SUBSTANCE DESCRIPTION
Burdock (or Arctium Lappa) is a plant of the genus Arctium native to Europe and Northern Asia and is now widespread throughout the United States as well, where it grows as a weed. The typical habitat for this plant is: uncultivated areas, hedges, the edges of roads and the banks of streams but also ruderal environments and forest paths. In Japan and parts of Europe, it is cultivated and eaten as a vegetable. A member of the daisy family, burdock is a stout, common weed.
The prickly heads of these plants (burrs ) are noted for easily catching on to fur and clothing (being the inspiration for Velcro ) thus providing an excellent mechanism for seed dispersal Most animals avoid ingesting these plants.
The plant grows to a height of about 3 - 4 feet. It has purple flowers that bloom between the months of June and October. Burdock has wavy, heart shaped leaves that are green on the top, whitish and woollen underneath.
The deep roots, which are used medicinally, are brownish green, or nearly black on the outside. They must be collected before flowering or in Autumn. The seeds are used to prepare a decoction (liquid made by boiling down the herb in water), for the treatment of gout . The burdocks are sometimes confused with the cockleburs (genus Xanthium) and rhubarb (genus Rheum). Burdock has been used for centuries to treat a host of ailments. It has been traditionally used in Spring as a "blood purifier" to clear the bloodstream of toxins, as a diuretic (helping rid the body of excess water by increasing urine output), as a topical remedy for skin problems such as eczema, acne, and psoriasis and to improve digestion. In Traditional Chinese Medicine, burdock is often used with other herbs for sore throat and colds. Extracts of burdock root are found in a variety of herbal preparations, as well as homeopathic remedies.
Nowadays Burdock is used in medicine too. Among its properties it is worth mentioning the antiphlogistic one, the hypoglycemic , the diaphoretic , the stomachic , the fungicide, the antibacterial ones. Some active elements , the lignans like Arctigenin resulted cytotoxic against some lines of cancer cells. It is important to remember that the green, above-ground portions may cause contact dermatitis in humans due to the lactones the plant produces.
CLASSIFICATION
- Kingdom: Plantae
- Division: Magnoliophyta
- Class: Magnoliopsida
- SubClass: Asteridae
- Order: Asterales
- Family: Asteraceae
- SubFamily: Cichorioideae
- Genus: Arctium
- Species: A. Lappa
MAIN CONSTITUENTS
Burdock contains a series of active elements that make it useful in the treatment of several medical conditions, among which are the following:
•Fenolic acids like caffeic acid ;
•B complex vitamins, amminoacid, potassium e magnesium;
• inulin , tannins e resins;
•Polyunsaturated compound;
•Bitter element;
•lignans ( arctigenin ).
ANALYSIS OF THE MAIN MOLECULES
1. Caffeic acid is an organic compound that is classified as hydroxycinnamic acid . This yellow solid consists of both phenolic and acrylic functional groups . It is found in all plants because it is a key intermediate in the biosynthesis of lignin, one of the principal sources of biomass.
a. Biosynthesis caffeic acid
Caffeic acid, which is unrelated to caffeine , is biosynthesized by hydroxylation of coumaroyl ester of quinic ester. This hydroxylation produces the caffeic acid ester of shikimic acid , which converts to chlorogenic acid . It is the precursor to ferulic acid , coniferyl alcohol , and sinapyl alcohol , all of which are significant building blocks in lignin. The transformation to ferulic acid is catalyzed by the enzyme caffeic acid-O-methyltransferase.
Caffeic acid and its derivative caffeic acid phenethyl ester ( CAPE ) are produced in many kinds of plants.
b. Biotransformation caffeic acid
Caffeate O-methyltransferase is an enzyme responsible for the transformation of caffeic acid into ferulic acid.
c. Biodegradation caffeic acid
Caffeate 3,4-dioxygenase is an enzyme that uses caffeic acid and oxygen to produce 3-(2-carboxyethenyl)-cis,cis-muconate.
2. Inulin is a glucidic polymer with molecular weight inferior to amid, water soluble and completely stored in vacuole. It is obtained from polymerization of β-D-fructose .
Through the action of inulase enzyme, the resulting hydrolysis generates fructose (a sugar recommended to diabetics).
