Demethyleneberberine: A possible treatment for Huntington's disease. (August 2021)

• Record Type: Journal Article
• Authors: Gupta, Saurabh; Khan, Arzoo; Vishwas, Sukriti; Gulati, Monica; Gurjeet Singh, Thakur; Dua, Kamal; Kumar Singh, Sachin; Najda, Agnieszka; Sayed, Amany A.; Almeer, Rafa; Abdel-Daim, Mohamed M.
• Is Part Of: Medical hypotheses. Volume 153(2021)
• Publication Date: 2021-08
• Subjects: Ach Acetylcholine -- AD Alzheimer's disease -- ADP Adenosine diphosphate -- ANT Adenine nucleotide translocator -- BBB Blood brain barrier -- BBR berberine -- CI cerebral ischemia -- COX-2 Cyclooxygenase-2 -- CNS Central nervous system -- DMB Demethyleneberberine -- ECR Electron chain reaction -- GABA Gamma aminobutyric acid -- HD Huntington disease -- Htt Huntingtin -- IL Interleukin -- Inos Inducible nitric oxide synthase -- MC Microglial cell -- mPTP Mitochondrial transition pore -- MyD88 Differentiated 88 -- MPT Mitochondrial permeability transition -- ND Neurodegenerative disease -- NF-κB nuclear factor-kB -- NMDA N-methyl-D-aspartate -- 3-NP 3-Nitropropionic acid -- PD Parkinson's disease -- PGE2 Prostaglandin E2 -- ROS/RNS Reactive oxygen/nitrogen species -- TCA Tricarboxilic acid -- TLR4 Toll-like receptor-4 -- TNF-α Tumor necrosis factor α; Huntington disease -- Demethyleneberberine -- Reactive oxygen/nitrogen species -- Oxidative stress -- Neuroinflammation; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Medicine; Periodicals; 610
• DOI: 10.1016/j.mehy.2021.110639
• Languages: English
• ISSNs: 0306-9877

Abstract

Abstract: Huntington disease (HD) is a type of neurodegenerative disease that is characterized by presence of multiple repeats (more than 36) of cytosine-adenine-guanine (CAG) trinucleotides and mutated huntingtin (mHtt). This can further lead to oxidative stress, enhancement in level of ROS/RNS, mitochondrial dysfunction and neuroinflammations. Many clinical and preclinical trials have been conducted so far for the effective treatment of HD however, none of the drugs has shown complete relief. The regeneration of neurons is a very complicated process and associated with multiple pathological pathways. Hence, finding a unique solution using single drug that could act on multiple pathological pathways is really cumbersome. In the proposed hypothesis the use of demethyleneberberine (DMB) as a potential anti-HD agent has been explained. It is a metabolite of berberine and reported to act on multiple mechanistic pathways that are responsible for HD. Present article highlights new mechanistic insights through which DMB inhibits ROS/RNS, oxidative stress, mitochondrial dysfunctions and neuroinflammation such as NFκB, TNF-α, IL-6 and IL-8, cytokinin. Further its action on cellular apoptosis and neuronal cell death are also reported.