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Hepatoprotective Effects of Arctium lappa Linne on Liver Injuries Induced by Chronic Ethanol Consumption and Potentiated by Carbon Tetrachloride
Abstract
Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were 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. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s).
... It is locally known as "Baba-Adam" and its roots have been used in Iranian traditional medicine for gout, rheumatoid arthritis and inflammatory diseases of skin [1]. The plant's root, leaves and seeds have several medicinal effects [2], including antiinflammatory [3], anti-bacterial [4], antiviral [5], anti-diabetic [6] anti-cancer activities [7] and hepatoprotective effects [8,9]. Arctium lappa has also been reported to have side-effects. ...
... In another study on the "extraction, quantification, formulation and evaluation of oral capsules from burdock fruits", the researchers aimed at using the capsule for its hepatoprotective effects. Moreover, according to other studies in which the hepatoprotective effect of A. lappa extract was determined by administrating the dose of 300 mg/kg [8,9], the same dose was decided to be used in sub-chronic toxicity test. In repeated treatment, administration of the extract at 300 mg/kg did not cause significant changes in body weight in the test group. ...
... In a study conducted in 2012, the results indicated the LD 50 of seeds was 9.3 mg extract/Kg body weight but the method and study duration was not mentioned [12]. In 2002, a study about hepatoprotective effects of A. lappa on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride showed the LD 50 of the plant higher than 2000 mg/kg, but only the liver tissue and its Res J Pharmacogn 6(2): 39-48 biochemical parameters were studied [9]; However, in the present study, both the acute and sub-chronic toxicity were evaluated along with changes in biochemical parameters and vital organs. ...
Background and objectives: Arctium lappa belonging to the Compositae (Asteraceae) family has been used as a medicinal and nutritional supplement in the world. The fruits, leaves and roots of the plant are well-known for their pharmaceutical effects. Toxicity of the fruit's extract in female rats was investigated in the present study. Methods: To assess the toxicity profile of Arctium lappa fruit extract (ALFE), it was administered to rats by gavage in acute and repeated models. The animals were divided into two groups: control and test groups. In the acute toxicity model, 1000 and 5000 mg/kg ALFE were administered to the animals. Toxic symptoms, body weight, death and abnormal behaviors were observed for 14 days. In the repeated toxicity model, ALFE (300 mg/kg) was daily administered for 4 weeks. Biochemical and histopathological changes were assessed and compared with the control group. Statistical significance was determined by one-way analyses of variance, followed by the Tukey test using GraphPad Prism 6. Results: No mortality was noticed in the acute test; therefore, the oral LD 50 value determined in the female rats was greater than 5000 mg/kg. In the repeated test, the animals received ALFE (300 mg/kg) and no mortality was observed. The hematology and serum chemistry parameters showed no statistically significant changes. The histopathological studies revealed evidences of microscopic lesions in two main organs lungs and small intestine. Conclusion: The results indicated that the oral acute toxicity of ALFE in the rats was of a low order with LD 50 being more than 5000 mg/kg. Moreover, they revealed slight tissue damage to several organs when sub-chronically administered at a dose of 300 mg/kg.
... A large number of studies have explored the de-toxifying and hepatoprotective properties of Articum Lappa. Lin SC et al. (2002) explored the hepatoprotective effects of Arctium lappa on liver damage induced by chronic ethanol consumption potentiated by carbon tetrachloride in rats. 300 mg/kg Articum lappa was given to the rats and showed significant improvement in various pathological and biochemical parameters, restored the glutathione content and improved histopathological lesions. ...
... 300 mg/kg Articum lappa was given to the rats and showed significant improvement in various pathological and biochemical parameters, restored the glutathione content and improved histopathological lesions. The authors attributed the results to antioxidative properties of this plant which decreased the oxidative stress of damaged hepatocytes [27]. Further research has shown that Arcticum lappa root extract has hepatoprotective effect on cadmium toxicity in adult Wistar rats in the liver function indicators [28]. ...
Arctium lappa commonly called Burdock has been used in Western folk medicine and traditional Chinese medicine for thousands of years with excellent results in skin diseases like eczema, psoriasis, and acne. It a biannual plant that belongs to Asteraceae family and is native to temperate and tropical regions of Asia including Iraq, Iran, India, and Nepal. This review was conducted to summarize the available scientific information obtained from literature, medical databases, laboratory studies and human clinical studies on Arctium Lappa. Its hypoglycemic property is attributed to total lignans. Two lignans extracted from this plant namely-Arctigenin and Lappaol F have anti-cancer properties. Arctigenin also has anti-hypertensive and anti-ulcer properties. The anti-oxidant property is attributed chlorogenic acid and caffeic acid. The root extracts of this plant are hepato-protective and help in collagen neo-synthesis leading to reduction in wrinkle formation in mature skin. The homoeopathic preparations of Articum Lappa have been pharmacologically proven beneficial for acne.
... [6] In addition, root extract presented hepatoprotective effects in murine models of liver injuries. [7] Arctium species have many scientifically proven biological properties related to phenolic compounds, which includes reduction of inflammation, antitumor action, antidiabetic, antimicrobial, antifungal and antioxidant. [8,9] This review presents general knowledge on A. lappa, including its main primary and secondary metabolites and associated biological activities as well as potential medicinal use. ...
... [90] Furthermore, polysaccharides obtained from extracts of A. lappa regulated lipid metabolism in animal models for type 1 and 2 diabetes. [79,80] Different other properties have also been reported as effective in the treatment of several conditions including, acne, [130] anti-aging, [44,131] antiobesity, [89] skin whitening agent, [19] anti-constipation and intestinal flora regulation, [83] neuroprotective effect, [13,82] hepatoprotective, [7,78,86] anti-tuberculosis, [61] anti-ulcer, [24,56] and cachexia induced by cancer. [132] ...
Arctium lappa L., also known as burdock, is an edible wild plant which has the ability to grow in distinct environments and is considered a weed in several parts of the world. This species has great value in the biological and medical fields with its major secondary components being phenolic compounds and terpenes, substances rich in desired biological activities as antioxidant, antimicrobial, antitumor and anti‐inflammatory. In addition, burdock leaves extracts have shown a modulatory effect on the complement system, which plays an important role in the development of inflammatory diseases, with an inhibitory effect on all complement pathways. Thus, natural products with those relevant activities are promising agents for healthcare applications. Therefore, the species A. lappa may represent an interesting asset for researching and developing new therapies for inflammatory afflictions.
... 8 Arctium lappa L. (family Asteraceae; commonly known as burdock, greater burdock, lappa, thorny burr, beggar's buttons) is a medicinal plant that is native to temperate regions of Europe and Asia, although it has been widely naturalised and is now common in disturbed regions globally. Arctium lappa roots have been used for hundreds of years as traditional medicines by multiple European, Asian and North American cultures 10 for a variety of purposes including to improve the immune system and enhance metabolism, 11 as well as for its anti-inflammatory, [12][13][14][15] anticancer, 16,17 and antibiabetic properties, 18,19 Many of these illnesses are caused by bacterial pathogens and several studies have reported that A. lappa leaf extracts inhibit the growth of Bacillus subtilus, Lactobacillus acidophilus and Pseudomonas aeruginosa. 20 However, MIC values were not determined in that study so it is not possible to compare the activity to other extracts in other studies. ...
... The non-toxicity of the A. lappa root extracts is unsurprising as this species has long been used in several traditional medicine systems to treat a wide variety of diseases. [10][11][12][13][14][15][16][17][18][19][20] However, in vitro studies using further human cell lines are required to verify their safety. Furthermore, in vivo testing is also required to confirm that the extracts and combinations retain efficacy and remain nontoxic in complex biological systems. ...
Introduction: An increase in antibiotic resistance and a corresponding decrease in antimicrobial discovery have directed researchers towards alternative therapies, including plant based medicines. However, synergistic combinations of plant extracts with conventional antibiotics may be a far more effective approach in overcoming resistance and potentiating the activity of antibiotics that are otherwise ineffective against resistant bacterial strains. Methods: The antibacterial activity of Arctium lappa L. root extracts was investigated by disc diffusion and quantified by liquid dilution and solid phase MIC assays. The extracts were also combined with a range of conventional antibiotics and tested against various microbial triggers of autoimmune diseases. The ΣFIC values obtained from these assays were used to determine the class of combinational effects. Toxicity was evaluated by Artemia nauplii mortality and HDF cytotoxicity assays. Results: Methanolic and ethyl acetate A. lappa root extracts showed good inhibitory activity against several microbial triggers of autoimmune inflammatory diseases, including P. mirabilis, P. vulgaris and A. baylyi. The aqueous extract was also a noteworthy inhibitor of A. baylyi growth. Of further interest, some combinations of the A. lappa root extracts and conventional antibiotics potentiated bacterial growth inhibition compared to the individual components alone. One synergistic and six additive interactions were noted. Notably, no antagonistic interactions were evident, indicating that all combinations
... Data are mean ± SEM, (n=3). * Significantly different from CCl4 group at p<0.05 Liver injuries induced by CCl4 are the best characterized system of xenobiotic-induced hepatotoxicity and commonly used models for the screening of anti-hepatotoxic and/ or hepatoprotective activities of drugs [36]. Since the changes associated with CCl4 induced liver damage are similar to that of acute viral hepatitis [37], CCl4 mediated hepatotoxicity was chosen as the experimental model. ...
... It has been established that CCl4 is accumulated in hepatic parenchyma cells and metabolically activated by cytochrome P450 dependent monooxygenases to form a trichloromethyl radical (CCl3). The CCl3 radical alkylates cellular proteins and other macromolecules with simultaneous attack on polyunsaturated fatty acids, in presence of oxygen, to produce lipid peroxides, leading to liver damage [36]. Thus, antioxidant or free radical generation inhibition is important in protection against CCl4 induced liver lesions. ...
Hepatoprotective activity was measured for Erythrina crista-galli extract as well as fractions. Fractions II and III have shown a remarkable protective effect against CCl4-induced hepatocyte injury. This was evidenced by their ability to significantly ameliorate CCl4-induced elevation in ALT and AST levels. This is supported by the notion that pretreatment of hepatocytes with either Erythrina crista-galli extracts or fractions significantly alleviated CCl4- induced GSH and SOD depletion and replenished CCL4 reduction of TAC. Hepatoprotective activity mechanism is attributed at least in part, to the free radical scavenging and antioxidant activity of the phenolic compounds present in the extract proved by the phytochemical screening of the fractions.
... Arctium lappa commonly known as burdock is a perennial plant (Lin et al. 2002). In Europe and Asia, it is used to treat sore throats and skin diseases such as boils, rashes, and acne (Chan et al. 2011). ...
Plants have been utilized medicinally for centuries and continue to be a source of many well-known treatments today. They are an essential component of our healthcare system as they heal variety of diseases. These plants possess therapeutic characteristics in one or more of their organs. They are not distinguishable from other plants by morphological traits other than their pharmacological effects and the presence of medicinal ingredients. Most plants synthesize a wide variety of bioactive chemical substances through metabolism. Bioactive substances are secondary plant metabolites that cause pharmacological or toxicological effects on humans and animals. Phytochemicals such as alkaloids, terpenoids, glycosides, and phenols have various pharmacological properties such as antibacterial, anticancer, antiviral, antimalarial, diuretic, and antioxidants. These plants are becoming more widely used across the world. Medicinal plants have played an important part in sustainable human health management, leading to an increase in interest in alternative medicines.
... В фармации используют корни лопуха обыкновенного в виде отваров, экстракты -в таблетированных, дражированных лекарственных формах [1,9]. Применяются внутрь в качестве желчегонного, потогонного, диуретического, противовоспалительного, противоопухолевого, иммуностимулирующего, ан-тиоксидантного, гиполипидемического, гепатопротекторного, противодиабетического, ранозаживляющего средства, стимулирующего обмен веществ и детоксикацию организма; наружно -для лечения угревой сыпи, фурункулеза, экземы [10][11][12][13][14][15][16][17][18][19][20][21][22][23]. ...
