A Research Update on Exendin-4 as a Novel Molecule Against Parkinson's Disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, and its consequences severely influence the quality of a patient's life and mobility. PD is characterized by bradykinesias with tremors and/or rigidity. Pathophysiologically, PD is associated with the gradual degeneration of dopaminergic neurons in the substantia nigra pars compacta of the midbrain, neuroinflammation, increased accumulation of the alpha (α)-synuclein, overburden of oxidative stress, and mitochondrial dysfunction. To date, there are no effective therapies with underlying shreds of evidence that alters the progression of PD. Exendin-4, a glucagon-like peptide 1 (GLP-1) receptor agonist, has gained attention for its tremendous neuroprotective potential against numerous neurodegenerative disorders, including PD. Further, several pieces of research evidence have suggested the beneficial role of Exendin-4 in PD-like experimental models. The present review article highlights the preclinical and clinical evidence of the therapeutic benefits of Exendin-4 against PD. Exendin-4 reverses the PD-like symptoms in experimental animals by dramatically minimizing the loss of dopaminergic neuronal and accumulation of α-synuclein in the PD-like brain. Further, it also reduces the mitochondrial toxicity and expression of pro-inflammatory mediators such as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. These observations designate that Exendin-4 is a multifactorial compound that could be considered a safe, effective, and new ingredient for developing clinically useful pharmacotherapy for managing PD-like manifestations.

Social determinants of tobacco use among tribal communities in India: Evidence from the first wave of Longitudinal Ageing Study in India.

BACKGROUND: Evidence on tobacco use among indigenous communities is scarce with available literature based either on a specific region or a particular tribe. Considering the large tribal population in India, it is pertinent to generate evidence on tobacco use among this community. Using nationally representative data, we aimed to estimate the prevalence of tobacco use and assess its determinants and regional variations among older tribal adults in India. METHODS: We analysed data from Longitudinal Ageing Study in India (LASI), wave-1 conducted in 2017-18. A sample of 11,365 tribal individuals aged ≥ 45 years was included in this study. Descriptive statistics was used to assess the prevalence of smokeless tobacco (SLT), smoking, and any form of tobacco use. Separate multivariable regression models were executed to assess the association of various socio-demographic variables with different forms of tobacco use, reported as adjusted odds ratio (AOR) with 95% confidence interval. RESULTS: The overall prevalence of tobacco use was around 46%, with 19% of smokers and nearly 32% smokeless tobacco (SLT) users. Participants from the lowest MPCE quintile group had a significantly higher risk of consuming (SLT) [AOR: 1.41 (95% CI: 1.04-1.92)]. Alcohol was found to be associated with both smoking [AOR: 2.09 (95% CI: 1.69-2.58)] and (SLT) [AOR: 3.05 (95% CI: 2.54-3.66)]. Relatively higher odds of consuming (SLT) were associated with the eastern region [AOR: 6.21 (95% CI: 3.91-9.88)]. CONCLUSION: This study highlights the high burden of tobacco use and its social determinants among the tribal population in India, which can help tailor anti-tobacco messages for this vulnerable population to make tobacco control programs more effective.

Smokeless tobacco utilization among tribal communities in India: A population-based cross-sectional analysis of the Global Adult Tobacco Survey, 2016-2017.

Introduction: Evidence on smokeless tobacco use is scarce among indigenous communities, with the available literature based either on a specific tribe or on a particular region. Therefore, we aimed to estimate the prevalence of smokeless tobacco and assess its correlation among tribal communities in India. Methods: We utilized data from the Global Adult Tobacco Survey-2 conducted in 2016-2017. A total of 12,854 tribal people aged >15 years were included in this study. The utilization of smokeless tobacco was estimated using the weighted proportion, and its correlates were assessed by multivariable logistic regression reported as an adjusted odds ratio (AOR) with a 95% confidence interval. Results: The prevalence of smokeless tobacco use was 32%. Participants aged 31-45 years [AOR: 1.66 (1.37-2.00)], who were men [AOR: 2.37 (1.94-1.90)], and who were daily wage/casual laborers [AOR: 5.32 (3.39-8.34)] were observed to have a significant association with smokeless tobacco. Willingness and attempt to quit smokeless tobacco were higher in Eastern India (31.2%) and central India (33.6%), respectively. Discussion: We observed one-third of the tribal individuals used smokeless tobacco in India. Tobacco control policies should prioritize men, rural residents, and individuals with fewer years of schooling. Culturally appropriate and linguistically tailored messages are required for behavioral change communication.

Molecular mechanisms regulating the pharmacological actions of icariin with special focus on PI3K-AKT and Nrf-2 signaling pathways.

Icariin is a primary active component of the traditional Chinese medicinal plant Epimedium grandiflorum. A range of pharmacological effects of icariin has been researched by modern science to explain its traditional medicinal uses. Attributing to the wide range of pharmacological properties like anti-osteoporosis, anti-inflammation, anti-oxidative stress, anti-depression, and anti-tumor property possessed by icariin, it is now being considered a potential therapeutic agent for a wide variety of disorders ranging from neoplasm, neurodegenerative disorders, osteoporosis, and cardiovascular diseases. Various signaling pathways including NFκB/NALP3, IGF-1, MiR-223-3p/ NALP3, TLR4/ NFκB, and WNT1/ß-catenin are involved in the different biological actions exerted by icariin. Apart from these pathways, PI3K-AKT (Phosphoinositide 3 kinase-Protein kinase B) and Nrf-2 (nuclear erythroid 2-related factor 2) signaling pathways are two important pathways that form the fundamental basis for the pharmaceutical efficacy of icariin. This review gives an overview of previous in vitro and in vivo studies that investigated the potential role of icariin via PI3K-AKT and Nrf-2 signaling pathways to provide greater insights into its potential clinical use in a variety of disorders.