• Natural Product Sciences
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• v.17 no.2
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• pp.90-94
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• 2011

An in vitro bioassay-guide revealed that the methanol (MeOH) extract of the whole plant of Patrinia saniculaefolia (Valerianaceae) showed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin $D_2$ ($PGD_2$) and leukotriene $C_4$ ($LTC_4$) in mouse bone marrow-derived mast cells (BMMCs). Phytochemical study of the MeOH extract of this plant led to the isolation of twelve compounds; ${\beta}$-farnesene (1), squalene (2), nardostachin (3), patridoid I (4), patridoid II (5), patridoid II-A (6), oleanolic acid (7), oleanonic acid (8), 23-hydroxyursolic acid (9), oleanolic acid 3-O-${\alpha}$-L-arabinopyranoside (10), oleanolic acid 3-O-${\beta}$-D-glucopyranoside (11), oleanolic acid 3-O-[${\beta}$-D-xylopyranosyl-(1${\rightarrow}$3)-${\beta}$-D-(6-O-butyl)glucuronopyranoside] (12). Among the compounds, 4 and 5 strongly inhibited both the COX-2-dependent $PGD_2$ generation with $IC_{50}$ values of 8.7 and 13.6 ${\mu}M$, respectively, and the generation of $LTC_4$ in the 5-LOX dependent phase with $IC_{50}$ values of 41.7 and 46.9 ${\mu}M$, respectively, which suggest that the anti-inflammatory activity of P. saniculaefolia might occur in part via the inhibition of both $PGD_2$ and $LTC_4$ generation by 4 and 5.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.5
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• pp.464-467
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• 2001

Aplastic anemia is a hematopoietic disorder characterized by marked reduction or absence of erythoid, granulocytic, and megakariocytic cells in the bone marrow with resultant pancytopenia. To control of infection & bleeding secondary to leukopenia and thrombocytopenia, the inflammatory lesions in oral & maxillofacial area should be removed. Material & Method: The extractions were performed on 21 patients with severe aplastic anemia. The initial, pre-operative and postoperative CBCs were checked up. Amount and kind of transfused platelet in each patient and increment of platelet level were recorded. The complications were documented. Result : A mean of 2.9 teeth were extracted from each patient(ranging between 1 and 13). Furthermore, surgical extractions including ostectomy and odontectomy of the third molar were performed on 11 patients. The preoperative WBC levels presented between $600/{\mu}L$ and $5000/{\mu}L$(mean $2376/{\mu}L$). The WBC values decreased by an average of $145/{\mu}L$ per patient after extractions had been performed. The teeth of 16 patients were extracted under 10.0g/dL, and the mean change in postoperative hemoglobin levels in comparison with preoperative hemoglobin levels was -0.06 per patient. The initial platelet levels were between 1000/(L and $81,000/{\mu}L$(mean $20,174/{\mu}L$). In five patients, extractions were performed with platelet levels less than $50,000/{\mu}L$. Conclusion : The results suggest that more active and preventive treatments in the oral and maxillofacial area are possible and are necessary to remove the infectious foci on the patients with severe aplastic anemia. We report the results of our experiences and literature reviews in treatment of the patients with severe aplastic anemia in our department.

• Parasites, Hosts and Diseases
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• v.58 no.1
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• pp.7-14
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• 2020

Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human population worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effective drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4-HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expression of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1-mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.

• Restorative Dentistry and Endodontics
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• v.26 no.4
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• pp.285-295
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• 2001

The objective of this study was to investigate the inhibitory effect of taurine and alendronate on the osteoclast differentiation. Osteoblasts and bone marrow cells from 1-2 day old mouse were co-cultured in 10% fetal bovine serum - minimal essential media (FBS-MEM). Osteoclast differentiation was induced by adding the sonicated extracts of Porphyromonas gingivalis (P.gingivalis). Osteoclasts were identified using tartrate resistant acid phosphotase staining (TRAP). Alendronate of 10$^{-7}$, 10$^{-6}$, 10$^{-5}$M and taurine of 500, 1000, 1500$\mu\textrm{g}$/ml were added respectively. The cytotoxic effects of alendronate and taurine were examined using MTT(3-(4,5-dimethylthiazol -2-yl-2,5-diphenyltetrazo- lium bromide) method. After culturing with the sonicated extracts of P.gingivalis, the amounts of IL-6 in the culture supernatant were measured and compared using the ELISA method. The results were as follows : 1. Osteoclasts were differentiated at the concentration of 0.01~0.1$\mu\textrm{g}$/ml sonicated extracts of P.gingivalis. (P<0.05). 2. Alendronate inhibited osteoclasts differentiation at the concentration of 10$^{-5}$ M when the concentration of sonicated extracts of P.gingivalis was 0.01$\mu\textrm{g}$/ml. 3. Taurine inhibited osteoclasts differentiation at the concentration of 1500$\mu\textrm{g}$/ml when the concentration of sonicated extracts of P.gingivalis 0.01$\mu\textrm{g}$/ml. 4. In cytotoxic test (MTT test), no cytotoxic effect was evident in all concentrations of alendronate and taurine. 5. Taurine (10$^{-5}$M) and alendronate(1500$\mu\textrm{g}$/ml) did not change the amounts of IL-6 induced by sonicated extracts of P.gingivalis significantly.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.617-623
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• 2006

