• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1507-1515
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• 2006

Angelica gigantis (AG), Rehamaninae Radix(RR), Paenia japonica (PJ), and Polygoni multiflori Radix (PM) have been used as medicinal plants to tonify the blood. General function of the drugs have been known to nourish blood and control the heart and liver meridians. Recently, several studies have proposed mechanisms by which some oriental medicinal herbs work on the immune system. However, it is uncertain whether aqueous-extract of these drugs has immunomodulatory effect yet. In this study, I investigated the immune promotive effects of the water-extracted AG, RR, PJ and PM. The water-extracted AG, RR, PJ and PM inhibited NO production and iNOS expression in LPS stimulated RAW 264.7 macrophage cell line. Among these extracts, AG and PM induced expression of IL-2 and IFN${\gamma}$ in mouse spleen cells. In the flow cytometry analysis, PM-stimulated mouse spleen cells showed an increase in B-cell phenotype (CD45R/B220). The oral administration of Polygoni multiflori water-extracts to mice having S-180 abdominal dropsy cancer prolonged life-span more than control mice. These data suggest that among these extracts, PM has cellular and humoral immune-enhancement effect through IL-2 and IFN${\gamma}$ cytokine production, the regulation of NO production in macrophage cells and the B cell production in spleen cells.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.29-38
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• 2023

Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E₂, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.3
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• pp.251-256
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• 2022

Backgrounds/Aims: Postoperative pain management is a key to enhanced recovery after surgery. The aim of this study was to evaluate clinical effect of preoperative intravenous (IV) non-steroidal anti-inflammatory drugs (NSAIDs) on relief of postoperative pain in patients after laparoscopic cholecystectomy. Methods: This single center, retrospective study was conducted between September 2019 and May 2020. A total of 163 patients were divided into two groups: Ibuprofen group (preoperative IV ibuprofen, n = 77) and Ketorolac group (preoperative IV ketorolac, n = 86). The primary outcome was postoperative pain score measured immediately in the recovery room. Results: There was no difference in demographic characteristics between the two groups of patients. Postoperative pain score measured immediately in the recovery room was significantly higher in the Ibuprofen group than in the Ketorolac group (mean value: 5.09 vs. 4.61; p = 0.027). The number of patients who needed analgesics immediately in the recovery room was also higher in the Ibuprofen group than in the Ketorolac group (28 [36.4%] vs. 18 [20.9%]; p = 0.036). Conclusions: In this study, preoperative IV injection with ketorolac reduced postoperative pain and analgesic requirement in the recovery room more effectively than that with ibuprofen. However, both showed similar effects on peak pain and pain at discharge. Numbers of patients requiring additional analgesics were also similar between the two groups.

• Journal of Environmental Health Sciences
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• v.32 no.3
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• pp.227-234
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• 2006

There has been increasing concern in recent years about the occurrence, fate and toxicity of pharmaceutical products in aquatic environment. Although these compounds have been detected in a wide variety of environmental samples including sewage effluent, surface waters, ground water and drinking water, their concentrations generally range from the low ppt to ppb levels. It is therefore often thought to be unlikely that pharmaceuticals will have a detrimental effect on the environment. This study was conducted to determine the endocrine disruption effects of the several pharmaceutical residues in water using adult Japanese medaka (Oryzias latipes). The common antibiotics were used sulfa durgs (sulfamethoxazole and sulfamethazine) and tetracycline drugs (oxytetracycline and tetracycline). Positive control that was induced Vtg (vitellogenin) in male fish was used $17\beta$-estradiol. Vtg was qualified and quantified through Western blotting and ELISA. After SDS gel electrophoresis, the dominant protein band was identified to molecular weight approximately 205 kDa in whole body samples of vitellogenic female. In female medaka exposed to $17\beta$estradiol, there was no significant difference in total protein induction. In contrast, three to five day exposure of male fish to $17\beta$-estradiol resulted in more than 60.0% increase of total protein compared to that of control males (p<0.01). In case of antibiotics, female fish didn't show significant difference, but male fish was showed significant difference. In addition, Vtg induction in male fish was observed with all the test chemicals. On concentrations greater than 0.1 ppm of sulfamethoxazole, 1 ppm of sulfamethazine, 1 ppm of oxytetracycline and 20 ppm of tetracycline, Vtg induction was increased in a dose response manner. This study is one of the early reports suggesting potential endocrine disruption mechanism of antibiotic pharmaceutical products in aquatic ecosystem. Although the effect concentrations obtained from this study were high as unrealistically as in environments, it is endocrine disruption that we should be considered as one of the important consequences of pharmaceutical contamination at water environment, and warrants due attention in future researches.

