The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-m...The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process.Cellulose derivatives of different substitution groups and molecular weights,including HPMC,HPC,and MC,were evaluated as the primary stabilizer of probucol nanosuspension.Ternary stabilizers system composed of a primary stabilizer(cellulose derivative,i.e.HPC),a nonionic surfactant(Pluronic R F68),and an anionic surfactant(SDS)was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media.The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4°C or 25°C.The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate(>60%at 2 h)compared to other cryoprotectant.The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats.The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.展开更多
Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and indi...Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety （QTc intervals） were set, respectively. Probucol significantly reduced total cholesterol （P 〈 0.001）, low-density lipoprotein cholesterol （LDL-C）, （P = 0.01）, and high-density lipoprotein cholesterol （HDL-C） （P 〈 0.001） compared with conventional therapy. Cilostazol was effective in increasing HDL-C （P = 0.002） and reducing triglycerides levels （P 〈 0.01） compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein （Ox-LDL, P = 0.065）. No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.展开更多
Autophagy and apoptosis have been regarded as important processes in the development of diabetic erectile dysfunction(DMED).Probucol is considered to have anti-apoptotic effects,but its relationship with autophagy has...Autophagy and apoptosis have been regarded as important processes in the development of diabetic erectile dysfunction(DMED).Probucol is considered to have anti-apoptotic effects,but its relationship with autophagy has not been reported.The aim of this study was to investigate the effects and mechanisms of probucol on erectile function.Thirty Sprague–Dawley(SD)male rats(12 weeks old)were fasted for 12 h.Twenty SD rats were injected with a single intraperitoneal injection of 60 mg kg−1 streptozotocin(STZ).Ten rats were given vehicle only and used as a sham group.After 72 h,20 STZ-treated rats with random blood glucose concentrations consistently greater than 16.7 mmol l^−1 were used as successfully established diabetic rats.The diabetic rats were divided randomly into two groups and treated with a daily gavage of probucol at a dose of 0 or 500 mg kg^−1 for 12 weeks.After treatment,the intracavernous pressure(ICP)was used to measure erectile function upon electrical stimulation of the cavernous nerve.After euthanasia,penile tissue was examined using immunohistochemistry and Western blot to assess the protein levels of B-cell lymphoma-2(Bcl-2),BCL2-associated X(Bax),microtubule-associated protein light chain 3-II(LC3-II),mammalian target of rapamycin(mTOR),and sequestosome 1(P62).Caspase-3 activity was measured to determine apoptosis using a caspase-3 assay kit.After 12 weeks of treatment,the erectile function of the probucol group was significantly better than that of the DM group(P<0.05).Bax and LC3-II protein expression and caspase-3 activity were significantly lower in the probucol group than those in the DM group(all P<0.05),while Bcl-2,mTOR,and P62 protein expression levels were significantly higher than those in the DM group(all P<0.05).We demonstrated that probucol inhibited apoptosis and autophagy in STZ-induced diabetic rats.展开更多
Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. Th...Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group （0.5 g, twice daily） or the control group using a 1： 1 treatment ratio. IR was determined using a homeostatic model assessment-IR （HOMA-IR） index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate （eGFR）, body mass index （BMI）, cholesterol, triglycerides, high-density lipoprotein （HDL）, low-density lipoprotein （LDL）, and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased （P 〈 0.001） compared to the value before treatment （average decrease： 1.45; range： -2.90 to -0.43）. The HOMA-IR index in the control group increased （average increase： 0.54; range： -0.38 to 1.87）. For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR （P = 0.041）, cholesterol （P = 0.001）, fasting insulin （P 〈 0.001）, and fasting C-peptide （P = 0.001）. Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.展开更多
Objective We investigated the protective effect of probucol in rats with acute renal failure caused by various ischemia-reperfusion injuries(IRIs) after surgery.Methods Forty male Sprague-Dawley rats were randomly div...Objective We investigated the protective effect of probucol in rats with acute renal failure caused by various ischemia-reperfusion injuries(IRIs) after surgery.Methods Forty male Sprague-Dawley rats were randomly divided into a sham operation group(S group), ischemia reperfusion group(IR group), probucol low-dose treatment group(probucol + IR group 1, P+ IR1 group; probucol 250 mg/kg intragastric administration daily), and probucol high-dose treatment group(P + IR2 group; probucol 500 mg/kg intragastric administration daily). Rats in the S and IR groups were