Huperzine A Ameliorates Cognitive Deficits and Oxidative Stress in the Hippocampus of Rats Exposed to Acute Hypobaric Hypoxia

Abstract

Acute exposure to high altitudes can cause neurological dysfunction due to decreased oxygen availability to the brain. In this study, the protective effects of Huperzine A on cognitive deficits along with oxidative and apoptotic damage, due to acute hypobaric hypoxia, were investigated in male Sprague-Dawley rats. Rats were exposed to simulated hypobaric hypoxia at 6,000 m in a specially fabricated animal decompression chamber while receiving daily Huperzine A orally at the dose of 0.05 or 0.1 mg/kg body weight. After exposure to hypobaric hypoxia for 5 days, rats were trained in a Morris Water Maze for 5 consecutive days. Subsequent trials revealed Huperzine A supplementation at a dose of 0.1 mg/kg body weight restored spatial memory significantly, as evident from decreased escape latency and path length to reach the hidden platform, and the increase in number of times of crossing the former platform location and time spent in the former platform quadrant. In addition, after exposure to hypobaric hypoxia, animals were sacrificed and biomarkers of oxidative damage, such as reactive oxygen species, lipid peroxidation, lactate dehydrogenase activity, reduced glutathione, oxidized glutathione and superoxide dismutase were studied in the hippocampus. Expression levels of pro-apoptotic proteins (Bax, caspase-3) and anti-apoptotic protein (Bcl-2) of hippocampal tissues were evaluated by Western blotting. There was a significant increase in oxidative stress along with increased expression of apoptotic proteins in hypoxia exposed rats, which was significantly improved by oral Huperzine A at 0.1 mg/kg body weight. These results suggest that supplementation with Huperzine A improves cognitive deficits, reduces oxidative stress and inhibits the apoptotic cascade induced by acute hypobaric hypoxia.

Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats

“…Our present investigation showed the remarkable elevation of caspase-3 activity in the cerebral cortex and hippocampus of diabetic rat brain and this effect was blocked by HupA treatment, implicating that HupA decreased neuronal death in a diabetic rat model. Consistently, it was previously illustrated that HupA attenuated caspase-dependent neuronal apoptosis in the hippocampus of rats during acute hypobaric hypoxia [31]. Moreover, HupA treatment also ameliorated serum deprivation-induced apoptosis via inhibiting mitochondria-dependent caspase-3 activity in cultures of rat cortical neurons [32].…”

“…Animals in each experiment were randomly assigned to four groups: (1) control group (Con) ( n = 8), with normal rats that received saline intraperitoneally (physiological saline 0.1 mL/100 g); (2) vehicle group (DM) ( n = 8), the diabetic rats that received saline intraperitoneally (physiological saline 0.1 mL/100 g); (3,4) HupA groups (DM + HupA (0.05) and DM + HupA (0.1)) ( n = 8), diabetic rats treated with HupA at doses of 0.05 and 0.1 mg/kg, respectively. The dosage and dosing frequency of HupA were selected according to the previous reports [18,31]. HupA was freshly prepared by dissolving in the physical saline and injected intraperitoneally once a day.…”

Original article Assessment of antioxidative activity of alkaloids from Huperzia selago and Diphasiastrum complanatum using in vitro systems

“…Additional studies are necessary to reveal which components are responsible for antioxidative properties of the selected fractions, and to determine the exact mechanism of their antioxidative activity. It was previously suggested that HupA possesses potent antiapoptotic, neuroprotective and antioxidative properties [34,43,51,52,56]. Our study demonstrated that this alkaloid is not a direct scavenger of free radicals, and other mechanisms are responsible for its antioxidative potential.…”

Effects of Pre-Workout Supplements on Power Maintenance in Lower Body and Upper Body Tasks

“…This supplement has been shown to increase blood levels of ATP [22], increase exercise levels in sedentary individuals from a single dose [23], and enhance responses to chronic resistance training [24]. The supplement Huperzine has been shown to have positive effects on brain function, specifically decreasing cognitive deficits and oxidative stress in the rodent model after hypobaric hypoxia [25], and has been shown in conjunction with other supplements to enhance upper body strength endurance performance [6] and anaerobic sprint performance [26].…”