Ursolic Acid

1) Conditions Studied

Ursolic acid has been studied for a range of conditions, including but not limited to:

• Cancer
• Diabetes
• Muscle wasting (cachexia)
• Obesity
• Cardiovascular diseases
• Inflammatory conditions
• Alzheimer's disease

2) Efficacy in Treating Conditions

Research on ursolic acid indicates potential benefits in treating some conditions, although many studies are preliminary or conducted in animal models or in vitro. Clinical trials in humans are needed to confirm these findings and to establish the efficacy and safety of ursolic acid in treating these conditions.

3) Health Benefits

Ursolic acid has been associated with various health benefits, which include:

• Antioxidant activity
• Anti-inflammatory properties
• Anticancer potential
• Regulation of blood sugar levels
• Improvement in lipid metabolism
• Promotion of muscle growth and reduction in muscle atrophy
• Neuroprotective effects

4) Downsides

Despite the potential health benefits, ursolic acid may have downsides, including:

• Possible side effects, such as gastrointestinal discomfort
• Interactions with medications
• Limited bioavailability when taken orally
• Lack of comprehensive human clinical trials to fully understand safety and efficacy

5) Genetic Variations

There is limited information on the interaction between ursolic acid and specific genetic variations. Some preliminary studies suggest that genetic factors could influence the metabolism and effectiveness of ursolic acid. However, more research is needed to determine if it is particularly beneficial or harmful for individuals with specific genetic variations.

Ursolic Acid Research Summary

Ursolic acid, a natural pentacyclic triterpenoid, is found in various plants and has been a subject of research due to its numerous pharmacological properties. Below are summaries of research articles focusing on ursolic acid and its potential health benefits.

Pharmacokinetics and LC-MS Method Development

A sensitive LC-MS method was developed to measure ursolic acid levels in rat plasma, a key component in Lu-Ying extract. This method showed good linearity, precision, accuracy, and a quantification limit of 10 ng/ml. It was successfully applied to a pharmacokinetic study in rats, revealing a half-life of 4.3 hours and peak concentration of 294.8 ng/ml for ursolic acid.

Insulin Signaling and Diabetes

Ursolic acid has been identified as an inhibitor of Protein Tyrosine Phosphatase 1B (PTP1B), a negative regulator of the insulin signaling pathway. A derivative of ursolic acid was synthesized with a Ki of 283 nM, showing increased effectiveness. This derivative also stimulated glucose uptake, suggesting therapeutic benefits for diabetes and obesity management.

Angiogenesis Promotion

Studies on human umbilical vein endothelial cells indicated that ursolic acid increases levels of adhesion molecules and angiogenic growth factors, promoting angiogenesis through the PI3K-Akt signaling pathway.

Insulin Activity Enhancement

Ursolic acid demonstrated insulin-mimetic and insulin-sensitizing effects, enhancing insulin's effect on receptors and amplifying insulin signaling, suggesting potential as a therapeutic agent for diabetes.

Exercise-Induced Benefits

Irisin, a myokine produced during exercise, was found to have multiple beneficial roles in muscle growth and fat metabolism, with implications for managing metabolic diseases.

Anti-Cancer and Antiproliferative Effects

Compounds isolated from grape stems, including ursolic acid, displayed antiproliferative effects on cancer cells, indicating potential applications in cancer treatment.

Lipase Inhibition

Ursolic acid and other triterpenes from Actinidia arguta roots exhibited inhibitory activity against pancreatic lipase, suggesting potential for obesity treatment.

Obesity and Metabolic Disorders

In mice, ursolic acid was found to enhance muscle growth, increase brown fat, and improve exercise capacity, leading to better glucose tolerance and reduced obesity.

Pharmaceutical Interactions

Ursolic acid, identified in cranberry juice, was found to inhibit cytochrome P450 3A enzymes, indicating possible drug-dietary substance interactions.

Quantitative Analysis in Herbal Medicine

A reliable RP-HPLC method was developed to measure oleanolic acid and ursolic acid in Damnacanthus indicus, providing data for quality control and research.

Muscle Protein Anabolism

Ursolic acid was shown to sustain the activation of the mTORC1 signaling pathway following resistance exercise in rat skeletal muscle.

Chemical Constituents of Medicinal Plants

Research on plants like Gentiana striata and Eriobotrya japonica led to the isolation of several compounds, including ursolic acid, with various potential health benefits.

Alpha-Amylase Inhibition

Ursolic acid, among other compounds, was found to inhibit alpha-amylase, contributing to the medicinal properties of Phyllanthus amarus against diabetes.

Diabetic Nephropathy Treatment

Ursolic acid showed potential as a treatment for diabetic nephropathy by reducing early lesions and inhibiting molecular pathways associated with diabetes.

Anti-Obesity Effects

Ursolic acid prevented the increase of blood plasma triacylglycerol levels in rats, inhibiting phosphodiesterase activity and promoting fat breakdown.

Aromatase Inhibition

Ursolic acid from Ilex paraguariensis was found to inhibit aromatase, an enzyme involved in estrogen production, suggesting potential use in breast cancer treatment.