intragastrically administered with warm water every day. After 1 week, the kidney IRI rat models were prepared, after which the rats were fed for another week, and blood, urine, and the kidney tissue specimens were retained. A series of biochemical indices, superoxide dismutase(SOD), and malondialdehyde in the serum and kidney tissues were detected, and pathological changes in renal tissue were observed.Results Twenty-four-hour urinary protein excretion, urinary NAGase, Cys C, blood urea nitrogen(BUN), and creatinine were significantly lower in the P + IR1 and P + IR2 groups than in the IR group(P < 0.05). Superoxide dismutase in the serum and renal tissue increased significantly, malondialdehyde decreased significantly(P < 0.05), renal pathological injury was alleviated, and the kidney index improved significantly(P < 0.05).Conclusion Probucol can relieve various types of acute renal failure in postoperative rats.展开更多
Background Oxidative stress plays an important role in atherogenesis, which raises the possibility of using antioxidants to ameliorate atherosclerosis. In this research, we aim to determine the effects of probucol on ...Background Oxidative stress plays an important role in atherogenesis, which raises the possibility of using antioxidants to ameliorate atherosclerosis. In this research, we aim to determine the effects of probucol on atherosclerosis in rats. Methods Forty-five male adult Wistar rats were randomly and equally allocated to three groups, control group （Group N）, model group （Group M） and probucol group （Group P）. High-lipid diet and intraperitoneal injection of Vitamin D3 were given to establish rats atherosclerosis （AS） model. Group P was intragastrically administered Probucol after 8 weeks. At the end of 16 weeks, all the rats were weighted and sacrificed for detecting the levels of triglycerides （TG）, total cholesterol （TC）, low-density lipoprotein （LDL）, high-density lipoprotein （HDL）, oxidized low-density lipoprotein （OX-LDL） and malonaldehyde （MDA） in serum and the activity of serum superoxide dismutase （SOD）. The histomorphologieal changes of the aorta were observed under light microscope. Results The body weight of rats in Group M and Group P were lighter than that in Group N （P 〈 0.01）, and rats in Group P were heavier than those in Group M （P 〈 0.01）. The contents of TC, TG and LDL-C in serum were obviously elevated in Group M and Group P compared with those in Group N （P 〈 0.01）, and the content of HDL in Groups M and P was lower than that in Group N （P 〈 0.01）. The contents of TC and LDL-C in serum were significantly lower in Group P than those in Group M （P 〈 0.01 ）. However, the contents of TG and HDL in Groups M and P showed no statistically significant differences with each other （P 〉 0.05）. The serum OX-LDL and MDA levels significantly increased, SOD activity decreased in Groups M and P compared with Group N （P 〈 0.01）, while the levels of OX-LDL and MDA in Group P were lower than those in Group M （P 〈 0.05）. No vessel lesion was found in Group N. The endothelial damage of the aorta was more significantly severe in Group M than in Group N, while the vessel lesion was less severe in Group P than in Group M. Conclusion Probucol can prevent atherogenesis and play a crucial role in inhibition of oxidative stress.展开更多
Objectives Bone morphogenetic protein-2 (BMP-2) plays an key role both in vascular development and pathophysiological processes. However, the mechanisms of oxidized low density lipoprotein (ox-LDL) and combinated with...Objectives Bone morphogenetic protein-2 (BMP-2) plays an key role both in vascular development and pathophysiological processes. However, the mechanisms of oxidized low density lipoprotein (ox-LDL) and combinated with atorvastatin or probucol on BMP-2 expression are entirely unknown in human umbilical vein cells. Methods The HUVECs were treated by ox-LDL and combinated with atorvastatin, probucol. The expression of BMP-2, NF-κB65, PPARγ mRNA was examined by RT-PCR analysis and ELISA method. The MDA and SOD were detected by routine methods. Results Ox-LDL can induced BMP-2 mNRA expression, associated with NF-κB65 mNRA expression activation. Both atorvastatin and probucol can suppress BMP-2 and NF-κB65 expression induced by oxLDL and upregulate the expression of PPARγ. Furthermore, the increase of supernatant MDA levels and decrease of supernatant SOD levels resulted from oxLDL treatment can be reversed by probucol or atorvastatin. Conclusions OxLDL-induced BMP-2 mNRA expression can be suppressed by atorvastatin and probucol, which may be accomplished by activating NF-κB65 expression and upregulating the expression of PPARγ. Our findings also indicate that that BMP-2 mNRA expression includes the activation of reactive oxygen species.展开更多