In our ongoing search for bioactive compounds originating from the endemic species in Korea, we found that the hexane and EtOAc fractions of the MeOH extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin $D_2\;(PGD_2)$ and leukotriene $C_4\;(LTC_4)$ in mouse bone marrow-derived mast cells. By activity-guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3), scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with ${\beta}-sitosterol$ (1), were isolated from the hexane fraction, and two phenethyl alcohol derivatives, viz. 2-methoxy-2-(4'-hydroxyphenyl)ethanol (7) and 2-hydroxy-2-(4'-hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (10), and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc fraction using silica gel column chromatography. In addition, D-mannitol (13) was isolated from the BuOH fraction by recrystallization. Two of the coumarins, scopoletin (4) and (+)- marmesin (6), the two phenethyl alcohol derivatives (7, 8) and the three flavonoids (9-11) were isolated for the first time from this plant. Among the compounds isolated from this plant, the five coumarins as well as the three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results suggest that the anti-inflammatory activity of D. takeshimana might in part occur via the inhibition of the generation of eicosanoids.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.39
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• pp.1.1-1.7
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• 2017

Background: Multiple myeloma (MM) is characterized by a neoplastic proliferation of plasma cells primarily in the bone marrow. Bisphosphonates (BP) are used as supportive therapy in the management of MM. This study aimed to analyze the incidence, risk factors, and clinical outcomes of medication-related necrosis of the jaw (MRONJ) in MM patients. Methods: One hundred thirty MM patients who had previous dental evaluations were retrospectively reviewed. Based on several findings, we applied the staging and treatment strategies on MRONJ. We analyzed gender, age, type of BP, incidence, and local etiological factors and assessed the relationship between these factors and the clinical findings at the first oral examination. Results: MRONJ was found in nine male patients (6.9%). The mean patient age was 62.2 years. The median BP administration time was 19 months. Seven patients were treated with a combination of IV zoledronate and pamidronate, and two patients received single-agent therapy. The lesions were predominantly located in the mandible (n = 8), and the most common predisposing dental factor was a history of prior extraction (n = 6). Half of the MRONJ were related to diseases found on the initial dental screen. Patients with MRONJ were treated with infection control and antibiotic therapy. When comparing between the MRONJ stage and each factor (sign, location, etiologic factor, BP type, treatment, and outcome), there were no significant differences between stages, except for between the stage and sign (with or without purulence). Conclusions: For prevention of MRONJ, we recommend routine dental examinations and treatment prior to starting BP therapy.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.848-853
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• 2005

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

• Korean Journal of Medicinal Crop Science
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• v.19 no.4
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• pp.287-299
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• 2011

Pharmacological effects of Panax ginseng have been demonstrated in cardiovascular system, endocrine secretion and immune system, together with antitumor, anti-stress and anti-oxidant activities. Modern scientific data show protective effect of ginseng against bone marrow cell death, increased survival rate of experimental animals, recovery of hematopoietic injury, immunopotentiation, reduction of damaged intestinal epithelial cells, inhibition of mutagenesis and effective protection against testicular damages, caused by radiation exposure. And also, ginseng acts in indirect fashion to protect radical processes by inhibition of initiation of free radical processes and thus reduces the radiation damages. The research has made much progress, but still insufficient to fully uncover the action mechanism of ginseng components on the molecule level. This review provides the usefulness of natural product, showing no toxic effects, as an radioprotective agent. Furthermore, the further clinical trials on radioprotection of ginseng need to be highly done to clarify its scientific application. The effective components of ginseng has been known as ginsenosides. Considering that each of these ginsenosides has pharmacological effect, it seems likely that non-saponin components might have radioprotective effects superior to those of ginsenosides, suggesting its active ingredients to be non-saponin series. These results also show that the combined effects of saponin and non-saponin components play an important role in the radioprotective effects of ginseng.

• Journal of Microbiology and Biotechnology
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• v.30 no.9
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• pp.1395-1403
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• 2020

There is an increasing interest in using inactivated probiotics to modulate the host immune system and protect against pathogens. As the immunomodulatory function of heat-killed Lactobacillus brevis KCTC 12777BP (LBB) and its mechanism is unclear, we investigated the effect of LBB on immune response based on the hypothesis that LBB might exert stimulatory effects on immunity. In the current study, we demonstrate that administration of LBB can exert immune-stimulatory effects and promote clearance of foreign matters through enhancing phagocytosis. Treatment with LBB induced the production of TNF-α, IL-6, and nitric oxide in macrophages. Importantly, LBB directly increased the phagocytic activity of macrophages against bacterial particles. LBB was able to promote the production of TNF-α in bone marrow-derived macrophages and splenocytes and also increase the proliferation rate of splenocytes, suggesting that the immune-stimulating activity of LBB can be observed in primary immune cells. Investigation into the molecular mechanism responsible revealed that LBB upregulates TAK1 activity and its downstream ERK, p38, and JNK signaling pathways. To further confirm the immunomodulatory capability of LBB in vivo, we orally administered LBB to mice and assessed the effect on primary splenocytes. Splenocytes isolated from LBB-treated mice exhibited higher TNF-α expression and proliferative capacity. These results show that heat-killed L. brevis, a wildly consumed probiotic, may provide protection against pathogens through enhancing host immunity.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.245-252
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• 2003

Posttransplant lymphoproliferative disease(PTLD) has emerged as a potential life-threatening complication of immunosuppressive therapy after organ transplantation. The occurrence of PTLD is usually associated with an Epstein-Barr virus(EBV) infection in patients who are treated by aggressive immunosuppressive therapy. PTLD is represented by diverse manifestations ranging from reactive lymphoid hyperplasia to high grade malignant lymphoma. This is a case report of a late PTLD in a child. The patient is a 14-year-old girl, who presented as malignant lymphoma 44 months after successful renal transplantation. There was no evidence of EBV infection. On bone marrow study, many neoplastic lymphoid cells were defected. Aggressive chemotherapy for PTLD had resulted in clinical remission. However the patient expired from uncontrolled sepsis and septic shock after 77 days.