Studies Show that Palo Azul May Have Anti-Cancer activity

The research on palo azul’s effect against cancer is limited, but there are a few studies which show that it may have beneficial anti-carcinogenic effects due to its antioxidant activity and its flavonoid rich content. Although antioxidant rich foods and teas may have beneficial anti-carcinogenic effects…it’s important to consider that while they may help, they’re not a cure and you should follow your physician’s advice.

1. Anti-tumor

This 2018 study mentions that “(palo azul) is used for the empirical treatment of cancer, infections, diarrhea, inflammation, and pain.” The researchers found that “the main component in (palo azul) was D-pinitol (26.93%), which has been reported to exert antidiabetic, antitumor, and anti-inflammatory effects.”

Another 2018 study explains that one of D-pinitol’s signaling pathways include “anti-cancer, through inhibition of TNF-ᾳ and suppression of NF-ⱪB pathway.”

This 1998 study found that palo azul’s flavonoids “displayed moderate cytotoxic activity against KB cell lines.”

Another 2021 study similarly found that “(palo azul), showed slight cytotoxic activity against the cell lines KB (nasopharyngeal carcinoma), and P388 (murine leukemia).”

According to the National Cancer Institute, “cytotoxic agents are a substance that kills cells, including cancer cells. These agents may stop cancer cells from dividing and growing and may cause tumors to shrink in size.”

KB cell lines are human epithelial carcinoma cells.

National Cancer Institute: Leukemia is a broad term for cancers of the blood cells.

2. Antioxidant

This 2014 study explains how palo azul’s antioxidant activity neutralizes hydroxyl radicals which are carcinogenic:

“Hydroxyl radical is one of the ROS (reactive oxygen species) formed in biological systems, causing DNA strand breakage, which brings about carcinogenesis, mutagenesis and cytotoxicity.[45] The addition of (palo azul) to the reaction mixture removes hydroxyl radicals and prevents further damage. The (palo azul) observed value indicates that the bark extract is a better hydroxyl radical scavenger than the standards BHT, Trolox and mannitol with values of 74.28, 73.59, 64.12 and 69.67%, respectively. (Palo azul) is a source of antioxidant compounds, especially for scavenging the highly reactive hydroxyl radicals.”

This 2016 study similarly mentions that “ROS can be responsible for the attack to biological macromolecules such as nucleic acids, proteins, membrane lipids, and carbohydrates, causing damage in the cell, which has been implicated in cardiovascular diseases, cancer, neurodegenerative disorders, and diabetes. Scavenging of hydrogen peroxide by (palo azul) was found to be better compared to the ascorbic acid (Vitamin C).”

In this quote, the researchers explain palo azul’s beneficial biological mechanisms against ROS:

“There was a significant increase of lipid peroxide in the liver, kidney, and pancreas in diabetes mice. However, the administration of (palo azul) improved these levels in the treated groups with respect to the diabetic control group. The production of ROS including hydroxyl, superoxide anions and hydrogen peroxide, nitric oxide, DPPH, ABTS radicals, protein oxidation, and lipid peroxidation can be enhanced by treatment with (palo azul).”

Another 2014 study also mentions that “as a member of reactive species, ONOO- (nitrous oxide) has been implicated in several major chronic diseases such as diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer and atherosclerosis” and “(palo azul) was shown to have a moderate scavenging activity against ONOO-.”

This 2013 review explains why antioxidants are essential for combating carcinogenesis:

“It is well known that due to oxidative stress cancer initiation may take place and thus potent antioxidants show potential to combat progression of carcinogenesis. Potential of antioxidant as an anticancer agent depends on its competence as an oxygen radical inactivator and inhibitor [70, 72, 133]. Therefore diets rich in radical scavengers would diminish the cancer-promoting action of some radicals [134].

What is oxidative stress?

Oxidative stress is an imbalance between free radicals and antioxidants in the body. This medical review explains that “oxidative stress may lead to cellular damage which is related to various health ailments such as diabetes, cancer, CVD, neurodegenerative disorders and ageing.”

Due to palo azul’s high antioxidant capacity, this 2021 study found that palo azul “can reduce the oxidative stress caused by the imbalance between reactive oxygen species (ROS) because of its free radical scavenging activity.“

What are free radicals?

Free radicals are atoms with a single valence electron that cause damage to the body associated with diabetes, cancer, aging, atherosclerosis, Parkinson’s, Alzheimer’s and many other diseases.

2. Inhibit Lipid Peroxidation

This 2007 study found that palo azul “reduced the peroxyl formed by AAPH during the initiation of lipid peroxidation, preventing lipid peroxidation.”

This 2014 study explains that lipid peroxidation is “a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs)” and one of the byproducts of this process is malondialdehyde (MDA). The researchers mention that “MDA appears to be the most mutagenic product of lipid peroxidation” and it is “an important contributor to DNA damage and mutation.”

