• Toxicological Research
• /
• v.17
• /
• pp.271-280
• /
• 2001

We report on the applicability oj a method recently developed in our laboratory for measuring the antioxidant potential of isolated chemicals and extracts derived from natural products. Peroxyl radicals generated by thermal homolysis of 2,2'-azobis-amidinopropane (ABAP) oxidize $\alpha$-keto-${\gamma}$-methiolbutyric acid (KMBA) to ethylene, which is monitored by gas chromatography. Inhibition of ethylene formation in the presence of antioxidants that compete with KMBA for peroxyl radicals is the basis of the Total Oxyradical Scavenging Capacity Assay (TOSCA; Winston et al., 1998). Antioxidative activities of water-soluble extracts of American green tea, the anti-hepatotoxic flavonolignan from milk thistle (Silybum marianum) silybin, Ginkgo biloba extract EGb 761, and a series of naturally occuring sesquiterpene lactones (all ger-macranolides found in in fungi, liverworts, and plants) were studied. The specific TOSC value per $\mu$M silybin was 5.2, which is essentially comparable to that of Trolo $x^{ⓡ}$, a water-soluble vitamine E analog. Tea and Ginkgo extracts exhibited potent peroxyl radical scavenging capacity with values, respectively of =1700 and 1000 $\mu$mols Trolo $x^{ⓡ}$ equivalent per gram dry matter. The known anti-inflammatory activity of some germacranolides prompted study of their antioxidant capacity. None of the lactones exhibited antioxidant capacity toward peroxyl radicals comparable to Trolo $x^{ⓡ}$; costunilide, the most lipophilic, had a TOSC value = to glutathione. The potential role of peroxyl radicals in lipidperoxidation, other cellular damage, and var-ious disease states suggest a possible preventive role for silybin, green tea and Ginkgo biloba in oxidative stress caused by these free radical species.ecies.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.1
• /
• pp.117-124
• /
• 2017

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interferon (IFN)-${\gamma}$, and interleukin (IL)-$1{\beta}$] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-${\alpha}$; 5 ng/ml, IFN-${\gamma}$; 5 ng/ml, and IL-$1{\beta}$; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

• Korean Journal of Clinical Laboratory Science
• /
• v.50 no.3
• /
• pp.337-344
• /
• 2018

Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.45 no.2
• /
• pp.209-216
• /
• 2019

Ultraviolet rays (UV) cause photoaging by inducing skin photodamages such as erythema and sunburn. Silymarin is a mixture of antioxidant polyphenols extracted from Silybum marianum fruit (S. m), which is known as milk thistle. It is known to protect skin tissues from UV treatment and antioxidant effects. In this study, we aimed to identify the photoprotective effects of S. m extract, which has silymarin in the epidermis layer of the skin. We found that the extract can function as a UV filter, so it can reduce DNA damage by UV treatment. Especially, we found that, in the stratum corneum, the extract can suppress the protein carbonylarion and DNA damages caused by suberythemal dose of UV treatment which does not induce erythema in the skin. UV treatment also increased protein carbonylation levels in the stratum corneum by oxidation, but it was prevented by applying the extract. The extract can absorb UV with minimal phototoxicity. Together, our study suggests that S. m extract can be used as a photo-protective ingredient to avoid photoaging of the skin.

• Journal of Life Science
• /
• v.33 no.10
• /
• pp.776-782
• /
• 2023

Silymarin, which is derived from dried Silybum marianum (milk thistle) seeds and fruits, possesses various beneficial properties, such as hepatoprotective, antioxidative, anti-inflammatory, and anticancer activity. This research aimed to explore the antioxidative activity of silymarin against oxidative stress and understand its molecular mechanism in RAW 264.7 cells. The study employed cell viability and reactive oxygen species (ROS) formation assays and western blot analysis. The results demonstrated that silymarin effectively reduced intracellular ROS levels induced by lipopolysaccharide (LPS) in a dose-dependent manner without causing any cytotoxic effects. Moreover, silymarin treatment significantly upregulated the expression of heme oxygenase (HO)-1, a phase II enzyme known for its potent antioxidative activity. Additionally, silymarin treatment significantly induced the expression of nuclear factor-erythroid 2 p45-related factor (Nrf) 2, a transcription factor responsible for regulating antioxidative enzymes, which was consistent with the upregulated HO-1 expression. To investigate the involvement of key signaling pathways in maintaining cellular redox homeostasis against oxidative stress, the phosphorylation status of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) was estimated by western blot analysis. The results showed that silymarin potently induced HO-1 expression, which was mediated by the phosphorylation of p38 MAPK. To further validate the antioxidative potential of silymarin-induced HO-1 expression, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was employed and attenuated by silymarin treatment, as identified by a selective inhibitor for each signaling molecule. In conclusion, silymarin robustly enhanced antioxidative activity by inducing HO-1 via the Nrf2/p38 MAPK signaling pathway in RAW 264.7 cells.

• Journal of Life Science
• /
• v.27 no.4
• /
• pp.442-449
• /
• 2017

We analyzed the content of total phenolic and silymarin compounds of Cirsium japonicum (CJ), and its antioxidant activities and Liver protective effects were compared with those of Silybum marianum (SM). The total phenolic content in the aerial part ($97.22{\pm}5.51mg/g$) of CJ is higher than that in the underground part ($85.32{\pm}3.06mg/g$). The total silymarin content of CJ was 55.56% of SM, with the underground part ($0.47{\pm}0.03mg/g$) having higher content than the aerial part ($0.18{\pm}0.02mg/g$). The antioxidant activity of CJ was generally slightly lower than that of milk thistle, and the underground part of CJ generally had higher activity compared to the aerial part. When CJ extracts were processed at 1 mg/ml, DPPH activities were $83.76{\pm}0.60$ and $88.28{\pm}0.17%$, and FRAP activities were $77.63{\pm}0.70$ and $82.83{\pm}0.39%$ for extracts from aerial part and underground part, respectively. ABTS activities were $68.60{\pm}1.24$ and $63.41{\pm}0.57%$ for underground and aerial part respectively when extracts were processed at 0.1 mg/ml. The Liver protective effects of CJ were higher in the extracts from underground part compared to the aerial part, Liver cells were damaged by treating them with t-BHP, $H_2O_2$ and Ethanol, and then they were treated with 0.2 mg/ml CJ extracts. The survival rates of the damaged liver cells were $49.58{\pm}0.34$, $76.87{\pm}1.10$ and $71.73{\pm}0.58%$ respectively, which were higher than the cells not treated with extracts.