Research On Pharmacological Activities Of Arctium Lappa L.Root And Its Chemical Constituents

Sexual relationships are among the most important social and biological relationships in human life. Male sexual dysfunction (MSD) affects not only sexual relationships, but also overall quality of life. MSD includes erectile dysfunction (ED), ejaculation dysfunction, and hypogonadism, and represents a serious public health problem. ED is one of most prevalent male sexual complaints. ED, sometimes called "impotence", is the repeated inability to get or maintain a firm enough erection to allow sexual intercourse.It has been estimated that around1in10men will experience recurring impotence problems at some point in their lives. Although ED does not affect life expectancy, it can have a significant negative impact on an individual's well-being and quality of life. MSD is a medical problem that affects both young and old men, and despite advances in modern and orthodox medicines, its effective control by drugs or adjuvant therapies is affected by drug efficacy and safety, as well as cost. Continuing research is therefore needed to develop and investigate safe and effective new drugs for the treatment of MSD. Plants are an important source of medicines and play a key role in the health of the world's population. The use of plant materials to treat sexual disorders has a long history in most countries, and plant materials have proven effective in improving sexual desire and sexual behavior in male animals. Some of mixture or compound from plants have been used to treat with ED.Arctium lappa L is a traditional Chinese medicinal and an edible perennial plant of the family Compositae. It has also been used therapeutically in Europe, North America and Asia for hundreds of years. The plant has been cultivated as a vegetable in Japan for many years. In Traditional Chinese Medicine, Arctium lappa L. root is recommended as an aphrodisiac agent, and used for the treatment of impotence and sterility. In Hawaii, the roots of this herb are sometimes given as a wedding gift because of their aphrodisiac powers. However, these claims are largely based on subjective opinions rather than scientific observations, and the effects of Arctium lappa L. root on sexual behavior have not been scientifically validated. This study therefore evaluated the potential aphrodisiac properties of this plant extract by investigating the effects of sexual behavior and evaluation of the anabolic and reproductive activity of aqueous extract of Arctium lappa L. roots in male rats.ED often has multiple underlying causes, any agent that can relax corpus cavemosum smooth muscle strips is desirable to become the drug to treat ED. Arctium lappa L. root has been traditionally used as a "blood purifier" to clear the blood stream of toxins and anti-hypertension. For this reason.we investigated the effect of aqueous extract of Arctium lappa L.(burdock) roots on rat thoracic aorta vascular circles and the underlying mechanisms.Arctiin is a dibenzylbutyrolactone lignan compound also known as burdock glycosides. Arctiin is found in the Arctium lappa L root, leaf and seeds. Vasodilator function of arctigenin has been reported in the scientific literature. The arctigenin is an important structural element to determine the pharmacodynamics of arctiin. We investigate arctiin on the molecular level to expand its application for the treatment of ED in the future. We also studied the relaxation effect and the mechanism of the arctiin on isolated corpus cavernosum smooth muscle strips.In addition.we also investigated antidiabetic effect of Arctium lappa L.root eEthanolic extract in streptozotocin-induced diabetic rats.1. Effect of aqueous extract of Arctium lappa L.(burdock) roots on the sexual behavior of male ratsMethods:Seventy-five albino male rats were randomly divided into five groups of15rats each. Rats in group1(control) were administered10mL/kg body weight distilled water (vehicle), group2received60mg/kg body weight sildenafil citrate (Viagra), while those in groups3,4, and5were given300.600, and1,200mg/kg body weight, respectively, of aqueous extract of Arctium lappa L. roots in the same volume. Female albino rats were made receptive by hormonal treatment. Sexual behavior parameters in male rats were monitored on days3,7and15by pairing with receptive females (1:3). Male serum testosterone concentrations and potency were also determined. Results:Oral administration of Arctium lappa L. roots extract at600 and1,200mg/kg body weight significantly increased the frequencies