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Effects of a novel isoflavonoid from the stem bark of Alstonia scholaris against fructose-induced experimental cataract

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Journal of Integrative Medicine 2019年第5期17卷 374-382页

作者： Pranay Soni Rajesh Choudhary Surendra H.Bodakhe department of pharmacology Institute of Pharmaceutical SciencesGuru Ghasidas Vishwavidyalaya

Objective: The present study investigated the anticataract activity of a novel isoflavonoid, isolated from stem bark of Alstonia scholaris, against fructose-induced experimental ***: The bioactivity of fractions extracted from A. scholaris, an isolated isoflavonoid(ASII) was screened using in vitro(goat lens) and in vivo(albino rats) experimental cataract models. For the in vivo evaluation, albino rats(12–15 weeks old) were divided into five groups(n = 6). Group I(normal)received 0.3% carboxymethyl cellulose solution(10 m L/[kgád], p.o.). Group II(control) received 10%(w/v)fructose solution in their drinking water. Groups III–V received ASII at three different doses, 0.1, 1.0 and10 mg/(kgád), concurrently with 10%(w/v) fructose solution. Treatment was given daily for 8 consecutive weeks. During the protocol, systolic blood pressure, diastolic blood pressure, blood glucose level and lenticular opacity were monitored at 2-week intervals. Pathophysiological markers(catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione and malondialdehyde) in eye lenses were examined at the end of the 8-week treatment ***: The results of in vitro study showed that A. scholaris extract and the active fraction(A3) reduced the lenticular opacity as compared to toxic control group. The in vivo study showed that 8-week administration of ASII(0.1, 1.0 and 10 mg/[kgád], p.o.) led to significant reduction in blood pressure and blood glucose level and retarded the initiation and evolution of cataractogenesis, compared to the fructoseinduced cataract model control. Additionally, ASII treatment led to significant improvement in lens antioxidants(catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione) and decreased lens malondialdehyde, compared to the control group(group II).Conclusion: Results revealed that administration of ASII played a crucial role in the reduction of cataract formation in diabetic and hypertensive models.

关键词： Isoflavonoid Oxidative stress Alstonia scholaris Hypertension Diabetes Cataract

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Induction of systemic lupus erythematosus syndrome in BALB/c mice by immunization with active chromatin

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Acta Pharmacologica Sinica 2004年第6期25卷 105-109页

作者： Hong LI, Yun-yi ZHANG, Ya-nan SUN, Xi-yi HUANG, Yong-feng JIA, Duan LI2 department of pharmacology, Schoolof Pharmacy, Fudan University, Shanghai 200032, China department of pharmacology School of Pharmacy Fudan University Shanghai 200032 China

AIM: To establish an animal model for systemic lupus erythematosus (SLE)-like syndrome in mice. METHODS: BALB/c mice were immunized with active chromatin isolated from ConA-actived syngeneic spleno-lymphocytes. Plasma samples of mice were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of IgG anti-dsDNA, -ssDNA, and anti-histone antibodies. Tumor necrosis factor-α (TNF-α) in serum was measured by ELISA. Spleno-lymphocyte proliferation assays and the levels of interferon-γ (IFN-γ) in supernatants were tested respectively. Proteinuria was measured. Kidneys were examined by direct immunohistochemical method and light microscopy. RESULTS: Anti-ds DNA, ssDNA, and histone antibodies were induced in active chromatin-immu- nized mice, the proliferation response of splenocytes to ConA and LPS were reduced, levels of interferon-γ in supernatants and TNF-α in serum were lowered. Lupus nephritis was assessed by the presence of Ig deposits, glomerular pathology and proteinuria. CONCLUSION: The active chromatin-induced SLE-like mouse model was similar to idiopathic SLE in human.