Inulin is found mainly in the tuber of Helianthus tuberosus and in chicory. From a dietary point of view it represents a soluble fiber. In medicine the urine excretion of inulin previously administered is one of the methods used to determine the speed of glomerular filtration .
3. Arctigenin is a dibenzylbutyrolactone lignan isolated from Arctium Lappa. In fact Arctigenin is a bioactive constituent from dried seeds of Arctium Lappa and it is a common medicinal herb preparation in China where it is used clinically as a therapeutic agent to treat inflammation. Some of the Arctigenin effects have a role in memory and have neuroprotective effects. Lignans are transformed into a number of estrogenic metabolites by human intestinal bacteria.
It has been reported to exhibit antiviral, antioxidant, antitumor and anti-inflammatory activities, which are mainly mediated through its inhibitory effect on factor-kappa B ( NF-κB ) nuclear transcription. But the role of arctigenin in STAT 3 (signal transducer and activator of transcription 3) signaling pathways is still unclear. Arctigenin might have an action as a suppressor of STAT 3 and this action could sensitize cancer cells to a chemotherapeutic drug cisplatin .
a. Biochemical pathway
The JAK-STAT signaling pathway may be activated by diverse ligands, including cytokines and growth factors , which mediate the immune and inflammatory response. The JAK family consists of four members, namely, JAK1, JAK2, JAK3, and TYK2. The stimulation of cells with suitable ligands, induces the receptor oligomerization and causes the local aggregation of associated JAKs, which results in their activation by phosphorylation. JAKs are activated by tyrosine transphosphorylation, which allows them to phosphorylate their major downstream targets-STATs. When tyrosine is phosphorylated by JAKs, STATs are translocated to the nucleus to regulate the transcription of target genes,such as iNOS and COX-2 .Cytokine-derived immune signaling is strictly regulated with respect to both magnitude and duration.
The SOCS (Suppressor of cytokine signaling) family proteins are negative feedback regulators of the JAK-STAT signal pathway. The SOCS family consists of eight members, CIS (cytokine-induced SH2 protein) and SOCS1-7. SOCS protein inhibits JAK-STAT signaling by directly interacting with JAK family proteins or with phosphorylated tyrosine residues in the cytokine receptors. It has been proved that Arctigenin effectively inhibits iNOS (mRNA, protein) gene expression and enzyme activity. Its anti-inflammatory effects appear in part to be due to the suppression of the ROS-dependent JAK-STAT inflammatory signaling pathway. Like as N-acetyl-L-cysteine , Arctigenin markedly inhibits the phosphorylation of STAT1 and 3, thus blocking their translocation to the nucleus as we can see in
Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway. 2011, Oct . In addition, the induction of SOCS3 is likely to be one of the mechanisms underlying the Arctigenin-mediated inhibition of JAK-STAT signaling. Arctigenin induces SOCS3 transcripts and pro-inflammatory cytokines secretion, including TNF-alpha and IL-6 in a dose-dependent manner.
For further references:
In vitro anti-inflammatory effects of arctigenin, a lignan from Arctium lappa L., through inhibition on iNOS pathway. 2009, Feb 20
BURDOCK AND DIABETES
Some Study (like:
New expectations from the well-known medicinal properties of Arctium lappa. 2012, Feb 23 or
Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice. 2011, Nov 18 )
proved that Arctigenin has a role in the Type 2 diabetes pathway, described as follows:
AMP-activated protein kinase ( AMPK ) serves as a major regulator of energy homeostasis and is activated by different glucose-lowering agents. Indeed, AMPK has been identified as an attractive target for the development of innovative molecules to treat type 2 diabetes. Arctigenin activates muscle uptake of glucose and inhibits hepatocyte gluconeogenesis and lipogenesis by reducing mitochondrial respiration and inducing AMPK activity. In fact arctigenin increases AMPK phosphorylation and stimulates glucose uptake in L6 myotubes and in isolated skeletal muscles but it inhibits the respiration of L6 myotubes or isolated mitochondria with a specific effect on respiratory complex I. Importantly, it is reported that arctigenin improves glucose and lipid metabolism in ob/ob mice. Based on this evidence, the studies suggest that arctigenin may represent a valuable lead compound for developing innovative glucose-lowering molecules. In particular, arctigenin might provide new insight and opportunities for selective modulation of subcutaneous and visceral fat mass.
