Pharmacological activities of gallic acid and its derivatives in different diseases
| Disease category | Compound name | Model | Effects | References |
|---|---|---|---|---|
| Anti-inflammatory |
Gallic acid |
In vitro: LPS-induced inflammation in A549 lung cancer cells In vivo: LPS-induced inflammation in mice |
In vitro: ↓HAT, ↓p300 & CBP acetyltransferase, p300-mediated RelA acetylation, NF-κB–regulated antiapoptotic & cell survival genes expression, p300-induced p65 acetylation, LPS-induced p65 translocation to the nucleus, ↑cytosolic IĸBα In vivo: ↓p65 acetylation, IFN-, IL-6, IL-1β & NF-κB–regulated antiapoptotic genes expression |
(72) |
| Gallic acid |
In vitro: zymosan-induced damage in human PMN In vivo: zymosan-induced acute food pad swelling in mice |
In vitro: interference with PMN function, ↓MPO & reduction rate of cytochrome c In vivo: ↓footpad swelling size |
(71) | |
| Gallic acid ethyl ester | Acetic acid-induced abdominal constriction, formalin-induced nociception, capsaicin-induced nociception, rat paw hyperalgesia induced by substance-P, bradykinin, PGE2 or carrageenan | ↓Acetic acid-induced abdominal constrictions, ↓formalin-induced licking, ↓hyperalgesia induced by substance P & bradykininNo significant change in capsaicin-induced nociception |
(70) | |
| Bergenin (C-glycoside of 4-O-methyl gallic acid) | Mycobacterium tuberculosis-induced inflammatory arthritis in mice | ↓Inflammatory arthritis, ↓IL-2, IFN-γ, TNF-α, IL-4 & IL-5 | (69) | |
| Gallic acid |
In vitro: AEGs- treated rabbit chondrocytes In vivo: collagenase-induced knee osteoarthritis in rabbit |
In vitro: ↓ROS, collagen II & aggrecan degradation, NO, i-NOS, COX-2, PGE2 ↑GSH, SOD In vivo: ↓knee Mankin’s score |
(73) | |
| Cardiovascular |
Gallic acid | ISO-induced myocardial infarction in rats | ↓Myocardial injury, ↓TC, TG, LDL-C, VLDL-C, MDA, ↑HDL-C, CAT & GPx, ↑membrane-bound Na+/K+, Ca2+ & Mg2+ ATPase | (85) |
| Gallic acid | ISO-induced cardiotoxicity in rats | ↓CK-MB & LDH, ↓lysosomal membrane damage, LPO, ↑GSH |
(86) | |
| Gallic acid | Lindane-induced cardiotoxicity | ↓CK, LDH & LPO, ↑GSH, SOD, GPx & GST, ↑membrane bound Na+/K+ & Mg2+ ATPase & ↓ Ca2+ATPase | (87) | |
| Gallic acid | Evaluation of antioxidant enzymes in the heart of male Sprague-Dawley rats | ↑Cardiac SOD, GPx, CuZnSOD, CAT, GSH/GSSG ratio, heme oxygenase-1 & Nrf2 | (88) | |
| Gallic acid | AGEs-induced cardiac remodeling in rats | ↓Cardiac fibrosis, ↓TNF-α, TGF-β, MMP-2 & MMP-9 | (89) | |
| Gallic acid | STZ-induced myocardial dysfunction in diabetic rats | ↓CK-MB, ↓LDH, LPO, LDL-C & VLDL-C, ↓MBP, SBP & bradycardia, collagen content, ↑CAT, SOD, GSH |
(90) | |
| Gallic acid | Isoproterenol-induced myocardial infarction in rats | ↓CK-MB, ↑SOD, CAT, GPx, GST, GSH, Vit C & E, ↓troponin-T, LDH-1 & LDH-2 | (58) | |
| Gallic acid | Fructose-enriched-diet-induced cardiac fibrosis | ↓BP, HOMA-IR, ↓NADPH oxidase subunits gp91 phox & p22 phox, ↓collagen I & osteopontin | (91) | |
