Scutellarin

Glaucoma is a multi-factorial degenerative optic neuropathy disease. The core pathological change caused by various etiologies is the death of retinal ganglion cells (RGCs). Oxidative stress response is one of the important microscopic mechanisms through which glaucoma mechanically damages RGCs. Scutellarin (SCU) is a flavonoid glycoside extracted from the traditional Chinese medicinal material Erigeron breviscapus. It has been proven to exert various pharmacological effects, such as anti-inflammatory, antioxidant, anti-tumor, and anti-neurodegenerative effects. However, its role in protecting the optic nerve in glaucoma remains unclear.

This study aims to identify the specific mechanism of SCU on the R28 cell injury model induced by continuous hydrostatic pressure (CHP) combined with oxygen-glucose deprivation (OGD).

The continuous hydrostatic pressure device was placed in a tri-gas incubator, which was set to maintain a stable, humidified environment at 37°C with 5 % CO₂, 1 % O₂, and 94 % N₂. A model was then created under a continuous hydrostatic pressure of 150 mbar for 24 h to simulate the pathological changes of optic nerve injury under high intraocular pressure conditions, mimicking chronic glaucoma. Cell viability, morphology, apoptosis, and histological changes were subsequently observed. To further investigate the molecular mechanisms, CCK8 assays, ROS assays, flow cytometry, EdU assays, immunofluorescence staining, and Western blots were performed.

Following CHP combined with OGD injury modeling, the expression of ROS and the oxidative stress injury gene 4-HNE was significantly increased. Concurrently, Keap1, a key upstream negative regulator of Nrf2, showed increased expression, while nuclear Nrf2 expression decreased, and the expression of the antioxidant factor HO-1 increased. Furthermore, the expression of p-IKKβ, p-IκBα, and p-p65 was significantly enhanced, indicating the activation of the Nf-kB signaling pathway. The expression of key apoptotic factors Bax and C-caspase-3 was elevated, while Bcl-2 expression was reduced. After SCU intervention, R28 cell proliferation was effectively promoted through the inhibition of oxidative stress. This intervention significantly inhibited the expression of ROS and 4-HNE, decreased Keap1 expression, and increased nuclear Nrf2 expression, thereby further promoting the elevated expression of the antioxidant defense gene HO-1. SCU also significantly inhibited the expression of p-IKKβ, p-IκBα, and p-p65, synergistically regulating and activating the Keap1/Nrf2 pathway, and inhibiting the Nf-κB pathway, thereby further downregulating the expression of apoptosis factors Bax and C-caspase-3, and upregulating Bcl-2 expression.

This study demonstrated that in the R28 cell injury model induced by continuous hydrostatic pressure combined with oxygen-glucose deprivation, SCU can promote the proliferation of R28 cells and reduce the expression of apoptotic factors through the antioxidant stress effect mediated by the Keap1/Nrf2/Nf-κB signaling pathway. This finding provides a potentially effective candidate compound and a mechanistic approach for the drug treatment of glaucoma optic nerve protection.

The characteristic flavor of mutton, commonly described as "muttony" or "goaty", limits consumer acceptance and market potential. This study evaluated the effects of four thyme phenolics, including gallic acid (GA), rosmarinic acid (RA), scutellarin (SCU), and apigenin-7-O-glucuronide (A7G), on the interaction between myofibrillar protein (MP) and six key off-flavor compounds. Gas chromatography-mass spectrometry showed that all four phenolics reduced MP binding with odorants and enhanced their release, with SCU and RA showing the strongest effects. Spectroscopic analyses demonstrated that phenolics induced MP conformational changes, such as decreased α-helix and β-sheet content, reduced surface hydrophobicity, and lower sulfhydryl levels. Docking and simulation confirmed that hydrophobic interactions and hydrogen bonding dominated phenolic-MP binding, and SCU exhibited the highest binding stability among tested phenolics and was likely to competitively displace 4-methyloctanoic acid. These findings provide molecular insights into how thyme phenolics promote off-flavor release and support their application in improving mutton sensory quality.