• Biomedical Science Letters
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• v.14 no.3
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• pp.147-155
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• 2008

In previous works, we found that solvent extract of Opuntia humifusa Raf., a member of the lactaceae family, displayed potent anti-oxidative and anti-inflammatory activities. Thus, all solvent fractions, except for the water layer, showed potent scavenging effects. According to activity-guided fractionation, one of active radical scavenging principles in the ethyl acetate fraction was found to be taxifolin. In this study, we investigated whether taxifolin showed anti-oxidative activity. In addition, taxifolin modulated nitric oxide (NO) release and the expression of pro-inflammatory cytokine mRNA such as interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-${\alpha}$. Taxifolin showed potent anti-oxidant activity with the $IC_{50}\;of\;8.5{\pm}1.4\;and\;9.3{\pm}1.0{\mu}M$ using xanthine/xanthine oxidase (XO) assay and 2,2-Diphenyl-lpicrylhydrazyl radical (DPPH) assay, respectively. We next determined the role of taxifolin on the immunomodulating activity using murine macrophage cell line RAW264.7 cells. Taxifolin dose-dependently inhibited NO production in lipopolysaccharide (LPS)-activated RAW264.7. It also significantly blocked the expression of inducible NO synthase (iNOS) mRNA in the LPS-stimulated RAW264.7 cells. In addition, taxifolin potently suppressed the expression of IL-$1{\beta}$, IL-6 and GM-CSF mRNA in LPS-activated RAW264.7 cells, but not that of TNF-${\alpha}$ Moreover, taxifolin significantly inhibited the transcriptional activity of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein -1 (AP-1). These results suggest that taxifolin may downregulate inflammatory iNOS, IL-$1{\beta}$, IL-6 and GM-CSF gene expressions through inhibition of NF-K and AP-1 activation in LPS-stimulated RAW264.7 cells.

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.327-334
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• 2003

We evaluated the anti-arthritic effect of a new diet-supplement product containing red ginseng, glucosamine, shark cartilage, ascorbic acid and manganese chloride for the relieving arthritic symptoms. Anti-inflammatory activities of the aqueous extract of red ginseng (250 and 500 mg/kg), glucosamine (240 mg/kg) and shark cartilage (240 mg/kg) were tested individually on vascular permeability and carrageenan-induced paw edema. Glucosamine and shark cartilage showed the inhibition of vascular permeability by 29.6 and 32.9%, respectively. Red ginseng (500 mg/kg) and shark cartilage showed the inhibition of carrageenan-induced paw edema at 0.5, 1, 2 and 3 hr. The supplement (red ginseng mixture: RGM) composed of red ginseng (43.5%), glucosamine (25.0%), shark cartilage (25.0%), ascorbic acid (5.0%) and manganese chloride (1.5%) was prepared and its inhibitory activities including vascular permeability and carrageenan-induced paw edema were comparable to anti-inflammatory drugs such as diclofenac and ibuprofen. It was also tested on adjuvant-induced arthritis in rats as one of chronic arthritic tests and Randall-Selitto assay as an analgesic test. RGM showed the inhibition against the swelling of rat paws induced by Mycobacterium tuberculosis at a dose of 1,500 mg/kg. Determination of cytokines of the sera sampled from arthritis-induced animals indicated that RGM increased the levels of $interferon-{\gamma}$ and interleukin-6, representing the immunostimulatory effect by red ginseng. RGM treatment moderately reduced the production of NO in RAW 264.7 cells in a dose-dependent manner. Taken together, these results support that RGM can be applicable for the improvement of arthritic as a new diet-supplement.

• Journal of Korean Medicine for Obesity Research
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• v.17 no.1
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• pp.1-9
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• 2017

Objectives: This study was performed to identify the anti-inflammatory effect of Pulsatilla koreana (PK) methanol extract on lipopolysaccharide (LPS) induced inflammatory. Methods: There were five groups. They were control group, LPS-exposed PK methanol extract group ($0{\mu}g/ml$, $10{\mu}g/ml$, $30{\mu}g/ml$, $100{\mu}g/ml$). To measure out cytotoxicity of PK, we performed the MTT assay. To evaluate the anti-inflammatory effect of PK, we examined the inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines (interleukin $[IL]-1{\beta}$, IL-6, tumor necrosis $factor-{\alpha}$ [$TNF-{\alpha}$], IL-10). Results: 1. The extract of PK (${\sim}100{\mu}g/ml$) itself did not have any cytotoxic effect in RAW 264.7 cells. 2. The concentration of plasma NO and PGE2 in PK methanol extract group showed a lower values than those of control group. 3. The concentration of plasma $IL-1{\beta}$, plasma IL-6, and plasma $TNF-{\alpha}$ in PK methanol extract group showed a lower values than those of control group. 4. The concentration of Plasma IL-10 in PK methanol extract groups showed higher than control group; however, these values showed no significantly different. Conclusions: According to this study, the extract of PK could be used as a protective agent against inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.6
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• pp.874-885
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• 2012

