• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.639-652
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• 2006

Objective : The etiology of chronic prostatitis is likely multifactorial, resulting from either a cascade of events after an initiating factor or from a variety of etiologic mechanisms. There is substantiating evidence to support the role of the inflammatory responses in its pathogenesis, and the clinical value in the evaluation of therapeutic efficacy. Forsythiae Frucus has been traditionally used in treatment of inflammatory diseases, including of prostatitis and urinary tract inflammation. In this study, we investigated the effects of Forsythiae Frucus on inflammatory cytokines and cyto-pathological alternation in the rat model of chronic non-bacterial prostatitis induced by castration and $17{\beta}$-estradiol treatment. Methods : Two-month-old rats were treated with $17{\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis. which is similar to human chronic prostatitis in histopathological profiles. Forsythiae Frucus as an experimental specimen, and testosterone as a positive control, were administered orally. The prostates were evaluated by histopathologlcal parameters including the epithelial score and epithelio-stromal ratio for glandular damage. and the expression of inflammatory cytokine genes including interleukin (IL)-$1{\beta}$, IL-5, IL-12, tumor necrosis factor (TNF)-$\alpha$. eotaxin, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(cox-2). Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation. the rats treated with Forsythiae Frucus showed a diminished range of tissue damage. Epithelial score was improved in the Forsythiae Frucus group over that of the control (P<0.05). The epithelia-stromal ratio was lower in the Forsythiae Frucus group when compared to that of the control (P<0.05). In the reverse transcription-polymerase chain reaction (RT-PCR) of inflammatory cytosine genes. Forsythiae Frucus inhibited the expression of IL-$1{\beta}$, TNF-$\alpha$, iNOS, cox-2 genes, while it modulated the expression of IL-5, which is an anti-inflammatory cytokine. Conclusions : These findings suggest that Forsythiae Frucus may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the immune modulation including the suppression of inflammatory cytokines and increase of anti-inflammatory cytokines. From theses results. we suggest that Forsythiae Frucus could be a useful remedy agents for treating chronic non-bacterial prostatitis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.902-908
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• 2006

Tetrandra is the root of Stephania tetrandra 5. Moore (family Menispermaceae), or of Aristolochia frangchi Wu (family Aristolochiaceae). It is a Differ-flavored and cold-property herb acting on the urinary bladder, kidney and spleen meridiands. Known biological effects of this herb are expelling wind to relieve pain and inducing diuresis to alleviate edema. This herb also has anti-inflammatory and anti-hypersensitivity actions. Recent studies have shown that Stephanniae Tetrandrae Radix has antimicrobial effects, namely, a protective effect on acute renal failure induce by gentamicin sulfate and a suppressive effect against clostridium perfringes. However, there is a lack of studies concerning the immunological activities of this herb. The present study was conducted to evaluate the immunological activities of Stephanniae Tetrandrae Radix on the regulatory mechanisms of cytokines and nitric oxide (NO) in Raw 264.7 cells. Cell viability was measured by MTT assay after the treatment of Stephanniae Tetrandrae Radix extract (STRE) and NO production was monitored by measuring the nitrite content in culture medium. COX-2 and iNOS were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidences that STRE inhibited the production of nitrite and nitrate (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta})$ and interleukin-6 (IL-6) in Raw 264.7 cells activated with lipopolysaccharide (LPS). These findings showed that STRE could produce some anti-inflammatory effects which might play a role in adjunctive therapy in Gram-negative bacterial infections.

• Journal of Life Science
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• v.18 no.4
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• pp.537-541
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• 2008

White adipose tissue is now recognized as an important endocrine organ which secretes various signal factors and proteins termed 'adipokine'. Haptoglobin (Hp), which has been known as an acute phase protein, belongs to the adipokine. However, the function of Hp in adipose tissue remains unclear. To verify the role of Hp in preadipocytes, in this study, 3T3-L1 preadipocyte cells were stably transfected with human Hp gene and Hp-overexpressing cells were made. The Hp had no effect on cell growth of preadipocytes. By RT-PCR and Western blot analysis, the Hp inhibited gene expression of IL-6 and COX-2 and enhanced HO-1 synthesis in preadipocytes. Moreover, invasion assay showed the Hp suppressed migration of monocytes to preadipocytes. These findings suggest that the Hp may inhibit an inflammatory reaction in adipose tissue by regulating the expressions of pro-inflammatory and anti-inflammatory mediators, and by repressing monocytes/macrophages infiltration.

