Ursolsäure

Dosis: 500mg/Tag

Inhalt

1. Sarkopenie
2. Adipositas
3. Toxoplasmose
4. Covid-19
5. Krebs
6. Fibrosen
7. Multiple Sklerose
8. Kognitive Schwächen
9. Colitis
10. Alterung
11. Entzündungen
12. Alzheimer
13. Arteriosklerose
14. Parkinson
15. Depressionen

1.  Sarkopenie

mRNA Expression Signatures of Human Skeletal Muscle Atrophy Identify a Natural Compound that Increases Muscle Mass

Ursolsäure, eine in Äpfeln angereicherte natürliche Verbindung, reduzierte die Muskelatrophie und stimulierte die Muskelhypertrophie bei Mäusen. Dies geschah, indem es die Insulin/IGF-I-Signalübertragung im Skelettmuskel verstärkte und die atrophieassoziierte mRNA-Expression im Skelettmuskel hemmte. Wichtig, Die Wirkung von Ursolsäure auf die Muskulatur wurde von einer Verringerung der Adipositas, des Nüchternblutzuckers sowie des Plasmacholesterins und der Triglyceride begleitet. Diese Ergebnisse identifizieren eine potenzielle Therapie für Muskelatrophie und möglicherweise andere Stoffwechselerkrankungen.

Amino Acid Sensing in Skeletal Muscle

Ursolic acid is a pentacyclic triterpene acid found in several edible herbs and fruits, including apples. Tomatidine is a steroidal alkaloid derived from tomato plants and green (unripe) tomatoes. The chemical structures of ursolic acid and tomatidine are shown in Figure 2. Recent studies in mice found that dietary supplementation with either ursolic acid or tomatidine blunts ATF4 activity in aged skeletal muscle. Consistent with this reduction in ATF4 activity, ursolic acid and tomatidine significantly reduced age-related deficits in strength, skeletal muscle quality and skeletal muscle mass [49] (Figure 2).



2. Adipositas

mRNA Expression Signatures of Human Skeletal Muscle Atrophy Identify a Natural Compound that Increases Muscle Mass

Ursolsäure reduzierte das Fettgewicht durch Verringerung der Adipozytengröße (Figuren 6D – 6F). Begleitet wurde dies von einer signifikanten Reduktion des Plasma-Leptinspiegels, der eng mit dem Fettgewicht korrelierte (Abbildungen 6G und H). Obwohl Ursolsäure Leptin reduzierte, veränderte es die Nahrungsaufnahme nicht ( Abbildung S4 ). Wichtig ist, dass Ursolsäure auch die Plasmatriglyceride (Abbildung 6I) und Cholesterin (Abbildung 6J). Ursolsäure veränderte jedoch nicht das Gewicht des Herzens (Abbildung 6A), Leber oder Niere ( Abbildung S4 ), noch erhöhte es Plasmamarker für Hepatotoxizität oder Nephrotoxizität (Alanin-Aminotransferase, Bilirubin und Kreatinin) ( Abbildung S4 ). Somit hatte diätetische Ursolsäure zwei Hauptwirkungen: Skelettmuskelhypertrophie und reduzierte Adipositas.

Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.



3. Toxoplasmose

The Mechanism of Action of Ursolic Acid as a Potential Anti-Toxoplasmosis Agent, and Its Immunomodulatory Effects

These results demonstrate that ursolic acid not only causes anti-T. gondii activity/action by effectively inhibiting the survival of T. gondii and the subcellular organelles of T. gondii, but also induces specific immunomodulatory effects in T. gondii-infected immune cells. Therefore, this study indicates that ursolic acid can be effectively utilized as a potential candidate agent for developing novel anti-toxoplasmosis drugs, and has immunomodulatory activity.

4. Covid-19

Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective

In virtue of its anti-inflammatory and antioxidant effects, ursolic acid may minimize SARS-CoV-2 infection-induced complications. Also, by regulating RAS and inflammatory signaling pathways, ursolic acid might effectively reduce the development of ALI in ARDS in Covid-19. In this state, this perspective discusses how ursolic acid can mitigate hyper inflammation and oxidative stress in Covid-19.

The possible role of ursolic acid in Covid-19: A real game changer

Therefore, UA could avert SARS-CoV-2 infection from causing ALI. This opinion proposed that UA might be a potential candidate therapy against Covid-19 and can mitigate post-Covid-19 complications such as lung fibrosis. In this regards, forthcoming studies are reasonable to substantiate the therapeutic role of UA in Covid-19.