• BMB Reports
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• v.39 no.2
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• pp.171-177
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• 2006

Nonsteroidal anti-inflammatory drugs such as indomethacin (IN) can exert anti-colorectal cancer (CRC) activity through cyclooxygenase independent mechanism, but the exactly biological mechanism is not completely known. Here we use proteomic tools to investigate the molecular mechanism of this action. First, nude mice bearing tumors derived from subcutaneous injection with human CRC cell line HCT116 were randomly allocated to groups treated with or without indomethacin. Later, tumor lumps were incised and then total proteins extracted. After separated with two-dimensional electrophoresis, thirty-one differently expressed spots were found between IN-treated and non-IN-treated groups, of which 25 spots decreased and 6 spots increased in abundance in IN-treated group. Through matrix-assisted laser desorption ionization time of flight mass spectrometry and then NCBInr and SWISS-PROT databases searching, 12 protein spots were finally identified including galectin-1, annexin A1, annexin IV, trancription factor BTF3A, calreticulin. Most of the identified proteins are correlated with tumor's biological prosperities of proliferation, invasion, apoptosis and immunity, or take part in cell's signal transduction. From above we thought that indomethacin can exert its effect on colorectal cancer through regulating several proteins' expression directly or indirectly. Further study of these proteins may be helpful in founding new targets of drugs for cancer chemotherapy.

• Advances in Traditional Medicine
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• v.6 no.4
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• pp.274-285
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• 2006

Allium sativum (Family Amaryllidaceae or Liliaceae) is used worldwide for various clinical uses like hypertension, cholesterol lowering effect, antiplatelets and fibrinolytic activity etc. Due to these common house hold uses of Allium sativum, as a herbal supplements, and failure of patients to inform their physician of the over-the-counter supplements they consume leads to drugnutrient interactions with components in herbal supplements. Today these types of interactions between a herbal supplement and clinically prescribed drugs are an increasing concern. In vitro studies indicated that garlic constituents modulated various CYP (cytochrome P450) enzymes. CYP 3A4 is abundantly present in human liver and small intestine and contributes to the metabolism of more than 50% of commonly used drugs including nifedipine, cyclosporine, erythromycin, midazolam, alprazolam, and triazolam. Extracts from fresh and aged garlic inhibited CYP 3A4 in human liver microsomes. The in vivo effects of garlic constituents are found to be species depended and the dosing regimen of garlic constituents appeared to influence the modulation of various CYP isoforms. Studies have indicated that the inhibition of various CYPs by organosulfur compounds from garlic was related to their structure also. Studies using in vitro, in vivo, animal and human models have indicated that various garlic constituents can be the substrates, inhibitors and or inducers of various CYP enzymes. The modulation of CYP enzyme activity and expression are dependent on the type and chemical structure of garlic constituents, dose regime, animal species and tissue, and source of garlic thus this review throws light on the possible herb drug interaction with the use of garlic.

• Korean Journal of Medicinal Crop Science
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• v.25 no.3
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• pp.165-174
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• 2017

Background: Traditional plant drugs, are less toxic and free from side effects compared to general synthetic drugs. They have been used for the treatment of diabetes and associated renal damage. In this study, we evaluated effect of Hachimi-jio-gan against diabetic renal damage in a rat model of type 1 diabetic nephropathy induced by subtotal nephrectomy plus streptozotocin (STZ) injection, and in Otsuka Long-Evans Tokushima Fatty (OLETF) rats and db/db mice as a model of human type 2 diabetes, and its associated complications. To explore the active components of Hachimi-jio-gan, the antidiabetic effect of corni fructus, a consituent of Hachimi-jio-gan, and 7-O-galloyl-${{\small}D}$-sedoheptulose, a phenolic compound isolated from corni fructus, were investigated. Methods and Results: We conducted an extensive literature search, and all required data were collected and systematically organized. The findings were reviewed and categorized based on relevance to the topic. A summary of all the therapeutic effects were reported as figures and tables. Conclusions: Hachimi-jio-gan serves as a potential therapeutic agent to against the development of type 1 and type 2 diabetic nephropathy. From the results of characterization active components of corni fructus, 7-O-galloyl-${\small}D$-sedoheptulose is considered to play an important role in preventing and/or delaying the onset of diabetic renal damage. 7-O-Galloyl-${\small}D$-sedoheptulose is expected to serve as a novel therapeutic agent against the development of diabetic nephropathy.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.145-149
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• 2007

