Emerging evidence discloses the involvement of calcium channel protein in the pathological process of liver diseases.Transient receptor potential cation channel subfamily C member 3(TRPC3),a ubiquitously expressed non...Emerging evidence discloses the involvement of calcium channel protein in the pathological process of liver diseases.Transient receptor potential cation channel subfamily C member 3(TRPC3),a ubiquitously expressed non-selective cation channel protein,controls proliferation,inflammation,and immune response via operating calcium influx in various organs.However,our understanding on the biofunction of hepatic TRPC3 is still limited.The present study aims to clarify the role and potential mechanism(s)of TRPC3 in alcohol-associated liver disease(ALD).We recently found that TRPC3 expression plays an important role in the disease process of ALD.Alcohol exposure led to a significant reduction of hepatic TRPC3 in patients with alcohol-related hepatitis(AH)and ALD models.Antioxidants(N-acetylcysteine and mitoquinone)intervention improved alcohol-induced suppression of TRPC3 via a miR-339-5p-involved mechanism.TRPC3 loss robustly aggravated the alcohol-induced hepatic steatosis and liver injury in mouse liver;this was associated with the suppression of Ca^(2+)/calmodulin-dependent protein kinase kinase 2(CAMKK2)/AMP-activated protein kinase(AMPK)and dysregulation of genes related to lipid metabolism.TRPC3 loss also enhanced hepatic inflammation and early fibrosis-like change in mice.Replenishing hepatic TRPC3 effectively reversed chronic alcohol-induced detrimental alterations in ALD mice.Briefly,chronic alcohol exposure-induced TRPC3 reduction contributes to the pathological development of ALD via suppression of the CAMKK2/AMPK pathway.Oxidative stress-stimulated miR-339-5p upregulation contributes to alcohol-reduced TRPC3.TRPC3 is the requisite and a potential target to defend alcohol consumption-caused ALD.展开更多
Penthorum chinense Pursh(PCP)is a popular traditional medicinal plant in China,widely used for the treatment of a variety of liver diseases.Although it has been long recognized that the main active elements of PCP are...Penthorum chinense Pursh(PCP)is a popular traditional medicinal plant in China,widely used for the treatment of a variety of liver diseases.Although it has been long recognized that the main active elements of PCP are contained in ethyl acetate fraction(EAF),little is known so far in terms of the relative effectiveness of EAF derived from the stems versus leaves of this plant.In the current study,we prepared EAF by reflux extraction and sequential extraction from the stems(SEAF)and leaves(LEAF)of PCP and tested their hepatoprotective efficacies.The extract rates and flavonoid contents of LEAF were higher than those of SEAF.EAFs(>50μg·mL^(–1))prevented lipid accumulation in cells and protected against lipotoxicity injury when the concentration exceeded 25μg·mL^(–1).More than 95%free radicals released by 2,2-diphenyl-1-picrylhydrazyl(DPPH)were eliminated by 25μg·mL^(–1)SEAF and 50μg·mL^(–1)LEAF,respectively.Further,EAFs(25μg·mL^(–1))also showed protective antioxidant effects,with the activity of LEAF being significantly higher than that of SEAF.EAFs(10 mg·mL^(–1))also showed similar unspecific bacteriostatic activity.In comparison with SEAF,LEAF contained more flavonoids and had a higher anti-oxidation capability and for these reasons we suggest it should be better for clinical use.展开更多
基金supported by grants from the National Natural Science Foundation of China(81973041,82273625,82103839,and 82103838)Zhejiang Natural Science Foundation(LR20H260001 and LZ21H030001)Zhejiang Chinese Medicine University Postgraduate Scientific Research Fund Project(2022YKJ17).
文摘Emerging evidence discloses the involvement of calcium channel protein in the pathological process of liver diseases.Transient receptor potential cation channel subfamily C member 3(TRPC3),a ubiquitously expressed non-selective cation channel protein,controls proliferation,inflammation,and immune response via operating calcium influx in various organs.However,our understanding on the biofunction of hepatic TRPC3 is still limited.The present study aims to clarify the role and potential mechanism(s)of TRPC3 in alcohol-associated liver disease(ALD).We recently found that TRPC3 expression plays an important role in the disease process of ALD.Alcohol exposure led to a significant reduction of hepatic TRPC3 in patients with alcohol-related hepatitis(AH)and ALD models.Antioxidants(N-acetylcysteine and mitoquinone)intervention improved alcohol-induced suppression of TRPC3 via a miR-339-5p-involved mechanism.TRPC3 loss robustly aggravated the alcohol-induced hepatic steatosis and liver injury in mouse liver;this was associated with the suppression of Ca^(2+)/calmodulin-dependent protein kinase kinase 2(CAMKK2)/AMP-activated protein kinase(AMPK)and dysregulation of genes related to lipid metabolism.TRPC3 loss also enhanced hepatic inflammation and early fibrosis-like change in mice.Replenishing hepatic TRPC3 effectively reversed chronic alcohol-induced detrimental alterations in ALD mice.Briefly,chronic alcohol exposure-induced TRPC3 reduction contributes to the pathological development of ALD via suppression of the CAMKK2/AMPK pathway.Oxidative stress-stimulated miR-339-5p upregulation contributes to alcohol-reduced TRPC3.TRPC3 is the requisite and a potential target to defend alcohol consumption-caused ALD.
基金This study was supported by National Natural Science Foundation of China(81473393,31600003).
文摘Penthorum chinense Pursh(PCP)is a popular traditional medicinal plant in China,widely used for the treatment of a variety of liver diseases.Although it has been long recognized that the main active elements of PCP are contained in ethyl acetate fraction(EAF),little is known so far in terms of the relative effectiveness of EAF derived from the stems versus leaves of this plant.In the current study,we prepared EAF by reflux extraction and sequential extraction from the stems(SEAF)and leaves(LEAF)of PCP and tested their hepatoprotective efficacies.The extract rates and flavonoid contents of LEAF were higher than those of SEAF.EAFs(>50μg·mL^(–1))prevented lipid accumulation in cells and protected against lipotoxicity injury when the concentration exceeded 25μg·mL^(–1).More than 95%free radicals released by 2,2-diphenyl-1-picrylhydrazyl(DPPH)were eliminated by 25μg·mL^(–1)SEAF and 50μg·mL^(–1)LEAF,respectively.Further,EAFs(25μg·mL^(–1))also showed protective antioxidant effects,with the activity of LEAF being significantly higher than that of SEAF.EAFs(10 mg·mL^(–1))also showed similar unspecific bacteriostatic activity.In comparison with SEAF,LEAF contained more flavonoids and had a higher anti-oxidation capability and for these reasons we suggest it should be better for clinical use.