• Journal of Microbiology and Biotechnology
• /
• 제31권7호
• /
• pp.1011-1021
• /
• 2021

The root bark of Ulmus davidiana var. japonica (Japanese elm) is used in Korea and other East Asian countries as a traditional herbal remedy to treat a variety of inflammatory diseases and ailments such as edema, gastric cancer and mastitis. For this study, we investigated the lipid metabolism and anti-obesity efficacy of ethyl alcohol extract of Ulmus davidiana var. japonica root bark (UDE). First, HPLC was performed to quantify the level of (+)-catechin, the active ingredient of UDE. In the following experiments, cultured 3T3-L1 pre-adipocytes and high-fat diet (HFD)-fed murine model were studied for anti-obesity efficacy by testing the lipid metabolism effects of UDE and (+)-catechin. In the test using 3T3-L1 pre-adipocytes, treatment with UDE inhibited adipocyte differentiation and significantly reduced the production of adipogenic genes and transcription factors PPARγ, C/EBPα and SREBP-1c. HFD-fed, obese mice were administered with UDE (200 mg/kg per day) and (+)-catechin (30 mg/kg per day) by oral gavage for 4 weeks. Weight gain, epididymal and abdominal adipose tissue mass were significantly reduced, and a change in adipocyte size was observed in the UDE and (+)-catechin treatment groups compared to the untreated control group (^***p < 0.001). Significantly lower total cholesterol and triglyceride levels were detected in UDE-treated HFD mice compared to the control, revealing the efficacy of UDE. In addition, it was found that lipid accumulation in hepatocytes was also significantly reduced after administration of UDE. These results suggest that UDE has significant anti-obesity and lipid metabolism effects through inhibition of adipocyte differentiation and adipogenesis.

• Journal of Ginseng Research
• /
• 제45권1호
• /
• pp.98-107
• /
• 2021

Background: Ginseng extracts and ginseng-fermented products are widely used as functional cosmetic ingredients for their whitening and antiwrinkle effects. Recently, increasing attention has been given to bioactive metabolites isolated from endophytic fungi. However, little is known about the bioactive metabolites of the fungi associated with Panax ginseng Meyer. Methods: An endophytic fungus, Penicillium sp. SNF123 was isolated from the root of P. ginseng, from which acremonidin E was purified. Acremonidin E was tested on melanin synthesis in the murine melanoma cell line B16F10, in the human melanoma cell line MNT-1, and in a pigmented 3D-human skin model, Melanoderm. Results: Acremonidin E reduced melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells with minimal cytotoxicity. qRT-PCR analysis demonstrated that acremonidin E downregulated melanogenic genes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), while their enzymatic activities were unaffected. The antimelanogenic effects of acremonidin E were further confirmed in MNT-1 and a pigmented 3D human epidermal skin model, Melanoderm. Immunohistological examination of the Melanoderm further confirmed the regression of both melanin synthesis and melanocyte activation in the treated tissue. Conclusion: This study demonstrates that acremonidin E, a bioactive metabolite derived from a fungal endophyte of P. ginseng, can inhibit melanin synthesis by downregulating tyrosinase, illuminating the potential utility of microorganisms associated with P. ginseng for cosmetic ingredients.

• Journal of Periodontal and Implant Science
• /
• 제52권5호
• /
• pp.383-393
• /
• 2022

Purpose: Aloe-emodin (AE), a natural anthraquinone abundant in aloe plants and rhubarb (Rheum rhabarbarum), has long been used to treat chronic inflammatory diseases. However, AE's underlying mechanisms in periodontal inflammation have not been fully elucidated. Acidic mammalian chitinase (AMCase) is a potential biomarker involved in bone remodeling. This study aimed to evaluate AE's effect on periodontitis in rats and investigate AMCase expression. Methods: Eighteen Sprague-Dawley rats were separated into the following groups: healthy (group 1), disease (group 2), vehicle (group 3), AE high-dose (group 4), and AE low-dose (group 5). Porphyromonas gingivalis ligatures were placed in rats (groups 2-5) for 7 days. Groups 4 and 5 were then treated with AE for an additional 14 days. Saliva was collected from all groups, and probing pocket depth was measured in succession. Periodontal pocket tissues were subjected to histomorphometric analysis after the rats were sacrificed. Bone marrow-derived macrophages and murine macrophages were stimulated with receptor activator of nuclear factor-κB ligand (RANKL) and treated with different concentrations of AE. AMCase expression was detected from the analysis of saliva, periodontal pocket tissues, and differentiated osteoclasts. Results: Among rats with P. gingivalis-induced periodontitis, the alveolar bone resorption levels and periodontal pocket depth were significantly reduced after treatment with AE. AMCase protein expression was significantly higher in the disease group than in the healthy control (P<0.05). However, AE inhibited periodontal inflammation by downregulating AMCase expression in saliva and periodontal pocket tissue. AE significantly reduced RANKL-stimulated osteoclastogenesis by modulating AMCase (P<0.05). Conclusions: AE decreases alveolar bone loss and periodontal inflammation, suggesting that this natural anthraquinone has potential value as a novel therapeutic agent against periodontal disease.

