Browsing by Author "Mbara, Kingsley Chimaeze"

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    Targeting AMPK signaling
    (ELSEVIER, 2025) Mbara, Kingsley Chimaeze; Kheoane, Poloko Stephen; Tarirai, Clemence
    Berberine (黄连素, hu´ang li´an sù) is a time-honored remedy in Traditional Chinese Medicine (TCM) that is found in various medicinal herbs and used to treat diabetes mellitus (DM), infections, diarrhea, and dysentery. Berberine, the major active component of Coptidis rhizome (黄连, huanglian), Phellodendri cortex (黄柏, huangbai), and Mahoniae caulis (亮叶十大功劳, Gong Lao Mu), exhibits several pharmacological activities, including antioxidant, anti-inflammatory, anti-apoptotic, cardioprotective, antineoplastic, antimicrobial, and antidiabetic effects. Antidiabetic effects of berberine are partly attributed to the activation of AMP-activated protein kinase (AMPK), which is a key mechanism and a potential treatment strategy for DM and its compli- cations. This review discusses recent studies on the significant roles of berberine in activating AMPK for treating DM and its complications. Method: We have comprehensively searched online databases like Scopus, PubMed, and Google Scholar for ar- ticles published in English between 2016 and 2025 using different permutations of these keywords: “Berberine”, “AMPK”, “Diabetes Mellitus”, “Diabetic nephropathy”, “Diabetic neuropathy”, “Diabetic retinopathy”, “Diabetic cardiomyopathy”, “Diabetic hepatic steatosis,” “Diabetic bone diseases”, “Diabetic atherosclerosis”, “Diabetic cognitive dysfunction”, “Diabetic lung injury” and “Other diabetic complications” to compile this narrative re- view. Out of 1750 initially retrieved articles, 183 were included based on their relevance to treating DM or its complications through the AMPK signaling pathway, pharmacokinetics, and translational potential. Non-English articles and studies not focused on AMPK activation by berberine and that did not address DM and its compli- cations were excluded. Results: The literature review found that berberine consistently activates AMPK across various preclinical studies of DM. The activation of AMPK is frequently mediated by pathways involving LKB1 and CAMKKβ. Berberine’s activation of AMPK positively impacts glucose uptake, insulin sensitivity, lipid metabolism, oxidative stress, and inflammatory responses. Evidence from animal models demonstrated its efficacy in ameliorating complications such as diabetic nephropathy, neuropathy, retinopathy, cardiomyopathy, hepatic steatosis, bone diseases, atherosclerosis, cognitive dysfunction, and lung injury. Clinical trials reported significant reductions in fasting blood glucose (FBG), HbA1c, and lipid levels, with minimal side effects, at standard doses. Discussion: AMPK activation by berberine plays a central role in cellular energy homeostasis, modulating key processes such as gluconeogenesis, lipogenesis, oxidative stress, and inflammation, which contribute to its therapeutic efficacy in metabolic dysfunction and DM-related complications. However, challenges remain Abbreviations: ACC, acetyl-CoA carboxylase; AMD, age-related macular degeneration; AMPK, AMP-activated protein kinase; ATGL, adipose triglyceride lipase; C/ EBPβ, CCAAT/enhancer-binding protein beta; CPT-1, carnitine palmitoyltransferase 1; CypD, cyclophilin D; DCM, diabetic cardiomyopathy; DM, diabetes mellitus; DN, diabetic neuropathy; DPN, diabetic nephropathy; DR, diabetic retinopathy; eNOS, endothelial nitric oxide synthase; ERK, extracellular Signal-regulated Kinases; GSK3β, glycogen synthase kinase 3β; HIF-1α, hypoxia-Inducible Factor 1-alpha; IR, insulin resistance; IRS-1, insulin receptor substrate-1; LKB1, Liver Kinase B1; mTOR, mechanistic target of rapamycin; NAFLD, non-alcoholic fatty liver disease; NEU1, Neuraminidase-1; Nrf2, nuclear factor (erythroid-derived 2)-related factor 2; NF-?B, nuclear factor kappa-light-chain-enhancer of activated B cells; OA, osteoarthritis; PEPCK, phosphoenolpyruvate carboxykinase; PGC-1a, peroxisome proliferator-activated receptor ? coactivator 1 a; PI3K, phosphatidylinositol 3-kinases; RA, rheumatoid arthritis; ROS, reactive oxygen species; Runx2, Runt-related transcription factor 2; SCD1, stearoyl-CoA desaturase 1; SIRT-1, sirtuin-1; SIRT-3, sirtuin-3; SREBP-1c, sterol regulatory element-binding protein 1; TGF-ß1, trans- forming growth factor-beta 1; TORC2, target of rapamycin complex 2