We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a synthetic trans-stilbene analogue acting as a potent inhibitor of human cytochrome P450 1B1, induces apoptotic cell death in human cancer cells. In the present studies, we report the mechanisms of apoptotic cell death by TMS in human promyelocytic leukemic HL-60 cells. We found that treatment of HL-60 cells with TMS suppressed the cell growth in a concentration-dependent manner with $IC_{50}$ value of about 0.8 ${\mu}M$. Immunoblot experiments revealed that DMHS-induced apoptosis was associated with cleavage of poly (ADP-ribose) polymerase. The release of cytochrome c from mitochondria into the cytosol was significantly increased in response to TMS. TMS caused activation of caspase-3 in a concentration-dependent manner and TMS-mediated caspase-3 activation was partially prevented by the caspase inhibitor, zVAD-fmk. Interestingly, we found that the cytotoxic effect of anticancer drugs such as paclitaxel, docetaxel, or etoposide was enhanced in the presence of TMS. Simultaneous treatment with TCDD also significantly increased cytotoxic effects of TMS alone or TMS and anti-cancer agents. Taken together, our present results indicated that TMS leads to apoptotic cell death in HL-60 cells through activation of caspase-3 activity and release of cytochrome c into cytosol. The ability of TMS to increase cytotoxic effect of anticancer drugs may contribute to its usefulness for cancer chemotherapy.

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.129-136
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• 2013

Objectives: Among many new drugs that are under investigation with intent to treat cancer, oral kinase inhibitors are proven to be effective in numerous clinical trials and easy to administer. Due to these advantages the use of oral kinase inhibitors is increasing. Oral kinase inhibitors are metabolized by CYP450 which can result either increase of adverse effect or decrease of drug effect by drug interaction when used concurrently with other agents. In this research, the medication records of patients on oral kinase inhibitors from Oct. 2010 to Nov. 2011 were reviewed to investigate potential drug interactions. Methods: From Oct. 2010 to Nov. 2011, cancer patients in Inha University Hospital who took oral kinase inhibitors more than once were included. The patients' medication records were reviewed to list out concurrent medications that have interaction potential with oral kinase inhibitors, the frequency of concurrent use, and the severity of interaction result using Micromedex$^{(R)}$ and Lexicomp-online$^{(R)}$ as references. Results: As a result, 90 cases of drug with interaction potential were prescribed by Micromedex$^{(R)}$ and 179 cases by Lexicomp-online$^{(R)}$ data. In case of severity, 33.3% by Micromedex$^{(R)}$ and 26.3% by Lexicomp-online$^{(R)}$ were categorized as Major and 65.6% by Micromedex$^{(R)}$ and 72.6% by Lexicomp-online$^{(R)}$ as Moderate. The number of adverse events was 92 cases which 58.7% were on skin and 19.6% on Gastro-intestinal tract. Conclusions: Considerable number of drug with interaction potential was used though each oral kinase inhibitors showed differences in extent. Hence there exists the risk of drug interaction in patients taking oral kinase inhibitors with other drugs.

• The Journal of Pediatrics of Korean Medicine
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• v.20 no.1
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• pp.109-135
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• 2006

Objective : In the present study, the author tried to investigate whether six oriental medical prescriptions named gamisingitang (SGT), gamijungtang (IJT), gamicheongpyetang (CPT), galhwengchihyosan (CHS), chwiyeontong (CYT), sigyoungcheongpyetang (SCPT) significantly affect mucin release from cultured hamster tracheal surface epithelial (HTSE) cells. Methode : Confluent HTSE cells were inetabolically radiolabeled with $^{3}H-glucosamine$ for 24 hrs and chased for 30 min in the presence of drugs aforementioned, respectively, to assess the effect of each drug on $^{3}H-mucin$ release. Possible cytotoxicities of effective drugs were assessed by measuring lactate dehydrogenase(LDH) release. Additionally, total elution profiles of control spent media and treatment sample (CPT, CHS, SCPT and CYT) through Sepharose CL-4B column were analysed and effect of CPT, CHS and CYT on MUC5AC mRNA expression in cultured HTSE cells were invsetigated. Results : (1) SGT and IJT did not affect mucin release without cytotoxicity; (2) CPT, SCPT and CHS significantly stimulated mucin release from cultured HTSE cells, with significant cytotoxicity; (4) CPT, CHS, SCPT and CYT chiefly affected the 'mucin' release and did not affect significantly the release of the releasable glycoproteins with less molecular weight than mucin. This result suggests that the four herbal prescriptions specifically affect the release of mucin ; (5) CTP and CHS did not significantly affect the expression levels of MUC 5AC mRNA, however, CYT significantly inhibit the expression levels of MUC 5AC mRNA. Conclusion : CYT can decrease the synthesis of mucin at gene level in cultured HTSE cells.