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Wednesday, May 12, 2021

Compound in Medicinal Herb Shows Anti-fibrotic Potential - Pulmonary Fibrosis News

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Magnesium lithospermate B, a compound found in a traditional Chinese medicinal herb, eased several features of pulmonary fibrosis (PF) in a mouse model of the disorder.

According to investigators, the anti-fibrotic effects of this plant compound were comparable to those of Esbriet (pirfenidone), an approved treatment for idiopathic pulmonary fibrosis (IPF), highlighting the compound’s promising therapeutic potential for the treatment of PF.

Findings were reported in the study, “Anti-Fibrosis Effects of Magnesium Lithospermate B in Experimental Pulmonary Fibrosis: By Inhibiting TGF-βRI/Smad Signaling,” was published in the journal Molecules.

Magnesium lithospermate B (MLB) is a key component of the traditional Chinese herb Salvia miltiorrhiza, also known as red sage and danshen. Past studies have found the compound to be safe, well-tolerated, and capable of reducing fibrosis (tissue scarring) in the liver and kidneys by inhibiting the TGB-beta signaling pathway. 

TGF-beta is also a major driver of fibrosis in IPF, causing cells called fibroblasts to differentiate into myofibroblasts that produce several proteins found in fibrotic scars, such as collagen, fibronectin, and alpha smooth muscle actin (alpha-SMA).

A group of scientists from the Chinese Academy of Science and their colleagues recently investigated MLB’s therapeutic potential as a PF treatment by evaluating its ability to reduce signs of fibrosis in a mouse model of the disease.

Researchers treated mice with bleomycin, an agent often used to trigger the onset of PF. While some did not receive further treatment and were used as controls, others received daily intraperitoneal (into the abdomen) injections of MLB. For comparison purposes, researchers also treated a third group of bleomycin-treated mice with oral Esbriet.

As expected, bleomycin-treated mice that did not receive any further treatment developed extensive lung damage, accompanied by excessive collagen deposition.

A seven-day MLB treatment course lessened signs of lung injury and lowered the levels of several fibrosis markers. These included alpha-SMA, TGF-beta, multiple types of collagen, and inflammatory molecules. In most cases, these improvements were comparable to those seen in animals treated with Esbriet.

MLB treatment also significantly decreased the levels of phosphorylated Smad2 and Smad3, two proteins associated with TGF-beta activation, and increased the levels of Smad7, a protein that limits TGF-beta activity. Of note, phosphorylation is a chemical modification in which a phosphate group is added to a molecule.

Experiments done in lab-grown cells supported the results seen in mice.

MLB treatment also prevented TGF-beta from triggering human lung fibroblasts to grow into collagen-producing myofibroblasts. It also inhibited collagen and fibronectin production without causing toxicity.

Additional experiments also indicated MLB might exert its effect by interfering with the production or degradation of TGF-beta receptor 1 (TGF-betaR1), a protein receptor TGF-beta needs to interact with in order to trigger fibrosis.

“In summary,” the investigators concluded, “our results demonstrated that MLB could alleviate experimental pulmonary fibrosis both in vivo and in vitro, suggesting that MLB has great potential for pulmonary fibrosis treatment.”

Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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May 12, 2021 at 07:00PM
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Compound in Medicinal Herb Shows Anti-fibrotic Potential - Pulmonary Fibrosis News

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