Clinical efficacy of sodium aescinate administration following endovenous laser ablation for varicose veins.

BACKGROUND: Endovenous interventions and minimally invasive procedures are effective in the management of varicose veins. However, they can cause postoperative discomfort. OBJECTIVE: To evaluate the clinical efficacy of sodium aescinate (SA) in improving edema, pain, vein-specific symptoms, and quality of life in patients following endovenous laser ablation (EVLA) for varicose veins. METHODS: In this single-center randomized controlled trial (RCT), patients were allocated into two groups: in Group A, 60 mg SA was administered twice daily for 20 days, and in Group B (control), no venoactive drug was prescribed. The Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system for chronic venous disorders was used to assess the varicose veins. The circumferences of the calf and ankle were recorded for evaluating edema. The 10-point Visual Analog Scale (VAS), Venous Clinical Severity Score (VCSS), and Aberdeen Varicose Veins Questionnaire (AVVQ) were used to measure the pain intensity, overall varicose vein severity, and patient's quality of life, respectively. RESULTS: The study included 87 patients (mean age, 59.9 ± 10.7 years; 54 men) with CEAP class C2-C5 varicose veins who underwent EVLA and phlebectomy or foam sclerotherapy. The calf circumference recovered quicker in Group A than in Group B by days 10, 21, and 30 (difference from baseline was 1.04 ± 0.35 vs 2.39 ± 1.15 [p < .001], 0.48 ± 0.42 vs1.73 ± 1.00 [p < .001], and 0.18 ± 0.64 vs 0.82 ± 0.96 [p < .001], respectively). The ankle circumference recovered quicker in Group A than in Group B by days 10 and 21 (the difference from baseline was 1.37 ± 0.52 vs 2.36 ± 0.93 [p < .001] and 0.58 ± 0.60 vs 1.14 ± 0.88 [p = .002], respectively). Pain relief was achieved quicker in Group A than in Group B (0.257 ± 1.097 [p = .0863] vs 0.506 ± 1.250 [p = .0168] by day 21). There were no significant differences in the VCSS and AVVQ scores between both groups. There were no drug-related adverse effects. CONCLUSIONS: SA, in combination with compression therapy, can relieve edema and alleviate pain in patients following EVLA for varicose veins.

Sodium aescinate ameliorates chronic neuropathic pain in male mice via suppressing JNK/p38-mediated microglia activation.

OBJECTIVE: A study confirmed that sodium aescinate (SA) can effectively relieve bone cancer pain, but its role in neuropathic pain (NP) remains confused. METHODS: Eighty male mice were randomly divided into four groups: sham+vehicle, sham+SA (40 µg/L, intrathecal injection), chronic contraction injury (CCI)+vehicle, CCI+SA. Behavioral assessments were used to evaluate the locomotor activity and paw withdrawal threshold (PWT) of mice. At the end of the study, spinal cord tissues were collected for histopathological analysis. The JNK/p38 signaling activation, Iba-1 expression, pro-inflammatory cytokines levels, and microglia subtype were assessed by western blotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and flow cytometry with CD86/CD206, respectively. RESULTS: Early treatment with SA delayed the development of mechanical allodynia in CCI mice. Repeated SA treatment could prominently increase the reduction of PWT induced by CCI, and improve the locomotor activity of CCI mice. Mechanically, CCI surgery induced significant up-regulation of p-JNK and p-p38 protein levels, increased number and M1/M2 ratio of microglia, as well as pro-inflammatory factors in the spinal cords of mice, which could be blocked after SA administration. CONCLUSIONS: SA might suppress the activation of microglia and neuroinflammation by selectively inhibiting the JNK/p38 signaling pathway, thereby alleviating CCI-induced NP in male mice.

Sodium aescinate induces renal toxicity by promoting Nrf2/GPX4-mediated ferroptosis.

