Inhibitory effect of flavonoids from Glycyrrhiza uralensis on expressions of TGF-β1 and Caspase-3 in thioacetamide-induced hepatic fibrosis in rats

Hepatic fibrosis represents an important event in the progression of chronic liver injury to cirrhosis, and is characterized by excessive extracellular matrix proteins aggregation. Early fibrosis can be reversed by inhibiting hepatocyte injury, inflammation, or hepatic stellate cells activation, so the development of antifibrotic drugs is important to reduce the incidence of hepatic cirrhosis or even hepatic carcinoma. Here we demonstrate that Schisandrol B (SolB), one of the major active constituents of traditional hepato-protective Chinese medicine, Schisandra sphenanthera, significantly protects against hepatocyte injury, while Wedelolactone (WeD) suppresses the TGF-β1/Smads signaling pathway in hepatic stellate cells (HSCs) and inflammation, the combination of the two reverses hepatic fibrosis in mice and the inhibitory effect of the combination on hepatic fibrosis is superior to that of SolB or WeD treatment alone. Combined pharmacotherapy represents a promising strategy for the prevention and treatment of liver fibrosis.

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Real-time monitoring of liver fibrosis through embedded sensors in a microphysiological system

Nano Convergence ◽

10.1186/s40580-021-00253-y ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Hafiz Muhammad Umer Farooqi ◽

Bohye Kang ◽

Muhammad Asad Ullah Khalid ◽

Abdul Rahim Chethikkattuveli Salih ◽

Kinam Hyun ◽

...

Keyword(s):

Cell Culture ◽

Liver Fibrosis ◽

Real Time ◽

Hepatic Fibrosis ◽

Transforming Growth Factor ◽

Cell Monolayer ◽

Embedded Sensors ◽

Matrix Deposition ◽

Tgf Β1

AbstractHepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor β1 (TGF-β1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-β1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.

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Attenuation of diethyl nitrosamine-induced hepatocellular carcinoma by taxifolin and/or alogliptin: The interplay between toll-like receptor 4, transforming growth factor beta-1, and apoptosis

Human & Experimental Toxicology ◽

10.1177/09603271211008496 ◽

2021 ◽

pp. 096032712110084

Author(s):

AM Kabel ◽

HH Arab ◽

MA Abd Elmaaboud

Keyword(s):

Hepatocellular Carcinoma ◽

Transforming Growth Factor Beta ◽

Caspase 3 ◽

Transforming Growth Factor ◽

Liver Function Tests ◽

Toll Like Receptor ◽

Caspase 9 ◽

Toll Like Receptor 4 ◽

Growth Factor Beta ◽

Tgf Β1

Hepatocellular carcinoma (HCC) is the most common form of liver malignancies worldwide. Alogliptin is an anti-diabetic that may have effective anticancer properties against many types of malignancies. Taxifolin is a flavonoid that has potent antioxidant, and anti-inflammatory properties. The objective of this study was to explore the impact of alogliptin and/or taxifolin on diethyl nitrosamine-induced HCC in rats. One hundred male Wistar rats were divided into five equal groups as follows: Control; HCC; HCC + Alogliptin; HCC + Taxifolin; and HCC + Alogliptin + Taxifolin group. The survival rate, liver function tests, tissue antioxidant enzymes, malondialdehyde (MDA), nuclear factor (erythroid derived 2)-like 2 (Nrf2), transforming growth factor beta 1 (TGF-β1), interleukin 1 alpha (IL-1α), and toll-like receptor 4 (TLR4) were measured. Also, hepatic caspase 3, caspase 9, beclin-1, and c-Jun NH2-terminal kinase (JNK) in addition to serum alpha-fetoprotein (AFP) and α-L-Fucosidase (AFU) were assessed. Specimens of the liver were subjected to histopathological examination. Alogliptin and/or taxifolin induced significant improvement of liver function tests with significant increase in the survival rate, tissue antioxidant enzymes, Nrf2, caspase 3, caspase 9, Beclin-1 and JNK activities associated with significant decrease in serum AFP and AFU, tissue MDA, TGF-β1, IL-1α and TLR4 expression compared to HCC group. These results were significant with taxifolin/alogliptin combination when compared to the use of each of these agents alone. In conclusion, taxifolin/alogliptin combination might be used as adjuvant therapy for attenuation of HCC.

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Alterations of mast cells and TGF-β1 on the silymarin treatment for CCl4-induced hepatic fibrosis

World Journal of Gastroenterology ◽

10.3748/wjg.v11.i8.1141 ◽

2005 ◽

Vol 11 (8) ◽

pp. 1141 ◽

Cited By ~ 59

Author(s):

Da-Hee Jeong

Keyword(s):

Mast Cells ◽

Hepatic Fibrosis ◽

Tgf Β1

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Interleukin-13 and transforming growth factor-β1 inhibit spontaneous sleep in rabbits

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.279.3.r786 ◽

2000 ◽

Vol 279 (3) ◽

pp. R786-R792 ◽

Cited By ~ 17

Author(s):

Takeshi Kubota ◽

Jidong Fang ◽

Tetsuya Kushikata ◽

James M. Krueger

Keyword(s):

Growth Factor ◽

Proinflammatory Cytokines ◽

Transforming Growth Factor ◽

Inhibitory Effect ◽

Transforming Growth Factor Β1 ◽

Light Period ◽

Sleep Regulation ◽

Cytokine Network ◽

Physiological Sleep ◽

Tgf Β1

Proinflammatory cytokines, including interleukin-1β and tumor necrosis factor-α are involved in physiological sleep regulation. Interleukin (IL)-13 and transforming growth factor (TGF)-β1 are anti-inflammatory cytokines that inhibit proinflammatory cytokines by several mechanisms. Therefore, we hypothesized that IL-13 and TGF-β1 could attenuate sleep in rabbits. Three doses of IL-13 (8, 40, and 200 ng) and TGF-β1 (40, 100, and 200 ng) were injected intracerebroventricularly 3 h after the beginning of the light period. In addition, one dose of IL-13 (200 ng) and one dose of TGF-β1 (200 ng) were injected at dark onset. The two higher doses of IL-13 and the highest dose of TGF-β1 significantly inhibited spontanenous non-rapid eye movement sleep (NREMS) when they were given in the light period. IL-13 also inhibited NREMS after dark onset administration; however, the inhibitory effect was less potent than that observed after light period administration. The 40-ng dose of IL-13 inhibited REMS duration during the dark period. TGF-β1 administered at dark onset had no effect on sleep. These data provide additional evidence for the hypothesis that a brain cytokine network is involved in regulation of physiological sleep.

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