Artesunate Provides Neuroprotection against Cerebral Ischemia–Reperfusion Injury <i>via</i> the TLR-4/NF-κB Pathway in Rats

Abstract

Inflammation has an important role in ischemia/reperfusion (I/R) injury. Artesunate (ART) has anti-microbial and anti-inflammatory pharmacological activities, and it is used for various types of serious malaria, including cerebral malaria. ART maintains a high concentration in the brain but little is known about the neuroprotective effect of ART against brain I/R injury. We studied the neuroprotection of ART against brain I/R injury and its underlying mechanism. In this study, rats were subjected to middle cerebral artery occlusion (MCAO) for 2 hours. After 24 hours of reperfusion, neurological deficits, cerebrum water content, infarct volume, HE-staining, MPO activity, and proinflammatory cytokine levels were measured. Administration of 20, 40, 80, and 160 mg/kg ART i.p. 10 min after MCAO significantly decreased brain water content and improved neurological deficits in a dose-dependent manner. A 80 mg/kg dosage was optimal. ART significantly reduced infarct volume, suppressed MPO activity and diminished the expressions of TLR-4, MyD88, NF-κB, TNF-α, and IL-6 in the area of the ischemic cortex. The neuroprotective action of ART against focal cerebral I/R injury might be due to the attenuation of inflammation through the TLR-4/NF-κB pathway.

Artesunate alleviates intracerebral haemorrhage secondary injury by inducing ferroptosis in M1‐polarized microglia and suppressing inflammation through AMPK/mTORC1/GPX4 pathway

“…Several artemisinin derivatives revealed anti-inflammatory effects in the neurological system. 13,27 Moreover, ELISA results showed that artesunate inhibited the levels of the M1-related inflammatory IL-1β and TNF-α in ICH rats. In summary, ICH injury in SD rats is associated with microglial overactivation and M1-related inflammation.…”

“…Consistent with a previous study, we found that artesunate significantly alleviated ICH injury in rats, as shown by neurological deficits, haematoma volume and brain oedema. Several artemisinin derivatives revealed anti‐inflammatory effects in the neurological system 13,27 . Moreover, ELISA results showed that artesunate inhibited the levels of the M1‐related inflammatory IL‐1β and TNF‐α in ICH rats.…”

“…Male SD rats ( n = 125) weighing 320–350 g were randomly divided into the following five groups: sham, vehicle (ICH) and artesunate groups (20, 50 and 70 mg/kg) 26,27 . Rats without motor function injury ( n = 4) or that died ( n = 12) were excluded from the study.…”

“…Male SD rats (n = 125) weighing 320-350 g were randomly divided into the following five groups: sham, vehicle (ICH) and artesunate groups (20, 50 and 70 mg/ kg). 26,27 Rats without motor function injury (n = 4) or that died (n = 12) were excluded from the study. In the artesunate group, rats received artesunate at 20, 50 or 70 mg/kg (A3731, Sigma, USA) via intraperitoneal injection for three consecutive days before ICH induction, while rats in the vehicle group received a 0.5 ml 1% DMSO injection.…”

Therapeutic potential of artemisinin and its derivatives in managing kidney diseases

“…Zhao X demonstrated that artemisinin modulated the TLR4/NF-κB signaling and delayed microglia’s activation of immune-inflammatory responses by microglia ( Zhao et al, 2022 ). Chen et al (2021b) exhibited that ART reduced the expression of TLR-4, MyD88, NF-κB, TNF-α, and IL-6 in ischemic cortical regions through the TLR-4/NF-κB pathway. Chen YX confirmed that ART could reduce the expression levels of TLR4, p-NF-κB, p-p38, Bcl2 associated X (Bax), and caspase-9, increase the expression of B cell lymphoma-2 (Bcl-2) in a dose-dependent manner, inhibit the TLR4/NF-κB signaling pathway, and downregulate the levels of TNF-α, IL-8 and interferon-gamma (IFN-γ) ( Chen et al, 2019 ).…”