1.1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex
Shengsuo MA ; Bing YANG ; Yang DU ; Yiwen LV ; Jiarong LIU ; Yucong SHI ; Ting HUANG ; Huachong XU ; Li DENG ; Xiaoyin CHEN
Journal of Pharmaceutical Analysis 2023;13(9):984-998
Ulcerative colitis(UC)is characterized by chronic relapsing intestinal inflammation.Currently,there is no effective treatment for the disease.According to our preliminary data,1,8-cineole,which is the main active compound of Amomum compactum Sol.ex Maton volatile oil and an effective drug for the treat-ment of pneumonia,showed remarkable anti-inflammatory effects on colitis pathogenesis.However,its mechanism of action and direct targets remain unclear.This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate so-dium salt-induced colitis mouse model.The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells.In addition,1,8-cineole targets were revealed by drug affinity responsive target stability,thermal shift assay,cellular thermal shift assay,and heat shock protein 90(HSP90)adenosine triphosphatases(ATPase)activity assays.The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function.Mech-anistically,1,8-cineole directly interacted with HSP90 and decreased its ATPase activity,also inhibited nucleotide-binding and oligomerization domain-,leucine rich repeat-,and pyrin domain-containing 3(NLRP3)binding to HSP90 and suppressor of G-two allele of SKP1(SGT1)and suppressed NLRP3 inflammasome activation in macrophages.These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.
2.A systematic strategy for screening therapeutic constituents of (Turcz) Baill infiltrated blood-brain barrier oriented in lesions using ethanol and water extracts: a novel perspective for exploring chemical material basis of herb medicines.
Yiwen ZHANG ; Xinyan LV ; Jiameng QU ; Xin ZHANG ; Mingyang ZHANG ; Hao GAO ; Qian ZHANG ; Ran LIU ; Huarong XU ; Qing LI ; Kaishun BI
Acta Pharmaceutica Sinica B 2020;10(3):557-568
, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of remains obscure. In this study, to explore the active constituents of , we compared pharmacodynamics and chemical profiles / of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.
3.Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults.
Yanbo ZHANG ; Canqing YU ; Shuohua CHEN ; Zhouzheng TU ; Mengyi ZHENG ; Jun LV ; Guodong WANG ; Yan LIU ; Jiaxin YU ; Yu GUO ; Ling YANG ; Yiping CHEN ; Kunquan GUO ; Kun YANG ; Handong YANG ; Yanfeng ZHOU ; Yiwen JIANG ; Xiaomin ZHANG ; Meian HE ; Gang LIU ; Zhengming CHEN ; Tangchun WU ; Shouling WU ; Liming LI ; An PAN
Chinese Medical Journal 2023;136(2):141-149
BACKGROUND:
Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps.
METHODS:
A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis.
RESULTS:
During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed.
CONCLUSIONS
ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Adult
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Humans
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Cardiovascular Diseases/prevention & control*
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East Asian People
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Prospective Studies
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Risk Factors
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Smoking