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Context Socheongryongtang is a traditional Korean medical prescription used to treat pulmonary diseases. Objective This study investigated the therapeutic mechanism of socheongryongtang for pulmonary diseases. Materials and methods Seventy BALB/c mice were used: control, 0.8 mg/kg/study LPS intranasal instillation, 1 mg/kg/day Spiriva oral administration for five days, two socheongryongtang groups (150 or 1500 mg/kg/day orally treatment for five days). To illuminate the anti-COPD mechanism, several factors were evaluated such as WBC and differential counts in BALF and IgE in serum, morphological changes, and changes of COPD-related cytokines (TNF-α, IFN-γ, TGF-β) and chemokines (CXCL1, CCL-2, CCR2) in the lung. In order to confirm the statistical significance, all results were compared under p

Cassia obtusifolia L., of the Leguminosae family, is used as a diuretic, laxative, tonic, purgative, and natural remedy for treating headache, dizziness, constipation, tophobia, and lacrimation and for improving eyesight. It is commonly used in tea in Korea. Various anthraquinone derivatives make up its main chemical constituents: emodin, chrysophanol, physcion, obtusifolin, obtusin, au rantio-obtusin, chryso-obtusin, alaternin, questin, aloe-emodin, gluco-aurantio-obtusin, gluco-obtusifolin, naphthopyrone glycosides, toralactone-9-β-gentiobioside, toralactone gentiobioside, and cassiaside. C. obtusifolia L. possesses a wide range of pharmacological properties (e.g., antidiabetic, antimicrobial, anti-inflammatory, hepatoprotective, and neuroprotective properties) and may be used to treat Alzheimer’s disease, Parkinson’s disease, and cancer. In addition, C. obtusifolia L. contributes to histamine release and antiplatelet aggregation. This review summarizes the botanical, phytochemical, and pharmacological features of C. obtusifolia and its therapeutic uses.

Madi-Ryuk (MDR) is a traditional Korean medicine and it has been widely used in Korea to treat arthritis and we previously reported the anti-allergic inflammatory effect of MDR in vitro model. However, therapeutic evidence of MDR on in vivo model of allergic inflammatory reaction has not yet been demonstrated. The research purpose was to investigate the efficacy of MDR and its active ingredient tannic acid (TA) in ovalbumin (OVA)-induced AR mice model. OVA-challenged AR mice orally medicated MDR or its active ingredient TA daily for ten days. In mice having a AR, MDR and TA prominently diminished number of rubs and levels of histamine, IgE, thymic stromal lymphopoietin, interleukin (IL)-1β, IL-4, IL-5, IL-13, IL-33, and tumor necrosis factor-α. In addition, protein expression levels and activities of caspase-1 were declined by oral medication of MDR and TA. Decline in levels of macrophage inflammatory protein-2 and intercellular adhesion molecules-1 and reduction in penetrations of inflammatory cells into inflamed tissue were also noted in MDR and TA groups. Taken together, identification of MDR effect in preclinical models suggests that MDR may be a therapeutic drug for the treatment and prevention of AR.

Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called “Man HyungJa” in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.

