Effect and potential mechanism of sodium ferulate on corneal endothelial dysfunction and CEC injury / 中国药房

OBJECTIVE To investigate the effect and potential mechanism of sodium ferulate （SF） on corneal endothelial dysfunction and corneal endothelial cell （CEC） injury. METHODS The male New Zealand rabbits were divided into control group， benzalkonium chloride （BAK） group and BAK+SF group， with 6 rabbits in each group. Except for control group， the other groups were given BAK into the anterior chamber to induce bullous keratopathy model， and BAK+SF group then given SF solution 200 mg/kg intraperitoneally the next day after surgery， twice a day， for consecutive 14 d. The transparency of corneal and edema of corneal stroma in each group of rabbits （before and on the 1st， 7th， and 14th day after surgery） were observed， and the corneal thickness （14th day after surgery） and intraocular pressure （1st to 14th day after surgery） were measured. On the 14th day after operation， the corneal endothelial structure was evaluated and the expressions of functionally related proteins [phalloidin， zonula occludens-1 （ZO-1）， Na+/K+-ATPase， Ki67] were detected. On the 14th day after surgery， the corneal tissue was collected in BAK group， the primary rabbit CECs were isolated and cultured， and they were divided into blank group and SF groups with different mass concentrations. The cell viabilities after being cultured for different time， and the protein expressions of Ras homologous gene family A （RhoA）， bone morphogenetic protein receptor 1A （BMPR1A） and BMRP2 were determined in each group. RESULTS Compared with BAK group， the transparency of corneal and edema of corneal stroma were gradually improved， and the corneal thickness was significantly decreased in BAK+SF group （P＜0.05）. The rabbit CECs in BAK+SF group were only damaged to zone B and showed a normal hexagonal endothelial cells structure. The protein expressions of phalloidin， ZO-1， Na+/K+-ATPase and Ki67 in BAK+SF group were significantly increased （P＜0.05）. When SF concentration was lower than and equal to 200 mg/L， it could promote the proliferation of rabbit CEC， in concentration manner （P＜0.05） and time-dependent trend. SF at concentrations of 50， 100， and 200 mg/L could up-regulate the protein expressions of RhoA， BMPR1A and BMPR2 in concentration-dependent manner （P＜0.05）. CONCLUSIONS SF can improve the transparency of corneal and edema of corneal stroma in bullous keratopathy model rabbits， reduce corneal thickness， maintain the integrity of corneal endothelium structure， and promote the recovery of corneal endothelial function； this compound can promote the proliferation of CEC， the mechanism of which may be related to the activation of RhoA-ROCK-BMP pathway.

Inhibitory effect of sodium ferulate on inflammatory response in migraine rats based on c-Jun N-terminal kinase / p38 mitogen-activated protein kinase signaling pathway / 解剖学报

[Abstract] Objective To explore the inhibitory effect of sodium ferulate (SF) on the inflammatory response in migraine rats by regulating the c-Jun N-terminal kinase (JNK) / p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Methods The migraine rat model was prepared by intraperitoneal injection of nitroglycerin. After successful modeling, the rats were randomly grouped into model group, SF low dose (SF-L) group (50 mg/ kg), SF high dose (SF-H) group (100 mg/ kg), SF+JNK inhibitor (SF + SP600125) group (SF 100 mg/ kg +SP600125 10 mg/ kg), and SF+JNK activator [SF + anisomycin(AN)] group (SF 100 mg/ kg +AN 5 mg/ kg), 12 in each group, another 12 SD rats without treatment were taken as blank group. The behavioral changes of the rats in each group were observed 24 hours after the administration, the levels of 5-hydroxytryptamine (5-HT), nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum were detected by ELISA, the neuronal apoptosis in brain tissue was observed by TUNEL staining, immunohistochemistry was used to evaluate the expressions of TNF-α, IL-6 and calcitonin gene-related peptide (CGRP) in brain tissue, Western blotting was used to detect the expressions of JNK/ p38 MAPK pathway-related proteins in brain tissue. Results Compared with the blank group, the number of times of scratching the head and climbing the cage of the rats in the model group increased significantly, and the apoptosis rate of neurons increased significantly; the content of 5-HT in serum decreased significantly, and the levels of NO, TNF-α and IL-6 increased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of phosphorylated JNK (p-JNK) / JNK and phosphorylated p38 MAPK(p-p38 MAPK) / p38 MAPK in brain tissue obviously increased (all P<0. 05). Compared with the model group, the number of times of scratching the head and the times of climbing the cage of the rats in the SF-L group and the SF-H group reduced significantly, and the neuron apoptosis rate reduced significantly; the content of 5-HT in serum increased significantly, and the levels of NO, TNF-α and IL-6 decreased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of p-JNK/ JNK and p-p38 MAPK/ p38 MAPK in brain tissue obviously decreased (all P<0. 05). Compared with SF-H group, the protective effect of SF on migraine rats in SF+SP600125 group enhanced significantly; the protective effect of SF on migraine rats in the SF+AN group reversed significantly. Conclusion SF may inhibit the expression of JNK/ p38 MAPK signaling pathway, effectively inhibit neurogenic inflammatory response in migraine rats, reduce neuronal apoptosis, and achieve a protective effect on migraine rats.

