Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down‐Regulating Connexin 43

Chu, Hang; Huang, Chuyi; Gao, Zhen; Dong, Jing; Tang, Yuping; Dong, Qiang

doi:10.1002/ptr.5868

Cited by 21 publications

(27 citation statements)

References 29 publications

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“…Paeoniflorin (PF; Figure a) is a major pharmacologically active ingredient derived from Paeonia lactiflora Pall, which has been widely applied in traditional Chinese medicine to treat various diseases for centuries (Arentz et al, ; Parker et al, ). Recent years, PF has been confirmed to exhibit anti‐inflammatory, antiviral, antibacterial, antioxidant, antinociceptive, and immunoregulatory therapeutic activity (Chu et al, ; Xu, Xu, & Deng, ). An increasing number of evidences report that PF can improve cholestasis (Z. Chen et al, ), hepatitis (M. Chen et al, ), non‐alcoholic fatty liver disease (Ma et al, ), and hepatic I/R injury (Tao, Wen, Song, & Wang, ).…”

Section: Introductionmentioning

confidence: 99%

Paeoniflorin protects against liver ischemia/reperfusion injury in mice via inhibiting HMGB1‐TLR4 signaling pathway

Xie

Gong

et al. 2018

Phytotherapy Research

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Hepatic ischemia/reperfusion (I/R) injury is a major cause of high morbidity and mortality after liver resection, transplantation, and hemorrhagic shock. Paeoniflorin (PF), the main substance of glucosides in Radix Paeoniae Alba, has been widely used to treat various hepatic inflammatory diseases including I/R injury. However, the underlying mechanisms of PF on hepatic I/R injury remain further investigated. In this study, the liver I/R model was performed by clamping the portal vein and hepatic artery with an atraumatic clamp for 90 min followed by 6 hr reperfusion. PF (100 mg/kg) was given three times a day by gavage before I/R. The blood and hepatic samples were collected to evaluate liver injury and molecular indexes. The results showed that PF pretreatment significantly inhibited I/R-induced serum ALT and AST activities (40.3% and 53.8% those of I/R group, respectively), hepatic pathological damages and hepatic apoptosis (P < 0.01), and infiltration of neutrophils into liver. In addition, PF suppressed the production of pro-inflammatory cytokines (P < 0.01), decreased the expression of high mobility group box-1 (HMGB1), and down-regulated toll-like receptors 4 (TLR4) and phosphorylated ERK1/2, JNK1/2, p38, and NF-κB signal molecules expression in the I/R-operated mice. These findings indicated that PF played a protective role in liver I/R injury, and this protection was associated with inhibition of I/R-activated HMGB1-TLR4 signaling pathway to attenuate hepatic inflammation responses.

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Section: Introductionmentioning

confidence: 99%

Paeoniflorin protects against liver ischemia/reperfusion injury in mice via inhibiting HMGB1‐TLR4 signaling pathway

Xie

Gong

et al. 2018

Phytotherapy Research

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“…Pathophysiologically, astrocytic Cx43 has been connected to ischemic stroke [ 42 , 43 ], to the formation of brain edema, for instance after ischemia or trauma [ 44 , 45 ], to cancers of diverse tissues (reviewed by [ 46 ]), or to the response to mechanical stress [ 47 ], making the regulation and functionality of Cx43 subject of many studies [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

First Responders to Hyperosmotic Stress in Murine Astrocytes: Connexin 43 Gap Junctions Are Subject to an Immediate Ultrastructural Reorganization

Beckmann

Recktenwald

Ferdinand

et al. 2021

Biology

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In a short-term model of hyperosmotic stress, primary murine astrocytes were stimulated with a hyperosmolar sucrose solution for five minutes. Astrocytic gap junctions, which are mainly composed of Connexin (Cx) 43, displayed immediate ultrastructural changes, demonstrated by freeze–fracture replica immunogold labeling: their area, perimeter, and distance of intramembrane particles increased, whereas particle numbers per area decreased. Ultrastructural changes were, however, not accompanied by changes in Cx43 mRNA expression. In contrast, transcription of the gap junction regulator zonula occludens (ZO) protein 1 significantly increased, whereas its protein expression was unaffected. Phosphorylation of Serine (S) 368 of the Cx43 C–terminus has previously been associated with gap junction disassembly and reduction in gap junction communication. Hyperosmolar sucrose treatment led to enhanced phosphorylation of Cx43S368 and was accompanied by inhibition of gap junctional intercellular communication, demonstrated by a scrape loading-dye transfer assay. Taken together, Cx43 gap junctions are fast reacting elements in response to hyperosmolar challenges and can therefore be considered as one of the first responders to hyperosmolarity. In this process, phosphorylation of Cx43S368 was associated with disassembly of gap junctions and inhibition of their function. Thus, modulation of the gap junction assembly might represent a target in the treatment of brain edema or trauma.

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“…Moreover, the combined use of paeoniflorin and astragaloside IV was shown to reduce the incidence of ischemic brain edema via the downregulation of connexin 43, which was associated with downregulation of Cx43, resulting in a decrease in AQP4 [22]. The results obtained in the present study have also shown that AQP4 is the key link in the glial lymphatic system, a new clearance system in the brain which was identified in the rodent brain in 2012, and considered as a new anatomical route for CSF-interstitial fluid flow [23].…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with Shenxiong Drop Pill induces AQP4- mediated neuroprotective effect on middle cerebral artery occlusion in rats

Jin¹,

Deng²,

Chen³

et al. 2020

Trop. J. Pharm Res

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Purpose: To investigate the neuroprotective effect of Shenxiong Drop Pill (SXDP) pretreatment on rats with middle cerebral artery occlusion (MCAO) in rats, and the mechanism involved.Methods: Ninety-nine SD rats were randomly assigned to 4 groups: control group, MCAO group, shamoperated group and SXDP group. The MCAO model was established via thread occlusion. Rats in the SXDP group was administered SXDP 7 days before induction of MCAO. Neurological deficit score (NDS) was determined using Bederson's neurological behavioral scoring method, while cerebral infarction volume was measured using TTC staining. Integrated optical density (IOD) of Nissl Body was evaluated via Nissl staining. Brain water content was measured using dry-wet method. The expression level of AQP4 in brain tissues was determined using immunocytochemistry.Results: The SXDP treatment resulted in significant reduction in NDS, marked improvement in IOD of Nissl Body, and significant reductions in cerebral infarction volume, brain water content, and expression level of AQP4, relative to control (p< 0.05).Conclusion: These results suggest that SXDP pretreatment exerts neuroprotective effect against cerebral ischemia in rats by decreasing in cerebral edema through a mechanism involving downregulation of the expression of AQP4. Keywords: Middle cerebral artery occlusion, Cerebral ischemia, Aquaporins-4, Cerebral edema, Neuroprotection

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Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down‐Regulating Connexin 43

Cited by 21 publications

References 29 publications

Paeoniflorin protects against liver ischemia/reperfusion injury in mice via inhibiting HMGB1‐TLR4 signaling pathway

Paeoniflorin protects against liver ischemia/reperfusion injury in mice via inhibiting HMGB1‐TLR4 signaling pathway

First Responders to Hyperosmotic Stress in Murine Astrocytes: Connexin 43 Gap Junctions Are Subject to an Immediate Ultrastructural Reorganization

Pretreatment with Shenxiong Drop Pill induces AQP4- mediated neuroprotective effect on middle cerebral artery occlusion in rats

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