关键词： systemic lupus erythematosus chromatin autoantibody tumor necrosis factor interferon type II B-lymphocytes T-lymphocytes female enzyme-linked immunosorbent assay

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Increased salt sensitivity induced by sensory denervation: role of superoxide

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Acta Pharmacologica Sinica 2004年第12期25卷 60-66页

作者： Alex F CHEN,Donna H WANG department of Medicine and pharmacology & Toxicology Michigan State University East Lansing MI 48824 USA department of Medicine and pharmacology & Toxicology Michigan State University East Lansing MI 48824 USA

AIM: To test the hypothesis that production of superoxide in mesenteric resistance arteries is increased and con- tributes to the development of hypertension induced by sensory denervation plus high salt intake. METHODS: Newborn Wistar rats were given capsaicin 50 mg/kg sc on the 1st and 2nd d of life. After weaning, male rats were grouped as follows and treated for 3 weeks with: capsaicin pretreatment plus normal sodium diet (0.5 %, CAP-NS), CAP plus high sodium diet (4 %, CAP-HS), control plus NS (CON-NS), or CON-HS. Both tail-cuff systolic blood pressure and mean arterial pressure (MAP) were measured in each of the groups. Western blot analysis was used for measurement of manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) in the mesenteric resistance arteries. Lucigenin chemiluminescence assay was used for superoxide production in the mesenteric resistance arteries. The Griess method was used for measurement of nitrite/nitrate levels in plasma. RESULTS: Both tail-cuff pressure and MAP were higher in CAP-HS compared with CAP-NS, CON-HS, and CON- NS rats (P<0.05). Both MnSOD and eNOS in the mesenteric resistance arteries were increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, nitrite/nitrate levels in plasma were not different among 4 groups. Acute iv administration of tempol, a membrane-permeable superoxide scavenger, de- creased MAP in both CAP-HS and CON-HS when compared with their respective controls. However, the de- creases of MAP between these two groups were not different. Chronic treatment with tempol failed to prevent the development of hypertension in CAP-HS rats. Superoxideproduction in the mesenteric resistance arteries was increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, chronic treatment with tempol did not prevent the increase of mesenteric superoxideproduction in CAP-HS rats. CONCLUSIONS: Regardless of increased vascular MnSOD levels, salt

关键词： superoxides tempol afferent neurons capsaicin denervation dietary sodium chloride nitric oxide

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Update on pharmacological treatment of acute coronary syndrome without persistent ST segment elevation myocardial infarction in the elderly

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Journal of Geriatric Cardiology 2017年第7期14卷 457-464页

作者： Coskun Usta Ash Bedel department of pharmacology Faculty of Medicine Akdeniz University Antalya Turkey

The increase in cardiovascular disease prevalence with ageing has been attributed to several age-related changes such as changes in the vascular wall elasticity, the coagulation and haernostatic system and endothelial dysfunction, among other causes. There is a 50% increased mortality risk per 10-year increase in age starting at 65 years old. Here, we aimed to discuss pharmacological treatment in acute coronary syndrome （ACS） without persistent ST segment elevation myocardial infarction in the elderly. The main aim of ACS treatment in elderly people is at preventing ischemia, myocardial damage and complications. A meta-analysis suggests that invasive revascularization therapy is probably most useful in older patients. Dual antiplatelet therapy is currently the standard of care post-ACS. Platelet P2Y12 inhibitors are among the most commonly used medications worldwide, due to their established benefits in the treatment and prevention of arterial throm- bosis. The main recommendation is to tailor antithrombotic treatment, considering body weight, renal function （Class I, level C） and careful evaluation of life expectancy, comorbidities, risk/benefit profile, quality of life and fxailty when invasive strategies are considered （Class IIa, level A） on top of the different recommendations given for a general non ST elevation ACS population. It is obvious that potent P2Y12 in- hibitors will continue to play an important role in pharmacological treatment for elderly ACS patients in the future.

关键词： Acute coronary syndrome Pharmacological interactions The elderly Treatment

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Norisoboldine, a natural aryl hydrocarbon receptor agonist, alleviates TNBS-induced colitis in mice, by inhibiting the activation of NLRP3 inflammasome

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Chinese Journal of Natural Medicines 2018年第3期16卷 161-174页

作者： LV Qi WANG Kai QIAO Si-Miao DAI Yue WEI Zhi-Feng department of pharmacology of Chinese Materia Medica China Pharmaceutical University

