The Biological Activities and Therapeutic Potentials of Baicalein Extracted from Oroxylum indicum: A Systematic Review

Salleh, Nik Nur Hakimah Nik; Othman, Farah Amna; Kamarudin, Nur Alisa; Tan, Suat Cheng

doi:10.3390/molecules25235677

Cited by 49 publications

(32 citation statements)

References 51 publications

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“…Another compound present in Scutellaria baicalensis , but also in Oroxylum indicum , is baicalein [ 117 , 118 ]. Same as the abovementioned flavonoids, baicalein was found to be active against a variety of cancer cells and thereby acted via different pathways [ 119 ], however, also with limited oral bioavailability [ 120 ].…”

Section: Resultsmentioning

confidence: 99%

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Jöhrer

Ҫiҫek

2021

Cancers

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A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced and selective induction of apoptosis when substituted in position 7 of the isoquinoline moiety. Interestingly, out of the phenolic compound class, two of the most noteworthy constituents belong to the relatively small subclass of xanthones, rendering this group a good starting point for possible further drug development. The class of terpenoids also provides noteworthy constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells. Moreover, triterpenoids containing a lactone ring and/or quinone-like substructures, e.g., bruceantin, whitaferin A, withanolide F, celastrol, and pristimerin, displayed remarkable activity, with the latter two compounds acting as inhibitors of both NF-κB and proteasome chymotrypsin-like activity.

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Section: Resultsmentioning

confidence: 99%

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Jöhrer

Ҫiҫek

2021

Cancers

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“…The application of baicalein, as a main bioactive ingredient extracted from the root of medical herb Scutellaria baicalensis , has been studied in the treatment of a variety of cancers, such as breast cancer, NSCLC, nasopharyngeal carcinoma, hepatocellular carcinoma, and the underlying mechanisms mainly focus on inducing apoptosis and autophagy, cell cycle arrest, inhibiting proliferation and invasion of tumor cells ( Bie et al, 2017 ; Yan et al, 2018 ; Guo et al, 2019 ; Nik Salleh et al, 2020 ; Zhang et al, 2020 ). In addition to malignant cells, increasing evidence demonstrated the dominant role of the large proportions of immune cells within the TME in orchestrating tumor progression and resistance to anti-tumor drugs ( Cassetta and Pollard, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Scutellaria baicalensis (also known as Chinese Huang Qin) is one of the most widely used herbs in TCM formula for treating various diseases, such as diarrhea, insomnia, and acute respiratory infection. Baicalein, one of the major bioactive compounds isolated from Scutellaria baicalensis, has been demonstrated multiple pharmacological effects, including anti-inflammatory, antiviral, anti-adipogenesis and cardiovascular protective effects ( Liu et al, 2016 ; Nik Salleh et al, 2020 ). Recent studies revealed that baicalein exerted anti-tumor activities in various solid tumors, such as non-small-cell lung cancer (NSCLC), and breast cancer ( Yan et al, 2018 ; Zhao et al, 2018 ; Nik Salleh et al, 2020 ; Zhang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Baicalein, one of the major bioactive compounds isolated from Scutellaria baicalensis, has been demonstrated multiple pharmacological effects, including anti-inflammatory, antiviral, anti-adipogenesis and cardiovascular protective effects ( Liu et al, 2016 ; Nik Salleh et al, 2020 ). Recent studies revealed that baicalein exerted anti-tumor activities in various solid tumors, such as non-small-cell lung cancer (NSCLC), and breast cancer ( Yan et al, 2018 ; Zhao et al, 2018 ; Nik Salleh et al, 2020 ; Zhang et al, 2020 ). Previous reports have shown the underlying mechanisms of baicalein on suppressing the proliferation and invasion of cancer cells by inducing autophagy and apoptosis, targeting arachidonic acid pathway, inhibiting AMPK or PI3K/AKT signaling pathways ( Yarla et al, 2016 ; Yan et al, 2018 ; Ke et al, 2019 ; Deng et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Baicalein Potentiated M1 Macrophage Polarization in Cancer Through Targeting PI3Kγ/ NF-κB Signaling

Wang

Liu

et al. 2021

Front. Pharmacol.