BURDOCK AND SKIN
The discovery of drugs that can be used for the treatment of allergic disease is important in human health. Arctium Lappa (AL) has been used as a traditional medicine in Brazil and throughout Asia and is known to have an anti-inflammatory effect. AL has inhibitory effects on degranulation and the release of mediators as well as on inhibition of cys-leukotriene biosynthesis by basophils in peripheral blood mono-nuclear cells (PBMCs) in vitro (
In vitro and in vivo anti-allergic effects of Arctium lappa L.2008, Aug 14 ).
Therefore an estract of burdock can be used for some skin disease. For example it can be used against atopic dermatitis. Atopic dermatitis is a chronic, allergic inflammatory skin disease that is accompanied by markedly increased levels of inflammatory cells, including eosinophils , mast cells , and T cells .
A butanol extract of A.Lappa (ALBE) can show anti-allergic or anti-inflammatory effects against this disease as we can see in
Anti-allergic and anti-inflammatory effects of butanol extract from Arctium Lappa 2011, Feb 8 . In fact this compound inhibits the β-hexosaminidase release in RBL-2H3 cells (rat basophil leukemia cells) and suppresses mRNA expression and protein secretion of IL-4 and IL-5 induced by ConA-treated primary murine splenocytes. Additionally, ALBE (100 μg/mL) suppresses not only the transcriptional activation of NF-κB, but also the phosphorylation of MAPKs in ConA-treated primary splenocytes.
Moreover burdock was also studied as an agent against the signs of aging. Chronic tissue inflammation involving the generation of cytokines (e.g., interleukin-6 ) and tumor necrosis factor-alpha might contribute to the cutaneous aging process. In vivo home-in-use studies using an Arctium lappa fruit extract-containing formulation were carried out to determine procollagen and hyaluronan synthesis , hyaluronan synthase-2 gene expression, and reduction of wrinkle volume after treatment. A natural A. lappa fruit extract significantly improves the metabolism of the dermal extracellular matrix and leads to a visible wrinkle reduction in vivo.
Natural Arctium lappa fruit extract improves the clinical signs of aging skin. 2008, Dec 7
BURDOCK AND ANTI-INFLAMMATORY ACTIVITIES
Burdock (A.Lappa = AL) was studied and was analyzed to discover a possible protective role against inflammations. For example, the role of AL against ulcerative colitis was studied. The histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-alpha were also decreased in AL-treated groups ( Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model. 2012, Sept 7 ).
Some derivates from A.Lappa have also a role as anti-ulcerigenic and gastroprotective. The sesquiterpene onopordopicrin (ONP)-enriched fraction (termed the ONP fraction), obtained from A. lappa leaves was evaluated in experimental in vivo models in rodents, mimicking this disease in humans as you can see in Anti-ulcerogenic mechanisms of the sesquiterpene lactone onopordopicrin-enriched fraction from Arctium lappa L. (Asteraceae): role of somatostatin, gastrin, and endogenous sulfhydryls and nitric oxide. 2011, Dec 22 . ONP fraction (50 mg/kg, p.o.) significantly inhibited the mucosal injury induced by ethanol/HCl solution (75%), indomethacin/bethanecol (68.9%), and stress (58.3%).When the ONP fraction was investigated in pylorus ligature, it did not induce alteration in the gastric volume but did modify the pH and total acid concentration of gastric juice. ONP fraction significantly increased serum somatostatin levels (82.1±4.1 vs. control group 12.7±4 pmol/L) and decreased serum gastrin levels (62.6±6.04 vs. control group 361.5±8.2 μU/mL). Mucus production was not significantly altered by the ONP fraction.
Arctium Lappa may have a hepatoprotective role in case of damage to the liver by ethanol. It significantly improves various pathological and biochemical parameters which are worsened by ethanol plus CCl 4 -induced liver damage, such as the ethanol plus CCl 4 -induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions.
Source: Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride. 2002, Sept-Oct .
