Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases
Abstract
:1. Introduction
2. Structure and Biochemistry of UA
3. Biological Potency of UA
4. Bioavailability and Pharmacokinetic Properties of UA
5. Pharmacological Aspects of UA
5.1. Anti-Diabetic Effect of UA
5.2. Neuroprotective Effect of UA
5.3. Anti-Inflammatory Effect of UA
5.4. Anti-Cancer Effect of UA
6. Drug Delivery System
7. Preclinical and Clinical Studies of UA
7.1. In Vitro Studies
7.2. Clinical Trials
8. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ursolic acid | UA |
mitochondrial membrane permeabilization | MMP |
cyclooxygenase 2 | COX-2 |
nuclear Factor Kappa B | NF-κB |
mechanistic target of rapamycin | mTOR |
chronic lymphocytic leukemia | CLL |
reactive oxygen species | ROS |
hydrogen peroxide | H2O2 |
non-small cell lung cancer | NSCLC |
non-Hodgkin lymphomas | NHL |
tumor necrosis factor | TNF |
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Plants Species (Family) | Vegetal Part | UA Content (mg or g) | Type of Study | Biological Effects | References |
---|---|---|---|---|---|
Eucalyptus obliqua (Myrtaceae) | leaves | nr | in vivo | Neuroprotective agent | [70,71] |
Malus pumila (Rosaceae) | fruits | nr | in vitro | Anti-tumor | [72] |
Tribulus arabicus (Zygophyllaceae) | aerial parts | 1 g | in vitro and in vivo | Anti-hyperuricemic activity | [73] |
Panax ginseng (Araliaceae) | roots | nr | in vivo | Anti-hyperlipidemic and anti-oxidant effects | [74] |
Bursera cuneata (Burseraceae) | aerial parts | 33.3 mg | in vitro and in vivo | Anti-inflammatory and anti-histaminic activity | [75] |
Sambucus australis (Adoxaceae) | aerial parts | 180 mg | in vitro | Antibacterial and anti-oxidant | [76,77] |
Fragrae fragrans (Gentianaceae) | fruits | 91 g | in vitro | Anti-proliferation | [78] |
Saurauja roxburghii (Actinidiaceae) | leaves | nr | in vitro | Cytotoxicity against glioma cells | [79] |
Ocimum sanctum (Lamiaceae) | whole plant | 11.21 mg | in vitro | Anticancer and anti-proliferation | [80] |
Disease | Experimental Subject | Dosage | Beneficial Effects | References |
---|---|---|---|---|
Diabetes | 3T3-L1 adipocytes | 1 μg/mL for 10 min | ↑ Akt, insulin receptor, and GLUT 4 ↑ Glycogen synthase kinase-3β | [84] |
Diabetes | Streptozotocin-injected male ICR mice | 0.5 g/kg for 4 weeks | ↓ TNF-α and Glucose ↑ Insulin (pancreatic, plasma) | [85] |
Diabetes | Streptozotocin-injected male mice | 200 mg/kg per day for 6 weeks | ↓ Adipocyte dysfunction ↓ Fasting blood glucose ↓ PPAR γ and aP2 ↑ Bone formation | [86] |
Metabolic syndrome | Diagnostics of metabolic syndrome patients | Orally 150 mg/kg for 12 weeks | ↓ Body weight, BMI, and waist circumference ↓ Fasting glucose | [87] |
Subarachnoid hemorrhage (SAH) | Male Sprague Dawley experimental SAH rat model | 25 and 50 mg/kg at 0.5, 24, and 47 h after SAH | ↓ MDA ↑ Neurological score ↑ Cerebral vasospasm ↓ BBB permeability (EB content) ↑ GSH/GSSH ratio, SOD activity, and Catalase activity ↓ Apoptotic index ↓ Caspase-3, -9 mRNA expression | [88] |
Parkinson’s disease | Male Swiss albino mice | 5, 25, and 50 mg/kg for 21 days | ↑ Rotarod test ↑ Hanging time ↓ Nitrite level ↓ Narrow beam walking test ↑Acidhomovanilic acid ↑ Dopamine | [89] |
Cerebral ischemia and reperfusion injury | Male Sprague Dawley rats | 5, 10, and 20 mg/kg at 0.5, 24, and 47 h after reperfusion | ↓ Neurological deficit score ↓ Infarct volume ↑ PPARγ protein level ↑ Number of intact neurons ↓MMP-2 & -9 protein levels | [90] |
IL-1β or TNF-α- induced C6 glioma invasion | Rat C6 glioma cells | 5, 10, and 20 μM for 24 h | ↓ MMP-9 activity by TNF-α or IL-1β ↓ IκB kinase activity by IL-1β or TNF-α ↓ IκBα activity by IL-1β or TNF-α ↓ NF-κB activity | [91] |
D-Galactose-induced neurodegenerative changes | Male Kunming strain mice | 10 mg/kg for 8 weeks | ↓ ROS level ↓ AGEs level ↓ Number of CD11b-stained cells, ↓ Carbonyl protein level GFAPstained cells, and RAGE- positive cells ↓ iNOS, IL-6, IL-1β, COX-2, and TNF-α protein levels | [92] |
Domoic acid-induced cognitive deficits | Male ICR mice | 100 mg/kg for 3 weeks | ↑p-Akt ↑ HO-1 ↑ p-FOXO1 ↑ Complex I-V ↑ Electron transport chain activity ↑ APR and ATP | [93] |
Adrenocorticotrophic hormone-producing pituitary adenoma | AtT20 cells (mouse corticotrophic tumor cell line) | 10, 20, and 40 μM for 24 h | ↓ ACTH release ↓ POMC mRNA expression ↓ ACTH protein level ↑ p-JNK/JNK protein level | [94] |
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Alam, M.; Ali, S.; Ahmed, S.; Elasbali, A.M.; Adnan, M.; Islam, A.; Hassan, M.I.; Yadav, D.K. Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases. Int. J. Mol. Sci. 2021, 22, 12162. https://doi.org/10.3390/ijms222212162
Alam M, Ali S, Ahmed S, Elasbali AM, Adnan M, Islam A, Hassan MI, Yadav DK. Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases. International Journal of Molecular Sciences. 2021; 22(22):12162. https://doi.org/10.3390/ijms222212162
Chicago/Turabian StyleAlam, Manzar, Sabeeha Ali, Sarfraz Ahmed, Abdelbaset Mohamed Elasbali, Mohd Adnan, Asimul Islam, Md. Imtaiyaz Hassan, and Dharmendra Kumar Yadav. 2021. "Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases" International Journal of Molecular Sciences 22, no. 22: 12162. https://doi.org/10.3390/ijms222212162