Progress in anti-inflammatory effects of escin / 中国药理学与毒理学杂志

The fraction of horse chestnut seeds was named escins, which mainly consists of A, B, C, and D escin. Accumulating evidence suggests that escin exerts potent anti-inflammatory and anti-edematous effects. The effects of escin on inflammation and edema have been confirmed in various models. In a study in 1961, intravenous administration of escin was found to reduce acute edema in a rat paw. In the same study, escin was found to inhibit the increase in vascular permeability induced by egg white injection. Escin dose-dependently reduced the capillary permeability in chlo?roform-induced local inflammation in the abdominal skin surface of rabbits. The anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary perme?ability in rats. Escin gel decreased the contents of PGE2, TNF-α, and IL-1β, and reduced the raw edema and capillary permeability. The carrageenan-induced paw edema and pleuritis in bilaterally adrenalectomized rats were used to inves?tigate the anti-inflammatory effects of escin and glucocorticoid alone or combined. Co-administration of escin with corti?sone significantly reduced the volume of exudates and the number of white blood cells of exudates. The findings sug?gest escin can synergize with glucocorticoids to enhance their anti-inflammatory effect. The anti-inflammatory effect of escin was investigated in carrageenan-induced paw edema and acetic acid-induced capillary permeability in mice. Escin showed an anti-inflammatory effect, which is similar to that seen with dexamethasone treatment. However, escin showed a longer duration of the anti-inflammatory response than that of dexamethasone. Furthermore, escin had no signif?icant effects on spleen index, thymus index , proliferative capacity of splenocytes, lymphocyte count, and phagocytic rate. The findings suggest that escin is a potent anti-inflammatory drug with long-lasting anti-inflammatory effects without any immunosuppressive effects. Traditionally the mechanism of anti-inflammatory effect of escin is supposed to be rela?tive to release of PGF2α and corticosterone. The early studies showed that escin might promote the release of PGF2αand affect the pituitary adrenal system, stimulate the release of adrenocorticotropic hormone (ACTH) and glucocorticoid, which may explain its anti-inflammatory and anti-edema effects. Escin has glucocorticoid-like anti-inflammatory effect. However, escin did not exhibit an anti-inflammatory effect in low dose. Combination of suboptimal concentrations of escin with corticosterone inhibited the release of inflammatory factors including NO, TNF-αand IL-1βin the LPS-stimulated macrophage cells. Previous studies demonstrate that escin combined with glucocorticoid produced synergistic anti-inflammatory effects. The potential synergistic mechanisms may be associated with the property which escin regulates the glucocorticoid receptor (GR) signaling pathway. Escin can upregulate the expression of GR, promote the combina?tion of glucocorticoid and GR, then promote the activated GR transfer into the nucleus. Activated GR will inhibit the acti?vation of NF-κB directly, thus further inhibiting the expression of TNF-αand IL-1βand other inflammatory factors. Escin could inhibit 11β-HSD2 but not 11β-HSD1, thus decrease the metabolism of glucocorticoid. Escin and glucocorticoids have similar chemical structures. This indicate that one of the anti-inflammatory mechanisms of escin may be due to its stimulating GR by binding to it. Eacin might be a partial agonist of GR. A good many of researches have demonstrated the anti-inflammatory properties of escin, and shed light on the underlying mechanisms by which escin exerts these effects. Escin, as an oral or intravenous formulation, or a topical gel, inhibits inflammation, producing measurable improve?ments in edema and acute lung injury. Further clinical studies of escin are needed to demonstrate these properties in larger patient populations.

Escin alleviates chemotherapy-induced peripheral neuropathic pain by inducing autophagy in the spinal cord of rats / 南方医科大学学报

OBJECTIVE@#To investigate the effect of escin in relieving chemotherapy-induced peripheral neuropathic pain in rats and explore and the underlying mechanism.@*METHODS@#Eighteen SD rats were randomly divided into 3 groups (@*RESULTS@#The rats in both the escin preconditioning group and escin postconditioning group showed obviously increased thresholds of mechanical allodynia and thermal hyperalgesia as compared with those in the control group (@*CONCLUSIONS@#Escin can alleviate chemotherapy-induced peripheral neuropathic pain in rats possibly by upregulating the expressions of autophagy-related proteins in the spinal cord.

Anti-inflammatory effect of external use of escin on cutaneous inflammation: possible involvement of glucocorticoids receptor / 中国天然药物

Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor (GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (P38MAPK) and activator protein-1 (AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1β. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.