The Voronezh region has traditionally been the most significant area for crop production and agriculture. However, the development of mineral resources, the implementation of chemical fertilisers in agriculture, and the consequences of the Chernobyl accident have highlighted the necessity to ensure the food industry has access to safe and effective plant raw materials. The use of low-quality plant raw materials and products derived from them represents a significant source of exposure to various ecotoxicants, including radionuclides, which can enter the human body. Objective: to examine the accumulation of the most significant artificial and natural radionuclides in the roots of a large burdock plant, harvested in different territories of the Voronezh region, with a view to determining the extent of the anthropogenic impact. Materials and methods. Under experimental conditions, the specific activity of the main long-lived artificial radioisotopes (cesium-137, strontium-90) and naturally occurring radionuclides (thorium-232, potassium-40, radium-226) on a spectrometer (RADEK MKGB-01 radiometer) was determined in samples of the upper layers of soils and roots of large burdock. Results. All of the studied samples of large burdock roots, which had been prepared in natural and artificial phytocenoses in the Voronezh region, met the existing radiation safety requirements (first group). With an increase in the specific activity of strontium-90, cesium-137, thorium-232, potassium-40, radium-226 in the soil, there was an accompanying increase in the specific activity of these radionuclides in the roots of a large burdock. Correlation analysis of the specific activity of artificial and natural radionuclides in the soil and roots of large burdock revealed a highly significant relationship between these numerical indicators, thereby confirming the predominant transposed pollution. Conclusion. The accumulation patterns in roots of large burdock, naturally occurring and anthropogenic radionuclides are described by mathematical dependencies, with an accuracy of approximation that is as high as possible.
... To increase reproducibility and accelerate the progression of alcoholic liver fibrosis, the addition of a secondary hepatotoxin such as CCl 4 may be an optimal approach. Several studies have utilized chronic alcohol feeding along with CCl 4 to induce liver injury and fibrosis, as well as to evaluate the hepatoprotective effect of potential therapeutics in rodent models [9,[42][43][44][45][46][47][48][49][50][51][52]. However, CCl 4 , as a secondary hit or accelerating agent, does not directly correspond to human disease. ...
Although alcohol is a well-known causal factor associated with liver diseases, challenges remain in inducing liver fibrosis in experimental rodent models. These challenges include rodents’ natural aversion to high concentrations of alcohol, rapid alcohol metabolism, the need for a prolonged duration of alcohol administration, and technical difficulties. Therefore, it is crucial to establish an experimental model that can replicate the features of alcoholic liver fibrosis. The objective of this study was to develop a feasible rat model of alcoholic liver fibrosis that emulates human drinking patterns and combines low-dose chemicals within a relatively short time frame. We successfully developed an 8-week rat model of alcoholic liver fibrosis that mimics chronic and heavy drinking patterns. Rats were fed with a control liquid diet, an alcohol liquid diet, or alcohol liquid diet combined with multiple binges via oral gavage. To accelerate the progression of alcoholic liver fibrosis, we introduced low-dose carbon tetrachloride (CCl4) through intraperitoneal injection. This model allows researchers to efficiently evaluate potential therapeutics in preclinical studies of alcoholic liver fibrosis within a reasonable time frame.
... Arctium lappa L. (family Asteraceae; commonly known as burdock, greater burdock, lappa, thorny burr, beggar's buttons) is a medicinal plant that is native to temperate regions of Europe and Asia, although it has been widely naturalised and is now common globally. Arctium lappa roots have been used for hundreds of years as traditional medicines by multiple European, Asian and North American cultures 9 for a variety of purposes including to improve the immune system and to enhance metabolism, 10 as well as for its anti-inflammatory, [11][12][13][14] anti-cancer, 15,16 and anti-biabetic properties. 17,18 Many of these illnesses are caused by bacterial pathogens and several studies have reported that A. lappa leaf extracts inhibit the growth of Bacillus subtilis, Lactobacillus acidophilus and Pseudomonas aeruginosa. ...
Introduction: An increase in antibiotic resistance and a corresponding decrease in antimicrobial discovery have directed researchers towards alternative therapies, including plant based medicines. However, synergistic combinations of plant extracts with conventional antibiotics may be a far more effective approach in overcoming resistance and potentiating the activity of antibiotics that are otherwise ineffective against resistant bacterial strains. Materials and Methods: The antibacterial activity of Arctium lappa L. root extracts was investigated by disc diffusion and quantified by liquid dilution and solid phase MIC assays. The extracts were also combined with a range of conventional antibiotics and tested against various microbial triggers of autoimmune diseases. The ΣFIC values obtained from these assays were used to determine the class of combinational effects. Toxicity was evaluated by Artemia nauplii mortality and HDF cytotoxicity assays. Results: Methanolic and ethyl acetate A. lappa root extracts showed good inhibitory activity against several gastrointestinal bacterial pathogens. They were particularly good inhibitors of S. sonneii and B. cereus, with MIC values in the range 150-250μg/mL. The aqueous extract was also a noteworthy inhibitor of B. cereus growth. Of further interest, some combinations of the A. lappa root extracts and conventional antibiotics potentiated bacterial growth inhibition compared to the individual components. Four synergistic and five additive interactions were noted. Notably, no antagonistic interactions were evident, indicating that all combinations could be used without decreasing the antibacterial activity of the components. All extracts were non-toxic in the ALA and HDF assays. Conclusion: Arctium lappa root extracts have potential as inhibitors of bacterial gastrointestinal pathogens. Furthermore, extract components may also potentiate the activity of some antibiotics that are relatively ineffective alone. Isolation and identification of these compounds may be beneficial in drug design against several gastrointestinal bacterial pathogens.
... 24 Due to its composition, A. lappa has a wide range of medicinal properties, such as antiinflammatory, 164,165,170 anti-burning sensation, anti-infective, depurative, hemostatic, hair tonic, analgesic, 164 anticancer, antidiabetic, antiviral, 163 antibacterial against both Gram-positive and Gram-negative bacteria, 166 and hepato-protective effects. 167,168 The plant has been utilized in the treatment of different cancer types (breast, ovary, bladder, pancreas), malignant melanoma and lymphoma. It has been established that it relieves the pain, lessens the tumor size and enhances the survival phase. ...
"Medicinal plants have played an important role in the development of human health care and culture, serving as both medicine and food. Herbal drugs have been used for centuries for the treatment of several diseases and many of the new medicines are produced based on recent research on their traditional uses. Medicinal plants of the Middle East are regarded as a rich resource of different valuable bioactive compounds. Such compounds extracted from natural resources maintain many potential health benefits. The application of bioactive compounds is, however, rather limited in food and drug formulations because of their poor bioavailability, fast release and low solubility. Thus, encapsulation can protect the bioactive compounds from environmental stress, improve their physicochemical functionalities, reduce the potent toxicity of drugs, modify the release of encapsulated active materials, reduce dosage, enhance their health-promoting and anti-disease activities. This review discusses the importance of the pharmaceutical properties of thirty-two species of relevant medicinal plants native to the Middle East and their uses in various industrial applications. "
... Arctium lappa, commonly known as burdock, is a widely cultivated perennial herb 89 . Scientific analyses demonstrate Arctium lappa has antioxidant 90 , antiinflammatory 91 , antidiabetic 92 , antimicrobial 93 , antiviral 94 , anticancer 95 , and hepatoprotective 96 properties. ...
Wound healing is the process by which skin repairs itself. Wound healing can be divided into 4 phases: haemostasis, inflammation, proliferation, and remodelling. In humans, keratinocytes re-form a functional epidermis (re-epithelialization) as rapidly as possible, closing the wound and reestablishing tissue homeostasis. Dermal fibroblasts migrate into the wound bed and proliferate, creating granulation tissue rich in extracellular matrix proteins and supporting the growth of new blood vessels. Ultimately, this is remodelled over an extended period, returning the injured tissue to a state similar to that before injury. Dysregulation in any phase of the wound healing cascade delays healing and may result in various skin pathologies, including non-healing, hypertrophic scarring and chronic ulceration. Various plant products have been used in the treatment of wounds over the years. Recognizing the important role of traditional plants, we have undertaken an extensivesurvey of literature reporting the use of medicinal plants for wounds. We describe the activeingredients, bioactivities, clinical uses of 8 medicinal plant species. Several species including curcuma longa, honey, Terminalia chebula, Aloe vera, Centella asiatica, Arctium lappa, Commiphora myrrha, showing wound healing activities by their antiinflammatory and antioxidant mechanisms.
... Arctium lappa L. is among the most popular plants in the traditional Chinese pharmacopoeia. Extracts from Arctium lappa L. exhibit a wide range of pharmacological effects on various diseases, including hypertension, gout, arteriosclerosis and other inflammatory disorders (7,23). These effects originate from the biological activities of its components, such as caffeoylquinic acid derivatives, lignans and various flavonoids (24). ...
Arctium lappa L., also known as burdock, is a popular medicinal plant in traditional Chinese medicine due to its potential therapeutic properties. Saccharides from Arctium lappa L. root (ALR-S) have been extensively studied for their anti-inflammatory and anti-diabetes effects. Platelets play a pivotal role in thrombosis. The present study describes the effects of ALR-S on platelet activation and thrombosis using a laser injury thrombosis in vivo model. The study also measured the effects of ALR-S on platelet activation by analysing aggregation, ATP release, platelet spreading, adhesion and clot retraction in vitro. Specifically, the effects were ALR-S concentration-dependent inhibition of platelet aggregation and ATP release. Activated platelets pretreated with ALR-S showed diminished CD62P expression levels and fibrinogen binding, as measured by flow cytometry. ALR-S inhibited platelet spreading on fibrinogen and adhesion on collagen under shear. ALR-S attenuated platelet activation by decreasing oxidative stress and thrombus formation. These results demonstrated the antiplatelet effects of ALR-S, suggesting the antithrombotic and cardiovascular protective activities of ALR-S as a functional food.
... Antimutagenic and hepatotoxic protective effects were reported in a small number of cases. Studies on the main components of burdock have reported the efficacy of the lignan components arctigenin and acrtiin isolated from burdock fruit [16][17][18]. As such, although studies on the efficacy of burdock extract and its main ingredients are gradually progressing, it is Mechanism of related antiinflammatory action has not been sufficiently reported yet. ...
... uma herbácea de origem europeia, pertencente à família Asteraceae. Tem sido cultivada há muito tempo no Japão e em Taiwan, onde é consumida in natura(MORITA et al., 1993) e utilizada como bebida para hipertensão, gota, arteriosclerose, hepatite e outras desordens inflamatórias. As raízes são utilizadas, popularmente, como diurético e antipirético.(LIN et al., 2002). nutricionais: possui diversas propriedades terapêuticas, tais como: depurativa, cicatrizante, digestiva, sudorífera, antibiótica, diurética, antisséptica, antibacteriana, anti-inflamatória, antifúngica. É rica em fibras, vitamina B, C, D, potássio, fósforo, manganês, cobre, ferro e antioxidantes.(LIMA, 2006).Usos culinários: as raízes ...
Breve revisão de algumas espécies subutilizadas pela população atualmente, incluindo identificação e usos culinários das PANC - Plantas Alimentícias Não Convencionais
... Hydroalcoholic solution of Arctium lappa root extract has hypolipidemic, hepatoprotective, and antidiabetic effects on nicotinamide-streptozotocininduced type 2 diabetes (Ahangarpour et al. 2017). Lin and Lin (2002) found that hepatotoxicity induced by ethanol and potentiated by carbon tetrachloride (CCl 4 ) could be alleviated with 1 and 7 days of A. lappa treatment. In another study, Souza et al. (2014) found that A. lappa root extract protected liver function against cadmium toxicity. ...
... The phenolic content of burdock is antioxidant too [16,17]. As previous studies confirmed that Arctium lappa extract has hepatoprotective effect [18], there is no survey related to AG alone (which is one of the constituents of Arctium lappa), has the same effect, knowing that AG has an antioxidant [19], anti-inflammatory [20], and gastroprotective properties [21]. This study was aimed to investigate the hepatoprotective effect of AG on CCl 4 -induced liver toxicity in experimental rats, in terms of hepatic markers, MMP-2, oxidative stress, and histopathological changes. ...
Background
In spite of the huge advances in recent medicine, there is no effective drug that completely protects the liver from toxic materials. This study was conducted to investigate the hepatoprotective effect of arctigenin from burdock ( Arctium lappa ) against carbon tetrachloride (CCl 4 )-induced liver injury.
