• The Korea Journal of Herbology
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• v.37 no.3
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• pp.9-19
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• 2022

Objectives : Angelicae Gigantis Radix (AG) is a plant of the Ranunculus family. AG have been reported to have various pharmacological effects on human health which include uterine growth promotion, anti-inflammatory, analgesic, and immune enhancement. However, research on dermatitis disease is insufficient. Therefore, we investigated the effects of AG on tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) stimulated HaCaT cell. Methods : To investigate the effect of AG on HaCaT cell, HaCaT cells were pre-treated with AG for 1 hour and then stimulated with TNF-α/IFN-γ. After 24 hours, media and cells were harvested to analyze the inflammatory mediators. Concentration of human interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α in the media were assessed by ELISA. mRNA expression of human thymus and activation-regulated chemokine (TARC), IL-6, and IL-8 were analyzed by RT-PCR. Additionally, the mechanisms of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway were investigated by Western blot. Results : The treatment of AG inhibited gene expression levels of IL-6, IL-8, and TARC and protein expression levels of IL-1β, MCP-1, and GM-CSF. Also, AG significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation and NF-κB translocation in TNF-α/IFN-γ stimulated HaCaT cell. Conclusions : Taken together, these results demonstrate that AG can alleviate inflammatory diseases such as atopic dermatitis by regulating the expression of inflammatory cytokines. Also, it suggest that AG may a promising candidate drug for the treatment of inflammatory disease such as atopic dermatitis.

• Korean Journal of Acupuncture
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• v.39 no.2
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• pp.43-53
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• 2022

Objectives : Paeonia lactiflora Pallas (PLP) have been reported to have pharmacological effects such as anti-inflammatory and analgesic. However, it is not yet known whether PLP extract has anti-inflammatory effect on HaCaT cells, human keratinocyte. Methods : To confirm the anti-inflammatory effect of PLP on keratinocyte, TNF-𝛼/IFN-𝛾-stimulated HaCaT cells were used. HaCaT cells were pre-treated with PLP for 1h before stimulation with TNF-𝛼/IFN-𝛾. Then HaCaT cells were stimulated with TNF-𝛼/IFN-𝛾 for 24 h, the cells and media were harvested to measure the inflammatory cytokines levels. Granulocyte-macrophage colony stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), interleukin 1 beta (IL-1𝛽), and TNF-𝛼 were analyzed by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression of thymus and activation-regulated chemokines (TARC), IL-6, and IL-8 were measured by reverse transcription-polymerase chain reaction (RT-PCR). We also investigated the inhibitory mechanism of the mitogen-activated protein kinase (MAPKs) including ERK, JNK, and p38 and nuclear factor-kappaB (NF-𝜅B) by PLP using western blot. Results : PLP did not show cytotoxicity in HaCaT cells. In TNF-𝛼/IFN-𝛾-stimulated HaCaT cells, PLP significantly inhibited the expression of GM-CSF, MCP-1 IL-1𝛽, TNF-𝛼, TARC and IL-6. PLP inhibited the phosphorylation of ERK and translocation of NF-𝜅B into the nucleus. Conclusions : These results indicate that PLP could ameliorate the TNF-𝛼/IFN-𝛾-stimulated inflammatory response through inhibition of MAPK and NF-kB signal pathway. This suggests that PLP could be used beneficial agent to improve skin inflammation.

• Journal of dental hygiene science
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• v.23 no.4
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• pp.282-295
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• 2023

Background: Secretory leukocyte protease inhibitor (SLPI) protects tissues from proteases and promotes cell proliferation and healing. SLPI also reduces periodontal inflammation and alveolar bone resorption by inhibiting proinflammatory cytokine expression in rat periodontal tissues and osteoblasts. However, little is known of the role of SLPI in the expression of osteoclast regulatory factors from osteoblasts, which are crucial for the interaction between osteoblasts and osteoclasts. Therefore, we aimed to determine the effects of SLPI on the regulation of osteoclasts and osteoblasts in LPS-treated alveolar bone and osteoblasts. Methods: Periodontitis was induced in rats using LPS. After each LPS injection, SLPI was injected into the same area. Immunohistochemical analysis was performed with antibodies against SLPI, RANKL, OPG, and Runx2 in the periodontal tissue. RT-PCR and western blotting were performed to determine the expression levels of SLPI, RANKL, OPG, and Runx2 in LPS- and SLPI/LPS-treated MC3T3-E1 cells. SLPI/LPS-treated MC3T3-E1 cells were also stained with Alizarin Red S. Results: Immunohistochemical analysis showed that the expression levels of SLPI, OPG, and Runx2 were higher while that of RANKL was lower in the LPS/SLPI group relative to those in the LPS group. The mRNA and protein expression of SLPI, OPG, and Runx2 was higher in SLPI/LPS/MC3T3-E1 cells than in LPS/MC3T3-E1 cells, and RANKL expression was lower. During differentiation, OPG and Runx2 protein levels were higher whereas RANKL levels were lower in SLPI/LPS/MC3T3-E1 than in LPS/MC3T3-E1 cells on days 0, 4, 7, and 10. In addition, mineralization and matrix deposition were higher in SLPI/LPS/MC3T3-E1 than in LPS/MC3T3-E1 on days 7 and 10. SLPI decreased RANKL expression in LPS-treated alveolar bone and osteoblasts but increased the expression of OPG and Runx2. Conclusion: SLPI can be considered as a regulatory molecule that indirectly regulates osteoclast activation via osteoblasts and promotes osteoblast differentiation.

