1.62,P=0.000),decreased Bax (P=0.000)and APQ-4[(359.55±16.12)% vs.(124.53±20.35)%,P=0.000]expressions,increased Bcl-2 (P=0.036)expression,and obviously lowered P38MAPK [(300.30±33.26)% vs.(132.54±10.21)%,P=0.000]expression. Conclusion Safranal exerts its neuroprotective function through anti-apoptosis,anti-inflammation and anti-edema in the rat model of spinal cord injury.