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Parkinson's disease (PD) is a complex and debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The pathogenesis of PD is intimately linked to the roles of two key molecular players, α-synuclein (α-syn) and Parkin. Understanding the intricate interplay between α-syn and Parkin is essential for unravelling the molecular underpinnings of PD. Their roles in synaptic function and protein quality control underscore their significance in neuronal health. Dysregulation of these processes, as seen in PD, highlights the potential for targeted therapeutic strategies aimed at restoring normal protein homeostasis and mitigating neurodegeneration. Investigating the connections between α-syn, Parkin, and various pathological mechanisms provides insights into the complex web of factors contributing to PD pathogenesis and offers hope for the development of more effective treatments for this devastating neurological disorder. The present compilation provides an overview of their structures, regional and cellular locations, associations, physiological functions, and pathological roles in the context of PD.
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Doença de Parkinson , Ubiquitina-Proteína Ligases , alfa-Sinucleína , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Humanos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Animais , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologiaRESUMO
Diabetes mellitus (DM) is an endocrinological disorder in which blood sugar levels get elevated and if unmanaged, it leads to several critical complications. Existing therapies or drugs are not able to attain absolute control of DM. Moreover, associated side/adverse effects associated with pharmacotherapy further worsen the Quality of life of patients. Present review is focused on therapeutical potential of flavonoids in management of diabetes and diabetic complications. Plenteous literature has established significant potential of flavonoids in the treatment of diabetes and diabetic complications. A number of flavonoids are found to be effective in treatment of not only diabetes but progression of diabetic complication was also found to be attenuated with the use of flavonoids. Moreover, SAR studies of some flavonoids also indicated the that efficacy of flavonoids is increased with a change in functional group of flavonoids in the treatment of diabetes and diabetic complications. A number of clinical trials are into action to investigate the therapeutic potential of flavonoids as first-line drugs or as adjuvants for treatment of diabetes and diabetic complications.. Owing to their diverse mechanism of action, efficacy and safety, flavonoids may be conscripted as potential candidate for treatment of diabetic complications.
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ETHNOPHARMACOLOGICAL RELEVANCE: Iris Kashmiriana Baker, a traditional medicinal plant, is native to Asia, found in India, Nepal, Afghanistan, Pakistan, as name indicates majorly it's found in Kashmir region of India. Ethnopharmacologically this plant has been used there for the management of joint pain, but there was no scientific literature available. This species also comes under critically endangered species. AIM OF THE STUDY: The current study aims to evaluate the effect of Iris kashmiriana Baker against nociception and rheumatoid arthritis in experimental rats with In-silico model. MATERIAL AND METHODS: Various extracts of the plant were investigated for their in-vitro antioxidant activity. Acute inflammation and FCA induced in rat model, then acetic acid-induced writhing in mice were used. These anti-rheumatic results were justified by the computational method. RESULTS: The total phenolic and flavonoid concentration of HE extracts were found to be 95.30 ± 2.80 mg/g and 18.18 ± 5.88 mg/g respectively. IC50 and maximum inhibition of HE extracts against DPPH and H2O2 were also effective. Among different doses, 400 mg/kg of HE extracts showed significant (p<0.001) reduction in acute inflammation (16.42 %), in analgesic activity, the HE extract was found statistically (p<0.001) reduced (60.15 %) and in arthritis model, maximum inflammation reduced (25.9%) was found with hydro ethanol extract and statistical significant (p<0.001). and the paw thickness was reduced (27.4 %). Antioxidant activity of HE extract was found to be optimum (37.01%, p<0.001), Superoxide dismutase concentration was found to be optimum (65.12%, p<0.001). In Histopathology, HE 400 mg/kg showed mild inflammation only. The weight of the thymus and spleen were also determined and the HE 400 mg/kg extract inhibited the increase in weight of these organs compared with positive group (28.26 %, and 25.11 %), respectively. CONCLUSION: Among all the different extracts and various doses, the iris kashmiriana Baker hydro-ethanolic (60:40) 400 mg/kg extract showed the best response among all different extracts.
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Artrite Reumatoide , Extratos Vegetais , Ratos , Camundongos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Nociceptividade , Peróxido de Hidrogênio , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Etanol/uso terapêutico , PaquistãoRESUMO
Although the brain is very accessible to nutrition and oxygen, it can be difficult to deliver medications to malignant brain tumours. To get around some of these issues and enable the use of therapeutic pharmacological substances that wouldn't typically cross the blood-brain barrier (BBB), convection-enhanced delivery (CED) has been developed. It is a cutting-edge strategy that gets beyond the blood-brain barrier and enables targeted drug administration to treat different neurological conditions such as brain tumours, Parkinson's disease, and epilepsy. Utilizing pressure gradients to spread the medicine across the target area is the main idea behind this diffusion mechanism. Through one to several catheters positioned stereotactically directly within the tumour mass, around the tumour, or in the cavity created by the resection, drugs are given. This method can be used in a variety of drug classes, including traditional chemotherapeutics and cutting-edge investigational targeted medications by using positive-pressure techniques. The drug delivery volume must be optimized for an effective infusion while minimizing backflow, which causes side effects and lowers therapeutic efficacy. Therefore, this technique provides a promising approach for treating disorders of the central nervous system (CNS).