Anti-inflammatory effect of external use of escin on cutaneous inflammation: possible involvement of glucocorticoids receptor / 中国天然药物

Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor (GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (P38MAPK) and activator protein-1 (AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1β. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.

Application of Multi-stage Countercurrent Extraction Technology in the Extraction Process of Aesculi / 世界科学技术-中医药现代化

This study was aimed to optimize the extraction process of Aesculi. The extraction process of Aesculi wasoptimized through orthogonal experiment while the transfer rate of escin Ia and escin Ib. And the yield of dry extract. wasadopted as marks. And ratio of solid to liquid, the ethanol concentration, extraction time and extraction temperature werestudies. The results showed that optimized extraction conditions of Aesculi were determined as follows. The ratio of solidto liquid was 1: 10, the ethanol concentration was 70％, extracted for 20 minutes ever stage and the extractiontemperature was 60℃. It was concluded that the extraction process is efficacious for general flavone and icariinextraction. The method is suitable for the standardized production technology of Aesculi.

Neuroprotective effects ofβ-aescinate on brain edema in rat model of traumatic brain injury / 天津医药

Objective To explore the neuroprotective effects ofβ-aescinate on brain edema in rats of traumatic brain injury (TBI). Methods A total of 78 male SD (Sprague Dawley) rats were randomly divided into three groups: sham-operation group (Sham), traumatic brain injury group (TBI) andβ-aescinate group, with 26 rats in each group. Rats of Sham group were anesthetized and surgically prepared only, but were not induced by cortical contusion. Electronic brain cortical damage impactor (eCCI) was used for establishing TBI model in TBI group and β-aescinate group after opening the bone window. TBI group was only established TBI model, but no intervention. After establishment of TBI model in β-aescinate group, β-aescinate (5 mg/kg body weight) was intraperitoneally injected, once every 24 hours. The modified neurological severity scores (mNSS) was used for evaluating changes of neurological function. After 48 hours, SD rats were sacrificed for hematoxylin and eosin (H&E) staining (n=6). Additionally, water content of the brain tissue was evaluated using the wet-to-dry weight ratio (n=10). Evans blue assay was performed to investigate the blood-brain barrier (BBB) permeability (n=4). The expression of aquaporin 4 (AQP4) was measured by Western blot assay (n=6). Results Compared with the Sham group, neurologic deficit, increased brain water content and the expression of AQP4 were found in TBI group (all P<0.05). Moreover, BBB permeability was destroyed. However, β-aescinate can improve the neurological function, reduce the brain water content and significantly decrease the expression of AQP4 in TBI rats. The BBB permeability was significantly improved in treatment group (all P<0.05). Conclusion These findings suggest that β-aescinate can reduce cerebral edema and improve neurological outcome in SD rats after TBI. This neuroprotection may be related with the down-regulation of AQP4 protein.

The multicenter randomized controlled prospective trail of sodium aescinate on recovery of abdominal surgery / 中华普通外科杂志

Objective To evaluate the efficacy and safety of sodium aescinate for abdominal operation in general surgery.Methods A multicenter,prospective and open labeled trail was conducted.Data of 2001 patients in PPS group who had undergone either conventional treated (n =500) or sodium aescinate treated (n =1 501) for abdominal operation in general surgery were analyzed.In the sodium aescinate treated group,sodium aescinate was given by ivgtt 12 h before the surgery started,and 20 mg daily after the surgery for 6 days.Time to recovery of gastrointestinal sounds (TRGS),time to recovery of passage of gas (TRPG),and time to recovery of bowel movements (TRBM) were recorded to evaluate the bowl function recovery.The difference of incision edema was observed by the evaluate edema level.Results The TRGS of sodium aescinate treated group was significantly shorter than that of the conventional treated group,P ＜ 0.01.The TRPG of sodium aescinate treated group was significantly shorter than that of the conventional treated group,P ＜ 0.01.The TRBM of sodium aescinate treated group was significantly shorter than that of the conventional treated group,P ＜ 0.01.The incision edema of sodium aescinate treated group was better than that of conventional treated group.The rate of adverse event was low in the sodium aescinate treated group,phlebitis was the most common one,accounting for 0.66％.No serious adverse event happened.Conclusion Sodium aescinate is effective and safe in accelerating patients recovery in general surgery.

