Comprehensive In Silico Analysis of Uncaria Tomentosa Extract: Chemical Profiling, Antioxidant Assessment, and CLASP Protein Interaction for Drug Design in Neurodegenerative Diseases.

BACKGROUND: Uncaria tomentosa is a traditional medicinal herb renowned for its anti-inflammatory, antioxidant, and immune-enhancing properties. In the realm of neurodegenerative diseases (NDDS), CLASP proteins, responsible for regulating microtubule dynamics in neurons, have emerged as critical players. Dysregulation of CLASP proteins is associated with NDDS, such as Alzheimer's, Parkinson's, and Huntington's diseases. Consequently, comprehending the role of CLASP proteins in NDDS holds promise for the development of innovative therapeutic interventions. OBJECTIVES: The objectives of the research were to identify phytoconstituents in the hydroalcoholic extract of Uncaria tomentosa (HEUT), to evaluate its antioxidant potential through in vitro free radical scavenging assays and to explore its potential interaction with CLASP using in silico molecular docking studies. METHODS: HPLC and LC-MS techniques were used to identify and quantify phytochemicals in HEUT. The antioxidant potential was assessed through DPPH, ferric reducing antioxidant power (FRAP), nitric oxide (NO) and superoxide (SO) free radical scavenging methods. Interactions between conventional quinovic acid, chlorogenic acid, epicatechin, corynoxeine, rhynchophylline and syringic acid and CLASP were studied through in silico molecular docking using Auto Dock 4.2. RESULTS: The HEUT extract demonstrated the highest concentration of quinovic acid derivatives. HEUT exhibited strong free radical-scavenging activity with IC50 values of 0.113 µg/ml (DPPH) and 9.51 µM (FRAP). It also suppressed NO production by 47.1 ± 0.37% at 40 µg/ml and inhibited 77.3 ± 0.69% of SO generation. Additionally, molecular docking revealed the potential interaction of quinovic acid with CLASP for NDDS. CONCLUSION: The strong antioxidant potential of HEUT and the interaction of quinovic acid with CLASP protein suggest a promising role in treating NDDS linked to CLASP protein dysregulation.

Targeting GM2 Ganglioside Accumulation in Dementia: Current Therapeutic Approaches and Future Directions.

Dementia in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB) is a progressive neurological condition affecting millions worldwide. The amphiphilic molecule GM2 gangliosides are abundant in the human brain and play important roles in neuronal development, intercellular recognition, myelin stabilization, and signal transduction. GM2 ganglioside's degradation requires hexosaminidase A (HexA), a heterodimer composed of an α subunit encoded by HEXA and a ß subunit encoded by HEXB. The hydrolysis of GM2 also requires a non-enzymatic protein, the GM2 activator protein (GM2-AP), encoded by GM2A. Pathogenic mutations of HEXA, HEXB, and GM2A are responsible for autosomal recessive diseases known as GM2 gangliosidosis, caused by the excessive intralysosomal accumulation of GM2 gangliosides. In AD, PD and DLB, GM2 ganglioside accumulation is reported to facilitate Aß and α-synuclein aggregation into toxic oligomers and plaques through activation of downstream signaling pathways, such as protein kinase C (PKC) and oxidative stress factors. This review explored the potential role of GM2 ganglioside alteration in toxic protein aggregations and its related signaling pathways leading to neurodegenerative diseases. Further review explored potential therapeutic approaches, which include synthetic and phytomolecules targeting GM2 ganglioside accumulation in the brain, holding a promise for providing new and effective management for dementia.

COVID-19: facts, figures, estimated relationships and analysis.

This study attempts an integrated analysis of the health and economic aspects of COVID-19 that is based on publicly available data from a wide range of data sources. The analysis is done keeping in mind the close interaction between the health and economic shocks of COVID-19. The study combines descriptive and qualitative approaches using figures and graphs with quantitative methods that estimate the plotted relationships and econometric estimation that attempts to explain cross-country variation in COVID-19 incidence, deaths and 'case fatality rates'. The study seeks to answer a set of questions on COVID-19 such as: what are the economic effects of COVID-19, focussing on international inequality and global poverty? How effective was lockdown in curbing COVID-19? What was the effect of lockdown on economic growth? Did the stimulus packages work in delinking the health shocks from the economic ones? Did 'better governed countries' with greater public trust and those with superior health care fare better than others? Did countries that have experienced previous outbreaks such as SARS fare better than those who have not? The study provides mixed messages on the effectiveness of lockdowns in controlling COVID-19. While several countries, especially in the East Asia and Pacific region, have used it quite effectively recording low infection rates going into lockdown and staying low after the lockdown, the two spectacular failures are Brazil and India. In contrast to lockdown, the evidence on the effectiveness of stimulus programs in avoiding recession and promoting growth is unequivocal. The effectiveness is much greater in the case of emerging/developing economies than in the advanced economies. Multilateral institutions such as the World Bank and the IMF need to work out a coordinated strategy to declare immediate debt relief and provide additional liquidity to the poorer economies to help them announce effective stimulus measures. COVID-19 will lead to a large increase in the global pool of those living in 'extreme poverty'. A poignant feature of our results is that while a significant share of health shocks from COVID-19 is borne by the advanced economies, the burden of 'COVID-19 poverty' will almost exclusively fall on two of the poorest regions, namely, Sub-Saharan Africa and South Asia.

The economic burden of non-communicable disease mortality in the South Pacific: Evidence from Fiji.

Non-communicable diseases (NCDs) have emerged as one of the major endemics in Fiji which is responsible for more than 80 percent of deaths annually. In this study, we estimate the economic burden of non-communicable disease mortality in Fiji. The specific impact of diabetes, cardiovascular disease, chronic respiratory disease and cancer-related mortality on Fiji's output is also investigated using the autoregressive distributed lag bounds tests approach to cointegration. The data used is compiled from Fiji Ministry of Health and Medical Services and World Health Organization's Mortality database. Overall, the study finds that NCD mortality rate together with cardiovascular disease, diabetes, chronic respiratory disease and cancer have a significant negative effect on output per capita of Fiji between 1972 and 2016. A one percentage point increase in NCD-mortality rate reduced output per capita by 0.012 percent. In addition, a percentage point increase in the mortality rates of cardiovascular disease, diabetes, chronic respiratory disease and cancer decreased output per capita by 0.018, 0.01, 0.031, and 0.035 percent, respectively. The findings conclude that NCD poses significant economic burden in Fiji and recommend policy innovations in lessening the high risk of NCD among the Fijian population.