Chaparral and Its Main Compound, Nordihydroguaiaretic acid (NDGA): Is it a Controversial Natural Substance?

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Larrea tridentata (Creosote Bush)

The botanical name Larrea tridentata is known by a number of different names:

  • Creosote bush or greasewood as a plant
  • Chaparral as a medicinal herb

In Mexico it is known as “gobernadora” which is Spanish for “governess,” due to its ability to secure more water by inhibiting the growth of nearby plants.

In Sonora, it is more commonly called “hediondilla”, which means “little smelly one.”

Larrea_tridentata_Anza-Borrego

Chaparral bush

The creosote bush has a resinous coating on the leaves that serves as a chemical defense against grazing by herbivores and against attack by insects. When the leaves drop on the desert ground, the resinous chemicals impregnate the soil surrounding the chaparral plant and discourage growth by other plant species.  This mechanism reduces competition for water and nutrients.

King Clone is thought to be the oldest creosote bush ring in the Mojave Desert. The ring is estimated to be 11,700 years old, making it one of the oldest living organisms on Earth. This single clonal colony plant of Larrea tridentata reaches up to 67 feet (20 m) in diameter, with an average diameter of 45 feet (14 m).

king_clone

King Clone

The creosote bush contains a number of important compounds, among others:

  • aglycones
  • halogenic alkaloids
  • saponins
  • sapogenins
  • tannins
  • sterols
  • monoterpenes
  • sesquiterpenes

There are also identified lignans in the Larrea species. They include:  1

  • nordihydroguaiaretic acid (NDGA) and its methylated derivatives
  • cyclolignans
  • furanoid lignans
  • 1 aryl tetralin lignans

Chaparral leaves also contain 3-O-methyl NDGA, another lignan.  2   3-O-methyl NDGA, like NDGA, has been shown to exert important antiviral properties by inhibition of viral replication; it also displays anti-inflammatory activity by means of potent cyclooxygenase-2 inhibition.  3

Chaparral also contains volatile oils, wax esters, sterols, and other hydrocarbons.

For a complete list of substances in Chaparral, see the following Table

The plant resin has been reported to contain a total of 19 flavonoid aglycones, some flavonoid glycosides, and a large quantity of essential oils.

The creosote plant has been used in traditional herbal medicine, but its use has been somewhat controversial.

Historically, the dry leaves, green stems, and fine twig tips of chaparral were used for various ailments. Since about 1969, these same plant components have been used as dietary supplements. Various forms have been available:

  • dried plant material for making teas (water extracts)
  • aqueous-alcoholic extracts or tinctures
  • tablets or capsules containing ground, dried plant material

There are not as many chaparral products on the market today as in the past, yet there are still manufacturers that produce the tea, capsules and tinctures.

Nordihydroguaiaretic acid (NDGA)

Nordihydriguaiaretic acid (NDGA), (nor·di·hy·dro·guai·a·ret·ic acid), also known as Masoprocol, is a lignan found in high amounts in the leaves and twigs of Larrea tridentata.  NDGA makes up to 50% of the resin covering the surface of the leaves. From 5 g to 10 g of NDGA can be extracted from 100 g of the dry leaves. Thus, the commercial source for NDGA comes from the Creosote bush. 4

NDGA comprises approximately 10 to 15 percent of the dry leaf weight, and this corresponds to 80% of all the phenolic compounds in the resin.

NDGA and other phenols of the leaf surface function as antimicrobial agents and as protection against herbivores, UV radiation and water loss. As such, they are potentially important in the preservation of the species in the desert milieu.

Cell culture and animal model studies have demonstrated that NDGA has biological properties, including the the following activities:  5

  • anticarcinogenic
  • antidiabetic
  • antiviral
  • antioxidant
  • anti-inflammatory
  • cardiovascular diseases

NDGA has been utilized in traditional healing practices for many years in a wide range of remedies, but at present, it application in clinical settings is limited due to reported toxicity in isolated cases.

However, Larrea-containing products remained on the over-the-counter, dietary-supplement market. Although consumption of low doses of such products appear to be harmless, high doses has been associated with dermatitis, nephrotoxicity, biliary toxicity, and hepatotoxicity in humans which includes fulminant liver failure, and renal cell carcinoma.

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NDGA possesses intrinsic hepatoxicity as the molecule is metabolized by the liver into O-methyl and glutathione conjugates.  This toxicity is virtually eliminated when NDGA is O-methylated.

The safety and possible toxicity from its application must still be determined in clinical studies.