Protective effects of sodium ferulate on flap transplantation via anti-inflammatory modulation and oxidative stress inhibition

Ischemia-reperfusion injury (IRI) has brought attention to flap failure in reconstructive surgery. To improve the prognosis of skin transplantation, we performed experimental IRI by surgical obstruction of blood flow and used sodium ferulate (SF) to prevent IRI in rats. After SF treatment, the morphological and histological changes of the skin flaps were observed by H&E and Masson's trichrome staining. We also detected the expression levels of COX-1, HO-1, and Ki67 by immunohistochemical and western blot analysis. Moreover, enzyme-linked immunosorbent assay was used to identify the content of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO) in peripheral blood and skin tissue. Compared with the model group, SF treatment significantly improved the recovered flap area (%) and promoted collagen synthesis. Cyclooxygenase-2 (COX-2) expression was significantly inhibited by heme oxygenase-1 (HO-1) induction after SF treatment. Furthermore, SF significantly inhibited the levels of TNF-α in peripheral blood, MPO and MDA in the skin tissue, and the increased synthesis of NO. Our results showed the protective effects of SF on IRI after flap transplantation and we believe that the protective effects of SF was closely related to the alleviation of the inflammatory response and the inhibition of the oxidative stress injury.

Protective Effect and Mechanism of Sodium Ferulate on Cerebral Ischemia-reperfusion Inflammatory Injury in Rats / 中国实验方剂学杂志

Objective: To investigate the protective effect of sodium ferulate on cerebral ischemia-reperfusion injury in rats and to explore its possible mechanism.Method: The cerebral ischemia reperfusion injury model was established by middle cerebral artery occlusion (MCAO) in SD male rats. 36 modeled rats with neurologic damage were randomly divided into 4 groups:model group, low,medium,high-dose sodium ferulate groups (25,50,100 mg·kg-1).Another nine rats were selected as a sham operation group.Neurological function was assessed by neurological scoring system in rats.Hematoxylin-eosin (HE) staining was performed to observe the pathological changes of the rats' brain. The levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum and brain tissues were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the protein expression of nucleus and cytoplasm nuclear factor-kappa B p65 (NF-κB p65) in brain tissues.Result: As compared with normal group, neurological deficit score was increased; the neuronal necrosis and inflammatory cell number were present;the serum and brain tissue levels of TNF-α, IL-1β and IL-6 were increased; nucleus/cytoplasm NF-κB p65 protein expression ratio was increased significantly in model group (PPPα, IL-1β and IL-6(PPκB p65 protein(PPConclusion: Sodium ferulate protects the brain against focal cerebral ischemia reperfusion injury, and the mechanism may be related to inhibiting nuclear translocation of NF-κB p65 protein to alleviate inflammatory response.

Effect of ferulate-heparin-poloxamer thermosensitive hydrogels on nerve regeneration in rats with spinal cord injury / 中国药理学通报

Aim To investigate the effect of ferulate-heparin-poloxamer (SF-HP) thermosensitive hydrogels on nerve regeneration in ratswith spinal cord injury, and provide experimental basis for clinical application. Methods SD rats were randomly divided into five groups: sham group, SCI group, SCI + HP group, SCI + SF group and SCI + SF-HP group. Rats were performed moderate contusion injuries using a vascular clip for 2 min to establish SCI animal model, then rats were given BBB score and inclined plate scoring function test after SCI. BDA tracing was employed to observe the recovery of nerve conduction function. Moreover, immunohistochemical staining and Western blot-were used to measure GAP43, Nestin and GFAP levels. Results BBB score and inclined plane test score significantly increased in SF-HP treated group as compared with the model group (P < 0. 01). Staining data showed that the structure of spinal cord was void, and this phenomenon was reversed after SF-HP administration. Data showed that the level of GAP43 and Nestin increased after SF treatment (P < 0. 05), the expression of GFAP decreased (P <0. 05), and the treatment effect of SF-HP hydrogels were better than those of SF alone (P < 0. 0 5) . BDA tracing data showed that the number of positive neurons markedly increased and the repair of nerve conduction function was significantly improved in SF-HP hydrogel group compared with SF group. Conclusion HP hydrogels enhance the effect of SF on the nerve regeneration in damaged spinal cord in rats.

