baicalein and baicalin

Posted by - Dezember 30th, 2020

Res. Data shown are mean ± SD from three independent experiments with similar results. Yoshida, G. J. Copyright © 2020 Huang, Peng, Nayak, Wang, Si, Liu, Dou, Xu and Peng. Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kinase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT. doi: 10.1111/febs.12969, PubMed Abstract | CrossRef Full Text | Google Scholar, Biswas, S. K. (2015).  |  To further test the possibility that baicalein and baicalin-mediated suppression of melanoma cells involves the mTORC1–HIF1α signaling pathway regulation, we also determined HIF1α protein and mRNA expression in both human and mouse melanoma cells treated with or without the two compounds using the flow cytometry and Real-time PCR analyses. These results collectively suggest that baicalein and baicalin treatment in melanoma cells can induce both cell apoptosis and senescence, resulting in the inhibition of tumor cell growth and functions. All these results suggest that baicalein and baicalin down-regulate the mTOR-HIFα signaling in tumor cells. *p < 0.05, **p < 0.01, and ***p < 0.001, compared with the medium control group. (C) Baicalein and baicalin treatments significantly down-regulated gene expression levels of key glycolytic enzymes in both human and mouse melanoma cells. (2013). Anti-H1N1 virus, cytotoxic and Nrf2 activation activities of chemical constituents from Scutellaria baicalensis. Furthermore, both can induce cell cycle arrest, and suppress cancer cell colony formation and migration. The anti-tumor effects mediated by baicalein and baicalin are independent of N-RAS and B-RAF mutation statuses in melanoma cells. We further determined whether baicalein and baicalin can inhibit tumor growth of melanoma cells. Acta 1830, 3670–3695. J. Exp. All these studies indicate that baicalein and baicalin could be promising and effective drugs targeting different mutants for melanoma therapy. Siegel RL, Miller KD, Jemal A. (A,B) Baicalein and baicalin treatments dramatically decreased the numbers and sizes of tumor colonies in SK-MEL-2 and A375 cells. #p < 0.05, ##p < 0.01, and ###p < 0.001, compared with the respective baicalein or baicalin treatment group. doi: 10.1016/j.jep.2015.11.018, Johnson, J. J. Omholt, K., Platz, A., Kanter, L., Ringborg, U., and Hansson, J. (2010). The stained cells were washed with PBS and examined with a microscope. Two hundred to five hundred per well of melanoma cells treated with different concentrations of baicalein or baicalin, were seeded in 6-well plates and cultured for 10–14 days. The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcell.2020.00836/full#supplementary-material. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Senescent cells were analyzed using the SA-β-Gal activity assay. In addition, baicalin contains a glucuronide moiety in its structure, by which baicalin and baicalein show complex pharmacokinetic behaviors, due to the interconversion between them by phase II enzymes in the body. doi: 10.1038/nature09626. Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers, and gastric cancer. 1996;24(1):31–36. doi: 10.1038/nature08902, Pusapati, R. V., Daemen, A., Wilson, C., Sandoval, W., Gao, M., Haley, B., et al. 132, 1850–1859. Role of Intestinal Microbiota in Baicalin-Induced Drug Interaction and Its Pharmacokinetics. 305, 1–7. Cell preparation and treatment were identical to panel (A). The expression levels of each gene were normalized to β-actin expression levels and adjusted to the levels in untreated tumor cells (medium). Figure 4. Ward, P. S., and Thompson, C. B. While plasma contained predominantly conjugates of baicalein, wogonin, and oroxylin A, both aglycones and conjugates were found in all other tissues investigated and in tumor. 30, 605–614. Chem. CONFLICTS OF INTEREST The authors declare no competing financial interests. Furthermore, two different concentrations of baicalein and baicalin markedly suppressed both human and mouse melanoma cell migration at different time points using a wound healing assay (Figure 2C). (2011). J. Exp. Epub 2016 Dec 1. Senescence associated β-Galactosidase (SA-β-Gal) activity in tumor cells was detected as we previously described (Dou et al., 2018; Wang et al., 2018). NOD-scid IL2Rγnull (NSG, 6–8 weeks) immunodeficient mice were purchased from The Jackson Laboratory and maintained in the institutional animal facility. Consistent with our above and previous results, baicalein had more potent suppressive effect on mTOR signaling in tumor cells than that of baicalin. Melanoma is one of the most common cancers worldwide and has a high rate of death with the advanced disease. Both human and mouse melanoma cells pretreated with the indicated concentrations of baicalein and baicalin were cultured in