| Gallic acid | Al2O3-induced myocardial injury | ↓LDH, CPK, CK-MB, TG, LDL, TNF-α & MDA, ↑HDL, GSH, SOD & CAT | (92) | |
| Gallic acid | Alloxan-induced diabetes & endothelial dysfunction | ↓MDA, ↑TAC & histamine vasodilatory response of mesenteric vascular bed | (93) | |
| Gallic acid | L-NAME-induced hypertension | ↓SBP, LV wall thickness & cardiac fibrosis, ↓hypertrophy markers, ↓HDAC1 & 2 | (94) | |
| Gallic acid | Cyclophosphamide-induced cardiorenal dysfunction | ↓MDA & H2O2, ↑CAT, GST, GSH & GPx | (95) | |
| Gastrointestinal |
Gallic acid | CCl4-induced hepatotoxicity in Charles Foster rats & Swiss albino mice | ↓Sleep time & paralysis time, ↓LPO, ↑hepatic amidopyrine-N-Demethylase, aniline & membrane-bound hepatic glucose-6-phosphatase activity, ↓hepatic TAG | (53) |
| Gallic acid | Hepatic ischemia & reperfusion injury in rats |
↓ALT, AST & LDH activities, ↑CAT & GPx, ↓MDA | (57) | |
| n-propyl gallate | Isolated perfused rat liver | ↓Gluconeogenesis, pyruvate carboxylation, glucose output inhibition |
(96) | |
| Gallic acid | Brush border disaccharidases inhibition in rats, LACA/L mice, BALB/c mice & rabbit | ↓Sucrase, maltase, trehalase & lactase activity | (97) | |
| Gallic acid | Primary HSC & hepatocytes | Cytotoxicity to HCS but not hepatocytes, ↑intracellular Ca2+ & calpain activity |
(98) | |
| Gallic acid | Ethanol-induced pancreatic injury in rats | ↑Cathepsin B activities, ↓cathepsin B & L enzymes release, cytosolic/lysosomal ratio of cathepsin B & L, pancreatic tissue injury | (99) | |
| Gallic acid | Ethanol-induced liver damage in rats | ↓AST, ALT, LDH activity, ↑paraoxonase & arylesterase activity | (54) | |
| Gallic acid | Gastric mucosal lesions caused by ischemia-reperfusion injury in rats | ↓Total area of gastric lesions, ↓caspase-3 & i-NOS | (47) | |
| Gallic acid |
In vitro: rat gastric epithelial cells In vivo: indomethacin & diclofenac-induced gastropathy |
In vitro: ↓mucosal cell death, ↑mitochondrial dehydrogenases In vivo: ↓mitochondrial protein carbonyl formation, ↓LPO & caspase-9 activation, ↑thiol content & MMP |
(48) | |
| Tryptamine-gallic acid |
In vitro: rat gastric epithelial cells In vivo: indomethacin-induced gastropathy |
In vitro: ↓intramitochondrial ROS generation In vivo: ↓mucosal cell death, gastropathy, mitochondrial protein carbonyl formation, ↓LPO, bcl-2 expression & caspase-9 activation, ↑thiol content & bax expression |
(100) | |
| Gallic acid | DSS-induced experimental colitis in mice | ↓DAI & colon shortening, ↓IL-21, IL-23, MDA, ↑SOD, GPx, CAT, GR, Nrf2, UDP-GT & NQO1 | (50) | |
| Gallic acid | DSS-induced colitis in mice | ↓MPO activity, i-NOS, COX-2, p65-NF-κB & IL-6/p-STAT3Y705 activation | (51) | |
| Gallic acid | Paracetamol-induced liver damage in mice | ↓ALT, AST, ALP, & ↓TNF-α, ↑SOD, CAT, GSH, GPx & GST | (101) | |
| Trimethylgallic acid esters | CCl4-induced liver damage in rats | ↓Vacuole formation, inflammation & necrosis, ↓AST, ALT, TG, TC, LPO & ↓TNF-α, ↑SOD, CAT & GSH | (102) | |