Perforated whole-cell patch recording of L-type calcium current with β-escin in osteoblasts / 中国病理生理杂志

[ ABSTRACT] AIM:To establish a perforated whole-cell patch-clamp technique withβ-escin to record L-type cal-cium current (ICa,L) in osteoblasts.METHODS:ROS 17/2.8 is a rat osteoblast-like osteosarcoma cell line.β-escin was applied to the pipette solution to permeabilize the cell membrane and the perforated patch recording mode was obtained. RESULTS:β-escin at concentration of 50μmol/L easily permeabilized the cell membrane and obtained a perforated patch recording mode in 2~7 min.This technique prevented ICa,L rundown and preserved cytoplasmic signaling pathways.CON-CLUSION:β-escin may be used as an alternative ionophore for perforated patch-clamp studies in osteoblasts and results in minimal rundown that could facilitate recordings of ICa,L in osteoblasts.

The clinical study of edoravone combined with escin monosodium on acute cerebral hemorrhage / 中国基层医药

Objective To investigate the clinical effect of edoravone combined with escin monosodium on the treatment of acute cerebral hemorrhage .Methods 60 patients suffered from acute cerebral hemorrhage were randomly divided into control group and observation group .Each group had 30 patients.The control group was conventionally treated by the internal medicine .On the basis of the research on the control group ,the observation group were treated by edoravone combined with escin monosodium intravenous drip .After the treatment of 14 days,28 days,the recovery of neural function,focus volume,clinical effect were evaluated.Results Comared with the control group,after the treatment of 14 days,28 days,NIHSS score was obviously lower than that of the control group ,the difference was sig-nificant (t=2.136,t=4.117,P0.05).After the treatment of 28 days,hema-toma and edema of the differences were statistically significant (t=3.140,t=2.367,P<0.01,P<0.05).The com-parison of the clinic effect of the two groups ,the total effect was statistically significant (χ2 =6.650,P <0.01). Conclusion Edaravone combined with escin monosodium on the treatment of cerebral hemorrhage can significantly improve neurologic impairment and cerebral hematoma .Clinical effect is definite and safe .

Sodium aescinate reduces glial fibriallary acidic protein expression after spinal cord injury / 中国组织工程研究

BACKGROUND:The methylprednisolone pulse therapy in early period of spinal cord injury can attenuate the pathological degree of spinal cord injury, however no breakthrough was found within recent 20 years. OBJECTIVE:To observe the protection effects of sodium aescinate on the nerve cellapoptosis and expression of glial fibrial ary acidic protein (GFAP) in the early spinal cord injured rats. METHODS:Spinal cord injury models were established with the modified Al en’s method in 180 Sprague-Dawley rats, and were randomly divided into three groups, with 60 rats in each group. Immediately after injury, the rats in three groups were intraperitoneal y injected with sodium aescinate (5 mg/kg), methylprednisolone (100 mg/kg) and equal saline, respectively, once per day. At 8 hours, 24 hours, 96 hours and 7 days, 14 days after injury, rats were sacrificed and the injured segments were resected for hematoxylin-eosin staining and immunohistochemical staining, the nerve cellapoptosis and GFAP expression were detected. RESULTS AND CONCLUSION:The apoptotic nerve cells were seen at 8 hours after injury and the number of apoptotic cells reached the peak at 7 days, the edema was attenuated at 14 days without less nerve cellapoptosis in al groups, significantly fewer apoptotic nerve cells can be seen in sodium aescinate and methylprednisolone groups compared with the control group (P0.05), which was lower than methylprednisolone group (P<0.05);after 96 hours, methylprednisolone group and sodium aescinate group were both significantly lower than control group (P<0.05). Furthermore, the decreasing expression was observed in al groups after 7 days. Sodium ascinate has obvious protection effects on nerve cells in spinal cord injured rats and promotes neurological function through decreasing GFAP expression after injury. The efficacy of sodium ascinate is equal to that of methylprednisolone within 2 hours.

Synergetic use of tripterygium wilfordii and aescine for treatment of posttraumatic acute lung injury / 中华创伤杂志