Ethnopharmacological relevance Phlomoides umbrosa (Turcz.) Kamelin & Makhm (P. umbrosa, Lamiaceae) is also known as “Caosu” in China and “Han Sok-Dan” in Korea. It has been used as a traditional medicine for hundreds of years. This plant is not only as a traditional medicine to alleviate diseases such as colds, arthritis, osteoporosis, but also as a food additive. Aim of the study This review provides up-to-date investigations of this plant, including its botany, traditional uses, pharmacology, phytochemistry, clinical research, cytotoxicity, and safety evaluation. The possible purposes and perspectives for future research of P. umbrosa are also discussed. Materials and methods Information on the studies of P. umbrosa is collected from scientific journals and reports via library and electronic data search (PubMed, Baidu Academic, Google Scholar, Science Direct, ACS, Web of Science, and CNKI). Meanwhile, it is also obtained from published works of folk records, ethnopharmacological literature, Ph.D. and Masters Dissertation. Results Phytochemical research reveals that this plant contains triterpenoids, iridoids, phenylethanoids, flavonoids, essential oil, microelement, etc. The extract of P. umbrosa exhibits extensive pharmacological activities including anti-osteoporosis, anti-allergic, anti-bacterial, anti-nociceptive, anti-inflammatory, anti-oxidant, anti-cancer. Almost no obvious toxicity or side effects is observed and recorded for P. umbrosa. Conclusions This review summarizes traditional uses, botany, pharmacology, phytochemistry, clinical research, cytotoxicity, and safety evaluation of P. umbrosa, and presents the constituents and their corresponding chemical structures found in P. umbrosa comprehensively for the first time. Meanwhile, modern pharmacological studies also are extensively investigated at present. It is worth mentioning that P. umbrosa promotes children's growth as well as the application of clinical research. Although there are clinical studies on P. umbrosa, its pharmacokinetics needs to be further elucidated. Besides, P. umbrosa is also limited in identifying active compounds and clarifying pharmacological mechanisms. Similarly, modern researches on the traditional application of P. umbrosa should also be urgently confirmed, such as treatment of fractures and hemostasis. It is believed that this review will provide a theoretical basis and valuable data for future in-depth research and application.

It is well established that physiological stress has an adverse effect on the male reproductive system. Experimental studies have demonstrated the promising effects of MOTILIPERM in male infertility. MOTILIPERM extract is composed of three crude medicinal herbs: Morinda officinalis How (Rubiaceae) roots, Allium cepa L. (Liliaceae) outer scales, and Cuscuta chinensis Lamark (convolvulaceae) seeds. The present study aimed to investigate the possible mechanisms responsible for the effects of MOTILIPERM on testicular dysfunction induced by immobilization stress. Fifty male Sprague Dawley rats were divided into five groups (10 rats each): a normal control group (CTR), a control group administered MOTILIPERM 200 mg/kg (M 200), an immobilization-induced stress control group (S), an immobilization-induced stress group administered MOTILIPERM 100 mg/kg (S + M 100), and MOTILIPERM 200 mg/kg (S + M 200). Stressed rats (n = 30) were subjected to stress by immobilization for 6 h by placing them in a Perspex restraint cage, while controls (n = 20) were maintained without disturbance. Rats were administrated 100 or 200 mg/kg MOTILIPERM once daily for 30 days 1 h prior to immobilization. At the end of the treatment period, we measured body and reproductive organ weight; sperm parameters; histopathological damage; reproductive hormone levels; steroidogenic acute regulatory protein (StAR); biomarkers of oxidative stress; and apoptosis markers. MOTILIPERM treatment improved testicular dysfunction by up-regulating (p < 0.05) sperm count, sperm motility, serum testosterone level, StAR protein level, Johnsen score, and spermatogenic cell density in stressed rats. MOTILIPERM decreased oxidative stress by increasing (p < 0.05) testicular superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione peroxidase-4 (GPx 4), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) levels and decreasing (p < 0.05) malondialdehyde (MDA) and reactive oxygen species/reactive nitrogen species (ROS/RNS) levels. Furthermore, MOTILIPERM down-regulated (p < 0.05) cleaved caspase 3 and BCL2 associated X protein (Bax) levels; increased pro caspase-3 and B-cell lymphoma 2 (Bcl-2) levels; and upregulated testicular germ cell proliferation in stressed rats. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels also significantly (p < 0.05) decreased after pretreatment with MOTILIPERM in stressed rats. Collectively, our results suggest that, in immobilization-mediated stress-induced testicular dysfunction, MOTILIPERM sustains normal spermatogenesis via antioxidant and anti-apoptotic activities by activating the NRF/HO-1 signaling pathway.