Pharmacological research progress of sodium ferulate in cardio-cerebral vascular disease / 中草药

Sodium ferulate is the sodium salt of ferulic acid, an extract of traditional Chinese herbal medicines for promoting blood circulation and detoxification, and it is rich in sources, with few side effects and high safety. Sodium ferulate has many pharmacological effects, which is a cardiovascular drug researched and developed independently in China. It was first approved in 1990 for the clinical treatment of cardiovascular diseases. In recent years, the clinical application of sodium ferulate has become increasingly widespread, and the research field is continuously expanding. Sodium ferulate is effective in treating respiratory diseases, diabetes and complications, and protecting the liver and kidney from damage. Meanwhile it has been widely used in cardiovascular diseases. Here we reviewed the research status of the prominent pharmacological effects of sodium ferulate on cardiovascular diseases in the past 30 years, mainly focusing on the antithrombotic effects, the protection of blood vessels, and the anti-oxidative effect of sodium ferulate. It is expected to provide guidance for clinical applications of sodium ferulate.

Protective effect of sodium ferulate against lipopolysaccharide-induced preterm delivery and intra-uterine fetal death in mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of sodium ferulate (SF) on lipopolysaccharide (LPS)-induced preterm delivery and intra-uterine fetal death (IUFD). METHODS Pregnant Kunming mice were subcutaneously pretreated with SF (25 or 50 mg · kg-1) from gestational day (GD) 10 to GD 15 and with the single injection of LPS (150μg·kg-1, ip) on GD15.5. The incidence of preterm delivery and IUFD was observed. HE staining was used for uterine and placental histological evaluation. The levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) as well as the activities of glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) were detected in the maternal liver, placenta, and fetal liver using commercial kits. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in amniotic fluid were evaluated by enzyme linked immunosorbent assay. RESULTS For LPS group, the incidence of preterm was 47.8%, delivery time was (17.5 ± 1.3) d, and the pups′survival rate was only 42.6%. Compared with LPS-treated group, SF 50 mg · kg-1 group showed a lower incidence of preterm (14.3%, P<0.01), longer gestational days (18.4 ± 0.5, P<0.05), and a higher pups′survival rate (75.6%, P<0.01). SF 50 mg · kg-1 restored the LPS-induced GSH both in the maternal and fatal liver (a tendency without statistical significance), GST activity〔(163±82) kU·g-1 protein vs (95±90) kU·g-1 protein, P<0.01)〕in the placenta, TBARS content〔(2.5±0.4)μmol·g-1 protein vs (3.1±0.6)μmol·g-1 protein, P<0.01〕in the fetal liver, and TNF-αlevel〔(11±8) ng·L-1 vs (20±8) ng·L-1, P<0.01〕in the amniotic fluid. SF also attenuated LPS-induced placental congestion and neutrophil infiltra?tion in the uterus. CONCLUSION SF may protect against LPS-induced preterm delivery and IUFD, and anti-oxidation as well as anti-inflammation may contribute to these effects.

Bioassay of antiplatelet aggregation bioactivity in Chuanxiong Rhizoma with related Chinese patent drugs / 中草药

