An overview of the pharmacological activities of scopoletin against different chronic diseases. (May 2022)

• Record Type: Journal Article
• Authors: Parama, Dey; Girisa, Sosmitha; Khatoon, Elina; Kumar, Aviral; Alqahtani, Mohammed S.; Abbas, Mohamed; Sethi, Gautam; Kunnumakkara, Ajaikumar B.
• Is Part Of: Pharmacological research. Volume 179(2022)
• Publication Date: 2022-05
• Subjects: AChE Acetylcholinesterase -- ACP Acid phosphatase activity -- AD Alzheimer's Disease -- ADA Adenosine-deaminase -- AGII Angiotensin II -- AhR Aryl hydrocarbon receptor -- ALD Alcoholic liver disease -- ALP Alkaline phosphatase -- ALT Alanine transaminase -- AMPK AMP-activated protein kinase -- Apaf Apoptotic protease activating factor -- AST Aspartate aminotransferase -- ATP Adenosine triphosphate -- Bad BCL2 associated agonist of cell death -- Bax Bcl-2 associated X, apoptosis regulator -- Bcl-2 B-cell lymphoma 2 -- Bcl-XL B-cell lymphoma-extra-large -- BDC Bile duct cancer -- Bim Bcl-2-like protein 11 -- BMP-2 Bone morphogenetic protein 2 -- BMC Bone mineral content -- BM-DCs Bone marrow derived dendritic cells -- BMD Bone mineral density -- CAT Catalase -- CCA Cholangiocarcinoma -- CD Cluster of Differentiation -- CDC42 Cell division cycle 42 -- Cdks Cyclin-dependent kinases -- CFA Complete Freund's adjuvant -- CHOP C/EBP homologous protein -- CNS Central nervous system -- Cox Cyclooxygenase -- CRC Colorectal cancer -- CSF3 Colony stimulating factor 3 -- CVDs Cardiovascular diseases -- CYP1A1 Cytochrome P450, family 1, subfamily A, polypeptide 1 -- CYP98A3 Cytochrome P450 98A3 -- DC Dendritic cells -- DGAT2 Diglyceride acyltransferase -- DIRAS3 GTP-binding protein Di-Ras3 -- DMBA Dimethylbenzanthracene -- DMF Dimethylformamide -- DMSO Dimethyl sulfoxide -- EAE Experimental autoimmune encephalomyelitis -- EGFR Epidermal growth factor receptor -- eIF2 Eukaryotic initiation factor 2 -- ER Endoplasmic reticulum -- ERK Extracellular signal-regulated kinase -- FA Fatty acid -- FAS Fas cell surface death receptor -- FCGR Fc-gamma receptor -- FDA Food and Drug Administration -- FLS Fibroblast-like synoviocytes -- GAGs Glycosaminoglycans -- GATA3 GATA binding protein 3 -- GBD Global Burden of Disease -- GLUT9 Glucose transporter -- GPx Glutathione peroxidase -- GRP78 Glucose regulated protein 78 -- GSH Glutathione -- GST Glutathione S-transferase -- G6PD Glucose-6-phosphate dehydrogenase -- HCC Hepatocellular carcinoma -- ICH Intracerebral haemorrhage -- IgE Immunoglobulin E -- ILs Interleukins -- iNOS Inducible nitric oxide synthase -- IRIS1 Insulin receptor substrate 1 -- Iκα Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha -- ITGA9 Integrin alpha 9 -- JA Jasmonate -- LC3 II Microtubule-associated protein 1A/1B-light chain 3 II -- LLC Lewis lung carcinoma -- LPO Lactoperoxidase -- MAPK Mitogen-activated protein kinase -- MDA Malondialdehyde -- MHC Major histocompatibility complex -- MIA Monosodium iodoacetate -- MMPs Matrix metalloproteinases -- MMPD Mitochondrial membrane potential depolarization -- MPO Myeloperoxidase -- mTOR Mammalian target of rapamycin -- MyD88 Myeloid differentiation primary response 88 -- NAFLD Non-alcoholic fatty liver disease -- NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells -- NO Nitric oxide -- OA Osteoarthritis -- OAT1 Organic anion transporter 1 -- OPG Osteoprotegerin -- PA Palmitic acid -- PAP Prostatic acid phosphatase -- PARP Poly (ADP-ribose) polymerase -- PCNA Proliferating cell