Toxicity Issues with NDGA

Reports of chaparral toxicity are inconsistent.  The toxicity of creosote bush has been demonstrated through in vitro and in vivo studies. The reported toxic doses in humans and experimental animals always exceeded the traditional use of the plant.

NDGA has been utilized in traditional healing practices for many years in a wide range of remedies, but at present, it application in clinical settings is limited due to reported toxicity in isolated cases. Its use as a food antioxidant was initially approved by the Meat Inspection Division of the US War Food Administration in 1943. It was utilized commercially in the United States as a preservative for fats and butter until it was shown to induce a cystic nephropathy in the rat; thereafter, it was removed from the FDA’s list of generally regarded as safe (GRAS) agents in 1968.  6  7  8

Although a number of the known components of chaparral exhibit cytotoxic activity under various conditions, these effects are judged to be weak and require high concentrations of the substance, and thus would extrapolate to the ingestion of large amounts of chaparral in order to exhibit potential toxic activity in humans.  9  Thus, there may be adverse effects associated with consumption of excessively large amounts of chaparral. 

However, its clinical applications, safety and toxicity, are still to be determined in clinical studies.

Renal (Kidney) and Hepato (Liver) Toxicity Issues with NDGA

There have been a total of 15 reported cases of hepatotoxicity related to chaparral use.  Nine of these reported cases were temporally related to chaparral use as a single known agent and six reported cases of possible hepatotoxicity.  10 11 12

After cessation of chaparral use, five cases exhibited documented recovery.  One case exhibited abnormal liver function upon rechallenge. In one case, the patient had hepatitis C and prior drug and ethanol abuse, and required an orthotopic liver transplant.  In three cases, the patient had prior history of alcohol abuse or underlying liver disease.  13

In other cases there was evidence of liver function tests became significantly abnormal with clinically evident jaundice, yet these tests were reversed upon discontinuation of chaparral use. .

Of the 15 reported cases, 1 case reported that chaparral tea had been ingested and 11 cases were associated with ingestion of capsules or tablets containing chaparral.  For all the preparations of chaparral, the tea has the least amount of NDGA. 

These cases seem to exhibit an association between chaparral consumption and hepatotoxicity.  However, a pre-existing factors may have contributed to the results, such as:  14

  • pre-existing liver disease
  • excessive alcohol use
  • hepatitis
  • chronic acetaminophen use

Government Warnings Regarding NDGA

Three separate governments have issued warnings on the use of chaparral as an internal medicine.  These three governments are the United States, Canada and the United Kingdom.

United States

The United States Food and Drug Administration has issued warnings about the health hazards of ingesting chaparral or using it as an internal medicine, and discourages its use. 15

NDGA possesses an inherent toxicity and was withdrawn from use by the United States Food and Drug Administration in 1968 for causing cystic nephropathy in rats. High doses of the plant extract were shown to cause hepatotoxicity, dermatitis, biliary toxicity, and other ailments, in part as a result of NDGA effects. 16

The United States Food and Drug Administration (FDA) removed NDGA from its GRAS (Generally Regarded as Safe) list in 1970 because of reports that the compound can cause lesions in the lymph nodes and kidneys.

In 1992, the FDA issued a warning that use of chaparral has been associated with liver damage. The FDA suggested that people using chaparral should stop and see a physician about having liver function tests done.

At the time, FDA did not have any evidence that any liver damage was permanent. There were only a limited number of cases: two cases where the liver function returned to normal after chaparral use was stopped; and another who was gravely ill at the time of the warning.

In a press release issued in December 1992, the FDA Commissioner conveyed a public advisory against the purchase or consumption of chaparral because it was associated with acute toxic hepatitis.  The FDA advised chaparral users to stop taking chaparral immediately and to consult a physician.

Canada

In 2005, Health Canada issued a warning to consumers to avoid using the leaves of Larrea species because of the risk of damage to the liver and kidneys. 17

Canadian regulations do not allow chaparral as a non-medicinal ingredient for oral-use products.

United Kingdom

Cancer Research UK state that: “If you are interested in trying chaparral, or any other alternative therapy, talk to your doctor first. We recommend that you don’t replace your conventional cancer treatment with any type of alternative cancer therapy such as chaparral. This could seriously harm you.”  18

Low Dose Chaparral Study

A study from July 2004 published in The Journal of Alternative and Complementary Medicine, entitled, “The Safety of Low-Dose Larrea tridentata (DC) Coville (Creosote Bush or Chaparral): A Retrospective Clinical Study”, sought to determine whether internal use of low doses of Larrea tridentata tincture or topical applications of this traditional herbal medicine are safe.

