Huntington's disease is a very uncommon, neurological disease diagnosed by chorea (abnormal involuntary movements), behavioural manifestations, psychological behavioral symptoms, and cognitive impairment, which develop at the age of 30-50 years, and severity increases with age. 1-2 Worldwide prevalence ranges from 5.96 to 13.7 per 100,000. 3 The exact pathogenic mechanism underlying HD has not been explained yet but mitochondrial dysfunction, excitotoxicity, neuroinflammation, oxidative stress, neurochemical imbalance, and apoptosis are the most well-accepted mechanisms. [4][5] Tetrabenazine and Deutetrabenazine are the only drugs that have been approved by the US FDA for treatment of chorea related to HD but it has their limitations like drug interaction and side effects. [6][7][8] 3 nitro propionic acid (3-NP) induced rat model of HD is found to be the most suitable preclinical model. 9 It is a mycotoxin, at chronic administration (10 mg/kg/day, 3-6 weeks) induces some features similar to those displayed by HD patients. The 3-NP model can mimic and reproduce the hyperkinetic and hypokinetic symptoms of HD, depending on the time and dose administered, thus allowing the initial and late phases of HD to be evaluated. [10][11][12] Bioflavonoids belong to a group of natural substances with variable phenolic structures and exhibit a variety of activities including antioxidant, anti-inflammatory, antiallergic, antiviral, and anticarcinogenic properties. [13][14] While there have only been a few studies on the potential beneficial effects of flavonoids in HD models, the published results suggest specific flavonoids could be of potential clinical use against HD. 15 Silymarin, a flavonolignan from the seeds of milk thistle (Silybum marianum), is a mixture of mainly three flavonolignans, which are silidianin, and silychristine, silybin and here silybin is considered to be more active. 16 Silymarin significantly inhibits the LPS (lipopolysaccharide)-induced activation of microglia and the production of inflammatory mediators, such as tumour necrosis factoralpha and nitric oxide (NO), and reduced the damage to dopaminergic neurons and protects the neurons of SNC (substantia nigra pars compacta). [17][18] Quercetin is categorized as a flavonol, prominently found in variety of fruits and vegetables. 19 Quercetin reverses 3-NP induced inhibition of respiratory chain complexes, restores ATP level, attenuates mitochondrial oxidative stress in terms of lipid peroxidation, and prevents mitochondrial swelling. Long-term treatment with quercetin can safely and effectively improve selected elements of motor performance and increase muscle mass during initial phases of aging. 20 Hesperidin, a bioflavonoid, is an abundant and inexpensive by-product of 'Citrus cultivation' with abundant of pharmacological properties and medicinal uses. 21 Hesperidin inhibits elevation of TNF-α level, apoptosis, and excitotoxicity in a quinolinic acid-induced rat model of HD. 22 The role of hesperidin concentration of 100 mg/kg p.o. on reduction of MDA (...