Flavonoids Catechin In vitro /ex vivo Cells used (in vitro ) Inducer(s) Functions References Rat cerebellar granule cells Glutamate ↑ cell viability by inhibition of Ca2+ influx [78 ] Rat primary mesencephalic cultures MPP+ 2 O2 , 4-HNE, rotenone, and 6-OHDA ↓ apoptosis3 H] DA uptake[75 ] Catechin In vivo Type of animals (in vivo ) Disease model used (in vivo ) Functions References Rats Nil ↓ MOA-B activity[74 ] Quercetin In vitro /ex vivo Cells used (in vitro ) Inducer(s) Functions References N9 microglia LPS ↓ TNF-
and IL-1
mRNA levels↓ apoptosis and cell death[72 ] PC12 cells 6-OHDA ↓ apoptosis and cell death↓ nitric oxide overproduction and iNOS overexpression[73 ] Rat primary mesencephalic cultures MPP+ ↓ apoptosis[75 ] Rat cortical neuronal cultures A
↓ cytotoxicity, protein oxidation, lipid peroxidation, and apoptosis[79 ] PC12 cells MPP+ ↓ apoptosis and cell death↓ Bax and ↑ Bcl-2 expressions↓ AIF in cytosolic and nuclear fraction↓ cytochrome c levels in cytosolic fraction[80 ] P19 neurons H2 O2 ↑ neuronal viability↓ ROS production↓ nuclear condensation, caspase 3/7 activity, and PARP upregulation [76 ] SH-SY5Y cells H2 O2 ↓ cytotoxicity and LDH release↓ Bax and ↑ Bcl-2 expressions↓ caspase activation[81 ] Quercetin In vivo Type of animals (in vivo ) Disease model used (in vivo ) Functions References Zebra fish 6-OHDA ↓ dopaminergic neuron loss↓ TNF-
, IL-1
, and COX-2 overexpressions[73 ] Rats 6-OHDA ↑ striatal dopamine and antioxidant enzyme levels↓ protein carbonyl content in the striatum [77 ] Rats Repeated cerebral ischemia Improve spatial memory impairment↓ neuronal death [82 ] Rats pMCAO ↓ ischemic lesion[83 ] Rutin In vitro/ex vivo Cells used (in vitro ) Inducer(s) Functions References RAW 264.7 cells LPS ↓ nitric oxide production↓ iNOS gene expression[89 ] SH-SY5Y cells Aβ 42 ↓ ROS production↓ TNF-
and IL-1
productions[90 ] Rutin In vivo Type of animals (in vivo ) Disease model used (in vivo ) Functions References Rats 6-OHDA ↑ antioxidant enzymes activities↓ nitric oxide level [91 ] Rats Trimethyltin (TMT) ↓ IL-1
and IL-6 mRNA levels[92 ] Rats Cerebral ischemia ↓ neuronal death[93 ] Baicalein In vitro/ex vivo Cells used (in vitro ) Inducer(s) Functions References BV-2 microglia Hypoxia ↓ HIF-1 protein accumulation and transcriptional activation↓ iNOS, COX-2, and VEGF gene expressions[97 ] Primary midbrain LPS ↓ TNF-
, nitric oxide, and superoxide productions[94 ] SH-SY5Y cells 6-OHDA ↓ oxidative stress, mitochondrial dysfunction, caspase activity, and JNK activation[99 ] SH-SY5Y cells 6-OHDA ↓ apoptosis[100 ] HT22 mouse hippocampal neuronal cells Thapsigargin (TG) and brefeldin A (BFA) ↓ apoptosis↓ C/EBP homologous protein (CHOP) induction and ROS accumulation [101 ] Rat glioma C6 cells H2 O2 ↓ ROS-mediated cytotoxic effects[102 ] Primary microglia/BV-2 cells LPS/IFN-
↓ nitric oxide production and iNOS gene expression↓ NF-IL6 binding[98 ] PC12 cells Rotenone ↓ apoptosis↓ ROS production[103 ] Baicalein In vivo Type of animals (in vivo ) Disease model used (in vivo ) Functions References Rats Controlled cortical impact injury Improve functional recovery ↓ contusion volumes↓ the number of degenerating neurons↓ TNF-
