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<p>The present study is a good example of hybridization of allopathic and herbal bioactive to overcome the limitations of both. Sinemet, a mixture of L-3,4-dihydroxyphenylalanine (L-DOPA) and Carbidopa, is the only commercial drug prescribed for Parkinson’s disease (PD). Sinemet poses several risks of long-term side effects. Our earlier studies aimed to assess neuroprotective molecules to avert such risks have shown that the polyphenol Curcumin protects neuronal mitochondria against oxidative/nitrosative stress, induces glutathione synthesis in cell and animal models of PD. The objective was to design, synthesize and assess the neuroprotective activity of a hybrid conjugate of L-DOPA and Curcumin. While L-DOPA could elevate the dopamine content in vivo, Curcumin could inhibit oxidation, neuro-inflammation and protein aggregation thereby inhibiting neurodegeneration. A L-DOPA conjugate with pharmacophore of Curcumin (L-DOPA-MHB) was synthesized and characterized. Its neuroprotective ability was tested in male Sprague Dawley rats of PD in vivo. L-DOPA-MHB treatment exhibits improved PD-specific pathological markers in 6-OHDA-induced model of PD validated through rotarod test and apomorphine-induced rotation test. 6-OHDA-induced rats showed depleted level of tyrosine hydroxylase (TH) and increased level of cleaved caspase 3 in both substantia nigra (SN) and striatum (STR) regions of rat brain.</p>

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Design, Synthesis and In Vivo Assessment of the Neuroprotective Activity of a Novel Hybrid Conjugate of L-DOPA and Curcumin

  • 期刊论文

  • 发表日期：

    2025年7月5日

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  • Manoj K. Shrivash,
  • K. Amrutha,
  • Sarika Singh,
  • Unnati Soni,
  • Krishna Misra

摘要

The present study is a good example of hybridization of allopathic and herbal bioactive to overcome the limitations of both. Sinemet, a mixture of L-3,4-dihydroxyphenylalanine (L-DOPA) and Carbidopa, is the only commercial drug prescribed for Parkinson’s disease (PD). Sinemet poses several risks of long-term side effects. Our earlier studies aimed to assess neuroprotective molecules to avert such risks have shown that the polyphenol Curcumin protects neuronal mitochondria against oxidative/nitrosative stress, induces glutathione synthesis in cell and animal models of PD. The objective was to design, synthesize and assess the neuroprotective activity of a hybrid conjugate of L-DOPA and Curcumin. While L-DOPA could elevate the dopamine content in vivo, Curcumin could inhibit oxidation, neuro-inflammation and protein aggregation thereby inhibiting neurodegeneration. A L-DOPA conjugate with pharmacophore of Curcumin (L-DOPA-MHB) was synthesized and characterized. Its neuroprotective ability was tested in male Sprague Dawley rats of PD in vivo. L-DOPA-MHB treatment exhibits improved PD-specific pathological markers in 6-OHDA-induced model of PD validated through rotarod test and apomorphine-induced rotation test. 6-OHDA-induced rats showed depleted level of tyrosine hydroxylase (TH) and increased level of cleaved caspase 3 in both substantia nigra (SN) and striatum (STR) regions of rat brain.