Objective: To explore the influence of probucol-assisted retinal photocoagulation therapy on the visual performance and serum biochemical indexes in patients with early proliferative diabetic retinopathy. Methods: A t...Objective: To explore the influence of probucol-assisted retinal photocoagulation therapy on the visual performance and serum biochemical indexes in patients with early proliferative diabetic retinopathy. Methods: A total of 170 patients with early proliferative DR who were treated in the hospital between December 2014 and May 2017 were retrospectively analyzed and divided into the control group (n=107) who received retinal photocoagulation therapy alone and the probucol group (n=63) who received probucol-assisted retinal photocoagulation therapy. The differences in the contents of visual performance indexes as well as serum angiogenesis indexes, inflammatory mediators and oxidative stress indexes were compared between the two groups before treatment and after 6 weeks of treatment. Results: Before treatment, the differences in the levels of visual performance indexes as well as serum contents of angiogenesis indexes, inflammatory mediators and oxidative stress indexes were not statistically significant between the two groups of patients. After 6 weeks of treatment, mean vision, 30 visual acuity and 30-60 visual acuity of probucol group were higher than those of control group;serum angiogenesis indexes HIF-1, VEGF and Ang-2 contents were lower than those of control group;serum inflammatory mediators ICAM-1, IL-2, IL-23 and TNF-α contents were lower than those of control group;serum oxidative stress index MDA content was lower than that of control group whereas TAC content was higher than that of control group. Conclusion: Probucol-assisted retinal photocoagulation therapy can effectively optimize the visual performance and promote the homeostasis recovery in patients with early proliferative diabetic retinopathy.展开更多
Neurodegenerative disorders present complex pathologies characterized by various interconnected factors,including the aggregation of misfolded proteins,oxidative stress,neuroinflammation and compromised blood-brain ba...Neurodegenerative disorders present complex pathologies characterized by various interconnected factors,including the aggregation of misfolded proteins,oxidative stress,neuroinflammation and compromised blood-brain barrier(BBB)integrity.Addressing such multifaceted pathways necessitates the development of multi-target therapeutic strategies.Emerging research indicates that probucol,a historic lipid-lowering medication,offers substantial potential in the realm of neurodegenerative disease prevention and treatment.Preclinical investigations have unveiled multifaceted cellular effects of probucol,showcasing its remarkable antioxidative and anti-inflammatory properties,its ability to fortify the BBB and its direct influence on neural preservation and adaptability.These diverse effects collectively translate into enhancements in both motor and cognitive functions.This review provides a comprehensive overview of recent findings highlighting the efficacy of probucol and probucol-related compounds in the context of various neurodegenerative conditions,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and cognitive impairment associated with diabetes.展开更多
Background Probucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the ef...Background Probucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the effect of probucol on vascular remodeling in a rabbit model of established atherosclerosis. Methods Aortic atherosclerosis was induced by a combination of endothelial injury and 10 weeks＇ atherogenic diet. Animals were then randomized to receive the foregoing diet without or with 1% （wt/wt） probucol for 16 weeks. At the end of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical and gene expression studies were performed. Results Probucol significantly decreased vessel cross-sectional area, plaque area and plaque burden without effect on lumen area. More negative remodeling and less positive remodeling occurred in the abdominal aortas of probucol group than the control group （56% vs. 21%, 18% vs. 54%, respectively, both P〈0.01）. In addition, the probucol group showed a smaller mean remodeling index relative to the control group （0.93 ± 0.13 vs. 1.05 ± 0.16, P 〈0.01）. Furthermore, probucol treatment decreased macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S （all P 〈0.01）. Conclusions These findings suggest that probucol may attenuate the enlargement of atherosclerotic vessel walls and be associated with a negative remodeling pattern without affecting the lumen size. This effect may involve inhibition of extracellular matrix degradation and prevention of apoptosis in atherosclerotic plaques.展开更多
基金financial support from the National Basic Research Program of China(973 Program,No.2009CB930300)
文摘The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process.Cellulose derivatives of different substitution groups and molecular weights,including HPMC,HPC,and MC,were evaluated as the primary stabilizer of probucol nanosuspension.Ternary stabilizers system composed of a primary stabilizer(cellulose derivative,i.e.HPC),a nonionic surfactant(Pluronic R F68),and an anionic surfactant(SDS)was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media.The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4°C or 25°C.The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate(>60%at 2 h)compared to other cryoprotectant.The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats.The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.