Although the etiology of inflammatory bowel disease is still tmcertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine （NOR）, an alkaloid isolated from Radix Linderae, has previously been demonstrated to inhibit inflammation and IL-1,8 production. The present study was to examine the effect of NOR on colitis and the underlying mechanism related to NLRP3 inflammasome activation. Our results showed that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene sulfonic acid （TNBS）. Moreover, it significantly reduced expressions of cleaved IL-lfl, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1 cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL-1β but not ASC induced by lipopolysaccharide （LPS） and adenosine triphosphate （ATP）. Furthermore, NOR could activate aryl hydrocarbon receptor （AhR） in THP-1 cells, inducing CYP1A1 mRNA expression, and promoting dissociation of AhR/HSP90 complexes, association of AhR and ARNT, AhR nuclear translocation, XRE reporter activity and binding activity of AhR/ARNT/XRE. Both siAhR and a-naphthoflavone （a-NF） markedly diminished the inhibition of NOR on NLRP3 inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS level in LPS- and ATP-stimulated THP-1 cells, which was reversed by either siAhR or α-NF treatment. Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling pathway.

关键词： Norisoboldine Inflammatory bowel disease NLRP3 inflammasome Aryl hydrocarbon receptor

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Effects of esculentoside A on production of interleukin-1, 2, and prostaglandin E2

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Acta Pharmacologica Sinica 2004年第6期25卷 115-119页

作者： Zhen-yu XIAO, Qin-yue ZHENG, Yuan-ying JIANG, Bin ZHOU, Ming YIN2, Hong-bin WANG, Jun-ping ZHANG3 department of pharmacology,Second Military Medical University, Shanghai200433 2College of Pharmacy,Jiao Tong University, Shanghai 200030, China department of pharmacology Second Military Medical University Shanghai 200433 China

AIM: To investigate the influence of esculentoside A (EsA) on immunological function and its mechanism of anti- inflammation. METHODS: Interleukin-1 production was measured by thymocyte co-stimulating assay; the radio- activity of [3H]arachidonic acid (AA) was used to evaluate the release of AA; prostaglandin E2 production was measured with radioimmunoassay (RIA); IL-2 and IFN-γ were detected by ELISA method. RESULTS: EsA (3-12 μmol/L)could potently inhibit the production of IL-1 and PGE2 from both silent and LPS induced macrophages. EsA had no significant effect on the release of AA from murine macrophages. EsA could inhibit the production of IL-2 from murine lymphocytes induced by ConA, but not affect the production from silent lymphocytes. EsA showed no effect on the production of IFN-γ from both silent and ConA induced lymphocytes. CONCLUSION: EsA could affect the immunological function through inhibiting the production of IL-2 from activated splenocytes and the inhibition of production of IL-1 and PGE2 might be one of the anti-inflammation mechanisms of EsA.

关键词： esculentoside A interleukin-1 interleukin-2 prostaglandins E interferon-gamma

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Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2107-2123页

作者： Huiyang Wang Yueyang Liu Zhenkun Guo Minghui Cui Peng Pang Jingyu Yang Chunfu Wu department of pharmacology Shenyang Pharmaceutical UniversityShenyang 110016China

Cognitive impairment caused by chronic cerebral hypoperfusion(CCH)is associated with white matter injury(WMI),possibly through the alteration of ***,the autophagy—lysosomal pathway(ALP)dysfunction in white matter(WM)and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion(2VO).The results showed that cognitive impairment occurred by the 28th day after *** and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd *** the 14th day,abnormal accumulation of autophagy substrate,lysosomal dysfunction,and the activation of mechanistic target of rapamycin(MTOR)pathway were observed in WM,paralleled with mature oligodendrocyte *** indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal *** target the ALP dysfunction,enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1(BECN1)in oligodendrocytes reduced mature oligodendrocyte death,and subsequently alleviated the WMI and cognitive impairment after *** results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO,which was associated with the aggravation of WMI and cognitive *** study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.

关键词： Chronic cerebral hypoperfusion Two vessel occlusion White matter Cognitive impairment Oligodendrocyte Myelin sheath Autophagy-lysosomal pathway Mechanistic target of rapamycin

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Detection and quantitation of PS20, a phosphorothioate oligodeoxynucleotides in monkey plasma

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Acta Pharmacologica Sinica 2004年第6期25卷 99-104页

作者： Ming-mei SHANG, Hai-feng SONG2, Xiu-wen LIU, Zhong-ming TANG department of pharmacology and Toxicology, the Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China department of pharmacology and Toxicology the Institute of Radiation Medicine Academy of Military Medical Sciences

