This study examined the effect of tanshinoneⅡA (TSNⅡA) on the cardiac fibrosis induced by transforming growth factor β1 (TGF-β1) and the possible mechanisms. Cardiac fibroblasts were isolated from cardiac tissues ...This study examined the effect of tanshinoneⅡA (TSNⅡA) on the cardiac fibrosis induced by transforming growth factor β1 (TGF-β1) and the possible mechanisms. Cardiac fibroblasts were isolated from cardiac tissues of neonatal Sprague-Dawley (SD) rats by the trypsin digestion and differential adhesion method. The cells were treated with 5 ng/mL TGF-β1 alone or pretreated with TSNⅡA at different concentrations (10–5 mol/L, 10–4 mol/L). Immunocytochemistry was used for cell identification, RT-PCR for detection of the mRNA expression of connective tissue growth factor (CTGF) and collagen type Ⅰ (COLⅠ), Western blotting for detection of the protein expression of Smad7 and Smad3, and immunohistochemistry and immunofluorescence staining for detection of the protein expression of phosphorylated Smad3 (p-Smad3), CTGF and COLⅠ. The results showed that TGF-β1 induced the expression of CTGF, COLⅠ, p-Smad3 and Smad7 in a time-dependent manner. The mRNA expression of CTGF and COLⅠ was significantly increased 24 h after TGF-β1 stimulation (P<0.01 for all). The protein expression of p-Smad3 and Smad7 reached a peak 1 h after TGF-β1 stimulation, much higher than the baseline level (P<0.01 for all). Pretreatment with high concentration of TSNⅡA resulted in a decrease in the expression of p-Smad3, CTGF and COLⅠ (P<0.01). The protein expression of Smad7 was substantially upregulated after pretreatment with two concentrations of TSNⅡA as compared with that at 2h post TGF-β1 stimulation (P<0.05 for low concentration of TSNⅡA; P<0.01 for high concentration of TSNⅡA). It was concluded that TSNⅡA may exert an inhibitory effect on cardiac fibrosis by upregulating the expression of Smad7, suppressing the TGF-β1-induced phosphorylation of Smad3 and partially blocking the TGF-β1-Smads signaling pathway.展开更多
Two series of tanshinone IIA derivatives were synthesized and evaluated for their antitumor activities as Cdc25 phosphatase inhibitors.Most of them demonstrated potent Cdc25 inhibitory activity and powerful cytotoxici...Two series of tanshinone IIA derivatives were synthesized and evaluated for their antitumor activities as Cdc25 phosphatase inhibitors.Most of them demonstrated potent Cdc25 inhibitory activity and powerful cytotoxicity against A549 tumor cell line, producing IC_(50) values in very low micromolar range.At last,the preliminary SAR was discussed.展开更多
BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has sho...BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.展开更多
TanshinoneⅡA(TanⅡA)is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen(Radix Salviae Miltiorrhizae)that has various pharmacological properties,inclu...TanshinoneⅡA(TanⅡA)is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen(Radix Salviae Miltiorrhizae)that has various pharmacological properties,including anti-inflammatory,antibacterial,and antioxidative effects.Sepsis is a life-threatening organ dysfunction induced by a dysregulated host response to infection.Recently,increasing attention has been paid to sepsis-induced dysfunction of the intestine,cardiovascular system,lungs,kidneys,liver,and other organs.Experimental studies have shown that TanⅡA has therapeutic potential for sepsis-induced organ dysfunction owing to its anti-inflammatory,anti-apoptotic and regulatory effects on multiple signalling pathways.The purpose of this article is to evaluate the potential multiorgan protective effects of TanⅡA in sepsis.展开更多
OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatom...OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatoma mice model.METHODS: Hepa1-6 hepatoma-bearing mice were treated with TanⅡA for 14 d. Distribution and anti-tumor efficacy of PLD, and the structure and function of the tumor vasculature were evaluated using various techniques.RESULTS: TanⅡ A significantly reduced the micro-vessel density(MVD). After Tan vascular walls were betteⅡr s A treatment,the tumor tructured, as the increased coverage of the pericytes and the promoted contact of the basement membrane and endothelial cell. Functional tests showed that tumor hypoxia was improved and the exudation amount of Evans blue in the parenchyma of the tumor decreased. In addition, mice treated with TanA had greater PLD penetration distance intratumoⅡrally. Furthermore, combined therapy of Tanibited tumor growth.ⅡA and PLD significantly inhCONCLUSION: This study suggests that Tanasculature andⅡ h A helps normalizing the tumor vas therapeutic potential in increasing the distribution of chemotherapy drug in the tumor.展开更多
