Natural flavone; anti-inflammatory, anti-tumor, anti-oxidant, neuroprotective, anti-fungal activities

Baicalein (0-200 μM, 24 hours) can lower the levels of TNF-α and iNOS mRNA expression and decrease NO generation in LPS-activated RAW264.7 cells [1]. HT1080 is inhibited by baicalein (0-50 μM, 24 hours). In HT1080 cells, the expression of MMP-2, -9, and -14 as well as the activation of NF-κB are inhibited by scutellarein (0-50 μM, 24 hours) [3]. DPPH, ABTS+·, and ·OH have scavenging capabilities for baicalein (IC50 values of 16.84 μM, 3.00 μM, and 0.31 mM, correspondingly) [4].

In an HFD animal model, baicalein (50 mg/kg in diet for 16 weeks) demonstrated hepatoprotective, lipid-lowering, and anti-stress properties [2]. Baicalein, at doses of 50 and 500 mg/kg, controls the formation of tumors in the HT108 xenograft mouse model [3]. Neuronal damage can be mitigated and the neck's brain structure preserved by scutellarein (0–1.40 mmol/kg, neck) [5].

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Central obesity, dyslipidemia, inflammation, and hepatic steatosis were developed in mice fed with HFD. Administration of Sc at a dose of 50 mg/kg for 16 weeks effectively attenuated all obesity indicators tested. Further studies revealed the antagonistic effect of Sc on hyperlipidemia was a result of the repression of the lipid synthesis pathway, de novo pathway, HMGCR, promoting fatty acid oxidation (PPARα, CPT-1a) and increased cholesterol output (PPARγ-LXRα-ABCA1). The anti-inflammatory effect was attributed to blocking the expression of inflammatory genes, including TNF-α, IL-6, NF-κB.[2]

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Moreover, an in vivo experiment using Balb/c nude mice revealed that the volume and weight of the tumors were markedly reduced following treatment with scutellarein. We also analyzed the effects of scutellarein on the markers of metastasis, using the HT1080 cells. The results indicated that scutellarein potently inhibited cell migration, invasion and the expression and activity of matrix metalloproteinase (MMP)-2, -9 and -14. Furthermore, MMP activation and cell survival were suppressed due to the scutellarein-mediated downregulation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation. In conclusion, our data suggest that scutellarein has the ability to attenuate the development of fibrosarcoma and inhibit cancer cell metastasis.[3]

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Scutellarin had protective effects against neuronal injury, however, there are few studies on the protective effect of scutellarein, which is the main metabolite of scutellarin in vivo. This study investigated whether the neural injury by ischemia/reperfusion would be influenced by different doses of scutellarin and scutellarein. Male Wistar rats were orally administered with scutellarin and scutellarein at the doses of 0.09, 0.17, 0.35, 0.70, 1.40 mmol/kg, respectively; then after six consecutive days, they were subjected to global ischemia by occlusion of the bilateral common carotid arteries (BCCAO). After reperfusion for about 21 h, neurological and histological examinations were performed. The present results showed that scutellarein attenuated neuronal cell damage, reduced cerebral water content, regulated the expression of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), γ-aminobutyric acid (GABA) and taurine (Tau), and improved the Ca(2+)-ATPase and Na(+),K(+)-ATPase activity. Meanwhile, significant difference was found among various doses of scutellarin and scutellarein. Our studies indicated that scutellarin and scutellarein could improve neuronal injury, and scutellarein had better protective effect than scutellarin in rat cerebral ischemia[5].

Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, it is very difficult to obtain scutellarein in nature compared with scutellarin. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. The in vitro antioxidant activities of scutellarein were evaluated by measuring its scavenging capacities toward DPPH, ABTS(+•), (•)OH free radicals and its protective effect on H(2)O(2)-induced cytotoxicity in PC12 cells using MTT assay method. The results showed that essential point to the synthesis was the implementation of H(2)SO(4) in 90% ethanol in N(2) atmosphere; scutellarein had stronger antioxidant activity than scutellarin. The results have laid the foundation for further research and the development of scutellarein as a promising candidate for ischemic cerebrovascular disease[4].

