Demethyleneberberine: A possible treatment for Huntington's disease.

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.

Expanding the Arsenal Against Huntington's Disease-Herbal Drugs and Their Nanoformulations.

Huntington's disease (HD) is an autosomal fatal genetic disease in which degeneration of neuronal cells occurs in the central nervous system (CNS). Commonly used therapeutics are cludemonoamine depletors, antipsychotics, antidepressants, and tranquilizers. However, these drugs cannot prevent the psychotic, cognitive, and behavioral dysfunctions associated with HD. In addition to this, their chronic use is limited by their long-term side effects. Herbal drugs offer a plausible alternative to this and have shown substantial therapeutic effects against HD. Moreover, their safety profile is better in terms of side effects. However, due to limited drug solubility and permeability to reach the target site, herbal drugs have not been able to reach the stage of clinical exploration. In recent years, the paradigm of research has been shifted towards the development of herbal drugs based nanoformulations that can enhance their bioavailability and blood-brain barrier permeability. The present review covers the pathophysiology of HD, available biomarkers, phytomedicines explored against HD, ongoing clinical trials on herbal drugs exclusively for treating HD and their nanocarriers, along with their potential neuroprotective effects.

Influence of Forward Head Posture on Cervicocephalic Kinesthesia and Electromyographic Activity of Neck Musculature in Asymptomatic Individuals.

OBJECTIVE: The purpose of this study was to compare cervicocephalic kinesthesia and electromyographic (EMG) activity of neck muscles-upper trapezius (UT) and sternocleidomastoid (SCM)-between individuals with and without forward head posture (FHP) and to examine the correlation between cervicocephalic kinesthesia and craniovertebral angle (CVA). METHODS: Twenty-two asymptomatic individuals with FHP and 22 without FHP were recruited for the present study. Craniovertebral angle was measured, and those with CVA ≤53° were assigned to the FHP group, whereas those with CVA >53° were assigned to the control group. Thereafter, cervicocephalic kinesthesia and EMG activity of the neck muscles were assessed. Cervicocephalic kinesthesia was measured using a head repositioning accuracy test for all cervical spine motions. EMG activity of the UT and SCM muscles was recorded at rest and during activity. RESULTS: Position-sense error values were found to be significantly greater for all directions-ie, flexion, extension, side flexion, and rotation-in participants with FHP than those without (P < .05). EMG activity of the UT and SCM muscles was found to be significantly raised both at rest and during activity in individuals with FHP relative to the non-FHP group (P < .05). Position-sense error values showed a significant inverse correlation with CVA (P < .05). CONCLUSION: Findings of the present study suggest that cervicocephalic kinesthesia and activation patterns of the neck muscles may be significantly altered in individuals with FHP. Also, cervicocephalic kinesthesia is significantly associated with the severity of FHP.