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Recent developments in natural products for white adipose tissue browning

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Chinese Journal of Natural Medicines 2020年第11期18卷 803-817页

作者： MA Peng HE Ping XU Chun-Yang HOU Bi-Yu qiang gui-fen DU Guan-Hua State Key Laboratory of Bioactive Substance and Function of Natural Medicines Instiute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College and Bejing Key Laboratory of Drug Target and Screening ResearchBeijing 100050China Beijing Obstetrics and Gyecology Hospital Capital Medical UniversityBeijing 100026China

Excess accumulation of white adipose tissue(WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke,heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. Browning, inducing white adipose tissue to brown or beige(brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue(BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products(alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes(T2 DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.

关键词： Natural products Browning Brown adipose tissue White adipose tissue Obesity

Hypoglycemic activity of puerarin through modulation of oxidative stress and mitochondrial function via AMPK

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Chinese Journal of Natural Medicines 2020年第11期18卷 818-826页

作者： HOU Bi-Yu ZHAO Yue Rong MA Peng XU Chun-Yang HE Ping YANG Xiu-Ying ZHANG Li qiang gui-fen DU Guan-Hua State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College and Beijing Ke|Laboralory of Drug Target and Screening ResearchBeijing 100050China Beiing Obstetrics and Gynecology Hospital Capital Medical UniversityBeijing 100026China

Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. However, little is known about its direct effects on diabetes. The aim of our study is to investigate its antidiabetic effect in vivo and in vitro, and explore the underlying mechanism. We used type I diabetic mice induced by streptozotocin to observe the effects of puerarin on glucose metabolism. In addition, oxidative stress and hepatic mitochondrial respiratory activity were evaluated in type I diabetic mice. In vitro, glucose consumption in Hep G2 cells was assayed along with the q PCR detection of glucogenesis genes expression. Moreover, ATP production was examined and phosphorylation of AMPK was determined using Western blot. Finally, the molecular docking was performed to predict the potential interaction of puerarin with AMPK utilizing program Lib Dock of Discovery Studio 2018 software. The results showed that puerarin improved Hep G2 glucose consumption and upregulated the glucogenesis related genes expression. Also, puerarin lowered fasting and fed blood glucose with improvement of glucose tolerance in type I diabetic mice. Further mechanism investigation showed that puerarin suppressed oxidative stress and improved hepatic mitochondrial respiratory function with enhancing ATP production and activating phosphorylation of AMPK. Docking study showed that puerarin interacted with AMPK activate site and enhancing phosphorylation. Taken together, these findings indicated that puerarin exhibited the hypoglycemic effect through attenuating oxidative stress and improving mitochondrial function via AMPK regulation, which may serve as a potential therapeutic option for diabetes treatment.

关键词： Puerarin Diabetes Hypoglycemic Oxidative stress Mitochondrial function

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丹酚酸A对缺血/再灌注心肌的保护作用研究

中国药理学通报 2011年第8期27卷 1072-1076页

作者：杨秀颖强桂芬张莉杜冠华中国协和医科大学中国医学科学院药物研究所北京100050 航天中心医院北京100049

目的研究丹酚酸A对缺血/再灌注性心肌的保护作用及机制探讨。方法采用Sprague Dawley大鼠冠状动脉左前降支结扎10 min,再灌注2 h,评价丹酚酸A(1.5、***-1)静脉给药对在体状态下大鼠心律失常的影响。以利多卡因(5 ***-1)为阳性对照,各给... 详细信息

目的研究丹酚酸A对缺血/再灌注性心肌的保护作用及机制探讨。方法采用Sprague Dawley大鼠冠状动脉左前降支结扎10 min,再灌注2 h,评价丹酚酸A(1.5、***-1)静脉给药对在体状态下大鼠心律失常的影响。以利多卡因(5 ***-1)为阳性对照,各给药组均为结扎前10 min给药。同时评价丹酚酸A对培养的心肌细胞缺氧-复氧损伤的影响。结果丹酚酸A 1.5 ***-1剂量组静脉给药可降低由于心肌缺血/再灌注引起的心律失常发生率,减少肌酸激酶和肌酸激酶同工酶MB从胞体中的漏出。另外,丹酚酸A可防止心肌细胞缺氧-复氧损伤,提高细胞内ATP水平,降低细胞线粒体的膜电位和细胞内钙水平。结论丹酚酸A对缺血/再灌注性心肌具有保护作用,可能是通过抗氧化、抑制钙离子内流、保护线粒体功能、增加心肌细胞中ATP的含量实现的。

关键词：丹酚酸A 大鼠再灌注损伤心律失常心肌细胞缺氧复氧线粒体

美国FDA上市减肥药不良反应研究进展与安全性思考

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中国新药杂志 2023年第20期32卷 2113-2120页

