Narrow Results

Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway occurs commonly in cancer cells and endothelial cells, and contributes to angiogenesis. Wogonin is a compound with many biologically relevant properties. We previously reported that wogonin blocked IL-6-induced angiogenesis through suppression of VEGF expression, an important regulator of angiogenesis. However, the pathway involved in the suppressive effect of wogonin on IL-6-induced VEGF has not been completely clarified. This study aimed to investigate the molecular mechanisms participating in the suppression of wogonin on IL-6-induced VEGF in vitro, focusing on IL-6R/JAK1/STAT3/VEGF pathway. Both STAT3 siRNA and wogonin treatment resulted in an abolition of the expression of VEGF. Moreover, our data revealed that wogonin treatment after STAT3 knock-down did not further suppress VEGF expression. The addition of IL-6R siRNA or wogonin resulted in a decrease in the expression level of the phosphorylated JAK1 protein. Furthermore, wogonin significantly decreased the amount of phosphorylated STAT3. Finally, by EMSA, wogonin suppressed IL-6-induced STAT3 binding activity in a concentration-dependent manner. Taken together, our results show that wogonin suppresses IL-6-induced VEGF by modulating the IL-6R/JAK1/STAT3 signaling pathway. Based on this study, we suggest that wogonin may provide a new potential therapeutic option for treatment of IL-6-related pathological angiogenesis.

Scutellaria baicalensis (Huangqin in Chinese) is a major traditional Chinese medicine (TCM) herb, which has a long history of use in the treatment of a variety of symptoms correlated with cancer. In the past decade, the potential of S. baicalensis and single compounds derived from it as anticancer agents targeting various pathways has received extensive research attention. Specifically, the proliferation and metastases inhibiting properties of the single compounds in cancer have been studied; however, the underlying mechanisms remain unclear. This review summarizes the various mechanisms, pathways and molecular targets involved in the anticancer activity of S. baicalensis and its single compounds. However, the aim of this review is to provide a more thorough view of the last 10 years to link traditional use with modern research and to highlight recently discovered molecular mechanisms. Extracts and major flavonoids derived from S. baicalensis have been found to possess anticancer effects in multiple cancer cell lines both in vitro and in vivo. Further investigation is warranted to better understand the underlying mechanisms and to discover novel targets and cancer therapeutic drugs that may improve both the survival and quality of life of cancer patients.

Obesity leads to structural and functional changes in the heart and has become a global burden of disease. Wogonin is a natural flavonoid which possesses cardioprotective, neuroprotective, and anti-cancer properties. However, the effects of wogonin on obesity-induced cardiac injury remain unclear. In this study, the high-fat diet (HFD)-induced obese mice model was successfully established. Moreover, HFD induced a fat mass and cardiac injury in mice. More importantly, wogonin treatment reduced fat mass and improved cardiac function of HFD mice. Consistently, wogonin ameliorated myocardial lipid metabolism in HFD-induced obese mice by reducing triglyceride (TC), total cholesterol (TG), and non-esterified fatty acid (NEFA) levels in serum, as well as the TG and free fatty acids (FFA) levels in heart tissues. Interestingly, wogonin treatment alleviated myocardial pyroptosis in HFD-induced obese mice. Through bioinformatic analysis, the IL-17 signaling pathway was predicted to be modulated by wogonin. Results showed that wogonin deactivated the IL-17 signaling pathway in HFD mice. These findings suggested that wogonin ameliorated obesity-induced disorders of lipid metabolism and cardiac injury via suppressing pyroptosis and deactivating the IL-17 signaling pathway, which provided a novel therapeutic strategy for HFD-induced cardiac injury.

Radiotherapy plays a crucial role in the multimodal treatment of breast cancer. However, radioresistance poses a significant challenge to its effectiveness, hindering successful cancer therapy. Emerging evidence indicates that Nrf2 and HIF-1$\alpha$ are critical regulators of cellular anti-oxidant responses and that their overexpression significantly promotes radioresistance. Wogonin (WG), the primary component isolated from Scutellaria baicalensis, exhibits potential antitumor and reversal of multidrug resistance activities. Nevertheless, the role of WG in radioresistance remains unclear. This study aims to explore the effects of WG on the radioresistance of breast cancer. Our results indicate that Nrf2 and HIF-1$\alpha$ overexpression was observed in breast cancer tissues and was correlated with the histological grading of the disease. Radiation further increased the levels of Nrf2 and HIF-1$\alpha$ in breast cancer cells. However, WG demonstrated the ability to induce cell apoptosis and reverse radioresistance by inhibiting the Nrf2/HIF-1$\alpha$ pathway. These effects were also confirmed in xenograft mice models. Mechanistically, WG enhanced the level of the Nrf2 inhibitor Keap1 through reducing CpG methylation in the promoter region of the Keap1 gene. Consequently, the Nrf2/HIF-1$\alpha$ pathway, along with the Nrf2- and HIF-1$\alpha$-dependent protective responses, were suppressed. Taken together, our findings demonstrate that WG can epigenetically regulate the Keap1 gene, inhibit the Nrf2/HIF-1$\alpha$ pathway, induce apoptosis in breast cancer cells, and diminish acquired radioresistance. This study offers potential strategies to overcome the limitations of current radiotherapy for breast cancer.

Colorectal cancer is the third leading cause of cancer-related death worldwide. Hence, there is a need to identify new therapeutic agents to improve the current repertoire of therapeutic drugs. Wogonin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antitumor activity. Our study aimed to further explore the inhibitory effects of wogonin on colorectal cancer and its specific mechanism. The results showed that wogonin significantly inhibited the proliferation of colorectal cancer cells as well as their ability to invade and metastasize. We detected phosphorylation of tumor-associated signaling pathways using a phosphorylated protein microarray and found that wogonin intervention significantly inhibited the phosphorylation level of the AKT protein in colorectal cancer cells. Through in vitro and in vivo experiments, it was confirmed that wogonin exerted its antitumor effects against colorectal cancer by inhibiting phosphorylation in the AKT pathway. Our discovery of wogonin as an inhibitor of AKT phosphorylation provides new opportunities for the pharmacological treatment of colorectal cancer.

Scutellaria baicalensis (Huangqin in Chinese) is a major traditional Chinese medicine (TCM) herb, which has a long history of use in the treatment of a variety of symptoms correlated with cancer. In the past decade, the potential of S. baicalensis and single compounds derived from it as anticancer agents targeting various pathways has received extensive research attention. Specifically, the proliferation and metastases inhibiting properties of the single compounds in cancer have been studied; however, the underlying mechanisms remain unclear. This review summarizes the various mechanisms, pathways and molecular targets involved in the anticancer activity of S. baicalensis and its single compounds. However, the aim of this review is to provide a more thorough view of the last 10 years to link traditional use with modern research and to highlight recently discovered molecular mechanisms. Extracts and major flavonoids derived from S. baicalensis have been found to possess anticancer effects in multiple cancer cell lines both in vitro and in vivo. Further investigation is warranted to better understand the underlying mechanisms and to discover novel targets and cancer therapeutic drugs that may improve both the survival and quality of life of cancer patients.