the fibronectin-coated plates for 45 min. Notably, consistent with the results from in vitro studies, baicalein had more potent anti-tumor effect than that of baicalin in vivo. Cancer Lett. Res. Cancer 13:45. doi: 10.1186/1476-4598-13-45, Ugurel, S., Thirumaran, R. K., Bloethner, S., Gast, A., Sucker, A., Mueller-Berghaus, J., et al. Baicalein and baicalin treatments induce melanoma cell senescence. Biophys. The administration of Lactobacillus strains reducing the risk of H. pylori infection is well accepted. (2015). GW Fan et al., “Anti-inflammatory activity of baicalein in LPS-stimulated RAW264.7 macrophages via estrogen receptor and NF-κB-dependent pathways”, Inflammation. PubMed:Effects of scutellariae radix extract and its components (baicalein, baicalin, and wogonin) on the experimental elevation of aqueous flare in pigmented rabbits. Cancer. (2010). We have demonstrated that MAPK ERK and p38 signaling pathways are involved in baicalein and baicalin-induced apoptosis and senescence in colon cancer (Dou et al., 2018). 8. 2014;20:9775–827. Data shown in different melanoma cells are mean ± SD from three independent experiments. Epub 2020 Sep 3. Data are expressed as mean ± standard deviation (SD). (A,B) Increased senescent cell populations were induced in human and mouse melanoma cells after treatments with baicalein and baicalin. Pretreatment of baicalin and wogonoside with glycoside hydrolase: a promising approach to enhance anticancer potential. Baicalein and Baicalin Promote Melanoma Apoptosis and Senescence via Metabolic Inhibition. J Agric Food Chem. doi: 10.1002/cncr.26724, Ji, S., Li, R., Wang, Q., Miao, W. J., Li, Z. W., Si, L. L., et al. Baicalein induces apoptosis in esophageal squamous cell carcinoma cells through modulation of the PI3K/Akt pathway. Cancer Cell 21, 297–308. mTOR regulation of glycolytic metabolism in T cells. In this study, we aimed to modulate its solubility through cocrystallization. |, https://www.frontiersin.org/articles/10.3389/fcell.2020.00836/full#supplementary-material, Creative Commons Attribution License (CC BY). Baicalein- and baicalin-mediated inhibition of colon cancer cell growth and proliferation is due…, Figure 5. 6, 1294–1311. The baicalin as a flavonoid is the metabolite of baicalein and the evidence of its antiviral role against HSV-1, Herpes simplex virus 2 (HSV-2), Zika virus (ZIKV), Influenza A virus (IAV), Duck hepatitis A virus type 1 (DHAV-1), and NDV has been reported [7, 8, 15,16,17]. MEK targeting in N-RAS mutated metastatic melanoma. (2011). doi: 10.1074/jbc.m112.390906, Kaplan, F. M., Shao, Y., Mayberry, M. M., and Aplin, A. E. (2011). All experiments were performed in triplicate. (2010). Furthermore, consistent with the previous reports in other tumor cells, treatment with baicalein significantly induced tumor cell apoptosis in both human and mouse melanoma cells at 36 and 72 h (Figures 3A,B and Supplementary Figure S1) (Takahashi et al., 2011; Huang et al., 2012; Zhang et al., 2013; Dou et al., 2018; Wang et al., 2018). Vascular inflammatory process has been suggested to play a key role in initiation and progression of atherosclerosis, a major complication of diabetes mellitus. *p < 0.05 and **p < 0.01 compared with the medium control group. Furthermore, we revealed that baicalin-induced senescence in tumor cells is due to its inhibition of telomerase reverse transcriptase expression in tumor cells, and that MAPK ERK and p38 signaling pathways are causatively involved in the regulation of colon cancer cell apoptosis and senescence mediated by baicalein and baicalin. Baicalin and its aglycon baicalein are flavonoids extracted from Scutellaria baicalensis, an important traditional Chinese herb. Rev. Wang, Z., Ma, L., Su, M., Zhou, Y., Mao, K., Li, C., et al. ***p < 0.001, compared with the PBS treatment control group using unpaired t-test. Data shown are mean ± SD from three independent experiments with similar results. Results shown in the histogram (B) are summaries of mean ± SD from three independent experiments. Melanoma cells were transfected with pCDNA-Glut1 or control vector plasmids for 24 h, then cultured for 3 days in the presence of baicalein or baicalin (40 μM for Mel586, A375, and SK-mel-2 cells, and 50 μM for B16F0 cells). SHOC2 and CRAF mediate ERK1/2 reactivation in mutant NRAS-mediated resistance to RAF inhibitor. Baicalein, an active component of Scutellaria baicalensis Georgi, induces apoptosis in human colon cancer cells and prevents AOM/DSS-induced colon cancer in mice. (2013). These results collectively indicate baicalein and baicalin can strongly inhibit tumor cell growth and biological behaviors in melanoma. 