Anti-Fibrosis Effects of Magnesium Lithospermate B in Experimental Pulmonary Fibrosis: By Inhibiting TGF-βRI/Smad Signaling

Luo, Xiaoguang; Deng, Qiangqiang; Xue, Yaru; Zhang, Tianwei; Wu, Zhitao; Peng, Huige; Liu, Xuan; Pan, Guoyu

doi:10.3390/molecules26061715

Cited by 14 publications

(9 citation statements)

References 84 publications

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“…The TGF-β1 signaling pathway significantly affects the regulation of fibroblast activation, in which the key proteins Smad2 and Smad3 are the main downstream regulators that promote TGF-β1-mediated lung fibrosis ( Hu et al, 2018 ). We detected the effect of MR on the key proteins of TGF-β1/Smad signaling pathway by Western blotting, and the results showed that the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 were significantly reduced in TGF-β1-induced L929 cells treated with MR for 48 h ( Luo et al, 2021 ; Li Y. et al, 2022 ; Xiao et al, 2023 ) ( Figures 7A,B ). TGF-β1 treatment alone also showed elevated p-p38/p38, p-JNK/JNK, and p-ERK/ERK expression ratios and significant reductions in these ratios after the addition of MR ( Figures 7C,D ).…”

Section: Resultsmentioning

confidence: 99%

Anti-pulmonary fibrosis activity analysis of methyl rosmarinate obtained from Salvia castanea Diels f. tomentosa Stib. using a scalable process

Ma,

Liu,

Zhao

et al. 2024

Front. Pharmacol.

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Pulmonary fibrosis is a progressive, irreversible, chronic interstitial lung disease associated with high morbidity and mortality rates. Current clinical drugs, while effective, do not reverse or cure pulmonary fibrosis and have major side effects, there are urgent needs to develop new anti-pulmonary fibrosis medicine, and corresponding industrially scalable process as well. Salvia castanea Diels f. tomentosa Stib., a unique herb in Nyingchi, Xizang, China, is a variant of S. castanea. and its main active ingredient is rosmarinic acid (RA), which can be used to prepare methyl rosmarinate (MR) with greater drug potential. This study presented an industrially scalable process for the preparation of MR, which includes steps such as polyamide resin chromatography, crystallization and esterification, using S. castanea Diels f. tomentosa Stib. as the starting material and the structure of the product was verified by NMR technology. The anti-pulmonary fibrosis effects of MR were further investigated in vivo and in vitro. Results showed that this process can easily obtain high-purity RA and MR, and MR attenuated bleomycin-induced pulmonary fibrosis in mice. In vitro, MR could effectively inhibit TGF-β1-induced proliferation and migration of mouse fibroblasts L929 cells, promote cell apoptosis, and decrease extracellular matrix accumulation thereby suppressing progressive pulmonary fibrosis. The anti-fibrosis effect of MR was stronger than that of the prodrug RA. Further study confirmed that MR could retard pulmonary fibrosis by down-regulating the phosphorylation of the TGF-β1/Smad and MAPK signaling pathways. These results suggest that MR has potential therapeutic implications for pulmonary fibrosis, and the establishment of this scalable preparation technology ensures the development of MR as a new anti-pulmonary fibrosis medicine.

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Section: Resultsmentioning

confidence: 99%

Anti-pulmonary fibrosis activity analysis of methyl rosmarinate obtained from Salvia castanea Diels f. tomentosa Stib. using a scalable process

Ma,

Liu,

Zhao

et al. 2024

Front. Pharmacol.

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“…Recent studies show this to include the brain as well , 74,75,76 . Magnesium possesses the capacity to down regulate this SMAD pathway in the liver 77 and the lungs 78 . IFN-γ also appears capable in this regard 79 .…”

Section: Tgf and Ifnmentioning

confidence: 99%

Long Covid and Neurodegenerative Disease

Chambers¹

2023

Preprint

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Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased TGF beta/IFN gamma with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4+ and CD8+ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, …. In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF beta/IFN gamma and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis. Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.

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“…Combination of SM and ligustrazine were viewed to attenuate bleomycin-induced pulmonary fibrosis in rats via modulating TNF-α and TGF ( Huang et al, 2018 ). Both the lipophilic ingredients (tanshinone IIA and cryptotanshinone) and hydrophilic ingredients (salvianolic acid A, salvianolic acid B, and magnesium lithospermate B) from SM have protective effects against pulmonary fibrosis, including reducing the proliferation of lung fibroblasts and protecting the alveolar epithelial integrity ( Pan et al, 2014 ; Liu et al, 2018 ; Zhang Y. et al, 2019 ; Luo et al, 2021a ).…”

Section: Pharmacological Actions Of Salvia Miltiorrhiza ...mentioning

confidence: 99%

Salvia miltiorrhiza in thorax and abdomainal organ fibrosis: A review of its pharmacology

Zhao

Ping

et al. 2022

Front. Pharmacol.

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Organ fibrosis is a common pathological change that finally results in organ failure, which involves the destruction of parenchyma cells, the activation of mesenchymal cells and the imbalance of immunological cells. In recent years, although some breakthroughs have been made in understanding the pathogenesis and therapeutics of organ fibrosis, no registered drugs could directly target the fibrotic process, which constitutes a major biomedical challenge. Salvia miltiorrhiza (SM) is a well-known medicinal plant in China, which has been widely applied because of its pharmacological effects on anti-oxidative, anti-myocardial infarction, anti-fibrotic, anti-inflammatory, and anti-neoplastic properties. Accumulated evidence suggested that SM played critical roles against organ fibrosis in vivo and in vitro experiments by its multiple biological compounds. In this review, we discussed the recent advances on the phytochemistry and pharmacological mechanisms of SM and its active ingredients in liver, lung, kidney, and heart fibrosis, which might help to promote the treatment of fibrotic diseases in thorax and abdomainal viscera in clinic.

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Anti-Fibrosis Effects of Magnesium Lithospermate B in Experimental Pulmonary Fibrosis: By Inhibiting TGF-βRI/Smad Signaling

Cited by 14 publications

References 84 publications

Anti-pulmonary fibrosis activity analysis of methyl rosmarinate obtained from Salvia castanea Diels f. tomentosa Stib. using a scalable process

Anti-pulmonary fibrosis activity analysis of methyl rosmarinate obtained from Salvia castanea Diels f. tomentosa Stib. using a scalable process

Long Covid and Neurodegenerative Disease

Salvia miltiorrhiza in thorax and abdomainal organ fibrosis: A review of its pharmacology

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