作者：周围马鹏许天姝张丽杜冠华强桂芬国家药品监督管理局药品审评中心北京100022 北京协和医学院/中国医学科学院药物研究所药物靶点研究与新药筛选北京市重点实验室北京100050 内蒙古医科大学呼和浩特010107

本文综述了1887年至今获得美国FDA批准上市的17种减肥药在临床试验期间及上市后的相关不良反应,包括仍在市的6种以及因瓣膜性心脏病、自杀倾向、致癌风险等原因遭撤市的11种减肥药。减肥药在降低肥胖患者体重以及代谢获益的同时也会引... 详细信息

本文综述了1887年至今获得美国FDA批准上市的17种减肥药在临床试验期间及上市后的相关不良反应,包括仍在市的6种以及因瓣膜性心脏病、自杀倾向、致癌风险等原因遭撤市的11种减肥药。减肥药在降低肥胖患者体重以及代谢获益的同时也会引发各种不良反应,包括精神神经系统不良反应、致癌风险、心脏毒性、肝损伤、胰腺毒性、肾毒性、消化道不良反应等诸多不良反应;其中,美国FDA会对严重不良反应进行黑框警告,而具有致命性的严重不良反应药物则被勒令撤市。本文在归纳减肥药不良反应的同时对其安全性进行深度思考,以期为减肥药的研发及临床医生与患者正确使用减肥药提供相关参考,保护人民生命健康。

关键词：肥胖减肥药不良反应安全性美国FDA

Different lipids remodeling signature demonstrated heterogeneity of white adipose tissue browning

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中国药理学与毒理学杂志 2019年第10期 921-921页

作者： HE Ping HOU Bi-yu YANG Xiu-ying ZHANG Li qiang gui-fen DU Guan-hua State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

OBJECTIVE White adipose tissue(WAT)browning confers beneficial effects on metabolic ***, visceral adipose tissue(VAT) is not as susceptible to browning as subcutaneousadipose tissue(SAT).Therefore, interpreting the heterogeneity of VAT and SAT in brown remodeling is extremely important. METHODS We first investigated the effects of beta-3 adrenergic stimulation by CL316, 243 on systemic metabolism. Then, highcoverage targeted lipidomics approach with multiple reaction monitoring(MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT using an Exion ultra performance liquid chromatography(UPLC)coupled with Sciex QTRAP 6500 Plus. RESULTS Beta-3 adrenergic stimulation notably ameliorated the systemic metabolism. Moreover, comprehensive lipidomics analysis elucidated different lipids adaptation between VAT and SAT in adrenergic-induced browning. CL316, 243 induced browning heterogeneity of VAT and SAT with more dramatic alteration of total lipid classes and individual molecular lipid species in VAT rather than SAT, though VAT is resistant to browning. Specifically, CL316, 243 stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. Further study uncovered that the lipids remodeling heterogeneity of VAT and SAT may attribute to a more significant alteration of lipids metabolism genes in VAT rather than SAT in response to CL316,243 treatment. CONCLUSION Our datasets provide acomprehensive analysis of lipids metabolic heterogeneity between VAT and SAT browning and may provide promising lipid targets to motivate WAT browning.

关键词： visceral adipose tissue subcutaneous adipose tissue browning heterogeneity beta-3 adrenergic receptor agonist

Salvianolic acid A protects vascular endothelial function in type 2 diabetic rats via suppression of AGEs and oxidative stress

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Salvianolic acid A protects vascular endothelial function in...

Puerarin alleviates skeletal muscle atrophy in type 1 diabetic rats

中国药理学会第十次全国学术会议

作者： qiang gui-fen,YANG Xiu-ying,ZHANG Li,ZHU Xiao-ming, WANG Shou-bao,SUN Lan,YANG Hai-guang,DU Guan-hua

Objects:To investigate the effect of Salvianolic acid A,a water soluble compound isolated from Danshen(Salvia Miltrorrhiza),on diabetes-induced vascular endothelial dysfunction(VED) in diabetic rats and to research the mechanism in cultured human endothelial cells(***926).Methods High-fat diet and streptozotocin(STZ)-induced diabetic rats were treated with Salvianolic acid A for ten *** lipid,blood glucose and serum

关键词： Salvianolic acid A vascular endothelial dysfunction oxidative stress AGEs NOS

来源： cnki会议评论

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中国药理学与毒理学杂志 2019年第10期 927-927页

作者： YIN Lin CHEN Xi LI Na JIA Wei-hua WANG Nuo-qi HOU Bi-yu qiang gui-fen YANG Xiu-ying DU Guan-hua Beijing Key Laboratory of Drug Target Identification and Drug Screening Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

