Sodium Aescinate Alleviates Neuropathic Pain in Rats by Suppressing the TLR4/NF KB Pathway Activation after Paclitaxel Chemotherapy

Background: Emerging evidence suggests that chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of chemotherapeutic drugs. Many experiments have proved that sodium aescinate (SA) has definite pharmacological effects such as anti-infection, anti-exudation, anti-edema, anti-tumor as well as neuroprotection, and the drug side effects are mild. However, no study has explored whether SA is involved in the analgesic effect of paclitaxel (PAC) induced neuropathic pain in rats. Methods: Rats were given an intraperitoneal injection of PAC (2.5 mg/Kg intraperitoneally on days 1, 3, 5, and 7), while SA 25 mg/kg intraperitoneally was administered daily for 14 consecutive days. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats were examined on experimental days 3, 5, 7, 11, 14. All rats were sacrificed on day 15 of the experiment, and L4-6 spinal cords were removed. Subsequently, immunohistochemistry, HE staining, ELISA, RT-qPCR, Western blotting were applied to evaluate cytoskeletal protein expression (NF-L and NF-M), spinal nerve structural integrity, proinflammatory factor contents (TNF-α, IL-1β, and IL-6), and protein content of the TLR4/NF-κB pathway, respectively. Results: After the rats developed PAC induced pain behaviors, multiple injections of SA rendered the rats with elevated MWT and TWL values, decreased expression of NF-L and NF-M in the spinal cord, materially downregulated content of proinflammatory factors, and reduced amounts of TLR4 and p-NF-κB protein levels. Conclusions: The results of the present study preliminarily indicate that SA has an analgesic effect on rats with CIPN induced by PAC injection, and the mechanism may be related to blocking the TLR4/NF-κB signaling pathway, inhibiting the expression of proinflammatory factors, and alleviating cytoskeletal disorders.

Anti-proliferation and apoptosis-inducing effects of sodium aescinate on retinoblastoma Y79 cells

AIM:To investigate the anti-proliferation and apoptosisinducing effects of sodium aescinate(SA)on retinoblastoma Y79 cells and its mechanism.METHODS:Y79 cells were cultured at different drug concentrations for different periods of time(24,48,and 72 h).The inhibitory effect of SA on proliferation of Y79 cells was detected by the cell counting kit-8(CCK-8)assay,and the morphology of Y79 cells in each group was observed under an inverted microscope.An IC50 of 48 h was selected for subsequent experiments.After pretreatment with SA for 24 and 48 h,cellular DNA distribution and apoptosis were detected by flow cytometry.Real-time qunatitative polymerase chain reaction(RT-qPCR)and Western blot were used to assess changes in related genes(CDK1,CyclinB1,Bax,Bcl-2,caspase-9,caspase-8,and caspase-3).RESULTS:SA inhibited proliferation and induced apoptosis of Y79 cells in a time-dependent and concentrationdependent manner.Following its intervention in the cell cycle pathway,SA can inhibit the expression of CDK1 and Cyclin B1 at the mRNA and protein levels,and block cells in the G2/M phase.In caspase-related apoptotic pathways,up-regulation of Bax and down-regulation of Bcl-2 caused caspase-9 to self-cleave and further activate caspase-3.What’s more,the caspase-8-mediated extrinsic apoptosis pathway was activated,and the activated caspase-8 was released into the cytoplasm to activate caspase-3,which as a member of the downstream apoptotic effect group,initiates a caspase-cascade reaction that induces cell apoptosis.CONCLUSION:SA inhibits the proliferation of Y79 cells by arresting the cell cycle at the G2/M phase,and induces apoptosis via the caspase-related apoptosis pathway,indicating that SA may have promising potential as a chemotherapeutic drug.

Protective Effects of the Preconditioning with Different Doses of Sodium Aescinate on Tourniquet-induced Ischemic Reperfusion

Objective：To evaluate the protective effects of sodium aescinate（SA）preconditioning on the tourniquet-induced ischemia-reperfusion（l/R）injury after limbs operation.Methods：Seventy-five patients with gradeⅠ-Ⅱissued by American Society of Anesthesiology undergoing lower limb operation were randomly assigned to 3 groups：the control group,low-dose SA-treated group and high-dose SA-treated group;each group enrolled 25 patients.The patients were treated with 5 mg and 10 mg SA 30 min before tourniquet inflation in the two treatment groups separately,while the patients in the control group received normal saline.Venous blood samples were obtained before tourniquet was inflated（T0 baseline）.And 5（T1）,10（T2）,20（T3）min after tourniquet was released.The nitric oxide（NO）,malondialdehyde（MDA）and superoxide dismutase（SOD）levels were determined by commercial kits.Meanwhile,arterial pressure（MAP）and heart rate（HR）were monitored from an automatic invigilator.Results：In the control group,MDA and NO levels were increased,and SOD and MAP were decreased significantly after tourniquet deflation compared to TO baseline（P0.05）.After tourniquet deflation,MDA and NO levels in the two treated groups were significantly decreased;meanwhile,SOD levels and MAP were increased,and the variations of HR were more stable compared with the control group（all P0.05）.There was no significant difference in all of the above between the two treated groups（P0.05）. Conclusion：The protective effects of SA preconditioning on tourniquet-induced limb l/R injury might possibly contribute to the increasing of SOD levels,and MAP and the decreasing of MDA and NO levels.