In the present study, the possibility of whether the pharmacological effects of Scutellariae Radix Aqueous Extracts(SR) were favorably changed by report that lipopolysaccharide(LPS)-induced rat acute lung injury was treated with Red-Koji(Monascus purpureus 12002) fermentation. Three different dosages of Red-Koji fermented SR extract(fSR), 125, 250 and 500 mg/kg were orally administered once a day for 28 days before LPS(Escherichia coli 0111:B4) treatments, and then 5 hours after LPS treatment(500 ${\mu}g$/head, intra trachea instillation), all rats were sacrificed. Changes in the body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters(pH, $PaO_2$ and $PaCO_2$) bronchoalveolar lavage fluid(BALF) protein, lactate dehydrogenase(LDH) and proinflammatory cytokine tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), interleukin-$1{\beta}$(IL-$1{\beta}$) contents, total cell numbers, neutrophil and alveolar macrophage ratios, lung malondialdehyde(MDA), myeloperoxidase(MPO), proinflammatory cytokine TNF-${\alpha}$ and IL-$1{\beta}$ contents were observed with histopathology of the lung, changes on luminal surface of alveolus(LSA), thickness of alveolar septum, number of polymorphonuclear neutrophils(PMNs). As results of LPS-injection, dramatical increases in lung weights, pulmonary transcapillary albumin transit increases in $PaCO_2$, decreases in pH of arterial blood and $PaO_2$, increases of BALF protein, LDH, TNF-${\alpha}$ and IL-$1{\beta}$ contents, total cells, neutrophil and alveolar macrophage ratios, lung MDA, MPO, TNF-${\alpha}$ and IL-$1{\beta}$ contents increases were detected with decreases in LSA and increases of alveolar septum and PMNs numbers, respectively as compared with intact control. Especially fSR 125 mg/kg showed quite similar favorable effects on the LPS-induced acute lung injuries as compared with 60 mg/kg of ${\alpha}$-lipoic acid and 250 mg/kg of SR. The results suggest that over 125 mg/kg of fSR extracts showed favorable effects on the LPS-induced acute lung injury mediated by their antioxidant and anti-inflammatory effects. Moreover, increases of the pharmacological effects of SR on LPS-induced acute lung injury were observed by Red-Koji fermentation in this study, at least 2-fold higher.

• Food Science of Animal Resources
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• v.31 no.5
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• pp.701-709
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• 2011

This study was performed to establish an effective extraction method of pig placenta extract that could be used for a putative functional food supplement with immunomodulatory effects. In the present study, we used different temperatures (4, 37, 60, 80, and $100^{\circ}C$) and different solvents (chloroform, NaOH, and phosphate buffered saline [PBS]) to extract the pig placenta. Among the different placenta extracts yielded by the different extraction methods, placenta extract (PE) in PBS at $80^{\circ}C$ for 30 min (referred to as PE-PBS80) showed a significant increase of nitric oxide production of up to 22.97 ${\mu}M/10^5$ cells at a 1 mg/mL dose (p<0.05 ) in J774A.1 cells than other extracts and control tested. Using PE-PBS80, further animal challenges were performed to identify the immune-enhanced effects. As a result, orally administered PE-PBS80 showed a significant increase in blood T and B cell activities and immunoglobulin (IgG and IgM) production. IgG and IgM levels increased to 41.53 mg/mL at a 20 mg dose on day 7 and to 27.38 mg/mL at a 10 mg dose on day 14, respectively (p<0.05). Furthermore, PE-PBS80 was also able to significantly enhance the immune modulator cytokine levels (p<0.05) compared to the control and vehicle treatments. Among the evaluated cytokines, the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level increased to 28.89 pg/mL at extract doses of 20 and 50 mg, the interleukin-$1{\beta}$ (IL-$1{\beta}$) level increased to 21.52 pg/mL at extract doses of 10, 20, 50 and 75 mg and the interferon (IFN)-${\gamma}$ level increased to 18.24 pg/mL at extract doses of 10, 20, and 50 mg. Therefore, this study presents an effective method for extracting pig placenta extracts and also demonstrates that pig placenta extracts had significant immunomodulatory effects not only at the cellular level but also in a mouse model, suggesting that this material could be used as an excellent candidate functional food supplement.