Sodium aescinate (SA) is extracted from Aesculus wilsonii Rehd seeds and was first marketed as a medicament in German. With the wide application of SA in clinical practice, reports of adverse drug reactions and adverse events have gradually increased, including renal impairment. However, the pathogenic mechanisms of SA have not yet been fully elucidated. The toxic effects and underlying mechanisms of SA were explored in this study. Our data showed that SA significantly elevated the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and Kidney injury molecule 1 (Kim-1), accompanied by pathologically significant changes in renal tissue. SA induced NRK-52E cell death and disrupted the integrity of the cell membrane. Moreover, SA caused significant reductions in FTH, Nrf2, xCT, GPX4, and FSP1 levels, but increased TFR1 and ACSL4 levels. SA decreased glutathione peroxidase (GPx), glutathione (GSH) and cysteine (Cys) levels, but improved Fe2+, malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxidation levels, ultimately leading to the induction of ferroptosis. Importantly, inhibition of ferroptosis or activation of the Nrf2/GPX4 pathway prevented SA-induced nephrotoxicity. These findings indicated that SA induced oxidative damage and ferroptosis-mediated kidney injury by suppressing the Nrf2/GPX4 axis activity.

Chiral Supramolecular Hydrogel Enhanced Transdermal Delivery of Sodium Aescinate to Modulate M1 Macrophage Polarization Against Lymphedema.

Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, it is commonly administered intravenously in clinical practice and often accompanied by severe toxic side effects and short metabolic cycles. Herein, SA-loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA- loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L-type hydrogels are found to have preferable drug penetration over D-type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration.

Neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating SIRT1/NF-κB signaling pathway / 中国药房

OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 （SIRT1）/nuclear factor-κB （NF-κB） signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group， sodium aescinate low-dose group （1.8 mg/kg）， sodium aescinate high-dose group （3.6 mg/kg）， sodium aescinate+EX527 （sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg） group， with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally， once a day， for 21 consecutive days. Twenty-four hours after the end of the last administration， the motor and cognitive functions of rats were detected， and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine （DA） in the nigrostriatal and the expression levels of tyrosine hydroxylase （TH） and α-synuclein （α-Syn） in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 （IL-6）， IL-18]， anti-inflammatory factor （IL-10）， and the expression levels of SIRT1， phosphorylated NF-κB p65 （p-NF-κB p65） and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group， the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group； the number of rotations， escape latency， the expression levels of α-Syn in substantia nigra， the levels of serum pro-inflammatory factors， the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly （P＜0.05）； the target quadrant residence time， the content of DA in nigrostriatal， the expression level of TH in substantia nigra， the serum level of anti-inflammatory factor， and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened （P＜0.05）. Compared with model group， the damage degrees of neuron in sodium aescinate groups were alleviated， and the quantitative indicators were significantly improved， which were more significant in the high-dose group （P＜0.05）； EX527 could reverse the improvement effect of high-dose sodium aescinate （P＜0.05）. CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1， thereby reducing the neuroinflammation of rats with Parkinson’s disease， improving the motor and cognitive dysfunctions， and finally playing a neuroprotective role.

Sodium aescinate improve behavioral performance by inhibiting dorsal raphe nucleus NLRP3 inflammasome in Post-traumatic stress disorder Rat Model.

Growing evidence suggest that NLRP3 inflammasome activation in hippocampus and amygdala is involved in the pathophysiology of PTSD. Our previous studies have demonstrated that apoptosis of dorsal raphe nucleus (DRN) contributes to the pathological progression of PTSD. Recent studies by others have shown that in brain injury sodium aescinate (SA) has a protective effect on neurons by inhibiting inflammatory response pathways, thereby relieving symptoms. Here, we extend the therapeutic effects of SA to PTSD rats. We found that PTSD was associated with significant activation of the NLRP3 inflammasome in DRN, whereas administration of SA significantly inhibited DRN NLRP3 inflammasome activation and reduced DRN apoptosis level. SA also improved learning and memory ability and reduced anxiety and depression level in PTSD rats. In addition, NLRP3 inflammasome activation in DRN of PTSD rats impaired mitochondria function by inhibiting ATP synthesis and increasing ROS production, whereas SA can effectively reverse the pathological progression of mitochondria. We recommend SA as a new candidate for the pharmacological treatment of PTSD.