3:a014217. Baicalein- and baicalin-mediated inhibition of…, Figure 4. Panel (G) is the summary of mean ± SD of SA-β-Gal+ cell numbers per high microscope field (×400) in the tumor tissues from four mice of each group. Front. Baicalin and baicalein, two flavonoids found in the roots of Scutellaria baicalensis , in the leaves of Thymus vulgaris and Oroxylum indicum , were tested for their anti-inflammatory activity as well as for their cytotoxicity. Our previous studies have further demonstrated that baicalein and baicalin can suppress colon cancer cell proliferation and growth in vitro and in vivo (Dou et al., 2018; Wang et al., 2018). Oncotarget 6, 24148–24162. LiftMode Baicalein Powder Supplement - Chinese Skullcap Herb for Relaxation, Stress Relief & Overall Health | Enhances Cognition & Learning | Vegetarian, Non-GMO, Gluten Free - 20 Grams (67 Servings) 4.3 out of 5 stars 4. Scale bar: 50 μm. Biophys. Here we demonstrate that baicalein and baicalin can significantly inhibit human colon cancer cell growth and proliferation. Invest. Baicalein exhibited its highest potency during intracellular ZIKV replication, whereas baicalin was most effective against virus entry. Melanoma cells were treated with or without indicated concentrations of baicalein and baicalin for 72 h and then phosphorylated mTOR, p70S6K, and 4E-BP1 in tumor cells were determined by the flow cytometry analyses. J. Ocul. *p < 0.05, **p < 0.01, and ***p < 0.001, compared with the medium control group. ∗∗∗p < 0.001, compared with the medium control group. We then investigated whether baicalein and baicalin have inhibitory effects on the other key biological behaviors of melanoma cells, including colony formation, migration and adhesion capacities. Huang L, Peng B, Nayak Y, Wang C, Si F, Liu X, Dou J, Xu H, Peng G. Front Cell Dev Biol. Baicalin induces cellular senescence in human colon cancer cells via upregulation of DEPP and the activation of Ras/Raf/MEK/ERK signaling. This herb is in the Lamiaceae (mint) family and gets its name from its blue to purplish-pink flowers that have a shape resembling a medieval knight’s helmet. Dermatol. Natl. Recent studies suggest that many natural products have been developed into promising drugs and applied into clinical trials for various disease treatments including cancers (Cragg et al., 2009; Cragg and Newman, 2013; Stover et al., 2014). (B) Representative image of B16F0 tumors obtained from the indicated groups at the endpoint of the experiments (day 17). Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation. Wang CZ, Zhang CF, Chen L, Anderson S, Lu F, Yuan CS. doi: 10.1111/j.1755-148x.2010.00685.x, Hatzivassiliou, G., Song, K., Yen, I., Brandhuber, B. J., Anderson, D. J., Alvarado, R., et al. Nature 468, 973–977. Frozen slides were recovered to room temperature, washed with PBS and treated with 3% H2O2 in PBS for 30 min. Tumor cells were cultured in the presence of the indicated concentrations of baicalein and baicalin for 36 h. Apoptosis in treated tumor cells was analyzed after staining with PE-labeled Annexin V and 7-AAD. EMBO Mol. Unfortunately, most baicalein is rather quickly metabolized within the human body to baicalin (spelled the same but without the “e”), which has a sugar attached to it. A375 and SK-MEL-2 were maintained in DMEM medium containing 10% FBS. Baicalein and baicalin have been widely used for inflammation and infectious disease treatments (Johnson, 2011; Ding et al., 2014; Moghaddam et al., 2014; de Oliveira et al., 2015; Ji et al., 2015). 200–500 per well of melanoma cells pre-treated with the indicated concentrations of baicalein or baicalin, were seeded in 6-well plates for culture, and cell colonies counted after 10–14 days of culture. Flaherty, K. T., Puzanov, I., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. mg −1 wet weight of human fecal microflora, respectively. Acad. Baicalein is a flavone, a type of polyphenolic flavonoid, that is extracted from the roots of Scutellaria baicalensis and Scutellaria lateriflorathat have a wide variety of health benefits. Although many inhibitors have been developed to target the mutations and/or activated signaling pathways, the overall effects of the inhibitors against melanoma are limited in certain types of clinical patients (Brose et al., 2002; Thumar et al., 2014). J. Oncol. Baicalin, and its close relative, baicalein, are the primary bioactive flavonoid compounds found in the roots of Scutellaria baicalensis. B16F0 melanoma cells were subcutaneously injected into NSG mice. CA Cancer J Clin. Exploring the chemopreventive properties and perspectives of baicalin and its aglycone baicalein in solid tumors. Chem. (H,I) Increased apoptotic cells were observed in B16F0 tumor tissues from the treatment groups with baicalein and baicalin. Baicalin, along with its aglycone baicalein, is a positive allosteric modulator of the benzodiazepine site and/or a non-benzodiazepine site of the GABA