Korean Thistle Research Articles

Plants with potential anti-ulcerogenic activity and possible mechanism of actions based on their phyto-constitutional profile.

Gastric ulcer, the most common disorder of the digestive tract is formed due to an imbalance between acid and mucus content of the stomach. However, the currently used western therapeutic regimens have many drawbacks like adverse effects, recurrence of gastric ulcers, are expensive, and also, may have interactions with other drugs. Hence, there is a need for effective alternative therapy. Medicinal herbs have been used since ancient times to treat several diseases and are also evidenced to be effective against gastric ulcers. It is also evident that medicinal herbs have been proved to be equally effective or superior as compared to the existing synthetic medicines. In this review, five herbs have been taken into consideration and assumed to be effective against gastric ulcers. Abrus mollis, Korean Thistle (Cirsium japonicum var. maackii), Astralagus complanatus Bunge, Bauhinia monandra, and Embelia ribes Burm f. are the herbs whose data is been collected and reviewed for their potential gastro-protective action. Although, their side effects and toxicity profile need to be further evaluated. Hence, the purpose of this review is to gather evidence of these five medicinal herbs and their probable mechanism of action against gastric ulcers based on their phyto-constitutional profile.

Cirsium Setidens Extracts Abrogate Actin Ring Formation and Bone-Resorbing Osteoclasts Through Inhibition of Core-Linked CD44 and Diffuse Cloud-Associated αvβ3 Integrin

Abstract Objectives Since enhanced bone resorption cause skeletal diseases, there is a growing need in therapeutics for combating bone-resorbing osteoclasts. Botanical antioxidants are being increasingly investigated for their health-promoting effects on bone. Cirsium setidens (Korean thistle) contains linarin, luteolin, pectolinarin, hispidulin, and apigenin with antioxidant and hepatoprotective effects. This study examined whether 1–20 μg/ml Cirsium setidens extracts (CSE) inhibited osteoclastogenesis of RANKL-exposed RAW 264.7murine. Methods RAW 264.7 murine macrophages were incubated with 1–20 μg/ml CSE for 5 days in the presence of 50 ng/ml RANKL. Tartrate-resistance acid phosphatase (TRAP) staining and its activity measurement were performed. Western blotting was done with target proteins involved in the osteoclast activation. Results Nontoxic CSE attenuated the RANKL-induced macrophage differentiation into multinucleated osteoclasts, and curtailed bone resorption through reducing lacunar acidification and bone matrix degradation. Linarin and pectolinarin were identified as major components of CSE, where linarin but not pectolinarin were effective in inhibiting formation of TRAP-positive osteoclasts. Linarin-rich CSE diminished the induction of αvβ3 integrin-associated proteins of paxillin, Pyk2 and gelsolin. Additionally, CSE deterred actin ring formation with attenuation of induction of F-actin-enriched podosome core proteins of CD44, Arp2/3 and cortactin. Nontoxic linarin and its aglycone acacetin reduced focal contact of osteoclasts to RGD peptide. The inhibition of integrin-mediated actin ring formation by CSE entailed disruption of TRAF6-c-Src-PI3K signaling of osteoclasts. Conclusions CSE was effective in retarding focal adhesion to bone matrix and active bone resorption of osteoclast via inhibition of core-linked CD44 and diffuse cloud-associated αvβ3 integrin. Funding Sources This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2019R1A2C1003218).