Summary: In order to study the effect of tanshinone Ⅱ A on growth and apoptosis in human hepatomacell line BEL-7402 in vitro, the human hepatoma cell line BEL-7402 was treated with tanshinone Ⅱ Aat various concentra...Summary: In order to study the effect of tanshinone Ⅱ A on growth and apoptosis in human hepatomacell line BEL-7402 in vitro, the human hepatoma cell line BEL-7402 was treated with tanshinone Ⅱ Aat various concentrations for 72 h. Growth suppression was evaluated by MTT assay; apoptosis-relat-ed alterations in morphology and biochemistry were ascertained under cytochemical staining (Hoechst33258), transmission electron microscopy (TEM), and DNA agarose gel electrophoresis. Apoptoticrate was quantified by flow cytometry (FCM). The results showed that Tanshinone ⅡA could inhibitthe growth of hepatoma cells in a dose-dependent manner, with IC50 value being 6.28μg/ml. Aftertreatment with 1-10μg/ml tanshinone Ⅱ A for 72 h, BEL-7402 cells apoptosis with nuclear cbro-matin condensation and fragmentation as well as cell shrinkage and the formation of apoptotic bodieswere observed. DNA ladder could be demonstrated on DNA electrophoresis. FCM analysis showedhypodiploid peaks on histogram, and the apoptotic rates at 5 μg/ml concentration for 12 h, 24 h, 36h, 48 h and 72 h were (2.32±0.16) %, (3.01±0.35) %, (3.87±0. 43) %, (6.73±0. 58) %and (20. 85 ±1. 74) % respectively, which were all significantly higher than those in the controlgroup (1.07±0. 13) %. It is concluded that Tanshinone ⅡA^ could induce human hepatoma cell lineBEL-7402 apoptosis, which may be related to the mechanism of growth inhibition.展开更多
基金supported by a grant from the Natural Science Foundation of Hubei Province of China(Nos.2009CDB092,2007ABA272)
文摘This study examined the effect of tanshinoneⅡA (TSNⅡA) on the cardiac fibrosis induced by transforming growth factor β1 (TGF-β1) and the possible mechanisms. Cardiac fibroblasts were isolated from cardiac tissues of neonatal Sprague-Dawley (SD) rats by the trypsin digestion and differential adhesion method. The cells were treated with 5 ng/mL TGF-β1 alone or pretreated with TSNⅡA at different concentrations (10–5 mol/L, 10–4 mol/L). Immunocytochemistry was used for cell identification, RT-PCR for detection of the mRNA expression of connective tissue growth factor (CTGF) and collagen type Ⅰ (COLⅠ), Western blotting for detection of the protein expression of Smad7 and Smad3, and immunohistochemistry and immunofluorescence staining for detection of the protein expression of phosphorylated Smad3 (p-Smad3), CTGF and COLⅠ. The results showed that TGF-β1 induced the expression of CTGF, COLⅠ, p-Smad3 and Smad7 in a time-dependent manner. The mRNA expression of CTGF and COLⅠ was significantly increased 24 h after TGF-β1 stimulation (P<0.01 for all). The protein expression of p-Smad3 and Smad7 reached a peak 1 h after TGF-β1 stimulation, much higher than the baseline level (P<0.01 for all). Pretreatment with high concentration of TSNⅡA resulted in a decrease in the expression of p-Smad3, CTGF and COLⅠ (P<0.01). The protein expression of Smad7 was substantially upregulated after pretreatment with two concentrations of TSNⅡA as compared with that at 2h post TGF-β1 stimulation (P<0.05 for low concentration of TSNⅡA; P<0.01 for high concentration of TSNⅡA). It was concluded that TSNⅡA may exert an inhibitory effect on cardiac fibrosis by upregulating the expression of Smad7, suppressing the TGF-β1-induced phosphorylation of Smad3 and partially blocking the TGF-β1-Smads signaling pathway.
基金support by program for New Century Excellent Talents in University (NCET)National Natural Science Foundation of China(No.305722321)Lab of Organic Functional Molecules,the Sino-French Institute of ECNU for supports.
