Inhibition of oxidative stress contributes to the protective effect of Herba Siegesbeckiae on ischemic stroke by PI3K/STAT3/FOXO3a signal axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Siegesbeckiae (HS), well-recognized among the commonly used traditional medicines, is popular as one of the in-clinic treatments for rheumatoid arthritis, ischemic stroke, paralysis, asthma, and allergic disorders. However, the underlying mechanisms of neuroprotection and the part played by HS in protection against neuronal apoptosis continue to be nebulous.

AIM OF THE STUDY: This study aims to explore whether HS can alleviate cerebral ischemic injury by protecting neurons and alleviating oxidative stress injury, and to elucidate the molecular mechanisms involved in PI3K/STAT3/FOXO3a signal pathway.

METHODS

In this study, both in vitro and in vivo experiments were performed to examine the neuroprotective effects of HS on oxidative stress injury and neuronal apoptosis. After the HS treatment, several assays were done to assess the neuroprotection, oxidative stress response, and neuronal apoptosis. Besides, to further clarify the role of HS on the PI3K/STAT3/FOXO3a signal pathway, the effects of combining the HS with an inhibitor, agonist, or siRNA were studied.

RESULTS

From the in vivo and in vitro experiments, it was evident that HS inhibited neuronal apoptosis to a significant degree and offered effective protection against oxidative stress injury by lowering the concentration of the reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH). Moreover, HS obviously up-regulated the principal proteins expression of the PI3K/STAT3/FOXO3a signal pathway, including the PI3K, p-Akt/Akt, and p-FOXO3a/FOXO3a. Additionally, HS reduced the fluorescence intensity of the STAT3 and FOXO3a, and advanced their nuclear translocation both in the in vitro and in vivo models. Nevertheless, after the combined treatment with HS and LY294002, Colivelin or siRNA-FOXO3a, these effects were reversed.

CONCLUSIONS

The present study gives pharmacological evidence, revealing that HS wields its protective actions by regulating the PI3K/STAT3/FOXO3a signal pathway, thus inhibiting oxidative stress injury and protecting the neurons from oxidative stress-generated damage. The current study emphasizes the potential of HS as a therapeutic means of treatment of oxidative stress conditions related to ischemic stroke.