Results
Arctigenin pre-administration reduced hepatotoxicity markers significantly as compared to CCl 4 group. In addition, both silymarin and arctigenin declined matrix metalloproteinase-2 (MMP-2) in the serum (1177 ± 176), (978 ± 135) significantly as compared to CCl 4 group (1734 ± 294). The hepatic antioxidant parameters (total glutathione, superoxide dismutase, and glutathione reductase) were significantly decreased after CCl 4 injection, an effect that has been prevented by pre-administration of both silymarin and arctigenin. Histological examinations illustrated that arctigenin reduced CCl 4 damage, where it decreased inflammation, congestion, and ballooning.
Conclusions
Arctigenin exerted a hepatoprotective effect against CCl 4 -induced liver damage in terms of suppressing MMP-2 and oxidative stress comparative to that of silymarin.
... direct drug intense toxicity, renal toxicity, hepatotoxicity, and cardiovascular diseases. The liver plays a key function in the metabolism of cholesterol and fatty acids that are negatively affected by DF intake (Lin et al., 2002). The liver also produces endogenous compounds like bilirubin, bile salts, taurocholate, and bile pigments and produces blood clotting factors, proteins and enzymes. ...
Diclofenac is used to treat rheumatism disorders, which are associated with the damages of renal, gastric and hepatic organs. Diclofenac is a pharmaceutical drug that is known to induce toxicity on its overdosage and long-term usage. Madhuca longifolia is known to have antioxidant, anti-inflammatory and anti-ulcer activity. It is an evergreen tree that is reported to have many ethnomedicinal uses. The other properties of Madhuca longifolia include anti-diabetic, analgesic and anti-microbial activities. Our study aims to evaluate the pre-treatment activity against the diclofenac-induced toxicity by the Madhuca longifolia aqueous leaf extract in Wistar albino rats for 10 and 15 days. Rats were divided as Group-I: Normal control, Group-II: Diclofenac on the last two days, Group-III and group-IIIa: Diclofenac + Aqueous Leaf Extract of Madhuca longifolia, Group-IV and group-IVb: Diclofenac + Silymarin, Group -V and group-Va: Aqueous Madhuca longifolia leaf extract. After the sacrifice, the rats were studied for antioxidant assay, renal enzyme markers, liver enzyme markers, and histopathological analysis of the kidney, stomach, intestine, and liver. As a result, we could identify that Madhuca longifolia has reduced the toxic changes in rats caused by diclofenac.
... The LD 50 for both animals was more than 15 g/kg, and the tincture failed to influence the body or organ weight (Oproshanska, 2014). The LD 50 for aqueous crude extracts of Arctium lappa roots (boiling of 100 g in 1 L for 1 h) was estimated to be higher than 2 g/kg in rats after oral administration (Lin et al., 2002). A crude aqueous extract of Arctium lappa (boiling of 20 g for 45 min) did not affect the fertility of female mice after subcutaneous injection twice a day for 5 day at the dose of 0.05-0.2 ...
Ethnopharmacological relevance
Herbal medicine in Russia has a long history starting with handwritten herbalist manuscripts from the Middle Ages to the officinal Pharmacopoeia of the 21st century. The "herbophilious" Russian population has accumulated a lot of knowledge about the beneficial effects of local medicinal plants. Yet, for a long time, Russian traditional and officinal herbal medicine was not well known to the international audience. In our previous comprehensive review, we discussed the pharmacological effects of specific plants included in the 11th edition of the Pharmacopoeia of the USSR, which was also for a while used in Russia. The 14th edition of the Russian Federation’s State Pharmacopoeia was implemented in 2018.
Aim of the review
The aims of the present review are: (i) to trace the evolution of medicinal plant handling from handwritten herbalist manuscripts to Pharmacopoeias; (ii) to describe the modern situation with regulatory documents for herbal medicinal products and their updated classification; (iii) to summarize and discuss the pharmacology, safety, and clinical data for new plants, which are included in the new edition of the Pharmacopoeia.
Methods
New medicinal plants included in the 14th edition of the Russian Federation’s State Pharmacopoeia were selected. We carefully searched the scientific literature for data related to traditional use, pharmacological, clinical application, and safety. The information was collected from local libraries in Saint-Petersburg, the online databases E-library.ru, Scopus, Web of Science, and the search engine Google scholar.
Results
Investigating the evolution of all medicinal plants referred to in the Russian Pharmacopoeias led us to the identification of ten medicinal plants that were present in all editions of civilian Russian Pharmacopoeias starting from 1778. In the 14th edition of the modern Russian Pharmacopoeia, medicinal plants are described in 107 monographs. Altogether, 25 new monographs were included in the 14th edition, and one monograph was excluded in comparison to the 11th edition. Some of the included plants are not endemic to Russia and do not have a history of traditional use, or on the other hand, are widely used in Western medicine. For 15 plants, we described the specificity of their application in Russian traditional medicine along with the claimed dosages and indications in officinal medicine. The pharmacology, safety, and clinical data are summarized and assessed for nine plants, underlining their therapeutic potential and significance for global phytopharmacotherapy.
Conclusions
In this review, we highlight the therapeutical potential of new plants included in the modern edition of the Russian Pharmacopoeia. We hope that these plants will play an imperative role in drug development and will have a priority for future detailed research.
... In addition, results obtained by Lin et al (1996) established the antioxidant influence of Arctium lappa extract by noticing the signalsstrengths of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-OOH in relative to superoxide dismutase (SOD) concentrations. Arctium lappa crude extract have a hepatoprotective effect by suppressing the free radicals in mice, besides its hepatoprotective ability which can be associated to the reduction of oxidative stress on liver cells by an enhancing cytochrome P-450 level, glutathione (GSH) and NADPH-cytochrome reductase action and reducing malondialdehyde (MDA) level (Lin et al, 2002). ...
The present study was done to evaluate the influence of Arctiumlappa leaves extract on some hematological and antioxidant against the effect of Chorambucilin female rats. Twenty four female rats were distributed into four collections: The first group (G1) was treated with distilled water only. The second group (G2) was handled with Chlorambucil at a daily dose (0.62 mg/kg). The third group (G3) was handled with Chlorambucil at a daily dose (0.62 mg/kg) and alcoholic extract of Arctiumlappa (600 mg/kg), the fourth group (G4) was handled with only Arctiumlappa (600 mg/kg).The levels of Glutathione peroxides, Superoxide dismutase, Hb, RBCs and WBCs count in G2 revealed a significant decrease as compared with G3, G4 and G1. The Glutathione peroxides, Superoxide dismutaseHb, RBCs and WBCs count in G3 showed no significant difference when compared with G1. The animals in G4 showed a significant increase in antioxidant enzymes, Hb and RBCs count as compared with all other treated groups. Histopathological section ofrat liver in G2 showed severs inflammatory cell infiltration between hepatic cells. Histopathological section ofrat liver in G3 showed kupffer cells proliferation. While Section in the liver of rat treated in G4 showed kupffercells proliferation, histopathological section in the bone tissue of rat in G2 showed inflammatory cells infiltration. Histopathological section in the bone tissue of rat G3 showedvery mild inflammatory cells. The bone tissue of rat G4 showedno inflammatory cells reaction in the region of the joint. From this study concluded Arctium lappa leaves extract have the ability to minimize the side effect of therapeutic dose of Chorambucil on liver enzymes and blood pictures. generation and oxidative stress (Conklin, 2004). In addition to its toxic effect to ordinary cells of body lead to cause haematological toxicity, liver damage, nephrotoxicity and neurons damage (Pichon et al, 2001). The target of this study is to estimate the effect of Arctium lappa leaves extract on some hematological and antioxidant against the effect of Chorambucilin female rats. MATERIALS AND METHODS Extraction of Arctium lappa leaves The Arctium lappa leaves were cleaned and and dried in shadow at 25 0 C then leaves were ground into fine particles using an electric blender and sieved, hundred and fifty grams of powder leaves were put in 1000 ml of ethanol (70%) and the extraction process was approved out by using Soxhlet apparatus for 18-12 hrs. The extract was dried by using evaporator at 45 0 C and then the extract was transported into clean glossy flask and was put in the incubator at 40°C for one day to dry (Fahimi et al, 201). Empirical design Twenty four female rats were involved four equal
... It purifies the blood by removing dangerous toxins. The extract from different parts of A. lappa has long been considered to be good for health because it helps to enhance the body's immune system and improves metabolic functions ( Lin et al., 2002). Tannin, arctigenin, arctiin, beta-eudesmol, caffeic acid, chlorogenic acid, inulin, trachelogenin, sitosterol-beta-D-glucopyranoside, lappaol, and diarctigenin are the main active ingredients isolated from this herb. ...
... ALRE has been suggested to confer its hepatoprotective effects against CCl4 and acetaminophen via its antioxidative effect [24]. The same authors have reported the protective effect of A. lappa against ethanol/CCl4-induced liver injury and attributed the obtained effects to the antioxidant activity of A. lappa extract [51]. ALRE has also enhanced antioxidant defenses and prevented liver injury induced by Cd in rats [47]. ...
Arctium lappa L (A. lappa) is a popular medicinal plant with promising hepatoprotective activity. This study investigated the protective effect of A. lappa root extract (ALRE) on lead (Pb) hepatotoxicity, pointing to its ability to modulate oxidative stress, inflammation, and protein kinase B/Akt/glycogen synthase kinase (GSK)-3β signaling. Rats received 50 mg/kg lead acetate (Pb(Ac)2) and 200 mg/kg ALRE or vitamin C (Vit. C) for 7 days, and blood and liver samples were collected. Pb(Ac)2 provoked hepatotoxicity manifested by elevated serum transaminases and lactate dehydrogenase, and decreased total protein. Histopathological alterations, including distorted lobular hepatic architecture, microsteatotic changes, congestion, and massive necrosis were observed in Pb(II)-induced rats. ALRE ameliorated liver function and prevented all histological alterations. Pb(II) increased hepatic lipid peroxidation (LPO), nitric oxide (NO), caspase-3, and DNA fragmentation, and serum C-reactive protein, tumor necrosis factor-α, and interleukin-1β. Cellular antioxidants, and Akt and GSK-3β phosphorylation levels were decreased in the liver of Pb(II)-induced rats. ALRE ameliorated LPO, NO, caspase-3, DNA fragmentation and inflammatory mediators, and boosted antioxidant defenses in Pb(II)-induced rats. In addition, ALRE activated Akt and inhibited GSK-3β in the liver of Pb(II)-induced rats. In conclusion, ALRE inhibits liver injury in Pb(II)-intoxicated rats by attenuating oxidative injury and inflammation, and activation of Akt/GSK-3β signaling pathway.
... today as a model substance to elucidate the mechanisms of action of hepatotoxic effects and to evaluate the hepatoprotective potential of various herbal extracts/ natural compounds [5] . CCl 4 -induced hepatotoxicity model closely resembles human cirrhosis [6] and can induce free radical mediated hepatitis in humans and non-human primates [7] . At low doses, CCl 4 leads to transient effects such as loss of Ca 2+ sequestration, impairment of lipid homeostasis, release of noxious or beneficial cytokines and apoptotic events recovered by regeneration of hepatocytes. ...
... Arctium lappa, commonly known as burdock, is a widely cultivated perennial herb [41]. Arctium lappa is used in North America, Europe, and Asia to treat sore throat and skin pathologies such as boils, rashes, and acne [42,43]. ...
Cutaneous wound healing is the process by which skin repairs itself. It is generally accepted that cutaneous wound healing can be divided into 4 phases: haemostasis, inflammation, proliferation, and remodelling. In humans, keratinocytes re-form a functional epidermis (reepithelialization) as rapidly as possible, closing the wound and reestablishing tissue homeostasis. Dermal fibroblasts migrate into the wound bed and proliferate, creating “granulation tissue” rich in extracellular matrix proteins and supporting the growth of new blood vessels. Ultimately, this is remodelled over an extended period, returning the injured tissue to a state similar to that before injury. Dysregulation in any phase of the wound healing cascade delays healing and may result in various skin pathologies, including nonhealing, or chronic ulceration. Indigenous and traditional medicines make extensive use of natural products and derivatives of natural products and provide more than half of all medicines consumed today throughout the world. Recognising the important role traditional medicine continues to play, we have undertaken an extensive survey of literature reporting the use of medical plants and plant-based products for cutaneous wounds. We describe the active ingredients, bioactivities, clinical uses, formulations, methods of preparation, and clinical value of 36 medical plant species. Several species stand out, including Centella asiatica , Curcuma longa, and Paeonia suffruticosa , which are popular wound healing products used by several cultures and ethnic groups. The popularity and evidence of continued use clearly indicates that there are still lessons to be learned from traditional practices. Hidden in the myriad of natural products and derivatives from natural products are undescribed reagents, unexplored combinations, and adjunct compounds that could have a place in the contemporary therapeutic inventory.