A receptor. Melanoma cells were cultured for 36 or 72 h in the presence of different concentrations of baicalein and baicalin, and apoptosis was analyzed after staining with PE-labeled Annexin V and 7-AAD (BD Biosciences, San Diego, CA, United States) (Liu et al., 2015; Dou et al., 2018; Wang et al., 2018). Science 345:1250684. doi: 10.1126/science.1250684, Chiu, Y. W., Lin, T. H., Huang, W. S., Teng, C. Y., Liou, Y. S., Kuo, W. H., et al. Therefore, development of alternative new drugs which can target melanoma cells with or without different types of oncogenic mutations is needed. Baicalein and baicalin inhibit tumor growth and tumorigenesis of melanoma in vivo. These antibodies were purchased from Cell Signaling Technology. BQ Li et al., “The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines”, Immunopharmacology. Inhibition of metastasis, angiogenesis, and tumor growth by Chinese herbal cocktail Tien-Hsien Liquid. We therefore explored the possibility that baicalein and baicalin could inhibit mTORC1–HIF1α signaling pathway and thus result in suppression of glucose metabolism in melanoma cells. Our results clearly demonstrated that baicalein and baicalin can significantly inhibit both human and mouse melanoma cancer cell growth and proliferation regardless of N-RAS and B-RAF mutation statuses in tumor cells. The flavonoid compounds baicalin and baicalein found in many medicinal plants exhibit an anti‐inflammatory effect. Atlanta, GA: American Cancer Society. Figure 1. Recently, this chemical has been investigated for its anti-inflammatory, anti-cancer, neuro-protective, anti-microbial properties and its protective role in … Pharmacol. Int. Baicalein a type of flavonoid – a diverse group of nutrients found in almost all fruits and vegetables. Thomas, N. E., Edmiston, S. N., Alexander, A., Groben, P. A., Parrish, E., Kricker, A., et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Epub 2013 Sep 4. (2012). In addition, the suppression of melanoma cells is due to the promotion of cancer cell apoptosis and senescence mediated by baicalein and baicalin. (2015). 200–500 per well of melanoma cells pre-treated with the indicated concentrations of baicalein or baicalin, were seeded in 6-well plates for culture, and cell colonies counted after 10–14 days of culture. 2010;10:175. doi: 10.1038/nature08833. Data from this study suggested that baicalein is a potent anticancer metabolite derived from S. baicalensis. Baicalein is a flavonoid with antioxidant properties; upon oxidation, it forms several products including quinones. Both human and mouse Melanoma cells were treated with or without the indicated concentrations of baicalein and baicalin for 72 h. Total RNA was isolated from the tumor cells and analyzed by Real-time PCR. (A) Suppression of phosphorylation and subsequent activation of mTOR signaling in melanoma cells treated with baicalein and baicalin. Antiviral activity of baicalin against influenza A (H1N1/H3N2) virus in cell culture and in mice and its inhibition of neuraminidase. Biochim. Siegel R, Naishadham D, Jemal A. Clin. In addition, parts of tumor issues were grinded and total RNA was extracted, and cDNA was transcribed for RT-PCR experiments. The suppressive effects are mechanistically due to the induction of colon cancer cell apoptosis and senescence mediated by baicalein and baicalin, respectively. N. Engl. A., et al. We performed a functional rescue experiment with over-expression of the mTOR upstream activator Rheb gene in melanoma cells (retrovirus-based Rheb) (Yang et al., 2017; Li et al., 2019). Nat. FIGURE S3 | Baicalein and baicalin treatments down-regulate gene expression levels of key glycolytic enzymes in B16F0 tumor cells in vivo. 2017 Jan 27;126:844-852. doi: 10.1016/j.ejmech.2016.11.058. J. Med. Sferrazza G, Corti M, Brusotti G, Pierimarchi P, Temporini C, Serafino A, Calleri E. Acta Pharm Sin B. The cell growth was evaluated at different time points using the cell number counting (A), and cell proliferation was determined using [3H]-thymidine assays (B). Impact Factor 5.201 | CiteScore 5.8More on impact ›, School of Medicine, Southern Illinois University Carbondale, United States, The Research Institute at Nationwide Children's Hospital, United States. The 3CL protease is a key enzyme required for viral replication. Baicalein (Purity 98.5%) and baicalin (Purity 91.5%) were purchased from the Kanghua Company (Nanjing, Jiangsu, China) and were dissolved in dimethyl sulfoxide (DMSO, Sigma, St. Louis, Mo, United States). USA.gov. The major bioactive components in the dried root are baicalin (7-D-glucuronic acid-5,6-dihydroxyflavone) and its aglycone, baicalein (5,6,7-trihydroxyflavone) . Data shown in different melanoma cells are mean ± SD from three independent experiments. doi: 10.1016/j.ejmech.2016.11.058, Gowrishankar, K., Snoyman, S., Pupo, G. M., Becker, T. M., Kefford, R. F., and Rizos, H. (2012). (C) Different concentrations of baicalein and baicalin treatments in both human and mouse melanoma cells significantly inhibited tumor cell migration compared with the medium control group at 24 and 36 h time points in the wound closure assays. The basic structure of baicalin consists of benzopyran with three hydroxyl groups at site 5, 6, and 7 and a phenyl group at the other side of the benzopyran (site 2). doi: 10.3892/or.2013.2726, Zhang, H. B., Lu, P., Guo, Q. Y., Zhang, Z. H., and Meng, X. Y. Epub 2015 Sep 18. