Dictamnine Ameliorates Cerebral Ischemia via Attenuating NLRP3 Inflammasome Signaling Pathway
Jing Li1, Qian Jiang2★★ Corresponding author
- 1Department of Neurology, Yichun People’s Hospital, Jiangxi, CHINA.
- 2Department of Emergency, Yichun People’s Hospital, Jiangxi, CHINA.
CORRESPONDENCE
Qian Jiang
Department of Emergency, Yichun People’s Hospital, Jiangxi, CHINA.
Received: 05-08-2024; Accepted: 06-11-2024.
Volume 21, Issue 4 · pp. 1343–1355 · PUBLISHED 2025 · DOI: 10.1177/09731296241307433
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ABSTRACT
Background: Stroke is a primary global health concern, resulting in substantial mortality and morbidity, with a significant proportion of cases attributed to ischemic stroke. While reperfusion therapies, including thrombus dissolution and removal of thrombus mechanically, are essential in the critical management of ischemic stroke, they can also lead to a paradoxical increase in neuronal damage due to reperfusion injury. Objectives: This phenomenon has a significant impact on elevating disability rates and mortality linked to stroke, with survivors often experiencing persistent cognitive, motor, and psychological impairments that significantly impact their quality of life. Furthermore, the long-term consequences of cerebral ischemic–reperfusion injury place a substantial burden on healthcare systems, caregivers, and families, highlighting the need for effective strategies to mitigate this devastating condition. Therefore, in the present investigation, we explored the efficacy of phytoalkaloid dictamnine potency in ameliorating neuronal damage caused by cerebral ischemic–reperfusion. Materials and Methods: In vivo condition, middle cerebral artery occlusion (MCAO) was performed in C57BL/6J mice and treated with different concentrations of dictamnine. The experimental animals were subjected to neurological scoring, and the tissue and blood samples were collected after the treatment period. Cerebral damage was assessed by analyzing the brain edema, infarct volume, and Evans blue stain leakage assay. Oxidative stress markers and antioxidants were quantified to investigate the oxidative damage. Results: Nitrates matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) were measured to examine the vasodilation and blood–brain barrier (BBB) disruption induced by MCAO. Nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and cytokines were measured to assess the neuroinflammation. The efficacy of dictamnine in attenuating NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome, and toll-like receptor 4 (TLR4) signaling was evaluated to confirm the pharmaceutical potency of dictamnine in ameliorating cerebral ischemic–reperfusion. In vitro, SH-SY5Y cells were subjected to oxygen and glucose deprivation/reperfusion (OGD/R) and subsequently incubated with varied concentrations of dictamnine. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) assay, and 4′,6-diamidino-2-phenylindole (DAPI) staining were performed with dictamnine-treated cells to confirm the inhibitory potency of dictamnine against the neuronal cell apoptosis induced by OGD/R. Dictamnine treatment effectively scavenged oxidative stress and inhibited the NLP3 and TLR4 signaling, thereby preventing neuroinflammation induced by MCAO. The results of our in vitro study also confirm the ameliorative potency of dictamnine against cerebral ischemic–reperfusion-induced neuronal damage. Conclusion: Altogether, our research findings prove dictamnine is a potent bioactive compound that can be further analyzed to be formulated as a drug to treat cerebral ischemia.
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Li, J., & Jiang, Q. (2025). Dictamnine Ameliorates Cerebral Ischemia via Attenuating NLRP3 Inflammasome Signaling Pathway. Pharmacognosy Magazine, 21(4), 1343–1355. https://doi.org/10.1177/09731296241307433