Inhibition of Osteoclast Activation and Bone Resorption by Korean Thistle Ethanol Extracts in Receptor Activator of NF-κB Ligand-differentiated Murine Macrophages (P06-061-19)

ObjectivesEnhanced bone resorption due to osteoclast activation cause skeletal diseases such as osteoporosis. Botanical antioxidants are being increasingly investigated for their health-promoting effects on bone. Korean thistle (Cirsium setidens Nakai), a wild perennial, is widely consumed as a food and traditional medicine in Korea and contains flavone-type flavonoids of luteolin, apigenin and acacetin with anti-inflammatory and antioxidant activities. This study examined whether Korean thistle extracts and their component acacetin inhibited osteoclast activation in receptor activator of NF-κB ligand (RANKL)-differentiated murine macrophages. MethodsRAW 264.7 murine macrophages were incubated with 10–20 μg/ml Korean thistle extracts and 20 μM acacetin for 5 days in the presence of 50 ng/ml RANKL. Tartrate-resistance acid phosphatase (TRAP) staining and its activity measurement were performed. Western blotting was done with target proteins involved in the osteoclast activation. ResultsNon-toxic Korean thistle extracts inhibited RANKL-induced formation of multinucleated osteoclasts and diminished TRAP activity enhanced in the osteoclast differentiation process. When Korean thistle extracts were treated to RANKL-exposed macrophages, the bone-resorbing activity was highly attenuated. The treatment of murine macrophages with 20 μg/ml Korean thistle extracts reduced cellular expression of carbonic anhydrase II, vacuolar-type H(+)-ATPase D2 and integrin αvβ3 elevated by RANKL, all involved in the bone resorption. Additionally, Korean thistle extracts reduced the expression of paxillin and cortactin elevated by RANKL, being concurrent with inhibition of induction of TRAF6, Src and PI3K. Korean thistle extracts blocked the formation of actin rings of osteoclasts enhanced by RANKL. Furthermore, the Korean thistle component, acacetin, diminished RANKL-promoted TRAP activity. ConclusionsKorean thistle extracts and acacetin deterred preosteoclasts from the cell-cell fusion and the organization of the cytoskeleton for bone resorption. Korean thistle and its effective flavonoid acacetin could be natural therapeutic agents combating osteoclastogenesis. Funding SourcesThis work (Grants No. C0501612) was supported by project for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Ministry of SMEs and Startups in 20.

Korean Thistle (Cirsium japonicum var. maackii (Maxim.) Matsum.): A Potential Dietary Supplement against Diabetes and Alzheimer's Disease.

In the search for natural products having a dual inhibitory action on diabetes and Alzheimer’s disease, this study investigated the activity of different parts of Korean thistle (Cirsium japonicum var. maackii (Maxim.) Matsum), and its fractional constituents by in vitro enzymatic and in silico molecular docking studies. Cirsium maackii has been used as a traditional medicine for the treatment of several diseases. The ethyl acetate and dichloromethane fractions of a leaf extract showed α-glucosidase and BACE1 inhibitory activity, respectively. Furthermore, the isolated compound, luteolin, exhibited concentration-dependent non-competitive inhibition against both α-glucosidase and BACE1 (IC50 = 51.27 ± 1.23 and 13.75 ± 0.26 μM; Ki value = 52.04 and 14.76 μM, respectively). Moreover, docking studies showed that luteolin formed a strong hydrogen bond with the peripheral binding amino acid residues, and hydrophobic interactions with the α-glucosidase and BACE1 enzymes. Therefore, Korean thistle may act as an important dietary supplement against diabetes and Alzheimer’s disease, especially the leaves, because of the preponderance of the active component, luteolin, making Korean thistle a promising candidate for more detailed in vitro and in vivo studies.

Discovery of a Highly Potent Tyrosinase Inhibitor, Luteolin 5-O-β-d-Glucopyranoside, Isolated from Cirsium japonicum var. maackii (Maxim.) Matsum., Korean Thistle: Kinetics and Computational Molecular Docking Simulation