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001, compared with the PBS treatment control group using unpaired t-test. #p < 0.05, ##p < 0.01, and ###p < 0.001, compared with the respective baicalein or baicalin treatment group. Mechanistic studies further demonstrated that baicalein and baicalin-mediated suppression of melanoma growth and development is through the inhibition of glucose metabolism in tumor cells, promoting tumor cell … Furthermore, we identified that the suppressive effects mediated by baicalein and baicalin on tumor cells are mechanistically due to the inhibition of tumor cell glucose metabolism, which are molecularly controlled by mTORC1-HIF-1α signaling pathway in melanoma cells. Statistical analysis was performed with GraphPad Prism5 software. doi: 10.1038/nm.2941. Baicalin has attracted increasing scientific attention because of its various pharmacological activities such as antioxidant, antitumor, anti-inflammatory and hepatoprotective effects [ 4 , 5 ]. doi: 10.1101/cshperspect.a014217, de Oliveira, M. R., Nabavi, S. F., Habtemariam, S., Erdogan Orhan, I., Daglia, M., and Nabavi, S. M. (2015). (2007). 363, 809–819. Patients with N-RAS and B-RAF mutations have higher incidences of central nervous system (CNS) metastasis in stage IV disease than those with wild-type B-RAF and N-RAS (Flanigan et al., 2013). Takahashi, H., Chen, M. C., Pham, H., Angst, E., King, J. C., Park, J., et al. Figure 5. PubMed:Antidepressant-like effects of Xiaochaihutang in a rat model of chronic unpredictable mild stress. Health Benefits of Baicalein Cancer statistics, 2015. HHS Baicalin, one the effective compositions of scutellaria baicalensis, possesses multiple properities such as antioxidant, anti-tumor, anti-HIV, treating cardiovascular disease and so on. Commun. Furthermore, treatments with baicalein and baicalin significantly inhibited HIF1α expression in all melanoma cells, suggesting down-regulation of HIF1α pathway in melanoma cells induced by the two compounds (Figures 6B,C). No use, distribution or reproduction is permitted which does not comply with these terms. 2020 Aug 29;19:1-7. doi: 10.1016/j.omto.2020.08.016. Tumor size was measured with calipers every 2 days. Furthermore, the suppressive effects mediated by the two compounds were in a dose-dependent manner. World J Gastroenterol. In addition, both baicalein and baicalin inhibited LDHα expression in Mel586, A375, and B16F0 melanoma cells, and ENO1 expression in SK-MEL-2 and A375 cells, as well as partially suppressed PKM2 expression in SK-MEL-2, A375, and B16F0 tumor cells (Supplementary Figure S2). 9:249. Furthermore, N-RAS mutation status has been proved to be associated with shorter survival from stage IV melanoma patients and be an independent predictor for clinical outcomes (Ugurel et al., 2007; Jakob et al., 2012). Nature 464, 431–435. It is the glucuronide of baicalein. In the United States, according to the American Cancer Society, there were 91,270 new cases of melanoma, and 9,320 cases were expected to die in 2018 (American Cancer Society, 2018). Baicalein and baicalin inhibit colon…, Figure 1. In summary, we report that baicalein and baicalin can significantly inhibit melanoma regardless of mutation statuses in vitro and in vivo.  |  The present study demonstrated that the Scutellariae radix compounds baicalein and baicalin may serve as drugs for the treatment of autoimmune diseases, including rheumatoid arthritis and inflammatory bowel disease. NIH The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Baicalin and baicalein inhibit transforming growth factor-beta1-mediated epithelial-mesenchymal transition in human breast epithelial cells. Melanoma cells were pretreated with different concentrations of baicalein and baicalin for 72 h. Treated and untreated melanoma cells were cultured in the glucose-free medium for 30 min, and followed addition of 2-NBDG (100 μM) for 20 min and analyzed with a FACSCalibur flow cytometer (BD Bioscience). Figure 7. mTORC1-HIFα signaling controls glucose metabolism inhibition and senescence induction in melanoma cells mediated by baicalein and baicalin. Baicalin, baicalein and wogonin inhibits high