Background Sarcopenia progresses in chronic kidney disease (CKD) and is positively correlated with mortality in end-stage kidney disease patients. Circulating irisin, an exercise-induced myokine, gradually decreases during CKD stage progression. Irisin inhibits the progression of kidney fibrosis, which is the final common outcome of CKD. Our preliminary study with C2C12 cells showed that Dojuksan, a herbal decoction, increases the expression of PGC1α (a regulator of irisin) and FNDC5 (a precursor of irisin). Hypothesis Dojuksan may increase circulating irisin and prevent the progression of kidney fibrosis. Study Design and Methods Unilateral ureteral obstruction (UUO) was performed on seven-week-old male C57BL/6 mice to induce kidney tubulointerstitial fibrosis. Dojuksan (50, 100, or 200 mg/kg/day) or losartan (1.5 mg/kg/day), a standard clinical treatment for CKD, was administered orally one day prior to surgery and continued for seven days thereafter. To determine the role of irisin released from muscles, TGFβ-stimulated murine proximal tubular epithelial cells (mProx24 cells) were treated with conditioned media (CM) from Dojuksan-treated C2C12 muscle cells transfected with FNDC5 siRNA. Results UUO mice exhibited muscle wasting along with progressive kidney injury. Similar to losartan, Dojuksan ameliorated kidney inflammation and fibrosis in UUO mice. Dojuksan, but not losartan, increased plasma irisin concentration in UUO mice. Dojuksan significantly increased basal FNDC5 expression and inhibited TNFα-induced and indoxyl sulfate-induced FNDC5 down-regulation in C2C12 cells. The TGFβ-induced collagen I (COL1) up-regulation in mProx24 cells was effectively inhibited by CM from C2C12 cells after Dojuksan treatment. Moreover, irisin inhibited TGFβ-induced COL1 in mProx24 cells, which was not affected by CM from C2C12 cells transfected with FNDC5 siRNA. Conclusion Dojuksan ameliorates kidney fibrosis through irisin-mediated muscle-kidney crosstalk, suggesting that Dojuksan may be used as an alternative therapeutic agent against CKD.

Background There are various Helicobacter species colonizing the stomachs of animals. Although Helicobacter species usually cause asymptomatic infection in the hosts, clinical signs can occur due to gastritis associated with Helicobacter in animals. Among them, Helicobacter pylori is strongly associated with chronic gastritis, gastric ulcers, and gastric cancers. As the standard therapies used to treat H. pylori have proven insufficient, alternative options are needed to prevent and eradicate the diseases associated with this bacterium. Cheonwangbosim-dan (CBD), a traditional herbal formula that is popular in East Asia, has been commonly used for arterial or auricular flutter, neurosis, insomnia, and cardiac malfunction-induced disease. Objectives The present study investigated the antimicrobial effect of CBD on H. pylori-infected human gastric carcinoma AGS cells and model mice. Methods AGS cells were infected with H. pylori and treated with a variety of concentrations of CBD or antibiotics. Mice were given 3 oral inoculations with H. pylori and then dosed with CBD (100 or 500 mg/kg) for 4 weeks or with standard antibiotics for 1 week. One week after the last treatment, gastric samples were collected and examined by histopathological analysis, real-time quantitative polymerase chain reaction, and immunoblotting. Results Our results showed that CBD treatment of AGS cells significantly reduced the H. pylori-induced elevations of interleukin-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In the animal model, CBD treatment inhibited the colonization of H. pylori and the levels of malondialdehyde, inflammation, proinflammatory cytokines, iNOS, and COX-2 in gastric tissues. CBD also decreased the phosphorylation levels of p38 mitogen-activated protein kinase family. Conclusions This study suggests that CBD might be a prospective candidate for treating H. pylori-induced gastric injury.