• Journal of Marine Bioscience and Biotechnology
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• v.13 no.2
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• pp.86-93
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• 2021

A high salt diet contributes to kidney damage by causing hypoxia and oxidative stress. Recently, an increase in dietary salt has been reported to induce an inflammatory phenotype in immune cells, further contributing to kidney damage. However, studies on the exact mechanism and role of a high salt diet on the inflammatory response in the kidneys are still insufficient. In this study, a cisplatin-induced acute kidney injury model using C57BL/6 mice was used to analyze the effect of salt intake on kidney injury. Results showed that high salt administration aggravated kidney edema in mice induced by treatment with cisplatin. Moreover, the indicators of kidney and liver function impairment were significantly increased in the group cotreated with high salt compared with that treated with cisplatin alone. Furthermore, the exacerbation of kidney damage by high salt administration was also associated with a decrease in the number of cells in the immune regulatory system. Additionally, high salt administration further decreased renal perfusion functions along with increased cisplatin-induced damage to proximal tubules. This was accompanied by increased expression of T cell immunoglobulin, mucin domain 1 (a biomarker of kidney injury), and Bax (a pro-apoptotic factor). Moreover, cisplatin-induced expression of proinflammatory mediators and cytokines, including cyclooxygenase-2 and tumor necrosis factor-α in kidney tissue, was further increased by high salt intake. Therefore, these results indicate that the kidney's inflammatory response by high salt treatment can further promote kidney damage caused by various pathological factors.

• Journal of Korean Medicine Rehabilitation
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• v.29 no.2
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• pp.115-133
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• 2019

Objectives The purpose of this study was to evaluate the effects of Curcumae Longae Rhizoma pharmacopuncture on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injection of MIA ($50{\mu}L$ with 80 mg/mL) into knee joint cavity of rats. Rats were divided into 6 groups. Normal group was injected by normal saline into knee joint cavity only. Control group was induced for osteoarthritis by MIA and orally administered with distilled water. Normal Saline group was induced for osteoarthritis by MIA and injected with normal saline $100{\mu}L$. Positive comparison group was injected with MIA and orally administered with indomethacin 5 mg/kg. Curcumae Longae Rhizoma pharmacopuncture low concentration (CL) group was induced for osteoarthritis by MIA and injected with Curcumae Longae Rhizoma pharmacopuncture low concentration $100{\mu}L$. Curcumae Longae Rhizoma pharmacopuncture high concentration (CH) group was induced for osteoarthritis by MIA and injected with Curcumae Longae Rhizoma pharmacopuncture high concentration $100{\mu}L$. Curcumae Longae Rhizoma pharmacopuncture was injected at ST35 and EX-LE4 each group (CL, CH). After that, hind paw weight distribution was measured and oxidative stress biomarker in serum, liver function biomarker in serum, western blot analysis were measured. Histological analysis of knee joint tissue was performed by hematoxylin and eosin staining, Safranin-O staining and Masson's trichrome staining. Results Hind paw weight distribution was significantly improved in both group. alanine aminotransferanse and aspartate aminotransferase were decreased significantly in CH group compare with Indomethacin threated group. Antioxidant enzyme glutathione peroxidase, Catalase and heme oxygenase-1 were increased in CH group compare with control group. Inflammatory cytokine cyclooxygenase-2, inducible nitric oxide synthase and interleukin-1 beta were decreased significantly in CH group. Histological analysis result shows that protective effects of joint and cartilage were observed in both CH and CL groups in a concentration-dependent. Conclusions The result suggest that Curcumae Longae Rhizoma pharmacopuncture has anti-oxidation effect, anti-inflammatory effect and also can prevent progression of osteoarthritis and protect joint cartilage.

• Journal of the Korean Dietetic Association
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• v.25 no.3
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• pp.217-228
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• 2019

There have been no published studies concerning the anti-inflammatory effects of corn silk on colon cancer cells. Thus, this study was conducted to investigate the effect of corn silk extract containing high levels of maysin on inflammation and its mechanism of action in colon cancer cells. SW 480 human colon cancer cells were treated with $1{\mu}g/mL$ of lipopolysaccharide (LPS) to induce inflammation, and next they were treated with different concentrations of corn silk extract (0, 5, 10 and $15{\mu}g/mL$). The concentrations of nitric oxide (NO) were determined. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), interleukin-1beta ($IL-1{\beta}$) and interleukin-6 (IL-6), were determined. Western blot analysis was performed to determine the protein expressions of nuclear factor-kappa B ($NF-{\kappa}B$) and mitogen-activated protein kinases, and the latter consists of extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK) and p38 MAP kinase (p38). The concentration of NO and the mRNA expression of iNOS were significantly and dose-dependently decreased in the corn silk-treated groups (P<0.05). The mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 were significantly increased in the LPS-treated group (P<0.05), but these expressions were significantly and dose-dependently decreased in the corn silk treated groups (P<0.05). The protein expressions of $NF-{\kappa}B$ (in a dose-dependent fashion), ERK (at 10 and $15{\mu}g/mL$), JNK (at $15{\mu}g/mL$) and p38 (at 10 and $15{\mu}g/mL$) were significantly decreased with corn silk treatments (P<0.05). In conclusion, corn silk extract containing high levels of maysin seems to inhibit the LPS-induced inflammatory responses in SW480 colon cancer cells via the $NF-{\kappa}B$ pathway.

