1.Resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by maintaining mitochondrial homeostasis via enhancing SIRT1 expression
Hongwei YE ; Yuming ZHANG ; Qi YUN ; Ruoli DU ; Lu LI ; Yuping LI ; Qin GAO
Journal of Southern Medical University 2024;44(1):45-51
Objective To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1(SIRT1)to maintain mitochondrial homeostasis.Methods Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose(HG)and treated with resveratrol for 72 h.The changes in superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,reactive oxygen species(ROS)level,and relative surface of the cells were examined,and the mRNA expressions of atrial natriuretic factor(ANF)and brain natriuretic peptide(BNP)and protein expressions of SIRT1,mitochondrial fusion related proteins optic atrophy protein 1(OPA1)and mitofusin 2,mitochondrial division related proteins dynamin-related protein 1(DRP1)and fission protein 1(FIS1),and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting.Results HG exposure significantly decreased SOD activity,increased MDA content,ROS production,relative cell surface,and the mRNA expressions of ANF and BNP in the cardiomyocytes;the protein expressions of SIRT1,OPA1,mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells(P<0.01).All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol(P<0.05).The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1(P<0.05).Conclusion Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress,the mechanisms of which involve enhancement of SIRT1 protein expression,regulation of mitochondrial fusion and division balance,and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.
2.Plumbagin protect against sepsis-induced myocardial injury in mice by inhibiting the JAK2/STAT3 signaling pathway to reduce cardiomyocyte pyroptosis
Ruoli DU ; Qi YUN ; Yiren WANG ; Xinyu DOU ; Hongwei YE ; Jiahui WANG ; Qin GAO
Journal of Southern Medical University 2024;44(11):2209-2219
Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.
3.The taste correction process of ibuprofen oral solution based on the combination of electronic tongue technology and artificial taste comprehensive evaluation
Rui YUAN ; Yun-ping QU ; Yan WANG ; Ya-xuan ZHANG ; Wan-ling ZHONG ; Xiao-yu FAN ; Hui-juan SHEN ; Yun-nan MA ; Jin-hong YE ; Jie BAI ; Shou-ying DU
Acta Pharmaceutica Sinica 2024;59(8):2404-2411
This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model:
4.Resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by maintaining mitochondrial homeostasis via enhancing SIRT1 expression
Hongwei YE ; Yuming ZHANG ; Qi YUN ; Ruoli DU ; Lu LI ; Yuping LI ; Qin GAO
Journal of Southern Medical University 2024;44(1):45-51
Objective To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1(SIRT1)to maintain mitochondrial homeostasis.Methods Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose(HG)and treated with resveratrol for 72 h.The changes in superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,reactive oxygen species(ROS)level,and relative surface of the cells were examined,and the mRNA expressions of atrial natriuretic factor(ANF)and brain natriuretic peptide(BNP)and protein expressions of SIRT1,mitochondrial fusion related proteins optic atrophy protein 1(OPA1)and mitofusin 2,mitochondrial division related proteins dynamin-related protein 1(DRP1)and fission protein 1(FIS1),and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting.Results HG exposure significantly decreased SOD activity,increased MDA content,ROS production,relative cell surface,and the mRNA expressions of ANF and BNP in the cardiomyocytes;the protein expressions of SIRT1,OPA1,mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells(P<0.01).All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol(P<0.05).The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1(P<0.05).Conclusion Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress,the mechanisms of which involve enhancement of SIRT1 protein expression,regulation of mitochondrial fusion and division balance,and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.
5.Plumbagin protect against sepsis-induced myocardial injury in mice by inhibiting the JAK2/STAT3 signaling pathway to reduce cardiomyocyte pyroptosis
Ruoli DU ; Qi YUN ; Yiren WANG ; Xinyu DOU ; Hongwei YE ; Jiahui WANG ; Qin GAO
Journal of Southern Medical University 2024;44(11):2209-2219
Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.
6.Chemical constituents of diterpenoids from Boswellia carterii.
Rong-Ye WANG ; Hui XIA ; Yong-Xiang WANG ; Hao HUANG ; Bo-Kai WANG ; Meng DU ; Yue-Lin SONG ; Yun-Fang ZHAO ; Jiao ZHENG ; Hui-Xia HUO ; Jun LI
China Journal of Chinese Materia Medica 2023;48(9):2464-2470
This paper explored the chemical constituents of Boswellia carterii by column chromatography on silica gel, Sephadex LH-20, ODS column chromatography, and semi-preparative HPLC. The structures of the compounds were identified by physicochemical properties and spectroscopic data such as infrared radiation(IR), ultra violet(UV), mass spectrometry(MS), and nuclear magnetic resonance(NMR). Seven diterpenoids were isolated and purified from n-hexane of B. carterii. The isolates were identified as(1S,3E,7E,11R,12R)-11-hydroxy-1-isopropyl-4,8,12-trimethyl-15-oxabicyclo[10.2.1]pentadeca-3,7-dien-5-one(1),(1R,3S,4R,7E,11E)-4,8,12,15,15-pentamethyl-14-oxabicyclo[11.2.1]hexadeca-7,11-dien-4-ol(2), incensole(3),(-)-(R)-nephthenol(4), euphraticanoid F(5), dilospirane B(6), and dictyotin C(7). Among them, compounds 1 and 2 were new and their absolute configurations were determined by comparison of the calculated and experimental electronic circular dichroisms(ECDs). Compounds 6 and 7 were obtained from B. carterii for the first time.
Molecular Structure
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Boswellia/chemistry*
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Diterpenes/chemistry*
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Mass Spectrometry
7. Treatment advice of small molecule antiviral drugs for elderly COVID-19
Min PAN ; Shuang CHANG ; Xiao-Xia FENG ; Guang-He FEI ; Jia-Bin LI ; Hua WANG ; Du-Juan XU ; Chang-Hui WANG ; Yan SUN ; Xiao-Yun FAN ; Tian-Jing ZHANG ; Wei WEI ; Ling-Ling ZHANG ; Jim LI ; Fei-Hu CHEN ; Xiao-Ming MENG ; Hong-Mei ZHAO ; Min DAI ; Yi XIANG ; Meng-Shu CAO ; Xiao-Yang CHEN ; Xian-Wei YE ; Xiao-Wen HU ; Ling JIANG ; Yong-Zhong WANG ; Hao LIU ; Hai-Tang XIE ; Ping FANG ; Zhen-Dong QIAN ; Chao TANG ; Gang YANG ; Xiao-Bao TENG ; Chao-Xia QIAN ; Guo-Zheng DING
Chinese Pharmacological Bulletin 2023;39(3):425-430
COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.
10.Research progress of Application of polysaccharide hydrogel based on dynamic covalent bond in drug delivery and tissue repair
YE Fan ; LI Siyu ; ZHANG Yun ; DANG Yunjie ; DU Qing
Chinese Journal of Modern Applied Pharmacy 2023;40(21):3047-3052
Abstract
Hydrogels are widely used in biomedical fields such as drug delivery, wound dressings and tissue engineering because of their good biocompatibility and biodegradability. According to the source of material, it can be divided into synthetic material hydrogel and natural material hydrogel. Natural polysaccharide hydrogel not only can be used as material, but also has unique pharmacological activity and better mechanical properties, gradually become the preferred material. Dynamic covalent hydrogels have attracted much attention due to their structural flexibility, self healing performance and environmental responsiveness. In this paper, the dynamic bond mode natural polysaccharide hydrogel systems are classified and summarized, and the research status of the construction of this kind of hydrogel in drug delivery and tissue repair are summarized, to provide reference for the application of new polysaccharide hydrogels in clinical application.


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