Table 4.
Summary of the different pharmacological properties of different phenolic compounds found in bee pollen.
| Molecules | Dosage, Route, and Exposure Duration | Pharmacological Properties | Involved Mechanisms | References |
|---|---|---|---|---|
| Caffeic acid | 6 mg/kg/day, orally for 45 days. | Anti-oxidative properties | ↑Non-enzymic antioxidants, ↓lipid peroxidation, and ↓TBARS level. | [177] |
| Cinnamic acid | 20 mg/kg/day, i.p for 40 days. | ↓lipid peroxidation, ↓ROS production ↑GSH, ↑SOD, and ↑CAT levels. | [178] | |
| Ferulic acid | 25 mg/kg/day, orally for 10 days. | ↓lipid peroxidation, ↓ROS levels, and ↓N-acetyl-β-glucosminidase activity. | [210] | |
| Ellagic acid | 10 and 30 mg/kg/day for 30 days. | Enhances the concentration of enzymatic antioxidant levels (SOD, CAT, and GPx), and ↓ MDA, ↓TNF-α, and ↓IL-1β. | [211] | |
| Quercetin | 50 mg/kg/day, i.p for 21 days. | Increases GSH level, SOD, GR, G, P, and CAT activity, and decreases the expression of TNFα, IL-1β, and IL-6. | [180] | |
| Kaempferol | 100 mg/ kg/day, i.p for 6 weeks. | Inhibits the activity of ASK1/MAPK signaling pathways (JNK1/2 and p38). | [212] | |
| Galangin | 8 mg/kg/day, i.p for 45 days. | ↓lipid peroxidation, ↑enzymatic and non-enzymatic antioxidants. | [213] | |
| Chrysin | 30 mg/kg/day, orally, for 14 days. | ↑GSH, ↓TBARS, ↓XO, and ↓NADPH levels | [214] | |
| Protocatechuic acid | 100 mg/kg/day, i.p for 7 days. | Prevents lipid peroxidation and the formation of NO, and enhances antioxidant enzymes. | [215] | |
| Apigenin | 0.625, 1.25, and 2.5 mg/mL. | ↓oxidative stress, GSH level ↑SOD activity, ↓IL-6, and ↓NF-κB levels. | [216] | |
| Luteolin | 100 and 200 mg/kg/ day, orally for 28 days. | ↓MDA, ↑GSH, ↑SOD ↑GPX ↑Nrf2, and ↑HO-1 Expressions. | [181] | |
| Rutin | 50 and 100 mg/kg/day, orally for 20 days. | ↑Production of antioxidant enzymes, ↓serum toxicity markers, and downregulation of (COX, 2p38-, MAPK, i-NOS, and NF-κB). | [179] | |
| Naringenin | 50 mg/kg/day, orally for 8 weeks. | Minimizes oxidative stress and enhances CAT, SOD GSH, and GPx levels. | [217] | |
| Pinocembrin | 10 mg/kg/day, orally for 7 days. | Decreases oxidative stress, and apoptotic and inflammatory markers. | [182] | |
| Caffeic acid | 100 mg/kg/day, orally for 4 weeks. |
Antidiabetic and anti-hyperglycemic properties | IL-6, ↓ IL-1β, ↓ TNF-α, ↓ MCP-1, ↓HbA1c, ↓ UGA, ↓ sorbitol, ↓ fructose, and ↑AMPKα2. | [218] |
| Ferulic acid | 10 mg/kg/day, orally for 15 days. | Down-regulation of NF- κB pathway. | [219] | |
| Cinnamic acid | 50 mg/kg/day, orally for 5 weeks. | ↑insulin secretion, ↑hepatic glycolysis, ↑adiponectin secretion ↑glucose uptake, ↑pancreatic β-cell functionality, and ↓protein glycation. | [186] | |
| Ellagic acid | 250 mg/kg/day, orally for 28 days. | ↑ insulin secretion, ↑β-cell number, ↑plasma total antioxidants, and ↑glucose intolerance. | [220] | |
| Quercetin | 10 and 30 mg/kg/day, i.p for 14 days. | ↑GLUTs, ↑IR-P, ↑GLUT4, ↑Glucose uptake, ↑pancreatic cell-β generation, ↑glucokinase activity, ↓α-glucosidase activity. | [221] | |
| Kaempferol | 50 mg/kg/day, orally for 12 weeks. 200 mg/kg/day, orally for 14 days. |
↓hepatic glucose production, ↑hexokinase activity, ↓hepatic pyruvate carboxylase activity, and gluconeogenesis. ↑GLP-1 and insulin release, ↑ cAMP, and Ca2+ intracellular levels. |