| Gallic Acid | Aspirin + pyrolus ligation-induced gastric ulcer in rats | ↓Ulcer index, gastric juice volume, free & total acidity, total protein, carbohydrates concentration, ↑SOD, CAT, GSH, GPx, GR & glucose-6-phosphate dehydrogenase | (103) | |
| Gallic acid | Bromobenzene-induced liver injury in rat | ↓Aniline hydroxylase & AMND activity, ↓LPO, ↑epoxide hydrolase activity |
(52) | |
| Gallic acid | CCl4-induced liver fibrosis in mice | ↓Liver fibrosis, HA, MDA, ALT, AST & GGT | (104) | |
| Gallic acid & piperine | Beryllium-induced hepatorenal dysfunction in rats | ↓Bilirubin, Cr, LDH, GGT, LPO, AST, ALT, ALP, ↑GSH, SOD & CAT | (105) | |
| Gallic acid | Lead-induced toxicity in blood, liver & kidney of rats | ↓LPO & carbonyl, prevention of body weight loss, ↑ALA-D activity, ↑SOD, CAT & GSH | (56) | |
| Gallic acid & ellagic acid | LPS-induced liver injury | ↓ALT, AST & i-NOS expression | (106) | |
| Gallic acid | CCl4-induced chronic liver injury in rats | ↓ALT, AST & MDA, ↑SOD, CAT, GSH, GR, GPx & GSH/GSST | (107) | |
| Gallic acid | Lindane-induced hepatorenal toxicity in rats | ↓ALT, AST, ALP, LPO, creatinine & urea, ↑GSH, CAT, SOD, GPx & GST | (108) | |
| Gallic acid | Beryllium-induced hepatorenal toxicity | ↓AST, ALT, ALP, LPO, AMND, ↑GSH, CAT, SOD, GPx & GST, ↓Cr & urea | (109) | |
| Gallic acid | Cyclophosphamide-induced hepatotoxicity in rats | ↓AST, ALT, MDA, ↑GSH, CAT, SOD & GST | (55) | |
| Gallic acid | Indomethacin-induced gastric ulcer in Swiss albino mice | ↑Ulcer healing, ↓PGE2 synthesis, ↑e-NOS/i-NOS ratio | (49) | |
| Metabolic | Gallic acid | Diet-induced obesity in mice | ↓TAG & FBS, ↓adipocyte size in the epididymal white adipose tissue, ↑PPAR expression, ↑Akt signaling pathway activity, ↓glucose tolerance & lipid metabolism | (59) |
| Gallic acid | High-fat-diet- & -STZ-induced type 2 diabetes in rats | ↓Body weight gain, FBS & FPI, ↑adipose tissue insulin sensitivity, Cytoprotective action on pancreatic β-cell, ↑PPARγ expression in treated tissue, liver & skeletal muscle, ↑insulin-dependent glucose transport, ↑interactions with the GLUT4, GLUT1, PI3K & p-Akt, ↓adipogenesis | (60) | |
| Gallic acid | High-fat-diet-induced dyslipidemia, hepatosteatosis & oxidative stress in rats | ↓Obesity, liver weight, peritoneal & epididymal adipose tissue weights, ↓serum TAG, phospholipid, TC, LDL-C, insulin & leptin, ↓lipid droplets size, ↓hepatic TAG & cholesterol, ↓oxidative stress & GSSG, ↑GSH, GPx, GR & GST | (61) | |
| Gallic acid | High-fructose-diet-induced diabetes | ↑Glucose uptake activity, ↓AUCglucose & HOMA-IR, ↓C-peptide, fructosamine & cardiovascular risk index, ↑IR, IR-1, PI3K, Akt/protein kinase B & GLUT-2, ↓F-1,6-BP, ↑hexokinase, PFK & aldolase | (62) | |
| Gallic acid | STZ-induced diabetic rats | ↑Vit C, ↓GSH, ↓LPO, ↑free radical scavenging property, Fe2+ chelating ability & Fe3+ reducing property, ↑CAT, GST, δ-aminolevulinic acid dehydratase & LDH, ↓purinergic enzymes | (63) | |
| Gallic acid | STZ-induced diabetic Wistar rats | ↓FBS, regeneration of β-cells, ↓TC, TAG, LDL-C, urea, uric acid, creatinine, ↑FPI, C-peptide & glucose tolerance restored the total protein, albumin & body weight | (110) | |