Fibrosarcoma is an aggressive and highly metastatic cancer of the connective tissue, for which effective therapeutic methods are limited. Recently, there has been a renewed interest in small molecular compounds from natural products in the treatment of cancer. In the present study, researchers investigated the compound, scutellarein, extracted from the perennial herb Scutellaria lateriflora, and it was found to possess anticancer potential. Cell proliferation assay and cell cycle analysis revealed that the proliferation rate of HT1080 human fibrosarcoma cells was significantly suppressed by treatment with scutellarein through the induction of apoptosis[3].

Animal/Disease Models: HFD mice [2]
Doses: 50 mg/kg
Route of Administration: In diet, 16 weeks
Experimental Results: diminished lipid accumulation and inflammatory factor levels in the liver. Lost weight.

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The study was conducted using a well-established mouse model of obesity induced by high-fat diet (HFD) feeding. Anti-obesity effects were assessed using body weight, abdominal circumference, white adipose tissue, adiposity index, and fatty liver index. Lipid lowering and liver protective effects were examined by blood sample analysis. Lipid dystopia deposition was confirmed by liver pathological sections. The signaling pathways of lipid metabolism and cytokine/inflammatory mediator were evaluated using Real-Time PCR and Western blot.[2]

Metabolism / Metabolites: Scutellarein has known human metabolites that include Scutellarein 7-O-glucuronide.

[1]. Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity. Korean J Physiol Pharmacol. 2015 Sep;19(5):441-9.

[2]. Novel anti-obesity effect of scutellarein and potential underlying mechanism of actions. Biomed Pharmacother. 2019 Sep;117:109042.

[3]. Scutellarein inhibits cancer cell metastasis in vitro and attenuates the development of fibrosarcoma in vivo. Int J Mol Med. 2015 Jan;35(1):31-8.

[4]. Synthesis and bio-activity evaluation of scutellarein as a potent agent for the therapy of ischemic cerebrovascular disease. Int J Mol Sci. 2011;12(11):8208-16.

[5]. Neuroprotective effects of scutellarin and scutellarein on repeatedly cerebral ischemia-reperfusion in rats. Pharmacol Biochem Behav. 2014 Mar;118:51-9.

Scutellarein is flavone substituted with hydroxy groups at C-4', -5, -6 and -7. It has a role as a metabolite. It is functionally related to an apigenin. It is a conjugate acid of a scutellarein(1-). Scutellarein has been reported in Salvia rosmarinus, Caryopteris tangutica, and other organisms.

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Scutellarein (Sc), a natural compound and an active ingredient of Erigeron breviscapus (vant.), shows anti-inflammatory and antioxidant properties and has the potential for obesity treatment. However, no previous in vivo study has been conducted to assess the role of Sc in obesity. This study investigated the effects of Sc on obesity and associated hyperlipidemia and fatty liver and explores the underlying mechanisms of action in a mouse model.[2]

C15H10O6

286.24

286.05

C, 62.94; H, 3.52; O, 33.54

529-53-3

529-53-3

5281697

Light yellow to yellow solid powder

1.4

O=C1C=C(C2=CC=C(O)C=C2)OC3=C1C(O)=C(O)C(O)=C3

JVXZRQGOGOXCEC-UHFFFAOYSA-N

InChI=1S/C15H10O6/c16-8-3-1-7(2-4-8)11-5-9(17)13-12(21-11)6-10(18)14(19)15(13)20/h1-6,16,18-20H

5,6,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one

Scutellarein; Scutellarein; 529-53-3; 6-Hydroxyapigenin; 5,6,7,4'-Tetrahydroxyflavone; 5,6,7-trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one; 4',5,6,7-tetrahydroxyflavone; 5,6,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one; 4',5,6,7-Tetrahydroxyflavone

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~57 mg/mL (~199.1 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (7.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)