Black Myrobalan (Terminalia chebula) as a potential multitarget neuroprotective agent: Translational insights and future directions in neurodegenerative diseases

Myrobalan or Haritaki ( Terminalia chebula Retz. ) has been integrated into Ayurvedic, Unani, and even Tibetan medicine systems for over 2000 years. The “King of Medicines” has traditionally been used for diverse ailments such as digestive issues, wound healing, and general body strengthening. Now, modern medicine is focusing on the myrobalan's potential neuroprotective properties and its use in Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis (ALS) neurodegenerative disorders. These ailments are characterized by some combination of enduring oxidative damage, mitochondrial dysfunction, neuroinflammation, irregular protein aggregation, and progressive neuron cell death. Most of the current treatment options revolve around addressing the symptoms of the diseases, which is insufficient as the underlying disease continues to progress. There is an urgent need to devise therapies that work simultaneously on multiple disease pathways. Some of the noted secondary metabolites in T. chebula include hydrolyzable tannins like chebulinic and chebulagic acid as well as corilagin. Others occur as phenolic acids such as gallic and ellagic acid and flavonoids quercetin and kaempferol. Moreover, glycosides, sterols, and a wide range of alkaloids are also present. A number of these compounds are known to possess multifunctional biological properties like scavenging ROS, activating Nrf2/ARE signaling, downregulating pro-inflammatory mediators through blockade of NF-κB, and exerting protective effects on the mitochondria, as well as modulating apoptosis via Bcl-2 and caspases. T. chebula extracts and some isolated compounds have also been shown to improve cognitive function, reduce neuroinflammation, and protect dopaminergic neurons, and ameliorate neurotoxic effects of amyloid-β or α-synuclein through in vitro and in vivo animal studies. A review of the contributions from the phytochemistry, mechanism of action, preclinical, translational, and adjunctive applications of Terminalia chebula in neurodegenerative disease therapy is presented here.