• 대한상한금궤의학회지
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• v.13 no.1
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• pp.21-44
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• 2021

Objective : This study aimed to assess the preventive effect of Bupleuri Radix aqueous extracts (BR) and red koji-fermented BR (fBR) in lipopolysaccharide (LPS)-induced acute lung injury in a rat model. Methods : Rats were administered 30, 60, or 120 mg/kg/day of fBR for 28 days before LPS treatments. All rats were sacrificed 5 h after LPS treatment (500 ㎍/head, intratracheal instillation). Body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters (pH, partial pressure [Pa] of O2, PaCO2), bronchoalveolar lavage fluid (BALF) protein, lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total cell numbers, neutrophil/alveolar macrophage ratios, lung malondialdehyde (MDA), and myeloperoxidase (MPO) were measured. In addition, histopathological changes including the luminal surface of alveoli (LSA), thickness of alveolar septum, and number of polymorphonuclear neutrophils (PMNs) were checked. Results : LPS injection led to increases in lung weights, pulmonary transcapillary albumin transit, BALF protein, LDH, TNF-α and IL-1β contents, total cells, neutrophil and alveolar macrophage ratios, lung MDA, MPO, alveolar septum thickness, and PMNs, and decreases in PaCO2 and pH of arterial blood and LSA. However, these LPS-induced acute lung injuries were inhibited by pretreatment of 30, 60, and 120 mg/kg of fBR. The most favorable effects were seen with 30 mg/kg fBR as compared with 60 mg/kg of α-lipoic acid and BR. Conclusions : fBR showed preventive effects on LPS-induced acute lung injury, which resembles acute respiratory distress syndrome. The mechanisms of action were likely via antioxidant and anti-inflammatory means.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.126-137
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• 2022

Background: Nonalcoholic steatohepatitis (NASH) is one of the main chronic liver diseases. NASH is identified by lipid accumulation, inflammation, and fibrosis. Jinan Red Ginseng (JRG) and licorice have been widely used because of their anti-inflammatory and hepatoprotective effects. Hence, this study assessed JRG and licorice extract mixtures' effects on NASH progression. Methods: Palmitic acid (PA) and the western diet (WD) plus, high glucose-fructose water were used to induce in vitro and in vivo NASH. Mice were orally administered with JRG-single (JRG-S) and JRG-mixtures (JRG-M; JRG-S + licorice) at 0, 50, 100, 200 or 400 mg/kg/day once a day during the last half-period of diet feeding. Results: JRG-S and JRG-M reduced NASH-related pathologies in WD-fed mice. JRG-S and JRG-M consistently decreased the mRNA level of genes related with inflammation, fibrosis, and lipid metabolism. The treatment of JRG-S and JRG-M also diminished the SREBP-1c protein levels and the p-AMPK/AMPK ratio. The FAS protein levels were decreased by JRG-M treatment both in vivo and in vitro but not JRG-S. Conclusion: JRG-M effectively reduced lipogenesis by modulating AMPK downstream signaling. Our findings suggest that this mixture can be used as a prophylactic or therapeutic alternative for the remedy of NASH.

• Parasites, Hosts and Diseases
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• v.59 no.6
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• pp.557-564
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• 2021

Macrophages play a key role in chronic inflammation, and are the most abundant immune cells in the tumor microenvironment. We investigated whether an interaction between inflamed prostate cancer cells stimulated with Trichomonas vaginalis and macrophages stimulates the proliferation of the cancer cells. Conditioned medium was prepared from T. vaginalis-infected (TCM) and uninfected (CM) mouse prostate cancer (PCa) cell line (TRAMP-C2 cells). Thereafter conditioned medium was prepared from macrophages (J774A.1 cell line) after incubation with CM (MCM) or TCM (MTCM). When TRAMP-C2 cells were stimulated with T. vaginalis, protein and mRNA levels of CXCL1 and CCL2 increased, and migration of macrophages toward TCM was more extensive than towards CM. Macrophages stimulated with TCM produced higher levels of CCL2, IL-6, TNF-α, their mRNAs than macrophages stimulated with CM. MTCM stimulated the proliferation and invasiveness of TRAMP-C2 cells as well as the expression of cytokine receptors (CCR2, GP130, CXCR2). Importantly, blocking of each cytokine receptors with anti-cytokine receptor antibody significantly reduced the proliferation and invasiveness of TRAMP-C2 cells. We conclude that inflammatory mediators released by TRAMP-C2 cells in response to infection by T. vaginalis stimulate the migration and activation of macrophages and the activated macrophages stimulate the proliferation and invasiveness of the TRAMP-C2 cells via cytokine-cytokine receptor binding. Our results therefore suggested that macrophages contribute to the exacerbation of PCa due to inflammation of prostate cancer cells reacted with T. vaginalis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.1
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• pp.1-6
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• 2022