Sodium aescinate inhibits microglia activation through NF-κB pathway and exerts neuroprotective effect.

Background: Microglia are resident immune cells of the central nervous system that sense environmental changes and maintain central nervous system homeostasis. Dysfunctional microglia produce toxic mediators that lead to neuronal death. Recent studies suggest that Sodium Aescinate has a neuroprotective effect. However, it is unclear whether Sodium Aescinate exerts neuroprotective effects by inhibiting activation of microglia. Method: Traumatic brain injury and lipopolysaccharide neuroinflammation model were used to evaluate the microglia activation in vivo. BV2 and primary microglia cells were used to assess the microglia activation in vitro. Molecular docking technique was used to predict the binding energy of Sodium Aescinate to NF-κB signaling pathway proteins. Result: Sodium Aescinate inhibited microglial activation in-vivo and in-vitro. Sodium Aescinate inhibited the activation of microglia in Traumatic brain injury and lipopolysaccharide mouse models. Sodium Aescinate also inhibited the expression of inflammatory proteins in BV2 and primary microglia cells. Western blot experiment showed that SA inhibited the activation of NF-κB pathway in BV2 and primary microglia cells. Molecular docking results also showed that Sodium Aescinate had a better affinity with the core protein of the NF-κB pathway. Western blot identified that SA inhibited activation of NF-κB pathway. In Traumatic brain injury model and conditioned medium experiment, Sodium Aescinate pretreatment inhibited inflammation and protected neuron. Conclusion: Our study confirmed that the protection effects of Sodium Aescinate on neurons by inhibiting microglia activation through NF-κB pathway.

Modification of sodium aescinate into a safer, more stable and effective water-soluble drug by liposome-encapsulation: an in vitro and in vivo study.

Sodium aescinate (SA) is often used for intravenous (IV) injection owing to its anti-inflammatory, anti-exudative, increasing venous tension, improving blood circulation and reducing swelling activities. However, the clinical application of SA is limited by strong irritation, short half-life and low bioavailability. To overcome these defects, we intended to modify SA by encapsualing it with liposomes . SA was mixed with a proper amount of phospholipid and lyophilized to prepare the liposome of sodium aescinate for injection (SA-Lip-I). Its physical properties, cumulative release and dilution stability were evaluated in vitro. Its pharmacodynamic characteristics were evaluated. Safety of SA-Lip-I was evaluated in terms of hemolysis, IV irritation and acute toxicity. The mean particle size of SA-Lip-I was 117.33±0.95 nm, polydispersity index (PDI) was 0.140±0.017, Zeta potential was -30.34±0.23 mv, The cumulative release of SA-Lip at 12 h was more than 80%, which met the release requirements of nanoparticles. SA-Lip-I was well stable in the four mediators and met the clinical medication requirements. In addition, SA-Lip-I had better efficacy than the SA-I and has a significant difference. Furthermore, SA-Lip-I did not induce hemolysis at 37°C, and produced by far milder venous irritation as compared with SA-I. In addition, LD50 of SA-Lip-I was 2.12 fold that of the commercial SA-I, with no obvious side effects.The modified SA-Lip-I is a promising preparation which can reduce the irritation and toxic side effects, improve the treatment effect to a certain extent, but greatly alleviate pain of the patient during treatment, achieving the optimal curative effect.

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

AIM: To investigate the anti-proliferation and apoptosis-inducing 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 72h). 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 48h was selected for subsequent experiments. After pretreatment with SA for 24 and 48h, 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 concentration-dependent manner. Following its intervention in the cell cycle pathway, SA can inhibit the expression of CDK1 and CyclinB1 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.

Sodium aescinate and its bioactive components induce degranulation via oxidative stress in RBL-2H3 mast cells.

