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Table 1 Health perspectives of mangiferin

From: Mangiferin: a natural miracle bioactive compound against lifestyle related disorders

Disorders Mechanisms Reference
Anticancer Inhibition of cdc25C and Chk1 mRNA expression
Inhibition of Erk1/2, Chk1, ATR, Akt, and Wee1, phosphorylation
cdc25C and cyclin B1 activation decreased
Progression of cell cycle inhibited through ATR-Chk1 DNA damage stress-response pathways
[37]
Apoptosis increased and proliferation restrained [40]
Activity of TNFα-induced MMP-9 decreased, lowering the activity of NF-κB (nuclear factor-κB)
Suppressed p50 and p65
[41]
Lowering β-glucuronidase, acidphosphatase, β-galactosidase and N-acetyl glucosaminidase activity [42]
Proliferation of CNE2 cells was inhibited by cell cycle arrest at G2/M phase
Down-regulates levels of mRNA and Bcl-2 protein, and up-regulates Bax
[44]
Serum-reduced TNFα and Hs-CRP (high-sensitivity C-reactive proteins) levels [45]
Inhibiting the expression of P-glycoprotein (P-gp) [46]
Increased stability of protein and expression of Nrf2 [47]
Increased accumulation of Nrf2 protein, Nrf2 binding enhanced in ARE, regulated expression of NQO1 [48]
Reduced expression of MMP-7 and -9, reversed EMT (epithelial-mesenchymal transition)
Inhibition of the beta-catenin pathway
[49]
Enhanced CDC2 and CCNB1 mRNA expression [51]
Up regulating the Nrf2 signaling target, and NAD(P)H dehydrogenase [quinone] 1 (NQO1) [43]
Up regulated levels of Fas [52]
Estrogen receptor alpha (ERα) activated [39]
Classical NFκB activation suppressed by IκB kinases (IKK) α/β
Additional NFκB-pathways inhibit
[54]
Inhibition of MeHg-induced DNA damage
Lowering the intracellular Ca2+ influx, MeHg-induced oxidative stress
Mitochondrial membrane depolarization inhibits
[55]
Significantly reduced NF-κBp65 nuclear entry, inhibition of NF-κB activation
Inhibition of XIAP (X-linked inhibitor of apoptosis protein) and Bcl-xL expression
[56]
Anti-inflammatory activity The expression of TNF-α, IL-6 and IL-1β was inhibited by LPS
Increased expression of IL-10
Inhibition of colonic shortening, colonic myeloperoxidase activity, NF-κB activation, 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced IRAK1 phosphorylation
Inhibition of IL-6, IL-1β and TNF-α (78%) expression
[59]
Reduced total inflammatory cell infiltration and eosinophil
Lowering the prostaglandin (PG) D2
Down regulated the levels of IL-3, IL-4, IL-5, IL-9, IL-13, IL-17, TNF-α and RANTES-related Th2
Th1-related cytokines expression increased in serum, such as IL-2, IL-10 and IL-12, interferon (IFN) -γ
Reduced abnormal mRNA levels of both Th2-type cytokines (IL-4, IL-5 and IL-13) and Th1 (IL-12 and IFN-γ)
[60]
Suppression of IL-6 production induced by LPS and expression of cystathionine-b-synthase (CBS) [61]
Inhibition of sepsis activated-MAPKs and NF-κB signaling
Upregulated activity and hemo oxygenase expression (HO) -1
[63]
Reduced PGE2 and 8-isoPGF2-alpha production
Lowering the protein synthesis of COX-2
[64]
Suppressed nitrite/nitrate ratio and myeloperoxidase activity
Lowering the level of plasma of TNF-α, IL-1β, monocyte chemoattractant protein-1 (MCP-1) and IL-6
[65]
Intercellular adhesion molecule-1 (ICAM-1) and NF-κB p65 phosphorylation down-regulated
Transcriptional activity of NF-κB suppressed
[66]
Significantly reduced total acidity and gastric secretion volume [67]
Diabetes prevention Glucose amount and pancreatic beta cell mass enhanced
AMPK and the activation of AMP-activated protein kinase (AMPK) phosphorylation
[69]
Sensitivity of insulin improved, lipid profile modulated and adipokine levels reverted [70]
TGF-β1 pathways, PKC isoforms (PKCα, PKCβ and PKCε), MAPK (P38, JNK and ERK1/2) modulated [72]
Lowering the β-cell apoptosis
Upregulate the cyclin D1, cyclin D2 and Cdk4 (cyclin-dependent kinase 4)
It promoted the regeneration of β-cells and the expression of duodenal and pancreatic homeobox gene 1 (PDX-1), glucose transporter 2 (GLUT-2), neurogenin 3 (Ngn3), glucokinase (GCK) and Forkhead box protein O1 (Foxo-1).
