• The Journal of Korean Medicine
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• v.38 no.4
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• pp.11-40
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• 2017

Objectives: We investigated whether a mixture of the main component of pomegranate concentrated powder (PCP) with appropriate proportions of Eucommiae Cortex (EC) and Achyranthis Radix (AR) could act synergistically as an effective treatment for osteoarthritis (OA). Methods: In order to evaluate the effects of PCP, EC, and AR against OA, knee thicknesses, maximum extension angle of each knee, anti - inflammation effects, the transcript levels of chondrogenic genes mRNA expressions in femur and tibia articular cartilage (AC) with synovial membrane (SM) were analyzed. In addition, the histopathology and immunohistochemistry of the femur and tibia AC or SM were performed. Results: The surgically-induced OA signs in rats were significantly inhibited by 28 days of continuous treatment of PCP, EC and AR single formulas, and PCP with EC:AR mixed formulas. Especially, PCP with EC:AR 4:1, 2:1 and 1:1 mixed formula treatment constantly showed significantly more favorable inhibitory activities, as compared with those of single formula of PCP, EC and AR treated rats. Conclusion: PCP and EC:AR 4:1 mixed formula showed similar OA refinement effects through potent anti-inflammatory pathways as compared with those of diclofenac treatment, and showed additional chondrocyte proliferating effects on the both femur and tibia AC.

• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.313-319
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• 2002

Rat skin permeation of various nonsteroidal antiinflammatory drugs (NSAIDs) was investigated in vitro using Franz diffusion cell at $37^{\circ}C$. The effect of various skin permeation enhancers was also observed as a preliminary study of developing transdermal delivery systems of NSAIDs. Lipophilicity of NSAIDs was determined from thε partition coefficient (log P) in 1-octanol/water and 1-octanol/IPB mutual-saturated solutions. The solubility was determined in water, isotonic phosphate buffer (IPB), and propylene glycol (PG) at $37^{\circ}C$. The rat skin permeation rate of acetaminophen, piroxicam, and aceclofenac was almost negligible, although they were saturated in PG. Addition of 1 % permeation enhancer increased the permeation rate of ketoprofen, ketorolac, and diclofenac. However, the skin permeation rate of ibuprofen did not increase with the addition of various enhancers. Among the permeation enhancers testεd, oleic acid was the most effective for various NSAIDs. Based on the daily dose, lipophilicity, and the skin permeation ratε achieved in this study, ketoprofen and ketorolac seem to be the most promising drug candidates for transdermal delivery systems, especially when formulated with unsaturated fatty acids, such as oleic acid.

• Mass Spectrometry Letters
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• v.7 no.4
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• pp.106-110
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• 2016

Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.

• The Korean Journal of Pain
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• v.19 no.2
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• pp.197-201
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• 2006

Background: There are cases in which shoulder pain persists long after shoulder joint surgery and this pain can not be reduced by intravenous patient controlled analgesia (IVPCA). Our purpose was to evaluate the effect of stellate ganglion block (SGB) on postoperative shoulder pain and also to investigate the effect of preventive SBG on complex regional pain syndrome (CRPS). Methods: Forty patients, who were evaluated to ASA class 1 and 2 and who were scheduled for shoulder joint surgery under general anesthesia, were randomly divided into 2 groups. The experimental group of patients (n = 20) received SGB with 0.5% mepivacaine 8 ml after induction of general anesthesia. The control group of patients (n = 20) received only general anesthesia. Their postoperative pain was assessed using the visual analog scale (VAS) at 30 min, 1, 2, 6, 12, 24 and 48 hours postoperatively. Whenever patients wanted supplemental analgesia, diclofenac sodium 75 mg was injected intramuscularly and the need for supplemental analgesia was recorded. Results: The experimental group of patients had significantly lower pain scores at 30 min, 1, 2 and 6 hours and also significantly lower analgesic requirement at 1, 2 and 6 hours. Conclusions: We found SGB was effective for controlling postoperative pain after shoulder joint surgery. Also, we could expect that SGB reduced the incidence of CRPS.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.612-618
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• 2008

