A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease
Abstract
:1. Introduction
2. Oxidative Stress and Alzheimer’s Disease (AD)
2.1. Contributory Sources of Oxidative Stress in AD
2.1.1. Accumulation of Abnormal Amyloid Beta
2.1.2. Activation of Glial Cells
2.1.3. Abnormal Cellular Pathways
3. Bioactive Compounds and Their Role in AD as Antioxidants
4. Lupeol as an Antioxidant and Anti-Inflammatory Agent (Neuroprotective Features)
4.1. Antioxidant Potentials of Lupeol
Role of Lupeol as an Antioxidant in Neuroprotection
Source | Mechanism | Model | Reference |
---|---|---|---|
Crataegus oxyacantha | ↓NF-κB, Vegf-A, IL-6, ↑FGF-2,TGF-β1, ↑collagen III, ↑IL-10 | Streptozotocin-induced hyperglycemic rats | [13] |
Mango Pulp, Egg, Plant, Cucumber, and Soybean | ↑NO, ↓Mg2+,Ca2+ ↓endonuclease III | Escherichia coli | [59] |
Hedera Nepalensis crude extract (HNC) | ↑CAT, SOD ↓GSH, dopamine, serotonin | In vivo STZ + AlCl3-induced diabetic AD | [60] |
Medicinal Plants | ↓NRCMs, ANP, ↓BNP, ↓β-MHC, NF-κB p65 | In vivo and in vitro cardiac hypertrophy in neonatal rat’s cardiomyocytes (NRCMs) | [61] |
Vegetables, Edible Fruits | ↓IκBα | In vivo dextran sulfate sodium (DSS)-induced acute colitis | [75] |
Fruits, Vegetables | ↓TGFβ1, ↑Nrf2 | In vivo LPS/D-galactosamine(D-GalN)-induced liver injury | [62] |
Stem Bark of C. Nurvala | ↓TC, PLTAG | In vivo triton-WR 1339-induced hyperlipidemia. | [63] |
Ficus pseudopalma Blanco (Moraceae) | ↓NO | Ethanolic leaf extract of F. pseudopalma | [64] |
Cassia Fistula | ↓MDA ↑SOD, GSH, CAT | In vivo anti-diabetic study l | [76] |
Banana Flower | ↑SOD, CAT, GPx ↑GSH, VitC, VitE | In vivo hyperglycemic model | [65] |
Medicinal Plants | ↑SOD, GST, G6PD, GSH, ↑GPX, γ-GT | In vivo chronic cadmium exposure in kidney | [77] |
Stem Bark of C. nurala | ↑SOD, CAT, GPx, ↑G6PD, GST, GR, ϒ-GT | In vivo cadmium-induced hepatotoxicity | [66] |
Mango Pulp Extract (MPE) | ↓ROS, ↑Cu, Zn-SOD, CAT, GR and GST | In vivo androgen-induced oxidative stress in prostate. | [78] |
Crataeva Nurvala Stem Bark | ↑GSH, Vit C, Vit E | In vivo CP-induced cardiotoxicity | [67] |
Crataeva Nurvala Buch-Ham (Capparidaceae) | ↓TC, TG, LDL VLDL ↑HDL | In vivo hypercholesterolemic atherosclerosis | [68] |
Betula Alnoides | ↓AChE, MDA, nitrite, ↑GSH | In vivo amyloid beta-induced neuronal damage | [69] |
Bombax Ceiba | ↑Tgel ↓rhodamine-B, 5,6-carboxyfluorescein | Molecular modeling studies, X-ray diffraction data and FTIR studies | [71] |
Crateva Adansonii Oliv. (Capparidaceae) | ↓MDA, ↑CAT, GSH | In vivo CCl4-induced hepatotoxicity | [72] |
Fruits, Vegetables, and Herbs | ↓Aβ, ↓NOS2 ↑Nrf2, HO-1 | In vivo Aβ-induced AD | [15] |
Vegetables, Fruits | ↑Nrf2, HO-1 | In vivo traumatic brain injury | [73] |
Vegetables and Fruits | ↑Nrf2, ↓P38 | In vivo ischemic toxicity | [74] |
4.2. Anti-Inflammatory Potential of Lupeol
Anti-Neuroinflammatory Features
Source | Mechanism | Model | Reference |