The tuber of Pinellia ternata (Thunb.) Brei (TPT) used in traditional Oriental medicine for the treatment of cough, sputum, vomiting, and insomnia, possesses antioxidant, antibacterial, and anti-inflammatory effects. Although recent studies have reported the anticancer effects of TPT in several cancer cells, it is still unclear whether TPT regulates tumor-associated macrophage (TAM) characterized by the immunosuppressive M2 macrophage phenotype. Our results showed that the ethanol extract of TPT (ETPT) suppressed the migration of RAW264.7 mouse macrophage cells and THP-1 human monocytes differentiated into macrophages towards the conditioned media (CM) collected from lung cancer cells, suggesting that ETPT would attenuate the recruitment of macrophages into tumors. In addition, ETPT suppressed the interleukin (IL)-4 or IL-6-induced M2 macrophage polarization in RAW264.7 cells. ETPT treatment not only downregulated the mRNA expression of M2 macrophage markers including arginase-1, mannose receptor C type 1 (MRC-1), and IL-10, but also inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and STAT6, general regulators of M2 macrophage polarization. Finally, the transwell assay results showed that the CM from M2-polarized RAW264.7 cells increased the migration of mouse lewis lung carcinoma (LLC) cells, while those from RAW264.7 cells co-treated with ETPT and IL-6 significantly reduced the migration of LLC cells. Taken together, our observations clearly demonstrate that ETPT suppressed the cancer cell migration by regulating macrophage recruitment and M2 macrophage polarization.

• Korean Journal of Organic Agriculture
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• v.30 no.1
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• pp.75-87
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• 2022

Reflux esophagitis (RE) is a gastroesophageal reflux disease (GERD) caused by repeated reflux of gastric acid into the esophagus. The present study investigated the protective effect of natural mineral water on esophageal injury induced by gastric acid reflux. The cytotoxicity of mineral water was confirmed using Cell viability, proliferation and cytotoxicity assay kit. The protective effect of mineral water on esophageal injury was investigated in RE rat model. The results showed that no cytotoxicity of mineral water was observed in RAW264.7 cells. Mineral water decreased the ratio of esophageal damage, inhibited the increase of inflammatory-protein expression levels and increased the mucosa protection and tight junction proteins expression level in RE control rat. The results suggest that mineral water may have the potential to protect esophageal damage caused by gastric acid reflux and the potential to alleviate reflux esophagitis.

• Tuberculosis and Respiratory Diseases
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• v.85 no.1
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• pp.67-73
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• 2022

Background: Bronchiectasis patients with neutrophilic airway inflammation develop symptoms of chronic cough, sputum production, and recurrent exacerbations. Roflumilast has anti-inflammatory actions via decreased neutrophilic airway inflammation. The effectiveness of roflumilast to reduce bronchiectasis exacerbation has never been evaluated. Methods: We conducted a double-blinded, randomized, placebo-controlled trial. Our primary objective was to assess the effect of roflumilast compared with that of a placebo in reducing exacerbation rates in bronchiectasis patients. The secondary objectives were the changes in forced expiratory volume in 1 second (FEV₁) and St. George's Respiratory Questionnaire (SGRQ). Bronchiectasis patients older than 18 years who had had two exacerbations during the previous 12 months were randomly assigned to receive either 500 ㎍ of either roflumilast or a placebo once daily for 6 months in a 1:1 ratio. Results: Forty bronchiectasis patients who had experienced exacerbations were screened. Thirty patients completed the study after 6 months of treatment: roflumilast group (n=15) and placebo group (n=15). The rates of exacerbations were 0.57 and 0.59 per patient in the roflumilast and placebo groups, respectively. Prebronchodilator FEV₁ increased by 0.07 L from baseline in the roflumilast group and decreased by 0.015 L in the placebo group, but the difference was not significant. No significant differences were observed in the change of SGRQ scores between the roflumilast and placebo groups. Roflumilast had significant side effects, including loss of appetite and headache. Conclusion: Roflumilast did not significantly affect the rate of exacerbations or quality of life. However, FEV₁ tended to improve more in the roflumilast group than in the placebo group.

• Journal of Veterinary Science
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• v.23 no.4
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• pp.61.1-61.10
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• 2022

Background: Although there are growing demands for stem cell-based therapy for companion animals in various diseases, a few clinical trials have been reported. Moreover, most of them are the results from only one or a few times of stem cell injection. Objectives: The aim of this study is to describe a long-term treatment with allogeneic adipose-derived stem cells (ASCs) in a dog with rheumatoid arthritis (RA), which is a rare canine disease. Methods: The dog with RA received intravascular injection of allogeneic ASCs derived from two healthy donors once a month for 11 months. To assess therapeutic effects of ASCs, orthopedic examination and clinical evaluation was performed. Cytokines of tumor necrosis factor-α and interleukin-6 in the plasma were measured using ELISA analysis. Results: Despite this repeated and long-term administration of allogeneic ASCs, there were no side effects such as immunorejection responses or cell toxicity. The orthopedic examination score for the dog decreased after ASCs treatment, and the clinical condition of the dog and owner's satisfaction were very good Conclusions: Although ASCs has been suggested as one of the options for RA treatment because of its anti-inflammatory and immunosuppressive functions, it has never been used to treat RA in dogs. The present report describes a case of canine RA treated with allogeneic ASCs for long-term in which the dog showed clinical improvement without adverse effects.