... In Iranian folk medicine, it has been noticed that the root of this plant has blood sugar-lowering activity (Brasileiro et al. 2006). Moreover, anti-inflammatory, hepatoprotective, and free radical scavenging activities of A. lappa root have been reported by many pharmacological studies and clinical trial investigations (Lin et al. 2002, Sohn et al. 2011. Phytochemical studies showed that A. lappa root is a rich source of phenols, saponins, lignans, tannin, and flavonoids (Al-Shammaa et al. 2017). ...
Type 2 diabetes mellitus (T2DM) is the most prevalent disease and becoming a serious public health threat worldwide. In recent years, numerous effective T2DM intervention regimens have been developed, with promising results. However, these regimens are not usually economically available, and they are not well tolerated due to treatment-related toxicities. The focus nowadays is to identify new effective therapeutic agents, with relatively low cost and low toxicity, which can be used regularly to control a progression of T2DM in the prediabetic population. Accordingly, there has been growing attention in herbal remedies that can be presented into the general population with the tiniest side effects and the maximal preventive outcome. This article reviews recent publications in experimental models of T2DM not revised before, and supporting the potential use of nutraceuticals and phytochemicals through different mechanisms with promising results in the context of T2DM.
... Once nanoparticles are presented in the cytoplasm, rough grained materials will existent which can cause direct damage and cell death [77]. The hepatoprotective effect of Arctium lappa L. can be attributed to its antioxidative role thus eliminating the deleterious effects of toxic metabolites and inducing liver cell regeneration [78]. Moreover, the histological changes in myocardiocytes are in the same line with those reported by EI-Morshedi et al. [79] who observed vacuolar degeneration, necrosis of myocardial cells and separation of the cardiac muscle bundles in the ZnO-NPs treated rats. ...
... Arctium lappa L. (popularly known as burdock) is widely used in popular medicine worldwide as a diuretic and antipyretic agent and has also been used to treat hypertension, gout, hepatitis, and other inflammatory disorders [17,18]. Interest in A. lappa extracts has grown due to their ample therapeutic potential [19][20][21]. A. lappa extracts contain several compounds, including flavonoids, lignans, tannins, phenolic acids, alkaloids, and terpenoids [20]. Interestingly, lignans from A. lappa exhibit antiproliferative and apoptotic effects over leukemic cells [22], and also have anti-tumoral effects on pancreatic cancer cell lines [23]. ...
Background: Arctium lappa has been used as popular medicinal herb and health supplement in Chinese societies. Bioactive components from A. lappa have attracted the attention of researchers due to their promising therapeutic effects. In this study, we investigated the effects of A. lappa hydroalcoholic extract (Alhe) during different models of inflammation, in vivo. Methods: The anti-inflammatory activity was evaluated through the air pouch model. For this, mice received an inflammatory stimulus with lipopolysaccharide (LPS) and were later injected with Alhe. To assess anti-tumoral activity, the animals were inoculated with B16F10 cells and injected with Alhe every 5 days, along the course of 30 days. Controls were submitted to the same conditions and injected with the vehicle. Peritoneal or air pouch fluids were collected to evaluate leukocyte counting or cellular activation via quantification of cytokines and nitric oxide. Results: Alhe injection reduced the neutrophil influx and production of inflammatory mediators in inflammatory foci after LPS or tumor challenges. Furthermore, Alhe injection reduced tumor growth and enhanced mice survival. Conclusions: Collectively, these data suggest that Alhe regulates immune cell migration and activation, which correlates with favorable outcome in mouse models of acute inflammation and melanoma progression.
... These results might be attributed to capability of Arctium lappa in the management the abnormality in DNA by the antioxidant possessions, this results agreed with results recorded by [18], when mentioned that the effect of Arctium lappa L extract as antioxidant was recognized by observing the signs power of superoxide dismutase (SOD) in relative to 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO)-OOH. Furthermore, the extract performance by enhancing glutathiones (GSH), and by dropping malondialdehyde (MDA), for this reasons the Arctium lappa L had raised abilities in free radicals scavenge [19]. The Pentoxifylline and gentamicin treated group showed inhibition in DNA abnormality in comparison with animals given gentamicin, this effect of Pentoxifylline may be regarded to it act as anti-inflammatory effect with phosphodiesterase suppressor that improves the intracellular cAMP, reduces free radicals anion and depress TNF-α, which is in charge for DNA breakdown, furthermore, the Pentoxifylline is saves the tissues from lipid peroxidation by free radicals which is responsible for reducing the H2O2, this action is regarded to the declining of the progress of endoperoxides as a result from the high cAMP intensities that prevent the cyclooxygenase by the arachidonic acid pathway, this result similar with results that recorded by [20], the a cut DNA damages in positive control group may be regarded to gentamicin was recognized to enhance the peroxidation of the lipid , ROS formation and by falling enzymes that act as antioxidant lead to oxidative and DNA degradation, the results agreed with results reported by [11]. ...
... Hydroalcoholic solution of Arctium lappa root extract has hypolipidemic, hepatoprotective, and antidiabetic effects on nicotinamide-streptozotocininduced type 2 diabetes (Ahangarpour et al. 2017). Lin and Lin (2002) found that hepatotoxicity induced by ethanol and potentiated by carbon tetrachloride (CCl 4 ) could be alleviated with 1 and 7 days of A. lappa treatment. In another study, Souza et al. (2014) found that A. lappa root extract protected liver function against cadmium toxicity. ...
Background
Herbal medicine plays an important role in health, particularly in remote parts of developing areas with few health facilities. According to WHO estimates, about three-quarters of the world's population currently use herbs or traditional medicines to treat various ailments, including liver diseases. Several studies have found that the use of medicinal plants was effective in the treatment of infectious and non-infectious diseases. Hepatitis and liver cirrhosis associated with many clinical manifestations can be treated with allopathic medicines, but reports of a number of side effects including immunosuppression, bone marrow suppression, and renal complications have motivated researchers to explore more natural herbal medicines with low or no side effects and with high efficacy in treating hepatic diseases.
Methods
Databases including PubMed, Medline, and Google Scholar were searched for findings on the hepatoprotective effects of plants.
Results
Various medicinal plants are used for the treatment of liver disorders. The range of alternative therapies is huge, and they are used worldwide, either as part of primary health care or in combination with conventional medicine. Hepatoprotective plants contain a variety of chemical constituents including flavonoids, alkaloids, glycosides, carotenoids, coumarins, phenols, essential oil, organic acids, monoterpenes, xanthenes, lignans, and lipids.
Conclusion
This review shows that numerous plants are found to contain hepatoprotective compounds. However, further studies are needed to determine their association with existing regimes of antiviral medicines and to develop evidence-based alternative medicine to cure different kinds of liver disease in humans.
... Topical to treat eczema, warts, baldness, skin ulcers and badly treated wounds (Bissett, 1994). Burdock is also characterized as being hypothermia,diuretic and blood purifier,stimulate of bile secretion and reduce blood sugar and alsoused to treat rheumatism and gonorrhea (Foster and Duke, 1990;Lin et al, 2002;Chauhan, 1999). Al-Snafi (2014) pointed out that the plant possesses anti-oxidant, antiinflammatory and anti-tumor properties due to the presence of many secondary metabolites such as phenols. ...
A fieldexperiment was carried out in the Experimental Researches Station (2), College of Agriculture, Al-Muthanna University in Iraq, during 2017-2018 to determine the effectof threelevels of nitrogen (0, 50 and 100 kg N.ha-1) and three harvesting dates (15 May, 5 June and 25 June) on growth of Arctium lappa L. and total phenols content in leaves. Randomized Complete Block Design was used with three replicates. The study revealed that the burdock plants that have been fertilized at the level (100Kg N.ha-1) significantly supervised inplant height, number of leaves, leaf area, shoot dry weight, root dry weight (51.02 cm, 12.80 leaf, 79.16dm 2 , 69.52g and 80.42g), respectively. While, the plants that have been fertilized at the level (50Kg N. ha-1) gave highest content of total phenols (43.82mg GAE. g-1 dw). Harvesting of plants at 25 June gave highest plant height (49.65 cm), number of leaves (11.29 leaf), leaf area (76.15 dm 2), shoot dry weight (66.36g), root dry weight (75.64g) and content of total phenols (43.33 mg GAE. g-1 dw).
... Allium sativum [15][16] Aqueous extracts showed no inhibitory effect while the ethanolic extracts exhibited strong inhibitory effect on both AHH and 3H-BP binding to the microsomal protein aryl hydrocarbon hydroxylase activity (AHH) and 3H-benzo (a) pyrene (3H-BP) binding to rat liver microsomal protein aqueous and ethanolic extracts Anchus strigosa [17][18][19] Arctium lappa was shown to suppress the CCl4 or acetaminophen-intoxicated mice as well as the ethanol plus CCl4induced rat liver damage. The hepatoprotective ability could be attributed to the decrease of oxidative stress on hepatocytes CCl4 or acetaminophenintoxicated mice as well as the ethanol plus CCl4-induced rat liver damage aqueous extract of the root, 300 mg/kg bw. by increasing glutathione (GSH), cytochrome P-450 content and NADPH-cytochrome C reductase activity and by decreasing malondialdehyde (MDA) content [20] It showed anticancer activity against N-diethylnitrosamine (DENA)-induced hepatic cancer in rats N-diethylnitrosamine (DENA)-induced hepatic cancer in rats flavonoid rhamnocitrin 4'-β-Dgalactopyranoside (RGP) obtained from leaves Astragalus hamosus [21][22] It decreased the level of AST, ALT, ALP and GGT. ...
The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Drug-induced hepatic injury is the most common reason cited for withdrawal of an approved drug. Many medicinal plants showed hepatoprotective activity. The current review will discuss the medicinal plants possessed hepatoprotective effects.
Wounds are common external or internal damages to the body, usually caused by a physical, chemical, or biological agents. There
exists natural repair wound healing repair in that includes immunological responses i.e., inflammation and necrosis. Naturally, body
repairs wounds itself, but the period of healing is relatively slow. This healing process may further be delayed by the pathogens
attack or weaker immune response. Wounds heal biochemically, but the time of the healing can be reduced by applying different
herbs like the plant-based treatments. Sub-continent is rich in having an immense variety of medicinal plants as well. This literature
review is about the role of different plants in wound healing, the efficacy of herbs on wound healing.
Previous studies have shown that alcohol abuse can cause serious liver damage and cirrhosis. The main pathway for these types of hepatocellular cell neurodegeneration is mitochondrial dysfunction, which causes lipid peroxidation and dysfunction of the glutathione ring and the defect of antioxidant enzymes in alcoholic hepatic cells. Alcohol can also initiate malicious inflammatory pathways and trigger the initiation and activation of intestinal and extrinsic apoptosis pathways in hepatocellular tissues that lead to cirrhosis. Previous studies have shown that curcumin may inhibit lipid peroxidation, glutathione dysfunction and restore antioxidant enzymes. Curcumin also modulates inflammation and the production of alcohol-induced biomarkers. Curcumin has been shown to play a critical role in the survival of alcoholic hepatocellular tissue. It has been shown that curcumin can induce and trigger mitochondrial biogenesis and, by this mechanism, prevent the occurrence of both intrinsic and extrinsic apoptosis pathways in liver cells that have been impaired by alcohol. According to this mechanism, curcumin may protect hepatocellular tissue from alcohol-induced cell degeneration and may therefore survive alcoholic hepatocellular tissue. . Based on these mechanisms, the protective functions of curcumin against alcohol-induced cell degeneration due to oxidative stress, inflammation, and apoptosis events in hepatocellular tissue have been recorded. Hence, in this research, we have attempted to evaluate and analyze the main contribution mechanism of curcumin cell defense properties against alcohol-induced hepatocellular damage, according to previous experimental and clinical studies, and in this way we report findings from major studies.