The study included a review of all people prescribed Larrea for internal or for topical use over a 22-month period.

Thirteen patients were identified for whom Larrea tincture for internal use was prescribed. An additional 20 female and 3 male patients were identified for whom an extract of Larrea in Ricinus communis (castor) oil for topical use was prescribed. No patient had any history of liver disease.

Larrea was prescribed as part of the usual care of each patient. In all cases it was given as either part of a complex herbal formula individualized for each patient containing less than 10% Larrea tincture or as an extract in Ricinus oil for topical use.

Serum liver enzyme levels as well as blood urea nitrogen and creatinine levels, glucose levels, electrolytes, bilirubin levels, iron levels, ferritin levels, lipid levels, and complete blood count (CBC) were available for analysis in four patients; general clinical history and physical examination findings were relied on in all other cases.

The four patients with complete before and after blood chemistry panels and CBC had no indication of liver damage from use of Larrea. This included one patient who was taking medications with significant potential for hepatotoxicity. No patient in the study, whether using Larrea for short term or long, internally or externally, showed any sign of organ damage during the period of follow-up.

The researchers concluded that relatively small intakes of Larrea tincture, or topical application of extracts in Ricinus oil, are safe when prescribed by a clinically trained botanical prescriber. Larrea should be used with caution in persons with a history of previous, or current, liver disease. It may be preferable to avoid the use of Larrea capsules because they have been associated with potentially dangerous overdosing.  19

Guidance from The American Herbal Products Association (AHPA)

In 1994 the American Herbal Products Association (AHPA) commissioned a review. Four case studies were examined and it was concluded that:

“… since the patients were ingesting chaparral during the time each developed acute hepatitis, most likely of a hepatocellular nature, it is reasonable to conclude a relationship exists between the ingestion and the disease. However, no clinical data were found in the medical records to indicate that chaparral is inherently a hepatic toxin. Moreover, each patient had a medical history not incompatible with prior liver disease. A fair conclusion is [that] the disease in each patient was the result of an individual idiosyncratic reaction to the drug [botanical product], possibly the result of an autoimmunologic reaction, which given the quantity of chaparral ingested in this country, must be exceedingly rare.”  20

The American Herbal Products Association has also provided guidance when consuming Chaparral:

“Seek advice from a health care practitioner before use if you have had, or may have had, liver disease. Discontinue use if nausea, fever, fatigue or jaundice (e.g., dark urine, yellow discoloration of the eyes) should occur.”  21

Some companies that sale Chaparral containing products, whether capsules or tinctures, provide labeling that contains the following informational language:
”Rare reports of serious liver disease have been associated with ingestion of chaparral.  Seek advice from a health care practitioner before use and, in so doing, inform them if you have had, or may have had, liver disease, frequently use alcoholic beverages, or are using any medications.  Discontinue use and see a doctor if vomiting, fever, fatigue, abdominal pain, loss of appetite, or jaundice (e.g., dark urine, pale stools, yellow discoloration of the eyes) should occur.”  22

Medical Research and Studies of Nordihydriguaiaretic acid (NDGA)

There are a number of well researched studies on the application of NDGA in various medical conditions.  A long (yet incomplete) list of these studies are listed in the Table below:

Medical Research and Studies of Nordihydriguaiaretic acid (NDGA)