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Baicalein is one of the bioactive compounds extracted from Scutellaria baicalensis. Recent studies indicated the antitumor effects of baicalein, however, the underlying mechanisms are needed to be further determined. In this study, we found that baicalein could inhibit the tumor growth in mice models of breast cancer and melanoma and worked as an immunomodulator to promote the infiltration of tumor-associated macrophages (TAMs) and skew the TAMs towards the M1-like phenotype. Baicalein also induced M1-like phenotype polarization in THP-1-derived macrophages. Meanwhile, the expression of pro-inflammatory factors associated with M1 macrophages, including TNF-α, IL-1β, CXCL9 and CXCL10, were increased after baicalein treatment. Mechanistically, the RNA-seq data suggested that baicalein potentiated the M1 macrophage polarization via the NF-κB/TNF-α signaling pathway. ELISA and confocal microscopy assay confirmed that baicalein significantly induced the production of TNF-α and the activation of NF-κB, while TNF-α neutralization inhibited baicalein-induced macrophage polarization toward M1, and NF-κB P65 knock-down suppressed baicalein-induced TNF-α production in THP-1-derived macrophages. Phosphoinositide 3-kinase (PI3k) γ has been reported as a key molecule in macrophage polarization, and inhibition of PI3Kγ activates the NF-κB-related inflammatory signals. Our pharmacological network analysis predicted that PI3Kγ might be one of the major targets of baicalein. The results from the docking program and surface plasmon resonance (SPR) confirmed that baicalein displayed good binding activity to PI3Kγ. We further found that baicalein not only exhibited a direct inhibitory effect on the protein kinase activity of PI3Kγ, but also reduced the mRNA and protein expression of PI3Kγ, indicating that baicalein might be a novel PI3Kγ inhibitor. In summary, baicalein mediated the TAMs skewing to M1-TAMs, and then retarded tumor growth. These effects, at least in part, were linked to the PI3Kγ/NF-κB signaling.

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“…Luteolin possesses an antibacterial effect in vivo, increasing membrane permeability [ 17 ], but does not directly perturb the model membranes in vitro [ 18 , 19 ]. Both baicalein and luteolin possess antitumor activity [ 20 , 21 ] and, as well as their derivatives, have been used in preclinical studies and in experimental oncology [ 22 , 23 , 24 , 25 , 26 , 27 ]. Epidemiological studies showed that foods rich in polyphenolic compounds (flavonoids, phenolic acids, lignans and stilbenes) included in the diet reduced the total risk of cancer by up to 50% [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3′-Disulfate

et al. 2021

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Widespread pathologies such as atherosclerosis, metabolic syndrome and cancer are associated with dysregulation of sterol biosynthesis and metabolism. Cholesterol modulates the signaling pathways of neoplastic transformation and tumor progression. Lanosterol 14-alpha demethylase (cytochrome P450(51), CYP51A1) catalyzes one of the key steps in cholesterol biosynthesis. The fairly low somatic mutation frequency of CYP51A1, its druggability, as well as the possibility of interfering with cholesterol metabolism in cancer cells collectively suggest the clinical importance of CYP51A1. Here, we show that the natural flavonoid, luteolin 7,3′-disulfate, inhibits CYP51A1 activity. We also screened baicalein and luteolin, known to have antitumor activities and low toxicity, for their ability to interact with CYP51A1. The Kd values were estimated using both a surface plasmon resonance optical biosensor and spectral titration assays. Unexpectedly, in the enzymatic activity assays, only the water-soluble form of luteolin—luteolin 7,3′-disulfate—showed the ability to potently inhibit CYP51A1. Based on molecular docking, luteolin 7,3′-disulfate binding suggests blocking of the substrate access channel. However, an alternative site on the proximal surface where the redox partner binds cannot be excluded. Overall, flavonoids have the potential to inhibit the activity of human CYP51A1 and should be further explored for their cholesterol-lowering and anti-cancer activity.

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The Biological Activities and Therapeutic Potentials of Baicalein Extracted from Oroxylum indicum: A Systematic Review

Cited by 49 publications

References 51 publications

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Baicalein Potentiated M1 Macrophage Polarization in Cancer Through Targeting PI3Kγ/ NF-κB Signaling

Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3′-Disulfate

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