Objective: To develop a bioassay method to quantify the antiplatelet aggregation bioactivity (AAB) of crude Chuanxiong Rhizoma, decotion pieces, and its Chinese patent medicine for quality assessment. Methods: Chuanxiong Rhizoma sample was extracted in water by reflux. The level of AAB in extract was quantified in vitro. The blood was taken from the heart of rabbit. The platelet aggregating in platelet-rich plasma was induced by adenosine-5'-diphosphate disodium salt. The ratio of platelet inhibition was chosen as AAB marker. Sodium ferulate was a reference. The amount of AAB in aqueous extract was quantified by the Amount reaction of parallel line analysis (2.2) method. The AAB data of herbal sample was calculated by combining the AAB of extract with its extraction rate. Moreover, AAB amounts were quantified in the eight samples including crude Chuanxiong Rhizoma, decoction pieces, and Chinese patent medicines to verify this developed method. Results: Both sodium ferulate and Chuanxiong extract showed significant AAB (P < 0.01). The reliability test for quantifying AAB in solidum ferulate and Chuanxiong Rhizoma extract was passed through, and the measured value was valid. The correlation coefficient was 0.993 4 (n = 4) between the amounts of solidum ferulate in the concentration range of 15-60 mg/mL and their ratios of platelet inhibition. The RSD for the amounts of AAB was 3.43% (n = 6) by six replicated tests with the confidence limit rate of 23.90% (n = 6). The AAB amounts were significantly different among tested samples, i.e. 3.183, 2.068, 1.957, and 1.931 U/g for four Chuanxiong Rhizoma crude samples, 1.304 and 1.021 U/g for Chuanxiong Rhizoma decotion pieces and processed slice with yellow wine, 0.506 and 0.919 U/g for Suxiao Jiuxin Pills and Lemai Granule. Conclusion: The developed method can accurately quantify the level of AAB in Chuanxiong Rhizoma crude, decoction pieces, and Chinese patent medicines, which can be used to assess the product quality of Chuanxiong Rhizoma.

Effects of Shenfukang Capsule Combined with Sodium Ferulate on Inflammatory Factors and Immune Function of Patients with Chronic Glomerulonephritis / 现代生物医学进展

Objective:To study the effect of shenfukang capsule combined with sodium ferulate on the inflammatory factors and immune function of patients with chronic glomemlonephritis.Methods:78 patients with chronic glomerulonephritis who admitted in our hospital from February 2015 to January 2016 were divided into the observation group and the control group according to the random number method.The control group was treated with sodium ferulate,and the treatment group was treated with Shenfukang capsule combined with sodium ferulate.The clinical curative effect,serum inflammatory factors levels and immune function before and after treatment were compared between two groups.Results:After treatment,the total clinical efficacy of observation group was significantly higher than that of the control group (P ＜0.05).The serum serum levels ofIL-6 observation group,TNF-α and hs-CRP,CD8 in the two groups were significantly higher than those before treatment,which were significantly lower in the observation group than those of the control group (P ＜0.05).After treatment,the levels of CD3,CD4 and CD4 / CD8 in the two groups were significantly higher than those before treatment (P ＜0.05),which were significantly higher in the observation group than those of the control group(P＜0.05).Conclusion:Shenfukang capsule combined with sodium ferulate could effectively relieve the inflammatory response and improve the immune function with good clinical curative effect in the treatment of chronic glomerulonephritis.

Effect of sodium ferulate injection on myocardial function in rat model with myocardial ischemia and reperfusion / 局解手术学杂志

Objective To explore the effect of sodium ferulate injection on myocardial function in rat model with myocardial ischemia and reperfusion. Methods Selected 60 rats aged 7 ~8 weeks (7. 26 ± 0. 36 weeks averagely) and randomly divided them into the sham group, myocardial reperfusion group, and the sodium ferulate group, with 20 rats in each group. Observed the changes of the cardiac func-tion indexes of the two groups after perfusion. Results Compared with the sham group,the degree of LVESP and ± dp/dmax decreased sig-nificantly (P<0. 05) in the myocardial reperfusion group and the sodium ferulate group. The descending degree of LVESP and ± dp/dmax 2 hours after reperfusion in the reperfusion group was significantly higher than that in the sodium ferulate group (P<0. 05). Compared with the sham group,the LVEDP of the other two groups showed a rising trend,and it was significantly lower 2 hours after reperfusion in the sodium ferulate group compared to the reperfusion group (P<0. 05). Proportion of apoptosis cells increased in the reperfusion group and the sodium ferulate group,and positive expression rate of Fas in the sodium ferulate group was significantly lower than the reperfusion group (P<0. 05). LDH and CK-MB of content in the blood of rats were significant increased,and it was higer in the reperfusion group compared with the sodium ferulate group (P<0. 05). Compared with the sham group,SOD content in the reperfusion group and the sodium ferulate group decreased obviously (P<0. 05). The MDA content increased,but the degree of increase was lower in the sodium ferulate group (P<0. 05). Conclu-sion Sodium ferulate could protect the myocardial function in rat model with myocardial ischemia and reperfusion to a certain degree.

