Journal of ethnopharmacology · 2025
Kudiezi injection attenuates apoptosis and neuroinflammation for ameliorating angiogenesis via miR-21/PDCD4/NF-κB axis in MCAO/reperfusion rats.
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Sun Mengjie, Han Guanghui, Yu Hongni, Wang Fengli
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: miR-21 has multiple neuroprotective effects in central nervous system (CNS) ischemic damage. Kudiezi (KDZ), a traditional Chinese medication, has a longstanding application in cerebral ischemia treatment and has been clinically confirmed to be effective for ischemic injury. However, its specific effects on miR-21 regulation are yet unclear.
AIM OF THE STUDY: Investigate the fundamental mechanisms of the anti-inflammatory as well as antiapoptotic effects of KDZ in rats subjected to middle cerebral artery occlusion-reperfusion(MCAO/R).
MATERIALS AND METHODS: MCAO rats were developed, and the TTC staining and Garcia JH scoring methods were used to detect infarct size and analyze the neuroprotective effects of KDZ on this rat model. Real-time PCR and miRNA antagomir lateral ventricular injection were used to evaluate the change in miR-21 after the KDZ treatment. Furthermore, multicolor fluorescent staining, TUNEL staining, and microvessel density detection were conducted to analyze the effects of KDZ on MCAO rats, which included anti-inflammatory, neuroprotective, and apoptosis inhibition effects. Additionally, Western blotting was employed to determine the amounts of relevant inflammatory agents and proteins expressed.
RESULTS: KDZ injection improved the infarct area and neurological function scores in MCAO rats, aggravated the level of miR-21 expression, and regulated protein levels, including toll-like receptor 4, programmed death cell factor 4 (PDCD4), mitogen-activated protein kinase (MAPK) (p38, ERK), and nuclear factor kappa-B (NF-κB) as well. Besides, KDZ injection can regulate the amounts of inflammatory factors, angiopoietins, and brain water content and also increase the level of tight junction proteins.
CONCLUSIONS: KDZ injection has a neuroprotective effect by increasing the quantity of miR-21 of MCAO rats, preventing the PDCD4/MAPK/NF-κB signaling pathway from being activated, drastically lowering the level of pro-inflammatory proteins, and reversing the increase of apoptosis factors in the brain.
AIM OF THE STUDY: Investigate the fundamental mechanisms of the anti-inflammatory as well as antiapoptotic effects of KDZ in rats subjected to middle cerebral artery occlusion-reperfusion(MCAO/R).
MATERIALS AND METHODS: MCAO rats were developed, and the TTC staining and Garcia JH scoring methods were used to detect infarct size and analyze the neuroprotective effects of KDZ on this rat model. Real-time PCR and miRNA antagomir lateral ventricular injection were used to evaluate the change in miR-21 after the KDZ treatment. Furthermore, multicolor fluorescent staining, TUNEL staining, and microvessel density detection were conducted to analyze the effects of KDZ on MCAO rats, which included anti-inflammatory, neuroprotective, and apoptosis inhibition effects. Additionally, Western blotting was employed to determine the amounts of relevant inflammatory agents and proteins expressed.
RESULTS: KDZ injection improved the infarct area and neurological function scores in MCAO rats, aggravated the level of miR-21 expression, and regulated protein levels, including toll-like receptor 4, programmed death cell factor 4 (PDCD4), mitogen-activated protein kinase (MAPK) (p38, ERK), and nuclear factor kappa-B (NF-κB) as well. Besides, KDZ injection can regulate the amounts of inflammatory factors, angiopoietins, and brain water content and also increase the level of tight junction proteins.
CONCLUSIONS: KDZ injection has a neuroprotective effect by increasing the quantity of miR-21 of MCAO rats, preventing the PDCD4/MAPK/NF-κB signaling pathway from being activated, drastically lowering the level of pro-inflammatory proteins, and reversing the increase of apoptosis factors in the brain.