[73]
Glo-1 mRNA expression, protein and enzymatic activity enhanced
Reduced mRNA and protein expression of receptors in advanced end products of glycation (AGEs) and advanced end products of glycosylation (RAGE) receptors
[74]
Reduce the concentration of RBCs sorbitol, malonaldehyde level
Inhibition of expansion of the glomerular extracellular matrix, and accumulation and transformation of growth factor-beta 1 over-expression
[76]
Preventing renal glomeruli fibrosis
Reduced the expression of alpha-smooth muscle collagen IV and actin
Reduced COX-2, NF-κB p65 and osteopontin subunit expression
Lowering the interleukin-1β
[71]
Cardiovascular preventive role The attenuated expression of NLRP3 and TXNIP, reduced production of IL-1β and IL-6, and the inhibited inhibition of the inflammatory activation of TXNIP/NLRP3
Mitochondrial Δψ restored
Activity of caspase-3 suppressed
Improved inhibition of ET-I secretion and NO production reduced
Increased AMPK inhibitor compound C and phosphorylation of AMPK
Inhibition of inflammation induced by TXNIP/NLRP3 activation related to stress in the endoplasmic reticulum of the endothelial cell
[78]
Reduction of serum lactate dehydrogenase (LDH) and creatine kinase levels, reduction of MDA levels [79]
Reduce diabetic cardiomyopathy (DCM), and to prevent the accumulation of collagen in the heart [80]
Improved effect of pathological changes induced by pH Reduction of the formation of lipid peroxides and retention of cardiac markers activity [81]
Mangiferin plays an important role in the reduction of triglyceride, free fatty acid (FFA) and cholesterol levels in both heart and serum and may also increase phospholipid levels of cardiac tissue in isoproterenol-induced cardiotoxic rats [82]
Lysosomal integrity preserved [81]
Oxidative stress Blood sugar reduced, elevated levels of plasma insulin and antioxidant enzymes increased such as CAT, glutathione peroxidase (GPx) and SOD [85]
Apoptotic cells induced and the normalized potential of the mitochondrial membrane and cellular-antioxidant levels [94]
Prevention of Ca2 + -induced depletion of antioxidant enzymes [95]
Cadmium-induced secretion of both IL-8 and IL-6 prevented [38]
Regulated production of Nrf2 and NLRP3 [87]
MnNCE and MnPCE ratio reduced, and increased the ratio of PCE/NCE [92]
MGLUT9 (murine glucose transporter 9) and uric acid transporter 1 (mURAT1) mRNA and protein levels were down-regulated
Upegulated the murine organic anion transporter 1 (mOAT1) Increased renal organic cation levels, as well as carnitine transporter (mOCTN1, mOCTN2, mOCT1 and mOCT2) expression levels
[91]
Decreased MDA levels, and content of TNF-α and IL-8 in lung tissues whereas the RAW264.7 macrophages COX-2 mRNA expression [90]
Prevented 6-hydroxydopamine (6-OHDA)-induced cell death Decreased the levels of IL-6 and MDA [89]
Inhibition of Pb(II)-induced mitogen-activated protein kinases (MAPKs) activation (phosphor-JNK phospho- p38, phospho-ERK 1/2), NF-κB nuclear translocation and apoptotic cell death. [122]
Neuro-protective role Decreased inflammatory cytokines levels, oxidative stress marker levels and hippocampal brain derivd neutrophic-factor (BDNF) content. [96]
