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.

Isolation and Quantitative Analysis of BACE1 Inhibitory Compounds from Cirsium maackii Flower

The purpose of our study was to evaluate anti-AD potential of Cirsium maackii flowers. MeOH extract, CH2Cl2, EtOAc, and n-BuOH fraction of this flower notably inhibited BACE1 (IC₅₀ = 76.47 ± 1.66, 22.98 ± 1.45, 8.65 ± 0.63, and 72.47 ± 3.04 µg/mL, respectively). β-amyrenone (49.70 mg) (1), lupeol acetate (1.43 g) (2), lupeol (1.22 g) (3), lupenone (23.70 mg) (4), β-sitosterol (1.01 g) (6), and β-sitosterol glucoside (13.00 mg) (7) from CH₂Cl₂, apigenin (100.20 mg) (8), luteolin (19.00 mg) (9), apigenin 7-O-glucuronide methyl ester (21.30 mg) (14), and tracheloside (53.70 mg) (5) from EtOAc, apigenin 5-O-glucoside (11.00 mg) (10), luteolin 5-O-glucoside (11.00 mg) (11) and apigenin 7-O-glucuronide (91.00 mg) (12) from n-BuOH, and luteolin 7-O-glucuronide (22.00 mg) (13) from H₂O fraction were isolated. HPLC showed high levels of 8, 9 and 12 in MeOH extract (33.07 ± 0.07, 31. 44 ± 0.17 and 16.89 ± 0.33 mg/g, respectively), EtOAc (161.01 ± 1.78, 96.93 ± 0.34 and 73.38 ± 0.06 mg/g, respectively), and n-BuOH fraction (32.18 ± 0.33, 44.31 ± 0.32 and 105.94 ± 0.36 mg/g, respectively). Since, 3 and 9 are well-known BACE1 inhibitors, the anti-AD activity of C. maackii flower might be attributable to their presence.

Protective effects of flavonoids isolated from Korean milk thistle Cirsium japonicum var. maackii (Maxim.) Matsum on tert-butyl hydroperoxide-induced hepatotoxicity in HepG2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Milk thistle leaves and flowers have been traditionally used as herbal remedy to alleviate liver diseases for decades. Korean milk thistle, Cirsium japonicum var. maackii (Maxim.) Matsum has been employed in traditional folk medicine as diuretic, antiphlogistic, hemostatic, and detoxifying agents. AIM OF THE STUDY: The aim of current investigation was to evaluate hepatoprotective properties of the MeOH extract of the roots, stems, leaves and flowers of Korean milk thistle as well as four isolated flavonoids, luteolin, luteolin 5-O-glucoside, apigenin and apigenin 7-O-glucuronide during t-BHP-induced oxidative stress in HepG2 cells. MATERIALS AND METHODS: Hepatoprotective potential of the MeOH extracts and flavonoids derived from Korean milk thistle against t-BHP-induced oxidative stress in HepG2 cells were evaluated following MTT method. Incubating HepG2 cells with t-BHP markedly decreased the cell viability and increased the intracellular ROS generation accompanied by depleted GSH levels. Protein expression of heme oxygenase (HO-1) and nuclear factor-E2-related factor 2 (Nrf-2) was determined by Western blot. RESULTS: Our findings revealed that pretreating HepG2 cells with MeOH extracts and bioactive flavonoids significantly attenuated the t-BHP-induced oxidative damage, followed by increased cell viability in a dose-dependent manner. The results illustrate that excess ROS generation was reduced and GSH levels increased dose-dependently when HepG2 cells were pretreated with four flavonoids. Moreover, Western blotting analysis demonstrated that protein expressions of Nrf-2 and HO-1 were also up-regulated by flavonoids treatment. CONCLUSIONS: These results clearly demonstrate that the MeOH extracts and flavonoids from Korean milk thistle protected HepG2 cells against oxidative damage triggered by t-BHP principally by modulating ROS generation and restoring depleted GSH levels in addition to the increased Nrf-2/HO-1 signaling cascade. These flavonoids are potential natural antioxidative biomarkers against oxidative stress-induced hepatotoxicity.

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.

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

OBJECTIVE: 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. METHODS: We used an in vitro AGE inhibition assay to evaluate the anti-diabetic complication potential of the methanol extracts of the selected Korean thistles. RESULTS: 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. CONCLUSIONS: 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.

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

OBJECTIVE@#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.@*METHODS@#We used an in vitro AGE inhibition assay to evaluate the anti-diabetic complication potential of the methanol extracts of the selected Korean thistles.@*RESULTS@#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.@*CONCLUSIONS@#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.

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

Objective:To evaluate inhibitory potential of sevenKorean thistles against the advanced glycation endproducts(AGE) formation as well as to identify responsible compounds from the most active species.Methods:We used anin vitroAGE inhibition assay to evaluate the anti-diabetic complication potential of the methanol extracts of the selectedKorean thistles.Results:Among the sevenKorean thistles, the leaves ofCirsium maackii(C. maackii) exhibited the most significant inhibitory activity againstAGE formation.By means of bioassay-directed fractionation, a lignan, chlorogenic acid and14 flavonoids were isolated from the active ethyl acetate soluble fraction of a methanol extract fromC. maackii leaves.Luteolin and its5-O-glucoside have been previously isolated; however, a lignan and13 known compounds were isolated for the first time fromC. maackiileaves in this study.Most of the isolated compounds exhibited inhibitory activities against potentialAGE formation.Among them, cernuoside was shown to be the most potentAGE inhibitor with anIC50 value of21.21 μmol/L.Most importantly, two major flavonoids, luteolin and its5-O-glucoside, also significantly inhibitedAGE formation, withIC50 values of 36.33 and37.47 μmol/L, respectively.Structure activity relationship revealed that the presence of free3' and4' dihydroxyl group in flavonoids skeleton played an important role inAGE inhibition. Conclusions:These results indicate thatC. maackii andC. maackii-derived flavonoids might be explored further to develop therapeutic agents for the prevention of diabetic complications due to their significant inhibitory activity againstAGE formation.

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

Objective: 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. Methods: We used an in vitro AGE inhibition assay to evaluate the anti-diabetic complication potential of the methanol extracts of the selected Korean thistles. Results: 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. Conclusions: 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.