The review summarizes information from the literature on the distribution, study of the composition and biological activity of metabolites, total extracts of plants of the genus Arctium L. of the world flora. In Russia, the roots of three species are allowed to be harvested and used: A. lappa, A. tomentosum, A. minus. To date, the most studied composition of metabolites and pharmacological properties of great burdock. The chemical composition of A. atlanticum, A. debrayi, A. leiobardanum, A. neumani, A. platylepis, A. pseudarctium, A. sardaimionense, A. scanicum, A. nemorosum and A. palladini has not been studied. About 360 substances related to polysaccharides, sesquiterpenes, triterpenes, fatty acids, phenolcarbonic acids, tannins, vitamins, lignans, sterols, polyacetylenes, amino acids, alkaloids, flavonoids, macro-and microelements and other were isolated and identified from the studied species. There are only a few publications about pharmacological activity of Arctium nemorosum, A. palladini, A. tomentosum and A. minus, and there is no information for other types. Total extracts and individual compounds of the studied burdock species in the experiment have a wide range of pharmacological activity. The information provided in the review shows that plants of the genus Arctium L., are promising for creating effective medicines. In addition, the fragmentation and lack of information on the composition of metabolites, pharmacological activity of most species of the genus burdock opens up great opportunities for researchers.
Liver, being one of the most fundamental and vital organ existing in human body and performing significant role in regulation of enormous number of biological processes including metabolism of biomolecules, secretion, storage, detoxification and excretion of xenobiotics from body. Accomplishment of all these processes leads to acute or chronic hepatic injuries and liver dysfunctions, which sequentially contributes to global health care threat as well as it is a concern for pharmaceutical industry as despite all advancements in medicine there is still a lack of completely assured hepato-protective drugs which stimulate and enhance liver function. However, nature full fills these vacant spaces by providing a number of plant derived hepatoprotective phytochemicals, which are comparatively less toxic and this leads to introduction of an alternative phytotherapeutic approach i.e., the use of poly herbal formulations for treatment of liver diseases. Throughout the world, herbalists claim the use of a number of remedial plants for treatment of hepatic dysfunctions. Nevertheless, recent research also reveals that not only phytochemicals, but also regulatory microRNAs are being transferred from plant to animal kingdom. Thus, this leads to an alternative concept of cross-kingdom gene regulation by non-coding tiny molecules i.e. orally consumed plant derived xeno-MIRs play a chief role in human health regulation. The abilities of microRNAs to regulate cross-kingdom gene regulation have prompted the hopes to explore this novel concept in diagnosis, prognosis and treatment as potential therapeutic and dietary supplements. The present review is aimed to compile the available data of promising hepatoprotective plants and introduce the cross-kingdom gene regulation approach as potential therapy for human health care.
Burdock root is the root of Arctium lappa L., a plant of the compositae family, which has the effects of dispersing wind and heat, detoxifying, and reducing swelling. In order to better control the quality of burdock root, a screening study of quality control indicators was carried out. The current research combines biological activity evaluation with chemical analysis to screen and identify the biologically active compounds of burdock root as chemical components for quality control of herbal medicine. The efficacy of 10 batches of ethanol extracts of burdock roots was evaluated by the tumor inhibition experiment in S180 tumor‐bearing mice. Simultaneously, the five main chemical components of these extracts were quantitatively measured by ultra‐high performance liquid chromatography combined with triple quadrupole mass spectrometry (UHPLC‐QqQ‐MS/MS). Pearson correlation analysis was used to establish the relationship between these extracts' biological activity and chemical properties. The results showed that chlorogenic acid, caffeic acid, and cynarin were positively correlated with the effect of inhibiting tumor growth, and further bioassays confirmed this conclusion. In conclusion, chlorogenic acid, caffeic acid, and cynarin can be used as quality control markers for burdock root's anti‐tumor effect.
Arctium lappa is a weed used in traditional medicine in the treatment of skin inflammation and digestive tract diseases. Arctium tomentosum is used in folk medicine interchangeably with Arctium lappa and, according to European Medicines Agency (EMA) monography, provides an equal source of Arctii radix (Bardanae radix), despite the small amount of research confirming its activity and chemical composition. The aim of the study was the comparison of the anti-lipoxygenase and the antioxidant activity, scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion (O2•−), and hydrogen peroxide (H2O2), of 70 % (v/v) ethanolic extracts from the aerial parts and the roots of Arctium lappa and Arctium tomentosum. In the tested extracts, the total polyphenols content and the chemical composition, analyzed with the HPLC–DAD–MSn method, were also compared. The extracts were characterized by strong antioxidant properties, but their ability to inhibit lipoxygenase activity was rather weak. A correlation between the content of polyphenolic compounds and antioxidant activity was observed. The extracts from A. lappa plant materials scavenged reactive oxygen species more strongly than the extracts from A. tomentosum plant materials. Moreover, the extracts from A. lappa plant materials were characterized by the statistically significantly higher content of polyphenolic compounds.
Neurodegenerative disorders are characterized by mitochondrial dysfunction and subsequently oxidative stress, inflammation, and apoptosis that contribute to neuronal cytotoxicity and degeneration. Recent studies reported that crocin, a carotenoid chemical compound common in crocus and gardenia flowers, has protective effects in neurodegenerative disorders due to its anti-oxidative, anti-inflammatory, and anti-apoptotic properties in the nervous system. This article reviews the new experimental, clinical, and pharmacological studies on the neuroprotective properties of crocin and its potential mechanisms to modulate metabolic oxidative stress and inflammation in neurodegenerative disorders.
The present study investigated the effect of drying temperature (50, 60, 70, and 80 °C) on the drying kinetics and water properties of burdock slices. The changes in water mobility and water distribution were characterized using ¹H low-field nuclear magnetic resonance (LF-NMR) and magnetic resonance imaging (MRI) techniques. The Page model satisfactorily described the hot-air drying curves of burdock. The drying kinetic curves showed that the second stage of drying corresponded exactly with when the relaxation times of free and immobile water decreased to the equilibrium points. MRI showed that water diffused from the center to the surface during drying. Overall, the LF-NMR, color and HPLC data showed that, at 60 °C, free water in burdock dissipated slowly, its color stability was higher, and its chlorogenic acid content was higher than at 70 and 80 °C. Significant correlations were found between moisture content, color and NMR parameters.
Introduction. Artemisia L. genus species are the promising sources for the manufacturing of drugs with hepatoprotective activity. They are used as appetizing, anthelmintic, bactericidal, choleretic and anti-inflammatory remedies. The pharmacological activity of Artemisia L. species is caused by the presence of different groups of biologically active substances. The aim of the study – to learn the acute toxicity and the effect of Artemisia absinthium and Artemisia vulgaris water-alcohol extracts on the progress of the toxic tetrachloromethane liver damage. Research Methods. The method of preclinical study of drugs safety was used to determine the acute toxicity. The investigation of hepatoprotective activity of Artemisia absinthium and Artemisia vulgaris extracts was performed using the model of acute tetrachloromethane hepatitis. Hepatoprotector of local manufacturer (“Silibor” tablets) was used as the reference drug. Results and Discussion. It was found that intragastric administration of Artemisia absinthium and Artemisia vulgaris extracts at the dose of 6000 mg/kg does not lead to the death of animals. There were no changes in the integral, hematological, biochemical parameters and in the morphological structure of the internal organs of experimental animals. It allows to characterize the extracts at this dose as almost non-toxic ones (V toxicity class, LD50>5000 mg/kg) according to the toxicity classification of substances. The results of Artemisia absinthium and Artemisia vulgaris extracts study indicate that they show the distinct hepatoprotective activity in condition of acute toxic liver damage. They suppress peroxide destructive processes and reduce the evolution of cytolysis syndrome and their effects are no inferior rather than the effect of tablets “Silibor”. Conclusions. The study of acute toxicity of Artemisia absinthium and Artemisia vulgaris extracts after their intragastric administration at the dose of 6000 mg/kg does not lead to the animals death. They were tidy and had the good appetite. The animals reacted adequately to sound and light stimulation. The processes of urination and defecation were unchanged. Breathing disorders and seizures were not observed. The investigated Artemisia absinthium and Artemisia vulgaris extracts demonstrate hepatoprotective activity in condition of acute toxic liver damage. This is proved by decreasing in the intensity of lipid peroxidation and in the toxicity of tetrachloromethane. Biochemical parameters of the animals’ blood and the liver homogenate became responded to the level of intact animals.
CCl4 intoxicated rats showed significant elevation in serum enzymes, bilirubin and lipid per oxidation of the liver tissues and reduction in serum total protein, superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase activity. Treatment with ethanol extract of Catharanthus pusillus whole plant altered the above parameters to the levels of near normal. All the above results were comparable with the standard drug silymarin (100mg/kg) treated group. Thus the present study ascertains that the ethanol extract of Catharanthus pusillus whole plant possesses significant hepatoprotective activity.
Nonalcoholic steatohepatitis (NASH) is considered growing risk factor for hepatocellular carcinoma development in high-income countries. Diet- and chemically induced rodent models have been applied for the translational study of NASH-associated hepatocarcinogenesis due to their morphological and molecular similarities to the corresponding human disease. Arctium lappa L. (burdock) root tea has been extensively consumed in Traditional Chinese Medicine due to its potential therapeutic properties. Indeed, the bioactive compounds of A. lappa root, as the polyphenols, have already showed antioxidant and anti-inflammatory properties in different in vivo and in vitro bioassays. In this study, we investigated whether burdock root ethanolic extract (BRE) administration attenuates NASH-associated hepatocarcinogenesis. Eight-week-old male Wistar rats received choline-deficient high-fat diet for 8 weeks and multiple thioacetamide doses for 4 weeks in order to induce NASH and preneoplastic glutathione-S-transferase pi (GST-P)+ preneoplastic foci. Subsequently, rats were treated with BRE (100 or 200 mg/kg body weight) or vehicle by oral gavage for 2 weeks. BRE displayed high levels of chlorogenic and caffeic acids and BRE administration reduced total fatty acid and lipid hydroperoxide levels, while increasing the activities of antioxidant superoxide dismutase and catalase enzymes in the liver. Furthermore, burdock intervention diminished the size of GST-P+ remodeling preneoplastic lesions (PNLs) and displayed a trend on reducing hepatocyte proliferation (Ki-67) inside them. These findings suggest that short-term exposure to BRE alleviated remodeling PNL development in NASH-associated hepatocarcinogenesis.
Introduction:
Gnetum ula is a notable medicinal plant used to cure various ailments. The stem part of the plant is used traditionally to treat jaundice and other disorders. The present work is to investigate the in vitro hepatoprotective and antioxidant activity of ethanol extract of stem of G. ula (GUE) and its isolated compound gnetol.
Methods:
Column chromatography was carried out for GUE and various column fractions were obtained. DPPH and reducing power assays were performed for GUE and column fractions. The potent fraction was characterized, interpreted and tested for in vitro hepatoprotective activity on the BRL3A cell line. In silico docking studies of gnetol compound on the protein TGF-β (transforming growth factor - β) and Peroxisome proliferator-activated receptor α (PPARα) was carried out.
Results:
DPPH scavenging and reducing power assay showed that the fourth column fraction has antioxidant potential than other fractions. The fourth column fraction was characterized to obtain gnetol compound. BRL3A cell line was used for the toxicity study of GUE and gnetol. Both, the extract and the isolated compound were found to be nontoxic with CTC50 value more than 1000 µg/mL. At the concentration of 200 µg/mL, GUE and gnetol offered cell protection of 50.2% and 54.3%, however, silymarin showed 77.15% protection at 200 µg/mL concentration against CCl4 treated BRL3A cell line. The docking results of the ligand molecule TGF-β showed that gnetol has the binding affinity of -7.0 and standard silymarin being -6.8. TGF-β showed good hydrophobic interactions and formed two hydrogen bonds with the amino acids. For PPARα protein, gnetol showed the binding affinity of -8.4 and silymarin with -6.5. Hydrogen bonding and good hydrophobic interactions against the amino acid molecules in relation to the PPARα protein are shown.