Effect of Sodium ferulate on glucocorticoid-induced osteoporosis / 中国药理学通报

Aim To study the influence of Sodium fer-ulate ( SF) on bone metabolism in glucocorticoid–in-duced osteoporosis rats. Methods Thirty cases of fe-male Wistar Rats(3-month-old) were divided into con-trol group, model group and SF group ( low-dose group, middle-dose group, high-dose group ) by ran-domized block design. Double fluorochrome labeling with calcein was performed before necropsy. The left tibia was taken for bone histomorphometry. Results In static parameters, the proximal tibia cancellous bone trabecular thickness, trabecular quantity and area ratio were significantly reduced in model group compared with control group;while compared with model group, those were increased in middle and high-dose SF group. Trabecular separation degree was increased in model group compared with control group, while it was decreased in middle and high-dose SF group compared with model group. In dynamic parameters, the calcula-tion parameters of cancellous bone mark perimeter rate and the bone formation rate were increased in model group compared with control group, in middle and high-dose SF group the bone formation rate was in-creased compared with model group. In bone cells, os-teoclast number per mm, osteoblast number per mm, percent osteoblast surface perimeter and percent osteo-clast surface perimeter were increased in model group compared with control group. In growth-plate, the thickness of growth-plate was increased in model group compared with control group. In bone cells and growth-plate there was no statistical significance between treat-ment group and model group. Conclusion This study demonstrates that SF can increase bone mass and im-prove bone structure,which may be related to the im-provement of bone formation. SF is effective for GIOP in rats.

Effects of Shenmai Injection Combined with Sodium Ferulate on the Infarct Size and Related Indicators of Pa-tients with Acute Myocardial Infarction / 中国药房

OBJECTIVE:To investigate the effects of Shenmai injection combined with sodium ferulate on infarct size and relat-ed indicators of patients with acute myocardial infarction. METHODS:110 patients with acute myocardial infarction were randomly divided into control group(55 patients) and observation group(55 patients). Patients in the control group received oxygen inhala-tion,coronary expansion by nitrates,water and electrolyte regulation and acid-base balance regulation,thrombolytic fibrinolytic agent utilization,sedation and analgesia by analgesics and other conventional treatments. Meanwhile,50 ml Shenmai injection was given to the control group,dissolved in 200 ml 5% Glucose injection,intravenously,twice a day;observation group was addition-ally given 0.2 g Sodium ferulate for injection,dissolved in 200 ml 5% Glucose injection,intravenously,twice a day. The treat-ment course for both groups was 14 d. Clinical efficacy in 2 groups was observed,myocardial infarction size before and after treat-ment was recorded,hemorheology indexes(whole blood viscosity,fibrinogen and erythrocyte aggregation index),catdiac enzymes index homocysteine(Hcy),and growth arrest-specific gene product 6(Gas6)before and after treatment together with the incidence of adverse reactions were detected. RESULTS:The total effective rate in observation group was significantly higher than it in con-trol group. The difference was statistically significant(P0.05). After treatment,the myocardial infarct size in 2 groups was reduced,hole blood viscosity,fibrinogen and erythro-cyte aggregation indexes were reduced,and these in observation group were lower than in control group;in the 8 day during the treatment,serum level of Hcy in observation group was reduced;in the 15 day,blood level of Hcy and Gas6 in observation groups was reduced,serum level of Hcy in control group was reduced,and these in observation group was lower than in control group. The differences were statistically (P<0.05). And there were no obvious adverse reactions during treatment. CONCLU-SIONS:Based on conventional treatment,Shenmai injection combined with sodium ferulate shows significant efficacy in the treat-ment of acute myocardial infarction,and can reduce blood level of Hcy and Gas6,improve hemorheology indexes and narrow the myocardial infarct size.

Simultaneous determination on absolute bioavailability of preparation of Chuanxiong Radix components in rats by method of AUAWC and HPLC / 中草药