---|---|---|---|
Edible Plants, such as Olive, Fig, Mango, Carrot, Soybean | ↓NF-kB, ↑Ki-67 | Skin wound healing in rats | [81] |
Stembark of D. Ferruginea Benth. | ↓IL-4, IL-5, IL-13 | In vivo animal model of allergic airway inflammation | [82] |
SHM Herbs | ↓TLR-4, NF-ĸB, IL-1 | In vivo rats with osteoarthritis | [83] |
Maytenus Salicifolia Reissek | ↓IL-6, IL-8 | In vitro rodent model of pan uveitis | [84] |
Vegetable Oils, Cereals, Fruits | ↓TNF-α, IL-1β, IL-6 | In vitro cerulein-induced acute pancreatitis in mice | [85] |
Vegetables, Fruits | ↓TLR4, TNF-α, IL-1β | In vivo mouse model of viral myocarditis induced by coxsackie Virus B3 (CVB3) | [86] |
White Cabbage, Pepper, Cucumber, Tomato, and Fruits such as Olive | ↓IL-12, IL6, IL-1β, TNF-α, CD86 ↑IL-10, ↑CD206 | In vivo and in vitro DSS-induced colitis mouse model | [87] |
Crateva Adansonii Leaf Extracts | ↓TNF-α, IL-1, IL-6 | In vivo and in silico approaches in rats | [88] |
Crude extract of Cariniana domestica Fruit Peels (CdE), | ↓MPO activity ↓Ear edema, inflammatory cell infiltration | Mouse model of skin inflammation | [89] |
Pyrus Pyrifolia | ↓iNOS, COX2 | LPS-activated RAW 264.7 and BV2 cell lines | [90] |
Olives, Mangos and Strawberries | ↓Bax, Cyt-C, caspase 9 ↓caspase 3, TNF-α, iNOS, IL-1β ↓ p-JNK, P38 | In vivo LPS-induced neuronal dysfunctions | [41] |
Olea Europaea (Olive), Mangifera Indica(Mango) | ↓TNF, iNOS and NLRP3 ↓IL-6 mRNA | In vitro LPS-induced neurodegeneration | [91] |
Celastrus paniculatus (CP) | ↓α-syn | In vivo C. elegans PD model | [92] |
Vegetables | ↑Nrf2/HO-1 ↓Iba-1, GFAP ↓p-NFkB, TNFα, COX-2, IL-1 ↓Casp3, Cyt-C, BAX/BCL2 | In vivo TBI-induced neurodegeneration in male wildtype C57BL/6 N mice | [73] |
Vitex Grandifolia | ↓ iNOS, NFkB | In vitro MAO-A and B-induced neuronal dysfunction and neuroprotection in mouse macrophages | [93] |
Peppers, Tomatoes, Olive Oil | ↑PI3K/Akt | In vivo cerebral ischemia–reperfusion injury in rat model | [95] |
Vegetables and Fruits | ↑Nrf2, ↓BAX/Bcl-2, caspase-3 ↓p38 MAPK | In vivo middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R)-induced cerebral ischemia. | [74] |
Medicinal Plants | ↓Antioxidant Activities | In vivo middle cerebral artery occlusion (MCAO)-induced ischemic stroke(nano approach) | [70] |
Pueraria Lobata Roots | ↓NO, iNOS, COX-2 ↓ ROS | In vitro study of RAW 264.7 murine macrophages | [94] |
Peppers, Tomatoes, Olive oil, Figs | ↑p-PDK1, p-Akt, pc-Raf, p BAD, ↓Casp-3 | In vivo cerebral ischemia–reperfusion injury in rats | [95] |
5. Neuroprotective Role of Lupeol in AD
6. Pharmacokinetics of Lupeol
Basic Challenges and Prospects to Boost the Pharmacokinetics and Pharmacodynamics of Lupeol
7. Safety and Toxicity Contour of Lupeol
8. Conclusions, Limitations and Future Remedies
Author Contributions
Funding
Conflicts of Interest
References
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Source | Mechanism | Model | Reference |