文摘Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety （QTc intervals） were set, respectively. Probucol significantly reduced total cholesterol （P 〈 0.001）, low-density lipoprotein cholesterol （LDL-C）, （P = 0.01）, and high-density lipoprotein cholesterol （HDL-C） （P 〈 0.001） compared with conventional therapy. Cilostazol was effective in increasing HDL-C （P = 0.002） and reducing triglycerides levels （P 〈 0.01） compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein （Ox-LDL, P = 0.065）. No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.
基金the National Natural Science Foundation of China(No.81873830)the Shandong Provincial Medicine and Health Science Technology Development Plan(No.2016WS0423)+1 种基金the Shandong Provincial Natural Science Foundation(No.ZR2016HB32 and No.ZR2017BH036)the Shandong Provincial Key Research Program(No.2017GSF218071,No.2018GSF118083,and No.2018GSF118142).
文摘Autophagy and apoptosis have been regarded as important processes in the development of diabetic erectile dysfunction(DMED).Probucol is considered to have anti-apoptotic effects,but its relationship with autophagy has not been reported.The aim of this study was to investigate the effects and mechanisms of probucol on erectile function.Thirty Sprague–Dawley(SD)male rats(12 weeks old)were fasted for 12 h.Twenty SD rats were injected with a single intraperitoneal injection of 60 mg kg−1 streptozotocin(STZ).Ten rats were given vehicle only and used as a sham group.After 72 h,20 STZ-treated rats with random blood glucose concentrations consistently greater than 16.7 mmol l^−1 were used as successfully established diabetic rats.The diabetic rats were divided randomly into two groups and treated with a daily gavage of probucol at a dose of 0 or 500 mg kg^−1 for 12 weeks.After treatment,the intracavernous pressure(ICP)was used to measure erectile function upon electrical stimulation of the cavernous nerve.After euthanasia,penile tissue was examined using immunohistochemistry and Western blot to assess the protein levels of B-cell lymphoma-2(Bcl-2),BCL2-associated X(Bax),microtubule-associated protein light chain 3-II(LC3-II),mammalian target of rapamycin(mTOR),and sequestosome 1(P62).Caspase-3 activity was measured to determine apoptosis using a caspase-3 assay kit.After 12 weeks of treatment,the erectile function of the probucol group was significantly better than that of the DM group(P<0.05).Bax and LC3-II protein expression and caspase-3 activity were significantly lower in the probucol group than those in the DM group(all P<0.05),while Bcl-2,mTOR,and P62 protein expression levels were significantly higher than those in the DM group(all P<0.05).We demonstrated that probucol inhibited apoptosis and autophagy in STZ-induced diabetic rats.
文摘Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group （0.5 g, twice daily） or the control group using a 1： 1 treatment ratio. IR was determined using a homeostatic model assessment-IR （HOMA-IR） index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate （eGFR）, body mass index （BMI）, cholesterol, triglycerides, high-density lipoprotein （HDL）, low-density lipoprotein （LDL）, and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased （P 〈 0.001） compared to the value before treatment （average decrease： 1.45; range： -2.90 to -0.43）. The HOMA-IR index in the control group increased （average increase： 0.54; range： -0.38 to 1.87）. For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR （P = 0.041）, cholesterol （P = 0.001）, fasting insulin （P 〈 0.001）, and fasting C-peptide （P = 0.001）. Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.