Ethnopharmacological relevance Dohongsamul-tang (DST) is a traditional herbal formula used to promote the blood circulation and inhibit inflammation, and also widely has been used in the treatment of patients with chronic liver diseases in Korea and China. Aim of the study This study aimed to investigate the effect of DST on regulation of lipid metabolism of chronic liver diseases in mouse model of non-alcoholic fatty liver diseases (NAFLD). Materials and methods In this study, we evaluated the effect of DST on high-fat and high-cholesterol diet (HFHC, 40% fat and 1% cholesterol)-induced NAFLD, and applied unbiased lipidomics using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF MS) coupled with multivariate analysis. Results DST improved hepatic morphology and reduced levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In addition, DST inhibited hepatic lipid accumulation through the downregulation of C/EBPα, PPARγ, and pAMPK. To further elucidate the effect of DST on hepatic lipid metabolism, we applied UPLC/Q-TOF MS-based lipidomics. The score plots of partial least squares-discriminant analysis (PLS-DA) showed that DST changed the lipid metabolic pattern of high-fat and high-cholesterol diet (HFHC) mice. Twenty-two lipid metabolites were selected as biomarkers regulated by DST and pathway analysis revealed that sphingolipid metabolism and glycerophospholipid metabolism were associated with the effect of DST on NAFLD. Among the 22 selected biomarkers, 14 were phospholipids, and DST significantly reversed the increased expression of lysophospholipase 3 (LYPLA3) and neuropathy target esterase (NTE), which are key enzymes in glycerophospholipid metabolism. Given that alterations in sphingolipids and phospholipids can have effects on apoptosis and insulin resistance (IR), we subsequently investigated changes in the expression of apoptosis-related proteins, including Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl2), and IR-related markers after DST treatment. We accordingly found that the ratio of Bax to Bcl-2 expression, a maker of apoptosis, was also elevated in HFHC mice and reduced by DST treatment. In addition, DST enhanced hepatic insulin signaling by upregulating the expression of insulin receptor substrate 1 (IRS-1) and phospho-protein kinase B (pAKT), and oral glucose tolerance test (OGTT) analysis indicated that this herbal preparation also ameliorated systemic IR. Conclusions This study suggested that DST might have an effect on NAFLD by regulating the metabolism of lipids such as phospholipids and sphingolipids and demonstrated that lipidomic profiling is useful to investigate the therapeutic effects of herbal decoctions from traditional Korean and Chinese medicine.

Background Artemisia scoparia Waldst. et Kitaib (AS) (Oriental wormwood, known as Bissuk in Korea) is a plant used in cosmetic and pharmaceutical treatments. However, the effect of AS on atopic dermatitis (AD) has not been described. Aim To examine the inhibitory effect of AS on AD using a murine model. Methods We applied either AS, the butanol-extracted fraction of AS (Bu-OH) or 3,5-dicaffeoyl-epi-quinic acid (DEQA, a major component of Bu-OH) topically for 3 weeks to 2,4-dinitrofluorobenzene (DNFB)-induced skin lesions in BALB/c mice. Results AS, Bu-OH and DEQA suppressed the clinical symptoms of DNFB-induced skin lesions and he associated scratching behaviour. Numbers of inflammatory cells infiltrating skin lesions were significantly reduced by AS or Bu-OH application but not by DEQA. In addition, AS significantly suppressed serum levels of histamine and IgE, while Bu-OH significantly suppressed serum levels of histamine, IgE, thymic stromal lymphopoietin (TSLP), interleukin (IL)-4 and IL-6, and DEQA significantly suppressed serum levels of histamine, IgE, TSLP and IL-4 in DNFB-induced AD mice. In skin lesions, AS and Bu-OH significantly reduced inflammatory cytokines, whereas DEQA did not. AS, Bu-OH and DEQA all significantly suppressed caspase-1 activities. Conclusions These results demonstrate the anti-AD effects of AS, Bu-OH and DEQA, and suggest that all three have therapeutic potential.

Woohwangcheongsimwon (WHC) is a mixture of herbal medicines that is widely prescribed in Korean traditional medicine. SIRT1 is known for its regulatory roles in energy metabolism, oxidative stress, and circadian rhythms. This study was designed to determine whether WHC can increase and mimic the biological reactions of SIRT1 activation. Ten-month-old male mice were divided into four groups: nontreated normal diet (ND), nontreated high-fat diet (HFD), WHC-treated ND, and WHC-treated HFD. Body weight and cognitive functions were evaluated after treatment. The hippocampal expressions of SIRT1 and PGC-1α were also measured. The components of WHC were identified by liquid chromatography. High-fat diet-fed mice gained more weight and demonstrated greater deficits in short-term and long-term cognitive functions. WHC suppressed the deleterious effects of a HFD on weight gain and cognitive decline, but showed no prominent effects on animals fed NDs. The herbal treatment also increased the expression of SIRT1 and PGC-1α in the hippocampus. Despite the induction of hippocampal SIRT1 expression by WHC, resveratrol was not present among the natural compounds identified. This expression might have contributed to the suppression of high-fat diet-induced memory deficits in mice treated with the herbal mixture.