AIM: To establish the method for quantitation of the phosphorothioate oligodeoxynucleotides (S-ODNs) in plasma. METHODS: Two solid-phase extraction columns combined with a strong anion-exchange column were utilized to remove proteins and lipids in plasma, and the salts were removed by a reverse-phase column followed by dialysis with a 2500 Da-cutoff membrane. The concentration of the tested S-ODNs, PS20, and its metabolites extracted from the plasma were determined by the method of non-gel sieving capillary electrophoresis (NGCE) with diode array detection in the presence of internal standard (IS). RESULTS: The method was with good base number specificity. Relative standard deviation % of both intra and inter assay were all less than 10 %, and the total mean recovery was about 91 %. The methodology was successfully used to determine the PK behavior of an anti-tumor antisense S-ODNs in monkeys and identify the metabolites with single base difference. CONCLUSION: The combined method of solid-phase extraction and NGCE could be used to study the pharmacokinetics of S-ODNs, and the main parameters of the methodology met the requirement of PK study.

关键词： antisense oligodeoxyribonucleotides thionucleotides rhesus monkey plasma solid-phase extraction capillary electrophoresis non-gel sieving internal standard

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An increase in opening of BKCa channels in smooth muscle cells in streptozotocin-induced diabetic mice

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Acta Pharmacologica Sinica 2004年第6期25卷 42-48页

作者： Chun-ling YE2, Bing SHEN4, Xian-da REN, Rong-jing LUO3, Sheng-yuan DING3, Fu-man YAN3, Jia-hua JIANG department of pharmacology, Pharmacy College of Ji-nan University, Guangzhou 510632 3department of Physiology, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510407 4department of Molecular Biology and Cell Biology, School ofLife Sciences, University of Sciences and Technology of China, Hefei 230036, China department of pharmacology Pharmacy College of Ji-nan University Guangzhou 510632 Chin

AIM: To investigate the changes of function of large conductance of calcium-activated potassium channels (BKCa channels) in thoracic aortic smooth muscle cells in early stage of streptozotocin (STZ)-induced diabetic C57BL/6J mice. METHODS: Vascular muscle tension in the isolated thoracic aortic rings of mice was compared, and the role of BKCa channels in relaxation of isolated mice thoracic aortic rings induced by acetylcholine (ACh) was determined. Meanwhile, single vascular smooth muscle cells (VSMCs) were isolated by collagenase, and BKCa currents were recorded by patch-clamp single channel recording technique in symmetric high potassium solution. RESULTS: Tetraethylammonium (TEA) 1 mmol/L, a selective calcium-activated potassium channel blocker, caused significant rightward shift in the concentration-response curves of ACh in the isolated thoracic aortic rings of diabetic mice and pD2 value of ACh-induced relaxation was decreased notably after TEA treatment [(6.3±0.4) vs (6.9±0.5), n=10 rings from 7 mice, P0.05]. Furthermore, conductance of BKCa channels in single thoracic aortic smooth muscle cells was decreased [(199±15) pS, n=10 cells from 7 mice vs (266±11) pS, n=12 cells from 6 mice, P<0.01], but probability of open of BKCachannels was increased [(0.51±0.28) vs (0.11±0.06), n=6 cells from 6 mice, P<0.01], and the mean closed time in diabetic mice was reduced [(15±15) vs (132±98), n=6 cells from 6 mice, P<0.05]. CONCLUSION: The opening of BKCa channels was increased in thoracic aortic smooth muscle cells in the early stage of STZ-induced diabetic C57BL/6J mice by reducing mean closed time, but the conductance of BKCa channels was decreased.

关键词： diabetes mellitus streptozotocin aorta patch-clamp techniques potassium channels calcium

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Teaching of pharmacology in Universiti Malaya and the other medical schools in Malaysia - a historical perspective

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Acta Pharmacologica Sinica 2004年第9期25卷 107-117页

作者： Si Mui SIM 50603 Kuala Lumpur department of pharmacology Faculty of Medicine Malaysia University of Malaya

Traditional pharmacology teaching has focused more on drug instead of therapeutics, such that although pharmacological knowledge is acquired, practical skills in prescribing remain weak. In Malaysia many new medical schools (both public and private) have been set up in the last 12 years due to a change in government policy, resulting in a wide spectrum of medical curricula. Universiti Malaya (UM) being the oldest medical school in

关键词： pharmacology teaching basic sciences Malaysian medical schools integrated curriculum problem-based learning

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