Objective To investigate the effect and mechanism of tripterygium wilfordii combined with aescine in treatment of acute lung injury (ALI) following trauma.Methods A total of 120 patients with posttraumatic ALI were divided into four groups:tripterygium wilfordii + aescine group (combined group),tripterygium wilfordii group,aescine group,and control group according to random number table,with 30 patients per group.Regardless of the same conventional therapy,the patients in combined group were treated by orally or gastrically administered tripterygium wilfordii multiglycoside as well as aescine intravenously,once a day for 12 days; on the contrary,the same method but only with tripterygium wilfordii or aescine was respectively performed in tripterygium wilfordii and aescine groups.Blood gas analysis before and after treatment,length of ICU stay,fatality rate and incidence of ARDS in each group were observed.Changes in levels of inflammatory mediators (TNF-oα,IL-1,IL-6 IL-8,etc)were detected at days 4,8,and 12 after medication.Results Shorter length of ICU stay and lower ARDS incidence as well as 12-day fatality rate were detected in each treatment group as compared with control group,especially in combined group (P ＜ 0.05).Respiratory rate,PaO2 and oxygenation index (PaO2/FiO2) in each treatment group presented better amelioration than those in control group and especially better results were observed in combined group (P ＜ 0.05).Plasma levels of TNF-α,IL-1,IL-6,and IL-8 in each treatment group were lower than those in control group (P ＜ 0.05).Conclusions Tripterygium wilfordii and aescine havetherapeutic effect on posttraumatic ALI.Moreover,synergetic use of the two drugs achieves synergistic effect and better outcome.

Mechanism of escin sodium in inhibition of human leukemia Jurkat cells proliferation / 中草药

Objective To investigate the effects of escin sodium on proliferation of human leukemia Jurkat cells and its possible mechanism. Methods The reduction of cellular viability was determined by MTT assay. Hoechst 33258 staining, DNA fragmentation assay, FITC-Annexin V-FITC/PI staining assay, and cytometric analysis were used to confirm the features of apoptosis and cell cycle. Western blotting assays were performed to explore the apoptotic pathway. Results Escin sodium inhibited the proliferation of Jurkat cells in both dose- and time-dependent manners. The morphological apoptosis, DNA fragmentation pattern, and the percentage of Annexin V+/PI- (early apoptosis) cells were markedly increased in escin sodium-treated Jurkat cells. Escin sodium activated Caspase-8, Caspase-9, and Caspase-3, degraded poly (ADP-ribose) polymerase (PARP), and attenuated Bcl-2 expression. Conclusion Escin sodium could inhibit the proliferation of Jurkat cells via the induction of apoptosis effectively.

Clinical research on effect of sodium aescinate plate on the edema of limb tibial plate fracture / 中国基层医药

ObjectiveTo study the clinical effect of sodium aescinate on the edema of limb tibial plate fracture.Methods69 patients with edema of limb of tibial plate fracture were randomly divided into two groups,treatment group(46 cases)and control group(23 cases).Both of them were transfused with 20％ mannitol(250ml,Bid ×7days).In addition,these patients in the treatment group were treated with sodium aescinate(30mg Qd × 7days).ResultsThe repercussive effect of the edema grade in the treatment group were obviously better than those in the control group(P ＜0.05 ).ConclusionSodium aescinate had a remarkable repercussive effect on the limb edema of tibial plate fracture.

Evaluation on effects of Hydroxyethyl Starch 130/0.4 combined with Sodium Aesinate Tablets in treating edema of tibiofibular fracture / 中国基层医药

ObjectiveTo observe the effect ofhydroxyethyl starch 130/0.4 combined with sodium aesinate tablets in treating edema of tibiofibular fracture(ETF).Methods105 ETF patients were randomly assigned to tow groups,the treated group ( n =55 ) was treated with hydroxyethyl starch 130/0.4 injection (20ml.kg - 1 · d - 1 ) with sodium aesinate tablet( 30mg,bid,po),while the control group (n =50) was treated with sodium aesinate for injection (20mg in 5％ GS 500ml,ivgtt,qd),observe the decrudescence time of the fracture edema.ResultsThe significant effective rate and total effective rate were 40.0％,94.5％ in treated group and 14.0％,84.0％ in control group,showing statistical significance( P ＜0.05).The decrudescence time of Ⅱ degree and Ⅲ degree edema in treated group were (5.75 ± 2.21 ),( 8.14 ± 2.49),and ( 7.09 ± 2.03 ),( 12.18 ± 3.76 ) in control group,the difference among them was significant( P ＜ 0.05 or P ＜ 0.01 ).ConclusionThe combined therapy of hydroxyethyl starch 130/0.4and sodium aesinate tablets has good clinical curating effect in treating edema of tibiofibular,and also can reduce the adverse reaction.

