• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3977-3982
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• 2012

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.

• The Korea Journal of Herbology
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• v.33 no.3
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• pp.45-53
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• 2018

Objectives : In cases of osteoarthritis, the hypofunction of the cartilage and joint leads to a limited range of joint motion, swelling, and pain, which is generally treated using pharmaceutical drugs (e.g., anti-inflammatory agents, cartilage protectants, and nonsteroidal anti-inflammatory drugs) or replacement arthroplasty. However, long-term drug treatment is associated with adverse effects on the gastrointestinal systems. The present study aimed to evaluate the ability of Giheolsotong-hwan to treat of osteoarthritis symptoms in the MIA-induced rat model based on histological analysis, and factors that are associated with inflammation and bone mineral metabolism. Methods : Giheolsotong-hwan was administered orally at doses of 200 mg/kg/day or 400 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate ($3mg/50{\mu}{\ell}$ of 0.9% saline) into the intra-articular space of the rats' right knee. The rats subsequently received the same doses of oral Giheolsotong-hwan for another 4 weeks. We evaluated the treatment effects based on serum biomarkers and histopathological analysis of the knee joints. Results : Compared to those in control rats, the Giheolsotong-hwan treatments significantly decreased the serum concentration of inflammation factors (i.e., $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $PGE_2$, and $LTB_4$), and bone degrade factors (i.e., MMP-9, CTX-II, and COMP). In addition, the Giheolsotong-hwan treatments significantly increased the concentration of glycosaminoglycans of bone defence factors, but no chage the TIMP-1. Furthermore, the Giheolsotong-hwan treatments effectively preserved the knee cartilage and proteoglycan. Conclusion : The results indicate that Giheolsotong-hwan treated osteoarthritis symptoms. Thus, Giheolsotong-hwan may be a novel oriental therapeutic option for the management of osteoarthritis.

• Journal of Periodontal and Implant Science
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• v.53 no.1
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• pp.20-37
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• 2023

Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.4
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• pp.513-522
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• 2017

This study was conducted to examine the relationships between milk and milk product intake and bone health. The data from the 2008~2011 Korean National Health and Nutrition Examination Survey (KNHANES) were used for data analysis. Subjects included 4,626 men and 6,144 women aged 19 to 64 years. Daily intake frequency of milk and milk products was obtained using a food frequency questionnaire and divided into two categories: less than one serving per day and more than one serving per day. Bone mineral density (BMD) values of total femur, femoral neck, and lumbar spine were compared based on daily intake frequency, and relationships between milk and milk product daily intake frequency and osteoporosis risk were evaluated based on logistic regression. In men aged 30~39, BMDs of total femur and femoral neck were significantly higher in the group that consumed milk more than one serving per day (P<0.05). Intake frequency of milk and milk products was also significantly related to both BMDs of total femur and femoral neck. The odds ratio (OR) for milk intake frequency (more than one serving per day) compared to intake frequency less than one serving per day was 0.36 [95% confidence interval (CI) 0.21~0.62], and the OR for milk and milk products intake frequency (more than one serving per day) was 0.49 (95% CI 0.28~0.86) in women aged 50~64. These results indicate that increased consumption of milk and its products is associated with reduced risk of bone health disease, and adequate intakes of milk and milk products might play an important role in maintaining optimum bone health. Further research on the causal relationship and dose-response association between milk intake and bone heath using prospective cohort data is required prior to applying the observed results to programs that prevent bone health problems.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.408-419
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• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.2
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• pp.1-16
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• 2013

Objectives: This study was performed to evaluate the effect of Dokhwalgisaengtang-gami water extract(DGG) on osteoporosis. Methods: The osteoclastogenesis and gene expression were determined in RANKL-stimulated RAW 264.7 cell. And osteoblastogenesis was also determined in rat calvarial cell. Results: The results were summarized as followes. 1. DGG decreased the number of TRAP positive cell in RANKL-stimulated RAW 264.7 cell. 2. DGG inhibited TRAP activity in RANKL-stimulated RAW 264.7 cell. 3. DGG decreased the expression of NAFTc1, MITF in RANKL-stimulated RAW 264.7 cell. 4. DGG increased the expression of iNOS, COX-2, IL-6 in RANKL-stimulated RAW 264.7 cell. 5. DGG decreased the expression of cathepsin K, MMP-9, TRAP in RANKL-stimulated RAW 264.7 cell. 6. DGG increased cell proliferation of rat calvarial cell. 7. DGG increased ALP activity in rat calvarial cell 8. DGG increased bone matrix protein, collagen synthesis and nodule formation in rat calvarial cell. Conclusions: It is concluded that DGG might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression. And DGG might increase the bone formation resulted from increase of osteoblast function.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.830-838
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• 2020

