Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms

Abstract

Purpose Catalpol is the main active component of Rehmannia glutinosa, which has a variety of pharmacological activities, including anti-inflammatory and anti-oxidative effects. This study investigates the feasibility of catalpol intranasal administration and its protective effect on acute cerebral ischemia in rats via anti-oxidative and anti-apoptotic mechanisms. Patients and Methods This study investigates the method of catalpol intranasal administration to evaluate the nasal mucosal toxicity, brain targeting and pharmacokinetics of catalpol. The protective effect of catalpol of intranasal administration on stroke-induced brain injury in rats and its mechanisms on oxidative stress pathway Nrf2/HO-1 and apoptosis were also investigated using middle cerebral artery occlusion (MCAO). Results The results showed that catalpol intranasal administration was safe and feasible with no hemolysis, no bad effect on the maxillary ciliary movement of bullfrog. After intranasal administration, the brain targeting index (DTI) of catalpol was greater than 1, which indicated that catalpol had good brain targeting after intranasal administration. The bioavailability of catalpol administered intranasally was higher than that of in plasma. In MACO model, catalpol intranasal administration could significantly reduce cerebral infarction volume, neurological dysfunction and brain edema. In addition, catalpol intranasal administration can also reduce the brain cell’s occurrence of apoptosis, promote the expression of Bcl-2 protein and inhibit the expression of Bax protein, reduce oxidative stress damage via up-regulating expression of Nrf2 and HO-1, increasing the activities of SOD and decreasing the activities of MDA. Conclusion Collectively, catalpol intranasal administration has good safety, stability and brain targeting. It can effectively protect the brain injury of the rat model of acute cerebral ischemia and provide the possibility of drug administration in the acute stage of cerebral ischemia, especially before entering the hospital.

The neuroprotective effect of Chinese herbal medicine for cerebral ischemia reperfusion injury through regulating mitophagy

“…Jionoside A1 is a native compound derived from Rehmannia glutinosa (Di-huang), a Chinese medicine that is commonly used to treat brain diseases, including stroke. Rehmannia glutinosa has been found to be neuroprotective against acute cerebral ischemia and to improve cognitive dysfunction ( Fu et al, 2022 ; Wang et al, 2022 ). Although the study did not show significant alterations in Parkin and FUNDC1 expression, it did reveal that Jionoside A1 significantly enhanced mitochondrial content and promoted mitophagy in OGD/R and MCAO/R models by upregulating the expression of NIX protein in ischemic stroke I/R injury ( Fu et al, 2022 ).…”

Therapeutic potential of plant iridoids in depression: a review

“…It also increased SOD activity and decreased MDA activity by up-regulating the expression of Nrf2 and HO-1, minimizing oxidative stress injury (Wang J et al. 2022 ). NBDD might be a potential and promising route of administration for the treatment of brain-related diseases in the future.…”

A study on the mechanism of Beclin-1 m6A modification mediated by catalpol in protection against neuronal injury and autophagy following cerebral ischemia

“…Catalpol (CAT), isolated from Rehmannia glutinosa , has many pharmacological activities including anti-oxidative and anti-inflammatory effects and exerts a protective role in cerebral ischemia (Wang et al 2022 ). A study on the mechanism of CAT in cerebral ischemia stated that CAT protected vascular structure and promoted angiogenesis in focal cerebral ischemic rats by activating the hypoxia-inducible factor 1-alpha (HIF-1α)/vascular endothelial growth factor (VEGF) pathway (Wang et al 2020 ).…”