Effects of bisbenzylisoquinoline alkaloids on alveolar macrophages: Correlation between binding affinity, inhibitory potency, and antifibrotic potential

Nan

Pharmacology & Toxicology

et al. 2000

Tetrandrine, an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to elicit antifibrotic effects in various cell types. In the present study, the effect of tetrandrine on liver fibrosis was investigated by using bile duct ligation and scission in rats as a model of hepatic fibrosis. Treatment with tetrandrine in fibrotic rats reduced serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels to 72%, 52% and 51% that of controls at 10 mg/kg/day, respectively. Liver hydroxyproline contents in tetrandrine-treated rats with bile duct ligation and scission were also reduced to 65% of that of control rats with bile duct ligation and scission at 10 mg/kg/day. The morphological characteristics of fibrotic liver, which appeared in control bile duct ligation and scission group, were improved in tetrandrine-treated bile duct ligation and scission group. We also examined the effect of tetrandrine on cultured rat hepatic stellate cells, which plays an important role in the pathogenesis of hepatic fibrosis, activation to investigate whether it could act mainly by direct action on rat hepatic fibroblastic cells. In cultured rat hepatic stellate cells, tetrandrine reduced DNA synthesis to 57% of control hepatic stellate cells at 10 mg/ml without affecting cell viability. Smooth muscle-a-actin expression, the phenotypic marker of activated hepatic stellate cells, was also decreased. We conclude that tetrandrine has an antifibrotic effect on liver fibrosis in rats induced by bile duct ligation and scission, indicating that it might exert a direct effect on rat hepatic stellate cells.Hepatic fibrosis is a consequence of severe liver damage that occurs in many patients with chronic liver disease. Regardless of many different causes, hepatic fibrosis is characterized by increased and altered deposition of newly formed extracellular matrix components such as collagens, proteoglycans, fibronectin and hyaluronic acid (Friedman 1993), leading to the complication of portal hypertension and hepatic failure.In the injured liver, these extracellular matrix components are produced in hepatic stellate cells in the space of Disse, which function in intact liver lobules as the primary storage area for retinoids (Hendrisks et al. 1985). During the course of ongoing liver fibrogenesis, hepatic stellate cells acquire myofibroblastic features, proliferate (Friedman et al. 1989;Hautekeete & Geerts 1997), synthesize increased amounts of extracellular matrix components (Shiratori et al. 1987) and express smooth muscle-a-actin . The transformation of hepatic stellate cells into myofibroblast-like cells is recognized as a critical step in hepatic fibrosis. Therefore, this cell type is an important target for antifibrotic therapy.Tetrandrine is a bis-benzyl isoquinoline alkaloid derived from Stephania tetrandra (Moore). This compound has been characterized pharmacologically to exhibit hypotensive, immunosuppressive properties (Sutter & Wang 1993), and inhibition of lipid perox...

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Tetrandrine on Experimental Hepatic Fibrosis Induced by Bile Duct Ligation and Scission in Rats

Nan

Pharmacology & Toxicology

et al. 2000

Journal of Biological Chemistry

“…Cell counts were performed using an electronic cell counter equipped with a cell sizing attachment (Coulter model Multisizer II with a 256C channelizer, Coulter Electronics, Hialeah, FL). The number of alveolar macrophages was determined by their characteristic cell diameter (26).…”

Section: Methodsmentioning

confidence: 99%

Activation of Mitogen-activated Protein Kinase p38 and Extracellular Signal-regulated Kinase Is Involved in Glass Fiber-induced Tumor Necrosis Factor-α Production in Macrophages

Zeidler

Young

et al. 2001

Self Cite

In a previous study, we demonstrated that the length of glass fibers was a critical determinant of fiber potency in induction of tumor necrosis factor (TNF)-␣ and that activation of NF-B was an important factor in this response. In the present study, we analyzed the role of mitogen-activated protein (MAP) kinases in the induction of TNF-␣ by glass fibers. Glass fibers induced phosphorylation of MAP kinases, p38, and ERK in primary rat alveolar macrophages, and this phosphorylation was associated with TNF-␣ gene expression. Long fibers were more potent than short fibers in activation of MAP kinases. Results from mechanistic analysis support that MAP kinases activate transcription factor c-Jun. The activated c-Jun acts on the TNF-␣ gene promoter through two binding sites, the cyclic AMP response element and the activator protein 1-binding site. These results suggest that in addition to the NF-B pathway for TNF-␣ production, glass fibers are able to activate c-Jun through MAP kinase pathways that lead to induction of TNF-␣ expression.

“…Silicosis is a representative fibrotic pulmonary disease. Tetrandrine (9) modulates TNF and collagen gene expression and could be used to treat silicosis alone or in combination with other therapies (Idec-Sadkowska et al 2006;Liu et al 1994;Xv and Zhou 2015;Chen et al 2018;Resit et al 1993;Castranova et al 1991). Tetrandrine (50 mg/kg, administered orally) was shown to inhibit the development of experimental silicosis of rats by reducing a 1 (I) and a 1 (III) collagen mRNA levels of silicotic rat lung, but this study was conducted without the use of positive control, and also lacks analysis of dose-effects relationship of tetrandrine (Idec-Sadkowska et al 2006;Liu et al 1994).…”

Section: Antifibrotic Effects In Pulmonary Diseasementioning

confidence: 99%

A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)

2020

Stephania tetrandra S. Moore (S. tetrandra) is distributed widely in tropical and subtropical regions of Asia and Africa. The root of this plant is known in Chinese as ''Fen Fang Ji''. It is commonly used in traditional Chinese medicine to treat arthralgia caused by rheumatism, wet beriberi, dysuria, eczema and inflamed sores. Although promising reports have been published on the various chemical constituents and activities of S. tetrandra, no review comprehensively summarizes its traditional uses, phytochemistry, pharmacology and toxicology. Therefore, the review aims to provide a critical and comprehensive evaluation of the traditional use, phytochemistry, pharmacological properties, pharmacokinetics and toxicology of S. tetrandra in China, and meaningful guidelines for future investigations.