Sodium aescinate (SA) is a vital salt of sodium escin from Aesculus wilsonii Rehd seeds. SA injection (SAI) has received great success in treating cerebral edema, venous reflux disease and other inflammatory conditions. Recently, high incidences of immediate hypersensitivity reactions were reported after SA infusion, which raised questions on safety and risk associated with its clinical application. This study was designed to check whether SAI and its four components induce degranulation using RBL-2H3 mast cells. For this purpose, we evaluated different treatment levels of SAI (20, 40, 60, 80 and 100 µg ml-1) and its four characteristic components, SA-A, SA-B, SA-C and SA-D, at 60 µg ml-1 in different tests including cell viability test, ß-hexosaminidase and histamine assays, oxidative stress indices, apoptosis analysis and intracellular calcium ions in RBL-2H3 cells. Our results demonstrated that SAI at 80 µg ml-1 and 100 µg ml-1, and its two components (SA-B and SA-D) at 60 µg ml-1 were responsible for disturbing cell morphology and cell viability, elevated levels of ß-hexosaminidase, histamine, modulation of oxidative stress indices, induced apoptosis and increase in intracellular calcium ions in RBL-2H3 cells, when compared with the control. Our results demonstrated for the first time that SAI was more likely to induce immediate hypersensitivity reactions attributable to degranulation via oxidative stress caused by SA-B and SA-D components. These results would not only be useful for the safety of end user but also for the industry to improve the quality of SA infusion.

Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance.

BACKGROUND: The development of paclitaxel (PTX) resistance seriously restricts its clinical efficacy. An attractive option for combating resistance is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. We have reported that flavokawain A (FKA) inhibited P-gp protein expression in PTX-resistant A549 (A549/T) cells, indicating that FKA combined with PTX may reverse PTX resistance. However, due to the variable pharmacokinetics of FKA and PTX, the conventional cocktail combination in clinics may cause uncertainty of treatment efficacy in vivo. MATERIALS AND METHODS: To synergistically elevate the anti-cancer activity of PTX and FKA in vivo, the national medical products administration (NMPA) approved sodium aescinate (Aes) was utilized to stabilize hydrophobic PTX and FKA to form polymer-free twin like PTX-A nanoparticles (NPs) and FKA-A NPs. RESULTS: The resulting nanoparticles prepared simply by nanoprecipitation possessed similar particle size, good stability and ultrahigh drug loadings of up to 50%. With the aid of Aes, these two drugs accumulated in tumor tissue by passive targeting and were efficiently taken up by A549/T cells; this resulted in significant suppression of tumor growth in A549/T homograft mice at a low PTX dose (2.5 mg·kg-1). Synergistic effects and reversed PTX resistance were achieved by the combination of PTX-A NPs and FKA-A NPs by inhibiting P-gp expression in tumor cells. CONCLUSION: Using NMPA-approved Aes to prepare twin-like nanoparticles without introducing any new materials provides an efficient platform for combination chemotherapy and clinical translation.

Sodium aescinate significantly suppress postoperative peritoneal adhesion by inhibiting the RhoA/ROCK signaling pathway.

BACKGROUND: Although mechanical barriers and modern surgical techniques have been developed to prevent postoperative adhesion formation, high incidence of adhesions still represents an important challenge in abdominal surgery. So far, there has been no available therapeutic drug in clinical practice. PURPOSE: In this study, we explored the efficacy of sodium aescinate (AESS) treatment against postoperative peritoneal adhesions, the potential molecular mechanism was also investigated. STUDY DESIGN AND METHODS: Sixty male Sprague-Dawley rats were randomly divided into 6 groups for the study: the blank, vehicle, positive control and three AESS administration groups (0.5, 1 and 2 mg/kg/d, intravenous administration for 7 days). Adhesions were induced by discretely ligating peritoneal sidewall. An IL-1ß-induced HMrSV5 cell model was also performed to explore possible functional mechanism. RESULTS: The results indicated that the incidence and severity of peritoneal adhesions were significantly lower in the AESS-treated groups than that in the vehicle and positive control group. AESS-treated groups showed that the secretion, activity, and expression of tPA in rat peritoneum were notably increased. The FIB levels in rat plasma were decreased. The immunohistochemical staining analysis demonstrated that collagen I and α-SMA deposition were significantly attenuated in AESS-treated peritoneal tissues. Besides, we found that AESS treatment reduced the protein levels of p-MYPT1. To further explore the mechanisms of AESS, both activator and inhibitors of RhoA/ROCK pathway were employed in this study. It was found that AESS-induced up-regulation of tPA was reversed by activator of ROCK, but the effects of ROCK inhibitors were consistent with AESS. CONCLUSION: Taken together, the findings of in vivo and in vitro experiments proved that AESS could significantly suppress postoperative peritoneal adhesion formation through inhibiting the RhoA/ROCK signaling pathway. Our researches provide important pharmacological basis for AESS development as a potential therapeutic agent on peritoneal adhesions.