Objective: The absolute bioavailability of the preparation of Chuanxiong Radix components in rats was simultaneously studied by two methods of area under absorbance-wavelength curve (AUAWC) and high performance liquid chromatography (HPLC), which would confirm the feasibility that AUAWC could be used to determine the absolute bioavailability of components of Chinese materia medica (CMM). Methods: Based on the random two-way cross-over design, 60 SD rats were given the injection of Chuanxiong Radix components by iv and the same amount of drug suspension of the tablet of Chuanxiong Radix components by ig, respectively. Blood samples were collected at various time points after the administration. Plasma concentration of the total components, sodium ferulate, and ligustrazine hydrochloride of the two preparations of Chuanxiong Radix components in rats was measured by AUAWC combined with HPLC. Pharmacokinetic parameters and absolute bioavailability were calculated by DAS 2.0 program and the data obtained by the two methods were compared. Results: After ig administration, AUC0-∞ of total components was (77.218±13.492) mg·min/L by AUAWC and AUC0-∞ of total component was (169.775±18.252) mg∙min/L for iv injection. The absolute bioavailability of tablet of ligustrazine hydrochloride were (69.134±4.853) and (16.422±2.584) mg∙min/L, respectively by HPLC. As for iv injection, AUC0-∞ of sodium ferulate and ligustrazine hydrochloride were (155.244±28.994) and (36.754±6.645) mg∙min/L, respectively. The absolute bioavailabilities of ig administration were 44.53% and 44.68%, respectively. The data obtained by AUAWC were similar to by HPLC. Conclusion: The method of AUAWC can be used to determine the absolute bioavailability on the mixed drugs in the tablet of Chuanxiong Radix components, which will be helpful to solve the problem that the total and individual drugs of the preparation can be coanalyzed together under the combination method of HPLC. It will provide better enlightenment to study the absolute bioavailability of the mixed drugs from Western compound chemicals or complex components in CMM.

Effects of tetramethylpyrazine-2′-O-sodium ferulate on swelling of astrocytes and expression of AQP4 after oxygen-glucose deprivation/reoxygenation / 中国药理学通报

Aim To explore the effects of tetrameth-ylpyrazine-2′-O-sodium ferulate (TSF)on the swelling of astrocytes and the expression of AQP4 after oxygen gl-ucose deprivatio /reoxygenation(OGD /Reox).Methods Astrocytes were divided into 4 groups:control group, OGD /Reox group,Ozagrel group and TSF group.The effects of TSF on astrocytes were investigated 6,1 2,24 and 48 h after OGD /Reox.The cell injury was assessed by measuring LDH activity and MTT.The expression levels of AQP4 protein of astrocytes were detected u-sing Western blot.Results OGD /Reox induced obvi-ous cell swelling and significant reduction of LDH in astrocytes whereas TSF remarkably attenuated OGD-in-duced astrocyte swelling and LDH reduction (P group(P 0.05 ).Conclusion TSF can attenuate OGD-induced swelling of astrocytes through decreasing the AQP4 expression.

Protective effects of sodium ferulate and oxymatrine on rats cerebral ischemia-reperfusion injury by reducing oxidative stress / 国际中医中药杂志

Objective To observe the protective effects of Sodium Ferulate (SF) combined with Oxymatrine (OMT) on rats cerebral ischemia-reperfusion injury (CIRI) and its mechanisms.Methods Rats were divided into a sham-operation, a model, a edaravone, a SF, a OMT and a low, a middle, a high dose of combination groups by random number table, with each group contained 12 rats. Edaravone (3 mg/kg), SF (25 mg/kg), OMT (50 mg/kg) and combination (SF 12.5 mg/kg + OMT 25 mg/kg; SF 25 mg/kg + OMT 50 mg/kg; SF 50 mg/kg + OMT 100 mg/kg) were injected intravenously to the rats. Normal saline were injected to rats of the sham-operation and the model groups. One injection was operated for continuous 5 days. At 30 minutes after last administration, CIRI was made on rats except for sham-operation. At 24 hours after reperfusion, rats were sacrificed. Infarcts volumes, superoxide dismutase (SOD) and malondialdehyde (MDA) were measured.Results Infarcts volumes (F=73.183,P<0.01) and MDA contents (F=17.104,P<0.01) were significantly reduced and SOD vitalities (F=11.417,P<0.01) was increased in the SF, OMT and the combination groups. Effects of the combination groups were significantly better than the SF or the OMT groups (P<0.05). Conclusion Combination of SF and OMT had good effects to treat CIRI. The mechanisms were connected with anti-oxidative damages.

Clinical study of atorvastatin and sodium ferulic acid on renal interstitial fibrosis of diabetic nephropathy / 中国生化药物杂志

Objective To observe the clinical efficacy of atorvastatin combined with sodium ferulic acid on renal interstitial fibrosis of diabetic nephropathy(DN).Methods According to the diagnostic and staging criteria of DN,56 patients of DN(Mogensen stage Ⅲ~Ⅳ)who hadn’t received lipid-lowering treatment in the last 2 months and glycemic control were within the standard were randomly divided into control group (n =28 )and experimental group(n=28).Control group were received basic treatment including diabetes diet,decreasing blood glucose level and adjusting blood pressure.Experimental group were added atorvastatin combined with sodium besides the basic treatment above-mentioned.The course is both 4 weeks in two groups.Changes of fasting plasma glucose(FPG),blood urea nitrogen(BUN),serum creatinine(SCr)and 24-hour urine albumin excretion rate (24hUAER),transforming growth factorβ1 (TGF-β1 )before and after the treatment in two groups were observed. Results The differences of FPG,BUN, SCr,24h UAER and TGF-β1 in two groups before and after treatment were statistically significant(P<0.01).Conclusion Atorvastatin combined with sodium ferulate can function cooperatively in the treatment of diabetic nephropathy and can delay renal interstitial fibrosis.

