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Anti-Inflammatory Properties of Bioactive Compounds from Medicinal Plants
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Health Benefits of Secondary Phytocompounds from Plant and Marine Sources, 2021
Muhammad Imran, Abdur Rauf, Anees Ahmed Khalil, Saud Bawazeer, Seema Patel, Zafar Ali Shah
Colchicine reduced the transcoronary (coronary sinus-arterial) gradients for IL-1β, IL-18, and IL-6 [29]. AMPK (AMP-activated protein kinase: a metabolic bio-sensor) having anti-inflammatory characteristics. MSU (mono-sodium urate) inhibited phosphorylated AMPK-α in bone marrow-derived macrophage production (BMDMs). According to in vitro and in vivo studies, colchicine at low concentration (10 nM) confirmed AMPKα phosphorylation, polarization of macrophage M2, decreased caspase-1 activation, and release of IL-1β and CXCL1 due to MSU crystals in BMDMs [30].
Insulin Resistance and Glucose Regulation
Published in Awanish Kumar, Ashwini Kumar, Diabetes, 2020
Pharmacologically, too, the activation of peroxisome proliferator activated receptor-γ (PPAR-γ) by the thiazolidinedione (TZDs) class of anti-diabetic results in an increase in the plasma adiponectin level, contributing to the insulin-sensitising effect of TZDs [22]. Mouse models of obesity and insulin resistance also displayed significantly lower expression of AdipoR1 and AdipoR2. Hepatic expression of AdipoR2 in animal models demonstrated increased expression of genes such as glucokinase (involved in hepatic glucose uptake) and PPAR-α. Further activation of AMP activated protein kinase (AMPK) resulted in a reduction in endogenous hepatic glucose production. Expression of both AdipoR1 and AdipoR2 resulted in increased fatty acid oxidation, decreased hepatic TG content and thus improved insulin sensitivity. Conversely, deactivation of both of the receptors resulted in high hepatic and plasma TG and significantly increased insulin resistance [23]. The adiponectin level was found to be decreased by increased plasma TNF-α in obesity. These two molecules, thus, have an inverse correlation. The common inflammatory molecule C-reactive protein (CRP), which is increased in obesity, is also inversely correlated with the level of adiponectin [24].
New Developments in Drug Treatment
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Alexander S. Pym, Camus Nimmo, James Millard
Metformin, a synthetically derived biguanide from the Galega officinalis plant, was introduced as a glucose-lowering treatment for type 2 diabetes mellitus (T2DM) in the 1950s. In addition to other proposed mechanisms of action, it is known to inhibit the mitochondrial respiratory chain in the human liver by activating AMP-activated protein kinase (AMPK), which switches on catabolic pathways generating cellular ATP and stops those involved in gluconeogenesis, leading to a reduction in glucose. It is of particular interest given that T2DM is associated with both an increased risk of developing active TB183 and worse outcomes once on treatment.184
Research progress on related mechanisms of uric acid activating NLRP3 inflammasome in chronic kidney disease
Published in Renal Failure, 2022
Miao Wang, Xin Lin, Xiaoming Yang, Yanlang Yang
AMPK (AMP-activated protein kinase) is a key regulatory pathway of cell energy metabolism. Serum uric acid can regulate AMPK-mTOR (mammalian target of rapamycin)-mitochondrial reactive oxygen species, and the HIF-1α (hypoxia inducible factor-1α) pathway mediates the enhancement of the inflammatory process [59]. A decrease in uric acid levels will lead to the activation of AMPK to reduce inflammation [60]. Hyperuricemia will further cause inflammation, autophagy, and mitochondrial dysfunction through damage to sodium-potassium pump signal transduction and eventually lead to cell damage. The AMPK-mTOR pathway is abundant in renal tubular epithelial cells [52]. Hyperuricemia can stimulate the activation of AMPK in proximal tubular epithelial cells, in this study, they found that UA stimulates AMPK activity as a protective mechanism; however, soon AMPK activity decreases, leading to the impairment of Na+-K+-ATPase signaling, which further triggers inflammation autophagy, and mitochondrial dysfunction and leads to cell injury. Sustained treatment with an AMPK activator significantly alleviated UA-induced alterations [61].
Therapeutic perspectives on the metabolism of lymphocytes in patients with rheumatoid arthritis and systemic lupus erythematosus
Published in Expert Review of Clinical Immunology, 2021
The glycolytic system is the major metabolic process involved in generating energy in immune cells. When T cells are exposed to specific antigens, co-stimulatory molecules activate PI3K and upregulate the expression of glucose transporter 1 (GLUT1), resulting in enhanced glucose uptake [26]. AMP-activated protein kinase (AMPK) plays an important role in the regulation of glucose metabolism. Activation of AMPK enhances glycolysis by increasing the expression of GULT and promoting glucose utilization [27]. Furthermore, the glycolytic system is more enhanced in the Th1, Th17, Tfh, and CD8+ cells compared to that in the quiescent cells [28,29] and is particularly important for Th1 and Th17 cell differentiation [29,30]. Overexpression of the GLUT1 gene in mouse T cells leads to increased glucose uptake and production of IL-2 and IFN-γ [31]. Deletion of GLUT1 decreases the utilization of glucose in the CD4 + T cells and suppresses their differentiation into effector T cells [32]. Blockade of the glycolytic system promotes Treg cell differentiation [29]. High expression of Glut1 is associated with Th cell activation and production of IL-17, which is associated with the disease severity of active SLE [33,34]. HIF1α is activated by mTOR and is involved in the differentiation of Th1, Th17, and CD8+ cells via enhanced glucose metabolism. HIF1α activity is promoted to induce Th1 and Th17 cell differentiation via glucolysis downstream of TCR signaling [35,36].
Therapeutic Effects of SGLT2 Inhibitor Ipragliflozin and Metformin on NASH in Type 2 Diabetic Mice
Published in Endocrine Research, 2020
Atsuo Tahara, Toshiyuki Takasu
Metformin, a biguanide, remains the most widely used first-line drug for the treatment of type 2 diabetes. It has been shown to improve insulin resistance and hyperglycemia via activation of the AMP-activated protein kinase (AMPK) pathway, and thereby enhances peripheral glucose uptake and reduces hepatic glucose production.31 Many studies have evaluated the use of agents such as metformin and pioglitazone for improving insulin resistance as a possible treatment for NASH.32,33 To date, a number of clinical studies have investigated the efficacy of metformin on NASH, with several trials indicating beneficial effects in patients with NASH.34 Marchesini et al.35 reported that metformin significantly reduced plasma ALT levels and attenuated hepatomegaly. In contrast, while most clinical studies have shown that metformin improves serum liver enzymes and insulin resistance, evidence on its effectiveness in ameliorating liver histological injury is inconsistent.7 Therefore, due to its metabolic effects and safety profile, metformin can attenuate hepatic steatosis and metabolic abnormalities including insulin resistance, and remains a promising drug for NASH therapy, although whether it ameliorates hepatic pathological injuries including fibrosis in NASH remains unclear.