• The Korea Journal of Herbology
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• v.37 no.1
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• pp.11-18
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• 2022

Objectives : Green gram (mung bean) has a cold nature and has been known to detoxify against various side effects that belong to hot in nature. In particular, since it has the effect of detoxifying fever and detoxification to treat swelling, it was also used externally to treat febrile dermatological diseases such as erysipelas and rubella. This study was designed to determine whether green gram exhibits anti-inflammatory effects on contact dermatitis in mice. Methods : We investigated the effects of green gram extract (70% ethanol extract) on skin lesion, skin thickness and weights, melanin and erythema index and spleen body weight ratio in mice with contact dermatitis induced by repeated application of 1-Fluoro-2,4-dinitrobenzene. Results : Topical application of green gram extract ameliorates skin lesions of contact dermatitis such as scale and roughness induces by 1-Fluoro-2,4-dinitrobenzene. green gram extract also suppressed enlargement of skin thicknesses and weights significantly. In addition, green gram extract treatment also lowered erythema index significantly compared to those in the control group. In the histopathological observation, green gram extract prevented epidermal hyperplasia and hyperkeratosis in inflamed tissues. Finally, green gram extract did not affect changes in body weights and the spleen body weight ratio, unlike dexamethasone, which significantly prevented body weight gain and lowered the spleen body weight ratio. Conclusions : These results imply that green gram, which is known to have a detoxifying effect in Korean medicine, can be used in the treatment of contact dermatitis.

• CELLMED
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• v.11 no.4
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• pp.20.1-20.23
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• 2021

Background: The pandemic COVID-19 caused by a novel coronavirus SARS-COV-2 has spread like a forest fire. This disease may have serious consequences for pregnant women. Presently, no specific drugs or vaccines exist to battle this disease and researches are underway. Unani medicine has a unique role in prevention and management during epidemics. Here, we reviewed the overview of COVID-19 infection and pregnancy, concept and practices in Unani medicine for flu-like epidemics in general and pregnancy, and safety of Unani drugs for the prevention and treatment of mild symptomatic cases of COVID-19 during pregnancy. Methodology: Unani classical texts and pharmacopoeia were meticulously explored for concepts and practices for flu-like epidemic diseases. Further, we browsed scientific databases such as PubMed, Scopus and others for an overview, epidemics and Unani medicine, effectiveness and safety of Unani drugs in COVID-19 and pregnancy. Results: Unani medicine includes prevention and management of flu-like epidemic include quarantine and isolation, aromatic herbal drugs fumigation and spraying for environmental disinfection, ilaj bid tadbir for health promotion and use of health-protecting drugs and symptom-specific drugs in general and related to pregnancy. Lahsun, asalussus, behidana, banafsha, zanjabeel, unnab, etc are in use since antiquity for the prevention and treatment of asymptomatic and mildly symptomatic pregnant women during infectious and epidemic diseases. Conclusion: Currently, the aforementioned plants are proven for antiviral, antioxidant, immunomodulatory and anti-inflammatory activities, probably useful in the COVID-19 pandemic. Additionally, scientific studies have provided new insight into the mechanism underlying the therapeutic effect of Unani medicines that are safe in pregnancy.

• Clinics in Shoulder and Elbow
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• v.25 no.2
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• pp.129-139
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• 2022

Background: Several therapeutic methods have been proposed for frozen shoulder syndrome. These include suprascapular nerve block, a simple and cost-effective technique that eliminates the need for nonsteroidal anti-inflammatory drug therapy. Methods: This was a clinical trial that included patients with unilateral shoulder joint stiffness. Patients were divided into three groups: those treated with isolated physiotherapy for 12 weeks (PT group), those treated with a single dose intra-articular injection of corticosteroid together with physiotherapy (IACI group), and those treated with a suprascapular nerve block performed with a single indirect injection of 8-mL lidocaine HCL 1% and 2 mL (80 mg) methylprednisolone acetate together with physiotherapy (SSNB group). The variables assessed were age, sex, side of involvement, dominant limb, presence of diabetes, physical examination findings including erythema, swelling, and muscle wasting; palpation and movement findings; shoulder pain and disability index (SPADI) score; and the visual analog scale (VAS) score pre-intervention and at 2-, 4-, 6-, and 12-week post-intervention. Results: Ninety-seven patients were included in this survey (34 cases in the PT group, 32 cases in the IACI group, and 31 cases in the SSNB group). Mean age was 48.55±11.06 years. Fifty-seven cases were female (58.8%) and 40 were male (41.2%). Sixty-eight patients had a history of diabetes (70.1%). VAS and SPADI scores and range of mototion degrees dramatically improved in all cases (p<0.001). Results were best in the SSNB group (p<0.001), and the IACI group showed better results than the PT group (p<0.001). Conclusions: Suprascapular nerve block is an effective therapy with long-term pain relief and increased mobility of the shoulder joint in patients with adhesive capsulitis.