Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the pre...Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.展开更多
Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus ...Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.展开更多
AIM:To determine the optimal dosage and mechanism of Ginkgolide B(BN52021) on severe acute pancreatitis(SAP) of rats.METHODS:Seventy male Wistar rats were randomly divided into seven groups(10 for each group).Shamoper...AIM:To determine the optimal dosage and mechanism of Ginkgolide B(BN52021) on severe acute pancreatitis(SAP) of rats.METHODS:Seventy male Wistar rats were randomly divided into seven groups(10 for each group).Shamoperation group(SO),SAP model group(SAP),dimethyl sulfoxide(DMSO) contrast group(DMSO),and groups treated with 2.5 mg/kg BN52021(BN1),5 mg/kg BN52021(BN2),10 mg/kg BN52021(BN3),and 20 μg/kg Sandostatin(SS).The SAP model was established in Wistar rats by injecting 5% sodium taurocholate retrogradely into the common bilio-pancreatic duct.The rats of SO,DMSO and BN52021 were injected with 0.9% NaCl,0.5% DMSO and BN52021 through femoral vein 15 min after the operation.The SS group was injected with Sandostatin subcutaneously.All rats were anaesthetized at 6 h after operation,and venous blood was collected to determine the levels of serum amylase and phospholipase A2(PLA2),and pancreas tissue was harvested and stained.RESULTS:There was no significant difference between the SAP and DMSO groups in serum amylase level,PLA2,ascites and pathologic score,but significant difference was found in SAP/DMSO groups compared with those in SO group(P < 0.05) and the levels of serum amylase,PLA2,ascites,and pathologic score were lower in the BN1,BN2,BN3 and SS groups than in the SAP and DMSO groups(P < 0.05).However,among BN1,BN2,BN3 and SS groups,BN2 had the best effect in decreasing the levels of serum amylase and PLA2(P < 0.05).Expression of platelet activating factor(PAF) receptor(PAFR) mRNA and protein showed no significant difference between the SAP and DMSO groups,or among BN1,BN2,BN3 and SS groups,but there was remarkable difference between SAP/DMSO group and SO group(P < 0.05),and expression of PAFR mRNA and protein was higher in the BN1,BN2,BN3 and SS groups than in the SAP and DMSO groups(P < 0.05).PAFR expression was observed in the nucleus and cytoplasm of pancreatic islet cells in Wistar rats by immunohistochemistry.CONCLUSION:By iv injection,5 mg/kg of BN52021 is the optimal dosage for SAP rats.BN52021 may inhibit the interaction/binding of PAF with PAFR.展开更多
In this paper a simple preparative method for isolation and purification of ginkgolides A and B was developed,As starting material,a commercially available standardized ginkgo extract (EGb761,containing 24% flavonoid ...In this paper a simple preparative method for isolation and purification of ginkgolides A and B was developed,As starting material,a commercially available standardized ginkgo extract (EGb761,containing 24% flavonoid and 6% terpene trilactones) was used,After a pretreatment step,optimized by the uniform design method ,the concentrated intermediate extract with high content of GA and gb(+90%) was separated into the individual terpenes by preparative liquid chromatography eluted with petroleum ether-ethylacetate,Analysis of products was carried out by means of HPLC-ELSD(evaporative light -scattering detector),The results show that ginkgolides A and B are obtained in higher yield and better purity.展开更多
Objective:To address the lack of research on invasive group B Streptococcus(GBS)infections in Malaysia and Southeast Asia through a comprehensive analysis of GBS isolates obtained from hospitals.Methods:Medical record...Objective:To address the lack of research on invasive group B Streptococcus(GBS)infections in Malaysia and Southeast Asia through a comprehensive analysis of GBS isolates obtained from hospitals.Methods:Medical records from patients with GBS infection isolated from the sterile site,such as blood and cerebrospinal fluid from 14 July 2019 to 15 December 2020,were reviewed from six major hospitals in Peninsular Malaysia.Inclusion criteria were invasive GBS,sterile sites and non-repeated GBS isolated from the same patients in the same admission.Viable isolates were re-identified for GBS and serotyped.Results:A total of 118 patients were eligible,with a majority of non-pregnant adults(76.3%).Over half of the patients(62.7%)had underlying medical conditions,with diabetes as the most common disease,followed by respiratory disease,renal disease,cardiovascular disease and skin and soft tissue disease.The most common manifestations were sepsis,followed by soft tissue abscess,diabetic foot ulcer,wet gangrene and cellulitis.The overall mortality was 7.6%.The most common serotype was serotype桋.Conclusions:Invasive GBS infection among non-pregnant adults showed a rising trend,particularly among diabetic individuals.The study underscores the importance of reducing risk factors and highlights the necessity of developing GBS vaccination as a preventive strategy for both infants and adults.展开更多
基金This research was funded by the National Natural Science Foundation of China(No.81773911,81690263 and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20180101).