Conclusion:
Gnetum ula stem extract and its isolated compound are safe and offered significant hepatoprotection against CCl4 induced toxicity. Isolated compound gnetol exhibited a potent antioxidant activity offering protection to liver damage. However, in vivo studies need to be carried out to validate the traditional use of G. ula .
In this study, online databases including Web Science, PubMed, Scopus and Science Direct, were searched for papers studied the hepatoprotective effects of medicinal plants against carbon tetrachloride, D-galactosamine (D-GalN), D-galactosamine (D-GalN)/ lipopolysaccharide (LPS), N, N-dimethylformamide (DMF), oxytetracyclin thioacetamide (TAA), nitrosodiethylamine, paracetamol, rifampin, INH, aflatoxins, iron-overload and oxidative stress induced hepatotoxicity and against hepatic cancer induced chemically.
Мета роботи. Дослідження гострої токсичності та гепатопротекторної активності трави полину гіркого та полину звичайного.
Матеріали і методи. Для визначення гострої токсичності використовували методику доклінічного вивчення безпечності лікарських засобів. Вивчення гепатозахисної активності екстрактів полину гіркого та полину звичайного проводили на моделі гострого тетрахлорметанового гепатиту. Як препарат порівняння використовували гепатопротектор вітчизняного виробництва таблетки «Силібор».
Результати й обговорення. В результаті проведеного дослідження встановлено, що внутрішньошлункове введення екстрактів трави полину гіркого та полину звичайного у дозі 6000 мг/кг не призводить до загибелі тварин, змін зі сторони інтегральних, гематологічних, біохімічних показників та морфологічної структури внутрішніх органів піддослідних тварин не виникає, що вказує на відсутність токсичної дії екстрактів в даній дозі, та характеризує їх як практично нетоксичні (V клас токсичності, LD50 > 5000 мг/кг) відповідно до класифікації речовин за токсичністю.
При гострому токсичному уражені печінки екстракти полину гіркого та полину звичайного проявляють виразну гепатопротекторну активність, пригнічуючи перекисні деструктивні процеси та зменшуючи розвиток синдрому цитолізу і практично не поступаються препарату порівняння «Силібор».
Висновки. Вивчення гострої токсичності після внутрішньошлункового введення екстрактів трави полину гіркого та полину звичайного у дозі 6000 мг/кг не призводило до загибелі тварин, вони були охайними, мали задовільний апетит, нормально реагували на звукові і світлові подразники, процеси сечовиділення і дефекації були у нормі, порушення дихання та судом не спостерігали.
Досліджувані екстракти полину гіркого та полину звичайного проявляють при гострому токсичному ураженні печінки гепатопротекторну активність, про що свідчить зниження інтенсивності процесу перекисного окислення ліпідів та зменшення токсичності дії тетрахлорметану, доводячи біохімічні показники крові та гомогенату печінки тварин до рівня інтактних.
Objective
The aim of the study was to evaluate the hepatoprotective activity of the bark extract (Ethanol: Water) in the ratio of (3:1) of Rhizophora mucronata (BERM) by intoxicating the HepG2 cell lines with different toxicants viz, CCL4, Ethanol and Paracetamol with different concentrations of the extract were used. The HepG2 cell lines were subjected to MTT Assay for studying the cytotoxicity.
Methods
HepG2 cells were plated using 96 well plate in 10% bovine serum, exposed to different toxicants viz, 2% CCl4, 60% Ethanol and 14 mM Paracetamol respectively. The various test concentrations (18.85, 37.5, 75, 150 and 300 μg/ml) of bark extract of Rhizophora mucronata was added and incubated for 24 hours. Medium was removed after incubation period and 0.5 mg/ml MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was added and again incubated for 4 hours at 37oC. Then MTT was removed the crystals was dissolved in DMSO and absorbance was measured at 570 nm.
Results
The result showed that dose dependent increase in percentage of viability at the doses of 18.85, 37.5, 75, 150, 300 μg/ml. The results for the CCl4 intoxicated, at 300 μg/ml of the concentration of the extract, the % of viable cells was found out to be 99.6%, for Ethanol intoxicated, 97.67%, and Paracetamol induced, 75.37%, IC50 was 21.53 μg/ml, 12.61 μg/ml and 21.42 μg/ml respectively.
Conclusion
Thus, we conclude that, the extract possesses defensive effect against different toxicants and can be used as an alternate drug for hepatotoxicity.
Sumario: It is difficult to extrapolate the dose-response relation in CCl4 (carbon tetrachloride) induced hepatotoxicity from the high concentrations used in animal studies to the low concentrations generally encountered by man in the workplace. Therefore, the dose-response relation of inhalation exposure at low concentration must be investigated when trying to determine a TLV of exposure concentration for man. In the present study, it is investigated the dose-response relations of CCl4 induced hepatic damage in chronic ethanol treated and one day food deprived rats with biochemical and histopathological methods
A new isozyme of cytochrome P-450 has been purified to electrophoretic homogeneity from hepatic microsomes of rabbits treated chronically with ethanol. Several criteria indicate that the ethanol-inducible cytochrome, which has a minimal molecular weight of 51,000 and is designated form 3a on the basis of its relative electrophoretic mobility, is distinct from the known isozymes of P-450. As judged spectrally, the new isozyme is high spin in the oxidized state, as is form 4, but differs in that the spin state is unperturbed by nonionic detergents. The absolute spectrum of the ferrous carbonyl complex of form 3a is red shifted as compared to that of forms 2, 3b, 3c, 4, and 6 and exhibits a maximum at 452 nm. The amino acid composition of form 3a is different from that of the other isozymes, and both the NH2- and COOH-terminal sequences are distinct; form 3a has an NH2-terminal alanine and a carboxyl-terminal leucine residue. Peptide mapping by sodium dodecyl sulfate-polyacrylamide gel electrophoresis following treatment with papain, chymotrypsin, or Staphylococcus aureus V8 protease and by high performance liquid chromatography following trypsinolysis indicates that form 3a is a unique gene product. This cytochrome displays the highest activity of all of the rabbit isozymes in the oxidation of ethanol to acetaldehyde and the p-hydroxylation of aniline when reconstituted with NADPH-cytochrome P-450 reductase and phospholipid in the presence of NADPH and oxygen.
The inclusion of 8% mineral oil in a fat-free diet causes severe growth retardation in rats. In the present study, this growth retardation was found to be primarily due to the reduction in nutrient intake, but not to the exacerbation of essential fatty acid deficiency. In addition, the growth retardation caused by mineral oil ingestion was prevented by the concurrent inclusion of 10% water-insoluble dietary fiber [gobo fiber prepared from Arctium lappa L. (gobo in Japanese) or cotton cellulose powder] or 5% fatty acids (C12-C18) as well as glycerol monostearate. The prevention of growth retardation by these substances was due to their ability to inhibit mineral oil absorption from the intestinal lumen.
The role of lipid peroxidation in the pathogenesis of alcoholic liver disease has been a subject of controversy. In order to study this question we measured hepatic glutathione and diene conjugates in liver biopsies from 16 alcoholics with different stages of liver injury and 8 nonalcoholics with liver disease. Patients with alcoholic liver disease were found to have decreased hepatic glutathione compared to patients with liver disease unrelated to alcohol (22.1±2.5 vs 33.5±4.6 nmol/mg protein,P<0.05). The decrease in glutathione was accompanied by an increase in diene conjugates in hepatic lipids (3.37±0.14 vs 2.26±0.21 OD at 232 nm/mg lipid,P<0.001). The changes were present in all stages of alcoholic liver damage including fatty liver but unrelated to nutritional status in these patients. They support the concept that lipid peroxidation may be an important mechanism in the pathogenesis of alcoholic liver disease.
Conditions for accurate measurement of catalytic activity of aspartate aminotransferase and alanine aminotransferase in human serum have been reinvestigated. The basic variables (kind of buffer, buffer concentration, pH, ion effects, and the influence of pyridoxal-5-phosphate) can now be considered optimized. On this basis, the kinetic parameters of both aminotransferases were determined, i.e., Michaelis and inhibitor constants for substrates and reaction products. With a mathematical approach for two-substrate enzyme reactions the substrate concentrations were calculated from the viewpoints "most economical," "most convenient," and "lowest variability." Also the conditions for the indicator reactions have been newly defined with respect to a kinetic model. All calculated data were rechecked experimentally and it can be shown that both approaches fully agree. Furthermore, we show that the mathematical approach allows more precise recommendations for optimized methods. For technical reasons, the catalytic activity of aspartate aminotransferase in human serum can only be measured as a 0.96 fraction of its theoretical maximum velocity, the catalytic activity of alanine aminotransferase as a 0.91 fraction. The assay conditions for a Reference Method are finally described and recommendations are made for optimized routine methods for determination of the catalytic activity of these transferases in human serum.
Publisher Summary This chapter discusses microsomal lipid peroxidation. Lipid peroxidation is a complex process known to occur in both plants and animals. It involves the formation and propagation of lipid radicals, the uptake of oxygen, a rearrangement of the double bonds in unsaturated lipids, and the eventual destruction of membrane lipids, producing a variety of breakdown products, including alcohols, ketones, aldehydes, and ethers. Biological membranes are often rich in unsaturated fatty acids and bathed in an oxygen-rich, metal-containing fluid. Lipid peroxidation begins with the abstraction of a hydrogen atom from an unsaturated fatty acid, resulting in the formation of a lipid radical. The formation of lipid endoperoxides in unsaturated fatty acids containing at least 3 methylene interrupted double bonds can lead to the formation of malondialdehyde as a breakdown product. Nonenzymic peroxidation of microsomal membranes also occurs and is probably mediated in part by endogenous hemoproteins and transition metals. The direct measurement of lipid hydroperoxides has an advantage over the thiobarbituric acid assay in that it permits a more accurate comparison of lipid peroxide levels in dissimilar lipid membranes.
Structural transformation of arctiin and tracheloside, major components of seeds of Arctium lappa and Carthamus tinctorius, were investigated using rat gastric juice (pH 1.2-1.5) and rat large intestinal flora in vitro. Quantitative analysis of lignans and their metabolites was carried out by high performance liquid chromatography. Both lignans were stable in rat gastric juice and arctiin was rapidly transformed to arctigenin in rat large intestinal flora, followed by conversion to the major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-butyrolactone. On the other hand, tracheloside also decreased dependently with time and was converted to trachelogenin and its major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-2-hydroxybutyrola ctone. These experiments suggest that in the course of metabolism of lignans, firstly a cleavage of the glycosidic bond occurred and then demethylation of the phenolic methoxy group in the alimentary tract followed.
Hot aqueous extracts of medicinal plants were tested for their inhibitory effect on the binding of platelet activating factor (PAF) to rabbit platelets. The extracts of Forsythia suspensa VAHL. (Oleaceae), Arctium lappa L. (Compositae) and Centipeda minima (L.) A. BRAUN et ASCHERS (Compositae) showed significant activities. Since the main constituents of F. suspensa and A. lappa are lignans, 30 lignans were tested for their inhibitory effects on PAF binding to platelets and 9 lignans were found active. Four sesquiterpenes were isolated as active compounds from C. minima. In particular 6-O-angeloylplenolin and 6-O-senecioyplenolin are the most potent and specific PAF antagonists found in this study.
Activity of lysosomal enzymes, such as N-acetyl-beta-D-glucosaminidase (NAG), was assayed in exudate on a rat model of Bordetella pertussis vaccine pleurisy. Thiobarbituric acid (TBA)-reactive substances (TBA.R) and superoxide dismutase (SOD) activity were then monitored in the exudate on the acute phase response in this inflammatory model. Retention of the exudate in the pleural space increased rapidly after the challenge, and the exudate volume at 24 h reached about three times the volume at 6 h. The activity of SOD at 6 h was shown to be higher than that at 24 h after the challenge, thus showing negative correlations with TBA-R levels and exudate volume. The levels of TBA.R rapidly increased and reached maximum values at 24 h. It was concluded that the above three parameters correlated to the acute phase response in this inflammatory model.
