Pharmacological basis for application of scutellarin in Alzheimer's disease: Antioxidation and antiapoptosis

Abstract

Scutellarin (SC), mainly extracted from the Chinese herb Erigeron breviscapus (vant.), has been reported to possess various pharmacological activities; however, its effects on Alzheimer's disease (AD) have not been systemically reported. The protective effects of SC on AD were investigated using an L-glutamic acid (L-Glu)-damaged HT22 cell apoptosis model and an aluminum chloride plus D-galactose-induced AD mouse model. In L-Glu-damaged HT22 cells, SC significantly increased cell viability, inhibited lactate dehydrogenase release, reduced caspase-3 activity and suppressed apoptosis, which were determined via an MTT assay, an in vitro Toxicology Assay kit, a Caspase-3 activity assay kit, and propidium iodide and Annexin V staining. Furthermore, SC suppressed the accumulation of intracellular reactive oxygen species (ROS), restored the dissipation of mitochondrial membrane potential, enhanced the expression of antiapoptotic proteins and reduced the expression of pro-apoptotic proteins, as determined by immunofluorescence assays and western blotting. In AD mice, SC enhanced vertical and horizontal movements in an autonomic activity test, and reduced the escape latency time in the water maze test. SC reduced the deposition of amyloid β1–42 (Aβ1-42) and the expression of phosphorylated-Tau in the hippocampus as determined by immunohistochemistry analysis, but enhanced the serum levels of Aβ1–42 of AD mice as determined by ELISA. ELISA analyses also revealed that SC enhanced the levels of acetylcholine, and superoxide dismutase in serum and brain lysate, whereas reduced the levels of ROS in brain lysate of AD mice. The present study confirmed that the protective effects of SC in AD in vitro and in vivo are associated with its antioxidant and antiapoptotic properties.

Advances in Chemistry and Bioactivity of Magnoflorine and Magnoflorine-Containing Extracts

“…The oxidative stress plays a prominent role in AD progression through the aggregation of amyloid β (Aβ), which generally accompanies an increased ROS production. Despite previous demonstration of the antioxidant properties of MGN, in this case, MGN did not show inhibitory effect of ROS within tested concentrations [84].…”

“…The MGN's effect has been examined on cyclooxygenase-2 (COX-2), which is known as an important pro-infammatory mediator, and its key product: (prostaglandin E 2 ) PGE2. The experiment showed that expression of both proteins was significantly increased after MGN pre-treatment in LPS-activated U937 macrophages in a dose-dependent manner [84]. Moreover, MGN promoted the phosphorylation and ubiquitynation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), which is responsible for inhibition of NF-κB transcription activity.…”

Docosahexaenoic Acid Increases the Potency of Soluble Epoxide Hydrolase Inhibitor in Alleviating Streptozotocin-Induced Alzheimer’s Disease-Like Complications of Diabetes

“…Nevertheless, a decrease in the level of ACh (Hu et al, 2018) in the brain and an increase in the level of AChE in the hippocampus are documented in Alzheimer’s disease. Further, a reduction in the level of nicotinic receptors, one of the receptors of ACh is noticed in AD patients (Whitehouse et al, 1988; Maelicke and Albuquerque, 2000).…”

Scutellarin Suppresses Platelet Aggregation and Stalls Lesional Progression in Mouse With Induced Endometriosis

“…Of course, this was a very crude estimation. Given that the dosage used orally for mouse ranged from 20 mg/kg 42 to as high as 60 mg/kg 43 which amounts to approximately 5 to 20 mg/kg by iv injection, we decided to have the low- and high-dose set to be 7.5 and 15 mg/kg, respectively.…”