L-theanine from Camellia sinensis (L.) attenuates 3-NP-induced Huntington's disease-like alterations by remedying behavioral patterns and modulating neurotransmitters across three distinct brain regions: evidence from in-vivo and in-silico approaches.

Huntington's disease (HD) is a neurological condition with limited treatment. Its hallmarks are progressive loss of neurons, chorea, cognitive, motor, and metabolic impairments. The current study uses 3-nitropropionic acid (3-NP) to cause HD-like indications in rats. L-theanine (L-TH), an active component of Camellia sinensis, has already been shown to possess anti-inflammatory and anti-oxidant effects. The impact of the isolated phytoconstituent, L-TH, on 3-NP-induced changes in three distinct brain regions was assessed in the current study. The animals received a 7-day pretreatment consisting of normal saline, extract of C. sinensis (100 and 200 mg/kg b.w., i.p.), L-TH (10 mg/kg b.w., i.p.), and standard Tetrabenazine (TBZ, 25 mg/kg, b.w., i.p.). The administration of 3-NP (10 mg/kg b.w., i.p.) to the treatment groups began on the 8th day of the protocol and continued until the 21st day. The brain homogenates underwent biochemical and neurochemical assessments. In conclusion, L-TH improved behavioral outcomes and attenuated 3-NP-induced neurochemical alterations in brain homogenates. Histopathological analysis revealed lower levels of tissue damage in the L-TH-treated group compared to the 3-NP group. Molecular docking studies further indicated favorable interactions of L-TH with the HTT protein. These findings suggest that L-TH may attenuate 3-NP-induced Huntington's disease-like alterations in rats. However, additional studies using genetic HD models and molecular mechanisms are required to confirm its therapeutic efficacy and underlying mode of action.