Three models of free radical-induced cell injury are presented in this review. Each model is described by the mechanism of action of few prototype toxic molecules. Carbon tetrachloride and monobromotrichloromethane were selected as model molecules for alkylating agents that do not induce GSH depletion. Bromobenzene and allyl alcohol were selected as prototypes of GSH depleting agents. Paraquat and menadione were presented as prototypes of redox cycling compounds. All these groups of toxins are converted, during their intracellular metabolism, to active species which can be radical species or electrophilic intermediates. In most cases the activation is catalyzed by the microsomal mixed function oxidase system, while in other cases (e.g. allyl alcohol) cytosolic enzymes are responsible for the activation.
A single dose of CCl4 when administered to a rat produces centrilobular necrosis and fatty degeneration of the liver. These hepatotoxic effects of CCl4 are dependent upon its metabolic activation in the liver endoplasmic reticulum to reactive intermediates, including the trichloromethyl free radical. Positive identification of the formation of this free radical in vivo, in isolated liver cells and in microsomal suspensions in vitro has been achieved by e.s.r. spin-trapping techniques. The trichloromethyl radical has been found to be relatively unreactive in comparison with the secondarily derived peroxy radical CCl3O2., although each free radical species contributes significantly to the biological disturbances that occur. Major early perturbations produced to liver endoplasmic reticulum by exposure in vivo or in vitro to CCl4 include covalent binding and lipid peroxidation; studies of these processes occurring during CCl4 intoxication have uncovered a number of concepts of general relevance to free-radical mediated tissue injury. Lipid peroxidation produces a variety of substances that have high biological activities, including effects on cell division; many liver tumours have a much reduced rate of lipid peroxidation compared with normal liver. A discussion of this rather general feature of liver tumours is given in relation to the liver cell division that follows partial hepatectomy.
Ethanol metabolism was studied in four healthy volunteers by intravenous infusion of a mixture of [1,1-2H2]ethanol (1.0 mmol/kg) and [2,2,2-2H3]ethanol (1.0 mmol/kg) followed by blood sampling at 10-min intervals. The concentrations of ethanols labeled with 1, 2, 3, and 4 deuterium atoms were determined by gas chromatography/mass spectrometry of the 3,5-dinitrobenzoates. During the first 30 min mono- and tetradeuteriated molecules appeared rapidly, which indicates that a fraction of the ethanol was formed from acetaldehyde by exchange. This fraction was calculated to be 38-58% and the hydrogen incorporated during the reduction was mainly (63-82%) derived from C-1 of ethanol, indicating slow exchange of enzyme-bound NADH. After 30 min the elimination followed first-order kinetics with t1/2 of 18-31 min and with a small primary isotope effect (1.05-1.11). This indicates almost complete removal of ethanol from blood passing through the liver when the concentration is low (below 1 mM). The results indicate that as long as hepatic blood flow is not limiting, the rate of alcohol dehydrogenase-catalyzed elimination of a small dose of ethanol in vivo is limited by the dissociation of NADH from the enzyme and by the rates of oxidation of acetaldehyde and reoxidation of NADH.
This assay of plasma lipoperoxides involves hydrolysis in dilute H3PO4 at 100 degrees C; complexation of malondialdehyde (MDA), a hydrolysis product, with thiobarbituric acid (TBA); methanol precipitation of plasma proteins; fractionation of the protein-free extract on a C18 column; and spectrophotometric quantification of the MDA-TBA adduct at 532 nm. The detection limit was 0.15 mumol of MDA per liter of plasma. Run-to-run precision (CV) averaged 8 to 13%. Analytical recovery of MDA after addition of tetraethoxypropane standards to 21 specimens of human or rat plasma averaged 98% (SD 7%). Lipoperoxide concentrations (as MDA) averaged 0.60 (SD 0.13) mumol/L in plasma specimens from 41 healthy persons and 1.4 (SD 0.3) mumol/L in plasma specimens from 12 control rats. Mean lipoperoxide concentrations were 1.5 to 2.3 times as great in plasma sampled from rats one to three days after subcutaneous administration of NiCl2 at dosages (250 to 750 mumol per kilogram body wt) previously shown to induce lipid peroxidation in lung, liver, and kidney.
In this article studies from the laboratory and others on the possible implication of lipid peroxidation in some experimental models of cellular injury have been reviewed. A great deal of the evidence presented above seems to suggest that peroxidation of membrane lipids is a relevant factor in the production of cellular damage by drugs and chemicals. Lipid peroxidation can cause deleterious effects on cellular functions both directly, by producing loss of membrane structure, and indirectly, by causing the evolution of toxic products, especially reactive aldehydes such as alkenals, capable of reaching molecular targets at a distance. The occurrence of lipid peroxidation does not exclude that other factors such as the covalent binding of reactive metabolites of toxic chemicals play a role in damaging cellular functions, and probably many events are the results of various pathogenetic mechanisms. The evidence obtained in our studies, however, suggests that, at least in some experimental models in vitro and in vivo, lipid peroxidation seems to explain the attendant cellular injury better than the other putative causes. Caution, however, is needed with respect to claims of the occurrence of lipid peroxidation in in vivo situations in which the evidence is only indirect, and in which the conclusions have been drawn by inference. Nevertheless, it appears at present that the concept that lipid peroxidation occurs in living tissues, and that it may play a causative role in the induction of cell injury, is one of the truly important acquisitions of current experimental pathology and toxicology.
Rates of exchange catalysed by alcohol dehydrogenase were determined in vivo in order to find rate-limiting steps in ethanol metabolism. Mixtures of [1,1-2H2]- and [2,2,2-2H3]ethanol were injected in rats with bile fistulas. The concentrations in bile of ethanols having different numbers of 2H atoms were determined by g.l.c.-m.s. after the addition of [2H6]ethanol as internal standard and formation of the 3,5-dinitrobenzoates. Extensive formation of [2H4]ethanol indicated that acetaldehyde formed from [2,2,2-2H3]ethanol was reduced to ethanol and that NADH used in this reduction was partly derived from oxidation of [1,1-2H2]ethanol. The rate of acetaldehyde reduction, the degree of labelling of bound NADH and the isotope effect on ethanol oxidation were calculated by fitting models to the found concentrations of ethanols labelled with 1-42H atoms. Control experiments with only [2,2,2-2H3]ethanol showed that there was no loss of the C-2 hydrogens by exchange. The isotope effect on ethanol oxidation appeared to be about 3. Experiments with (1S)-[1-2H]- and [2,2,2-2H3]ethanol indicated that the isotope effect on acetaldehyde oxidation was much smaller. The results indicated that both the rate of reduction of acetaldehyde and the rate of association of NADH with alcohol dehydrogenase were nearly as high as or higher than the net ethanol oxidation. Thus, the rate of ethanol oxidation in vivo is determined by the rates of acetaldehyde oxidation, the rate of dissociation of NADH from alcohol dehydrogenase, and by the rate of reoxidation of cytosolic NADH. In cyanamide-treated rats, the elimination of ethanol was slow but the rates in the oxidoreduction were high, indicating more complete rate-limitation by the oxidation of acetaldehyde.
A method for the analysis of nanogram quantities of glutathione has been developed which is based on the catalytic action of GSH or GSSG in the reduction of Ellman reagent (DTNB) by a mixture of TPNH and yeast glutathione reductase. Unlike previous methods of analysis the procedure described here effectively measures the total glutathione (GSH + GSSG) content of unknown mixtures and is not subject to appreciable interference by the presence of other thiol components. It is suggested that the catalytic action of glutathione in this system resides in the continual enzymic regeneration of GSH, present initially or formed enzymically from GSSG, following its interaction with the sulfhydryl reagent.The sensitivity of the method is such as to permit the determination of total glutathione in extracellular tissue fluids such as plasma, saliva, and urine normally containing very low levels of this material, essentially without pretreatment of the sample. The same is true for glutathione determinations of whole blood, in which the preliminary procedure is confined to the preparation of a 1:100 hemolyzate from as little as 10 μl of sample.Following published procedures, the pretreatment of tissue extracts with NEM to form an enzymically inactive complex with free GSH allowed the determination of the low levels of oxidized glutathione normally present therein. The use of the foregoing analytical method in the determination of total and oxidized glutathione contents of rat blood, kidney, and liver gave values in good agreement with those obtained by previous investigators.
The effects of an acute dose of a diet containing ethanol (3g/kg) on hepatic redox state was compared in rats fed ethanol for 25 days and in their littermates given isocaloric carbohydrate. In both groups, cytoplasmic and mitochondrial redox states of pyridine nucleotides shifted to a more reduced level, but the changes were much less extensive in rats chronically fed ethanol. This metabolic adaption may reflect the oxidation of ethanol by a pathway not involving alcohol dehydrogenase, such as the microsomal ethanol osidizing system, which increases in activity after chronic ethanol ingestion.
A novel method is described for determining serum triglycerides, in which an enzymatic hydrolysis replaces the more commonly used saponification procedure. Under the conditions of the assay, the enzymatic hydrolysis can be completed in less than 10 min by the combined action of a microbial lipase and a protease. The authors demonstrated complete hydrolysis of triglycerides by thin layer chromatography of the reaction products, by recovery of glycerol from sera of known triglycerides content, and by comparison of triglyceride assays on a number of sera assayed by their method vs. the AutoAnalyzer procedure. The hydrolysis is directly coupled to the enzymatic determination of glycerol, and is followed through absorbance changes at 340 nm. The assay is simple, rapid, and requires only 50 μl or less of sample. Because the enzymes used do not release glycerol from other compounds in serum, the hydrolysis can be considered specific for triglycerides.
To assess the quantitative relationship between fat content of the diet and lipid accumulation in the liver after alcohol ingestion, rats were given various isocaloric liquid diets, containing 18% of total calories as protein and 36% as ethanol or isocaloric carbohydrate. The remainder of the calories consisted of varying amounts of fat (2, 5, 10, 15, 25, 35, or 43% of total calories) and corresponding amounts of carbohydrate. Dietary fat consisted of ethyl linoleate (2% of total calories), to avoid essential fatty acid deficiency, and an olive-corn oil mixture. After 24 days of ethanol and 43% of calories as fat, hepatic triglycerides increased seven- to eightfold. With 35% of calories as fat, the increase was fivefold and with 25%, only two- to threefold. No significant decrease in hepatic lipid accumulation was achieved by further reduction in the dietary fat; a diet with 25% of calories as fat (about half that of the average United States diet) appears, therefore, to be optimal for minimizing the steatogenic effects of ethanol.
An excess of dietary protein did not affect the ethanol-induced steatosis, and even a combination of a high protein-low fat diet did not achieve full protection against the ethanol-induced hepatic deposition of lipids in the liver. The ethanol effect persisted unchanged for periods up to 3-5 months.
To determine whether prolonged ethanol intake can produce a fatty liver, even when associated with a diet containing adequate amounts of protein, minerals and vitamins, rats were given liquid diets containing 18% of calories as casein, supplemented with methionine (0.3 mg/kcal) and cystine (0.5 mg/kcal), choline (0.25 mg/kcal), fat (35% of total calories), adequate minerals and vitamins and, in the control diet, 47% of the calories as carbohydrates. A littermate of each control rat was pair-fed with the same diet in which carbohydrates had been isocalorically replaced with alcohol to the extent of 36% of the total calories. These diets assured continued growth in all animals and normal liver in the controls, whereas in the rats fed with alcohol, fatty liver developed, which was evident both morphologically and on chemical analysis; after 24 days of alcohol, hepatic triglycerides had increased on the average sixfold and cholesterol esters fivefold, compared with those of the controls. These studies demonstrate that prolonged alcohol intake can produce a fatty liver even when given with a diet with nutritionally adequate content of protein, vitamins and minerals, and an amount of fat less than that of the average American diet.
A desmutagenic factor was isolated from burdock (Arctium lappa Linne). This factor reduced the mutagenicity of mutagens that are active without metabolic activation, such as 4-NO2-1,2-DAB and 2-NO2-1,4-DAB, as well as mutagens such as ethidium bromide, 2-aminoanthracene, Trp-P-1 and Trp-P-2 requiring S9 for metabolic activation. It is resistant to heat and proteolytic enzymes and sensitive to treatment with MnCl2. The partially purified principles had a molecular weight higher than 300 000 and showed characteristics of a polyanionic substance. An irreversible diminution of the mutagen was confirmed by treatment of 2-NO2-1,4-DAB or Trp-P-2 with the burdock factor.
