Naoluo Xintong capsule ameliorates apoptosis induced by endoplasmic reticulum stress in rats with cerebral ischemia/ reperfusion injury

Abstract

Background: Naoluo Xintong (NLXT) capsuleis a newly developed drug recorded in the Chinese Pharmacopoeia. It is derived from traditional Chinese medicine (TCM) NLXT decoction, and has been widely used to treat cerebrovascular diseases in clinic. However, it is currently unknown whether it improve cerebral ischemia reperfusion (I/R) injury. Methods:The effect of NLXT on regional cerebral blood flow (rCBF) was examined using Laser Doppler flower. The Terminal deoxyribonucleotide transferase-mediated Nick end labeling (Tunel) assay was performed to determine the effects of NLXT on apoptosis. Subsequently, cerebral water content and TTC staining were measured to assess cerebral edema and infarct volume, respectively. The protein expression levels were analyzed with Immunofluorescence and western blot assays. Results:The results indicated that NLXT ameliorated MCAO-induced cerebral I/R injury by decreasing infract volume, inhibition of apoptosis, and upregulation rCBF. In addition, it decreased the expression of key protein involved endoplasmic reticulum (ER)-stress, including glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP) and Caspase-12 at 24 h following reperfusion. This was accompanied reduced degradation level of TRPC6 and increased phosphorylation of cAMP/Ca 2+ response elementbinding protein (p-CREB), and decreased calpain-specific αII-spectrin breakdown product (SBDP145) activity. Interestingly, inhibition of mitogen-activated protein kinase (MEK) activity abolished the effect of NLXT on CREB activity.Conclusions: Collectively, the results indicated that NLXT can improve I/R injury therapy by activating TRPC6/MEK/CREB signaling pathway to attenuate ER-stress related neuronal apoptosis.

Effects of Electroacupuncture on Neural Function and Expression of Inflammation-Related Proteins NLRP3/Caspase-1 in Rats with Ischemic Stroke

“…We speculate that electroacupuncture may inhibit neuroin ammation and promote nerve function repair in ischemic stroke. Studies have shown that microglia are activated after cerebral ischemia, producing large amounts of neurotoxic molecules and pro-in ammatory cytokines that exacerbate brain damage [13][14][15][16][17]. Because of their prevalence in the central nervous system, NLRP3 in ammatory vesicles are highly concerned [18][19][20].…”

Electroacupuncture Regulates Endoplasmic Reticulum Stress and Ameliorates Neuronal Injury in Rats with Acute Ischemic Stroke

“…Caspase 12 belongs to the conserved caspase family, which is present on the cytoplasmic surface of the ER. It has been demonstrated that the activation of caspase 12 is essential for ERS-induced apoptosis, and non-ERS-mediated apoptosis does not involve activation of caspase 12 [37][38][39]. When ERS occurs, Ca 2+ release activates procaspase 12 into caspase 12 and subsequently activates caspase 9 and caspase 3, which leads to an apoptotic caspase cascade [40].…”

The role of JAK/STAT signaling pathway in cerebral ischemia-reperfusion injury and the therapeutic effect of traditional Chinese medicine: A narrative review

“…It could also reduce the expression of caspase-12 within 24 hours of CIRI, ultimately improve CIRI. [117]…”

“…It could also reduce the expression of caspase-12 within 24 hours of CIRI, ultimately improve CIRI. [117] For the effects on cell proliferation and differentiation, Naoluo Xintong Decoction not only facilitates the mRNA expression of SOCS5, but also restrains the level of prolactin receptor and the JAK/STAT pathway. Thus, Naoluo Xintong Decoction promotes the differentiation of neural stem cells into neurons and their migration.…”