In the present study, the natural flavonoid luteolin 5-O-β-d-glucopyranoside isolated from the Korean thistle, Cirsium japonicum var. maackii (Maxim.) Matsum., for the first time, found to be a strong competitive inhibitor against mushroom tyrosinase (IC50 = 2.95 ± 0.11 μM, Ki = 3.02 μM for l-tyrosine; IC50 = 8.22 ± 0.18 μM, Ki = 11.56 μM for l-3,4-dihydroxyphenyl-alanine), which outperformed luteolin and 5-deoxy luteolin (3′,4′,7-trihydroxyflavone), showing noncompetitive and competitive inhibition only in l-tyrosine, respectively, emphasizing the importance of glycosylation at 5-OH position of luteolin. Furthermore, molecular modeling of luteolin 5-O-β-d-glucopyranoside showed strong H-bond interaction with Arg268 and peroxide ion (Per402) present between the copper ions. Additionally, the luteolin 5-O-β-d-glucopyranoside–tyrosinase complex was stabilized by electrostatic and hydrophobic interactions formed with key catalytic residues; however, in luteolin, these were lacking. Therefore, Cirsium maackii...

The effects of MS-10 dietary supplement, mixture of Korean thistle and thyme extracts, on bone health, and symptoms in menopausal women

In menopausal women, estrogen deficiency closely affects bone health. Previous studies report that MS-10, a combined extract of Cirsium japonicum and Thymus vulgaris, increases the efficiency of estrogen by activating the estrogen receptor. Here, the ability of MS-10 to enhance bone health and quality of life in women with menopausal symptoms was tested. Treatment with MS-10 induced alterations in the gene expression profile related with bone health of SaOS-2 osteoblast-like cells. MS-10 increased alkaline phosphatase (ALP) activity and osteocalcin, and reduced tartrate-resistant acid phosphatase (TRACP) activity in osteoblast-like cells. A clinical study showed that treatment with MS-10 (500 mg/day for 3 months) led to a significant decrease in ALP and osteocalcin levels. Also, women’s scores on the Menopause-Specific Quality of Life questionnaire that takes into account vasomotor, psychosocial, physical, and sexual health, improved by 18.8%. In conclusion, the herbal material MS-10 may improve menopausal symptoms, including bone health.

Optimization of alkaline hot-water extraction conditions for production of polyphenolic compounds and flavonoids from Korean thistle (Cirsium japonicum)

Optimization of alkaline hot-water extraction conditions for production of polyphenolic compounds and flavonoids from Korean thistle (Cirsium japonicum)

Response of Major Wild Leafy Vegetables to ControlledAtmosphere Storage

The effects of controlled atmosphere (CA) on quality maintenance and storage potential were estimated in four major, wild, leafy vegetables, specifically focusing on the incidence of CA-related disorders. After harvest, vegetables were precooled to 4-5°C with a pilot-scale pressure pre-cooler. As a control treatment, perforated modified atmosphere packaging (MAP) was performed using 20 × 25 cm (W × L) polypropylene film bags with 8 punch holes. For CA treatments, two regimens were applied as 1% O2combined with 5% or 10% CO2atmospheric compositions. Discoloration was evaluated during storage and on the shelf. The resulting storage potential was determined by overall marketability. The vegetables used in this study could be sorted into two groups based on their sensitivity to CA or MA-related disorders. Aster scaber (edible aster) and Cirsium setidens (Korean thistle) were sensitive to carbon dioxide and/or low oxygen injuries. As a typical symptom of physiological disorder, blackening discoloration increased under high carbon dioxide conditions over 5%. Storage potential of vegetables at 0°C in the MAP condition was approximately 3 weeks for edible aster and 4 weeks for Korean thistle leaves. Allium ochotense (myeongyi) and Heracleum moellendorffii (East Asian hogweed) did not show low oxygen and high carbon dioxide injuries even under the 1% O2 + 10% CO2 regimen. Storability of these two commodities was longer than 4 weeks under both MAP and CA conditions. In myeongyi leaves, CA effects were clearly observed under 1% O2 + 5-10% CO2 conditions while in East Asian hogweed leaves, the beneficial effects were similar to those in MAP storage.