文摘Two series of tanshinone IIA derivatives were synthesized and evaluated for their antitumor activities as Cdc25 phosphatase inhibitors.Most of them demonstrated potent Cdc25 inhibitory activity and powerful cytotoxicity against A549 tumor cell line, producing IC_(50) values in very low micromolar range.At last,the preliminary SAR was discussed.
基金Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects,No.Z202000962023 Guangxi University Young and Middle-Aged Teachers’Basic Research Ability Improvement Project,No.2023KY0091+1 种基金National Natural Science Foundation of China,No.82260241the Natural Science Foundation of Guangxi Province,No.2015GXNSFAA139171 and No.2020GXNSFAA259053.
文摘BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.
基金Natural Science Foundation of Hubei Province:Mechanism of Degenerative Aortic Valve Calcification Induced by Inflammatory Responses in Valvular Interstitial Cells(No.2020CFB577)。
文摘TanshinoneⅡA(TanⅡA)is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen(Radix Salviae Miltiorrhizae)that has various pharmacological properties,including anti-inflammatory,antibacterial,and antioxidative effects.Sepsis is a life-threatening organ dysfunction induced by a dysregulated host response to infection.Recently,increasing attention has been paid to sepsis-induced dysfunction of the intestine,cardiovascular system,lungs,kidneys,liver,and other organs.Experimental studies have shown that TanⅡA has therapeutic potential for sepsis-induced organ dysfunction owing to its anti-inflammatory,anti-apoptotic and regulatory effects on multiple signalling pathways.The purpose of this article is to evaluate the potential multiorgan protective effects of TanⅡA in sepsis.
基金Supported by National Natural Science Foundation of China(CN):Vascular Normalization by Huoxuehuayu medicine Induces decrease of the Interstitial Fluid and Improves Drug Penetration in Tumors(No.81202784)
文摘OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatoma mice model.METHODS: Hepa1-6 hepatoma-bearing mice were treated with TanⅡA for 14 d. Distribution and anti-tumor efficacy of PLD, and the structure and function of the tumor vasculature were evaluated using various techniques.RESULTS: TanⅡ A significantly reduced the micro-vessel density(MVD). After Tan vascular walls were betteⅡr s A treatment,the tumor tructured, as the increased coverage of the pericytes and the promoted contact of the basement membrane and endothelial cell. Functional tests showed that tumor hypoxia was improved and the exudation amount of Evans blue in the parenchyma of the tumor decreased. In addition, mice treated with TanA had greater PLD penetration distance intratumoⅡrally. Furthermore, combined therapy of Tanibited tumor growth.ⅡA and PLD significantly inhCONCLUSION: This study suggests that Tanasculature andⅡ h A helps normalizing the tumor vas therapeutic potential in increasing the distribution of chemotherapy drug in the tumor.
基金This project was supported by a grant from Natural Sciences Foundation of Hubei Province(No.2000J064).
文摘Summary: In order to study the effect of tanshinone Ⅱ A on growth and apoptosis in human hepatomacell line BEL-7402 in vitro, the human hepatoma cell line BEL-7402 was treated with tanshinone Ⅱ Aat various concentrations for 72 h. Growth suppression was evaluated by MTT assay; apoptosis-relat-ed alterations in morphology and biochemistry were ascertained under cytochemical staining (Hoechst33258), transmission electron microscopy (TEM), and DNA agarose gel electrophoresis. Apoptoticrate was quantified by flow cytometry (FCM). The results showed that Tanshinone ⅡA could inhibitthe growth of hepatoma cells in a dose-dependent manner, with IC50 value being 6.28μg/ml. Aftertreatment with 1-10μg/ml tanshinone Ⅱ A for 72 h, BEL-7402 cells apoptosis with nuclear cbro-matin condensation and fragmentation as well as cell shrinkage and the formation of apoptotic bodieswere observed. DNA ladder could be demonstrated on DNA electrophoresis. FCM analysis showedhypodiploid peaks on histogram, and the apoptotic rates at 5 μg/ml concentration for 12 h, 24 h, 36h, 48 h and 72 h were (2.32±0.16) %, (3.01±0.35) %, (3.87±0. 43) %, (6.73±0. 58) %and (20. 85 ±1. 74) % respectively, which were all significantly higher than those in the controlgroup (1.07±0. 13) %. It is concluded that Tanshinone ⅡA^ could induce human hepatoma cell lineBEL-7402 apoptosis, which may be related to the mechanism of growth inhibition.