Conclusion

The body of research on ursolic acid demonstrates its diverse pharmacological effects, including its potential to manage diabetes, obesity, cancer, and other metabolic disorders. Its impact on insulin signaling, angiogenesis, muscle growth, and lipid metabolism highlights its therapeutic potential across various health areas.

References:

1. LC-MS determination and pharmacokinetic studies of ursolic acid in rat plasma after administration of the traditional chinese medicinal preparation Lu-Ying extract
2. Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake
3. [Chemical constituents from Gentiana striata]
4. Modulation of angiogenic factors by ursolic acid
5. Insulin-mimetic and insulin-sensitizing activities of a pentacyclic triterpenoid insulin receptor activator
6. Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans
7. Bioassay-guided isolation of antiproliferative compounds from grape (Vitis vinifera) stems
8. A new pancreatic lipase inhibitor isolated from the roots of Actinidia arguta
9. Mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid
10. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease
11. Inhibitory effect of chalcones and their derivatives from Glycyrrhiza inflata on protein tyrosine phosphatase 1B
12. Inhibition of breast tumor growth and angiogenesis by a medicinal herb: Ocimum gratissimum
13. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene
14. Ursolic acid and rosiglitazone combination alleviates metabolic syndrome in high fat diet fed C57BL/6J mice
15. Isolation and identification of intestinal CYP3A inhibitors from cranberry (Vaccinium macrocarpon) using human intestinal microsomes
16. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
17. alpha-Amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus
18. Ursolic acid inhibits early lesions of diabetic nephropathy
19. Anti-lipase and lipolytic activities of ursolic acid isolated from the roots of Actinidia arguta
20. Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition
21. [Determination of oleanolic acid and ursolic acid in Damnacanthus indicus from different places by RP-hPLC]
22. Ursolic acid stimulates mTORC1 signaling after resistance exercise in rat skeletal muscle
23. Ursolic acid effect on atherosclerosis: apples and apples, or apples and oranges?
24. Studies of selected plant raw materials as alternative sources of triterpenes of oleanolic and ursolic acid types
25. Inhibition of protein tyrosine phosphatase 1B by ursane-type triterpenes isolated from Symplocos paniculata
26. 11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches
27. Ursolic acid directly promotes protein accretion in myotubes but does not affect myoblast proliferation
28. Anti-glycative effects of oleanolic acid and ursolic acid in kidney of diabetic mice
29. Quantitation of ursolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry and its pharmacokinetic study
30. Ursolic acid causes DNA-damage, p53-mediated, mitochondria- and caspase-dependent human endothelial cell apoptosis, and accelerates atherosclerotic plaque formation in vivo
31. Diet and atherosclerosis in apolipoprotein E-deficient mice
32. mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass
33. Antiangiogenic potential of three triterpenic acids in human liver cancer cells
34. Aromatase inhibitors from Urtica dioica roots
35. Pentacyclic triterpenoic acids: new chemoprotective compounds. Minireview
36. [Effects of ursolic acid on c-Cbl-associated protein expression in 3T3-L1 adipocytes with insulin resistance]
37. Anti-metastatic properties of the leaves of Eriobotrya japonica
38. Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia
39. A new ursane-type nor-triterpenoid from the leaves of Eucommia ulmoides Oliv
40. Pentacyclic triterpenoids from the aerial parts of Lantana camara and their nematicidal activity
41. Pentacyclic triterpenoids from the aerial parts of Lantana camara and their nematicidal activity
42. [A new cardiac glycoside from Periploca forrestii]
43. Antioxidant and anti-inflammatory effects of Orthosiphon aristatus and its bioactive compounds
44. Anti-diabetic potential of ursolic acid stearoyl glucoside: a new triterpenic gycosidic ester from Lantana camara
45. Ursolic acid ameliorates thymic atrophy and hyperglycemia in streptozotocin-nicotinamide-induced diabetic mice
46. A potent sperm motility-inhibiting activity of bioflavonoids from an ethnomedicine of Onge, Alstonia macrophylla Wall ex A. DC, leaf extract
47. Ursolic Acid-induced elevation of serum irisin augments muscle strength during resistance training in men
48. Protein tyrosine phosphatase 1B inhibitory by dammaranes from Vietnamese Giao-Co-Lam tea
49. Quantification of eugenol, luteolin, ursolic acid, and oleanolic acid in black (Krishna Tulasi) and green (Sri Tulasi) varieties of Ocimum sanctum Linn. using high-performance thin-layer chromatography
50. The natural triterpene maslinic acid induces apoptosis in HT29 colon cancer cells by a JNK-p53-dependent mechanism
51. Inhibitory effect of ursolic acid derivatives on recombinant human aldose reductase
52. Plant-based corosolic acid: future anti-diabetic drug?
53. Re: Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia
54. Inhibitory effects of ursolic acid on hepatic polyol pathway and glucose production in streptozotocin-induced diabetic mice
55. Antiangiogenic activity of ursolic acid
56. Oleanolic acid
57. Ursolic acid protects diabetic mice against monocyte dysfunction and accelerated atherosclerosis
58. Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

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