• Parasites, Hosts and Diseases
• /
• 제60권5호
• /
• pp.309-315
• /
• 2022

Inflammatory bowel disease (IBD) is a chronic and recurrent illness of the gastrointestinal tract. Treatment of IBD traditionally involves the use of aminosalicylic acid and steroids, while these drugs has been associated with untoward effects and refractoriness. The absence of effective treatment regimen against IBD has led to the exploration of new targets. Parasites are promising as an alternative therapy for IBD. Recent studies have highlighted the use of parasite-derived substances, such as excretory secretory products, extracellular vesicles (EVs), and exosomes, for the treatment of IBD. In this report, we examined whether EVs secreted by Giardia lamblia could prevent colitis in a mouse model. G. lamblia EVs (GlEVs) were prepared from in vitro cultures of Giardia trophozoites. Clinical signs, microscopic colon tissue inflammation, and cytokine expression levels were detected to assess the effect of GlEV treatment on dextran sulfate sodium (DSS)-induced experimental murine colitis. The administration of GlEVs prior to DSS challenge reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. Our results indicate that GlEV can exert preventive effects and possess therapeutic properties against DSS-induced colitis.

• Journal of Veterinary Science
• /
• 제25권1호
• /
• pp.4.1-4.14
• /
• 2024

Background: Lawsonia intracellularis is the causative agent of proliferative enteropathy and is associated with several outbreaks, causing substantial economic loss to the porcine industry. Objectives: In this study, we focused on demonstrating the protective effect in the mouse model through the immunological bases of two vaccine strains against porcine proliferative enteritis. Methods: We used live-attenuated Salmonella Typhimurium (ST) secreting two selected immunogenic LI antigens (Lawsonia autotransporter A epitopes and flagellin [FliC]-peptidoglycan-associated lipoprotein-FliC) as the vaccine carrier. The constructs were cloned into a Salmonella expression vector (pJHL65) and transformed into the ST strain (JOL912). The expression of immunogenic proteins within Salmonella was evaluated via immunoblotting. Results: Immunizing BALB/c mice orally and subcutaneously induced high levels of LI-specific systemic immunoglobulin G and mucosal secretory immunoglobulin A. In immunized mice, there was significant upregulation of interferon-γ and interleukin-4 cytokine mRNA and an increase in the subpopulations of cluster of differentiation (CD) 4⁺ and CD 8⁺ T lymphocytes upon splenocytes re-stimulation with LI antigens. We observed significant protection in C57BL/6 mice against challenge with 10^6.9 times the median tissue culture infectious dose of LI or 2 × 10⁹ colony-forming units of the virulent ST strain. Immunizing mice with either individual vaccine strains or co-mixture inhibited bacterial proliferation, with a marked reduction in the percentage of mice shedding Lawsonia in their feces. Conclusions: Salmonella-mediated LI gene delivery induces robust humoral and cellular immune reactions, leading to significant protection against LI and salmonellosis.

• Parasites, Hosts and Diseases
• /
• 제62권1호
• /
• pp.30-41
• /
• 2024

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.

• Anatomy and Cell Biology
• /
• 제57권1호
• /
• pp.97-104
• /
• 2024

Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model. Here, we compared the efficacy of a KE-supplemented Atkins-type diet (ATD-KE) to a classic KD in controlling tumor progression and enhancing survival in a clinically relevant orthotopic patient-derived xenograft GBM model. Our findings demonstrate that ATD-KE preserves body weight (percent change from the baseline; 112±2.99 vs. 116.9±2.52 and 104.8±3.67), decreases blood glucose (80.55±0.86 vs. 118.6±9.51 and 52.35±3.89 mg/dl), and increases ketone bodies in blood (1.15±0.03 mM vs. 0.55±0.04 and 2.66±0.21 mM) and brain tumor tissue (3.35±0.30 mM vs. 2.04±0.3 and 4.25±0.25 mM) comparable to the KD (results presented for ATD-KE vs. standard diet [STD] and KD, respectively). Importantly, the ATD-KE treatment significantly enhanced survival compared to the STD and was indistinguishable from the KD (47 days in STD vs. 56 days in KD and ATD-KE), suggesting that a nutritionally balanced low carbohydrate ATD combined with KE may be as effective as the KD alone in reducing brain tumor progression. Overall, these data support the rationale for clinical testing of KE-supplemented low-carb diet as an adjunct treatment for brain tumor patients.