SystemConditionAbstractReference
Cardiovascular
Vascular cell adhesion molecule 1
NDGA has been shown to markedly inhibit the ability of TNF-α to activate the expression of vascular cell adhesion molecule 1 (VCAM-1) mRNA levels at concentrations that did not inhibit the activation of transcriptional factor NF-κB. These results suggest that activation of the lipoxygenase pathway and c-Fos activation may mediate, at least in part, the effect of TNF-α in regulating the expression of VCAM-1 in human microendothelial cells.1
Platelet-derived growth factor
NDGA was also found to selectively inhibit platelet-derived growth factor (PDGF)-stimulated DNA synthesis in Swiss 3T3 cells, diploid murine cells and rat and human fibroblasts.2
Cell Metabolism
Mitochondria
Nordihydroguaiaretic acid (NDGA) from plant creosote bush (Larrea divaricata L.) stimulates respiration of mung bean mitochondria with all respiratory substrates examined. Maximum respiratory stimulation occurred with externally added NADH where rates were over twice state IV rates (6), with a half maximal stimulation occurring at 72 μM. 3
Metabolism
Life extension
Pooling data from all three sites, a log-rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test.4
Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses, might prove to postpone death and various age-related outcomes reproducibly in mice. 5
Our objectives were to correct this impairment by administration of nordihydroguaiaretic acid (NDGA), a potent reducing agent, and to determine the effect on adult longevity of the mosquito. NDGA supplements were included in the axenic larval medium or adult diet of mosquitoes of different ages. The mean adult life spans of both sexes increased 42-64% over controls (P less than 0.025), and the most effective doses were 0.001% for females and 0.005% for males. This NDGA effect was dependent on the age when feeding was initiated, since only biosynthetically active larvae and young adults were responsive. Also the effect was not due to dietary restriction. These results confirm the life span-enhancement effect of NDGA using defined conditions and establish the importance of redox status in the aging process.6
Antioxidant
In this paper, it was evaluated the in vitro peroxynitrite (ONOO(-)), singlet oxygen ((1)O(2)), hydroxyl radical (OH(v)), hydrogen peroxide (H(2)O(2)), superoxide anion and hypochlorous acid (HOCl) scavenging capacity of NDGA. It was found that NDGA scavenges: (a) ONOO(-) (IC(50) = 4 +/- 0.94 microM) as efficiently as uric acid; (b) (1)O(2) (IC(50) = 151 +/- 20 microM) more efficiently than dimethyl thiourea, lipoic acid, N-acetyl-cysteine and glutathione; (c) OH(v) (IC(50) = 0.15 +/- 0.02 microM) more efficiently than dimethyl thiourea, uric acid, trolox, dimethyl sulfoxide and mannitol, (d) (IC(50) = 15 +/- 1 microM) more efficiently than N-acetyl-cysteine, glutathione, tempol and deferoxamine and (e) HOCl (IC(50) = 622 +/- 42 microM) as efficiently as lipoic acid and N-acetyl-cysteine. It is concluded that NDGA is a potent in vitro scavenger of ONOO(-), (1)O(2), OH(v), and HOCl and is able to prevent lung tyrosine nitration in vivo.7
Antioxidant pathway Nrf2/HO-1
We found that nordihydroguaiaretic acid (NDGA), a powerful antioxidant from Larrea tridentate, activates the antioxidant pathway Nrf2/heme oxygenase-1 (HO-1) in cerebellar granule neurons and protects them against H2O2 or 3-nitropropionic acid-induced neurotoxicity. The role of HO-1 in this protective effect was made evident by using an HO inhibitor, tin-mesoporphyrin. Our study identifies NDGA as a new potential therapeutic tool to activate the Nrf2/HO-1 axis for protection against oxidative stress.8
Nonalcoholic fatty liver disease
Nonalcoholic fatty liver disease, one of the most common causes of chronic liver disease, is strongly associated with metabolic syndrome. Nordihydroguaiaretic acid (NDGA) has been reported to inhibit lipoprotein lipase; however, the effect of NDGA on hepatic lipid metabolism remains unclear. The beneficial effects of NDGA on HFD-induced hepatic triglyceride accumulation are mediated through AMPK signaling pathways, suggesting a potential target for preventing NAFLD.9
Hypertriglyceridemia
Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote bush, has been shown to have profound effects on the core components of the metabolic syndrome (MetS), lowering blood glucose, free fatty acids (FFA) and triglyceride (TG) levels in several models of dyslipidemia, as well as improving body weight (obesity), insulin resistance, diabetes and hypertension, and ameliorating hepatic steatosis. In the present study, a high-fructose diet (HFrD) fed rat model of hypertriglyceridemia was employed to further delineate the underlying mechanism by which NDGA exerts its anti-hypertriglyceridemic action. These findings suggest that NDGA ameliorates hypertriglyceridemia and hepatic steatosis primarily by interfering with lipogenesis and promoting increased channeling of fatty acids towards their oxidation. 10
