Cynaropicrin Averts the Oxidative Stress and Neuroinflammation in Ischemic/Reperfusion Injury Through the Modulation of NF-kB

Abstract

Cerebral ischemia and successive reperfusion are the prevailing cause of cerebral stroke. Currently cerebral stroke is considered to be one of the prior causes for high mortality, disability, and morbidity. Cynaropicrin, a sesquiterpene lactone, exhibits various pharmacologic properties and also has an anti-inflammatory property associated with the suppression of the key pro-inflammatory NF-κB pathway. The protective effect of cynaropicrin against oxidative stress and neuroinflammation during CIR injury through the modulation of NF-κB pathway was studied in the current investigation. The experimental rats split into 5 groups as sham-operated control group (group 1), middle cerebral artery occlusion (MCAO)-induced rats (group 2), MCAO rats treated with cynaropicrin (diluted in saline) immediately 2 h after MCAO with 5, 10, and 25 mg/kg administration orally were designated as groups 3, 4, and 5, respectively. In MCAO-induced animals, the severity of ischemic was evident by the elevated level nitrate, MDA, MMPs, inflammatory mediators, Bax, caspase-3, and NF-κB. The level of Nrf-2, antioxidant enzymes, Bcl-2, and IL-10 was reduced in the MCAO-induced animals. Treatment with cynaropicrin in dosage-based manner increased the level of antioxidant enzymes, IL-10, Nrf-2, and Bcl-2 in the animals which indicates the antioxidative effect of cynaropicrin. The level of nitrate, MDA, MMPs, proinflammatory cytokines, inflammatory mediators, Bax, caspase-3, and NF-κB was reduced in the rats treated with cynaropicrin in a dosage-based manner. Experimental animals treated with cynaropicrin in a dosage-dependent way showed a defensive mechanism against oxidative stress and neuroinflammation by inhibiting the NF-κB pathway.

Microglia at the blood brain barrier in health and disease

“…In addition, much like endogenous antioxidant mechanisms, exogenous antioxidants function as free radical scavengers, neutralizing ROS. Numerous studies have explored the ability of antioxidants to reduce inflammation and oxidative damage by down-regulating NF-κB and elevating Nrf2 ( Li et al, 2016 ; Caglayan et al, 2019 ; Wang et al, 2021 ; Barber et al, 2023 ; Habotta et al, 2023 ; Jin and Leng, 2023 ). Nrf2 also induces expression of brain derived neurotrophic factor (BDNF), a key molecule in synaptic plasticity and learning and memory ( Tang et al, 2022 ).…”

Functional and Therapeutic Potential of Cynara scolymus in Health Benefits

“…Furthermore, this natural product has been associated with inhibiting NF-κB. Jin et al demonstrated that cynaropicrin exhibits anti-inflammatory properties by suppressing the NF-κB pathway [ 25 ]. This evidence has been reinforced by other research findings showing that cynaropicrin was able to reduce both the oxidative stress and neuroinflammation in an animal model of ischemic/reperfusion injury in a dose-dependent manner by inhibiting the NF-κB transcriptional activation pathway.…”

“…NF-κB activation is recognized as an immediate response following the onset of stroke and plays an important role in the disruption of blood-brain barrier, inflammation, and cellular apoptosis. This implies that cynaropicrin has the potential to serve as an effective therapeutic agent for cerebral ischemia-reperfusion injury [ 25 ].…”

“…Antioxidant action [41] Sesquiterpene lactones Cynaropicrin Anti-inflammatory action [19] Antiparasitic action [20] Anti-tumor action [23,26] Antioxidant action [25] Neuroprotective action [25] Sesquiterpene lactones Dehydrocynaropicrin Grosheimin Cynaratriol 8-deoxy-11,13-dihydroxygrosheimin Anti-inflammatory action [27]…”

Induction of Apoptosis by Cynaropicrin in Human Colon Cancer Cell Line HCT-116 through the Mitochondria-mediated Apoptotic Pathway

“…Owing to these multiple specific potentials, cynaropicrin seems to be more significant and will serve towards the development of pharmaceutical substances (Elsebai et al, 2016). A recent study revealed that cynaropicrin demonstrated strong cytotoxicity on glioblastoma cells (Rotondo et al, 2022), melanoma cells (De Cicco et al, 2021), and revealed antioxidative and anti-neuroinflammatory activity in an ischemic stroke model (Jin & Leng, 2022).…”