5. Krebs

Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update

In terms of cancer treatment, ursolic acid interacts with a number of molecular targets that play an essential role in many cell signaling pathways. It suppresses transformation, inhibits proliferation, and induces apoptosis of tumor cells. Although ursolic acid has many benefits, its therapeutic applications in clinical medicine are limited by its poor bioavailability and absorption. To overcome such disadvantages, researchers around the globe have designed and developed synthetic ursolic acid derivatives with enhanced therapeutic effects by structurally modifying the parent skeleton of ursolic acid.

5.1. Bronchialkrebs

Evidence of the Beneficial Effects of Ursolic Acid against Lung Cancer

In this review, we summarize recent research examining the effects of ursolic acid and its derivatives on lung cancer. Data from in vitro cell culture and in vivo animal studies show potent anticancer effects of ursolic acid and indicate the need for clinical studies.

5.2. Magenkrebs

Inhibition of Proliferation of SGC7901 and BGC823 Human Gastric Cancer Cells by Ursolic Acid Occurs Through a Caspase-Dependent Apoptotic Pathway

Ursolic acid inhibited the viability of SGC7901 and BGC823 cells but not GES-1 cells. Ursolic acid treatment significantly induced apoptosis in SGC7901 and BGC823 cells when compared with GES-1 cells (P<0.05), and significantly increased the activation of caspase-3, caspase-8, caspase-9, poly ADPribose polymerase (PARP), and the production of reactive oxygen species (ROS). Treatment of SGC7901 and BGC823 cells with ursolic acid for 72 h did not induce necroptosis.

5.3. Darmkrebs

Ursolic Acid Induces Apoptosis in Colorectal Cancer Cells Partially via Upregulation of MicroRNA-4500 and Inhibition of JAK2/STAT3 Phosphorylation

Overall, our findings provide evidence that usolic acid induces apoptosis in colorectal cancer cells partially via upregulation of miR-4500 and inhibition of STAT3 phosphorylation as a potent anti-cancer agent for colorectal cancer therapy.

5.4. Melanom

Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway

The results revealed that ursolic acid exerts significant (p<0.01) growth-inhibitory effects on SK-MEL-24 cells. The IC50 of ursolic acid against SK-MEL-24 cells was 25 μM. Our investigation of the underlying mechanism revealed that ursolic acid prompts apoptotic cell death of the SK-MEL-24 cells, which was linked with increased expression of Bax and Caspase 3 and 9, and decreased expression of Bcl-2. Ursolic acid also halted the SK-MEL-24 cells at G0/G1 phase of the cell cycle and also downregulated the expression of Cyclin B1 and Cdc25. Ursolic acid significantly (p<0.01) inhibited the migration and invasion of SK-MEL-2 cells, indicative of its anti-metastatic potential. Finally, ursolic acid inhibited the MAPK/ERK pathway by suppressing the expression of p-P38 and p-ERK.



6. Fibrosen

6.1. Nierenfibrose

The Protective Effect of Ursolic Acid on Unilateral Ureteral Obstruction in Rats by Activating the Nrf2/HO-1 Antioxidant Signaling Pathway

Subsequently, we observed that the protective effect of UA on renal interstitial fibrosis after UUO in rats was reversed. Combining all the research results, we proved that UA has a protective effect on renal interstitial fibrosis after UUO in rats, which may be achieved by activating the Nrf2/HO-1 signaling pathway.

6.2. Leberfibrose

Ursolic acid improves the bacterial community mapping of the intestinal tract in liver fibrosis mice

In conclusion, in liver fibrosis, the microbiota of different parts of the intestines have different degrees of disorder, and UA can improve this disorder. This may be a potential mechanism for UA to achieve anti-fibrosis. This study provides theoretical guidance for the UA targeting of intestinal microbiota for the treatment of liver fibrosis.



7. Multiple Sklerose

A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination

Our data demonstrate that UA has great potential as an agent for MS, especially at the chronic-progressive stage, because of its capacity in both immunomodulation and neural repair.



8. Kognitive Schwächen

Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways

We found that UA significantly improved cognitive deficits of LPS-treated mice in open field, step-through passive avoidance and Morris water maze tasks. One potential mechanism of this action was attributed to the decreased production of pro-inflammatory markers including COX-2, iNOS, TNF-α, IL-1β, IL-2 and IL-6 in LPS-treated mouse brain.



9. Colitis

Ursolic Acid Regulates Intestinal Microbiota and Inflammatory Cell Infiltration to Prevent Ulcerative Colitis

UA could significantly reduce the richness of intestinal flora to avoid the inflammatory response due to the destruction of the intestinal epithelial barrier. The function of UA against UC was through reducing intestinal flora abundance and regulating inflammatory and fatty acid metabolism signaling pathways to affect immune cell infiltration and cytokine expression.



