Protective effects of andrographolide against cerebral ischemia‑reperfusion injury in mice

Abstract

Ischemic stroke is one of the most common causes of mortality worldwide and is a primary cause of disability and mortality in adults. There is an unmet need for drugs that can effectively treat ischemic stroke. Hence, the present study explored the neuroprotective effects of andrographolide (Andro) in a mouse model of bilateral common carotid artery occlusion, and systematically evaluated the potential mechanisms underlying its effects. The effects of Andro on mouse brain tissue following cerebral ischemia-reperfusion injury (cIRI) were evaluated by histopathological (H&E and Nissl) and immunofluorescence [glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN)] staining. A traditional chinese medicine-based network pharmacology method was performed to establish and analyze compound-target-disease and function-pathway networks in order to elucidate the possible mechanisms responsible for the protective role of Andrographis paniculata in CIRI. In addition, western blot analysis and RT-qPCR was performed to evaluate the expression and activation of signaling proteins predicted to be involved in this mechanism. The amelioration of histopathological alterations was observed in mice pre-treated with Andro. Immunofluorescence staining revealed that Andro decreased the expression of GFAP and increased the expression of NeuN, and significantly decreased the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α). Network pharmacology analysis revealed that neuroinflammatory response and apoptosis were associated with the effects of Andrographis paniculata on cIRI. Western blot analysis revealed that the mice pre-treated with Andro exhibited an upregulated protein expression of tropomyosin receptor kinase B (TrkB), p-PI3K and p-Akt, as well as a decrease in the expression of GFAP and an increase in the expression of NeuN. In addition, the data of RT-qPCR indicated that the mice pre-treated with Andro exhibited a significantly decreased expression of encoding IL-1β mRNA, IL-6 mRNA and TNF-α mRNA in the brain compared to the untreated mice following CIRI. On the whole, the findings of the present study suggest that pre-treatment with Andro exerts a protective effect against cIRI, which may be partly related to its potential to reduce neuroinflammatory response and apoptosis in patients with stroke.

Andrographolide contributes to spinal cord injury repair via inhibition of apoptosis, oxidative stress and inflammation

“…However, Andro treatment significantly increased the expression of GAP43 in the injured tissues and decreased the number of astrocytes, which in turn mitigated glial scarring and promoted axonal regeneration, eventually bridging the gaps at lesion sites and restoring tissue continuity. These results are consistent with previous findings (Liang et al, 2017;Li et al, 2021).…”

Dexmedetomidine Inhibits Gasdermin D-Induced Pyroptosis via the PI3K/AKT/GSK3β Pathway to Attenuate Neuroinflammation in Early Brain Injury After Subarachnoid Hemorrhage in Rats

“…A previous study showed that the administration of Dex in critically ill patients could improve cardiovascular and ventilatory outcomes during the intensive care unit stay (Castillo et al, 2019). Several other studies have shown that Dex exerts protective effects against apoptosis, necrosis, and autophagy in the brain both in vitro and in vivo (Cui et al, 2015;Kong et al, 2017;Liu et al, 2020). Dex has been shown to attenuate early brain injury in rats with SAH by suppressing the activation of the TLR4/NF-κB pathway (Yin et al, 2018).…”

Efficacy of puerarin in rats with focal cerebral ischemia through modulation of the SIRT1/HIF-1α/VEGF signaling pathway and its effect on synaptic plasticity

“…Brain tissue was extracted and weighed, and normal saline was added to prepare 10% tissue homogenate as described previously [ 15 ]. The tissue homogenate was centrifuged at 3000 rpm for 15 min at 4 °C, and the supernatant was taken and stored at −20 °C.…”