The following is their explanation of MDA’s biological mechanisms which contribute to cancer:

“MDA-DNA adducts may lead to mutations (point and frameshift), strand breaks, cell cycle arrest, and induction of apoptosis. This MDA-induced DNA alteration may contribute significantly to cancer and other genetic diseases.”

This study explains that MDA is a “highly reactive dialdehyde produced upon the breakdown of peroxidated PUFAs” and its toxicity stems from its ability to “facilitate protein cross-linking, and cause mutagenesis.”

This 2018 study showed that palo azul “increased the activity of anti-stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx).” Moreover, palo azul “significantly suppressed the formation of malondialdehyde (MDA) and lipid oxidation (LPO).”

The researchers mention that “ROS can induce oxidative stress, producing severe intracellular damage that can lead to cell death, and they are elevated in various pathological conditions and diseases including atherosclerosis, age-related disorders, diabetes, rheumatoid arthritis, cancer, inflammatory diseases and neurodegenerative disease.”

They found that palo azul “restored the enzymatic antioxidant system that was able to reduce ROS production, decreasing the generation of MDA” and “MDA level was significantly reversed” in the group treated with palo azul.

The researchers concluded the following: “The antioxidant defense in zebrafish exposed to glucose was overwhelmed; as a consequence of the free radical production that exceeds the scavenging capability of cells and its antioxidants mechanisms, leading to increased MDA levels. (Palo azul) restored the enzymatic antioxidant system that was able to reduce ROS production, decreasing the generation of MDA.”

3. Upregulates PPARy

This 2013 study showed that “palo azul up-regulated expression and transcriptional activity of PPARγ.” The researchers concluded that “because PPARs are known to play a major clinical role in the etiopathogenesis of metabolic diseases such as diabetes mellitus, arteriosclerosis, cardiovascular pathologies, and cancer [30], palo azul is expected to be used for a wide variety of such diseases.”

This 2011 study found that “PPAR-γ activation inhibits the proliferation of malignant cells, including those derived from liposarcoma, breast adenocarcinoma, prostate carcinoma, colorectal carcinoma, non-small-cell lung carcinoma, pancreatic carcinoma, bladder cancer, gastric carcinoma, and glial tumors of the brain.”

4. Rich in Flavonoids

Plenty of studies have shown that palo azul is incredibly rich in the flavonoid subclass of polyphenols. This study actually measured palo azul’s total polyphenolic content at 856.60 mg/g and these studies (1, 2) measured green tea’s total polyphenolic content between 122-430 mg/g, so palo azul scored around 2-7 times higher!

This 2013 review similarly mentions that “many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities.”

The authors cite studies in which “fruits and vegetables having flavonoids have been reported as cancer chemopreventive agents [72, 115].”

Moreover, this 2018 meta-analysis found that “high intake of dietary flavonols, flavones and anthocyanidins may decrease the risk of colorectal cancer.”

This 2016 review mentions that “flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties.

The researchers cite several studies which found that “various flavonoids such as tannins, stilbenes, curcuminoids, coumarins, lignans, quinones and other flavonoids have chemopreventive properties and also contribute to induce apoptosis by arresting the cell cycle, regulating carcinogen metabolism and ontogenesis expression.”

Below is their explanation for the biological mechanisms of flavonoids’ cancer-inhibiting effects:

“Antioxidant activity and scavenging free radicals, modulation of carcinogen metabolism, regulation of gene expression on oncogenes and tumour-suppressor genes in cell proliferation and differentiation, induction of cell cycle arrest and apoptosis, modulation of enzyme activities in detoxification, oxidation and reduction, anti-inflammatory properties and action on other possible targets.”

A) Regulate Gene Expression of Oncogenes and Tumor-Suppressor Genes

Not that Gene! Nobody can regulate Gene Simmons! We’re talking about genes as in the physical units of heredity which are made up of DNA.

Oncogenes are a mutated genes that contribute to the development of a cancer. According to the American Cancer Society, an oncogene is a proto-oncogene that mutates and becomes a “bad gene that can become permanently turned on or activated when it is not supposed to be. When this happens, the cell grows out of control, which can lead to cancer. An oncogene could be compared with a gas pedal that is stuck down, which causes the cell to divide out of control.”

They also explain that “tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes don’t work properly, cells can grow out of control, which can lead to cancer.”

* In other words…flavonoids showed the ability to suppress bad genes that lead to cancer because of their antioxidant and anti-inflammatory properties.

A 2005 study which supports these findings explains similar mechanisms for flavonoids’ anti-cancer properties:

“Dietary flavonoids critically influence several cellular and immune processes associated with the development and progression of cancer. It is clear that these food components possess the propensity to modulate a variety of biological events associated with cancer progression and development, such as cell proliferation, apoptosis, cell differentiation and neovascularization.”

B) Modulate Cell Proliferation and Neovascularization

The American Cancer Society explains that cell proliferation is how quickly a cancer cell copies its DNA and divides into 2 cells. If the cancer cells are dividing more rapidly, it means the cancer is faster growing or more aggressive.