Observation of the curative effects of sodium aescinate tablet on traumatic leg swelling / 中国基层医药

ObjectiveTo discuss the curative effects of sodium aescinate tablet on traumatic leg swelling.Methods168 cases were divided into four groups.54 cases of Ⅰ degree leg swelling were randomly divided into two groups,one group were treated with no drug and the other with sodium aescinate tablet.114 cases of Ⅱ and Ⅲ degree leg swelling were randomly divided into two groups,one group were treated with mannitol and the other with mannitol and sodium aescinate tablet.All cases were treated for 7 days and observed on leg swelling.ResultsThe curative effects of group with sodium aescinate tablet were superior to the group with no drug.The curative effects of group with both sodium aescinate tablet and mannitol are superior to group with mannitol.ConclusionSodium aescinate tablet had obviously curative effects on trautic leg swelling.Both sodium aescinate and mannitol could be used to treat leg swelling of Ⅱ and Ⅲ degree.

Effect observation on sodium aescinate for injection combined with percutaneous laser disc decompression in treating lumbar disc herniation / 中国医师进修杂志

Objective To study the therapeutic effect of sodium aescinate for injection combined with percutaneous laser disc decompression (PLDD) in treating lumbar disc herniation (LDH). Methods Ninety-eight cases of LDH were divided into 2 groups by means of random number table: treating group and control group, 49 cases in each group. The treating group were given the treatment of sodium aescinate for injection after received PLDD,the control group were given mannitol for injection after received PLDD. The operation evaluation criteria of lumbago and backache of Chinese medical association spine group was taken to value the therapeutic effect at 7 days, 1 month, 3 months and 6 months postoperation. At the same time,C-reactive protein (CRP) content in serum were measured at preoperation and 1, 3, 7 days postoperation.Results At 7 days postoperation, the excellent and good rate of the treating group was significantly higher than that of the control group[93.9%(46/49) vs. 55.1%(27/49),P ＜ 0.01], at 1, 3 and 6 months postoperation,the excellent and good rate had no statistically significant between the two groups (P ＞0.05). At 3 days postoperation, the serum CRP content in the treating group [(13.0 ± 2.2) mg/L] was lower than that of the control group [(31.0 ± 5.3) mg/L], there were significant differences between the two groups (P ＜ 0.01).Conclusions Sodium aescinate for injection combined with PLDD can control postoperative inflammation reaction effectively, improve the therapeutic effect. Therefore it should be a valid method in treating LDH.

Studies on the Chemical Constituents of Japanese Buckeye Seed (Aesculus turbinata)Part Ⅱ * Isolation and Identification of Escin IVc and Isoescins Ia, Ib / 中草药

Three triterpenoid saponins were isolated from 90％ ethanolic extract of the seeds of Aes-culus turbinata Bl.. Their structures were identified on the basis of spectral data as escin IVc:22α-O-tigloyl-28-O-acetylprotoaescigenin 33-O-[β-D-glucopyranosyl (1→2)][β-D-glucopyranosyl (1→4)]-β-D-glucopyranosiduronic acid (Ⅰ), isoescin Ia: 21β-O-tigloyl-28-O-acetylprotoaescigenin-3β-O-[β-D-glucopy-ranosyl (1→2)][β-D-glucopyranosyl (1→4)]-β-D-glucopyranosiduronic acid (Ⅳ), and isoescin Ib:21β-O-angeloyl-28-O-acetylprotoaescigenin-3β-O-[β-D-glucopyranosyl (1→2)][β-D-glucopyr anosyl (1→4)]-β-D-glucopyranosiduronic acid (Ⅴ). Escin IVc and isoescins Ia, Ib were obtained for the first time from thisplant. Escins Ia, Ib, IVc and isoescins Ia, Ib had inhibitory effect against recombinant HIV-1 protease atconcentration of 100 μmol/L in vitro.

Effects of ?-sodium aescinate on hemorrhage brain edema and AVP contents in rats / 第二军医大学学报

Objective: To observe the content of AVP changes in brain regions and pituitary of intracerebral hemorrhagic rats before and after treatment by ? sodium aescinate. Methods: Animal model was established by injecting collagenase into left caudoputamen of adult rats. Radioimmunoassay(RIA) was performed to measure the content changes of AVP, dye wet Weight methods was used to measure the changes of water contents in brain. Results: Compared with control group, the water content was increased significantly ( P

The effect of Aescin on chronic venous insufficiency:a randomized controlled multi-center clinical trial / 中国普通外科杂志

0.05). Body weight, blood pressure, blood routine test and blood biochemical parameters did not change in the two groups. Only mild side reactions of aescin was found and there was no dropout in the study group, whereas 7 patients dropped out in the control group due to the intolerance for the pressure. Conclusion Aescin has similar efficacy and fewer side effects compared with the compression stocking method in the treatment of chronic venous insufficiency.