Skullcapflavone II

FASEB J . 2019 Feb;33(2):2026-2036.

Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling[Pubmed: 30216110]

Abstract Many bone diseases, such as osteoporosis and rheumatoid arthritis, are attributed to an increase in osteoclast number or activity; therefore, control of osteoclasts has significant clinical implications. This study shows how Skullcapflavone II (SFII), a flavonoid with anti-inflammatory activity, regulates osteoclast differentiation, survival, and function. SFII inhibited osteoclastogenesis with decreased activation of MAPKs, Src, and cAMP response element-binding protein (CREB), which have been known to be redox sensitive. SFII decreased reactive oxygen species by scavenging them or activating nuclear factor-erythroid 2-related factor 2 (Nrf2), and its effects were partially reversed by hydrogen peroxide cotreatment or Nrf2 deficiency. In addition, SFII attenuated survival, migration, and bone resorption, with a decrease in the expression of integrin β3, Src, and p130 Crk-associated substrate, and the activation of RhoA and Rac1 in differentiated osteoclasts. Furthermore, SFII inhibited osteoclast formation and bone loss in an inflammation- or ovariectomy-induced osteolytic mouse model. These findings suggest that SFII inhibits osteoclastogenesis through redox regulation of MAPKs, Src, and CREB and attenuates the survival and resorption function by modulating the integrin pathway in osteoclasts. SFII has therapeutic potential in the treatment and prevention of bone diseases caused by excessive osteoclast activity.-Lee, J., Son, H. S., Lee, H. I., Lee, G.-R., Jo, Y.-J., Hong, S.-E., Kim, N., Kwon, M., Kim, N. Y., Kim, H. J., Lee, Y. J., Seo, E. K., Jeong, W. Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling.

Int Immunopharmacol. 2012 Apr;12(4):666-74.

Skullcapflavone II inhibits ovalbumin-induced airway inflammation in a mouse model of asthma.[Pubmed: 22314230]

Skullcapflavone II is a flavonoid derived from Scutellaria baicalensis, a widely used herbal medicine in anti-inflammatory and anticancer therapy in Korea. Skullcapflavone II antagonized the bradykinin receptor more potently than any of the other flavonoids derived from this plant.
METHODS AND RESULTS:
Here, we were investigated its therapeutic effects in a mouse model of ovalbumin (OVA)-induced allergic asthma. Administration of Skullcapflavone II significantly reduced airway hyperresponsiveness (AHR), airway eosinophilia, Th2 cytokine production, and increased transforming growth factor-β1 (TGF-β1) levels in bronchoalveolarlavage (BAL) fluids and lungs from OVA-sensitized and -challenged mice. Skullcapflavone II administration also significantly suppressed subepithelial collagen deposition and goblet cell hyperplasia, elevated Smad7 expression and suppressed pSmad2/3 levels.
CONCLUSIONS:
Collectively, these findings indicate that Skullcapflavone II, a potential bradykinin antagonist, reduced the major pathophysiological features of allergic asthma, at least in part by acting on TGF-β1/Smad signaling pathways. Thus, Skullcapflavone II may have therapeutic potential for the treatment of allergic asthma.

Arch Pharm Res. 1999 Feb;22(1):18-24.

Inhibition of cyclooxygenase/lipoxygenase from human platelets by polyhydroxylated/methoxylated flavonoids isolated from medicinal plants.[Pubmed: 10071954]

Various flavonoid derivatives were previously reported to possess the inhibitory activity on cyclooxygenase/lipoxygenase. And these properties of flavonoids might contribute to their anti-inflammatory activity in vivo.
METHODS AND RESULTS:
In this study, several polyhydroxylated/methoxylated flavonoid derivatives such as oroxylin A, wogonin, Skullcapflavone II, tectorigenin and iristectorigenin A were isolated from the medicinal plants. These compounds were evaluated for their inhibitory effects on cyclooxygenase/lipoxygenase from the homogenate of human platelets in vitro. It was found that isoflavones including daidzein and tectorigenin possessed the inhibitory activity on cyclooxygenase, although the potency of inhibition was far less than that of indomethacin. In addition, oroxylin A, baicalein and wogonin inhibited 12-lipoxygenase activity without affecting cyclooxygenase, which suggested that 5,6,7- or 5,7,8-trisubstitutions of A-ring of flavone gave favorable results.
CONCLUSIONS:
The IC50 values of oroxylin A and NDGA against 12-lipoxygenase were found to be 100 and 1.5 microM, respectively.