1.Curcumae Rhizoma: An anti-cancer traditional Chinese medicine.
Yu LUO ; Lin ZHU ; Zhengyu REN ; Jian XIAO ; Erwei HAO ; Jiahong LU ; Jinmin ZHAO ; Chun YAO ; Yitao WANG ; Hua LUO
Chinese Herbal Medicines 2025;17(3):428-447
Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.
2.5.0T and 3.0T Coronary Magnetic Resonance Angiography Based on Compressed Sensing Acceleration:A Comparative Study
Shihai ZHAO ; Zhengyu XU ; Yubo GUO ; Gan SUN ; Lu LIN ; Yining WANG
Chinese Journal of Medical Imaging 2025;33(7):706-711
Purpose To compare the 5.0T gradient echo coronary magnetic resonance angiography(CMRA)using compressed sensing(CS)acceleration technology(5.0TCS-CMRA)vs.3.0T gradient echo-CMRA(3.0TCS-CMRA)using CS.Materials and Methods Twenty-five healthy volunteers aged 23 to 30 years from December 16,2023 to January 14,2024 at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences were prospective enrolled in this study.The interval between 3.0TCS-CMRA and 5.0TCS-CMRA was within two weeks.3.0TCS-CMRA used T2 preparation and 5.0TCS-CMRA did not use T2 preparation.The image quality scores,coronary artery length,signal-to-noise ratio(SNR)and contrast-to-noise ratio between coronary blood and adjacent myocardium or tissue(CNRmyo-blood)were evaluated.Results On 5.0TCS-CMRA,the SNR and CNRmyo-blood of the proximal right coronary artery(RCA)in 25 healthy volunteers were significantly higher than those of 3.0TCS-CMRA(SNR:318.07±94.06 vs.223.81±51.19,t=-5.609,P<0.001;CNRmyo-blood:212.75±91.44 vs.149.70±59.53,Z=-3.619,P<0.001),while the SNR and CNRmyo-blood of proximal left anterior descending coronary artery(LAD)and left circumflex coronary artery(LCX)were not significantly higher than those of 3.0TCS-CMRA(SNR:315.52±102.49 vs.306.35±92.85,t=-0.627,P=0.536;289.72±88.79 vs.272.87±84.68,t=-1.226,P=0.232;CNRmyo-blood:135.83±93.53 vs.203.94±74.30,t=4.132,P<0.001;117.66±79.63 vs.161.60±78.91,t=3.127,P=0.005).The length of the three coronary arteries measured by 5.0TCS-CMRA was significantly shorter than that of 3.0TCS-CMRA[RCA:(126.04±31.54)mm vs.(137.20±29.93)mm,t=2.911,P=0.008;LAD:(122.68±24.63)mm vs.(134.24±23.38)mm,Z=-3.026,P=0.002;LCX:(57.07±26.70)mm vs.(68.27±24.02)mm,t=2.552,P=0.018].There was no significant difference in the scanning time required between 3.0TCS-CMRA and 5.0TCS-CMRA[(8.60±2.84)min vs.(8.30±2.32)min,Z=-0.183,P=0.855].The image scores of the three major coronary arteries of 5.0TCS-CMRA were significantly lower than those of 3.0TCS-CMRA(RCA:2.52±0.59 vs.3.16±0.69,Z=-3.258,P=0.001;LAD:2.72±0.74 vs.3.24±0.66,Z=-2.540,P=0.011;LCX:2.44±0.71 vs.3.00±0.87,Z=-2.462,P=0.014).Conclusion In the absence of T2 preparation,5.0TCS-CMRA can still show obvious advantages in the SNR and CNRmyo-blood of proximal RCA compared with 3.0TCS-CMRA,which suggests the application potential of 5.0TCS-CMRA.In the future,a suitable T2 preparation pulse or potential alternative may significantly improve the performance of the 5.0TCS-CMRA.