The present study aimed to evaluate the effect of radiation mutant Perilla frutescens var. crispa on bone metabolism and the inflammatory response in a monosodium iodoacetateinduced rat model of osteoarthritis. radiation mutant Perilla frutescens var. crispa was administered orally at doses of 25, 50 or 100 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate (3 mg/50 μl of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral radiation mutant Perilla frutescens var. crispa for another 4 weeks. It was evaluated that the treatment effects based on serum biomarkers, and morphological and histopathological analysis of the knee joints. Compared with those in control rats, the radiation mutant Perilla frutescens var. crispa treatments significantly reduced the serum levels of inflammation, bone metabolism markers (i.e., COX-2, LTB4, MMP-3, and COMP), and the amount of fibrous tissue. Otherwise, it was significantly increased the concentration of TIMP-1 and calcitonin. In addition, the radiation mutant Perilla frutescens var. crispa treatments effectively preserved the knee cartilage and synovial membrane. As a result, it indicates that radiation mutant Perilla frutescens var. crispa prevented and alleviated osteoarthritis symptoms. Thus, radiation mutant Perilla frutescens var. crispa can be used in food and drug material for the management of osteoarthritis.

• Journal of the Korean Applied Science and Technology
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• v.38 no.2
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• pp.368-377
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• 2021

The present study aimed to evaluate the effects of radiation mutant Perilla frutescens var. crispa and Atractylodes macrocephala Koidzumi complex extract(Perilla frutescens var. crispa complex extract) on the mediators related to degenerative arthritis in a monosodium iodoacetate-induced rat model of degenerative arthritis. Perilla frutescens var. crispa complex extract was administered orally at doses of 25, 50 or 100 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate (3 mg/50 µl of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral Perilla frutescens var. crispa complex extract for another 4 weeks. It was evaluated that the treatment effects based on serum bio-markers, and morphological and histopathological analysis of the knee joints. Compared with those in negative control rats, the Perilla frutescens var. crispa complex extract treatments significantly reduced the serum levels of inflammation, bone metabolism markers (i.e., TNF-α, MMP-3, COX-2, PGE₂, COMP, and Aggrecan). Otherwise, it was significantly increased the production of CTX-2 in cartilage absorption mediators. In addition, the Perilla frutescens var. crispa complex extract treatments effectively preserved the knee cartilage and synovial membrane. As a result, it indicates that the Perilla frutescens var. crispa complex extract improved degenerative arthritis symptoms. Thus, the Perilla frutescens var. crispa complex can be used in food material for the management of degenerative arthritis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.46.1-46.9
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• 2019

Background: Oral squamous cell carcinoma (OSCC) constitutes a group of tumors that exhibit heterogeneous biology, histopathology, and clinical behaviors. Case presentation: A 73-year-old male had a whitish leukoplakia-like lesion around inflamed peri-implant area (#42, #43, and #44), and this lesion had transformed to OSCC within 3 years. He underwent mass resection, selective neck dissection, and reconstructive surgery. To detect any carcinogenesis progression, we examined the removed tumor tissue as well as the patient's preoperative and postoperative sera to identify causative oncogenic proteins using immunoprecipitation high-performance liquid chromatography (IP-HPLC). Conclusions: The protein expression levels of p53, E-cadherin, β-catenin, MMP-10, HER2, NRAS, Met, HER2, and ERb were significantly lower in the serum collected on postoperative day 10 than in the preoperative serum, and if these proteins are consistently not elevated in the serum 3 months after surgery compared with the preoperative serum, these proteins can be potential oncogenic proteins. However, we also found that the serum extracted 3 months after the operation had elevated levels of oncogenic proteins compared with that of the preoperative and 10-day postoperative serum indicating the possibility of tumor recurrence. At postoperative follow-up period, ipsilateral neck metastasis and second primary lesion were found and additional surgery was performed to the patient. IP-HPLC using the patient's serum shows the possibility of oncogenic protein detection. However, follow-up IP-HPLC data is needed to find out patient-specific prognostic factors.

• Korean Journal of Plant Resources
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• v.30 no.3
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• pp.272-279
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• 2017

EP was obtained through 20% ethanol extraction of Pueraria lobata root, and the fermented form of EP, FEP, was prepared from the EP after incubating with Lactobacillus rhamnosus vitaP1. There was no significant toxicity by EP and FEP up to $1000{\mu}g/ml$ in NIH-3T3, HaCaT, and B16F10 cells. In addition to antioxidant potentials of EP and FEP determined by DPPH and ABST assays, we confirmed increase of procollagen type I and elastin synthesis by supplementation of the EP and FEP at the concentration of $50{\mu}g/ml$ using ELISA kits. The protein expression levels of matrix metalloprotease (MMP)-1, -3, and -9, those are involved in the degradation of collagen or other skin matrix proteins, were remarkably suppressed while their inhibitory protein metallopeptidase inhibitor 1 (TIMP-1) was greatly up-regulated by supplementation of the EP and FEP at a concentration of $50{\mu}g/ml$. Taken together, both EP and FEP supplementation could be involved in the suppression of the skin wrinkle formation through inhibiting degradation of collagen and stimulating the synthesis of collagen and elastin. The results showed that the anti-wrinkle potential of the EP and FEP will be a promising candidate for developing cosmeceutical compounds or products.