| Gallic acid | Fructose-induced metabolic syndrome & cardiac fibrosis in rats | ↓Insulin resistance, ROS & NADPH overproduction, collagen I & osteopontins | (98) | |
| Gallic acid |
In vitro: porcine pancreatic lipase kit In vivo: high-fat-diet-induced obesity in mice |
In vitro: ↓pancreatic lipase activity In vivo: ↓weight gain, ↑feces neutral fat |
(111) | |
| Gallic acid | STZ-induced diabetes in rats | ↑FPI, hepatic hexokinase activity, CAT, SOD, GPx, ↓FBS, HbA1C, G6PD & fructose-1, 6-bisphosphatase, LPO | (112) | |
| Gallic acid | STZ-induced diabetes in rats | ↓FBS, HbA1C, LPO, ↑FPI, Vit C, SOD, CAT, GSH, GR, GST, GPx, HMG-CoA reductase activity | (113) | |
| Gallic acid | Alloxan-induced diabetes in rats | ↓FBS, ↑FPI, GSH, GPx, CAT, SOD & osmotic fragility of RBCs | (114) | |
| Gallic acid | STZ-induced diabetes in rats | ↓FBS, brain LPO, SOD, CAT, GR, GST, GPx, brain lipids | (37) | |
| Gallic acid | Chromium-induced thyroid dysfunction | ↓SOD & GST up-regulation, ↓NO, i-NOS, TNF-α, IL-6 & COX-2 | (115) | |
| Gallic acid |
In vitro: high glucose toxicity in NRK 52E rat proximal tubular epithelial cells In vivo: high fat diet/STZ- induced diabetes in rats |
In vitro: ↓p38 MAPK, NF-κB activation In vivo: ↓FBS, HbA1C, HOMA-IR, body weight, Cr, Cr clearance, BUN, IL-1β, IL-6, TNF-α & ↓MDA, ↓renal p38 MAPK, NF-κB activation, TGF-β, fibronectin, ↑GSH, GSST, GSH/GSST ratio, GR, CAT, SOD & GPx |
(116) | |
| Gallic acid | STZ-induced diabetes & oxidative stress in rats | ↓ROS & lipid peroxidation, ↑SOD & δ-ALA-D, CAT, GST & vit C | (117) | |
| Neuropsychological |
Gallic acid | 6-Hydroxydopamine induced oxidative stress in rats | ↑Passive avoidance memory, ↑TTM, GPx, ↓MDA | (65) |
| Gallic acid | STZ-induced memory deficits & oxidative stress in rats | ↑Passive avoidance & spatial memory, performance, ↑TTM, SOD, GPx & CAT, ↓MDA | (118) | |
| Gallic acid | EPM in rats | ↑Time spent & entries in the open arms of EPM, ↓locomotor activity, involvement of 5-HT1A receptors | (119) | |
| Gallic acid | Sodium fluoride-induced oxidative stress in rat brain | ↓LPO, ↑SOD & GSH | (120) | |
| Gallic acid | STZ-induced oxidative damage in rat brain | ↓MDA, ↑TTM, CAT, SOD & GPx, ↑ Na+/K+, Ca2+ & Mg2+ ATPases activity | (121) | |
| Gallic acid | Spinal cord injury-induced oxidative stress in rat | ↓LPO, ROS, nitrite, NF-kB & COX-2 ↑GSH, CAT, SOD & GPx |
(122) | |
| Gallic acid (as chitosan nanoparticles) | Scopolamine-induced amnesia & locomotor activity | ↓Transfer latency in the EPM test, ↑spatial learning & memory in MWM, ↓AChE activity, | (66) | |
| Gallic acid | Tyrosine hydroxylase Gal4/UAS-X RNAi Drosophila melanogaster model of Parkinson's disease | ↑Locomotor activity, protection of dopaminergic neurons, ↑life span & climbing abilities | (123) | |
| Gallic acid | Cyclophosphamide-induced neurotoxicity in rats | ↓Neurotoxicity, ↓cerebellar & cerebral MDA & nitrite, ↑CAT, GST & SOD | (55) | |