3.Dabuyuan Jian improves learning and memory ability of mild cognitive impairment mice via modulating PPARγ/NF-κB signaling pathway
Weiyi LI ; Mengjie TIAN ; Lu JIANG ; Zongxing ZHANG ; Daozhong LIU ; Zhuoma BAO ; Zhengyu WANG ; Lin YUAN
Chinese Journal of Pathophysiology 2025;41(2):287-293
AIM:To investigate the potential effect of Dabuyuan Jian(DBYJ)on peroxisome proliferator-acti-vated receptor γ(PPARγ)/nuclear factor-κB(NF-κB)signaling pathway and related inflammatory proteins in mice with mild cognitive impairment(MCI),and to explore the mechanism of DBYJ in improving the learning and memory ability of MCI mice.METHODS:Forty C57BL/6 male mice were randomly divided into 5 groups,including negative control(NC)group,D-galactose(D-Gal)group,D-Gal+DBYJ group,D-Gal+GW9662(PPARγ inhibitor)group and D-Gal+GW9662+DBYJ group,with 8 mice each.The mice in NC group were subcutaneously injected with 0.9%saline solution on the back of the neck for 8 weeks,while those in the remaining 4 groups were subcutaneously injected with D-Gal(100 mg·kg-1·d-1)on the back of the neck for 8 weeks to establish the MCI model.From week 5 to week 8,the mice in D-Gal+GW9662 and D-Gal+DBYJ+GW9662 groups were intraperitoneally injected with GW9662(1 mg·kg-1·d-1).From week 5,the mice in D-Gal+DBYJ and D-Gal+DBYJ+GW9662 groups were treated with DBYJ(13.2 g/kg)by gavage,while those in the re-maining 3 groups were administered an equal volume of purified water for 4 weeks.The Morris water maze(including posi-tioning navigation experiment and space exploration experiment)was used to assess the learning and memory ability of the mice.The structural integrity of the hippocampus of the mice was assessed by hematoxylin-eosin(HE)staining.Nissl staining was used to evaluate damage to hippocampal neurons in mice,and Western blot was applied to detect the protein levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),PPARγ,P65 and phosphorylated P65(p-P65)in the hippocampus of the mice.RESULTS:Compared with NC group,the escape latency of the mice in D-Gal+D-Gal and D-Gal+GW9662 groups significantly increased(P<0.01),while the number of platform crossing and the duration of staying in the target quadrant within 60 s significantly decreased(P<0.01).The number of neurons in the CA3 region remarkably decreased(P<0.01),and pyramidal cell disarrangement and neuronal shrinkage were observed.The levels of TNF-α,IL-1β and p-P65 were up-regulated,while the expression of PPARγ was down-regulated(P<0.05).Compared with D-Gal group,the escape latency of the mice in D-Gal+DBYJ group significantly decreased(P<0.01),while the number of plat-form crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P<0.01).The number of neurons in the CA3 region increased(P<0.01),the pyramidal cells were more neatly arranged,and the cytoarchitec-ture was intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regu-lated(P<0.05).Compared with D-Gal+GW9662 group,significantly decreased escape latency was observed in D-Gal+DBYJ+GW9662 group(P<0.01),and the number of platform crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P<0.05).The number of neurons in the CA3 region increased(P<0.01),the pyrami-dal cells were arranged more neatly,and the cytoarchitecture was relatively intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regulated(P<0.05).The effects shown in D-Gal+DBYJ+GW9662 group were inferior to those in D-Gal+DBYJ group,indicating that the therapeutic effect of DBYJ was inhibited after the addition of GW9662.CONCLUSION:Dabuyuan Jian improves the learning and memory ability of MCI mice,and the mechanism may be related to the expression of key proteins in the PPARγ/NF-κB signaling pathway.