10. Alterung

Dietary ursolic acid improves health span and life span in male Drosophila melanogaster

In this study, UA was dietarily administered to w1118 D. melanogaster which significantly elongated the health and life span of males. Spargel (srl) is the Drosophila orthologue of mammalian peroxisome proliferator-activated receptor-gamma coactivator 1 α(PGC1α), an important regulator of energy homeostasis and mitochondrial function. Our results indicate that the health-promoting effect of UA, demonstrated by a significant increase in climbing activity, occurs via an upregulation of srl expression leading to a metabolic shift in the fly without reducing fecundity or gut integrity. Moreover, UA affected the flies‘ microbiota in a manner that contributed to life span extension.



11. Entzündungen

Potent Anti-Inflammatory Activity of Ursolic Acid, a Triterpenoid Antioxidant, Is Mediated through Suppression of NF-κB, AP-1 and NF-AT

Treatment of cells with UA prior to allogenic transplantation significantly delayed induction of acute graft-versus-host disease in mice and also significantly reduced the serum levels of pro-inflammatory cytokines IL-6 and IFN-γ. UA treatment inhibited T cell activation even when added post-mitogenic stimulation demonstrating its therapeutic utility as an anti-inflammatory agent.



12. Alzheimer

A High Content Drug Screen Identifies Ursolic Acid as an Inhibitor of Amyloid β Protein Interactions with Its Receptor CD36*An external file that holds a picture, illustration, etc.

Our data indicate that cell-based high-content screening of small molecule libraries for their ability to block binding of Aβ to its receptors is a useful tool to identify novel inhibitors of receptors involved in AD pathogenesis. Our data also suggest that ursolic acid is a potential therapeutic agent for AD via its ability to block Aβ-CD36 interactions.



13. Arteriosklerose

Ursolic Acid Attenuates Atherosclerosis in ApoE−/− Mice: Role of LOX-1 Mediated by ROS/NF-κB Pathway

The evaluation in vitro suggested that UA significantly decreased endothelial LOX-1 expression induced by LPS both in mRNA and protein levels. Pre-treatment of UA also inhibited TLR4/MyD88 signaling activated by LPS. Moreover, UA reduced ROS production and suppressed the activation of NF-κB stimulated by LPS. Particularly, the evaluation in vivo further verified the conclusion obtained in vitro. In ApoE−/− mice fed with an atherogenic diet, both UA (100 mg/kg/day) and simvastatin significantly attenuated atherosclerotic plaque formation and shrunk necrotic core areas. The enhanced expression of LOX-1 in atherosclerotic aorta was also dramatically decreased by administration of UA. Taken together, these results suggested that UA, with anti-atherosclerotic activity through inhibition of LOX-1 mediated by ROS/NF-κB signaling pathways, may become a valuable vascular protective candidate for the treatment of atherosclerosis.



14. Parkinson

Antioxidant and Anti-inflammatory Mechanisms of Neuroprotection by Ursolic Acid: Addressing Brain Injury, Cerebral Ischemia, Cognition Deficit, Anxiety, and Depression

The MPTP-induced PD mouse model has been used to study the effect of UA (5 mg/kg, 25 mg/kg, and 50 mg/kg, p.o. for 21 days). The treatment at the most effective dose of 25 mg/kg was shown to improve behavioral deficits, restored altered dopamine level, and protect dopaminergic neurons in the MPTP-intoxicated mouse [105]. It also ameliorated the MPTP-induced increase of MDA and nitric oxide (NO) levels which is in line with the antioxidant profile of UA in other CNS pathologies.



15. Depressionen

Monoamine Oxidase and Dopamine β-Hydroxylase Inhibitors from the Fruits of Gardenia jasminoides

Ursolic acid exhibited significant inhibition of DBH (214 μmol/L), weak inhibition of MAO-B (780 μmol/L), and no inhibition against MAO-A. Consequently, G. jasminoides fruits are considerable for development of biofunctional food materials for the combination treatment of depression and neurodegenerative disorders.

Wirkung

Ursolsäure zeigte eine signifikante Hemmung von DBH (214 μmol/l) (wandelt Dopamin um in Noradrenalin), eine schwache Hemmung von MAO-B (780 μmol/l) und keine Hemmung von MAO-A. 

Recent studies on ursolic acid and its biological and pharmacological activity

Artikel


Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities

Ursolic Acid and Its Derivatives as Bioactive Agents

Ursolic acid in health and disease

Table 1

Examples of ursolic acid concentrations in plants and fruits.

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Abbreviations: DW: dry weight; FW: fresh weight.