| Gallic acid | Reserpine-induced vacuous chewing movements in rats | ↓Vacuous chewing movements | (124) | |
| Gallic acid | Lead-induced locomotor damage & brain oxidative stress in rats | ↑Locomotor & exploratory activities by attenuating crossing & rearing time, ↓brain levels of Pb, ↑SOD & ↑GSH | (125) | |
| Gallic acid | Sodium nitroprusside oxidative stress-induced mitochondrial impairment | ↓NO level, ↓mitochondrial protein tyrosine nitration, ↓LPO, ↓protein carbonyl, ↑GSH & ↓MPT | (126) | |
| Gallic acid |
In vitro: sodium hydrosulfite-induced mitochondrial dysfunctions in SH-SY5Y cells In vivo: cerebral ischemia/reperfusion-induced by middle cerebral artery occlusion |
In vitro: protects against cytotoxicity of SH-SY5Y cells, ↓mitochondrial dysfunction, ↓level of mitochondrial ROS by ↓MitoSOX-fluorescence intensity, ↓intracellular DCF-fluorescence intensity, ↓intracellular MDA, by modulating mitochondrial dysfunctions by ↑oxygen consumption In vivo: ↓total infarct volume |
(127) | |
| Gallic acid (as chitosan nanoparticles) | FST & TST in rat | ↓Immobility in FST & TST, ↓MAO-A activity & MDA, ↑GSH & CAT | (128) | |
| Gallic acid | Aβ-induced toxicity in cultured rat cortical neurons | ↓Apoptotic neuronal death, ↓(Ca2+)c elevation & ROS formation, ↑glutamate release | (64) | |
| Gallic acid | H2O2-induced apoptosis in rat pheochromocytoma PC12 cells | Gallic acid & EGCG: ↓cell viability methyl gallate: ↑cell viability, ↓mitochondrial depolarization, caspase-9 activation & DNA degradation |
(68) | |
| Gallic acid | Immobilization-induced Swiss male albino mice | ↓Plasma nitrite in both unstressed & stressed mice, ↓plasma corticosterone, ↓n-NOS activity, ↓anxiety in behavioral tests | (129) | |
| Gallic acid | Global ischemia/reperfusion in Wistar rats | ↑Gait performance, sensorimotor disorders, & hypoalgesia (high dose), ↑passive avoidance memory (low dose), improvement in behavioral motor activity tests | (130) | |
| Gallic acid | Experimental sciatic nerve crush in rats | Improved motor coordination & SNCV sciatic nerve conduction velocity, ↑delayed foot lifting | (131) | |
| Gallic acid | Aβ-induced AD in rats | Improved LTP amplitude & area under the curve, ↑PS Amp, ↓Aβ plaque |
(132) | |
| Gallic acid | H2O2-induced apoptosis in rat pheochromocytoma PC12 cells | ↓Cell viability, ↑PARP cleavage, ↑JNK phosphorylation, ↓Bcl-2 | (67) | |
| Gallic acid | STZ-induced cerebral oxidative stress in rats | ↑Weight loss, ↓hyperglycemia, HbA1C, LPO, AChE & purinergic enzymes, ↑radical scavenging & Fe2+ chelating ability, Vit C, GSH, CAT, GST, cerebral LDH & Na+/K+-ATPase activity | (133) | |
| Gallic acid |
In vitro: Aβ-induced neurotoxicity in murine microglial BV-2 cells & neuroblastoma Neuro-2A cells In vivo: Aβ-induced AD in ICR mice |
In vitro: ↓RelA acetylation & cytokine production, cell death, ↑viability of Neuro-2A, ↓memory deficits in Ab peptide-induced mice In vivo: ↓cytokine production, neuronal cell death, nuclear NF-κB & IL-1β |
(134) | |