of mount, intromission, and ejaculation frequency (p<0.05). The latencies of mount and intromission were significantly reduced and ejaculation latency was prolonged. Administration of the extract also reduced the post-ejaculatory interval. The standard drug (Viagra) was more effective than the extract. The extract significantly increased the frequencies of all components of penile reflexes as well as serum testosterone levels, compared with the distilled water controls.Conclusions:The results of this study demonstrate that aqueous extract of Arctium lappa L. roots enhances sexual behavior in male rats. The aphrodisiac effects of the plant extract may be related to the presence of flavonoids, saponins, lignans and alkaloids, acting via a multitude of central and peripheral mechanisms. These results thus support the traditional use of Arctium lappa L. root extract for treating impotence and sterility.2. Evaluation of the Anabolic and reproductive Activity of aqueous extract of Arctium lappa L. roots in male rats.Methods:twenty-four albino immature male rats and twenty-four albino adult male rats were randomly divided into four groups of6rats each. Rats in group1(control) were administered10mL/kg body weight distilled water (vehicle), while those in groups2,3, and4were given300,600, and1,200mg/kg body weight, respectively, of aqueous extract of Arctium lappa L. roots in the same volume. Before treatment the body weight of animals was recorded.After8days of treatment the body weight, testis, seminal vesicles, epididymis and prostate glands weight of immature animals were determined. After28days of treatment, the following parameters were evaluated:(ⅰ) the body and reproductive organ weight,(ⅱ) sperm count and spermatozoa morphology,(ⅲ), histoarchitecture of testis.(ⅳ) serum testosterone (ⅴ) Fructose levels in seminal vesicles (ⅵ) biochemical study on estimation of testicular cholesterol, sialic acid, proteins, malondialdehyde, nonprotein sulfhydryl (NP-SH). Results:There was a significant increase in the weight of the body and reproductive organ after8days of treatment.Administration of aqueous extract of Arctium lappa L. roots to adult male rats for28days, the histoarchitecture of testis was not significant changes as well as spermatozoa morphology were not affected.The sperm count, the levels of serum testosterone, fructose levels in seminal vesicle were markedly increased. Testicular sialic acid, proteins, nonprotein sulfhydryl (NP-SH) also were markedly increased. cholesterol levels was not significant changes.However,a decrease in the levels of malondialdehyde was observed.Conclusions:The result showed a positive effect of aqueous extract of Arctium lappa L. roots administration on the male reproductive function, since it stimulated the secretions of endocrine sensitive tissues, increased in spermatogenesis, improved anabolic activity.3. Vasodilatation induced by aqueous extract of Arctium lappa L. roots and its mechanisms.Methods:The study was performed with the model of isolate rat thoracic aorta rings in organ bath. Results:Aqueous extract of Arctium lappa L. roots did not directly relax or constrict vascular rings. Aqueous extract of Arctium lappa L. Roots (0.075-15mg/mL) caused concentration-dependent relaxation with PE (5×10-6mol/L) preconstricted aorta rings with or without endothelium; The extent of relaxation was larger in endothe lium-intact aortic rings than that in endothelium-denuded aortic rings. Relaxation effects were reduced partially but significantly by pretreatment with(ω-nirto-L-arginine methyl ester) L-NAME (10-4mol/L),(1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one)ODQ(10-5mol/L) in endothelium-intact aortic rings. However, they were not affected by indomethacin(10-5mol/L). The relaxation response of aqueous extract of Arctium lappa L. roots was significantly enhanced by potassium channel inhibitors TEA(Tetraethylammonium chloride). The aqueous extract of Arctium lappa L. Roots caused concentration-dependent relaxation in40mmol/L KCl aorta rings. Conclusion:Aqueous extract of Arctium lappa L. Roots causes relaxation of aortic rings through endothelium-dependent and independent pathways. The mechanisms might be involved the release of NO from endothelium and is possibly mediated by the activation of Ca2+channel. 