Effects of Sodium Ferulate treatment on the hypercoagulability of patients with plateau derived chronic cor pulmonale with acute ecacerbation phase at high altitude / 中国综合临床

Objective To explore the effects of Sodium Ferulateon treating patients with plateau derived chronic cor pulmonale in acute ecacerbation phase at high altitude.Methods Forty-one cases with plateau derived chronic cor pulmonale were randomly divided into treatment group (22 cases) and control group (19 cases).All the patients in the two groups were given the same routine treatments including anti-infection,expectorant,balancing hydro-electrolytic discord,persistent inspiration of low-flow oxygen and inhalation by ultrasonic nebulization.Patients in treatment group were plus given the Sodium Ferulate at dose of 300 mg by intravenous drop once daily for 2 weeks.Hemorrheology,hepatic and renal function were examined.Results After treatment,the level of whole blood viscosity and plasma viscosity in treatment group were (4.91 ± 1.60) mPa · s and (1.56 ± 0.49) mPa · s,lower than that before treatment ((5.78 ± 1.65) mPa · s and (1.87 ± 0.65) mPa · s,P =0.042,0.041).There were no significant difference in the control group in terms of whole blood viscosity and plasma viscosity.There was not abnormal change of hepatic and renal function of two groups after treatment.Conclusion Sodium Ferulate therapy was effective to treatment of the plateau derived chronic cor pulmonale in acute ecacerbation phase.

Synergy nerve protective effect and its mechanism of sodium ferulate and ginseng saponins Rg1 / 国际中医中药杂志

Objective Observe the synergy nerve protective effect and its mechanism of Sodium Ferulate (SF) and Ginseng saponins Rg1.Methods Ischemia-reperfusion injury models of rats were copied.The effects of SF,Ginsengsaponins Rg1 and the combination on infarction volume,lectin markers positive cells,peroxidase proliferation of activated receptorγ(PPAR-γ) mRNA expression,SOD activity and MDA content were observed.Results The blank control group didn't show infarction areas under TTC staining,and the cerebral infarction volume percentage of model control group,sodium ferulate group,ginsenoside Rg1 group and combination group was 44.2％,25.0％,20.4％,6.2％ respectively.The lectin positive cells number of blank control group,model control group,sodium ferulate group,ginsenoside Rg1 group and combination group were 11.4,44.6,27.8,23.0,13.4/500μm2 respectively; the PPAR-γmRNA expression were1883,1022,1473,1537,1843 respectively; the MDA content was 1.52,3.50,2.62,2.38,1.66 mmol/mg respectively; and the SOD acitivity was 71.54、73.14、81.72、82.22、91.10 U/mg respectively.Compared with model control group,sodium ferulate group,ginsenoside Rg1 group and combination group reduced the volume of cerebral infarcts (P＜0.01),inhibited the microglia activation(P＜0.01),increased the p PPAR-γ mRNA expression(P＜0.01),decreased the MDA content(P＜0.01) and increased SOD activity(P＜0.05,P＜0.01)significantly,and the effect of combination group was better than either sodium ferulate group or ginsenoside Rg1 group(P＜0.05,P＜0.01).Conclusion SF and Ginseng saponins Rg1 had collaborative neural protection and its activation on PPAR-γ may be one of the mechanisms.