文摘Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.
文摘Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.
基金Supported by Two grants from National Natural Science Foundation of China,No. 30300465 and No. 30772883
文摘AIM:To determine the optimal dosage and mechanism of Ginkgolide B(BN52021) on severe acute pancreatitis(SAP) of rats.METHODS:Seventy male Wistar rats were randomly divided into seven groups(10 for each group).Shamoperation group(SO),SAP model group(SAP),dimethyl sulfoxide(DMSO) contrast group(DMSO),and groups treated with 2.5 mg/kg BN52021(BN1),5 mg/kg BN52021(BN2),10 mg/kg BN52021(BN3),and 20 μg/kg Sandostatin(SS).The SAP model was established in Wistar rats by injecting 5% sodium taurocholate retrogradely into the common bilio-pancreatic duct.The rats of SO,DMSO and BN52021 were injected with 0.9% NaCl,0.5% DMSO and BN52021 through femoral vein 15 min after the operation.The SS group was injected with Sandostatin subcutaneously.All rats were anaesthetized at 6 h after operation,and venous blood was collected to determine the levels of serum amylase and phospholipase A2(PLA2),and pancreas tissue was harvested and stained.RESULTS:There was no significant difference between the SAP and DMSO groups in serum amylase level,PLA2,ascites and pathologic score,but significant difference was found in SAP/DMSO groups compared with those in SO group(P < 0.05) and the levels of serum amylase,PLA2,ascites,and pathologic score were lower in the BN1,BN2,BN3 and SS groups than in the SAP and DMSO groups(P < 0.05).However,among BN1,BN2,BN3 and SS groups,BN2 had the best effect in decreasing the levels of serum amylase and PLA2(P < 0.05).Expression of platelet activating factor(PAF) receptor(PAFR) mRNA and protein showed no significant difference between the SAP and DMSO groups,or among BN1,BN2,BN3 and SS groups,but there was remarkable difference between SAP/DMSO group and SO group(P < 0.05),and expression of PAFR mRNA and protein was higher in the BN1,BN2,BN3 and SS groups than in the SAP and DMSO groups(P < 0.05).PAFR expression was observed in the nucleus and cytoplasm of pancreatic islet cells in Wistar rats by immunohistochemistry.CONCLUSION:By iv injection,5 mg/kg of BN52021 is the optimal dosage for SAP rats.BN52021 may inhibit the interaction/binding of PAF with PAFR.
基金Supported by the Natural Science Foundation of Tianjin(No.993606911).
文摘In this paper a simple preparative method for isolation and purification of ginkgolides A and B was developed,As starting material,a commercially available standardized ginkgo extract (EGb761,containing 24% flavonoid and 6% terpene trilactones) was used,After a pretreatment step,optimized by the uniform design method ,the concentrated intermediate extract with high content of GA and gb(+90%) was separated into the individual terpenes by preparative liquid chromatography eluted with petroleum ether-ethylacetate,Analysis of products was carried out by means of HPLC-ELSD(evaporative light -scattering detector),The results show that ginkgolides A and B are obtained in higher yield and better purity.
基金the Research Grants from Universiti Putra Malaysia(UPM/800-3/3/1/GPB/2020/9683800)Ministry of Higher Education under the Fundamental Research Grant Scheme(FRGS/1/2023/WAB04/UPM/01/4).
文摘Objective:To address the lack of research on invasive group B Streptococcus(GBS)infections in Malaysia and Southeast Asia through a comprehensive analysis of GBS isolates obtained from hospitals.Methods:Medical records from patients with GBS infection isolated from the sterile site,such as blood and cerebrospinal fluid from 14 July 2019 to 15 December 2020,were reviewed from six major hospitals in Peninsular Malaysia.Inclusion criteria were invasive GBS,sterile sites and non-repeated GBS isolated from the same patients in the same admission.Viable isolates were re-identified for GBS and serotyped.Results:A total of 118 patients were eligible,with a majority of non-pregnant adults(76.3%).Over half of the patients(62.7%)had underlying medical conditions,with diabetes as the most common disease,followed by respiratory disease,renal disease,cardiovascular disease and skin and soft tissue disease.The most common manifestations were sepsis,followed by soft tissue abscess,diabetic foot ulcer,wet gangrene and cellulitis.The overall mortality was 7.6%.The most common serotype was serotype桋.Conclusions:Invasive GBS infection among non-pregnant adults showed a rising trend,particularly among diabetic individuals.The study underscores the importance of reducing risk factors and highlights the necessity of developing GBS vaccination as a preventive strategy for both infants and adults.