• Journal of Environmental Health Sciences
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• v.38 no.6
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• pp.541-549
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• 2012

Objectives: This study was undertaken in order to evaluate a potential mechanism involved in gastro-intestinal problems observed in autistic subjects and uses an animal model of autism investigation. Methods: BTBR T+tf/J, a mouse strain with typical socio-behavioral characteristics of autistic subjects and FVB mice with highly social behaviors as the control strain were used. Both genders of mice aged three weeks and six months were used from four separate litters for each strain. Serum was prepared following cardiac puncture, and mesenteric lymph nodes were collected for in vitro stimulation and enumeration of major immune cell proportion. Results: The level of serum IgA was significantly enhanced in six-month-old BTBR mice compared with three-week-old BTBR, which was not observed with the FVB control mice. The serum IgE level was also higher among BTBR mice than among age-sex matched FVB mice, respectively. Considering the ratio of interleukin-4 vs interferon-gamma production from mesenteric lymph node T cells, skewedness toward type-2 reactivities was observed. In addition, the proportion of B cells in mesenteric lymph nodes was significantly higher in BTBR mice than in FVB mice. Conclusion: Upregulation of mucosal immunity related with enhanced type-2 immune reactivity observed in BTBR mice could be involved with the etiology of gastro-intestinal abnormalities in autism.

• Herbal Formula Science
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• v.12 no.1
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• pp.195-208
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• 2004

Objective: This study was conducted to investigate the effects of Aconiti Tuber on the plasma IL-6 and $TNF-{\alpha}$ level in mice stimulated by intracerebroventricular(I.C.V.) Injection of Lipopolysaccharide(LPS). Method: 6 mice were assigned to each of the normal group, the control group, and the experimental group. In the normal group only saline was administered intragastrically, and in the control group LPS was injected intracerebro-ventricularly 1 hr after intragastric administration of saline. In the experimental groups (Aconiti Tuber 0.5g/kg, Aconiti Tuber 1.0g/kg, Aconiti Tuber 3.0g/kg) each sample was administered intragastrically to mice 1 hr prior to the stimulation by LPS I.C.V. Injection. To measure the plasma IL-6 and $TNF-{\alpha}$ level of mice, their blood samples were collected from retro-orbital plexus, immediately centrifuged at $4^{\circ}C$, and plasma was removed and stored frozen at $-83^{\circ}C$ for later determination of plasma IL-6 and $TNF-{\alpha}$. Result : 1. LPS I.C.V. Injection increased plasma IL-6 level significantly in a dose-dependent manner compared with normal group(P<0.01). The plasma IL-6 concentration reached a significant maximal level about 1 hr after LPS I.C.V. Injection(P<0.001). LPS I.C.V. Injection increased plasma $TNF-{\alpha}$ level significantly in a dose-dependent manner(P<0.05). The plasma $TNF-{\alpha}$ concentration reached a significant maximal level about 1 hr after LPS I.C.V. Injection(P<0.001). 2. Sample A group to which Aconiti Tuber(0.5g/kg) was administered intragastrically 1 hr prior to the stimulation by LPS I.C.V. Injection showed insignificant lower plasma IL-6 level in 1 hr than control group(P<0.0635), and sample B group (Aconiti Tuber 1.0g/kg) showed significant lower plasma IL-6 level in 1 hr than control group(P〈0.05), and sample C group (Aconiti Tuber 3.0g/kg) showed significant lower IL-6 plasma level in 1 hr than control group(P<0.01). 3. sample A group to which Aconiti Tuber(0.5g/kg) was administered intragastrically 1 hr prior to the stimulation by LPS I.C.V. Injection showed insignificant lower plasma $TNF-{\alpha}$ level in 1 hr than control group(P>0.05), and Both sample B(1.0g/kg) and sample C(3.0g/kg) groups showed significant lower $TNF-{\alpha}$ plasma level in 1 hr than control group(P<0.01). These data revealed that Aconiti Tuber might have the anti inflammatory effect by reducing the plasma IL-6 and $TNF-{\alpha}$ level in a dose dependent manner in mice LPS I.C.V. Injection.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.911-917
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• 2016