| Gallic acid | Chronic cerebral hypoperfusion-induced cognitive deficit & brain oxidative damage in rats | ↑Spatial memory, ↑TTM & GPx, ↓LPO | (135) | |
| Gallic acid & its derivatives | 6-OHD-induced neurotoxicity in human SH-SY5Y neuroblastoma cells | ↓Neurotoxicity, ↑GSH, ↓GSSG, ↓elevation in (Ca2+)I | (136) | |
| Oral health | Gallic acid | Streptococcus sobrinus 6715-induced enamel caries in rats | ↑Remineralization of enamel caries lesions, residual first molar enamel volume & mineral density values, ↓severity of molar enamel caries | (137) |
| Radiation-induced toxicity | Gallic acid | Whole body γ-radiation exposure in mice | ↑Rate of DNA repair process in peripheral blood leukocytes, bone marrow cells, & splenocytes, ↑GPx, GSH, ↓mortality, weight loss & LPO | (82) |
| Gallic acid |
In vitro: rat liver microsomes & plasmid pBR322 DNA exposed to γ-irradiation In vivo: whole body γ-irradiation in mice |
In vitro: ↓LPO in rat liver microsomes, ↓DNA damage in plasmid In vivo: ↓DNA damage in leukocytes |
(81) | |
| Respiratory | Gallic acid | Bleomycin-induced pulmonary fibrosis in rats | ↓Lesions & fibrosis, collagen content, hydroxyproline accumulation, LPO, ↓TNF-α & IL-1β, ↑GPx activity & TTM | (80) |
| Urinary |
Gallic acid | Doxorubicin-induced chronic kidney disease in rats | ↑Albumin, ↓AST, ↓ALT, ↓TG, ↓cholesterol, ↓LPO, ↓BUN | (79) |
| Gallic acid | Glyoxal-induced renal fibrosis in rats | ↓Renal fibrosis, ↓BUN, ALP, collagen I & III, MMP-2 & -9, NOx & ROS, ↑SOD | (78) | |
| Gallic acid | Ferric nitriloacetic acid-induced renal toxicity in rats | ↓Renal toxicity & cell proliferation, BUN, H2O2, renal microsomal LPO & quinone reductase, ↑CAT, xanthine oxidase, GPx, GST & G6PD | (77) | |
| Gallic acid | Cisplatin-induced nephrotoxicity in rats | ↓LPO, ROS, Cr, urea, uric acid, arginase activity, ↑SOD, CAT, GSH & GPx | (75) | |
| Gallic acid | Experimental renal ischemia-reperfusion in rats | ↓BUN, Cr, MDA | (74) | |
| Urogenital | Gallic acid | Cyclophosphamide-induced toxicity in testis & epididymis of rats | ↓Reproductive toxicity, nitrite, H2O2 & MDA ↑SOD, GST, FSH, LH & testosterone | (55) |
| Gallic acid | Cyclophosphamide-induced toxicity in testis & epididymis of rats | ↓MDA, NO, H2O2, ↑GSH, GPx, SOD, CAT & testosterone | (76) | |
| Gallic acid | STZ-induced oxidative stress in testis of rats | ↑SOD & CAT, ↓MDA, TNF-α, VEGF & NOS2 | (138) | |
| Dermal | Gallic acid |
In vitro: normal human dermal fibroblasts exposed to UVB In vivo: hairless mice exposed to UVB |
In vitro: ↓transcription factor activation protein 1 activity In vivo: ↓dryness, skin thickness, wrinkle formation & MMP-1, ↑elastin, type I procollagen & TGF-β1 |
(84) |
| Gallic acid |
In vitro: murine melanoma B16F10 cells In vivo: zebrafish, UVB-induced hyperpigmentation in mice ear |
In vitro: ↓melanin production & tyrosinase activity, melanogenesis regulatory genes, activation of the ERK pathway, involvement of AKT/GSK3b & PKA/CREB signaling In vivo: ↓body pigmentation in zebrafish, ↓hyperpigmentation of ear skin, inflammation, melanocytes activation & melanogenic genes |