In the present study, the anti-inflammatory effect of Haepyoejin-tang plus antler water extract was tested in formalin-injected chronic inflammation model in mouse hind paw. The test articles-100, 250, 500 mg/kg- were dosed once a day for 10 days, and changes on the body weight, paw weights were observed with histopathology of induced paw dorsum pedis. In addition, histomorphometry was also monitored at sacrifice. 15 mg/kg/10 mL of dexamethasone (DEXA) and diclofenac (DICLO) intraperitoneally dosed groups were used as reference groups. A significantly decrease of both absolute and relative paw weights were observed in all dosing groups including DEXA and DICLO groups compared to that of control, and a significantly decrease of the differences between intact and induced paw weights were also observed Haepyoejin-tang plus antler dosing groups compared to that of control. These histological signs-hypertrophy of paw dorsum pedis tissues were detected results from edematous changes on the cutaneous and subcutaneous tissues with severe infiltration of chronic inflammatory cells-were dramatically decreased in all dosing groups including DEXA and DICLO dosing groups compared to that of control. Especially, dose dependently decreases were detected in Haepyoejin-tang plus antler dosing groups compared to that of control. Base on these aforementioned results, it is concluded that Haepyoejin-tang plus antler have clear anti-inflammatory effect on the chronic inflammation induced by formalin injection.

• Journal of Biomedical Engineering Research
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• v.36 no.6
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• pp.291-295
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• 2015

Various types of implantable drug delivery devices have attracted significant attention for several decades to improve drug bioavailability and reduce side effects, thus enhancing therapeutic efficacy and patients' compliance. However, when implanted into the body, the devices may be influenced by the changes in physiological condition, such as temperature, pH or ionic concentration. Thus, the drug release rates could be also altered concurrently. Therefore, in this work, we employed an implantable ALZET$^{(R)}$ Osmotic Pump, which has been widely used to locally deliver various therapeutic agents and examined the effect of pH, temperature and ionic concentration on its drug release rate. For this, we performed in vitro cell tests to simulate the condition of local tissues influenced by the altered drug release rates, where we used diclofenac sodium as a model drug.

• Journal of Acupuncture Research
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• v.18 no.2
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• pp.200-213
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• 2001

Objectives : This study was purposed to investigate the Anti-inflammatory and Analgesic Effects of Gold injection Aqua-acupuncture on the experimental model of rheumatoid arthritis. Methods : The experimental groups were divided into 4 groups : Control group (group injected with normal saline), J-NS (group injected with normal saline into bilateral Choksamni(ST36)), J-GS (group injected with Gold Injection into bilateral Choksamni(ST36)), and N-GS (injected with Gold Injection into the blank locus of the root of mouse tail). In addition, Diclofenac-Na as a comparative medicine is injected into bilateral Choksamni(ST36) and the blank locus of the root of mouse tail. So we measured the mice paw edema induced by Carrageenin and Dextran, the chronic rat paw edema induced by adjuvant, vascular permeability induced by Acetic acid in mice, the writhing syndrome induced by Acetic acid in mice, the heat-induced pain threshold in mice. Results : The following result have been obtained. 1. The mice paw edema induced by Carrageenin was significantly decreased in J-GS as compared with the control group. 2. The mice paw edema induced by Dextran was significantly decreased in J-GS and N-GS as compared with the control group. 3. The chronic rat paw edema induced by Adjuvant was significantly decreased in J-GS and N-GS as compared with the control group. Serum Iron content was significantly decreased in J-GS and N-GS as compared with the control group. But the effect on the Serum Copper contents has no significance statistically. 4. Vascular permeability induced by Acetic acid in mice was significantly decreased in J-GS and N-GS as compared with the control group. 5. The level of Acetic acid-induced Writhing syndrome and Heat-induced Pain Threshold in mice were all significantly decreased in J-GS and N-GS as compared with the control group. Conclusion : According to the result, gold injection aqua-acupuncture has significant anti-inflammatory and analgesic effects on the experimental model of rheumatiod arthiritis.

