Ursolic Acid (UA) is a substance that comes from a variety of plants and herbs. It is part of a class of chemicals known as pentacyclic triterpenoids. It is primarily recognized for its potential role in cell growth regulation. Continue to read to learn more about the health benefits of ursolic acid.

What is Ursolic Acid?

Ursolic Acid (UA) is a substance that comes from a variety of plants and herbs. It is part of a class of chemicals known as pentacyclic triterpenoids. It is primarily recognized for its potential role in cell growth regulation.

My Experience With Ursolic Acid

This is a supplement I like to take, but the issue is getting quality ones.  I tried the Labrada Nutrition one and I didn’t feel anything.  I then tried a higher quality one and it was very good.

Health Benefits of Ursolic Acid

1) Ursolic Acid Has Anti-inflammatory Properties

Mechanism:

Cell culture study showed that Ursolic Acid enhanced autophagy (recycling) of macrophages by increasing the production of ATG5 and ATG16L1, which led to altered macrophage function.

Ursolic Acid reduced IL-1b secretion in macrophages in response to lipopolysaccharide (LPS) [R].

Ursolic acid is a STAT3 inhibitor, which means it suppresses Th1 and Th17 immune responses.

Ursolic Acid normalized PPARa activity and inhibited the exaggerated spinal cord inflammatory response and enhanced pain sensitivity [R].

2) Ursolic Acid Prevents Memory Impairment

One of the potential mechanisms of the neuroprotective effect was by lessening the accumulation of malondialdehyde (MDA) and depletion of glutathione (GSH) in the hippocampus (memory center).

Malondialdehyde (MDA) is one of the better-known indicators of cell membrane injury [R].

UA significantly suppressed the increase of IL-1b, IL-6, and TNF levels in the hippocampus (memory center) of Amyloid beta treated mice [R].

3) Ursolic Acid May Have Anti-Cancer Properties

Ursolic Acid at high doses decreased the following cancer markers: MMP-2, Ki-67, and CD34 (adhesion factor).

UA treatment strongly blocked the cancer survival AKT – GSK3b – β-catenin pathway, resulting in cell destruction.

UA at low concentrations enhanced the anti-tumoral effects of one cancer drug by up to 2-fold. Ursolic Acid is able to induce cell destruction in human gut cancer cells by blocking the AKT pathway [R].

Under toxic conditions, Ursolic Acid induces the production of various Nrf2 -mediated detoxifying/antioxidant enzymes [R].

Epigenetic effects of Ursolic Acid could potentially contribute to its beneficial effects, including the prevention of skin cancer [R].

Ursolic Acid could inhibit proliferation and reverse the drug resistance of ovarian cancer stem cells by suppressing ABCG2 and HIF-1a under different culture conditions, such as low oxygen [R].

4) Ursolic Acid Has Antimicrobial Properties

Mycobacterial infections are controlled by the activation of macrophages through type 1 cytokine production by T cells.

IFNy and TNF-a are essential for this process because they promote macrophage activation and iNOS production.

Ursolic Acid and Oleic Acid stimulate IFNy production and also increase iNOS and TNF production through NF-kB activation in mouse resting macrophages [R].

5) Ursolic Acid Reduces Post-stroke Damage

Abrupt reoxygenation due to the rapid restoration of blood flow is frequently associated with an exacerbation of tissue injury and an intense inflammatory response that is triggered by inflammatory mediators, such as MMPs.

Studies have shown that the activity of MMPs, particularly MMP9, is markedly increased after obstruction of blood flow. Excessive activation of MMP9 is deleterious to the brain [R].

Ursolic Acid leads to decreased production of MMP-2 and u-PA [R].

PPARy activation suppressed the inflammatory response in brain ischemia, and this finding suggests that PPARy might be critical in cases where the brain is restricted to blood (ischemia).

PPARy protein levels were increased after Ursolic Acid treatment in a dose-dependent manner [R].

6) Ursolic Acid has Liver-Protective Properties

UA inhibited growth and induced cell destruction of liver cancer cells through AMPK -mediated inhibition of DNA methyltransferase 1 (through SP1).

UA inhibited the growth of liver cancer cells through induction of IGFBP1 and FOXO3a. Increasing evidence suggests an important role of IGFBP in the development and progression of several types of cancers [R].

7) Ursolic Acid Combinations Increase Insulin sensitivity

The Ursolic Acid and Rosiglitazone combination ameliorated HFD-induced glucose intolerance and insulin resistance [R].

Ursolic acid was demonstrated to be an effective insulin-mimetic agent at doses above 50 μg/ml and as an insulin-sensitizer at doses as low as 1 μg/ml [R].

Mechanism:

The treatment stimulated the IRS1, PI3-kinase, Akt, and GLUT4 translocation and increases the production of insulin receptors to improve glucose intolerance [R].

8) Ursolic Acid Stimulates Muscle Growth

Ursolic acid enhances muscle insulin/ IGF-1 signaling, leading to Akt activation, muscle growth, and reduced fat and blood glucose [R].

Ursolic acid increases muscle at least in part by enhancing the IGF-I and insulin receptors [R].

One human study which gave healthy participants 150mg ursolic acid three times a day with meals for eight weeks alongside resistance training noted that supplementation was able to increase circulating IGF-1 concentrations by 22.8% relative to placebo (also given resistance training) [R].

Ursolic acid enhanced the production of myoglobin (∼2 folds) in concert with a remodeling of muscle fibers to mainly fast IIA (∼30%) and slow-twitch (∼4%) types [R].

Ursolic acid indirectly mimicked the beneficial effects of short-term calorie restriction and exercise (fast-oxidative) by directing the muscle composition toward oxidative metabolism [R].

Ursolic acid appears to have weak activity as an aromatase inhibitor (which would increase testosterone slightly) [R].

9) Ursolic Acid Causes Weight loss by Increasing Bodily energy expenditure

Ursolic acid increased muscle Akt activity in high fat-fed mice. Muscle Akt activity is known to increase energy expenditure and reduce obesity and its complications.

A proteomic study showed that a closely related triterpenoid activated insulin/IGF-I signaling, AMPK, JAK /Stat signaling, NFkB, and retinoic acid transmission.

Another possibility is that ursolic acid increases fight or flight activity, which is known to expand brown fat [R].

One study noted a decrease in circulating leptin levels associated with ursolic acid in rat feed, which is dependent on weight loss [R].

Potential Risks/Negatives

Due to the potent endothelial cell death-inducing the activity of UA, a systemic application of UA in the treatment of heart diseases seems unfavorable. The DNA damaging activity of UA may, however, constitute a serious problem [R].

A previous study has revealed that UA has the potential of sperm motility inhibition. Specifically, it causes breaking of bridges in between cells that are soon to be sperm, and the damaged cells then collect to form symplasts in the seminiferous tubules that are associated with male infertility [R].

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