基金Supported by Scientific Research Project of Hubei Provincial Health and Family Planning Commission(No.WJ2015Z042)
文摘Objective We investigated the protective effect of probucol in rats with acute renal failure caused by various ischemia-reperfusion injuries(IRIs) after surgery.Methods Forty male Sprague-Dawley rats were randomly divided into a sham operation group(S group), ischemia reperfusion group(IR group), probucol low-dose treatment group(probucol + IR group 1, P+ IR1 group; probucol 250 mg/kg intragastric administration daily), and probucol high-dose treatment group(P + IR2 group; probucol 500 mg/kg intragastric administration daily). Rats in the S and IR groups were intragastrically administered with warm water every day. After 1 week, the kidney IRI rat models were prepared, after which the rats were fed for another week, and blood, urine, and the kidney tissue specimens were retained. A series of biochemical indices, superoxide dismutase(SOD), and malondialdehyde in the serum and kidney tissues were detected, and pathological changes in renal tissue were observed.Results Twenty-four-hour urinary protein excretion, urinary NAGase, Cys C, blood urea nitrogen(BUN), and creatinine were significantly lower in the P + IR1 and P + IR2 groups than in the IR group(P < 0.05). Superoxide dismutase in the serum and renal tissue increased significantly, malondialdehyde decreased significantly(P < 0.05), renal pathological injury was alleviated, and the kidney index improved significantly(P < 0.05).Conclusion Probucol can relieve various types of acute renal failure in postoperative rats.
文摘Background Oxidative stress plays an important role in atherogenesis, which raises the possibility of using antioxidants to ameliorate atherosclerosis. In this research, we aim to determine the effects of probucol on atherosclerosis in rats. Methods Forty-five male adult Wistar rats were randomly and equally allocated to three groups, control group （Group N）, model group （Group M） and probucol group （Group P）. High-lipid diet and intraperitoneal injection of Vitamin D3 were given to establish rats atherosclerosis （AS） model. Group P was intragastrically administered Probucol after 8 weeks. At the end of 16 weeks, all the rats were weighted and sacrificed for detecting the levels of triglycerides （TG）, total cholesterol （TC）, low-density lipoprotein （LDL）, high-density lipoprotein （HDL）, oxidized low-density lipoprotein （OX-LDL） and malonaldehyde （MDA） in serum and the activity of serum superoxide dismutase （SOD）. The histomorphologieal changes of the aorta were observed under light microscope. Results The body weight of rats in Group M and Group P were lighter than that in Group N （P 〈 0.01）, and rats in Group P were heavier than those in Group M （P 〈 0.01）. The contents of TC, TG and LDL-C in serum were obviously elevated in Group M and Group P compared with those in Group N （P 〈 0.01）, and the content of HDL in Groups M and P was lower than that in Group N （P 〈 0.01）. The contents of TC and LDL-C in serum were significantly lower in Group P than those in Group M （P 〈 0.01 ）. However, the contents of TG and HDL in Groups M and P showed no statistically significant differences with each other （P 〉 0.05）. The serum OX-LDL and MDA levels significantly increased, SOD activity decreased in Groups M and P compared with Group N （P 〈 0.01）, while the levels of OX-LDL and MDA in Group P were lower than those in Group M （P 〈 0.05）. No vessel lesion was found in Group N. The endothelial damage of the aorta was more significantly severe in Group M than in Group N, while the vessel lesion was less severe in Group P than in Group M. Conclusion Probucol can prevent atherogenesis and play a crucial role in inhibition of oxidative stress.
文摘Objectives Bone morphogenetic protein-2 (BMP-2) plays an key role both in vascular development and pathophysiological processes. However, the mechanisms of oxidized low density lipoprotein (ox-LDL) and combinated with atorvastatin or probucol on BMP-2 expression are entirely unknown in human umbilical vein cells. Methods The HUVECs were treated by ox-LDL and combinated with atorvastatin, probucol. The expression of BMP-2, NF-κB65, PPARγ mRNA was examined by RT-PCR analysis and ELISA method. The MDA and SOD were detected by routine methods. Results Ox-LDL can induced BMP-2 mNRA expression, associated with NF-κB65 mNRA expression activation. Both atorvastatin and probucol can suppress BMP-2 and NF-κB65 expression induced by oxLDL and upregulate the expression of PPARγ. Furthermore, the increase of supernatant MDA levels and decrease of supernatant SOD levels resulted from oxLDL treatment can be reversed by probucol or atorvastatin. Conclusions OxLDL-induced BMP-2 mNRA expression can be suppressed by atorvastatin and probucol, which may be accomplished by activating NF-κB65 expression and upregulating the expression of PPARγ. Our findings also indicate that that BMP-2 mNRA expression includes the activation of reactive oxygen species.
