ABSTRACT
Current treatments modalities for major depressive disorder (MDD) mainly target the monoaminergic neurotransmission. However, the therapeutic inadequacy and adverse effects confine the use of these conventional antidepressants to a limited subset of MDD patients. The classical antidepressants are increasingly proving unsatisfactory in tackling the treatment-resistant depression (TRD). Hence, the focus of treatment is shifting to alternative pathogenic pathways involved in depression. Preclinical and clinical evidences accumulated across the last decades have unequivocally affirmed the causative role of immuno-inflammatory pathways in the progression of depression. There is an upsurge in the clinical evaluations of the drugs having anti-inflammatory effects as antidepressants. This review highlights the molecular mechanisms connecting the inflammatory pathways to the MDD and current clinical status of inflammation modulating drugs in the treatment of MDD.
Subject(s)
Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Humans , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/metabolism , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depressive Disorder, Treatment-Resistant/drug therapy , Inflammation/drug therapyABSTRACT
Acute myelogenous leukemia (AML) is a genetically heterogeneous and aggressive cancer of the Hematopoietic Stem/progenitor cells. It is distinguished by the uncontrollable clonal growth of malignant myeloid stem cells in the bone marrow, venous blood, and other body tissues. AML is the most predominant of leukemias occurring in adults (25%) and children (15-20%). The relapse after chemotherapy is a major concern in the treatment of AML. The overall 5-year survival rate in young AML patients is about 40-45% whereas in the elderly patients it is less than 10%. Leukemia stem-like cells (LSCs) having the ability to self-renew indefinitely, repopulate and persist longer in the G0/G1 phase play a crucial role in the AML relapse and refractoriness to chemotherapy. Hence, novel treatment strategies and diagnostic biomarkers targeting LSCs are being increasingly investigated. Through this review, we have explored the signaling modulations in the LSCs as the theragnostic targets. The significance of the self-renewal pathways in overcoming the treatment challenges in AML has been highlighted.
Subject(s)
Leukemia, Myeloid, Acute , Neoplastic Stem Cells , Adult , Aged , Bone Marrow/pathology , Child , Hematopoietic Stem Cells/metabolism , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/therapy , Neoplastic Stem Cells/pathology , RecurrenceABSTRACT
INTRODUCTION: The ethnobotanical survey of the South-western Satpuda ranges has continued for decades. However, very few disease-specific surveys and their pharmacological validation have been published. The present study aimed to identify, document, and pharmacologically validate the tribal knowledge on anti-inflammatory medicinal plants. METHODS: The field survey was conducted over a year from July 2015 to June 2016, scattered in the South-Western region of Satpuda Ranges. Documentation and identification of the medicinal herbs used often in the treatment of inflammatory conditions. Two plants, namely Eulophia herbacea Lindl., and Grewia flavescens A. Juss. were commonly used for inflammatory conditions. Phytopharmacological validation was done using carrageenan induced inflammation and CFA-induced arthritis. RESULTS: The current investigation identified 32 plants from 22 different families as anti-inflammatory plants. G. flavescens exhibited substantial antiarthritic action in complete Freund's adjuvant-induced arthritis in rats, and E. herbacea showed powerful anti-inflammatory activity in carrageenan-induced rat paw edema model. This activity might be attributed to the presence of gallic acid, quercetin, ß-sitosterol and lupeol. CONCLUSION: The research reveals that selected plants had anti-inflammatory properties in both acute and chronic inflammation. Further studies to highlight the exact mechanism of action of these plants are warranted.
Subject(s)
Anti-Inflammatory Agents , Inflammation/drug therapy , Plant Preparations , Animals , Anti-Inflammatory Agents/classification , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/drug therapy , Arthritis, Experimental/immunology , Disease Models, Animal , Humans , India , Phytotherapy/methods , Phytotherapy/statistics & numerical data , Plant Preparations/classification , Plant Preparations/pharmacology , Plant Preparations/therapeutic use , Plants, Medicinal/classification , Rats , Reproducibility of ResultsABSTRACT
The pathogenesis of Alzheimer's disease (AD) involves neurodegeneration following the deposition of ß-amyloid (Aß) plaques and neurofibrillary tangles in vulnerable brain regions. The vulnerability of the brain to reactive oxygen species (ROS) is now emerging as a key detrimental factor driving AD pathogenesis. Oxidative stress (OS) irreversibly damages cellular biomolecules and perturbs neuronal functions. Scientific evidence is emerging that supports the therapeutic effects of antioxidants in preventing the onset and delaying the progression of AD pathology. In this review, we highlight the role of the OS in AD and the importance of antioxidants in its treatment.