[188,222] | |
| Galangin | 4, 8, and 16 mg/kg/day, orally for 45 days. | Inhibition of DPP-4, ↓oxidative stress, and ↑antioxidant status. | [213] | |
| Chrysin | 40 mg/kg/day, orally for 16 weeks. | Inhibition of the TNF-α pathway, ↓secretion of pro-inflammatory cytokines, and ↓glucose and lipid peroxidation levels. | [223] | |
| Protocatechuic acid | 50 and 100 mg/kg/day, orally for 7 days. | ↑insulin sensitivity, ↓insulin resistance, ↓gluconeogenesis, and ↑glucose uptake. | [224] | |
| Apigenin | 1.5 mg/kg/day, i.p for 28 days. | Enhances GLUT4 translocation. | [225] | |
| Luteolin | 10 mg/kg/day, orally for 24 weeks. | Reduces oxidative stress and inhibits the STAT3 pathway. | [226] | |
| Rutin | 90 mg/kg/day, orally for 10 weeks. | Inhibition of polyol pathway, oxidative stress, and lipid peroxidation. | [187] | |
| Naringenin | 50 and 100 mg/kg/day, orally for 6 weeks. | Improvement of glucose and lipid metabolism, and ↓insulin resistance. | [227] | |
| Pinocembrin | 50 mg/ kg/day, orally for 10 days. | ↓ NF-κB and TNF-α levels. | [228] | |
| Resveratrol | 12 mg/kg/day, orally for 1 5 days. | Down-regulation of NF- κB pathway. | [219] | |
| Caffeic acid | 100 mg/kg/day, orally for 4 days. | Hepato-protective properties | Downregulation of CYP2E1 and the protection of DNA against oxidative damage. | [193] |
| Cinnamic acid | 20 mg/kg/day, orally for 10 days. | ↓NF-kB and ↓iNOS activities. | [229] | |
| Ellagic acid | 5 and 10 mg/kg/day, orally for 10 days | Up-Regulation of Nrf2 and HO-1 expression and inhibition of NF-κB signaling pathway. | [194] | |
| Quercetin | 20, 40, and 80 mg/kg/day, orally for 7 days. | Modulation of the expression of nuclear orphan receptors (CAR, PXR) and cytochrome P450 enzymes (CYP1A2, CYP2E1, CYP2D22, CYP3A11). | [230] | |
| Kaempferol | 20 mg/kg, twice a day, orally for 28 days. | ↓CYP2E1 activity and ↓ROS production. | [231] | |
| Galangin | 15, 3,0, and 60 mg/kg/day, orally for 15 days. | Activation of Nrf2 and HO-1 signaling pathway. | [232] | |
| Chrysin | 25 or 50 mg/kg, orally for 6 days. | Decreases the expression of COX-2, iNOS. | [233] | |
| Ferulic acid | 25, 50, and 100 mg/kg/day, orally for 7 days. | ↓ the expression TNF-α and IL-1β, upregulation of p-JNK, p-p38 MAPK, and Bcl-2. | [191] | |
| Protocatechuic acid | 25 and 50 mg/kg/day, i.p for 7 days. | ↓ oxidant species ↑antioxidant enzymes | [192] | |
| Apigenin | 10 mg/kg/day, orally for 3 weeks. | Enhances antioxidant defense mechanisms and decreases lipid peroxidation. | [234] | |
| Luteolin | 100 mg/kg/day, i.p for 7 days. | Modulation of Nrf2/HO-1 pathway and ↓oxidative stress. | [235] | |
| Rutin | 20 mg/kg/day, orally for 15 days. | ↑Antioxidant profile and regulation of Na+/K+ ATPase activity. | [236] | |
| Naringenin | 50 mg/kg/day, orally for 10 days. | ↑the enzymatic and non-enzymatic antioxidant levels, ↓NO, TNF-α, and IL-6 levels. | [190] | |
| Pinocembrin | 50 and 75 mg/kg/day, i.p for 10 days. | Modulation of Nrf2/HO-1 and NQO1 pathways. | [199] | |
| Resveratrol | 50 and 100 mg/kg/day, orally for 28 days | Modulation of SIRT1 and p53 pathways. | [237] | |
| Caffeic acid | 100 mg/kg/day, orally for 14 days. | Nephroprotective properties | Enhances the antioxidant defense system and reduces lipid peroxidation. | [238] |
