Ursolic acid treatment affects growth and apoptosis in cancer cells

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.

Ursolic Acid has the following applications:

Anti-cancer

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.
Under toxic conditions, Ursolic Acid induces the production of various Nrf2 -mediated detoxifying/antioxidant enzymes.
Epigenetic effects of Ursolic Acid could potentially contribute to its beneficial effects, including the prevention of skin cancer.
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.

Anti-inflammatory

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).
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.

Anti-microbial

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.

Liver-protective

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

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

Stimulates muscle growth

Ursolic acid enhances muscle insulin/ IGF-1 signaling, leading to Akt activation, muscle growth, and reduced fat and blood glucose.
Ursolic acid increases muscle at least in part by enhancing the IGF-I and insulin receptors.
Ursolic acid indirectly mimicked the beneficial effects of short-term calorie restriction and exercise (fast-oxidative) by directing the muscle composition toward oxidative metabolism.

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

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Fisetin, also called smoke tree extract, is a flavonol, a structurally distinct chemical substance that belongs to the flavonoid group of polyphenols. It can be found in many plants, where it serves as a coloring agent. Its chemical formula was first described by Austrian chemist Josef Herzig in 1891.

Fisetin can be found in various plants such as Acacia greggii, Acacia berlandieri, in the yellow dye young fustic from Rhus Cotinus (Eurasian smoke tree), in Butea frondosa (parrot tree), Gleditschia triacanthos, Quebracho Colorado, and the genus Rhus and in Callitropsis nootkatensis (yellow cypresses). It is also reported in mangoes. It is applied in the food field. And it has become a new raw material used in the food and beverage industry.

There are 7 applications of fisetin:

1. Fisetin can be used to cure rheumatism, dysentery, astrological, hernia, abdominal distension, toothache, traumatic injuries, and skin ulcer in clinical.

2. Fisetin can be used as an anti-inflammatory and antiproliferative.

3. Fisetin can indicate rheumatoid arthritis, diarrhea, stomach pain, hernia pain, abdominal distention, pain, bruises, swelling, sores, and carbuncles.

4. Natural fisetin dispels wind and dehumidifies.

5. Applied in the food field, it is a kind of nourishing food that has many benefits to the brain.

6. Applied in the pharmaceutical field, it can be used to treat coronary heart disease and has a better effect.

7. Applied in the cosmetic field, it owns the function of whitening, dispelling spots, anti-wrinkle, and activating skin cells.

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Artemisinin has many benefits for defeating malaria and other parasites.

Anti-malaria

Artemisinin has also proven itself as a safe and effective treatment for malaria in over two million patients.

Anti-cancer

Now studies are also showing that Artemisinin is effective against a wide variety of cancers as shown in a series of successful experiments. The most effective are leukemia and colon cancer. Intermediate activities were also shown against melanoma, breast, ovarian, prostate, CNS, and renal cancer.

Artemisinin’s Method of Action

Artemisinin contains two oxygen atoms linked together in what is known as an ‘endoperoxide bridge’, which reacts with iron atoms to form free radicals. Artemisinin becomes toxic to malaria parasites when it reacts with the high iron content of the parasites, generating free radicals, and leading to damage to the parasite.

By this same mechanism, Artemisinin becomes toxic to cancer cells which sequester relatively large amounts of iron compared to normal, healthy human cells. According to the Gordon Research Institute, tests have been conducted which show that Artemisinin causes rapid and extensive damage and death in cancer cells and yet has relatively low toxicity to normal cells.

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