New therapeutic aspects of flavones. The anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev

Tumor Immunology Program D030, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Cancer Treatment Reviews (Impact Factor: 7.59). 12/2008; 35(1):57-68. DOI: 10.1016/j.ctrv.2008.09.005
Source: PubMed


Traditional Chinese medicines have been recently recognized as a new source of anticancer drugs and new chemotherapy adjuvant to enhance the efficacy of chemotherapy and to ameliorate the side effects of cancer chemotherapies however their healing mechanisms are still largely unknown. Scutellaria baicalensis is one of the most popular and multi-purpose herb used in China traditionally for treatment of inflammation, hypertension, cardiovascular diseases, and bacterial and viral infections. Accumulating evidence demonstrate that Scutellaria also possesses potent anticancer activities. The bioactive components of Scutellaria have been confirmed to be flavones. The major constituents of Scutellaria baicalensis are Wogonin, Baicalein and Baicalin. These phytochemicals are not only cytostatic but also cytotoxic to various human tumor cell lines in vitro and inhibit tumor growth in vivo. Most importantly, they show almost no or minor toxicity to normal epithelial and normal peripheral blood and myeloid cells. The antitumor functions of these flavones are largely due to their abilities to scavenge oxidative radicals, to attenuate NF-kappaB activity, to inhibit several genes important for regulation of the cell cycle, to suppress COX-2 gene expression and to prevent viral infections. The tumor-selectivity of Wogonin has recently been demonstrated to be due to its ability to differentially modulate the oxidation-reduction status of malignant vs. normal lymphocytic cells and to preferentially induce phospholipase C gamma 1, a key enzyme involved in Ca(2+) signaling, through H(2)O(2) signaling in malignant lymphocytes. This review is aimed to summarize the research results obtained since the last 20 years and to highlight the recently discovered molecular mechanisms.

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    • "Baicalein, a major polyphenolic flavonoid from dried roots of Scutellaria baicalensis [1], has been shown to protect against a wide variety of malignancies [2,3,4,5,6,7,8]. Baicalein is effective at least in part by triggering apoptosis [2,4,7,9,10,11,12,13,14]. "
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    ABSTRACT: The polyphenolic flavonoid Baicalein has been shown to trigger suicidal death or apoptosis of tumor cells and is thus considered for the prevention and treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide. The present study explored whether Baicalein stimulates eryptosis. To this end, forward scatter was taken for measurement of cell volume, annexin-V-binding for phosphatidylserine-exposure, Fluo3 fluorescence for [Ca2+]i and fluorescent antibodies for ceramide abundance. As a result, a 48 h exposure of human erythrocytes to Baicalein was followed by significant decrease of forward scatter (≥10 µM), significant increase of the percentage of annexin-V-binding cells (≥25 µM), significant increase of [Ca2+]i (50 µM) and significant increase of ceramide abundance (50 µM). The effect of Baicalein (50 µM) on annexin-V-binding was significantly blunted but not abrogated by removal of extracellular Ca2+. In conclusion, at the concentrations employed, Baicalein stimulates suicidal erythrocyte death or eryptosis, an effect at least in part due to the combined effects of Ca2+ entry and ceramide formation.
    Toxins 09/2014; 6(9):2771-2786. DOI:10.3390/toxins6092771 · 2.94 Impact Factor
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    • "Accumulating evidence has demonstrated that both of them exhibit extensive pharmacological effects. Due to their relatively low toxicity and the abundance in the root of S. baicalensis, baicalin and baicalein became the most extensively researched components in recent years [16]. Over the past decade, a considerable amount of study has demonstrated that baicalin and baicalein display potent anticancer effects in various types of hematological malignancies [17]. "
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    ABSTRACT: Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized.
    Cancer Letters 08/2014; DOI:10.1016/j.canlet.2014.08.003 · 5.62 Impact Factor
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    • "Importantly, it shows no, or very little, toxicity to normal epithelial and normal peripheral blood and myeloid cells.5 In addition, Scutellaria barbata is widely used as an antitumor agent in China, and the chloroform fraction has been shown to have the strongest cytotoxicity on cancer cell lines, with a lower cytotoxic effect on a normal liver cell line.4 Similarly, although the drug concentration of BA-LP was significantly increased in the liver and lung, it was safe for the liver and lung to some extent. "
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    ABSTRACT: Baicalin (BA) is a major constituent of Scutellaria baicalensis Georgi, a medicinal herb. Previous pharmacokinetic studies of BA showed its low oral bioavailability. The aim of the present study was to develop a novel BA-loaded liposome (BA-LP) to enhance oral bioavailability. BA-LP, composed of BA, Tween(®) 80, Phospholipon(®) 90H, and citric acid at weight ratio of 96/50/96/50, respectively, was prepared by the effervescent dispersion technique and characterized in terms of morphology, size, zeta potential, encapsulation efficiency, and the in vitro release. Pharmacokinetics and biodistribution studies were carried out in rats after oral administration of BA-LP and a carboxymethyl cellulose suspension containing BA (BA-CMC) as a control. BA-LP exhibited a spherical shape by transmission electron microscopy observation. BA-LP had a mean particle size of 373±15.5 nm, zeta potential of -20.1±0.22 mV, and encapsulation efficiency of 82.7%±0.59%. The BA-LP showed a sustained-release behavior, and the in vitro drug-release kinetic model fit well with the Weibull distribution equation: lnln (1/(1-Q)) =0.609 lnt -1.230 (r=0.995). The oral bioavailability and the peak concentration of the BA-LP was threefold and 2.82-fold that of BA-CMC, respectively. The in vivo distribution results indicated that drug concentrations were significantly increased in the liver, kidney, and lung in the case of BA-LP, which were 5.59-fold, 2.33-fold, and 1.25-fold higher than those of BA-CMC, respectively. In conclusion, the study suggested that BA-LP might be a potential oral drug delivery system to improve bioavailability of BA.
    International Journal of Nanomedicine 08/2014; 9(1):3623-3630. DOI:10.2147/IJN.S66312 · 4.38 Impact Factor
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