4.5.0T and 3.0T Coronary Magnetic Resonance Angiography Based on Compressed Sensing Acceleration:A Comparative Study
Shihai ZHAO ; Zhengyu XU ; Yubo GUO ; Gan SUN ; Lu LIN ; Yining WANG
Chinese Journal of Medical Imaging 2025;33(7):706-711
Purpose To compare the 5.0T gradient echo coronary magnetic resonance angiography(CMRA)using compressed sensing(CS)acceleration technology(5.0TCS-CMRA)vs.3.0T gradient echo-CMRA(3.0TCS-CMRA)using CS.Materials and Methods Twenty-five healthy volunteers aged 23 to 30 years from December 16,2023 to January 14,2024 at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences were prospective enrolled in this study.The interval between 3.0TCS-CMRA and 5.0TCS-CMRA was within two weeks.3.0TCS-CMRA used T2 preparation and 5.0TCS-CMRA did not use T2 preparation.The image quality scores,coronary artery length,signal-to-noise ratio(SNR)and contrast-to-noise ratio between coronary blood and adjacent myocardium or tissue(CNRmyo-blood)were evaluated.Results On 5.0TCS-CMRA,the SNR and CNRmyo-blood of the proximal right coronary artery(RCA)in 25 healthy volunteers were significantly higher than those of 3.0TCS-CMRA(SNR:318.07±94.06 vs.223.81±51.19,t=-5.609,P<0.001;CNRmyo-blood:212.75±91.44 vs.149.70±59.53,Z=-3.619,P<0.001),while the SNR and CNRmyo-blood of proximal left anterior descending coronary artery(LAD)and left circumflex coronary artery(LCX)were not significantly higher than those of 3.0TCS-CMRA(SNR:315.52±102.49 vs.306.35±92.85,t=-0.627,P=0.536;289.72±88.79 vs.272.87±84.68,t=-1.226,P=0.232;CNRmyo-blood:135.83±93.53 vs.203.94±74.30,t=4.132,P<0.001;117.66±79.63 vs.161.60±78.91,t=3.127,P=0.005).The length of the three coronary arteries measured by 5.0TCS-CMRA was significantly shorter than that of 3.0TCS-CMRA[RCA:(126.04±31.54)mm vs.(137.20±29.93)mm,t=2.911,P=0.008;LAD:(122.68±24.63)mm vs.(134.24±23.38)mm,Z=-3.026,P=0.002;LCX:(57.07±26.70)mm vs.(68.27±24.02)mm,t=2.552,P=0.018].There was no significant difference in the scanning time required between 3.0TCS-CMRA and 5.0TCS-CMRA[(8.60±2.84)min vs.(8.30±2.32)min,Z=-0.183,P=0.855].The image scores of the three major coronary arteries of 5.0TCS-CMRA were significantly lower than those of 3.0TCS-CMRA(RCA:2.52±0.59 vs.3.16±0.69,Z=-3.258,P=0.001;LAD:2.72±0.74 vs.3.24±0.66,Z=-2.540,P=0.011;LCX:2.44±0.71 vs.3.00±0.87,Z=-2.462,P=0.014).Conclusion In the absence of T2 preparation,5.0TCS-CMRA can still show obvious advantages in the SNR and CNRmyo-blood of proximal RCA compared with 3.0TCS-CMRA,which suggests the application potential of 5.0TCS-CMRA.In the future,a suitable T2 preparation pulse or potential alternative may significantly improve the performance of the 5.0TCS-CMRA.
5.Dabuyuan Jian improves learning and memory ability of mild cognitive impairment mice via modulating PPARγ/NF-κB signaling pathway
Weiyi LI ; Mengjie TIAN ; Lu JIANG ; Zongxing ZHANG ; Daozhong LIU ; Zhuoma BAO ; Zhengyu WANG ; Lin YUAN
Chinese Journal of Pathophysiology 2025;41(2):287-293
AIM:To investigate the potential effect of Dabuyuan Jian(DBYJ)on peroxisome proliferator-acti-vated receptor γ(PPARγ)/nuclear factor-κB(NF-κB)signaling pathway and related inflammatory proteins in mice with mild cognitive impairment(MCI),and to explore the mechanism of DBYJ in improving the learning and memory ability of MCI mice.METHODS:Forty C57BL/6 male mice were randomly divided into 5 groups,including negative control(NC)group,D-galactose(D-Gal)group,D-Gal+DBYJ group,D-Gal+GW9662(PPARγ inhibitor)group and D-Gal+GW9662+DBYJ group,with 8 mice each.The mice in NC group were subcutaneously injected with 0.9%saline solution on the back of the neck for 8 weeks,while those in the remaining 4 groups were subcutaneously injected with D-Gal(100 mg·kg-1·d-1)on the back of the neck for 8 weeks to establish the MCI model.From week 5 to week 8,the mice in D-Gal+GW9662 and D-Gal+DBYJ+GW9662 groups were intraperitoneally injected with GW9662(1 mg·kg-1·d-1).From week 5,the mice in D-Gal+DBYJ and D-Gal+DBYJ+GW9662 groups were treated with DBYJ(13.2 g/kg)by gavage,while those in the re-maining 3 groups were administered an equal volume of purified water for 4 weeks.The Morris water maze(including posi-tioning navigation experiment and space exploration experiment)was used to assess the learning and memory ability of the mice.The structural integrity of the hippocampus of the mice was assessed by hematoxylin-eosin(HE)staining.Nissl staining was used