nuclear antigen -- PIK3CA Phosphatidylinositol 3-kinase catalytic alpha polypeptide -- PIK3R3 Phosphatidylinositol 3-kinase regulatory subunit gamma -- PI3K Phosphatidylinositol 3-kinase -- PKC Protein kinase C -- PLCD1 Phosphatidylinositol-4, 5-bisphosphate phosphodiesterase delta-1 -- PLCE1 Phosphatidylinositol-4, 5-bisphosphate phosphodiesterase epsilon-1 -- PMA Phorbol 12 myristate 13 acetate -- PPARγ Peroxisome proliferator-activated receptors gamma -- PTEN Phosphatase and tensin homolog -- RA Rheumatoid arthritis -- RANKL Receptor activator of nuclear factor kappa-Β ligand -- RHOD Ras homolog gene family, member D -- ROS Reactive oxygen species -- RND3 Rho family GTPase 3 -- Runx2 Runt-related transcription factor 2 -- SAH Systemic arterial hypertension -- SCP Scopoletin -- SD Sprague Dawley -- SOCS1 Suppressor of cytokine signaling 1 -- SOD Superoxide dismutase -- SREBP Sterol regulatory element-binding protein -- STAT3 Signal transducer and activator of transcription 3 -- STZ Streptozotocin -- TC Total cholesterol -- TIMP Tissue inhibitor of metalloproteinases -- TG Triglyceride -- Th2 T helper type 2 -- TLR4 Toll-like receptor 4 -- Tmax Time to reach maximum drug concentration -- TNF-α Tumour necrosis factor alpha -- TREM 1 Triggering receptor expressed on myeloid cells 1 -- TRP53 Transformation related protein 53 -- TSC2 Tuberous sclerosis complex 2 -- URAT1 Renal uric acid transporter -- VEGFA Vascular endothelial growth factor A; Scopoletin -- Cancer -- CVDs -- Neurological diseases, Metabolic diseases, Inflammatory diseases; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106202
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Chronic diseases are considered a major public health concern worldwide, and most of these diseases like cancer, cardiovascular, metabolic, and neurological disorders occur due to atypical regulation of multiple signaling pathways. It has also been observed that most of the currently approved therapies for these diseases fail to show prolonged efficacy due to their mono-targeted nature and are associated with the development of chemoresistance, thus restricting their utility. The plant-derived compounds, on the other hand, show multi-targeted nature, and thus these phytochemicals have gained wide attention as they offer negligible side effects. The present review aims to recapitulate the potential effects of one such phytochemical, Scopoletin, which was found to have a diverse range of pharmacological activities such as anti-cancer, anti-diabetic, anti-inflammatory, cardioprotective, hepatoprotective, etc. Scopoletin modulated multiple molecular signatures in cancer, including AMPK, EGFR, MAPK/ ERK, NF-κB, PI3K/Akt/ mTOR, and STAT3; regulated the levels of critical markers of metabolic diseases such as ALT, AST, TG, and TC; inflammatory diseases such as ILs and TNFs; neurological diseases such as AChE, etc. thus relieving the symptoms and severity associated with these diseases. Further, this compound has a non-toxic nature and possesses an excellent pharmacokinetic property, which warrants further investigation in clinical settings for developing it as a potential drug. Graphical Abstract: ga1 Highlights: Scopoletin, hydroxycoumarin can exhibit diverse pharmacological actions against various major chronic diseases. Scopoletin can target multiple molecular targets to attenuate disease progression. It is non-toxic in nature and exhibits excellent pharmacokinetic properties.