Bindal, Priya, Roy, Kaunava, Sarkar, Biplob, Rana, Natasha, Kapil, Lakshay, Singh, Charan, and Singh, Arti
Reduced blood flow (hypoxia) to the brain is thought to be the main cause of strokes because it deprives the brain of oxygen and nutrients. An increasing amount of evidence indicates that the Centella-Asiatica (HA-CA) hydroalcoholic extract has a variety of pharmacological benefits, such as antioxidant activity, neuroprotection, anti-inflammatory qualities, and angiogenesis promotion. Intermittent fasting (IF) has neurological benefits such as anti-inflammatory properties, neuroprotective effects, and the ability to enhance neuroplasticity. The current study evaluates the combined effect of IF (for 1, 6, and 12 days) along with HA-CA (daily up to 12 days) in adult zebrafish subjected to hypoxia every 5 min for 12 days followed by behavioral (novel tank and open-field tank test), biochemical (SOD, GSH-Px, and LPO), inflammatory (IL-10, IL-1β, and TNF-α), mitochondrial enzyme activities (Complex-I, II, and IV), signaling molecules (AMPK, MAPK, GSK-3β, Nrf2), and imaging/staining (H&E, TTC, and TEM) analysis. Results show that sub-acute hypoxia promotes the behavioral alterations, and production of radical species and alters the oxidative stress status in brain tissues of zebrafish, along with mitochondrial dysfunction, neuroinflammation, and alteration of signaling molecules. Nevertheless, HA-CA along with IF significantly ameliorates these defects in adult zebrafish as compared to their effects alone. Further, imaging analysis significantly provided evidence of infarct damage along with neuronal and mitochondrial damage which was significantly ameliorated by IF and HA- CA. The use of IF and HA-CA has been proven to enhance the physiological effects of hypoxia in all dimensions. A reduction in the supply of oxygen results in stroke through an elevation in oxidative stress, reactive oxygen species, mitochondrial dysfunction and inflammation. Elevated levels of ROS are accountable for the inhibition of AMPK following sub-acute term hypoxia, which is responsible for cell survival. Our treatment, namely IF and HA-CA, exhibit an effect and vice versa. [Display omitted] • Sub-acute hypoxia exposure produces alterations in zebrafish behavior, along with biological and cellular activity. • HA-CA and IF promote cell viability by regulating AMPK levels. • AMPK activation appears to improve mitochondrial enzyme activity, oxidative stress, and inflammation. • Elevated AMP to ATP ratio leads to AMPK activation, autophagy, and increased energy production in cerebral ischemia or hypoxia. [ABSTRACT FROM AUTHOR]