Neuroprotective Effects of Radix Scrophulariae on Cerebral Ischemia and Reperfusion Injury via MAPK Pathways

Meng, Xiangbao; Xie, Weijie; Qiao, Xu; Liang, Tian; Xu, Xudong; Sun, Guibo; Sun, Xiaobo

doi:10.3390/molecules23092401

Cited by 62 publications

(60 citation statements)

References 42 publications

(88 reference statements)

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“…High‐potassium preconditioning enhanced tolerance to cerebral I/R injury by inhibiting neuronal apoptosis, as revealed by decreased TUNEL staining of apoptotic cells and altered pro‐apoptotic and anti‐apoptotic protein expression. Apoptosis is involved in the pathogenesis and pathological mechanism of ischemic stroke (Meng et al, ). Members of the caspase family act as zymogens in cells and play significant roles in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

High‐potassium preconditioning enhances tolerance to focal cerebral ischemia‐reperfusion injury through anti‐apoptotic effects in male rats

Tan

Qin

et al. 2019

J of Neuroscience Research

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Imbalances between cellular K + efflux and influx are considered to be involved in cerebral ischemia-reperfusion (I/R) injury. High-potassium pretreatment alleviates this injury, but the underlying molecular mechanism is unclear. In this study, we sought to investigate whether high-potassium preconditioning enhances cerebral tolerance to I/R injury through an anti-apoptotic mechanism. Adult male Sprague-Dawley rats were randomly divided into four groups (n = 40/group): a sham-operated group, normal saline group (3.2 ml/kg saline, intravenous (IV)), and low-dose and high-dose potassium chloride (KCl) groups (40 and 80 mg/kg KCl solution, IV, respectively). Subsequently, the rats underwent 90 min of middle cerebral artery occlusion (MCAO) followed by 24 hr of reperfusion (MCAO/R). Neurological deficit scores, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin staining, and TUNEL assay were used to assess neural injury. The expression of apoptotic proteins, brain potassium levels, mitochondrial function and oxidative stress were detected to explore the potential mechanism. After 24 hr of reperfusion, in both KCl treatment groups, neurological deficits and the cerebral infarct volume were reduced, and the apoptosis index of neurons was decreased. Furthermore, high-potassium preconditioning increased brain K + , adenosine triphosphate (ATP), cytochrome c oxidase (COX) levels, reduced malondialdehyde level, improved Na + /K + -ATPase, succinic dehydrogenase and superoxide dismutase activities, upregulated anti-apoptotic protein expression, and downregulated pro-apoptotic protein expression. This study suggests that high-potassium preconditioning enhanced cerebral tolerance to I/R injury in a rat MCAO/R model.

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Section: Discussionmentioning

confidence: 99%

High‐potassium preconditioning enhances tolerance to focal cerebral ischemia‐reperfusion injury through anti‐apoptotic effects in male rats

Tan

Qin

et al. 2019

J of Neuroscience Research

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“…To mimic ischemic-like conditions in vitro , SH-SY5Ycells were exposed to oxygen and glucose deprivation and reperfusion (OGD/R) as we described previously [ 35 ]. Briefly, cells washed with PBS, then replaced with glucose-free DMEM (11966025, Gibco, U.S.), and incubated in an anaerobic incubator (Type III, COY Laboratory, U.S.) under the conditions of 37°C, 95% N 2 , and 5% CO 2 for different time (3 h, 4 h, 5 h, 6 h, 7 h, 8 h,).…”

Section: Methodsmentioning

confidence: 99%

“…Cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay [ 35 , 38 ]. The absorbance was measured at 490 nm via a microplate reader (M1000, Tecan Infinite, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Notoginseng Leaf Triterpenes Ameliorates OGD/R-Induced Neuronal Injury via SIRT1/2/3-Foxo3a-MnSOD/PGC-1α Signaling Pathways Mediated by the NAMPT-NAD Pathway