to evaluate damage to hippocampal neurons in mice,and Western blot was applied to detect the protein levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),PPARγ,P65 and phosphorylated P65(p-P65)in the hippocampus of the mice.RESULTS:Compared with NC group,the escape latency of the mice in D-Gal+D-Gal and D-Gal+GW9662 groups significantly increased(P<0.01),while the number of platform crossing and the duration of staying in the target quadrant within 60 s significantly decreased(P<0.01).The number of neurons in the CA3 region remarkably decreased(P<0.01),and pyramidal cell disarrangement and neuronal shrinkage were observed.The levels of TNF-α,IL-1β and p-P65 were up-regulated,while the expression of PPARγ was down-regulated(P<0.05).Compared with D-Gal group,the escape latency of the mice in D-Gal+DBYJ group significantly decreased(P<0.01),while the number of plat-form crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P<0.01).The number of neurons in the CA3 region increased(P<0.01),the pyramidal cells were more neatly arranged,and the cytoarchitec-ture was intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regu-lated(P<0.05).Compared with D-Gal+GW9662 group,significantly decreased escape latency was observed in D-Gal+DBYJ+GW9662 group(P<0.01),and the number of platform crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P<0.05).The number of neurons in the CA3 region increased(P<0.01),the pyrami-dal cells were arranged more neatly,and the cytoarchitecture was relatively intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regulated(P<0.05).The effects shown in D-Gal+DBYJ+GW9662 group were inferior to those in D-Gal+DBYJ group,indicating that the therapeutic effect of DBYJ was inhibited after the addition of GW9662.CONCLUSION:Dabuyuan Jian improves the learning and memory ability of MCI mice,and the mechanism may be related to the expression of key proteins in the PPARγ/NF-κB signaling pathway.
6.Predictive value of MRA combined with CTA for neurological function in elderly patients with cerebral infarction
Jian TAO ; Lei HAN ; Dongyang YU ; Zhengyu ZHAO ; Haifeng LU ; Yong LIU ; Chunsheng YANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(12):1452-1456
Objective To analyze the predictive value of magnetic resonance angiography(MRA)combined with CT angiography for the prognosis of neurological function in elderly patients with cerebral infarction and its influencing factors.Methods A total of 102 elderly patients with cere-bral infarction admitted to our hospital from April 2020 to August 2023 were recruited,and ac-cording to the modified Rankin scale(mRS),they were divided into good prognosis group(mRS score≤3,66 patients)and poor prognosis group(mRS score>3,36 patients).Their clinical data were collected.The stenosis rate of the lesion site was examined by MRA,and the Alberta stroke program early CT score(ASPECTS)was semi-quantitatively evaluated with CT angiography ex-amination.Multivariate logistic regression analysis was used to identify the influencing factors for poor neurological prognosis.ROC curve was plotted to analyze the predictive value of MRA com-bined with CT angiography for the prognosis.Results Advanced age,higher NIHSS score,larger white blood cell and neutrophil counts,and higher homocysteine level were observed in the poor prognosis group than the good prognosis group(P<0.01).The poor prognosis group had signifi-cantly higher stenosis rate and lower ASPECTS than the good prognosis group(P<0.01).Multi-variate logistic regression analysis showed that NIHSS score,white blood cell count,neutrophil count,stenosis rate and ASPECTS were independent risk factors for poor prognosis of neurologi-cal function in elderly patients with cerebral infarction(P<0.05,P<0.01).The AUC value of stenosis rate,ASPECTS and their combination in predicting poor prognosis of neurological func-tion in elderly patients with cerebral infarction were 0.745(95%CI:0.645-0.844)and 0.711(95%CI:0.598-0.824),and 0.891,respectively.The AUC value of the combination was the highest,with a sensitivity of 87.76%and a specificity of 63.65%.Conclusion NIHSS score,white blood cell count,neutrophil count,stenosis rate and ASPECTS are independent risk factors for poor prognosis of neurological function in elderly patients with cerebral infarction.The combina-tion of stenosis rate and ASPECTS based on MRA and CT angiography has the highest predictive value.