(83) | |
| Malignancy | Gallic acid | DMH-induced colon carcinogenesis in male Wistar rats | ↑SOD, GSH, GR, GPx, & CAT activity, LPO modification | (39) |
| Gallic acid | DMH-induced colon carcinogenesis | ↑Activity of phase I enzymes (cyt. P450 & cyt. b5), ↓activity of phase II enzymes (GST, DTD & GGT) | (139) | |
| Isobutyl gallate-3,5-dimethyl ether (IGDE) & methyl gallate-3,5-dimethyl ether (MGDE) |
In vitro: EAT & LLC1 cells In vivo: EAT cells /BALB/c mice & LLC1 cells /C57bl/6 mice |
In vitro: no significant cytotoxic effects In vivo: EAT cells ↑Survival (IGDE>MGDE), NK cells cytotoxicity In vivo (LLC1): ↓tumor size (IGDE>MGDE) |
(44) | |
| Gallic acid |
In vitro: HL-60 human promyelocytic leukemia In vivo: athymic nude mice model |
In vitro: induction of G1 cell cycle arrest, ↓cyclin D1, CDK4, cyclin E, CDK2, & cyclin A, ↑p27KIP expression In vivo: ↓Tumor progression |
(45) | |
| Gallic Acid | Diethylnitrosamine-induced hepatocellular carcinoma in rats | ↓Tumor size, AFP & CEA, ↓serum AST, ALT, ACP, ALP, LDH, GGT, ↓liver AgNORs & PCNA | (46) | |
| Gallic acid |
In vitro: human NCSLC NCI-H460 cells In vivo: mouse NCI-H460 xenograft model |
In vitro: ↓viability, induction of G2/M phase cell cycle arrest, ↑intracellular Ca2+, CDK1 activity, caspase-3, caspase-8 & caspase-9 activation, ↓ΔΨ In vivo: ↓tumor size |
(140) | |
| Gallic acid |
In vitro: LL-2 mouse lung cancer cells In vivo: LL-2 lung cancer cells transplanted in mice |
In vitro: ↓viability In vivo: ↓tumor size, ↑number or apoptotic cells in tumor, synergistic effects in combination with cisplatin |
(141) | |
| Gallic acid & methyl gallate | two-stage skin carcinogenesis in ICR mice | ↓average number of papillomas per mouse | (142) | |
| Gallic acid | 7,12-DMBA/croton oil- induced two-stage skin carcinogenesis in Swiss albino mice |
↓time of appearance & average number of papillomas per mouse, tumor incidence, ↓LDH total activity& LDH-isoenzymes, LPO, MMP-2 & MMP-9 activity & expression, ↑GST, SOD, CAT activity & GSH, synergistic effect with 5-FU | (40) | |
| Gallic acid |
In vitro: cell-free kinases, primary HUVECs, primary human dermal LECs, human HT29 colon carcinoma cells & MT-450 rat mammary carcinoma cells In vivo: MT-450 tumor-bearing rats |
In vitro: slight inhibition of RTKs, ↓VEGF-induced autophosphorylation of VEGFR-2 in HT29 cells, ↓proliferation & ↑apoptosis in all cell lines In vivo: ↓tumor angiogenesis, ↑metastasis |
(143) | |
| Pyrogallol |
In vitro: MCF10DCIS.com cells In vivo: xenograft mouse model of MCF10DCIS.com |
In vitro: induction of S phase cell cycle arrest ↑ROS In vivo: ↓tumor size, IR, IRS1, IGF-1R, p70S6K, & ERK phosphorylation, ↓IL-1β, involvement of AMPK & AKT/mTOR signaling |
(43) |