, IL-1
, and IL-6 mRNA and protein levels [104 ] Baicalin In vitro/ex vivo Cells used (in vitro ) Inducer(s) Functions References RAW 264.7 cells LPS ↓ nitric oxide production↓ iNOS and COX-2 gene expressions[118 ] RAW 264.7 cells and peritoneal macrophages LPS or IFN-
↓ nitric oxide production and iNOS expression↓ TNF-
, ET-1, and thromboxane A2 (TXA2)[106 ] PC12 cells Oxygen-glucose deprivation/H2 O2 ↓ ROS production↓ 5-LOX nuclear translocation↓ p38 phosphorylation[107 ] Baicalin In vivo Type of animals (in vivo ) Disease model used (in vivo ) Functions References Rats pMCAO ↓ neurological deficit scores and cerebral infarct volume↓ iNOS, COX-2 mRNA, and cleaved caspase-3 protein expressions↓ TLR2/4 and NF-
B expressions[108 , 109 ] Rats Spinal cord injury ↓ oxidant stress, proinflammatory cytokines expressions, and apoptosis[111 ] Rats Focal cerebral ischemic reperfusion injury ↓ NF-
B p65 level[110 ] Wogonin In vitro/ex vivo Cells used (in vitro ) Inducer(s) Functions References RAW 264.7 cells LPS ↓ PGE2 and nitric oxide productions↓ COX-2 expression and activity [112 –115 ] Microglia LPS ↓ nitric oxide production↓ TNF-
and IL-6 productions↓ NF-
B activity[116 ] Microglia MCP-1 ↓ NF-
B activity[117 ] Wogonin In vivo Type of animals (in vivo ) Disease model used (in vivo ) Functions References Mice LPS ↓ nitric oxide production↓ iNOS expression[113 ] Rats pMCAO ↓ infarct volume[119 ] Oroxylin A In vitro/ex vivo Cells used (in vitro ) Inducer(s) Functions References RAW 264.7 cells LPS ↓ nitric oxide production↓ iNOS and COX-2 gene expressions↓ NF-
B activation[120 ] Apigenin In vitro/ex vivo Cells used (in vitro ) Inducer(s) Functions References RAW 264.7 cells LPS ↓ COX-2 and iNOS expressions↓ NF-
B activation[123 ] PBMC LPS ↓ TNF-
, IL-6, and IL-1
productions[124 ] J774.2 macrophages LPS ↓ TNF-
and IL-1
mRNA levels[125 ] BV-2 microglia LPS ↓ nitric oxide and PGE2 productions↓ p38 and JNK phosphorylations[126 ] Apigenin In vivo Type of animals (in vivo ) Disease model used (in vivo ) Functions References Mice MCAO ↓ infarct volume↓ the number of microglia[126 ] Kaempferol In vitro/ex vivo Cells used (in vitro ) Inducer(s) Functions References J774.2 macrophages LPS ↓ TNF-
and IL-1
mRNA levels[125 ] J774 macrophages LPS ↓ PGE2 production↓ COX-2 and mPGES-1 mRNA levels[127 ] J774 macrophages LPS ↓ nitric oxide production↓ iNOS mRNA and protein expressions [128 ] RAW 264.7 cells LPS ↓ nitric oxide, PGE2 , and TNF-
productions[129 ] Kaempferol In vivo Type of animals (in vivo ) Disease model used (in vivo ) Functions References Rats Transient focal cerebral ischemia ↓ nitrosative-oxidative stress, protein nitrotyrosines, and apoptotic cell death[130 ] Hyperoside In vitro/ex vivo Cells used (in vitro ) Inducer(s) Functions References PC12 cells Sodium azide ↓ ROS production↓ caspase-3 activity and Bax expression[133 ] PC12 cells H2 O2 and tert-butyl hydroperoxide ↑ cell viability↓ apoptosis [132 ] Mouse peritoneal macrophages LPS ↓ TNF-
, IL-6, and nitric oxide productions[131 ] Hyperoside In vivo Type of animals (in vivo ) Disease model used (in vivo ) Functions References Rats MCAO ↓ infarct size and cerebral edema[134 ]