Antinflammatory effects may vary dipending on the different types and on the different parts of burdock employed. Burdock as a root vegetable or medicinal plants possesses considerably stronger antioxidant activity than common vegetables and fruits. An analysis has been effected in order to compare the various species and anti-inflammatory effects of their components ( Comparative analysis of caffeoylquinic acids and lignans in roots and seeds among various burdock (Arctium lappa) genotypes with high antioxidant activity. 2012, Apr 12 ) :
Caffeoylquinic acids and lignans in the crude extracts of both roots and seeds from different burdock genotypes were simultaneously characterized and systematically compared . A total of 14 lignans were identified in burdock seeds and 12 caffeoylquinic acids in burdock roots. High levels of caffeoylquinic acids were also detected in burdock seeds, but only trace amounts of lignans were found in burdock roots. Burdock seeds contained higher concentrations of lignans and caffeoylquinic acids than burdock roots.
BURDOCK AND CANCER
Pharmacological studies indicated that burdock roots have antiproliferative activities. To prove this, some researchers used hydroethanolic and total aqueous extract of A.Lappa roots that were supposed to have a scavenging activity by DPPH and also an antiproliferative effect in human cancer cell lines. The A. Lappa extract exhibited activity against cancer cell lines, especially for K562, MCF-7 and 786-0 cell lines ( Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts. 2011, Mar 23 .
The activity of Arctium Lappa in the cancer cells was also studied with another extract of this plant: tha arctiin. Arctiin is one of a major lignan constituent of Arctium lappa and has anti-cancer properties in animal models. It was recently reported that arctiin induces growth inhibition in human prostate cancer PC-3 cells. However, the growth inhibitory mechanism of arctiin remains unknown. Arctiin induces growth inhibition and dephosphorylates the tumor-suppressor retinoblastoma protein in human immortalized keratinocyte HaCaT cells.The growth inhibition caused by arctiin is associated with the down-regulation of cyclin D1 protein expression.
Furthermore, the arctiin-induced suppression of cyclin D1 protein expression occurs in various types of human tumor cells, including osteosarcoma, lung, colorectal, cervical and breast cancer ( MCF-7 cells ), melanoma, transformed renal cells and prostate cancer as we can see in Arctiin induces cell growth inhibition through the down-regulation of cyclin D1 expression. 2008, Mar .
Tumor cells generally proliferate rapidly and the demand for essential nutrients as well as oxygen always exceeds the supply due to the unregulated growth and the insufficient and inappropriate vascular supply. However, cancer cells show an inherent ability to tolerate extreme conditions, such as that characterized by low nutrient and oxygen supply, by modulating their energy metabolism. Thus, targeting nutrient-deprived cancer cells may be a novel strategy in anticancer drug development. Based on that, a novel screening method was established to discover anticancer agents that preferentially inhibit cancer cell viability under the nutrient-deprived condition. It seems that an extract of Arctium lappa exhibited 100% preferential cytotoxicity under the nutrient-deprived condition at a concentration of 50 microg/mL with virtually no cytotoxicity under nutrient-rich condition. Further investigation of the mechanism of action of arctigenin ( Identification of arctigenin as an antitumor agent having the ability to eliminate the tolerance of cancer cells to nutrient starvation. 2006, Feb 1 ) revealed that the compound blocked the activation of Akt induced by glucose starvation, which is a key process in the tolerance exhibited by cancer cells to glucose starvation.
Chemotherapy is the usual means of destroying tumor cells but it is often limited by the toxicity to other tissues in the body. Therefore, the identification of non-toxic chemotherapeutics from herbal medicines remains to be an attractive goal to advance cancer treatments. The identification of arctigenin (extract from A.Lappa) as tumor specific agent showed cytotoxicity to lung cancer (A549), liver cancer (HepG2) and stomach cancer (KATO III) cells, while no cytotoxicity to several normal cell lines.
Tumor specific cytotoxicity of arctigenin isolated from herbal plant Arctium Lappa .2012, Feb 16
BURDOCK AND ANTI-BACTERIC ACTIVITY
The antimicrobial activity of rough extracts from leaves of Arctium lappa and their phases was studied in vitro against Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis and Candida albicans. Arctium lappa constituents exhibited a great microbial inhibition potential against the tested endodontic pathogens.
Antimicrobial activity of Arctium lappa constituents against microorganisms commonly found in endodontic infections. 2006, Jan 12