Protective effect of cirsimaritin against streptozotocin-induced apoptosis in pancreatic beta cells

Maintaining glucose homoeostasis is essential for the survival of cells. Despite the various health benefits of Korean thistle (Cirsium japonicum var. maackii), their effects on pancreatic β-cell apoptosis in type 1 diabetes mellitus and the underlying mechanisms remain unclear, and experimentally investigated in this study. The effects of C. japonicum var. maackii and its active component cirsimaritin against streptozotocin (STZ)-induced cytotoxicity were assessed in INS-1 cells. By Western blotting analysis, protein expressions related to apoptosis were evaluated. The involvement of apoptosis was also confirmed with image-based cytometric assay and caspase activity tests. Cirsium japonicum var. maackii extract and cirsimaritin in non-toxic concentrations improved cell viability to near normal levels and protected INS-1 cells against STZ-induced damage. In addition, cirsimaritin reduced the intracellular oxidative stress induced by STZ. Cirsimaritin effectively suppressed apoptosis in pancreatic β cells by decreasing the activation of caspase-8 and caspase-3, BID and the DNA repair protein poly (ADP-ribose) polymerase (PARP) and increasing anti-apoptotic BCL-2 protein expression. This study demonstrates the therapeutic potential and action mechanism of cirsimaritin for the prevention and treatment of type 1 diabetes mellitus.

Luteolin 5-O-glucoside from Korean Milk Thistle,Cirsium maackii, Exhibits Anti-Inflammatory Activity via Activation of the Nrf2/HO-1 Pathway

Luteolin 5-O-glucoside is the major flavonoid from Korean thistle, Cirsium maackii. We previously reported the anti-inflammatory activities of luteolin 5-O-glucoside in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In this study, we determined the anti-inflammatory mechanisms of luteolin 5-O-glucoside through the inhibition of nitric oxide (NO) production in vitro and in vivo. Results revealed that luteolin 5-O-glucoside dose-dependently inhibited NO production and expression of iNOS and COX-2 in LPS-induced RAW 264.7 cells. Luteolin 5-O-glucoside also significantly inhibited the translocation of NF-κB, the activation of MAPKs, and ROS generation in LPS-induced RAW 264.7 cells. In addition, protein expressions of Nrf-2 and HO-1 were also upregulated by luteolin 5-O-glucoside treatment. Moreover, luteolin 5-O-glucoside inhibited λ-carrageenan-induced mouse paw edema by 65.34% and 48.31% at doses of 50 and 100 mg/kg body weight, respectively. These findings indicate potential anti-inflammatory effect of luteolin 5-O-glucoside particularly by downregulating NF-κB and upregulating HO-1/Nrf-2 pathway.

Effects of Pre-treatment on the Quality of Dried Korean Thistle (Cirsium Setidens Nakai)

Effects of Pre-treatment on the Quality of Dried Korean Thistle (Cirsium Setidens Nakai)

Inhibition of advanced glycation endproducts formation by Korean thistle, Cirsium maackii.

To evaluate inhibitory potential of seven Korean thistles against the advanced glycation endproducts (AGE) formation as well as to identify responsible compounds from the most active species. We used an in vitro AGE inhibition assay to evaluate the anti-diabetic complication potential of the methanol extracts of the selected Korean thistles. Among the seven Korean thistles, the leaves of Cirsium maackii (C. maackii) exhibited the most significant inhibitory activity against AGE formation. By means of bioassay-directed fractionation, a lignan, chlorogenic acid and 14 flavonoids were isolated from the active ethyl acetate soluble fraction of a methanol extract from C. maackii leaves. Luteolin and its 5-O-glucoside have been previously isolated; however, a lignan and 13 known compounds were isolated for the first time from C. maackii leaves in this study. Most of the isolated compounds exhibited inhibitory activities against potential AGE formation. Among them, cernuoside was shown to be the most potent AGE inhibitor with an IC50 value of 21.21 μ mol/L. Most importantly, two major flavonoids, luteolin and its 5-O-glucoside, also significantly inhibited AGE formation, with IC50 values of 36.33 and 37.47 μ mol/L, respectively. Structure activity relationship revealed that the presence of free 3' and 4' dihydroxyl group in flavonoids skeleton played an important role in AGE inhibition. These results indicate that C. maackii and C. maackii-derived flavonoids might be explored further to develop therapeutic agents for the prevention of diabetic complications due to their significant inhibitory activity against AGE formation.

