Irisin protects against cerebral ischemia reperfusion injury in a SIRT3-dependent manner DOI Creative Commons

Yushuang Cong,

Rui Guo, Chenglong Li

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

Cerebral ischemia-reperfusion (CIR) injury critically impacts stroke prognosis, yet effective therapeutic strategies remain limited. Irisin, an exercise-induced myokine, exhibits neuroprotective effects against cerebral ischemia. SIRT3, a mitochondrial deacetylase, is similarly implicated in mitigating injury. Given that irisin exerts protection via AMPK/PGC-1α pathway activation and SIRT3 acts downstream of PGC-1α , we hypothesized mediates irisin's neuroprotection CIR In vivo was modeled by inducing transient middle artery occlusion (MCAO) mice, while vitro conditions were replicated using oxygen-glucose deprivation (OGD) PC12 neuronal cultures. To elucidate the mechanistic role targeted interventions implemented: expression silenced transfection with small interfering RNA (siRNA), its enzymatic activity pharmacologically inhibited 3-TYP, selective inhibitor. Apoptotic systematically evaluated through TUNEL staining, Western blot analysis caspase-3, Bax Bcl-2. Oxidative stress parameters, including malondialdehyde (MDA) levels glutathione (GSH) content, measured colorimetric assays. Neurological function mice quantified modified Severity Score (mNSS). Our results demonstrated mitigates apoptosis oxidative dose-dependently activating signaling. At optimal dosage, effectively restored levels, reduced damage, improved neurological recovery models. Notably, significantly attenuated specific Further validation experiments revealed overexpression synergistically enhanced irisin-mediated OGD-induced injury, whereas knockout substantially diminished efficacy. data shown exerted protective at least part, activation. This study establishes irisin/SIRT3 as novel target for ischemic stroke, providing insights future interventions.

Language: Английский

From Traditional Efficacy to Drug Design: A Review of Astragali Radix DOI Creative Commons
Xiaojie Jin, Huijuan Zhang,

Xiaorong Xie

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 413 - 413

Published: March 14, 2025

Astragali Radix (AR), a traditional Chinese herbal medicine, is derived from the dried roots of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (A. mongholicus, AMM) or Bge membranaceus, AM). According to medicine (TCM) theory, AR believed tonify qi, elevate yang, consolidate body’s surface reduce sweating, promote diuresis and swelling, generate body fluids, nourish blood. It has been widely used treat general weakness chronic illnesses improve overall vitality. Extensive research identified various medicinal properties AR, including anti-tumor, antioxidant, cardiovascular-protective, immunomodulatory, anti-inflammatory, anti-diabetic, neuroprotective effects. With advancements in technology, methods such as computer-aided drug design (CADD) artificial intelligence (AI) are increasingly being applied development TCM. This review summarizes progress on over past decades, providing comprehensive overview its efficacy, botanical characteristics, distribution, chemical constituents, phytochemistry. aims enhance researchers’ understanding pharmaceutical potential, thereby facilitating further utilization.

Language: Английский

Citations

0

Irisin protects against cerebral ischemia reperfusion injury in a SIRT3-dependent manner DOI Creative Commons

Yushuang Cong,

Rui Guo, Chenglong Li

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

Cerebral ischemia-reperfusion (CIR) injury critically impacts stroke prognosis, yet effective therapeutic strategies remain limited. Irisin, an exercise-induced myokine, exhibits neuroprotective effects against cerebral ischemia. SIRT3, a mitochondrial deacetylase, is similarly implicated in mitigating injury. Given that irisin exerts protection via AMPK/PGC-1α pathway activation and SIRT3 acts downstream of PGC-1α , we hypothesized mediates irisin's neuroprotection CIR In vivo was modeled by inducing transient middle artery occlusion (MCAO) mice, while vitro conditions were replicated using oxygen-glucose deprivation (OGD) PC12 neuronal cultures. To elucidate the mechanistic role targeted interventions implemented: expression silenced transfection with small interfering RNA (siRNA), its enzymatic activity pharmacologically inhibited 3-TYP, selective inhibitor. Apoptotic systematically evaluated through TUNEL staining, Western blot analysis caspase-3, Bax Bcl-2. Oxidative stress parameters, including malondialdehyde (MDA) levels glutathione (GSH) content, measured colorimetric assays. Neurological function mice quantified modified Severity Score (mNSS). Our results demonstrated mitigates apoptosis oxidative dose-dependently activating signaling. At optimal dosage, effectively restored levels, reduced damage, improved neurological recovery models. Notably, significantly attenuated specific Further validation experiments revealed overexpression synergistically enhanced irisin-mediated OGD-induced injury, whereas knockout substantially diminished efficacy. data shown exerted protective at least part, activation. This study establishes irisin/SIRT3 as novel target for ischemic stroke, providing insights future interventions.

Language: Английский

Citations

0