Baicalein ameliorated cerebral ischemia-reperfusion injury dependent on calpain 1/AIF pathway

Cerebral ischemia-reperfusion (CIR) has become the leading cause of death and disability. Baicalein is a natural bioactive ingredient extracted from Scutellaria baicalensis Georgi and has neuroprotective activity. In our work, baicalein was found to reduce neurological deficits, brain water content, infarct area and neuronal death of rats induced by middle cerebral artery occlusion/reperfusion. In vitro, oxygen-glucose deprivation/reperfusion induced inordinate ROS production and apoptosis that could be reversed by baicalein. Our study revealed for the first time that baicalein has the potential to binds and inhibits the activity of calpain 1, thereby inhibiting AIF nuclear translocation. These findings demonstrated that baicalein protected against CIR injury via inhibiting AIF nuclear translocation by inhibiting calpain 1 activity.

Baicalein Attenuates Hepatocellular Carcinoma Cell Survival and Induces Apoptosis Through the miR‑3178/HDAC10 pathway

Hepatocellular carcinoma (HCC) is the most common type of hepatic malignancies with high mortality and poor prognosis and is the third most common cause of malignancies death worldwide which is more than 700,000 deaths per year. Baicalein, one of the major and bioactive flavonoid isolated from Scutellaria baicalensis Georgi, which is reported to have anti-proliferation effect in varying cancers, including HCC, whose underlying molecular mechanism is still largely unknown. In this study, the results showed that administration of baicalein significantly inhibited proliferation and colony formation, blocked cell cycle arrest at the S phase, and promoted apoptosis in HCC cells MHCC-97H and SMMC-7721 in vitro and reduced HCC tumor volume and weight in vivo. Increased microRNA (miR)‑3178 levels and decreased histone deacetylase 10 (HDAC10) expression were found in cells treated with baicalein and in patients’ HCC tissues. HDAC10 was identified as a target gene of miR‑3178 by luciferase activity and western blot. Both baicalein treatment and overexpression of miR-3178 could down-regulate protein expression of HDAC10 and inactivated AKT, MDM2/p53/Bcl2/Bax and FoxO3α/p27/CDK2/Cyclin E1 signal pathways. Not only that, knockdown of miR‑3178 could partly abolish the effects of baicalein and the restoration of HDAC10 could abated miR-3178-mediated role in HCC cells. Collectively, baicalein inhibited cell viability, blocks cell cycle and induces apoptosis in HCC cells by regulating the miR‑3178/HDAC10 pathway. This finding indicated that baicalein might be promising for treatment of HCC.

Baicalein Inhibits Metastatic Phenotypes in Nasopharyngeal Carcinoma Cells via a Focal Adhesion Protein Integrin β8

Baicalein, a prominent flavonoid from the indigenous herbal plant Scutellaria baicalensis Georgi, possesses broad-spectrum anticancer activities. However, the biological effects of baicalein on nasopharyngeal carcinoma (NPC) and its underlying mechanisms remain unclarified. Thus, in this study, we examined the effects of baicalein on NPC cell lines and investigated the corresponding molecular mechanism through transcriptome profiling. In the study, four NPC cell lines were treated with various concentrations of baicalein at different time points. Cellular toxicity and proliferative inhibition of baicalein were examined by MTT assay. Metastatic phenotypes of NPC cells were investigated by wound healing, transwell, and adhesion assays. Additionally, microarray experiments were performed to determine the cellular pathways affected by baicalein. The expression and localization of the integrin β8 were validated by western immunoblotting and immunofluorescence. Our results revealed that baicalein exhibited its cytotoxicity and antiproliferative activity on all tested NPC cell lines. It also significantly inhibited metastatic phenotypes at sub-lethal concentrations. Transcriptomic analysis showed that baicalein significantly affected the focal adhesion pathway in NPC, where integrin β8 was greatly diminished. Thus, the present study results suggested that baicalein inhibits the metastatic phenotypes of NPC cells by modulating integrin β8, one of the major molecules in a focal adhesion pathway.

Baicalein Ameliorates Aβ-Induced Memory Deficits and Neuronal Atrophy via Inhibition of PDE2 and PDE4

Inhibition of phosphodiesterase 2 and 4 (PDE2A and PDE4) increases the intracellular cAMP and/or cGMP levels, which may prevent Amyloid β 42 oligomers (Aβ) related cognitive impairment and dementias. Baicalein, one of natural flavones found in the root of Scutellaria baicalensis Georgi, has a wide range of pharmacological activities including antioxidant and anti-inflammatory effects. However, no studies suggest whether baicalein mediated anti-Alzheimer’s disease (AD) events involve PDEs subtypes-mediated neuroprotective pathways. The present study examined whether memory enhancing effects of baicalein on Aβ- induced cognitive impairment are related to regulating neuroplasticity via PDE2 and PDE4 subtypes dependent cAMP/cGMP neuroprotective pathway. The results suggested that microinjected of Aβ into CA1 of hippocampus induced cognitive and memory impairment in mice, as evidenced by decreased recognition index in the novel object recognition (NOR) task, impaired memory acquisition, retention and retrieval in the Morris water maze (MWM) and shuttle box tests. These effects were reversed by treatment with baicalein for 14 days. Moreover, Aβ-induced neuronal atrophy and decreased expression of two synaptic proteins, synaptophysin and PSD 95, were prevented by baicalein. The increased expression of PDE2A and PDE4 subtypes (PDE4A, PDE4B and PDE4D), and decreased levels of cAMP/cGMP, pCREB/CREB and BDNF induced by Aβ were also blocked by chronic treatment of baicalein for 14 days. These findings suggest that baicalein’s reversal of Aβ-induced memory and cognitive disorder may involve the regulation of neuronal remodeling via regulation of PDE2/PDE4 subtypes related cAMP/cGMP -pCREB-BDNF pathway.

