MOLECULAR AND CELLULAR MECHANISM UNDERLYING THE NEUROPROTECTIVE EFFECTS OF HERBAL EXTRACTS IN HYPOTHYROIDISM- INDUCED NEURONAL DYSFUNCTION

Insufficient synthesis of thyroid hormones, namely triiodothyronine (T3) and thyroxine (T4), which are necessary for healthy brain development and neuronal function, is the hallmark of hypothyroidism, a common endocrine condition. Cognitive impairment, mood swings, synapse malfunction, and heightened vulnerability to neurodegeneration are all intimately linked to thyroid hormone shortage. At the molecular level, oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired neurogenesis, altered neurotransmitter synthesis, and dysregulation of neurotrophic signaling pathways like cyclic AMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) are all involved in hypothyroidism-induced neuronal damage. Together, these modifications lead to apoptosis, synapse loss, and structural abnormalities in the cortical and hippocampus areas. Polyphenol-, flavonoid-, alkaloids-, terpene-, and saponin-rich herbal extracts have shown promise as neuroprotective agents against neuronal damage linked to thyroid hormone deprivation. By scavenging reactive oxygen species, boosting endogenous antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and maintaining mitochondrial integrity, these phytoconstituents provide antioxidant effects. Furthermore, a number of substances derived from plants reduce neuroinflammation by modulating inflammatory mediators by blocking pro-inflammatory cytokines and NF-κB activation. Additionally, herbal extracts modulate the Bax/Bcl-2 and caspase pathways to reduce apoptosis, restore synaptic plasticity, control cholinergic and monoaminergic neurotransmission, and increase neurotrophic signaling. Certain phytochemicals also maintain thyroid hormone homeostasis by influencing the hypothalamic-pituitary-thyroid (HPT) axis. This article objectively assesses the neuroprotective potential of herbal extracts and provides a thorough summary of the molecular and cellular mechanisms driving brain damage caused by hypothyroidism. Comprehending these multi-targeted pathways might aid in the creation of plant-based supplemental treatments meant to stop the neurodegeneration and cognitive decline linked to thyroid malfunction.