• Mass Spectrometry Letters
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• v.5 no.3
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• pp.84-88
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• 2014

Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at $0-25{\mu}m$ with CYP probes for 60 min at $37^{\circ}C$, it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half maximal inhibitory concentration ($IC_{50}$) values of 3.4 and $4.0{\mu}m$, respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with $IC_{50}$ values of 4.5 and $0.73{\mu}m$, respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.

• Journal of Dental Anesthesia and Pain Medicine
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• v.21 no.1
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• pp.1-14
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• 2021

This study aimed to evaluate and compare the pre-emptive analgesic efficacy of injected ketorolac to that of other agents for impacted third molar surgical removal in a healthy population. PubMed, Ovid SP, Cochrane databases were filtered from 1980 to July 2020 for potential papers using relevant MeSH terms and pre-specified inclusion and exclusion criteria independently by reviewers. Studies that compared pre-emptive intramuscular or intravenous administration of ketorolac to other agents were evaluated. The outcomes sought were self-reported postoperative pain (patient-perceived pain), median duration for rescue analgesic medication, total number of analgesics consumed in the recovery period, and global assessment (overall patient satisfaction) after the recovery period. Six studies were included in the final evaluation. The outcome of pain perception and the number of analgesics taken were significantly lower in the ketorolac group (intramuscular or intravenous) in most of the studies (n=5) than in the group of other drugs. The mean time for rescue analgesia intake was higher for the ketorolac group, and global assessment scores were also better in the ketorolac group. Although the included studies show significantly better outcomes such as postoperative pain, median time taken for rescue medication, total number of analgesics taken, and overall patient satisfaction with injected ketorolac group in comparison to injected diclofenac, dexamethasone, and tramadol, definitive conclusions cannot be made regarding the superiority of injected Ketorolac as a pre-emptive agent. A greater number of randomized control trials with a proper protocol are needed to make definitive conclusions.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.287-294
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• 2021

Background: Ginsenoside Rb1 (G-Rb1), one of the major active compounds in Panax ginseng, has already been shown to reduce inflammation in various diseases. Osteoarthritis (OA) has traditionally been considered a degenerative disease with degradation of joint articular cartilage. However, recent studies have shown the association of inflammation with OA. In the present study, we investigated whether Rb1 had an antiinflammatory effect on monoiodoacetate (MIA)-induced OA in ovariectomized rats as a model of postmenopausal arthritis. Methods: G-Rb1 at a dosage of 3 and 10 ㎍/kg body weight was administered every 3 days intraarticularly for a period of 4 weeks to observe antiarthritic effects. Diclofenac (10 mg/kg) served as a positive control. Results: The administration of Rb1 significantly ameliorated OA inflammatory symptoms and reduced serum levels of inflammatory cytokines. Furthermore, G-Rb1 administration considerably enhanced the expression of bone morphogenetic protein-2 and collagen 2A and reduced the levels of matrix metalloproteinase-13 genes, indicating a chondroprotective effect of G-Rb1. G-Rb1 also significantly reduced the expression of several inflammatory cytokines/chemokines (interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1)/CCL-2, interleukin [IL]-1β, and IL-6). Histological analysis demonstrated that G-Rb1 significantly attenuated the pathological changes in MIA-induced OA in ovariectomized rats. Safranin O and toluidine blue staining further demonstrated that G-Rb1 effectively prevented the degradation of cartilage and glycosaminoglycans, respectively. Conclusion: Overall, our results suggest that G-Rb1 exerts cartilage protective effect on MIA-induced ovariectomized OA rats, by inhibiting inflammatory mediators such as IL-6, IL-1β, MCP-1/CCL-2, cyclooxygenase-2 (COX-2), and prostaglandin E₂ (PGE2). These results shed a light on possible therapeutic application of G-Rb1 in OA.