OBJECTIVE Puerarin is an important isoflavone component of traditional Chinese medicine Pueraria lobata and has a wide range of pharmacological *** have shown that puerarin has a significant alleviation effect on diabetes and its complications. This article investigates the therapeutic effect of puerarin on rat skeletal muscle atrophy caused by type 1 diabetes. METHODS SD rats were fed adaptively for 1 week, then 10 rats were randomly divided into normal control *** rest were injected intraperitoneally with 65 mg·kg-1streptozotocin（STZ）. Blood was taken from the tip of the tail after 1 week and rats with fasting blood glucose levels above 16.5 mmol · L-1were chosen as type 1 diabetic rats, which randomly divided into two groups: diabetic model control group and puerarin administration group（n=10）. The administration group was treated with orally administration of puerarin at 100 mg·kg-1·d-1, while the normal control group and the diabetic model group were treated with corresponding dose of normal saline. At the end of the 8-week treatment, diabetes related indicators were detected including body weight, food-intake, fasting blood glucose and glucose tolerance test. Meanwhile,skeletal muscle atrophy correlative indicators like foreleg tensile force, time of wire hanging, persistent time on sloping plate, area of skeletal muscle and atrophy markers（F-box protein 32, Fbxo32 and tripartite motif containing63, Trim63） were also detected. RESULTS Puerarin(100 mg · kg-1) can lighten body weight and decrease food-intake of type 1 diabetic rats induced by STZ（P<0.05）. But there was no significant amelioration in glucose tolerance and fasting blood glucose level. As for skeletal muscle strength, puerarin can significantly enhance the foreleg tensile force（P<0.01）, time of wire hanging（P<0.05） and persistent time on sloping plate（P<0.01）.Besides, puerarin also showed a significant effect on enhancing the area of skeletal muscle（P<0.01）while reducing expressio

关键词： puerarin type 1 diabetes skeletal muscle atrophy muscular strength

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HPLC荧光检测法测定人血浆中的特拉唑嗪

华西药学杂志 2012年第3期27卷 316-318页

作者：刘曼张丹王国才强桂芬杨漫张娅喃刘会臣航天中心医院临床药理室北京100049

目的采用HPLC荧光检测法测定人血浆中的特拉唑嗪。方法采用Apollo C18色谱柱(150 mm×4.6 mm,5μm),流动相为乙腈-50 mmol·L-1磷酸二氢钾缓冲液(22∶78),流速1.1 mL·min-1,柱温30℃,进样量10μL,荧光检测器激发波长为238 nm、发射波长... 详细信息

目的采用HPLC荧光检测法测定人血浆中的特拉唑嗪。方法采用Apollo C18色谱柱(150 mm×4.6 mm,5μm),流动相为乙腈-50 mmol·L-1磷酸二氢钾缓冲液(22∶78),流速1.1 mL·min-1,柱温30℃,进样量10μL,荧光检测器激发波长为238 nm、发射波长为370 nm。以哌唑嗪为内标,血浆样本碱化后经乙醚-二氯甲烷(3∶2)提取后进样。结果特拉唑嗪的线性范围为0.5～125.0μg·L-1(r≥0.9983);日内、日间RSD均小于10%;平均提取回收率为88.0%±4.4%。结论所用方法简便、准确、灵敏,无杂质干扰,适用于临床上盐酸特拉唑嗪口服制剂的血药浓度监测及药动学研究。

关键词：特拉唑嗪高效液相色谱法荧光检测法人血浆

Optimizing the key parameter to accelerate the recovery of AMOC under a rapid increase of greenhouse gas forcing

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 39-45页

作者： Haolan Ren Fei Zheng Tingwei Cao qiang Wang International Center for Climate and Environment Science(ICCES) Institute of Atmospheric PhysicsChinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina College of Oceanography Hohai UniversityNanjingChina CAS Key Laboratory of Ocean Circulation and Waves Institute of OceanologyChinese Academy of Sciences and Pilot National Laboratory for Marine Science and Technology(Qingdao)QingdaoChina

Atlantic Meridional Overturning Circulation(AMOC)plays a central role in long-term climate variations through its heat and freshwater transports,which can collapse under a rapid increase of greenhouse gas forcing in climate *** studies have suggested that the deviation of model parameters is one of the major factors in inducing inaccurate AMOC *** this work,with a low-resolution earth system model,the authors try to explore whether a reasonable adjustment of the key model parameter can help to re-establish the AMOC after its *** a new optimization strategy,the extra freshwater flux(FWF)parameter is determined to be the dominant one affecting the AMOC’s *** traditional ensemble optimal interpolation(EnOI)data assimilation and new machine learning methods are adopted to optimize the FWF parameter in an abrupt 4×CO_(2) forcing experiment to improve the adaptability of model parameters and accelerate the recovery of *** results show that,under an abrupt 4×CO_(2) forcing in millennial simulations,the AMOC will first collapse and then re-establish by the default FWF parameter ***,during the parameter adjustment process,the saltier and colder sea water over the North Atlantic region are the dominant factors in usefully improving the adaptability of the FWF parameter and accelerating the recovery of AMOC,according to their physical relationship with FWF on the interdecadal timescale.

关键词： Recovery of AMOC 4×CO_(2)forcing Key parameter Parameter estimation Data assimilation Machine learning