Samarcandin protects against testicular ischemia/reperfusion injury in rats via activation of Nrf2/HO-1-mediated antioxidant responses

Abdel‐Kader, Maged S.; Abdel-Rahman, Rehab F.; Althurwi, Hassan N.; Soliman, Gamal A.; Ogaly, Hanan A.; Albaqami, Faisal F.

doi:10.1016/j.jsps.2023.05.007

Cited by 6 publications

(2 citation statements)

References 56 publications

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“…A natural compound library was screened by using RGS5–TNFR2 interaction-based NanoBit protein–protein assay. It was revealed that two compounds feshurin, also reported as samarcandin [ 58 ], and butein showed a profound inhibition on the RGS5–TNFR2 interaction in a dose-dependent manner (Fig. 6 E, F).…”

Section: Resultsmentioning

confidence: 94%

“…Moreover, RGS5-mediated activation of TNFR signaling can be precluded by using small molecular compounds feshurin and butein. Feshurin is one of the sesquiterpene coumarins from Ferula samarkandica Korovin, which protects against testicular ischemia/reperfusion injury and controls the inflammatory mediators [ 58 , 71 ]. Relatively, butein, a biologically active flavonoid that is known to be ubiquitous in medicinal plants, shows anti-inflammatory effects in multiple types of cells [ 72 – 75 ].…”

Section: Discussionmentioning

confidence: 99%

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RGS5 augments astrocyte activation and facilitates neuroinflammation via TNF signaling

Yin,

Ma,

Sun

et al. 2023

J Neuroinflammation

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Astrocytes contribute to chronic neuroinflammation in a variety of neurodegenerative diseases, including Parkinson's disease (PD), the most common movement disorder. However, the precise role of astrocytes in neuroinflammation remains incompletely understood. Herein, we show that regulator of G-protein signaling 5 (RGS5) promotes neurodegenerative process through augmenting astrocytic tumor necrosis factor receptor (TNFR) signaling. We found that selective ablation of Rgs5 in astrocytes caused an inhibition in the production of cytokines resulting in mitigated neuroinflammatory response and neuronal survival in animal models of PD, whereas overexpression of Rgs5 had the opposite effects. Mechanistically, RGS5 switched astrocytes from neuroprotective to pro-inflammatory property via binding to the receptor TNFR2. RGS5 also augmented TNFR signaling-mediated pro-inflammatory response by interacting with the receptor TNFR1. Moreover, interrupting RGS5/TNFR interaction by either RGS5 aa 1–108 or small molecular compounds feshurin and butein, suppressed astrocytic cytokine production. We showed that the transcription of astrocytic RGS5 was controlled by transcription factor early B cell factor 1 whose expression was reciprocally influenced by RGS5-modulated TNF signaling. Thus, our study indicates that beyond its traditional role in G-protein coupled receptor signaling, astrocytic RGS5 is a key modulator of TNF signaling circuit with resultant activation of astrocytes thereby contributing to chronic neuroinflammation. Blockade of the astrocytic RGS5/TNFR interaction is a potential therapeutic strategy for neuroinflammation-associated neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 94%