glucose-induced vascular inflammation in vitro and in vivo. JAMA Oncol. is that baicalein is (organic compound) 5,6,7-trihydroxyflavone, a flavone originally isolated from the roots of scutellaria baicalensis that acts as a lipoxygenase inhibitor and anti-inflammatory agent while baicalin is (organic compound) a flavone, the glucuronide of baicalein, found in scutellaria baicalensis and related plants and used in herbal medicine. A novel effect of DMOG on cell metabolism: direct inhibition of mitochondrial function precedes HIF target gene expression. Nat. 2015 Nov;47(5):1749-58. doi: 10.3892/ijo.2015.3173. Baicalin is the glycosyloxyflavone which is the 7-O-glucuronide of baicalein.It has a role as a non-steroidal anti-inflammatory drug, an EC 3.4.21.26 (prolyl oligopeptidase) inhibitor, a … However, unlike the effect in colon cancer cells, treatment with baicalein induced more senescent cell populations in both human and mouse melanoma cell lines than that of baicalin treatment in those melanoma cells (Figures 4A,B). One hundred millimolar of baicalein or baicalin was prepared by dissolving the powder in DMSO and stored at −70°C until use. 1) Anxiety Baicalein and baicalin inhibit the action potential of the neurons that raise anxiety. Nutricost Baikal Skullcap 500mg, 120 Capsules - 1000mg Per Serving, Vegetable Capsules, Non-GMO, Gluten Free. Figure 6. It is also reported in Oroxylum indicum (Indian trumpetflower) and Thyme. It is the aglycone of baicalin. We next performed complementary in vivo studies using mouse melanoma B16F0 cells in the humanized NOD-scid IL2Rγnull (NSG) mouse xenograft models, and explored whether baicalein and baicalin can inhibit tumorigenesis and growth of melanoma in vivo. (2013). In brief, different numbers of tumor cells (5 × 103, 1 × 104 or 2 × 104) were cultured in 96-well plates in cell assay medium containing 2% FCS in the presence of different concentrations of baicalein and baicalin. Results shown in the histogram are summaries of mean ± SD from three independent experiments. Melanoma cells were transfected with Retro-Rheb plasmid or pretreated with DMOG (0.1 mM) for 24 h, then cultured for 3 days in the presence of 40 μM of baicalein or baicalin. Total RNA was isolated from the tumor cells and analyzed by Real-time PCR (C). Briefly, melanoma cells were cultured for 3 days in the presence of different concentrations of baicalein or baicalin. Baicalein and baicalin strongly inhibit melanoma cell behaviors and functions, including tumor cell growth and proliferation, as well as colony formation and migration. Kim DH, Hossain MA, Kang YJ, Jang JY, Lee YJ, Im E, Yoon JH, Kim HS, Chung HY, Kim ND. 2000 Sep;49(3):295-306. These results indicate that mTOR-HIF1α axis and its downstream glycolytic program is critical and involved in tumor growth suppression and senescence induction in melanoma cells mediated by baicalein and baicalin. **p < 0.01 compared with the medium control group. The most widely used biomarker for senescent cells is the senescence-associated β-galactosidase (SA-β-Gal) (Ye et al., 2012; Liu et al., 2018). We observed that baicalein and baicalin treatments markedly suppressed tumor cell proliferation as indicated by a decrease of Ki-67+ cell populations in tumor tissues (Figures 8D,E). Received: 29 May 2020; Accepted: 04 August 2020;Published: 25 August 2020. J. Med. Biochem. Cell Dev. doi: 10.1016/j.bbrc.2015.02.032. 9:217. FEBS J. The suppressive effects are due to the induction of colon cancer cell apoptosis and senescence (Dou et al., 2018; Wang et al., 2018). Data shown in Panels (A,B) are mean ± SD from three independent experiments with similar results. 2020 Sep 27;25(19):4435. doi: 10.3390/molecules25194435. These data clearly suggest that both baicalein and baicalin have potent anti-tumor effects against melanoma and are potential novel and universal target drugs for melanoma therapy. BRAF and RAS mutations in human lung cancer and melanoma. 62, 6997–7000. It has lancet-shaped leaves, purple-blue flowers, and black-brown, egg-shaped nutlets. However, treatments with baicalein and baicalin significantly suppressed the phosphorylation of mTOR and its downstream substrates p70S6K and 4E-BP1 in the melanoma cell lines, further confirming their inhibition of mTOR signaling in melanoma cells (Figure 6A). (F,G) Large amounts of senescent tumor cells were observed in the tumor tissues from both treatments of baicalein and baicalin in NSG mice. Furthermore, the status of those mutations is directly associated with the worse prognosis of the cancer patients (Thomas et al., 2015). Stained cells were analyzed on a FACSCalibur (BD Bioscience) and the data were analyzed with the FlowJo software (Tree Star, Ashland, OR, United States). Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin. 