Improvement of Bronchial Immune Hypersensitivity Reaction Using Extracts from Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis Georgi

Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis Georgi (skullcap) have been used as safe raw materials for drinking or as traditional medicines in Korea. In this study, we investigated the potential therapeutic effects of ovalbumin-induced asthma in a mouse model. After establishing the model, mice were treated with a mixture of chrysanthemum and skullcap extracts at different mixing ratios (6 : 4, 7 : 3, and 8 : 2). Immune cell counts and the production of various inflammatory cytokines were measured using biochemical tests. Among the mixtures tested, the 7 : 3 ratio (CS73) showed the most pronounced effects. CS73 significantly reduced the levels of the inflammatory cytokines interleukin- (IL-) 1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, and IL-17E in the serum and bronchoalveolar lavage fluid of asthmatic mice. In addition, CS73 treatment significantly increased the production of IL-2 and interferon-γ and decreased the production of immunoglobulin E, histamine, and thymic stromal lymphopoietin in asthmatic mice compared to the control group. Our results suggest that the combination of chrysanthemum and skullcap extracts, especially at a 7 : 3 ratio, can be used to improve bronchial health and contribute to improved public health.

Development of a Simultaneous Analysis Method for Quality Control of a Traditional Herbal Formula, Daeshiho-Tang, Using 10 Marker Components

Daeshiho-tang (DSHT) is a traditional herbal formula consisting of six herbal medicines: Bupleurum falcatum L., Scutellaria baicalensis Georgi, Paonia lactiflora Pall., Pheum palmatum L., Poncirus trifoliata (L.) Raf., and Pinellia ternate (Thunb.) Makino. In this study, we developed a simultaneous analysis method based on high-performance liquid chromatography for the quality control of DSHT. Chromatographic separation of 10 marker components (gallic acid, albiflorin, paeoniflorin, naringin, benzoic acid, baicalin, poncirin, wogonoside, baicalein, and wogonin) was achieved using a water–acetonitrile system as the mobile phase with a SunFire C18 reversed-phase column. The developed analytical method was validated with respect to linearity, limit of detection, limit of quantitation, recovery, and precision. Among the 10 markers of DSHT in the established assay, baicalin, the main compound of Scutellaria baicalensis Georgi, was present in the highest concentration (36.86–46.17 mg/g). The validated assay will be useful for the quality control of DSHT.

Huanglianjiedu Decoction as an effective treatment for oral squamous cell carcinoma based on network pharmacology and experimental validation

Background Oral squamous cell carcinoma (OSCC) is one of malignant tumors in oral and maxillofacial region with high fatality. Huanglianjiedu Decoction (HLJDD) is a well-known traditional Chinese medicinal prescription, which consists of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Phellodendron amurense Rupr and Gardenia jasminoides J.Ellis. Some clinical studies showed HLJDD had good effectiveness on OSCC, but the mechanism is unclear. Methods In this study, potential components of HLJDD and putative targets were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Combining with potential targets of OSCC searched from Therapeutic Target Database (TTD) and Online Mendelian Inheritance in Man (OMIM), we drew protein–protein interaction (PPI) network by Cytoscape v3.2.0 software. After topological analysis we got core targets and further did Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then we did the in vitro experiments to verify the major biological processes (cell cycle, apoptosis and proliferation) and signaling pathways (mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), protein kinase B (AKT)) on OSCC cell lines, SCC-25 and CAL-27. Results The potential component targets number of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Phellodendron amurense Rupr and Gardenia jasminoides J.Ellis were 39, 93, 81and 88, respectively. Then we got 52 core targets which enriched in cell cycle, apoptosis, proliferation, MAPK activation etc. and obtained TOP30 pathways. On SCC-25 and CAL-27, HLJDD suppressed cell proliferation, induced late apoptosis and inhibited cell invasion and migration which were consistent with the results from network pharmacology analysis. Additionally, in cell cycle, we confirmed HLJDD inhibited G1 phase and arrested in S phase to reduce cell proliferation on SCC-25. In signaling pathways, HLJDD inhibited the phosphorylation of extracellular regulatory protein kinase 1/2 (ERK1/2) and NF-κB p65 (S468) on SCC-25 and CAL-27. Conclusions HLJDD played a potential therapeutic role on OSCC via inhibiting p-ERK1/2 and p-NF-κB p65 (S468). Graphical abstract