Xie

Zhu

Zhou

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Cerebral ischemic stroke (CIS) is a common cerebrovascular disease whose main risks include necrosis, apoptosis, and cerebral infarction. But few therapeutic advances and prominent drugs seem to be of value for ischemic stroke in the clinic yet. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stem and leaf have been confirmed to have neuroprotective effects against mitochondrial damages caused by cerebral ischemia in vivo. However, the potential mechanisms of mitochondrial protection have not been fully elaborated yet. Methods. The oxygen and glucose deprivation and reperfusion (OGD/R)-induced SH-SY5Y cells were adopted to explore the neuroprotective effects and the potential mechanisms of PNGL in vitro. Cellular cytotoxicity was measured by MTT, viable mitochondrial staining, and antioxidant marker detection in vitro.Mitochondrial functions were analyzed by ATP content measurement, MMP determination, ROS, NAD, and NADH kit in vitro. And the inhibitor FK866 was adopted to verify the regulation of PNGL on the target NAMPT and its key downstream. Results. In OGD/R models, treatment with PNGL strikingly alleviated ischemia injury, obviously preserved redox balance and excessive oxidative stress, inhibited mitochondrial damage, markedly alleviated energy metabolism dysfunction, improved neuronal mitochondrial functions, obviously reduced neuronal loss and apoptosis in vitro, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL markedly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions and OGD/R-induced SH-SY5Y cells and regulated the downstream SIRT1/2-Foxo3a and SIRT1/3-MnSOD/PGC-1α pathways. And FK866 further verified that the protective effects of PNGL might be mediated by the NAMPT in vitro. Conclusions. The mitochondrial protective effects of PNGL are, at least partly, mediated via the NAMPT-NAD+ and its downstream SIRT1/2/3-Foxo3a-MnSOD/PGC-1α signaling pathways. PNGL, as a new drug candidate, has a pivotal role in mitochondrial homeostasis and energy metabolism therapy via NAMPT against OGD-induced SH-SY5Y cell injury.

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“…The OGd/R model has been commonly recognized as the in vitro model simulating cIRI (44)(45)(46). First, the complete culture medium was discarded, and the cells were washed twice with 1X PBS.…”

Section: In Vitro Model Of Oxygen-glucose Deprivation/reoxygenation (mentioning

confidence: 99%

Astragaloside IV attenuates cerebral ischemia‑reperfusion injury in rats through the inhibition of calcium‑sensing receptor‑mediated apoptosis

Zhang

Zhao

et al. 2020

Int J Mol Med

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cerebral ischemia-reperfusion injury (cIRI), caused by the reperfusion of blocked vessels following ischemic stroke, can lead to secondary brain injury. Throughout cIRI, apoptosis serves an important role. Astragaloside IV is a potential neuroprotectant that alleviates cIRI by inhibiting apoptosis. The calcium-sensing receptor (caSR) is a G-protein-coupled receptor, the activation of which aggravates ischemia-reperfusion injury. The aim of the present study was to investigate whether the protective effect of Astragaloside IV on cIRI may be associated with the regulation of caSR. A rat middle cerebral artery occlusion/reperfusion (McAO/R) model and an oxygen and glucose deprivation/reoxygenation (OGd/R) model of pheochromocytoma (Pc12) cells were used to study the neuronal injury induced by cIRI. Neurological function scores (NFS), 2,3,5-triphe-nylterazolium chloride and hematoxylin and eosin staining were used to determine brain damage in rats. cell viability was measured to evaluate the injury of OGd/R Pc12 cells. Western blotting was used to examine the expression of proteins associated with apoptosis and caSR. The caSR antagonist NPS-2143 and agonist Gdcl 3 were used to further confirm the effects of caSR during the process of apoptosis. The results demonstrated that Astragaloside IV alleviated cIRI by decreasing the NFS of rats, reducing the infarction volume of the brain and promoting the viability of Pc12 cells, as well as inhibiting the expression of cleaved caspase-3 and caSR, which was induced by cIRI. The results of the present study suggested that the activation of caSR may be involved in cIRI-induced brain damage in rats, and that Astragaloside IV may alleviate cIRI by inhibiting caSR activation-induced apoptosis.

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Neuroprotective Effects of Radix Scrophulariae on Cerebral Ischemia and Reperfusion Injury via MAPK Pathways

Cited by 62 publications

References 42 publications

High‐potassium preconditioning enhances tolerance to focal cerebral ischemia‐reperfusion injury through anti‐apoptotic effects in male rats

High‐potassium preconditioning enhances tolerance to focal cerebral ischemia‐reperfusion injury through anti‐apoptotic effects in male rats

Notoginseng Leaf Triterpenes Ameliorates OGD/R-Induced Neuronal Injury via SIRT1/2/3-Foxo3a-MnSOD/PGC-1α Signaling Pathways Mediated by the NAMPT-NAD Pathway

Astragaloside IV attenuates cerebral ischemia‑reperfusion injury in rats through the inhibition of calcium‑sensing receptor‑mediated apoptosis

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