• Journal of Nutrition and Health
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• v.56 no.5
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• pp.469-482
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• 2023

Purpose: Obesity has emerged as a critical global public health concern as it is associated with and increases susceptibility to various diseases. This condition is characterized by the excessive enlargement of adipose tissue, primarily stemming from an inequity between energy intake and expenditure. The purpose of this study was to investigate the potential of sweet pumpkin powder in mitigating obesity and metabolic disorders in leptin-deficient obese (ob/ob) mice and to compare the effects of raw sweet pumpkin powder (HNSP01) and heat-treated sweet pumpkin powder (HNSP02). Methods: Leptin-deficient obese mice were fed a diet containing 10% HNSP01 and another containing 10% HNSP02 for 6 weeks. Results: The supplementation of ob/ob mice with HNSP01 and HNSP02 resulted in decreased body weight gain, reduced adipose tissue weight, and a smaller size of lipid droplets in the adipose tissue and liver. Furthermore, the ob/ob-HNSP01 and ob/ob-HNSP02 supplemented groups exhibited lower levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and insulin, as well as a reduced atherogenic index in comparison with the control group. Molecular analysis also demonstrated that the intake of HNSP01 and HNSP02 resulted in a diminished activation of factors associated with fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase, while concurrently enhancing factors associated with lipolysis, including adipose triglyceride lipase and hormone-sensitive lipase, in the adipose tissue. Conclusion: Taken together, these findings collectively demonstrate the potential of sweet pumpkin powder as a functional food ingredient with therapeutic properties against obesity and its associated metabolic disorders, such as insulin resistance and dyslipidemia.

• Korean Journal of Plant Resources
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• v.31 no.5
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• pp.466-477
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• 2018

In this study, the anti-inflammatory activities of the extracts of different parts of Hovenia dulcis such as leaves, stems, and roots were investigated. Among them, the roots extract (RE) showed the most potent suppressive effect against pro-inflammatory mediators in LPS-stimulated mouse macrophage cells. RE induced dose-dependent reduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitantly reduced the production of NO and $PGE_2$. Additionally, pre-treatment with RE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6, as well as mRNA levels. Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-kB) were also strongly attenuated by RE in RAW264.7 cell. Furthermore, RE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increase HO-1 activity in RAW264.7 macrophages. Therefore, these results indicate that RE strongly inhibits LPS-induced inflammatory responses by blocking NF-kB activation, inhibiting MAPKs phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that RE of H. dulicis and a major component, 27-O-protocatechuoylbetulinic acid could be applied as a valuable natural anti-inflammatory material.

• Journal of Life Science
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• v.19 no.5
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• pp.593-597
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• 2009

The uterus plays a critical role in pregnancy and steroid hormones, and both estrogen (E2) and progesterone (P4) especially play important roles in the cross-talk between embryos and uterus to support the pregnancy. E2 stimulates uterine growth during early pregnancy to prepare for implantation of embryos. This cross-talk during the implantation period involves hormones (E2 and P4) and growth factors, including insulin-like growth factor-I (IGF-I). In the uterus of a pregnant pig, the action of E2 is mediated by estrogen receptor-${\beta}$ (ER-${\beta}$). The expression of ER-a was much higher in early pregnancy than in mid- and late- pregnancy, suggesting E2 secretion from embryos enhances transcription of ER-a during early pregnancy. In order to prove whether IGF-I is an E2 target gene, quantitative real-time PCR was performed on ovariectomized murine uterus with E2 and/or P4 treatment(s). Increased IGF-I mRNA expression was observed with E2 treatment, however, it was not significantly induced by P4 treatment, which clearly demonstrates that, in mice, E2 depends on the activation of uterine IGF-I gene expression. The expression of IGF-I in the uterus of pigs was much higher in early pregnancy than in mid- and late- pregnancy and these data exhibited the same expression pattern with the ER-${\beta}$ gene expression in the uterus. It suggests that a positive co-relationship between IGF-I and ER-${\beta}$ expression exists in the uterus, and that both gene expressions of IGF-I and ER-${\beta}$ are regulated by E2. It further suggests that uterine the IGF-I gene expression might be initiated by E2 secreted from embryos to increase ER-${\beta}$ gene expression, and that this increased ER-${\beta}$ further stimulates the expression of IGF-I in the uterus during early pregnancy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.3
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• pp.298-305
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• 2017