Sodium aescinate provides neuroprotection in experimental traumatic brain injury via the Nrf2-ARE pathway.

Sodium aescinate (SA), a natural plant extract, has been proven to provide neuroprotection in neurological diseases. However, its role and the underlying pathophysiological mechanisms in traumatic brain injury (TBI) are still not well understood. The present study was aimed to investigate the protective effects of SA in both in vivo and in vitro TBI models. Mice or neurons were randomly divided into control, TBI, TBI + vehicle and TBI + SA groups. Neurologic severity score (NSS) was used to evaluate the neurological impairment. Brain water content and lesion volume were used to assess the brain injury degree. Malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were used to estimate oxidative stress. Western blot was used to determine the protein levels. Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick 3'-end labeling (TUNEL) staining were used to measure cell death and apoptosis. Our results revealed that treatment of SA could improve neurological function, decrease cerebral edema and attenuate brain lesion after TBI. Furthermore, administration of SA suppressed TBI-induced oxidative stress, neuron cell death and apoptosis. In addition, SA activated the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway after TBI. However, SA failed to provide neuroprotection following TBI in Nrf2-/- mice. Taken together, our results provided the first evidence that SA treatment played a key role in neuroprotection after TBI through the Nrf2-ARE pathway.

Sodium aescinate alleviates CC14-induced liver fibrosis in rats by inhibiting phosphorylation of 4EBP1 / 中国药理学通报

Aim To study the inhibitory effects of sodium aescinate in liver fibrosis induced by carbon tetrachloride (CCl4 ). Methods Forty-one male SD rats were recruited in this study and randomized into control group (n = 5), model group (n = 18), and sodium aescinate treated group (n = 18) . Masson staining was performed for collagen fiber detecting, and IHC staining was conducted for accessing the expression of interest proteins in rat liver. MTT and apoptosis assay were performed to evaluate the effects of sodium aescinate on HSC-T6 cells. The expression of interest proteins was detected by immunoblotting. Results Sodium aescinate alleviated the liver fibrosis induced by CCl4 through proliferation inhibition and apoptosis induction in HSC-T6 cells. Sodium aescinate also down-regulated the phosphorylation of 4EBP1, the expression of collagen I and collagen III. Conclusion Sodium aescinate alleviates liver fibrosis induced by CCl4,.

Application of near infrared spectroscopy analysis method in rapid detection of sodium aescinate / 药学实践杂志

Objective To establish a fast detection method of sodium aescinate by using near infrared (NIR) spectroscopy analysis method for the determination of the content of sodium aescinate for injection. Methods OPUS software was used to optimize the collected spectrum. PLS algorithm and factorization algorithm were used to establish quantitative model and qualitative model. Results The correlation coefficient of the quantitative model reached 0.9926, the RMSECV deviation was 0.253. The deviation between the predicted value of the sample and the true measured value was less than 5%, which could accurately predict the content of sodium aescinate. Conclution The qualitative model can effectively distinguish the samples of other varieties that have not participated in the modeling, and provide a reference for the rapid screening of the drug.

CARMA3/NF-κB signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate.