i-NOS: nitric oxide synthase; IL-2: interleukin-2; IFN-γ: interferon-γ; TNF-α: tumour necrosis factor-α; IL-4: interleukin-4; IL-5: interleukin-5; IL-1β: interleukin-1β; COX-2: cyclooxygenase-2; IL-6:i nterleukin-6, NO: nitric oxide; SOD: superoxide dismutase; GPx: glutathione peroxidase; VCAM-1: vascular cell adhesion molecule-1; HUVECs: human umbilical vein endothelial cells; TC: total cholesterol; TG: triglycerides; VLDL-C: very low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol; LDL: low-density lipoprotein; CAT: catalase; LPO: lipid peroxidation; GSH: glutathione; GST: glutathione-S-transferase; AGEs: advanced glycation end products; ECM: extracellular matrix; TGF-β: transforming growth factor- β; MMPs: matrix metalloproteinases; cTnT: cardiac troponin T; LDH: lactate dehydrogenase; ROS: reactive oxygen species; LAP: leucine aminopeptidase; y-GTP ;y-glutamyl transpeptidase; Bcl-2: B-cell lymphoma 2; IL-21: interleukin-21; IL-23: interleukin-23; UDP-GT: UDP glucuronosyltransferase; NQO1: NAD(P)H quinone dehydrogenase-1; MPO: myeloperoxidase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ALP: alkaline phosphatase; CCl4: carbon tetrachloride, HA; hyaluronic acid; MDA: malondialdehyde; γ -GT: γ -glutamyl transferase; ALP: alkaline phosphatase; ALA-D: aminolevulinic acid dehydratase; PDX-1: pancreas/duodenum homeobox 1; PPAR-γ: peroxisome proliferator-activated receptor γ; TBARS: 2-thiobarbituric acid reactive substances; MFB: medial forebrain bundle; H2O2: hydrogen peroxide; MWM: Morris water maze; EPM: elevated plus maze; MPT: membrane permeability transition; LPS: lipopolysaccharide; BUN: blood urea nitrogen; AChE: acetyl cholinesterase; MAO-A: Monoamine oxidase-A; G6PD: glucose-6-phosphate dehydrogenase; MAPKs: mitogen-activated protein kinases; AEGs: Advanced glycation end products; GLUT1: glucose transporter protein 1, GLUT4: glucose transporter protein 4; PI3K: phosphatidylinositol 3-kinase; p-Akt: phosphorylated protein kinase B; TAG: triacylglycerol; GSSG: glutathione disulfide;, AUCglucose: area under the curve for glucose; HOMA-IR: homeostasis model assessment insulin resistance; IRS-1: insulin receptor substrate-1; IR: insulin receptor; GLUT-2: glucose transporter protein 2;; F-1,6-BP: fructose-1,6-bisphosphatase; PFK: phosphofructokinase; a-CN: a-casein; STZ: streptozotocin; β-LG: β-lactoglobulin; Aβ: amyloid β Protein; (Ca2+): cytosolic Ca2+ concentration; MTT: 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide; H2DCF-DA: Hoechst 33342 dye, fluo-4 AM & 2_,7_-dichlorodihydrofluorescin diacetate; n-NOS: neuronal nitric oxide synthase; SNCV: sciatic nerve conduction velocity; LTP: long-term potentiation; PS Amp: population spikes amplitude; AUC: area under curve; CA-1: region I of hippocampus proper; AD: Alzheimer disease; PC12: pheochromocytoma cells; Bcl-2: B-cell lymphoma 2; JNK: c-Jun N-terminal protein kinase; , ICR: institute of cancer research; peroxidase, MDA: malondialdehyde, k-CN: kappa-casein, DCF: dichlorofluorescin, ; PGE2: prostaglandin E2; e-NOS: endothelial nitric oxide synthase; HSCs: hepatic stellate cells; UVB: ultraviolet B; TAC: total antioxidant capacity; L-NAME: NG-nitro-L-argininemethyl ester; SBP: systolic blood pressure; LV: left ventricle; HDAC: histone deacetylase; VEGF: vascular endothelial growth factor.