Atopic dermatitis is a chronic, relapsing inflammatory skin disease. This study aimed to investigate the therapeutic benefits of Aronia melanocarpa (AM) and Moringa oleifera seed extract (MO) on experimental atopic dermatitis. We examined the effects of AM or MO and their combination on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in BALB/c mice as well as tumor necrosis factor $(TNF)-{\alpha}$ and interferon $(IFN)-{\gamma}-stimulated$ HaCaT keratinocytes. Mice were orally treated with extract during repeated application of DNCB to shaved dorsal skin. Our results show that treatment with AM and MO in combination reduced histological manifestations such as epidermal hyperplasia and inflammatory cell infiltration. Furthermore, it significantly decreased skin thickness and serum immunoglobulin E (IgE) level compared to the AM or MO alone treated group. Combined extract of AM and MO suppressed expression of $TNF-{\alpha}/IFN-{\gamma}-induced$ T helper 2 (Th2) chemokines such as thymus and activation-regulated chemokine and macrophage-derived chemokine. To sum up, combination of AM and MO suppressed the inflammatory response and serum IgE as an indicator of several allergic diseases in DNCB-induced experimental atopic dermatitis and Th2 chemokine expression in HaCaT cells. This result suggests that combination of AM and MO could be a valuable strategy to improve atopic dermatitis.

• Journal of Acupuncture Research
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• v.21 no.4
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• pp.177-196
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• 2004

Objective : Rheumatoid arthritis is an autoimmune disease that pathogenesis is not fully understood and one of the most intractable musculoskeletal diseases. The concern in the immunopathogenesis of rheumatoid arthritis has been increased since 1980's and many immunotherapeutic agents including disease-modifying antirheumatic drugs (DMARDs) were developed and became the mainstay of treatment of rheumatoid arthritis. However, the cure of the disease has hardly been achieved. In oriental medicine, rheumatoid arthritis is related to Bi-Zheng(痺證), that presents pain, swelling, andlor loss of joint function as major clinical manifestations, and also known to be deeply involved in suppression of immune function related to weakness of Jung-Ki(正氣). The herbal medicine, empirically used, could be a potential resource of development of new immunotherapeutic agents for rheumatoid arthritis. Methods : We developed a search strategy using terms to include "rheumatoid arthritis and herbal medicine" combined with "Chinese medicine" and/or "Oriental medicine". The search was focused on experimental studies of herbal medicine (January 1999 to May 2004), which is known to have effects on immune function of patients with rheumatoid arthritis. Computerized search used Internet databases including KISS and RISS4U (Korea), CNKI (China), MOMJ (Main Oriental Medicine Journal, Japan), and PubMed. The articles were selected from journals of universities or major research institutes. Results : The literature search for experimental studies on effects of herbal medicine on immunity of rheumatoid arthritis retrieved a total of 21 articles (Korea; 8, China ; 12, Japan ; 1). Of 21 articles, 10 were related to single-drug formula, 2 to drug interaction, and 9 to multi-drug formula. Single-drug formula was mainly used for aqua-acupuncture and researches on active components. Studies of drug interaction emphasized harmony of Ki-Hyul(氣血) and balance of Han-Yeul(寒熱). Multi-drug regimen was mainly found among formulas for Bo-Ki-Hyul(補氣血) and Bo-Sin(補腎). Conclusion : Studies on rheumatoid arthritis were performed both in vitro and in vivo in vitro study, LPS-stimulated splenocytes and synoviocytes were treated with herbal medicine, resulting in proliferation and activation of immune cells and suppression of cytokine activities in vivo study CIA animal model demonstrated that herbal medicine decreased antibody production and improved function of immune cells. In cellular and molecular study herbal medicine showed profound effects on the level of mRNA expression of certain cytokines related to immune function. This study revealed that herbal medicine has significant immune modulatory action and could be used for recovery of immune dysfunction of rheumatoid arthritis patients.

• Proceedings of the KSAR Conference
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• 2000.10a
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• pp.10-12
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• 2000

Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$-subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$ -subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was. efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to consist of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t63I or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632-653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17-fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.929-937
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• 2016

The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.