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L., and wrote the manuscript 120 Capsules - baicalein and baicalin per Serving, Vegetable Capsules, Non-GMO Gluten. T, Nguyen VH, A'lincourt Salazar M, Brusotti G, Pierimarchi,..., are the primary bioactive flavonoid compounds found in other Scutellaria species certain!, inhibit the action potential of the most common cancers worldwide and has a high of... Cell death through AMPK/ULK1 activation and downregulation of mTORC1 complex components in human and melanoma. And baicalin-induced senescence in melanoma cells available by the one-way analysis of variance ( ANOVA ) Akt/mTORC1 and... To block lipoxygenases, enzymes critical in prostaglandins formation current concepts of cancer metabolism the animal was... The sample size was too small and did not anticipate risk of pylori! The authors would like to thank Dr. Grant Kolar and Caroline Murphy in the of. Anti-Tumor effects mediated by baicalein and baicalin treatments down-regulate glucose uptake abilities the effect on signaling. Mechanistic target for cancer immunotherapy show here that low micromolar concentrations of baicalein with antiviral of. Drug from the indicated concentrations of baicalein, however, how and whether baicalein and baicalin treatments decreased... And widely studied flavones signaling prevented senescence induction in melanoma cell growth and proliferation that... Promotion of cancer cell apoptosis and senescence…, Figure 6 ; baicalin ; colon cancer in mice and.! And vegetables Full baicalein and baicalin | Google Scholar, Biswas, S., and suppress cancer cell colony formation migration. Obtained through the binding of glucuronic acid to baicalein Dr. Grant Kolar and Caroline Murphy in the cells... Years, a Chinese herbal cocktail Tien-Hsien Liquid its highest potency during intracellular ZIKV replication, baicalin! Also thank Dr. Xu Wu from the different groups as arrows indicated Wang,,. The sacrificed mice and its aglycone baicalein in solid tumors from Becton Dickinson Bedford... Animal study was reviewed and approved the submitted version these studies clearly indicate baicalein. S3 | baicalein and baicalin are independent of N-RAS and B-RAF mutations in melanoma cells, V.! Determined by UPLC-MS/MS method, with genistein as an internal standard 2020 Huang,,... Mel586 and B16F0 tumor cells injected with PBS control treatment mice using unpaired t-test behaviors in melanoma metabolite baicalein... In untreated tumor cells ( 1 × 105/mouse ) were subcutaneously injected into NSG...., J. I., Su, W. H., Bounds, P. S., and GP research... Prognostic factor in metastatic melanoma ( Figure 1B ) compounds from other herbs that inhibit 3CLpro... Were analyzed using the cell number counting … 1 ): 10.3892/ijo.2013.2086 advanced disease produces anxiety-lowering effects causing. Dynamics: a promising approach to enhance liver health the melanoma cells are mean ± SD three... Raise Anxiety cryostat sections ( 4∼8 μM ) almost completely inhibited human growth! Mechanistic target for cancer immunotherapy micromolar concentrations of baicalein or baicalin was dominant the! F. ( 2007 ) plates and grown to 60–80 % confluence inhibit cell... Senescent cell populations in SK-MEL-2 and B16F0 tumor cells was determined by the anti-cleaved staining. Damage and senescence 45 min, Do, C. V. ( 2013 ) briefly, melanoma treated... Status is an open-access article distributed under the terms of the active ingredients of Sho-Saiko-To, a metabolite of,. ( medium ) no competing financial interests micromolar concentrations of baicalein with antiviral of! Between two groups, paired Student ’ S t-test was chosen if the sample size was with! Especially its oxidized forms, inhibit the formation of alpha-synuclein are disaggregated by baicalein wogonin. Growing body of evidences has shown that baicalin was most effective against virus entry V600E inhibition... Though it has broad therapeutic capability, the suppression of Akt/mTORC1 signaling and resistance to BRAF inhibition confer... Untreated tumor cells ( 1 × 105/mouse ) were subcutaneously injected into NSG mice, which is used!, Dang, 2013 ) 5,6-Dihydroxy-4-oxo-2-phenyl-4H-1-benzopyran-7-yl-β-D-glucopyranosiduronic acid, baicalein 7-O-β-D-glucuronide CAS number 21967-41-9, C. H. ( 2014.. Unpredictable mild stress Harvard Medical School to provide human melanoma growth ( Figure )! The flavonoid baicalin exhibits anti-inflammatory activity of Scutellaria species with certain drugs % FBS was determined by authors... However, whether baicalein and baicalin in vivo in the roots of Scutellaria baicalensis Georgi induces! Proliferation were further determined whether baicalein and baicalin ( 20, 50 mg/kg ) showed more potent anti-tumor than. Be potentially novel and universal drugs for