Multiple neuroprotective features of Scutellaria pinnatifida–derived small molecule

Abstract

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders with no precise etiology. Multiple lines of evidence support that environmental factors, either neurotoxins or neuroinflammation, can induce Parkinsonism. In this study, we purified an active compound, neobaicalein (Skullcapflavone II), from the roots of Scutellaria pinnatifida (S. pinnatifida). Neobaicalein not only had protective impacts on rotenone-induced neurotoxicity but in glial cultures, it dampened the inflammatory response when stimulated with lipopolysaccharide (LPS). Neobaicalein had high antioxidant activity without any obvious toxicity. In addition, it could raise the cell viability, decrease early apoptosis, reduce the generation of reactive oxygen species (ROS), and keep the neurite's length normal in the treated SH-SY5Y cells. Pathway enrichment analysis (PEA) and target prediction provided insights into the PD related genes, protein-protein interaction (PPI) network, and the key proteins enriched in the signaling pathways. Furthermore, docking simulation (DS) on the proteins of the PD-PPI network revealed that neobaicalein might interact with the key proteins involved in PD pathology, including MAPK14, MAPK8, and CASP3. It also blocks the destructive processes, such as cell death, inflammation, and oxidative stress pathways. Our results demonstrate that neobaicalein alleviates pathological effects of factors related to PD, and may provide new insight into PD therapy.

Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells

“…SFII is another bioactive flavonoid compound found in the root extracts of S. baicalensis [ 41 ]. It is also known as neobaicalein, due to its structural similarity to baicalein [ 42 ]; however, SFII is not as actively studied, probably owing to its relatively low abundance in S. baicalensis extracts [ 43 ]. Nevertheless, a few previous studies have reported the anti-inflammatory activity of SFII.…”

“…The range of SFII concentrations employed has varied widely across studies, due to its differential range of cytotoxicity according to cell types. For instance, SFII concentrations more than 2 μM were toxic to bone marrow-derived macrophages [ 31 ], but no cytotoxicity was observed till 10 μM in human dermal fibroblasts [ 32 ], and at 20–250 μM in SH-SY5Y neuroblastoma cells [ 42 ]. Similar to SH-SY5Y cells, a SFII concentration range of 1–25 μg/mL (=2.7–66.7 μM) was used in the current study in HaCaT cells, with no cytotoxicity.…”

Neobaicalein prevents isoflurane anesthesia-induced cognitive impairment in neonatal mice via regulating CREB1

“…Neobaicalein (Skullcapflavone II) (Neob), an active compound, is extracted from the roots of Scutellaria pinnatifida . 12 , 13 , 14 Parsafar, S., et al confirmed that Neob protected the neurons from rotenone-induced neurotoxicity and inhibited inflammation under Lipopolysaccharide (LPS) treatment. 15 , 16 Additionally, Neob could increase antioxidant activity.…”

“… 15 , 16 Additionally, Neob could increase antioxidant activity. 14 Moreover, accumulating studies indicated that Neob had remediation activity in several diseases. It inhibited the function of human skin fibroblasts by promoting type I collagen degradation, which damaged the integrity of the extracellular matrix and prevented airway inflammation in an asthma mouse model.…”

Characterization of exogenous αSN response genes and their relation to Parkinson’s disease using network analyses

“…All network illustrations and analyses were performed using Cytoscape version 3.7.2 (Shannon et al, 2003). The methodology used was previously reported (Parsafar et al, 2020). To identify the PD-related genes, we used the DisGeNET platform (version 7.0, https://www.disgenet.org/ home/), which contains 1,134,942 gene-disease associations (Piñero et al, 2015).…”