Effect of sodium ferulate on injury of gastric mucosa after traumatic hemorrhage shock resuscitation in rabbits / 中华急诊医学杂志

Objective To investigate the effect and mechanism of sodium ferulate (SF) on injury of gastric mucosa after traumatic hemorrhage shock resuscitation in rabbits.Methods One hundred healthy rabbits were randomly ( random number) divided into 4 groups ( n =25 in each group):control group ( A),model group ( B),pre-resuscitation SF group (C) and post-resuscitation SF group (D).The gastric mucosa injury model was established by using a method of comminuted fracture of femur and blood depletion.SF 30 mg/kg was injected into vein of rabbits' ear 20 min before resuscitation in group C and 30 min after resuscitation in group D,while rabbits of remaining groups received equal volume of normal saline instead.The gastric mucosa was obtained 90 min after resuscitation.The damage index (DI) of gastric mucosa was observed with method of Guth and the ultra-structure of parietal cell of stomach was observed under electronic microscope and the contents of TXB2 and 6-Keto-PGF1α in gastric tissue homogenate were determined with radio-immunity methods,and the ratios of TXB2/6-Keto-PGF1α were calculated.Data were analyzed by ANOVA ( LSD-t test ),and P ＜ 0.05 was considered as statistical significance. Results Under the electronic microscope,the secreting tubules were observed to be closed tightly in the parietal cells of stomach in the group A,showing a static status.However,in the group B,the number of normal secreting tubules was increased and the lumens were enlarged obviously.Compared with the group B,the number of normal secreting tubules was decreased and the enlargement of secreting tubules was not obvious in group C.The degree of changes in secreting tubules in group D was that between group C and group B.Compared with group A,the DI,the content of TXB2 and ratio of TXB2 to 6-Keto-PGF1α in other three groups were higher [DI: (81.5+13.6), (61.3+18.2), (70.5+17.2) vs.(4.2+2.7); the contents of TXB2:(4.95 +0.51),(3.75+0.64),(4.39±0.69) vs.(2.76±0.44); and the ratios of TXB2 to 6-KetoPGF1α:(0.064±0.002),(0.037±0.005), (0.049±0.002) vs.(0.027±0.002)] (P＜0.01),but the contents of 6-Keto-PGF1α in other 3 groups were lower [ (77.9±8.9),(96.4±11.2),(89.2+11.4) vs. (109.3±7.6)] (P＜0.05orP＜0.01).Compared with group B,theDI [ (61.3±18.2),(70.5±17.2) vs.(81.5±13.6)] and the contents of TXB2 [ (3.75±0.64), (4.39±0.69) vs.(4.95±0.51)] and the ratios ofTXB2 to6-Keto-PGF1α [ (0.037±0.005), (0.049±0.002) vs.(0.064 ±0.002)] in groups C and D were lower (P ＜ 0.05 or P ＜ 0.01 ),but the contents of 6-KetoPGF1α in groups C and D [ (96.4 ± 11.2),( 89.2 ± 11.4) vs.(77.9 ± 8.9) ] were higher ( P ＜ 0.05 or P ＜ 0.01 ).Compared with group C,the DI [ ( 70.5 ± 17.2) vs.61.3 ± 18.2) ] and the contents of TXB2 [ (4.39 ± 0.69) vs.(3.75 ± 0.64) ] and the ratios of TXB2 to 6-Keto-PGF1α [ (0.049 ± 0.002 ) vs.(0.037 +0.005) ] in group D were higher ( P ＜ 0.05 or P ＜ 0.01 ),but the content of 6-Keto-PGF1α in group D [ ( 89.2 ± 11.4 ) vs.(96.4 ± 11.2) ] was lower ( P ＜ 0.05 ).Conclusions SF can attenuate the injury of gastric mucosa after traumatic hemorrhage shock resuscitation in rabbits,and its therapeutic effects is better when it is administered before resuscitation than those as it is administered after resuscitation.The possible mechanism is associated with the effects of improving balance between TXB2 and 6-Keto-PGF1α and inhibiting the secreting function of parietal cell of stomach.

Clinical studies of sodium ferulate,deproteinized calf serum and high pressure oxygen on treating acute carbon monoxide poisoning / 中国医师进修杂志

Objective Discuss the treatment effect of sodium ferulate,deproteinized calf serum and high pressure oxygen on acute carbon monoxide poisoning.Methods Seventy-five cases with coma acute carbon monoxide poisoning were randomly divided into two groups:the treated group (37 cases) and the control group (38 cases).The two groups were treated with high pressure oxygen,high flow oxygen uptake and support treatment,The treated group were treated with sodium ferulate and deproteinized calf serum.The control group were treated with citicoline act medicaments.Result The occurrence and injury degree of myocardial damage and delayed encephalopathy were markedly attenuated (P ＜ 0.05),the time of coma was obviously decreased (P ＜0.01),the death rate was obviously difference (P ＜0.05) in the treated group compared with the control group.Conclusion Sodium ferulate,deproteinized calf serum injection possess obviously effect on acute carbon monoxide poisoning.