7.Efficacy and safety of hybrid surgery for the recanalization of carotid artery occlusion after stenting
Zhengyu WANG ; Guangdong LU ; Tao WANG ; Wenlong XU ; Xia LU ; Fei CHEN ; Bin YANG ; Peng GAO ; Yabing WANG ; Yanfei CHEN ; Yan MA ; Liqun JIAO
Chinese Journal of Cerebrovascular Diseases 2024;21(8):505-513
Objective To investigate the efficacy and safety of hybrid surgery for the recanalization of carotid artery occlusion after stenting.Methods Clinical data and results of 17 patients with occlusion after carotid artery stenting and treated with hybrid surgery from June 2016 to April 2023 at the Department of Neurosurgery Cerebral Blood Flow Reconstruction Center of Xuanwu Hospital,Capital Medical University were retrospectively analyzed.According to whether the recanalization was successful,17 patients were divided into the the successful recanalization group and the failed recanalization group.Successful recanalization was defined as achieving modified thrombolysis in cerebral infarction(mTICI)grade ≥2b and residual stenosis<50%.Baseline data(age,sex,body mass index,smoking history,alcohol consumption history,hypertension history,diabetes history,hyperlipidemia history,coronary heart disease history),clinical data(National Institutes of Health Stroke Scale[NIHSS]score at admission,fasting blood glucose,low density lipoprotein,high density lipoprotein,total cholesterol,triglyceride,occlusion side and segment,combination with severe stenosis or occlusion of the contralateral carotid artery,opening of the anterior communicating artery,opening of the posterior communicating artery,compensation of the external and internal carotid artery,compensation of the pia artery,stump morphology,and time from imaging diagnosis of occlusion to recanalization)were documented and compared between groups.The recanalization of occlusive vessels and perioperative complications were recorded.Imaging and clinical follow-up were performed 3,6 months and≥1 year after surgery.Results Among the 17 patients,the ratio of successful recanalization was 13/17.One patient had re-occlusion after operation,which was re-opened after thrombolysis,but neck hematoma with dyspnea occurred,and recovered after emergency operation.There was no postoperative stroke or death.The incidence of perioperative complications was 1/17.Compared with the successful recanalization group,the levels of high density lipoprotein and total cholesterol in the failed recanalization group were higher,and the differences between the groups were statistically significant(high density lipoprotein[1.3±0.3]mmol/L vs.[0.9±0.3]mmol/L,t=-2.139;total cholesterol:[4.2±0.8]mmol/L vs.[3.1±0.7]mmol/L,t=-2.649;both P<0.05);There were no significant differences in other baseline data and clinical data(all P>0.05).Imaging follow-up was completed in 9 of the 13 patients in the successful recanalization group,and the follow-up time was 3.8-36.9 months,with a median follow-up time of 22.8(12.8,34.7)months.Among them,1 patient(1/9)developed restenosis of recanalization vessels at 33.0 months after surgery and underwent stent implantation again.Conclusions The preliminary analysis showed that the occlusion after carotid artery stenting had better recanalization success and lower perioperative complications.In patients with chronic occlusion after carotid stenting,the application of a hybrid surgery for opening may be attempted under multimodal imaging assessment.
8.Activation of ALDH2 alleviates hypoxic pulmonary hypertension in mice by upregulating the SIRT1/PGC-1α signaling pathway
Lei WANG ; Fenlan BIAN ; Feiyang MA ; Shu FANG ; Zihan LING ; Mengran LIU ; Hongyan SUN ; Chengwen FU ; Shiyao NI ; Xiaoyang ZHAO ; Xinru FENG ; Zhengyu SUN ; Guoqing LU ; Pinfang KANG ; Shili WU
Journal of Southern Medical University 2024;44(10):1955-1964
Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.
9.Effect of asiaticoside on systolic blood pressure and relaxation of isolated thoracic aorta of rats
Guoqing LU ; Hongyan SUN ; Zhengyu SUN ; Leqiang LIU ; Lei WANG ; Ningning ZHANG ; Yuhang WANG ; Yiming HE ; Jiahui JI ; Xinyue LI ; Pinfang KANG ; Bi TANG
Journal of Southern Medical University 2024;44(3):523-532
Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.
10.Effect of asiaticoside on systolic blood pressure and relaxation of isolated thoracic aorta of rats
Guoqing LU ; Hongyan SUN ; Zhengyu SUN ; Leqiang LIU ; Lei WANG ; Ningning ZHANG ; Yuhang WANG ; Yiming HE ; Jiahui JI ; Xinyue LI ; Pinfang KANG ; Bi TANG
Journal of Southern Medical University 2024;44(3):523-532
Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

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