Polygonum cuspidatum, known by the common name Japanese
knotweed, is a tall, stout herbaceous perennial (Seiger, 2005) and is a
member of the Polygonaceae (Seiger, 2005). In China it is
referred to as Hu Zhanz.
Japanese knotweed is also known under the scientific names Fallopia japonica and Reynoutria japonica. The
leaves are alternately arranged and are oval with pointed tips and a
truncate base. They measure approximately 15 cm long by 7.5-10 cm
wide (Remaley, 2005). Clusters of tiny white flowers are produced
in the late summer, though reproduction is generally through rhizome
rather than seed production (Weston et al, 2005). Knotweed is native of
China, North and South Korea as well as Japan (Seiger, 2005). Outside
of its point of origin, Japanese knotweed was introduced as an
ornamental plant Remaley, 2005). It is widely distributed across
the United States and Canada and is found especially along
rivers. It has become established as an invasive species across
Eastern Europe, Great Britain and parts of the United States (Seiger,
in 1997) including Massachusetts, Connecticut, and California (USDA,
Because of its presence in China, it has been mainly used primarily in Traditional Chinese Medicine as well as in Asian cultures. The rhizome has been used as an anti-inflammatory, anti-tussitive, diuretic, emmenagogue, emollient, febrifuge, stomachic (Duke & Ayensu, 1985; Usher, 1974). Extracts of the plant have shown antitumor activity within Traditional Chinese Medicine (Duke & Ayensu, 1985).
Japanese knotweed contains compounds that are part of a group of organic chemicals called stilbenes, which are polyphenolic compounds attached by an ethylene (Vastano et al., 2000). The specific composition is dependent on the side chains. One common stilbene found in Japanese knotweed is resveratrol, which is 3,5,4'-Trihydroxystilbene. Resveratrol has two isomers: cis and trans, with the latter being the most abundant. Piceid, also known polydatin, is a glucoside form of resveratrol found in Japanese knotweed. Emodin is an anthraquinone derivative that occurs in extracts of knotweed (Vastano et al., 2000) and other plant species.
Resveratrol has been shown to have numerous effects, as assessed both in vitro and in vivo. It decreases the viscosity of the blood and act as anticoagulant to thin blood. Human blood was used for in vitro analysis, while rabbits were used for in vivo analysis. This study showed that this property of resveratrol allows it to be effective in treating cardiovascular disease by reducing thrombosis and embolisms that can block arteries and lead to myocardial and cerebral infarctions (Wang et. al, 2002). Resveratrol was successfully able to decrease platelet aggregation in patients that were resistant to aspirin. This in vitro study showed that resveratrol could be used to help treat these high risk vascular patients (Gyorgyi, 2006).
Resveratrol can also provide inflammation relief when used in therapeutically effective amounts and combined with Devil's claw, grapeskin, and syzygium (Charters et al, 2003). Research shows that extracts from P. cuspidatum inhibits inflammation in mouse ears in response to a topical application of 12-O- tetradecanoylphorbol-13-acetate (TPA) by inhibiting the development of edema and neutrophil infiltration, which is an essential part of the immune response. The extract at the doses of 2.5, 1.25, and 0.3 milligrams was found to be as effective as indomethacin, a non-steroidal anti-inflammatory drug, at reducing edema (Bralley et. al, 2008). Edema can lead to more serious complications such as congestive heart failure, so any alleviation is beneficial.
Resveratrol has been found to reduce the tumor volume, tumor weight, and lung metastasis at doses of 2.5 and 10 mg/kg in mice with highly metastatic lung carcinoma (LLC) tumors (Kimura, 2001). The inhibitory effects could not be explained by a natural killer or cytotoxic T-lymphocyte activation. Research suggests that the anti-tumor activities of resveratrol could be caused by the inhibition of DNA synthesis in LLC cells (Kimura, 2001). High doses of resveratrol have also been shown to inhibit cyclooxygenase expression in human uterine cancer cells in vitro. Cyclooxygenase is over expressed in endometrial cancer cells and makes these cells resistance to apoptosis (Sexton, 2006). Resveratrol caused apoptosis in five out of the six cell lines used by inhibiting the cyclooxygenase protein. Breast cancer metastasis was slowed down using human cell cultures with high doses of resveratrol by inhibiting lamellipodia extension (Azios, 2009). This property of resveratrol makes it a potential preventative agent of breast cancer. Low doses, however, have shown to increase metastasis and migration (Azios, 2009).
Resveratrol is a phytoestrogen and acts as an agonist to estrogen receptors in the body. Resveratrol has been shown to inhibit estradiol by binding to the estrogen receptors in vitro and activate the transcription reporter cells that are characteristic of the estrogen response (Gehm, 1997). An in vivo study conducted on rats show that there is no agonism to estrogen receptors on various target tissues, and has been shown to be an estrogen antagonist by not allowing estrogen to lower cholesterol (Turner 1999).
Many different doses of trans-resveratrol are available commercially, ranging from 20mg to 500mg. Cis-resveratrol is not commercially available because of little research on the effectiveness of the compound (Orallo, 2006). Japanese knotweed is included in several herbal preparations that contain other plants that have shown therapeutic success. One of these compositions is an herbal for alleviating menstrual discomfort, comprising therapeutically effective amounts of Japanese knotweed, chaste tree berry, Mexican wild yam, dandelion, Devil's claw, grapeskin, and syzygium (Charters et al, 2003). Another herbal composition is used for soothing muscles and joints, comprising of therapeutically effective amounts of Japanese knotweed, N-acetyl D-glucosamine, chondroitin sulfate, D-glucosamine hydrochloride, methylsulfonylmethane, grapeskin, syzygium, and Devil's claw (Charters et al, 2003). No severe adverse reactions have been identified even when taken in large doses (Udenigwe, 2008).
Other compounds found in Japanese knotweed, including polydatin (piceid) and emodin have been examined for their therapeutic value. Standard preparations of polydatin include 5, 10, and 25 mg tablets. Studies have shown that polydatin has lipid-lowering effect in hamsters (Du, et. al, 2009) and in rabbits (Xing, et. al, 2008). The results from the clinical trials suggest that polydatin has the potential to develop a hypolipemic agent to reduce lipid composition in the blood and/or to serve as a hepatoprotective drug.
Emodin has been shown to selectively inhibit casein kinase II by working as a competitive inhibitor against ATP. Casein kinase II, a ser/thr protein kinase, is an important enzyme in signal transduction pathways in cell proliferation and differentiation (Yim, 1999). Inhibiting this kinase would stop the transduction of the signal and the pathway would stop.
Polygonum cuspidatum has many different positive medicinal uses, mainly from the stilbene compound, resveratrol, and its derivatives. Severe side effects directly from the derivatives of the plant, which are unknown, make it a useful herbal remedy. The various research investigations on Japanese knotweed had a common thread of helping treat common ailments, such as decreasing cardiovascular disease and as an anticancer agent. These treatments can ultimately lead to an extended lifespan, which other research suggests (Valenzano et al, 2006).
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