Neovascularization refers to the growth of new blood vessels. Neo means new, and vascular refers to vessels. Neovascularization is associated with the growth of blood vessels that are part of abnormal tissue, such as tumors.

This essentially means that flavonoids showed the critical ability to control cell division and blood vessel growth that can lead to tumors.

5. Ursolic acid, Oleanolic & Betulinic Acid

These studies (1, 2) found that palo azul has “oleanolic acid (OA) and ursolic acid (UA)” and this 1995 study mentions that “both compounds have been noted for their antitumor-promotion effects.”

This 2018 study explains what ursolic acid is and its beneficial anti-carcinogenic effects:

“There is a growing interest in UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects. It exerts these effects in various tissues and organs: by suppressing nuclear factor-kappa B signaling in cancer cells, improving insulin signaling in adipose tissues, reducing the expression of markers of cardiac damage in the heart, decreasing inflammation and increasing the level of anti-oxidants in the brain, reducing apoptotic signaling and the level of oxidants in the liver, and reducing atrophy.”

This 2015 study explains that “NF-κB signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal, gastric and colorectal cancers.”

This 2022 study mentions that “oleanolic acid might be effective against dyslipidemia, diabetes and metabolic syndrome, through enhancing insulin response, preserving the functionality and survival of β-cells and protecting against diabetes complications, antiviral, anti-HIV, antibacterial, antifungal, anticarcinogenic, anti-inflammatory, hepatoprotective, gastroprotective, hypolipidemic and anti-atherosclerotic activities, as well as interfering in several stages of the development of different types of cancer.”

This study found that palo azul has betulinic acid, and according to this 2008 study,“betulinic acid is a natural product with a range of biological effects, for example potent antitumor activity.” The researchers mention that “this anticancer property is linked to its ability to induce apoptotic cell death in cancer cells by triggering the mitochondrial pathway of apoptosis.

They explain that betulinic acid only has cytotoxic effects against cancer cells and not healthy cells, therefore, it could be helpful in situations where chemotherapy fails:

“In contrast to the cytotoxicity of betulinic acid against a variety of cancer types, normal cells and tissue are relatively resistant to betulinic acid, pointing to a therapeutic window. Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail. Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers.”

6. Stigmasterols

These studies (1, 2) found that palo azul has stigmasterols, and this study mentions the following about stigmasterols:

“Stigmasterols have shown astonishing anticancer properties against various cancer cell lines through the different potential mechanisms of actions. Stigmasterol has been reported for its anticancer properties against a number of cancer cell lines including but not limited to lung, ovary, stomach, and estrogen-dependent human breast cancers. Stigmasterol is an important plant sterol that can inhibit the development of various cancerous cells by inhibiting the promotion and growth of apoptosis of cancer cells.”

7. Tyrosine Kinase

This 2011 study found that palo azul’s “flavonoids “inhibit tyrosine kinase” and they explain that “inhibition of these proteins results in growth inhibition and uncontrolled cell proliferation.”

Tyrosine kinase are protein kinases which “can become mutated, stuck in the “on” position, and cause unregulated growth of the cell, which is a necessary step for the development of cancer. Therefore, kinase inhibitors, such as imatinib and Osimertinib, are often effective cancer treatments.

8. Sesquiterpenes

Numerous studies have found sesquiterpenes in palo azul, and this 2013 study mentions that they have “potential for treatment of cardiovascular disease and cancer”

Palo azul also has cynaropicrin, which is a sesquiterpene, and this 2004 study found that cyranopicrin interrupts ERK activation which “may be linked to diseases such as virus-induced chronic inflammation, and invasion, migration, and metastasis of leukocyte cancer cells.”

What are reactive oxygen species (ROS)?

Reactive oxygen species are a type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell. A build up of reactive oxygen species in cells may cause damage to DNA, RNA, and proteins, and may cause cell death. Reactive oxygen species are free radicals.

This 2017 study mentions that there are “empirical studies exhibiting an association between AGEs and a variety of conditions such as decline in memory with age, cardiovascular complications, bone health, periodontitis, erectile dysfunction, peripheral artery disease, obstructive sleep apnea, cancer, elevated cellular oxidative and inflammatory state, Alzheimer’s disease, and risk for metabolic syndrome.”

Hence, this is why one of the medical reviews points out that “potent antioxidants show potential to combat progression of carcinogenesis.”

Due to palo azul’s high polyphenolic content, a 2014 study found that “(palo azul) possesses considerable antioxidant activity with reactive oxygen species (ROS) scavenging activity and demonstrated an anti-AGEs and inhibits oxidative stress.”

Conclusion

Oxidative stress, free radicals and lipid peroxidation can lead to cancer and other diseases, therefore we should consume lots of antioxidants to scavenge those free radicals and inhibit oxidative stress in order to stay healthy. This is why it’s so important to eat vegetables, fruit and drink tea everyday.