BACKGROUND: Primary hepatocellular carcinoma (HCC) is a very malignant tumor in the world. CARMA3 plays an oncogenic role in the pathogenesis of various tumors. However, the function of CARMA3 in HCC has not been fully clarified. AIM: To study the biological function of CAEMA3 in HCC. METHODS: Tissue microarray slides including tissues form 100 HCC patients were applied to access the expression of CARMA3 in HCC and its clinical relevance. Knockdown and overexpression of CARMA3 were conducted with plasmid transfection. MTT, colony formation, and apoptosis assays were performed to check the biological activity of cells. RESULTS: Higher expression of CARMA3 in HCC was relevant to poor prognostic survival (P < 0.05). Down-regulation of CARMA3 inhibited proliferation and colony formation and induced apoptosis in HCC cell lines, while increasing its expression promoted tumorigenesis. We also found that sodium aescinate (SA), a natural herb extract, exerted anti-proliferation effects in HCC cells by suppressing the CARMA3/nuclear factor kappa-B (NF-κB) pathway. CONCLUSION: Overexpression of CARMA3 in HCC tissues correlates with a poor prognosis in HCC patients. CARMA3 acts pro-tumorigenic effects partly through activation of CARMA3/NF-κB. SA inhibits HCC growth by targeting CARMA3/NF-κB.

Study on sodium aescinate inhibiting hepatocellular carcinoma by eif4a1 / 中国药理学通报

Aim To investigate the correlation between the expression of EIF4A1 and hepatocellular carcinoma (HCC) and the potential mechanism of sodium aescinate inhibiting the proliferation of hepatoma cell lines. Methods Immunohistochemistry was used to detect the expression level of EIF4A1 in tumor specimens of 80 patients with HCC. The results combined with clinical indicators and follow-up information were used to analyze their relevance. Annexin V-FITC/PI double staining method was employed to detect the effects of sodium aescinate on apoptosis of HepG2 and human L02 cell lines. Transwell migration assay was used to detect the effect of sodium aescinate on the migration of two cell lines. Western blot, qPCR and immunofluorescence were used to detect the expression changes of E1F4A1 of two cell lines after sodium aescinate treat ment. Results The expression of EIF4A1 significantly increased in HCC tissues, and the expression of EIF4A1 was correlated with tumor differentiation, tumor diameter and survival time. Sodium aescinate (40 jxmol • L"1) could significantly promote the apoptosis of liver cancer cell line and inhibit its migration a-bility, but had no effect on normal liver cell line. Sodium aescinate inhibited the growth and proliferation of hepatoma cell line while down-regulated the expression of hepatoma cell line EIF4A1. Conclusions EIF4A1 is associated with the development of HCC, and sodium aescinate can inhibit hepatoma cell line via affecting the expression of EIF4A1.

[The effect of pulmonary injury in rats induced by paraquat].

Objective: To study the effect of sodium aescinate on the development process of lung injury induced by paraquat. Methods: Forty-five health adult male SD rats were randomly divided into control group, PQ group, sodium aescinate group, and 15 rats in each group. The PQ group and sodium aescinate group were given a one-time intraperitoneal injection of 18mg/kg body weight of rats PQ, the control group was given the same amout normal saline. Rats in sodium aescinate group were injected 2 mg/kg body weight sodium aescinate into abdominal cavity for 7 days continually, but the same volume of saline was injected into the other groups. Finally, at 7, 14 and 28 days after PQ poisoning, five rats were kills for measuring lung tissue pathological changes and the value of TGF-ß(1), TNF-α, hydroxyproline in each group. Results: The expression of TNF-α in serum of 7th day [ (17.03±0.82) ng/ml] and 14th day [ (15.74±0.91) ng/ml] of sodium aescinate group were lower than the corresponding period of PQ groups', and the difference had statistical significance (P<0.05) . The expression of TGF-ß(1) in serum of 7th day[ (225.93±8.33) ng/ml], 14th day [ (216.62±9.48) ng/ml] and 28th[ (181.41±6.10) ng/ml] of sodium aescinate group were lower than the corresponding period of PQ groups', and the difference had statistical significance (P<0.05) . Lung tissue pathological changes showed, compared with control group, inflammatory injury at 7th day and fibrosis degree at 28th of rats' lung reduced on sodium aescinate group. The expression of hydroxyproline in rats' lung of 7th day[ (1.246±0.018) µg/mg], 14th day [ (1.269±0.034) µg/mg] and 28th[ (1.283±0.028) µg/mg] of sodium aescinate group were lower than the corresponding period of PQ groups', and the difference had statistical significance (P<0.05) . Conclusion: sodium aescinate could reduce the pulmonary inflammatory injury and hydroxyproline value of PQ poisoning rats, so sodium aescinate could ameliorate lung injury induced by PQ.