Prohibited dopamine depletion, and MPTP-induced interactive deficits [97]
Constrain tracheal reductions
Increased protein levels of cGMP and nitric oxide synthase at the cellular level
Eradicated the growth in cGMP levels
[98]
Improved cellular responses, antigen-specific IgM levels, and lymphoid organ weights [75]
Induced a significant increase in supernatant levels of nerve growth factor and TNF-α [100]
Prohibited from improved IL-1β and glucocorticoid (GC) plasma levels, and loss of redox balance and reduction in catalase brain levels
Prevented from increase in pro-inflammatory mediators such as TNF-α, NF-κB, TNF receptor 1, as well as synthesis enzymes such as iNOS and COX-2
[99]
Hyperlipidemia preventive strategy Regulated the metabolic pathways such as the glyoxylate, tricarboxylic acid (TCA)and taurine cycles [101]
Lowered the levels of proteins which are critical for lipogenesis, such as acetyl-CoA carboxylase 1 (Acac1) gene and fatty acid stearoyl-CoA desaturase 1 (Scd1) [102]
Increased cell viability, improved mitochondrial membrane potential [103]
Increased glucose and pyruvate oxidation and ATP production [104]
Protected from the mitochondrial NAD(P)H-linked substrates depletion and NADPH spontaneous oxidation [105]
Upregulated mRNA expression of PPAR-α, carnitine palmitoyltransferase 1 (CPT-1), and fatty acids (CD36)
Decreased the mRNA expression of sterol regulatory element binding protein 1C (SREBP-1c), diacylglycerol acyltransferase 2 (DGAT-2), acetyl coenzyme a carboxylase (ACC), and microsomal triglyceride transfer protein (MTP)
[15]
Upregulate the bone morphogenetic protein (BMP)-2, BMP-4 and transforming growth factor (TGF)-β
Upregulated containing gene 9 (SOX9), sex- influential region Y-box (SRY-box), aggrecan, type 2 α1 collagen (Col2α1) and cartilage link protein.
Reversed the production of BMP-2, SOX9, BMP-4, TGF- β, Col2α, aggrecan and cartilage link protein
Upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1β-stimulated MSCs
[107, 108]
Miscellaneous properties Inhibited IgE production, anaphylaxis reaction, histamine-induced vascular permeability, histamine release, and the lymphocyte proliferative response [109]
Inhibit the expression of COX-2 and leukocyte adhesion and rolling [118]
Binding activity of DNA of AP-1 (activator protein-1) inhibit, a factor of transcription for MMP-1 [111]
Protected normal human intestinal epithelial cells (HIECs) from radiation-induced injuries [112]
Inhibited nuclear factor (NF)-kappaB activation in scopolamine or TNF-alpha-stimulated BV-2 microglial cells [113]
Decreased expression of osteoclast gene markers such as calcitonin receptor, cathepsin K, V-ATPase d2 and DC-STAMP
Suppressed RANKL-induced activation of NF-κB, as well as p65 nuclear translocation and IκB-α degradation
[114]
Inhibited the passive cutaneous anaphylaxis (PCA) IgE-antigen complex
Inhibited the expression of pro-inflammatory cytokines TNF-α, IgE-antigen complexes, of IgE switching cytokines, IL-4
[9]
Possessed antibacterial activity against Bacillus pumilus and Salmonella agona [116, 117]
Ameliorated anxiety-like behaviour and also improved anhedonic behavior
Attenuated neuroinflammation in the prefrontal cortex
[121]