Acute or chronic treatment of rats with isopropanol caused a significant increase in hepatic cytochrome P-450 content and a two- to threefold increase in aniline hydroxylase and 7-ethoxycoumarin O-deethylase activities, but no significant change in ethylmorphine N-demethylase or benzo(a)pyrene hydroxylase activity. In rats treated with isopropanol and challenged with CCl4, liver toxicity of CCl4 was characteristically potentiated, as assessed by elevation of serum glutamic-pyruvic transaminase (SGPT) levels. Isopropanol pretreatment also potentiated CCl4-induced damage to the hepatic monooxygenase system. In addition to a decrease in cytochrome P-450, rats treated with isopropanol and challenged with CCl4 showed a nonspecific decrease not only in aniline hydroxylase and 7-ethoxycoumarin O-deethylase activities, but also in ethylmorphine N-demethylase, benzo(a)pyrene hydroxylase, and NADPH-cytochrome c reductase activities. These results were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of solubilized microsomes. The electrophoretic results showed that isopropanol pretreatment markedly potentiated the CCl4-caused destruction of cytochrome P-450 hemeproteins. The data strongly suggest that isopropanol increases one or more forms of cytochrome P-450 which selectively enhance the metabolism of CCl4 to an active metabolite. This active metabolite then causes a nonselective damage to the microsomal mixed-function oxidase system.
The role of lipid peroxidation in the pathogenesis of alcoholic liver disease has been a subject of controversy. In order to study this question we measured hepatic glutathione and diene conjugates in liver biopsies from 16 alcoholics with different stages of liver injury and 8 nonalcoholics with liver disease. Patients with alcoholic liver disease were found to have decreased hepatic glutathione compared to patients with liver disease unrelated to alcohol (22.1 +/- 2.5 vs 33.5 +/- 4.6 nmol/mg protein, P less than 0.05). The decrease in glutathione was accompanied by an increase in diene conjugates in hepatic lipids (3.37 +/- 0.14 vs 2.26 +/- 0.21 OD at 232 nm/mg lipid, P less than 0.001). The changes were present in all stages of alcoholic liver damage including fatty liver but unrelated to nutritional status in these patients. They support the concept that lipid peroxidation may be an important mechanism in the pathogenesis of alcoholic liver disease.
The rate of generation of reactive oxygen species (ROS) in hepatic microsomes was assayed using a fluorescent probe. This rate was stimulated in a manner proportional to the concentration of NADPH present. NADH could not be substituted for NADPH, and an inhibitor of mixed-function oxidases (SKF 525A) blocked stimulation by NADPH. This suggested the involvement of cytochrome P450 oxidase systems in ROS formation. Low molecular weight iron salts may not have been involved in the stimulated ROS formation since deferoxamine failed to eliminate the oxidative response to NADPH. Catalase only partially inhibited, and glutathione peroxidase did not significantly inhibit this response, implying that hydrogen peroxide does not play a key role. However, since NADPH-enhanced generation of reactive oxygen species was totally prevented by superoxide dismutase, superoxide was an obligatory intermediate. The presence of toluene, ethanol or phenobarbital did not enhance the production of NADPH-effected reactive oxygen species; free radical production was maximal in the absence of substrates subject to oxidation by cytochrome P450 enzymes. Hepatic cytochrome P450 oxidases are likely to contribute significantly to overall ROS formation, even under basal conditions where mixed-function oxidases are not induced.
In the Tsukamoto-French model, ethanol causes an important 10-20-fold induction of ethanol-inducible cytochrome P4502E1 (CYP2E1), mediated through enzyme stabilization and increased rate of gene transcription. The CYP2E1 induction results in a pronounced increase in the rate of NADPH-dependent microsomal lipid peroxidation, an elevation which is not seen after simultaneous administration of the CYP2E1 inhibitor diallylsulfide. Increased amounts of lipid peroxides are seen in plasma and red blood cells of both rats and humans during high ethanol intake. A mechanism for ethanol-dependent liver damage is proposed which involves the CYP2E1-dependent lipid peroxide formation, either directly by its capability to induce NADPH-dependent peroxidation in the microsomal membranes or indirectly by a hypoxia-mediated transformation of xanthine dehydrogenase to xanthine oxidase, in activation of Ito cells and Kupffer cells to yield cytokine and collagen production. The CYP2E1 gene is polymorphic among Caucasians. Four different unrelated or partially linked polymorphisms have been observed. One polymorphism in the 5'-flanking region has been described to be associated with altered enzyme expression in vitro, and the rare allele was found to be less frequent among Swedish patients having lung cancer when compared to two different control groups. Another polymorphism, detectable with Dra I restriction endonuclease fragment length polymorphism (RFLP), was localized to intron 6, and the rare allele was less common among Italian alcoholics with clinical signs of liver cirrhosis, as compared to controls. Several other mutations in the CYP2E1 gene were found to be associated with this allele. However, further research is needed to relate the CYP2E1 gene polymorphism with incidence of liver cirrhosis.
This article reviews current concepts on the pathogenesis and treatment of alcoholic liver disease. It has been known that the hepatotoxicity of ethanol results from alcohol dehydrogenase-mediated excessive generation of hepatic nicotinamide adenine dinucleotide, reduced form, and acetaldehyde. It is now recognized that acetaldehyde is also produced by an accessory (but inducible) microsomal pathway that additionally generates oxygen radicals and activates many xenobiotics to toxic metabolites, thereby explaining the increased vulnerability of heavy drinkers to industrial solvents, anesthetics, commonly used drugs, over-the-counter medications, and carcinogens. The contribution of gastric alcohol dehydrogenase to the first-pass metabolism of ethanol and alcohol-drug interactions is discussed. Roles for hepatitis C, cytokines, sex, genetics, and age are now emerging. Alcohol also alters the degradation of key nutrients, thereby promoting deficiencies as well as toxic interactions with vitamin A and beta carotene. Conversely, nutritional deficits may affect the toxicity of ethanol and acetaldehyde, as illustrated by the depletion in glutathione, ameliorated by S-adenosyl-L-methionine. Other "supernutrients" include polyunsaturated lecithin, shown to correct the alcohol-induced hepatic phosphatidylcholine depletion and to prevent alcoholic cirrhosis in nonhuman primates. Thus, a better understanding of the pathology induced by ethanol is now generating improved prospects for therapy.
Three decades of research in ethanol metabolism have established that alcohol is hepatotoxic not only because of secondary malnutrition, but also through metabolic disturbances associated with the oxidation of ethanol. Some of these alterations are due to redox changes produced by the NADH generated via the liver ADH pathway, which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Exaggeration of the redox change by the relative hypoxia, which prevails physiologically in the perivenular zone, contributes to the exacerbation of the ethanol-induced lesions in zone III. Gastric ADH also explains first-pass metabolism by ethanol; its activity is low in alcoholics and in females and is decreased by some H2 blockers. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last 20 years have culminated in the molecular elucidation of the ethanol-inducible cytochrome P450 (P4502E1) which contributes not only to ethanol metabolism and tolerance, but also to the selective hepatic perivenular toxicity of various xenobiotics. Their activation by P4502E1 now provides an understanding for the increased susceptibility of the heavy drinker to the toxicity of industrial solvents, anesthetic agents, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and even nutritional factors such as vitamin A. Ethanol causes not only vitamin A depletion, but it also enhances its hepatotoxicity. Furthermore, induction of the microsomal pathway contributes to increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation, decreased DNA repair; it is also associated with a striking impairment of the capacity of the liver to utilize oxygen. Moreover, acetaldehyde promotes GSH depletion, free-radical-mediated toxicity, and lipid peroxidation. In addition, acetaldehyde affects hepatic collagen synthesis; both in vivo (in our baboon model of alcoholic cirrhosis) and in vitro (in cultured myofibroblasts and lipocytes); ethanol and its metabolite acetaldehyde were found to increase collagen accumulation and mRNA levels for collagen. This new understanding may eventually improve therapy with drugs and nutrients. Encouraging results have been obtained with some "super" nutrients. On the one hand, SAMe, the active form of methionine, was found to attenuate the ethanol-induced depletion in SAMe and GSH and associated mitochondrial lesions. On the other hand, phosphatidylcholine, purified from polyunsaturated lecithin, was discovered to oppose the ethanol-induced fibrosis by decreasing the activation of lipocytes to transitional cells, and possibly also by stimulating collagenase activity, an effect for which dilinoleoylphosphatidylcholine, its major phospholipid species, was found to be responsible.
The effects of Arctium lappa L. (root) on anti-inflammatory and free radical scavenger activity were investigated. Subcutaneous administration of A. lappa crude extract significantly decreased carrageenan-induced rat paw edema. When simultaneously treated with CCl4, it produced pronounced activities against CCl4-induced acute liver damage. The free radical scavenging activity of its crude extract was also examined by means of an electron spin resonance (ESR) spectrometer. The IC50 of A. lappa extract on superoxide and hydroxyl radical scavenger activity was 2.06 mg/ml and 11.8 mg/ml, respectively. These findings suggest that Arctium lappa possess free radical scavenging activity. The inhibitory effects on carrageenan-induced paw edema and CCl4-induced hepatotoxicity could be due to the scavenging effect of A. lappa.
The experiments were carried out on male rats with different sensitivity to alcohol. To assess sensitivity to ethanol effects, we have used ethanol-induced sleep time and variations in rectal temperature of alcohol-intoxicated animals. Activity of alcohol dehydrogenase, microsomal ethanol-oxidizing system, catalase and aldehyde dehydrogenase in the liver as well as ethanol and acetaldehyde levels in the blood were determined after alcohol intoxication (3.5 g/kg, i.p., 8 days). The development of alcohol tolerance was accompanied by induction of the microsomal ethanol-oxidizing system in long-sleeping rats and in short-sleeping rats as well as by an increase in ethanol and acetaldehyde levels in the blood.
The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by CCl4 or acetaminophen in a dose-dependent manner and alleviated the severity of liver damage based on histopathological observations. In an attempt to elucidate the possible mechanism(s) of this hepatoprotective effect, glutathione (GSH), cytochrome P-450 (P-450) and malondialdehyde (MDA) contents were studied. A. lappa reversed the decrease in GSH and P-450 induced by CCl4 and acetaminophen. It was also found that A. lappa decreased the malondialdehyde (MDA) content in CCl4 or acetaminophen-intoxicated mice. From these results, it was suggested that A. lappa could protect the liver cells from CCl4 or acetaminophen-induced liver damages, perhaps by its antioxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4 or acetaminophen.
Since 1922 when Wu proposed the use of the Folin phenol reagent for
the measurement of proteins (l), a number of modified analytical pro-
cedures ut.ilizing this reagent have been reported for the determination
of proteins in serum (2-G), in antigen-antibody precipitates (7-9), and
in insulin (10).
Although the reagent would seem to be recommended by its great sen-
sitivity and the simplicity of procedure possible with its use, it has not
found great favor for general biochemical purposes.
In the belief that this reagent, nevertheless, has considerable merit for
certain application, but that its peculiarities and limitations need to be
understood for its fullest exploitation, it has been studied with regard t.o
effects of variations in pH, time of reaction, and concentration of react-
ants, permissible levels of reagents commonly used in handling proteins,
and interfering subst.ances. Procedures are described for measuring pro-
tein in solution or after precipitation wit,h acids or other agents, and for
the determination of as little as 0.2 y of protein.
Pharmaceutical Botany. Taipei, National Research Institute of Chinese Medicine
- Ws Kan
Dietary fiber and fat-derivatives prevent mineral oil toxicity in rats by the same mechanism Structural transformation of lignan compounds in rat gastrointestinal tract
- T Morita
- K Ebihara
- S Kiriyama
- T Fujimoto
- T Takeda
- S Nishibe
- Y Ogihara
26 Morita T, Ebihara K, Kiriyama S. Dietary fiber
and fat-derivatives prevent mineral oil toxicity
in rats by the same mechanism. J Nutr 123:
1575–1585;1993.
27 Nose M, Fujimoto T, Takeda T, Nishibe S,
Ogihara Y. Structural transformation of lignan
compounds in rat gastrointestinal tract. Planta
Med 58:520–523;1992.