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Cardiovascular and neurological diseases cause substantial morbidity and mortality globally. Moreover, cardiovascular diseases are the leading cause of death globally. About 17.9 million people are affected by cardiovascular diseases and 6.8 million people die every year due to neurological diseases. The common neurologic manifestations of cardiovascular illness include stroke syndrome which is responsible for unconsciousness and several other morbidities significantly diminished the quality of life of patients. Therefore, it is prudent need to explore the mechanistic and molecular connection between cardiovascular disorders and neurological disorders. The present review emphasizes the association between cardiovascular and neurological diseases specifically Parkinson's disease, Alzheimer's disease, and Huntington's disease.
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Transtornos Cerebrovasculares , Humanos , Transtornos Cerebrovasculares/etiologia , Doenças Cardiovasculares , Qualidade de Vida , Doenças do Sistema Nervoso CentralRESUMO
M. oleifera is the most adapted tree species in different medicinal eco-systems and has resilience against climate changes. This multiple-use tree provides healthy foods, snacks, honey, and fuel. Besides this, it has immense promising applicationsby offering antimicrobial and antibacterial activities for targeted uses. This validates the court of Hippocrates that let food be the medicine and medicine be the food for which moringa qualifies. In view of this, the antioxidant and in vitro antibacterial potency of the hydro-ethanolic extract of M. oleifera was evaluated on clinically isolated multidrug-resistant strains of Staphylococcus aureus. Furthermore, in vivo, the healing response of M. oleifera extract was analysed on corneal ulcers induced in rabbit eyes infected with methicillin-resistant Staphylococcus aureus. TheM. oleifera extract exhibited exponential antioxidant activity. In-vitro antibacterial activity was evaluated by agar well diffusion assay showing zone of inhibition ranging from 11.05±0.36 to 20±0.40 mm at concentrations of 20, 40, 80, and 160 mg/ml, whereas, in our finding, no zone of inhibition was observed below 20 mg/ml concentration, which indicated that there is threshold limit below which the antibacterial activity of M. oleifera extract is not observed. Furthermore, continuous application of 3% and 5% M. oleifera extract (eye drop) four times a day for 14 consecutive days showed a significant healing response of the eyes of rabbits with corneal ulcers. These results suggest that M. oleifera extract could be a viable alternative to existing antibacterial therapies for corneal ulcers. Additionally, there is a possibility of commercial formulation of M. oleifera extract in the form of deliverable pharmaceutical products; therefore, it should be explored further.
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Objective: This review aims to explore the impact of the COVID-19 pandemic on mental health, with a focus on the physiological and psychological consequences, including comorbidities. The goal is to understand the direct and indirect populations affected by mental distress and identify potential interventions. Methodology: A comprehensive literature search was conducted using various databases, including Google Scholar, ResearchGate, ScienceDirect, PubMed, PLoS One, and Web of Science. The search utilized relevant keywords to investigate the direct and indirect impacts of COVID-19 on mental health. The selected articles were critically evaluated and analyzed to identify key findings and insights. Main findings: Mental health, being an intrinsic component of overall well-being, plays a vital role in physiological functioning. The COVID-19 pandemic, caused by the emergence of the novel SARS-CoV-2 virus, has had a devastating global impact. Beyond the respiratory symptoms, individuals recovering from COVID-19 commonly experience additional ailments, such as arrhythmia, depression, anxiety, and fatigue. Healthcare professionals on the frontlines face an elevated risk of mental illness. However, it is crucial to recognize that the general population also grapples with comparable levels of mental distress. Conclusion: The COVID-19 pandemic has underscored the significance of addressing mental health concerns. Various strategies can help mitigate the impact, including counselling, fostering open lines of communication, providing mental support, ensuring comprehensive patient care, and administering appropriate medications. In severe cases, treatment may involve the supplementation of essential vitamins and antidepressant therapy. By understanding the direct and indirect impacts of COVID-19 on mental health, healthcare providers and policymakers can develop targeted interventions to support individuals and communities affected by the pandemic. Continued research and collaborative efforts are essential to address this pervasive issue effectively.