Lespedeza cuneata G. Don is an edible perennial herb used in traditional Korean medicine. We investigated the anti-proliferative properties and mechanism of L. cuneata extract. The ethanolic extract of L. cuneata dose-and time-dependently inhibited human colorectal cancer cell proliferation. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to test the effect of the extract on proliferation of HT-29 colorectal cancer cells. The extract inhibited HT-29 cell proliferation with an $IC_{50}$ value of $554.26{\pm}8.81{\mu}g/mL$. L. cuneata extract suppressed production of pro-inflammatory cytokines interleukin-6 and tumor necrosis $factor-{\alpha}$. Apoptosis was evaluated by analysis of DNA fragmentation, poly(ADP-ribose) polymerase cleavage, caspase-3 activity, and protein expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2). Our results demonstrated that the extract induced DNA fragmentation and characteristic morphological changes associated with apoptosis in HT-29 colorectal cancer cells. The extract also time- and dose-dependently up-regulated expression of the Bax and down-regulated expression of the Bcl-2. Furthermore, the extract dose- and time-dependently enhanced caspase-3 activity. Our findings provide evidence that L. cuneata extract may mediate its anti-proliferative effect via modulation of apoptosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.8
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• pp.1099-1106
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• 2016

The objective of this study was to evaluate the immunomodulatory activity of crude polysaccharide separated from Cudrania tricuspidata leaf. C. tricuspidata polysaccharide (CTP) was extracted by ethanol precipitation. Immunomodulation activity was tested in macrophage cells (RAW 264.7 and bone-marrow derived macrophage) and splenocytes. CTP treatment significantly increased cell proliferation up to $250{\mu}g/mL$ in both RAW 264.7 and bone-marrow derived macrophages. In this concentration range (below $250{\mu}g/mL$), nitric oxide and cytokine [tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6] production also significantly increased. Similarly, splenocyte proliferation dosedependently increased except for the $1,000{\mu}g/mL$ treated group. Regarding cytokine production activity in splenocytes, CTP treatment significantly increased production of Th 1 type cytokines [interferon $(IFN)-{\gamma}$] production but not Th 2 type cytokines (IL-4). Therefore, the results indicate that CTP may have a potential effect on immunomodulatory activity in various immune cells, and this is useful for development of immune enhancing adjuvant materials as a natural ingredient.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.505-513
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• 2018

Objective: This experiment investigated the effects of aflatoxin B1 (AFB1) alone or mixed with ochratoxin A (OTA) and/or zearalenone (ZEA) on the metabolism, immune function, and antioxidant status of dairy goats. Methods: Fifty lactating Laoshan dairy goats were randomly assigned to one of five treatment groups (n = 10) for 14 days. Goats were fed no additive (control) or administered with $50{\mu}g\;AFB1/kg$ dry matter (DM) (AFB1), $50{\mu}g\;AFB1/kg$ $DM+100{\mu}g\;OTA/kg$ DM (AFB1+OTA), $50{\mu}g\;AFB1/kg$ $DM+500{\mu}g\;ZEA/kg$ DM (AFB1+ZEA), or $50{\mu}g\;AFB1/kg$ $DM+100{\mu}g\;OTA/kg$ $DM+500{\mu}g\;ZEA/kg$ DM (AFB1+OTA+ZEA). Results: Dry matter intake and milk production were lower in goats fed AFB1+OTA+ZEA than in controls. Supplementation with AFB1, OTA, and ZEA significantly decreased red blood cell count, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean platelet volume, and significantly increased white blood cell count, when compared with the control group. Compared with control, the combination of AFB1, OTA, and ZEA significantly increased alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, total bilirubin (TBIL), interleukin-6, and malondialdehyde (MDA), but significantly reduced immunoglobulin A concentration, the activities of superoxide dismutase (SOD) and glutathione peroxides (GSH-Px), and total antioxidant capacity (T-AOC) in serum. Administration of AFB1 combined with OTA led to higher ALP, ALT, TBIL, and MDA, as well as lower milk production, SOD and GSH-Px activities, and T-AOC, than administration of AFB1 combined with ZEA. Conclusion: The mixture of AFB1, OTA, and ZEA exerted the greatest adverse effects on dairy goats, meanwhile the deleterious damage of the other mycotoxin combinations were in varying degrees. The findings of this study could provide guidance for the prevention and treatment of the consequences of contamination of animal feeds with combinations of mycotoxin.