Sodium aescinate inhibits proliferation of hepatocellular carcinoma through CARMA3/NF-κB signaling pathway / 中国药理学通报

Aim To investigate the expression of CAR-MA3, NF-κB in hepatocellular carcinoma tissues and the underlying mechanism of sodium aescinate in inhib-iting the proliferation of human hepatocellular carcino-ma cells. Methods The expression of CARMA3 and NF-κB in HCC tissues were detected by tissue microar-ray immunohistochemistry. MTT was used to determine the effect of sodium aescinate on the proliferation of HCC cells. Cell apoptosis was detected by flow cytom-etry. The expression of CARMA3, NF-κB protein in HepG2 and Hep3B cells treated with sodium aescinate was detected by Western blot and cell immunofluores-cence. Results Tissue microarray analysis showed that the expression of CARMA3 in HCC was up-regulated compared with the adjacent adjacent liver tissues, and the histopathological differentiation, TNM stage, tumor volume and prognosis were correlated. Sodium aesci-nate in 40 μmol·L-1concentration ( IC50) inhibited the growth of HCC cell lines, promoting its apoptosis, but without toxic effects on normal liver cells. Western blot and cell immunofluorescence detection of sodium aescinate could significantly inhibit the expression of CARMA3 and NF-κB. Conclusion Sodium aescinate can effectively inhibit the proliferation of HCC cells by inhibiting the activation of CARMA3/NF-κB signaling in HCC.

The effect of pulmonary injury in rats induced by paraquat / 中华劳动卫生职业病杂志

Objective@#To study the effect of sodium aescinate on the development process of lung injury induced by paraquat.@*Methods@#Forty-five health adult male SD rats were randomly divided into control group, PQ group, sodium aescinate group, and 15 rats in each group. The PQ group and sodium aescinate group were given a one-time intraperitoneal injection of 18mg/kg body weight of rats PQ, the control group was given the same amout normal saline. Rats in sodium aescinate group were injected 2 mg/kg body weight sodium aescinate into abdominal cavity for 7 days continually, but the same volume of saline was injected into the other groups. Finally, at 7, 14 and 28 days after PQ poisoning, five rats were kills for measuring lung tissue pathological changes and the value of TGF-β1, TNF-α, hydroxyproline in each group.@*Results@#The expression of TNF-α in serum of 7th day [ (17.03±0.82) ng/ml] and 14th day [ (15.74±0.91) ng/ml] of sodium aescinate group were lower than the corresponding period of PQ groups’, and the difference had statistical significance (P<0.05) . The expression of TGF-β1 in serum of 7th day[ (225.93±8.33) ng/ml], 14th day [ (216.62±9.48) ng/ml] and 28th[ (181.41±6.10) ng/ml] of sodium aescinate group were lower than the corresponding period of PQ groups’, and the difference had statistical significance (P<0.05) . Lung tissue pathological changes showed, compared with control group, inflammatory injury at 7th day and fibrosis degree at 28th of rats’ lung reduced on sodium aescinate group. The expression of hydroxyproline in rats’ lung of 7th day[ (1.246±0.018) μg/mg], 14th day [ (1.269±0.034) μg/mg] and 28th[ (1.283±0.028) μg/mg] of sodium aescinate group were lower than the corresponding period of PQ groups’, and the difference had statistical significance (P<0.05) .@*Conclusion@#sodium aescinate could reduce the pulmonary inflammatory injury and hydroxyproline value of PQ poisoning rats, so sodium aescinate could ameliorate lung injury induced by PQ.