Immunity
Antitumoral
We previously reported that aqueous extract of Larrea divaricata Cav. had an antiproliferative activity upon tumoral lymphoid cells (BW 5147), without affecting normal immunity. 11
Gliomas (Brain cancer)
It is concluded that the inhibitors of eicosanoid biosynthesis, NDGA and (to a lesser extent) ETYA, reduce in vitro cell proliferation in two glioma lines from both the rat and human. Since neither indomethacin nor acetylsalicylic acid altered DNA synthesis in these cell lines, this implicates the lipoxygenase products of arachidonic acid metabolism as important positive modulators in glioma cell division. 12
Neuroblastoma
In the present study in neuroblastoma, NDGA inhibits IGF-I-mediated activation of the IGF-IR and disrupts activation of ERK and Akt signaling pathways induced by IGF-I. NDGA inhibits growth of neuroblastoma cells and induces apoptosis at higher doses, causing IGF-I-resistant activation of caspase-3 and a large increase in the fraction of sub-G0 cells. In addition, NDGA inhibits the growth of xenografted human neuroblastoma tumors in nude mice. These results indicate that NDGA may be useful in the treatment of neuroblastoma and may function in part via disruption of IGF-IR signaling.13
Breast cancer
NDGA inhibited IGF-1 specific growth of cultured breast cancer cells with an IC50 of approximately 30 muM. NDGA treatment (intraperitoneal injection 3 times per week) also decreased the activity of the IGF-1R and the HER2/neu receptor in MCNeuA cells implanted into mice. This inhibition of RTK activity was associated with decreased growth rates of MCNeuA cells in vivo. These studies indicate that the anti-breast cancer properties of NDGA are related to the inhibition of two important RTKs.14
Prostate cancer
Collectively, this study shows that in prostate cells, NDGA induced a [Ca2+]i increase via releasing stored Ca2+ from the endoplasmic reticulum in a manner independent of phospholipase C activity, and by causing Ca2+ influx. NDGA also caused cytotoxicity at higher concentrations.15
NDGA is a butanediol with effects on tumor cells, including inhibition of insulin growth factor receptor (IGF-1R) autophosphorylation. In vitro studies suggest that NDGA attenuates androgen-mediated prostate cancer growth without competitive androgen receptor blockade. Its effects on PSA in pts were studied. NDGA is well tolerated with the exception of transaminase elevations which occur after approximately 3 cycles in a minority of patients. Combined with preclinical data, the modest effects on PSA kinetics suggest that further study on androgen dependent tumors is justified. 16
Skin cancer
Elevated activities of myeloperoxidase, xanthine oxidase and skin edema formation in TPA-treated mice were also lowered by NDGA indicating a restrained inflammatory response. Furthermore, results of histological study demonstrated inhibitory effect of NDGA on cellular inflammatory responses. This study provides a direct evidence of antioxidative and anti-inflammatory properties of NDGA against TPA-induced cutaneous inflammation and oxidative stress corroborating its chemopreventive potential against skin cancer.17
Lung cancer
NDGA suppresses lung cancer cell growth in cell lines exposed to NDGA 18
Pancreatic cancer
NDGA has been shown to be able to induce apoptosis in several human pancreatic and cervical cancer cell lines, which is thought to be due to its activity as a lipooxygenase inhibitor19
Inflammation
The beneficial activity of this plant has been linked to the compound nordihydroguaiaretic acid (NDGA) and its various substituted derivatives. Recently, tetra-O-methyl NDGA or terameprocol (TMP) has been shown to inhibit the growth of certain tumor-derived cell lines and is now in clinical trials for the treatment of human cancer. TMP inhibited the LPS-induced production of lipid mediators and several key inflammatory cytokines and chemokines, both in vitro and in vivo, raising the possibility that TMP might be useful as a treatment for a variety of inflammatory disorders.20
Another lipoxygenase inhibitor, nordihydroguaiaretic acid, potently inhibited the formation of both 5-HETE and dihydroxy acids, with an IC50 of 2 microM. The data suggest that ETYA can inhibit the enzymatic step whereby 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid is converted to leukotriene A4 in guinea pig polymorphonuclear leukocytes.21
The results showed that NDGA ameliorated neurological dysfunction, decreased infarct volume, and inhibited endogenous IgG exudation, neutrophils infiltration, ICAM-1 mRNA and protein expression 72 h after reperfusion. Moreover, NDGA reduced the levels of LTB4 and CysLTs 3 h after reperfusion. However, NDGA did not reduce the accumulation of macrophages/microglia 72 h after reperfusion. These results suggest that NDGA decreases neutrophil infiltration in the subacute phase of focal cerebral ischemia via inhibiting 5-LOX activation.22