文摘Objective: To explore the influence of probucol-assisted retinal photocoagulation therapy on the visual performance and serum biochemical indexes in patients with early proliferative diabetic retinopathy. Methods: A total of 170 patients with early proliferative DR who were treated in the hospital between December 2014 and May 2017 were retrospectively analyzed and divided into the control group (n=107) who received retinal photocoagulation therapy alone and the probucol group (n=63) who received probucol-assisted retinal photocoagulation therapy. The differences in the contents of visual performance indexes as well as serum angiogenesis indexes, inflammatory mediators and oxidative stress indexes were compared between the two groups before treatment and after 6 weeks of treatment. Results: Before treatment, the differences in the levels of visual performance indexes as well as serum contents of angiogenesis indexes, inflammatory mediators and oxidative stress indexes were not statistically significant between the two groups of patients. After 6 weeks of treatment, mean vision, 30 visual acuity and 30-60 visual acuity of probucol group were higher than those of control group;serum angiogenesis indexes HIF-1, VEGF and Ang-2 contents were lower than those of control group;serum inflammatory mediators ICAM-1, IL-2, IL-23 and TNF-α contents were lower than those of control group;serum oxidative stress index MDA content was lower than that of control group whereas TAC content was higher than that of control group. Conclusion: Probucol-assisted retinal photocoagulation therapy can effectively optimize the visual performance and promote the homeostasis recovery in patients with early proliferative diabetic retinopathy.
基金supported by the National Health and Medical Research Council of Australia(GNT2001090)Medical Research Future Fund(MRF1201204),MSWA,McCusker Charitable Research Foundation and the Wen Giving Foundation.
文摘Neurodegenerative disorders present complex pathologies characterized by various interconnected factors,including the aggregation of misfolded proteins,oxidative stress,neuroinflammation and compromised blood-brain barrier(BBB)integrity.Addressing such multifaceted pathways necessitates the development of multi-target therapeutic strategies.Emerging research indicates that probucol,a historic lipid-lowering medication,offers substantial potential in the realm of neurodegenerative disease prevention and treatment.Preclinical investigations have unveiled multifaceted cellular effects of probucol,showcasing its remarkable antioxidative and anti-inflammatory properties,its ability to fortify the BBB and its direct influence on neural preservation and adaptability.These diverse effects collectively translate into enhancements in both motor and cognitive functions.This review provides a comprehensive overview of recent findings highlighting the efficacy of probucol and probucol-related compounds in the context of various neurodegenerative conditions,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and cognitive impairment associated with diabetes.
文摘Background Probucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the effect of probucol on vascular remodeling in a rabbit model of established atherosclerosis. Methods Aortic atherosclerosis was induced by a combination of endothelial injury and 10 weeks＇ atherogenic diet. Animals were then randomized to receive the foregoing diet without or with 1% （wt/wt） probucol for 16 weeks. At the end of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical and gene expression studies were performed. Results Probucol significantly decreased vessel cross-sectional area, plaque area and plaque burden without effect on lumen area. More negative remodeling and less positive remodeling occurred in the abdominal aortas of probucol group than the control group （56% vs. 21%, 18% vs. 54%, respectively, both P〈0.01）. In addition, the probucol group showed a smaller mean remodeling index relative to the control group （0.93 ± 0.13 vs. 1.05 ± 0.16, P 〈0.01）. Furthermore, probucol treatment decreased macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S （all P 〈0.01）. Conclusions These findings suggest that probucol may attenuate the enlargement of atherosclerotic vessel walls and be associated with a negative remodeling pattern without affecting the lumen size. This effect may involve inhibition of extracellular matrix degradation and prevention of apoptosis in atherosclerotic plaques.