---|---|---|---|
Fruits, Vegetables, and Herbs | ↓Aβ, BACE1, GFAP, Iba-1 ↓p-NFkB, TNF-α, NOS2 ↑Nrf2, HO-1 | In vivo Aβ-induced AD mouse model | [15] |
Pueraria Lobata Roots | ↓Aβ, BACE1 | Comparative molecular Docking in AD studies | [97] |
Rhinacanthus Nasutus | ↓Glutamate and Aβ ↓ ROS | In vitro glutamate and Aβ-induced AD Mouse hippocampal HT-22 cell lines | [98] |
Betula Alnoides | ↓Aβ, TNFα, IL-1β, IL-6 | In vivo Aβ-induced AD Male Wistar Rats | [69] |
Hedera Nepalensis | ↓SOD, CAT and GSH | In vivo STZ-+ALCL3-induced diabetes-mediated AD | [60] |
Leea Indica | ↓BACE1 | Molecular docking and molecular dynamic based approaches in AD model | [96] |
Crataegus Oxyacantha | ↓AChE, BuChase | Using in vitro experimental results and the docking score in AChE-induced AD model | [104] |
Desmodium Triquetrum | ↓iNOS ↓IL-1b, IL-6, TNF-α ↓AChE | In vivo aluminum chloride (AlCl3)-induced neurotoxicity in AD Wistar Rats | [100] |
Mangroves | ↓Aβ, AChE | Molecular docking AD model | [103] |
Pharmacokinetics Parameters | Analytical Method/Animal Model | Reference |
---|---|---|
AUC: 9.2-folds ↑Cmax: 3.9-folds ↑T1/2: 15.3 ± 1.3 in SLN SLN enhanced AUC and Cmax and prolonged T1/2 | Solid–lipid nanoparticle (SLNs) loaded with Lupeol in Rats | [108] |
Tmax: 6.444 ± 0.851 h; Cmax: 8.071 ± 2.930 μg/mL. Post-administration times: stomach, 137.25 ± 19.94 ng/mg and small intestine, 99.00 ± 12.99 ng/mg. Excretion: fecal; T1/2e: 12 h post-administration (163.28 ± 9.83 μg/mg). F: 0.645 ± 0.0581 | UPLC-APCI+-MS/MS in CD-1 strain of Mice | [109] |
1 mg/kg dose of Lupeol i.v. administration. AUC0-t (h × ng/mL); 21,584.53 Cmax (ng/mL); 12,485.69 Kel (h − 1); 21,866.18 Tmax (h); 0.14, 0.08 T1/2 (h); 4.95 30 mg/kg dose of Lupeol orally administration. AUC0-t (h × ng/mL); 2190.49 Cmax (ng/mL); 133.33, Kel (h − 1); 2727.52 Tmax (h); 0.08, 4.67 T1/2 (h); 8.66 | LC–MS/MS Wistar Rat plasma | [110] |
AUC: 3.2 times higher after IV. MRT: 2.5× and t1/2: 4.1× | Lupeol-loaded PEGylated liposomes in Rat Model | [111] |
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Park, J.S.; Rehman, I.U.; Choe, K.; Ahmad, R.; Lee, H.J.; Kim, M.O. A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease. Nutrients 2023, 15, 3059. https://doi.org/10.3390/nu15133059
Park JS, Rehman IU, Choe K, Ahmad R, Lee HJ, Kim MO. A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease. Nutrients. 2023; 15(13):3059. https://doi.org/10.3390/nu15133059
Chicago/Turabian StylePark, Jun Sung, Inayat Ur Rehman, Kyonghwan Choe, Riaz Ahmad, Hyeon Jin Lee, and Myeong Ok Kim. 2023. "A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease" Nutrients 15, no. 13: 3059. https://doi.org/10.3390/nu15133059
APA StylePark, J. S., Rehman, I. U., Choe, K., Ahmad, R., Lee, H. J., & Kim, M. O. (2023). A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease. Nutrients, 15(13), 3059. https://doi.org/10.3390/nu15133059