| Ferulic acid | 50 mg/kg/day, orally for 8 weeks. | Modulation of AGEs, MAPKs (p38 and JNK), and NF-κB pathways, and ↓oxidative stress. | [197] | |
| Cinnamic acid | 50 mg/kg /day, orally for 7 days. | antioxidant expression GSH levels, SOD, CAT, and GPx activities. | [239] | |
| Ellagic acid | 10 mg/kg/day, orally for 30 days. | Stimulates the expression of SIRT1, ↓P53 protein level, ↓ROS production, and ↑enzymatic and non-enzymatic antioxidant system. | [198] | |
| Quercetin | 10 mg/kg/day, i.p for 10 weeks. | ↑antioxidant expression and ↓lipid peroxidation. | [240] | |
| Kaempferol | 100 mg/kg/day, orally for 28 days. | Inhibits RhoA/Rho Kinase mediated inflammatory pathway. | [241] | |
| Chrysin | 30 and 100 mg/kg, ip for 26 days. | ↑iNOS and PKC Levels, and ↓AGEs and RAGE. | [242] | |
| Protocatechuic acid | 25 and 50 mg/kg/day, i.p for 7 days. | ↓ oxidant species ↑antioxidant enzymes. | [192] | |
| Apigenin | 3 mg/kg/day, i.p for 7 days. | Reduces COXI and COXII, MDA levels and increases GSH level. | [195] | |
| Luteolin | 10 and 20 mg/kg/day, orally for 4 weeks. | Inhibition of RIP140/NF-κB pathway. | [243] | |
| Rutin | 100 mg/kg/day, orally for 14 days. | Suppresses NF-κB activation and TGF-β1/Smad3 signaling. | [244] | |
| Naringenin | 100 mg/kg/day, orally for 45 days. | ↓ oxidative stress and lipid peroxidation levels. | [196] | |
| Pinocembrin | 50 and 75 mg/kg/day, i.p for 10 days. | Modulation of Nrf2/HO-1 and NQO1 pathways. | [199] | |
| Resveratrol | 20 mg/kg/day, orally for 40 weeks. | Modulation of the NF-κB signaling pathway. | [245] | |
| Caffeic acid | 50 mg/kg/day, orally for 21 days. | Anti-inflammatory properties | inhibition of NO, prostaglandin E2, and NF-κB signaling pathways. | [201] |
| Ferulic acid | 100 mg/kg/day, orally for 6 weeks. | Inhibition of NADPH oxidase and NF-κB pathway. | [202] | |
| Cinnamic acid | 60 mg/kg/day, orally for 21 days. | Down-regulation of the NLRP3, NF- κB, and ASK1/MAPK signaling pathways. | [203] | |
| Ellagic acid | 1, 3, 10, and 30 mg/kg, i.p for 5 h. | Suppression of NF-κB pathway and NO, TNF-α, IL-6, COX-2 activity, and PGE2. | [246] | |
| Quercetin | 1 mg/kg/day, orally for 15 days. | Down-regulation of the NF-κB pathway. |
[208] | |
| Kaempferol | 2 and 4 mg/kg/day for 10 days. | Decreases the synthesis of IL-1β, TNF-α, IL-18, and IL-6. | [209] | |
| Galangin | 50 mg/kg per day, orally for 4 days. | Inhibits the expression of iNOS, COX-2, and pro-inflammatory cytokines. | [205] | |
| Chrysin | 40 mg/kg/day, orally for 16 weeks. | inhibition of NO, prostaglandin E2, and NF-κB signaling pathways. | [206] | |
| Protocatechuic acid | 20 mg/kg/day, orally for 8 weeks. | ↓IL-1β, ↓IL-6, and ↓TNF-α synthesis pathways. | [247] | |
| Apigenin | 20 and 40 mg/kg/day, orally for 28 days. | ↓TNF-α and IL-6 production. | [248] | |
| Luteolin | 100 mg/kg, i.p for 6 h. | ↑HO-1 expression, ↑IL-10, ↓TNF-α, and ↓IL-6 levels. | [249] | |
| Rutin | 30 mg/kg/day, orally for 14 days. | Inhibition of p38-MAPK pathway. | [250] | |
| Naringenin | 5, 10, and 20 mg/kg/day, for 16 days. | Up-regulation of Nrf-2/HO-1pathway and ↓NF-kB mRNA expression. | [251] | |
| Pinocembrin | 50 mg/kg/day, i.p for 24 days. | Down-regulation of NF-kB pathway. | [252] | |
| Resveratrol | 10 or 50 mg/kg/day, orally for 28 days. | Inhibition of COX-1 and COX-2 activities | [207] |
↑ represent increases; ↓ represent decreases.