DOSE-DEPENDENT CHRONIC TOXICITY SCREENING OF HINOKITIOL IN ZEBRAFISHES: BEHAVIORAL AND HISTOLOGICAL APPROACH

Objectives: Parkinson’s disease (PD) is categorized as a movement disorder symptomized by weakening the motor skills of the patients. The root cause of the disease is the neurodegenerative dopaminergic loss in the substantia nigra of the patient’s brain. This havoc disease majorly affects the people above the age of 60 years. Moreover, PD incidences strike almost 70% of the neurological disorders of the aged population worldwide. There are no perfect curative drugs in the medical world for the disease. Since the past few decades, several plant secondary compounds were in preclinical trials to treat this disease. Hinokitiol (HIN), a monoterpenoid from the heartwood of cupressaceous plants, is widely used in hair tonics, toothpaste, cosmetics, and food as an antimicrobial agent. It is well reported as an anti-stroke agent as well. Methods: In the present study, the dose-dependent (5, 10, 15, 20, and 25 mg/kg) chronic toxicity of HIN was studied for 28 days using zebrafishes. The toxicity was analyzed in vital organs such as brain, liver, kidney, spleen, heart, and blood count followed by behavioral toxicity to target the drug against parkinsonism. Results: The study revealed that the higher doses of 20 and 25 mg/kg HIN treatment were toxic to the fish brain, spleen, as well as cardiomyocytes. It showed a variation in blood count as well at 10 mg/kg dose itself. Conclusion: Hence, the study revealed the protective efficacy of the HIN at its therapeutic dosage of 5 mg/kg as a neuroprotective drug, with minimal vital organ toxicities

COMPARATIVE ANALYSIS OF POTENTIALITY OF ESCULIN AND HINOKITOL (Î’-THUJAPLICIN) AS ANTI-PARKINSONISM DRUGS: A PILOT IN SILICO STUDY

Objective: Parkinson's disease (PD) is a leading cause of mental disability and death worldwide. Even though there are many advances in drug development against PD, a potent low dosage drug with fewer side effects are still in its nursery. This is a pioneer in silico attempt to test the anti-PD actions of esculin and hinokitol to act novel drugs.Methods: In this study, using Auto dock tools 4.2, esculin and hinokitol (β-Thujaplicin) were predicted for its inhibitory actions with Alpha-Synuclein (AS) Apo site, Dopamine D3 Receptor (D3R), Glycogen Synthase Kinase-3 Beta (GSK3β), Mono Oxidase B (MAO-B), Parkin and Tyrosine 3-Hydroxylase (TH) with levodopa standard. The reliability of the 3D predicted model of these proteins were analysed using RAMPAGE. Further, the blood-brain barrier (BBB) crossing ability of the natural compounds were analysed using cbligand. The In silico ADME (Absorption, Distribution, Metabolism, Excretion) properties of esculin and hinokitol were compared with that of levodopa using molinspiration and admetSAR @ LMMD software.Results: The predictions were that hinokitol, being blood-brain barrier positive (BBB+) with fewer side effects could be a potent anti-PD drug than esculin as it proved to be blood-brain barrier negative (BBB-). Hinokitol was predicted to be good inhibitors of AS, MAO-B and Parkin.Conclusion: The study revealed that hinokitol could be a potent anti-PD drug, being BBB+. Hinokitol was additionally predicted as a good inhibitor of AS, MAO-B and Parkin than levodopa standard.Â