Indomethacin was the best inhibitor of the platelet cyclooxygenase (ID50 less than 10(-7)M) as assessed by measurement of 12-hydroxy-heptadecatrienoic acid (HHT); ETYA was the most potent inhibitor of the 12- and 15-lipoxygenases (ID50 approximately 3 X 10(-7)M) whereas NDGA was the most potent and selective inhibitor of the 5-lipoxygenase (ID50 approximately 3 X 10(-7)M).23
Lipoxygenase inhibitor
Results suggest that NDGA decreases neutrophil infiltration in the subacute phase of focal cerebral ischemia via inhibiting 5-LOX activation.24
Protozoa
Chaparral kills Entamoeba histolytica (a type of Detrimental Protozoa)25
H. pylori
The present study is the first demonstration that NDGA suppresses the SodB activity of H. pylori via repression of intracellular Fe2+ by FecA1 in vitro. Recent studies have indicated the inhibitory effect of NDGA against N-methyl-N-nitrosourea-initiated and H. pylori-promoted gastric carcinogenesis in Mongolian gerbils. This inhibitory effect of NDGA might be associated with antioxidant activity and inhibitory effects on the progression of gastritis. Therefore, it is expected that NDGA might be effective for both the eradication of H. pylori and the prevention of gastric carcinogenesis.26
Neurological
Alzheimer's beta-amyloid fibrils
We previously reported that nordihydroguaiaretic acid (NDGA) inhibited fAbeta formation from Abeta(1-40) and Abeta(1-42) dose-dependently in the range of 10-30 micromin vitro. The authors next compared the activity of NDGA to break down fAbeta(1-40) and fAbeta(1-42), with other molecules reported to inhibit fAbeta formation from Abeta and/or to degrade pre-formed fAbeta both in vivo and in vitro. At a concentration of 50 microm, the overall activity of the molecules examined in this study was in the order of: NDGA >> rifampicin = tetracycline > poly(vinylsulfonic acid, sodium salt) = 1,3-propanedisulfonic acid, disodium salt > beta-sheet breaker peptide (iAbeta5). In cell culture experiments, fAbeta disrupted by NDGA were less toxic than intact fAbeta, as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Although the mechanisms by which NDGA inhibits fAbeta formation from Abeta, as well as breaking down pre-formed fAbetain vitro, are still unclear, NDGA could be a key molecule for the development of therapeutics for Alzheimer’s disease.27
NDGA prevented neuronal injury and accumulation of ROS induced by iron, indicating a role for NDGA as an antioxidant in NDGA-mediated neuroprotection. Another lipoxygenase inhibitor (AA861) also protected against A beta and iron toxicity whereas the the 5-lipoxygenase-activating protein inhibitor L655,238 and the cyclooxygenase inhibitor indomethacin were ineffective. These findings suggest that NDGA can interupt a neurodegenerative pathway relevant to the pathophysiology of Alzheimer's disease.28
Neuroprotective
Furthermore, NDGA could prevent the inhibitory effect of IAA on aconitase activity, a marker of oxidative stress, suggesting that the protective effect of NDGA on IAA neurotoxicity was associated with the prevention of oxidative stress.29
Cerebral Aβ amyloidosis
Epidemiological studies have suggested that diets rich in phenolic compounds may have preventive effects on the development of dementia or Alzheimer's disease (AD). We investigated the effects of natural phenolic compounds, such as myricetin (Myr), rosmarinic acid (RA), ferulic acid (FA), curcumin (Cur) and nordihydroguaiaretic acid (NDGA) on the aggregation of amyloid β-protein (Aβ), using in vitro and in vivo models of cerebral Aβ amyloidosis. These data, together with an updated review of the literature, indicate that natural phenolic compounds have anti-amyloidogenic effects on Aβ in addition to well-known anti-oxidative and anti-inflammatory effects, hence suggesting their potential as therapeutic and/or preventive agents for cerebral Aβ amyloidosis, including AD and cerebral amyloid angiopathy (CAA). 30
Parkinson's disease
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons and the aggression of alpha Synuclein (αS) in the brain. Drosophila mutants and transgenes have provided a platform to understand the mechanistic insight associated with the degenerative diseases. A number of polyphenols have been reported to inhibit the αS aggregation resulting in the possible prevention of PD. The results suggest that the NDGA is potent in delaying the climbing disability of PD model flies and also supports the utility of this model in studying PD symptoms.31

 


Informational References:

Prototype Focused Monograph: Review of Liver-Related Risks for Chaparral – Dietary Supplements: A Framework for Evaluating Safety

U.S. National Library of Medicine – Chaparral

Memorial Sloan Kettering Cancer Center – Chaparral

 


Resources:

Arizona Natural Products – Pure Chaparral

Herb Pharma – Chaparral Liquid Tincture

 


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