• Journal of Life Science
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• v.29 no.9
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• pp.941-948
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• 2019

Colorectal cancer is a major health problem in industrialized countries. Ziyuglycoside II ($3{\beta}-3-{\alpha}$-1- arabinopyranosyloxy-19-hydroxyurs-12-en-28-oicacid), a triterpenoid saponin isolated from the roots of Sanguisorba officinalis L., possesses antioxidant, antiangiogenic, and anticancer properties. However, the therapeutic function of ziyuglycoside II in colitis-associated colorectal carcinogenesis is undefined. In the present study, the effect of ziyuglycoside II on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS) was explored. The AOM model recapitulates many features of human colon cancer, but it lacks an inflammatory component. DSS induces colitis and promotes AOM-induced colon cancer in mice. BALB/c mice were injected with AOM and administered 2% DSS in drinking water. The mice were given ziyuglycoside II (1 or 5 mg/kg) orally three times per week, and colonic tissue was collected at 64 days. Administration of ziyuglycoside II markedly diminished the formation of colonic tumors. Western blot and immunohistological analyses showed that ziyuglycoside II noticeably decreased nuclear factor kappa-B-positive cells and levels of inflammation-related proteins, such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interleukin-6 in colon tissue. It also prompted apoptosis. Ziyuglycoside II treatment augmented cleaved forms of caspase-3, caspase-7, and poly (ADP-ribose) polymerase in colonic tissues. In conclusion, ziyuglycoside II could defend against colitis-associated tumorigenesis in mice by inhibiting inflammation and inducing apoptosis. This shows a promising chemopreventive potential for its use in colitis-associated colon cancer.

• Journal of Korean Medicine Rehabilitation
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• v.31 no.1
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• pp.17-32
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• 2021

Objectives The present study was designed to find out the therapeutic effects and possible underlying mechanism of Buja-tang, a herbal complex formula on experimental monosodium iodoacetate (MIA)-induced osteoarthritis. Methods Osteoarthritis models were created via intra-joint injection of MIA (50 μL with 80 mg/mL) in rats. Rats were divided into five groups and each group consisted of seven. Normal group was not injected MIA and did a normal diet. Control group injected MIA and received distilled water. Indo injected MIA and oral administration of 5 mg/kg of indomethacin. BJTL injected MIA and oral administration of 100 mg/kg of Buja-tang. BJTH injected MIA and oral administration of 200 mg/kg of Buja-tang. We analyzed weight-bearing ability of hind paws, oxidative stress related factor, antioxidant protein, inflammatory protein, inflammatory messenger and cytokine in joint tissue. Pathological observation of knee cartilage tissue structures was also performed with hematoxylin & eosin and safranin-O chromosomes. Results Weight-bearing ability of hind paws showed a tendency to reduce pain. The incidence of nicotinamide adenine dinucleotide phosphate oxidase and p22phox in articular tissue was significantly reduced, and the incidence of nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 and superoxide dismutases was significantly increased. The incidence of phosphorylated inhibitor of κBα, nuclear factor-kappa B p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β decreased significantly. In pathological observation, cartilage tissue damaged by MIAs in biopsy has significantly recovered from Buja-tang administration. Conclusions Buja-tang has anti-inflammation, antioxidation and pain relief effects. So this is thought to inhibit the progress of osteoarthritis in rat caused by the MIA.

• The Korea Journal of Herbology
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• v.28 no.1
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• pp.83-90
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• 2013

Objectives : Tetramethylpyrazine (TMP) is an active ingredient in Ligusticum wallichii and has a wide range of neuroprotection effects. This study investigated anti-neuroinflammatory effect of TMP on brain regions in intracerebroventricular (i.c.v.) lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : TMP was administered intraperitoneally at doses of 10, 20, and 30 mg/kg at 1 h prior to LPS (3 mg/kg) i.c.v. injection. mRNA level of pro-inflammatory cytokines, including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$ and IL-6, was measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Cyclooxygenase-2 (COX-2) positive cells in the hypothalamus was also observed using immunohistochemistry at 24 h after the LPS injection. Results : At a dose of 30 mg/kg TMP significantly attenuated up-regulation of TNF-${\alpha}$ and IL-$1{\beta}$ mRNA in the cerebral cortex and IL-$1{\beta}$ mRNA in the hippocampus. In the hypothalamus, doses of 20 mg/kg and 30 mg/kg TMP significantly attenuated up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 mRNA induced by the LPS injection. In addition, TMP (30 mg/kg) significantly reduced the number of COX-2 positive cells in the hypothalamus. Conclusion : These results indicate that TMP has an anti-inflammatory effect on neuroinflammation, especially in the hypothalamus, induced by LPS i.c.v. injection and suggest that TMP-containing Ligusticum wallichii may play a modulatory role on the systemic responses following hypothalamic inflammation.

• BMB Reports
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• v.56 no.6
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• pp.359-364
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• 2023

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.