An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders
Abstract
:1. Introduction
2. Chemistry and Sources of TAN
TAN Source | Plant Part | Reference |
---|---|---|
Citrus poonensis (C. poonensis) | Peel | [32] |
C. exocarpium Rubram | Exocarp | [35] |
C. reticulata | Peel | [36] |
C. unshiu | Peel | [37] |
C. depressa Hayata | Peel | [38] |
Hura crepitans | Leaves, bark, roots | [39] |
Fructus aurantia | Fruit | [28] |
C. aurantifolia | Peel, fruit pulp | [40] |
C. mitis Blanco | Peel | [41] |
C. aurantium | Peel | [42] |
C. reticulate Cv. Suavissima | Fruit | [43] |
C. grandis Osbeck | Leaves | [44] |
C. reticulata *, Citrus paradisi | Fruit | [45] |
C. clementina | ||
C. sinensis | ||
C. paradise | ||
C. lumia Risso | ||
C. ichangensis Swingle * | Peel | [43] |
2.1. Physicochemical Properties of TAN
2.2. Metabolism and Pharmacokinetic Profile of TAN
2.3. Safety and Toxicity of TAN
3. Neuroinflammation and Therapeutic Potential of TAN
3.1. Effect of TAN in PD Models
3.2. Effect of TAN in AD Models
3.3. Effect of TAN on Ischemic Brain Injury Models
3.4. Effect of TAN on Neurogenesis and Cognitive Functions
4. Other Supporting Mechanisms of TAN in Neurodegeneration
4.1. Antioxidant Effect of TAN
4.2. Anti-Inflammatory Effect of TAN
4.3. Diabetes-Mediated Neurodegeneration and TAN
4.4. Peroxisome Proliferator Receptor-Gamma (PPAR-γ) Agonistic Effects of TAN
5. Limitations and Future Perspectives
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Properties | Values |
---|---|
Physical Description | Solid |
HBDC | 0 |
HBAC | 7 |
BP | 566 °C @ 760 mm Hg |
MP | 154 °C |
Solubility | 8.70 mg/L @ 25 °C |
LogP | 1.78 |
No. | Model | Experimental Design/Dose | Parameters Tested | Mechanism | Conclusion | Ref. |
---|---|---|---|---|---|---|
1 | 6-OHDA-induced PD rat model | 20 mg/kg/day for 4 days; p.o. | TH+ cells and striatal dopamine content | Reduced TH+ cells; increased striatal dopamine content | Neuroprotective agent | [21] |
2 | MPTP-induced rat PD model | 50, 100 or 200 mg/kg body weight for 20 days | Rotarod, working memory, object recognition, inflammatory mediators, cytokines | Enhanced memory and locomotion; decreased COX-2, iNOS, IL-1β, IL-6, and IL-2 | Neuroinflammation and dementia associated with PD | [48] |
3 | Transgenic Drosophila PD model | 5, 10 and 20 µM in diet for 24 days | Climbing ability, dopamine levels, antioxidant enzymes | Enhanced climbing ability and dopamine content; decreased oxidative stress | Enhanced behavioral pattern and antioxidant | [100] |
4 | Pilocarpine-induced mice | 50, 100, or 200 mg/kg for 10 days | Neuronal apoptosis and seizure severity | Regulation of PI3K/Akt signalling; decreased seizure-induced MMP-2, MMP-9, and AIF | Recovered PD-associated epileptic seizures | [102] |
5 | APPswe/PSEN1dE9 transgenic AD mice model | 100 mg/kg body weight/day | Cognitive functions, Aβ aggregation | Inhibited β-secretase both in vitro and in vivo | Anti-dementia effect | [22] |
6 | Aβ-induced rat primary neurons | 25 µM | Oxidative damage, Aβ aggregation | Reduced free radical damage and suppressed Aβ neurotoxicity | Neuroprotective effect | [103] |
7 | HepG2 cells in vitro and ischemic-reperfusion rat model | 100 μg/mL for in vitro and 200 mg/kg in vivo | Apoptosis and cell viability | Inhibited apoptosis, and reduced brain injury | Neuroprotection and ischemic stroke protection | [18] |
8 | OGD insult in HBMEC cells | 2.5, 5 and 10 µM | Cell viability, ROS levels, inflammatory pathways | Reduced ROS levels; ameliorated apoptosis; regulated JNK signaling | Protects brain injury and related neurogenerative diseases | [106] |
9 | Global cerebral ischemia in rats | 5,10, and 20 mg/kg, oral | Cognition and memory, AchE, Ach levels, ROS levels, inflammation markers | Increased memory and cognition; attenuated AchE and Ach activities; inhibited IL-6 and TNF-α, mitigating apoptosis | Neuroprotection, and antineuroinflammation | [24] |
10 | In vivo MCAO/R mice model and OGD/R injury in hippocampal HT22 cell in vitro | 5, 10 and 20 µM in vitro and 10 µM in vivo | Cell viability, neuronal pyroptosis | Attenuated pyroptosis and regulated Nrf-2 signaling | Neuroprotective effects | [107] |
11 | LM mice model | 5, 10 and 15 mg/kg | Cognitive functions, novel object recognition, inflammatory mediators | Recovered cognitio; decreased ERK ½, TNFα; and IL-1β expression; modulated RORα/γ target genes | Cognitive deficiency and related diseases | [23] |
12 | Potassium dichromate -induced brain injury in rats | 50 mg/kg; orally, for 14 days | Behavioral indices, ROS markers, inflammatory markers | Reduced ROS levels; inhibited TNF-α and IL-6; regulated Nrf2 signaling pathway | Neuroprotective effect, anti-neuroinflammation, antioxidant | [108] |
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Wani, I.; Koppula, S.; Balda, A.; Thekkekkara, D.; Jamadagni, A.; Walse, P.; Manjula, S.N.; Kopalli, S.R. An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders. Life 2024, 14, 504. https://doi.org/10.3390/life14040504
Wani I, Koppula S, Balda A, Thekkekkara D, Jamadagni A, Walse P, Manjula SN, Kopalli SR. An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders. Life. 2024; 14(4):504. https://doi.org/10.3390/life14040504
Chicago/Turabian StyleWani, Irshad, Sushruta Koppula, Aayushi Balda, Dithu Thekkekkara, Ankush Jamadagni, Prathamesh Walse, Santhepete Nanjundaiah Manjula, and Spandana Rajendra Kopalli. 2024. "An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders" Life 14, no. 4: 504. https://doi.org/10.3390/life14040504