• 대한핵의학회지
• /
• 제28권1호
• /
• pp.98-105
• /
• 1994

Metallothionein (MT)는 세포내에 존재하는 cystein이 풍부한 적은 단백질로서 핵의학적 영상이나 치료에 이응이 가능할 여러 금속성 방사성 동위원소와 결합한다. 본 연구는 sarcoma를 주사한 Balb/C mice에서 MT와 결합하는 방사성동위원소인 cadmium이 종양에 축적되는가를 확인하고, 그것이 핵의학적인 영상과 치료에 이용될 수 있는지와 Ga-67을 대신할 수 있는지를 보기 위해 종양과 정상조직에서 Cd-109과 Ga-67의 섭취율을 비교하고 종양과 정상조직의 비를 비교하였다. Balb/3T3 세포를 Molony murine sarcoma virus (MMSV)로 변형시킨 세포를 Balb/C mice의 왼쪽 서혜부에 피하로 주사한 후 종양이 $0.6{\sim}l.0cm^2$로 자랐을 때 $25{\mu}Ci$ Cd-109 chloride와 $40{\mu}Ci$ Ga-67 citrate을 피하주사 한 후 18 또는 72시간에 쥐를 희생하여 종양과 여러 정상조직을 제거하여 무게를 잰 후 방사능을 측정하였다. Cd-109의 종양섭취는 Ga-67과 비슷하나 대부분의 정상조직에 비해 (MT가 풍부한 간과 신장을 제외) Ga-67보다 높았다. 종양대 정상조직의 섭취비는 Cd-109이 Ga-67에 비해 배후방사능에 중요한 영향을 미치는 장기인 뼈, 장, 지방조직, 근육, 혈액에서 월등히 높아서 (P<0.001) 같은 종양에서 Ga-67보다 좋은 영상을 얻을 수 있으리라고 생각되며, MT에 결합하는 cadmium은 암의 종양영상과 치료에 이용될 수 있을 것으로 생각된다.

• 동국한의학연구소논문집
• /
• 제7권2호
• /
• pp.97-105
• /
• 1999

본 연구는 긴볼레기말 추출물의 항고지혈증 효과를 조사하기 위해 ICR 생쥐에 Triton WR-1339(TX) 복강주사로 인위적인 고지혈증을 유발시킨 후 긴볼레기말 추출물(30mg/kg)를 복강주사하여 시간의 경과에 따른 간세포내에서의 지방 축적 변화를 조직화학적으로 관찰하였다. TX 주사후 그물구조의 세포질을 가진 간세포가 간엽 전체에서 관찰되었고, 일부 간소엽에서는 간세포 손상으로 인한 간세포판 소실이 나타났다. 또한 간세포내 지방축적도 증가하여 전체 간소엽의 간세포에서 지방의 과출현을 확인 할 수 있었고, 지방의 크기도 대조군에 비해 증가된 것으로 관찰되었다. 그러나 긴볼레기말 추출물 주사군에서는 그물구조의 세포질을 가진 간세포의 수가 TX 주사군에 비해 감소되었고, 대부분의 간소엽에서 정상적인 간세포판의 배열을 확인할 수 있었다. 간세포내의 지방 축적과 크기도 감소된 경향으로 관찰되었다. 이상의 결과로 볼 때 해조류 긴볼레기말 추출물은 고지혈증이 유발된 생쥐 간세포 내에서의 과도한 지방축적을 감소시키는 항고지혈증 효과을 하는 것으로 사료된다.

• Molecules and Cells
• /
• 제39권11호
• /
• pp.790-796
• /
• 2016

Dental pulp is a highly vascularized tissue requiring adequate blood supply for successful regeneration. In this study, we investigated the functional role of stem cells from human exfoliated deciduous teeth (SHEDs) as a perivascular source for in vivo formation of vessel-like structures. Primarily isolated SHEDs showed mesenchymal stem cell (MSC)-like characteristics including the expression of surface antigens and in vitro osteogenic and adipogenic differentiation potentials. Moreover, SHEDs were positive for NG2, ${\alpha}$-smooth muscle actin (SMA), platelet-derived growth factor receptor beta ($PDGFR{\beta}$), and CD146 as pericyte markers. To prove feasibility of SHEDs as perivascular source, SHEDs were transplanted into immunodeficient mouse using Matrigel with or without human umbilical vein endothelial cells (HUVECs). Transplantation of SHEDs alone or HUVECs alone resulted in no formation of vessel-like structures with enough red blood cells. However, when SHEDs and HUVECs were transplanted together, extensive vessel-like structures were formed. The presence of murine erythrocytes within lumens suggested the formation of anastomoses between newly formed vessel-like structures in Matrigel plug and the host circulatory system. To understand underlying mechanisms of in vivo angiogenesis, the expression of angiogenic cytokine and chemokine, their receptors, and MMPs was compared between SHEDs and HUVECs. SHEDs showed higher expression of1VEGF, SDF-$1{\alpha}$, and $PDGFR{\beta}$ than HUVECs. On the contrary, HUVECs showed higher expression of VEGF receptors, CXCR4, and PDGF-BB than SHEDs. This differential expression pattern suggested reciprocal interactions between SHEDs and HUVECs and their involvement during in vivo angiogenesis. In conclusion, SHEDs could be a feasible source of perivascular cells for in vivo angiogenesis.