Oridonin prevents oxidative stress‐induced endothelial injury via promoting Nrf‐2 pathway in ischaemic stroke

Li, Lei; Cheng, Shu-qi; Guo, Wei; Cai, Zhenyu; Sun, Yang; Huang, Xinxin; Yang, Jin; Ji, Juan; Chen, Ya-Yun; Dong, Yinfeng; Cheng, Hong; Sun, Xiu‐Lan

doi:10.1111/jcmm.16923

Cited by 21 publications

(13 citation statements)

References 45 publications

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“…The neurological score measured by the mNSS test was performed before GBCA injections and found no significant difference among all groups ( p = 0.659) and either gadobutrol or gadopentetate failed to alter mNSS scores on day 1 p. i (p = 0.845) (Figure 3B). With TTC staining, the infarct area remained unstained (white) and non‐infarct area was stained red 25 . As shown in Figure 3C,D, there was no significant difference in infarct volume among all groups ( p = 0.961).…”

Section: Resultsmentioning

confidence: 87%

“…Scale bar = 100 μm stained red. 25 As shown in Figure 3C,D, there was no significant difference in infarct volume among all groups (p = 0.961). Meanwhile, Nissl staining showed consistent results (Figure 3E).…”

Section: 2mentioning

confidence: 76%

“…A tMCAO model was established according to the method described by Li et al 25 Briefly, the mice were anesthetized and a monofilament (0.18 ± 0.01 mm, L1800, Guangzhou Jialing Biotechnology, Guangzhou, China) was inserted from the right external carotid artery into the right internal carotid artery until it was encountered slight resistance to occlude the MCA for 1 h. The sham group underwent the same procedures except for insertion of the filament.…”

Section: Methodsmentioning

confidence: 99%

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Gadolinium retention in the ischemic cerebrum: Implications for pain, neuron loss, and neurological deficits

Huang

Jiang

et al. 2022

Magnetic Resonance in Med

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To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke.Methods: Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i. Results: Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p < 0.05; gadopentetate, p < 0.001) and 28 p. i of gadopentetate. (p < 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p > 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p < 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p < 0.05). Conclusions:Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.

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Section: Resultsmentioning

confidence: 87%

Section: 2mentioning

confidence: 76%

Section: Methodsmentioning

confidence: 99%

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Gadolinium retention in the ischemic cerebrum: Implications for pain, neuron loss, and neurological deficits

Huang

Jiang

et al. 2022

Magnetic Resonance in Med

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“…Oridonin could prevent NLRP3 inflammasome complex assembly against NLRP3 inflammasome activation (He et al, 2018). The study found oridonin prevented oxidative stress-induced endothelial injury via promoting the Nrf2 pathway and thereby repaired BBB integrity, alleviated neuroinflammation, and infarct volume after ischemic stroke (Li et al, 2021a).…”

Section: Novel Inhibitormentioning

confidence: 86%

NLRP3 Inflammasome Activation: A Therapeutic Target for Cerebral Ischemia–Reperfusion Injury

Wang

Ren

et al. 2022

Front. Mol. Neurosci.

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Millions of patients are suffering from ischemic stroke, it is urgent to figure out the pathogenesis of cerebral ischemia–reperfusion (I/R) injury in order to find an effective cure. After I/R injury, pro-inflammatory cytokines especially interleukin-1β (IL-1β) upregulates in ischemic brain cells, such as microglia and neuron. To ameliorate the inflammation after cerebral I/R injury, nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) inflammasome is well-investigated. NLRP3 inflammasomes are complicated protein complexes that are activated by endogenous and exogenous danger signals to participate in the inflammatory response. The assembly and activation of the NLRP3 inflammasome lead to the caspase-1-dependent release of pro-inflammatory cytokines, such as interleukin (IL)-1β and IL-18. Furthermore, pyroptosis is a pro-inflammatory cell death that occurs in a dependent manner on NLRP3 inflammasomes after cerebral I/R injury. In this review, we summarized the assembly and activation of NLRP3 inflammasome; moreover, we also concluded the pivotal role of NLRP3 inflammasome and inhibitors, targeting the NLRP3 inflammasome in cerebral I/R injury.

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“…The chemical structure of oridonin was first characterized by Fujita et al (Figure 1B). 25 In the following decades, accumulating evidence has indicated that oridonin exhibits multiple biological effects, including anticancer, 26 anti‐inflammatory, 23 antibacterial, 27 antioxidative, 28 antifibrotic, 29 and cytoprotective effects 30 in different disease models. Oridonin consists of four parts, including A, B, C, and D rings; furthermore, it also contains several hydroxyls, one ether, and one α, β‐unsaturated ketone that can form covalent bonds with cysteine residues.…”

Section: Oridonin and Its Derivative Compoundsmentioning

confidence: 99%

Direct cellular targets and anticancer mechanisms of the natural product oridonin

Yao

Liu

Sun

et al. 2023

MedComm – Future Medicine

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Cancer is one of the leading causes of death worldwide. The proliferation, survival, and metastasis of cancer cells are governed by a complex series of intracellular and extracellular signaling pathways. Therefore, efficient cancer therapy often requires the modulation of multiple targets. Besides, the modulation of several biological targets with a single drug can lead to synergistic therapeutic effects and avoid side effects associated with combination therapy. Oridonin, an ent-kaurane type diterpenoid isolated from Rabdosia rubescens, has been reported to possess potent antiinflammatory, antioxidant, anticancer, and neuroprotective activities. Among its many benefits, the anticancer effects have attracted the most attention because of its effectiveness in many tumor cells and its potential to overcome therapeutic resistance. Recently, several proteins involved in oncogenic signaling, including CRM1, PHGDH, HSP70, AML1-ETO, and STAT3, were identified as functional targets of oridonin and its analogs. The binding mechanism and the consequence of oridonin binding to these oncogenic proteins are summarized and discussed. These advances suggest that oridonin exhibits broad spectrum anticancer effects by targeting multiple oncogenic proteins mainly via Michael addition between its unsaturated ketone and the cysteines in the target proteins. Therefore, oridonin and its derivatives hold the potential to be developed as multitargeting anticancer drugs.

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Oridonin prevents oxidative stress‐induced endothelial injury via promoting Nrf‐2 pathway in ischaemic stroke

Cited by 21 publications

References 45 publications

Gadolinium retention in the ischemic cerebrum: Implications for pain, neuron loss, and neurological deficits

Gadolinium retention in the ischemic cerebrum: Implications for pain, neuron loss, and neurological deficits

NLRP3 Inflammasome Activation: A Therapeutic Target for Cerebral Ischemia–Reperfusion Injury

Direct cellular targets and anticancer mechanisms of the natural product oridonin

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