4. Effects of arctiin on relaxing the corpus cavernosum and its mechanisms.4.1. Effects of arctiin on relaxing the isolated rabbit corpus cavernosumMethods:The study was performed with the model of isolate rabbit corpus cavemosal strips in organ bath. The relaxant effects of Arctiin on phenylephrine-precontracted corpus cavemosal strips, preincubated with L-NAME(10-4mol/L) and ODQ(10"5mol/L) were respectively observed by using experimental method of smooth muscle strips. Effect of arctiin on relaxation of corpus cavernosum tissue induced by the sildenafil and acety-choline(ACH) were also respectively observed. Effects of arctiin on cGMP level in corpus cavernosum were measured by ELISA ethod. Rresult:The results showed Arctiin concentration-dependently relaxes the cavernosal muscle contraction induced by PE (EC50=0.54×10-4mol/L). This relaxant effects was partially antagonized with ODQ and L-NAME. Acetylcholine-induced relaxation was enhanced by arctiin in the presence of arctiin5,10,40μmol/L. Arctiin also exerted an increasing effect on the sildenafil citrate-induced relaxation, sildenafil also enhanced relaxant effect of arctiin, but arctiin more efficiently enhanced sildenafil induced relaxation.In the presence of sodium nitroprusside, arctiin increased cGMP concent in rabbit corpus cavernosum in a dose dependent manner.Conclusion:The relaxant effects of arctiin may be mechanisms might be involved the release of NO from endothelium and mediated by increasing cGMP leavels in corpus cavemosum for enhancing the relaxing activity.4.2. Effects of arctiin on cGMP level and the mRNA expression of endothelium nitric oxide synthases(eNOS)and phosphodiesterase5(PDE5) rat corpus cavernosum.Methods:In order to further investigate the mechanisms of action of arctiin, we assessed the effects of arctiin on the mRNA expression of endothelium nitric oxide synthases (eNOS) and phosphodiesterase5(PDE5) rat corpus cavernosum. After incubation with arctiin for1or3h respectively, the levels of eNOS and PDE5mRNA were examined by reverse transcription polymerase chain reaction (RT-PCR). Effects of arctiin on cGMP level in corpus cavernosum were measured by ELISA ethod. Result:Arctiin could obviously inhibit the mRNA expression of PDE5A1and PDE5A2mRNA expressions in the rat penis and bring on a pronounced decrease in PDE5A1(P<0.01). Arctiin also increased cGMP concentrations. The results illustrated that the relaxant effect was accompanied by an increase in cGMP levels.The effects of arctiin may be mediated by increasing cGMP leavels in corpus cavemosum for enhancing the relaxing activity. Arctiin also enhanced eNOS mRNA expression in rat penis corpus cavernosum.Conclusion:The present study indicated that the relaxation of Arctiin involved the NO-cGMP signal transduction pathway.5. Antidiabetic effect of burdock (Arctium lappa L.) root ethanolic extract in streptozotocin-induced diabetic ratsMethods:Antidiabetic effect of the root ethanolic extract of burdock (Arctium lappa L.) was evaluated in diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (70mg/kg).Normal and diabetic rats were divided into different groups (six rats each group) and orally administered with ethanolic extract of burdock (BRE)(200and400mg/kg) and glibenclamide (2.5mg/kg) for14days. Blood samples were collected from overnight fasted diabetic rats at3.7and14days of treatment and analyzed for blood glucose level. On day15blood samples werecollected from diabetic rats to estimate biochemical parameters, rats were sacrificed by single stunning and tissues were excised to measure their antioxidant and glycogen status. Results:The results show that the oral administration of burdock root ethanolic extract (BRE) significantly decreased blood glucose and increased insulin level in diabetic rats compared to the control diabetic group. Meanwhile, the levels of serum total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) in the BRE treated diabetic rats were lower, and the high density lipoprotein (HDL) level was higher than those index of the control diabetic rats. Furthermore, oral administration of BRE significantly decreased serum urea and creatinine as well as malondialdehyde (MDA) levels of liver and kidney tissues, while body weight gain and tissue glycogen content were elevated in diabetic rat, all of which indicate an improvement in diabetic state. In addition,400mg/kg body weight BRE treated group had a marked improvement of the glucose tolerance in normoglycemic rats. No hypoglycemic effects of BRE were observed in normal rats.Conclusion:The results demonstrate that possessed significant antidiabetic activity in diabetic rats and the antidiabetic effect of BRE might be related to their antioxidation action.It suggest that the plant may have therapeutic value in diabetes and related complications.