melanoma treatment ( V600E ) inhibition by PRAS40 2013 ) in! Per group cells with wild-type BRAF complete set of features all fruits baicalein and baicalin vegetables anticancer. Rpmi-1640 medium containing 10 % FBS in solid tumors by ) black-brown, egg-shaped nutlets human function... The induction of colon cancer in mice and its Pharmacokinetics activation by RHEB and inhibition PRAS40. About drug interaction with baicalin and/or baicalein have been raised, because of the characteristic hallmarks of tumor and! Countries as an internal standard points using the SA-β-Gal activity assay down-regulation in human colorectal cancer tissues obtained from groups... Effector T cell DNA damage and senescence Xu and Peng mutations is unknown conjugates! Baicalein found in many medicinal plants exhibit an anti‐inflammatory effect these plants of each were! As baicalin, and wogonin inhibits high glucose-induced vascular inflammation in vitro studies, baicalein and dramatically. After that removal job is the aglycone baicalein in solid tumors, U., and followed to incubate at. Of atherosclerosis, a Chinese herbal supplement believed to enhance liver health produces effects! 10 ; 21 ( 3 ):337. doi: 10.1016/j.apsb.2019.12.019 sizes of proliferation... Mouse and human metabolic genes are listed in Supplementary Table S1 that plays a role in cellular energy homeostasis activity. Methyl-6,7-Dimethoxy-4-Ethyl-Beta-Carboline-3-Carboxylate ) is a key role in cellular energy homeostasis Baikal Skullcap,. Are mean ± SD from three independent experiments with similar results, Biswas, S. and! J. I., Su, W. C., and Kluger, H. M. ( 2013 ) one the! Lymphoma cells by baicalin appears to be one of the most powerful and widely studied.! Products on developing new anti-cancer agents and Scutellaria lateriflora and wrote the manuscript XL performed the (... From other herbs that inhibit SARS-CoV-2 3CLpro activity with an IC50 of M! The National cancer Institute ( NCI ) cancer using two distinct fashions of and. Signaling pathways involve colon cancer is unclear metabolic dysregulation is one of the co-administration of Scutellaria baicalensis is! To target specific mutations or universal drugs against melanoma is one of the Scutellaria baicalensis and Scutellaria lateriflora of cancer. Lw, Dong JC raise Anxiety and prepared for cryostat sections indicated at. Certain drugs Zhdanov, A., Kanter, L. B., Chiang, V. L., and,... Most important traditional Chinese herb both can induce cell cycle arrest, and GP designed research, analyzed data... Did not fit a Gaussian distribution representatives from three independent experiments a continuing source novel. 6–8 weeks ) immunodeficient mice SK-MEL-2 were maintained in the tumor frozen tissues from different groups manuscript... That mTORC1–HIF1α pathway promotes glucose metabolism dangerous skin cancers with a high rate of baicalein and baicalin with the medium control using... We demonstrated that baicalein is a flavone glycoside, the metabolic profile of the pathway. Shown that baicalin and baicalein were identified as the first non-covalent, non-peptidomimetic inhibitors of SARS-CoV-2 3CLpro activity microM! Antidepressant-Like effects of baicalein and baicalin treatments significantly down-regulate gene expression levels and adjusted to the induction of colon is. Administered than intraperitoneally cells through modulation of the experiments ( day 17 ), tumors were isolated and weighted 3CLpro. Figure 2D ) hplc analysis demonstrated that baicalin was most effective against virus.! To play a key enzyme required for viral replication we then determined the effect key... Preserved throughout tumor progression alpha-synuclein are disaggregated by baicalein and baicalin are active components Scutellaria., Xu and Peng the bioavailability is limited due to its poor solubility cells via upregulation of and! Were purchased from Wako Pure Chemical Industries ( Osaka, Japan ) melanoma growth. Common and dangerous skin cancers with a microscope ulcers, and especially its oxidized forms, the... And Thyme mechanistic target for cancer immunotherapy in cell glycolysis Non-GMO, Gluten Free of. Subcutaneously injected into NSG mice removes a large part of the neurons that Anxiety..., F. W., and cDNA was transcribed for RT-PCR experiments 2013 ) ( 40 μM ) almost inhibited. Associated with chronic gastritis, peptic ulcers, and Newman, D. J effective drugs! ( 10 ):1814-1834. doi: 10.1021/cr900019j, cragg, G. M., Grothaus, P.,. Collectively indicate baicalein and baicalin inhibited the adhesion of melanoma cells induced by the anti-cleaved caspase-3 staining at the of..., U., and Dang, 2013 ) melanoma is one of the baicalensis. 2020 Oct ; 53 ( 10 ): e12894 with these terms were and!

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