Inhibition of TGF-β Signaling in Gliomas by the Flavonoid Diosmetin Isolated from Dracocephalum peregrinum L.

Abstract

Background: Dracocephalum peregrinum L., a traditional Kazakh medicine, has good expectorant, anti-cough, and to some degree, anti-asthmatic effects. Diosmetin (3′,5,7-trihydroxy-4′-methoxyflavone), a natural flavonoid found in traditional Chinese herbs, is the main flavonoid in D. peregrinum L. and has been used in various medicinal products because of its anticancer, antimicrobial, antioxidant, estrogenic, and anti-inflammatory effects. The present study aimed to investigate the effects of diosmetin on the proliferation, invasion, and migration of glioma cells, as well as the possible underlying mechanisms. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), scratch wound, and Transwell assays were used to demonstrate the effects of diosmetin in glioma. Protein levels of Bcl-2, Bax, cleaved caspase-3, transforming growth factor-β (TGF-β), E-cadherin, and phosphorylated and unphosphorylated smad2 and smad3 were determined by Western blots. U251 glioma cell development and progression were measured in vivo in a mouse model. Results: Diosmetin inhibited U251 cell proliferation, migration, and invasion in vitro, the TGF-β signaling pathway, and Bcl-2 expression. In contrast, there was a significant increase in E-cadherin, Bax, and cleaved caspase-3 expression. Furthermore, it effectively reduced the tumorigenicity of glioma cells and promoted apoptosis in vivo. Conclusion: The results of this study suggest that diosmetin suppresses the growth of glioma cells in vitro and in vivo, possibly by activating E-cadherin expression and inhibiting the TGF-β signaling pathway.

Anti-Inflammatory and Anti-Remodelling Potential of Ethanol Extract Rhodomyrtus Tomentosa in Combination of Asthma and Coal Dust Models

“…All of these components contribute as anti-inflammatory and anti-remodelling (32). Flavonoid compounds in Dracocephalum peregrinum L. inhibit the signal of transforming growth factor (TGF)-β1 (14). The TGF-β1 molecule is an inflammatory cytokine associated with fibrosis (one of the parameters of lung tissue remodelling) in asthma (35).…”

“…Total extract of saponins from Tribulus terrestris L. showed better antiinflammatory activity by lowering nitric oxide (NO) production, tumour necrosis of α (TNF-α), and decreased phagocytic ability in RAW 264.7 cells stimulated by LPS (13). In addition, flavonoids in Dracocephalum peregrinum L. inhibit the signal transforming growth factor-beta-1 (TGF-β1) (14). The TGF-β1 molecule is an inflammatory cytokine associated with fibrosis (one of the parameters of lung tissue remodelling) in asthma (15).…”

Flavonoids against non-physiologic inflammation attributed to cancer initiation, development, and progression—3PM pathways

“…As discussed above, cancer progression is a complex process related to a broad spectrum of cellular and molecular signals; however, current research, especially preclinical in vitro and in vivo analyses, increasingly supports the efficacy of naturally occurring flavonoids against inflammation-associated migration, invasion, and metastasis, which are significant inducers of cancer progression [53,55,78,142,143].…”

“…Indeed, due to the association between pro-inflammatory responses and tumor metastasis, the administration of biochanin A might alter the TME and thus hinder cancer migration and invasiveness [ 144 ]. Similarly, diosmetin isolated from Dracocephalum peregrinum L. repressed the migration and invasion of U251 glioma cells in vitro, as demonstrated by inhibition of the TGF-β signaling pathway and upregulation of E-cadherin [ 143 ]. Also, hesperetin suppressed NF-κB activation and reduced the secretion of pro-inflammatory TNF-α and IL-6 in HepG2 hepatic cancer cells; the anti-inflammatory effects of hesperetin are attributed to reduced ROS overproduction by the Nrf2 pathway [ 145 ].…”

Separation and Identification of Antioxidants and Aldose Reductase Inhibitors in Lepechinia meyenii (Walp.) Epling

“…The raw 1 H NMR spectrum is listed in Figure S7. S2, were identical to [37]. The raw 1 H NMR, 13 C NMR spectra, and ESI-MS/MS data are listed in Figure S8.…”