Scutellaria baicalensis and Their Natural Flavone Compounds as Potential Medicinal Drugs for the Treatment of Nicotine-Induced Non-Small-Cell Lung Cancer and Asthma

Abstract

Flavonoids as the largest group of natural phytochemical compounds have received significant attention, as demonstrated by clinical trials, due to their chemotherapeutic and/or pharmacological effects against non-small-cell lung cancer (NSCLC) and asthma. Scutellaria baicalensis (S. baicalensis), known as one of the most popular medicinal plants and used in several countries, contains natural active flavone constituents, with the major compounds of the roots being baicalein, baicalin, wogonin, wogonoside and oroxylin A. S. baicalensis and their compounds are proven to have inhibitory effects on NSCLC cells when used at different concentrations. However, the exact mechanisms by which these compounds exert their therapeutic effects against asthma remain unexplored. Indeed, the mechanisms by which S.baicalensis and its flavone compounds exert a protective effect against nicotine-induced NSCLC and asthma are not yet fully understood. Therefore, this review explores the mechanisms involved in the therapeutic potential of flavone-rich extracts from S. baicalensis in nicotine-induced NSCLC and asthma.

Insights into the Mechanisms of Action of Proanthocyanidins and Anthocyanins in the Treatment of Nicotine-Induced Non-Small Cell Lung Cancer

“…However, combination therapy of monoclonal antibody-based immunotherapy and chemotherapeutic agents has been shown to be a promising treatment strategy for NSCLC [ 15 ]. In addition, natural flavonoids present in fruits (e.g., citrus) in combination with chemotherapeutic agents, such as cisplatin, have shown anti-NSCLC effects, demonstrated by inhibition of the α7nAChR-mediated signaling pathways involved in cellular processes including proliferation, inflammation and anti-apoptosis [ 13 , 16 ].The health benefits of fruits are due to the high levels of bioactive flavonoids they contain, such as PCs and ACNs [ 17 , 18 ]. A large number of studies have documented the health benefits of natural flavonoids derived from fruits and plant foods, in relation to their biological attributes such as anti-diabetes/anti-cancer activity, reducing cardiovascular diseases and improving the blood lipid profile [ 17 , 18 , 19 ].…”

“…A recent review showed that flavone-rich extracts from Scutellaria baicalensis , and baicalein, baicalin, wogonin, wogonoside and oroxylin A, in particular, serve as potential adjuvant agents for the treatment of nicotine-induced NSCLC. These compounds exert anti-inflammatory, anti-angiogenesis, anti-proliferative and apoptotic/autophagic effects through inhibiting several cellular signaling pathways as potential molecular mechanisms [ 13 ].…”

“…Nicotine also induces epithelial-to-mesenchymal transition (EMT), which is the key step in enhancing tumor progression in NSCLC cells, resulting in upregulation of several transcription and growth factors via activation of α7nAChRmediated signaling pathways [12]. The mechanisms by which nicotine enhances tumor progression in NSCLC cells have been previously described in greater details [13]. In brief, nicotine binds to α7nAChR, activating the cellular signaling pathways involved in proliferation, metastasis, angiogenesis and anti-apoptosis/autophagy, which increases expression of EMT-associated molecules in NSCLC cells such as hypoxia inducible factor-1 (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor β (TGF-β), pathways involved in proliferation, metastasis, angiogenesis and anti-apoptosis/autophagy, which increases expression of EMT-associated molecules in NSCLC cells such as hypoxia inducible factor-1 (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor β (TGF-β), deca-pentaplegic homolog (Smad), B-cell lymphoma-2 (Bcl-2), metalloproteinases (MMPs), cyclinD1, Snail, twist, vimentin, fibronectin and N-cadherin [13].…”

“…The mechanisms by which nicotine enhances tumor progression in NSCLC cells have been previously described in greater details [13]. In brief, nicotine binds to α7nAChR, activating the cellular signaling pathways involved in proliferation, metastasis, angiogenesis and anti-apoptosis/autophagy, which increases expression of EMT-associated molecules in NSCLC cells such as hypoxia inducible factor-1 (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor β (TGF-β), pathways involved in proliferation, metastasis, angiogenesis and anti-apoptosis/autophagy, which increases expression of EMT-associated molecules in NSCLC cells such as hypoxia inducible factor-1 (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor β (TGF-β), deca-pentaplegic homolog (Smad), B-cell lymphoma-2 (Bcl-2), metalloproteinases (MMPs), cyclinD1, Snail, twist, vimentin, fibronectin and N-cadherin [13]. Figure 1 summarizes the mechanisms for nicotine in the development of NSCLC.…”

Borcalein: a Carborane‐Based Analogue of Baicalein with 12‐Lipoxygenase‐Independent Toxicity

“…[6] Several studies verify that baicalein has a broad anti-tumour activity against breast cancer cells, hepatocellular carcinoma, leukaemia, colon, lung and prostate cancer cells. [7] Furthermore, baicalein has beneficial effects in the treatment of gliomas, but high therapeutic doses are needed. [8] Since baicalein is known to be rapidly metabolised in vivo, [9] an improvement of metabolic stability is necessary to enhance the therapeutic efficiency.…”