Anti-inflammatory activity of Korean thistle Cirsium maackii and its major flavonoid, luteolin 5-O-glucoside

The anti-inflammatory activity of whole Cirsium maackii (family Compositae) plants and of its major flavonoid, luteolin 5-O-glucoside, was evaluated for their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein expression, and tert-butylhydroperoxide (t-BHP)-induced reactive oxygen species (ROS) generation in RAW 264.7 murine macrophage cells. The methanolic extract of C. maackii showed strong anti-inflammatory activity, and was thus fractionated with several solvents. The ethyl acetate-soluble fraction, exhibiting the highest anti-inflammatory activity potential, was further to yield a major flavonoid, luteolin 5-O-glucoside. We found that luteolin 5-O-glucoside, at a non-toxic concentration, inhibited LPS-induced NO production and t-BHP-induced ROS generation in a dose-dependent manner in RAW 264.7 cells. It also suppressed the expression of iNOS and COX-2 in LPS-stimulated macrophages. Furthermore, the efficacies of the methanolic extract of C. maackii in inhibiting both NO and ROS were attributed to its flavonoid content by HPLC analysis. These results indicated that C. maackii whole plants and its flavonoids inhibit the expression of iNOS and COX-2 in through the inhibition of ROS generation, and therefore can be considered as a useful therapeutic and preventive approach for the treatment of various inflammatory and oxidative stress-related diseases.

Three Alternative Crops to Reduce Soil Erosion for Mountain Agriculture

One of the problems for cultivating crops in the mountainous highland is soil erosion and nutrients runoff. Alternative cropping ways were searched to reduce soil erosion and to ensure farm income in the mountainous highland agricultural region. Three edible wild plants including goatsbeard, Korean thistle, and aster, were selected to test as alternative crops to reduce soil erosion in mountain agriculture of highland area. In the first year, the soil losses from the alternative cropping were 26 to 63 percents of the soil loss from summer radish cultivated by conservation tillage with contour and plastic film mulching. The relative soil losses in the second year ranged from 2.8 to 5.5 percents in comparison with radish cultivation. Rapid surface coverage contributed to successive soil loss protection by these alternative crops. Farm net profit of these crops was greater than that of radish. Monitoring of yields of Korean thistle or aster for further experiments, however, might be necessary for economic cultivation due to yield reduction caused by consecutive production.

Quantitative HPLC analysis of two key flavonoids and inhibitory activities against aldose reductase from different parts of the Korean thistle, Cirsiummaackii

Previously, the correlation between antioxidant activity and HPLC profiles of several Korean thistles has been recognized. In our ongoing study of the comparative evaluation of Korean thistles, we chose Cirsium maackii to assess the antioxidant and aldose reductase (AR) inhibitory activities of its varying parts, including the leaves, roots, stems, and flowers, along with two major components, luteolin 5- O-β- d-glucopyranoside ( 1) and the aglycone luteolin ( 2). In order to determine selective and efficient usage of the individual parts, HPLC quantitative analysis of the two key flavonoids of each C. maackii part has been performed for the first time. From the results of the comparative evaluation between the oxidative stress-related diabetic complications and quantitative phytochemical analysis from various parts of C. maackii, the content of 1 and 2 might contribute to the antioxidant and AR inhibitory activities of this thistle, clearly suggesting their potential for use in the development of therapeutic or preventive agents for diabetic complications and oxidative stress-related diseases. Furthermore, our present study will pave the way of the guidelines for the efficacy and differentiation and standardization of individual parts of this herbal material, and as such, this bioactive thistle could serve as an alternative source of 1 and 2.