Ethnopharmacological relevance Gangjihwan (DF) which is composed of Ephedra intermedia, Lithospermum erythrorhizon, and Rheum palmatum has been used for the treatment of obesity in traditional medical clinics in Korea. Aim of the study This study was conducted to standardize DF and elucidate its mechanism of action for inhibiting fat accumulation in adipocytes and adipose tissues. Materials and methods The herbal ingredients of DF were extracted in water, 30% ethanol or 70% ethanol and freeze-dried followed by HPLC analyses. 3T3-L1 adipocytes and high-fat diet-induced obese mice were treated with each of the three DF preparations. Messenger RNA and protein expression levels were measured by real-time qPCR and Western blotting. RNA-Seq analyses were conducted to examine the effects of DF treatment on whole transcriptome of adipocyte. Results (−)-Ephedrine and (+)-pseudoephedrine from E. intermedia, aloe-emodin and chrysophanol from R. palmatum and shikonin from L. erythrorhizon were identified as phytochemical components of DF. DF caused dose-dependent inhibition of fat accumulation in 3T3-L1 adipocytes. It also significantly reduced adipose tissue mass and adipocyte size in high-fat diet-induced obese mice. DF was found to down-regulate the expressions of the lipogenic transcription factors such as sterol regulatory element binding protein 1C (SREBP1C), peroxisome proliferator activated receptor gamma (PPARγ), and CCAAT/enhancer binding protein alpha (C/EBPα). Among the three preparations of DF, the 70% ethanol extract was the most effective. RNA-Seq analyses showed that DF treatment decreased the expression levels of up-regulators and increased those of down-regulators of lipogenic transcription factors. Conclusions DF preparations, among which 70% ethanol extract was the most effective, reduced fat accumulation in 3T3-L1 adipocytes and high-fat diet-induced obese mice through the down-regulation of lipogenic transcription factors SREBP1C, PPARγ and C/EBPα.

Ethnopharmacological relevance Larvae of the rhinoceros beetle (Allomyrina dichotoma) (ADL) are used ethnopharmacologically to treat gut-related disorders in Korea and China since 1596 and are also approved as a safe novel food with high nutritional value. Aim of the study: We investigated the protective effects of ADL extract against leaky gut disease using a Drosophila model and sought to elucidate the underlying biological mechanisms. Materials and methods We examined the protective effects of ADL extract (2 mg/mL) against the leaky gut disease using a dextran sulfate sodium (DSS)-induced leaky gut Drosophila melanogaster model. Results We found that oral administration of ADL extracts significantly increase the survival rate of DSS-fed Drosophila. Under conditions of DSS-induced gut damage, ADL extract reduced gut cell apoptosis and gut permeability, resulting in the maintenance of gut tissue homeostasis. Furthermore, we observed that oral administration of ADL extract can induce high levels of E-cadherin gene expression and also restored the original membrane localization of DSS-disrupted E-cadherin contiguous with the armadillo. Conclusion We concluded that ADL extract plays an important role in maintaining gut homeostasis through the up-regulation of E-cadherin and that it may have a protective effect against leaky gut syndrome.

Chemotherapeutics are often used to inhibit the proliferation of cancer cells. However, they can also harm healthy cells and cause side effects such as immunosuppression. Especially traditional oriental medicines long used in Asia, may be beneficial candidates for the alleviation of immune diseases. Cervus nippon mantchuricus extract (NGE) is currently sold in the market as coffee and health drinks. However, NGE was not widely investigated and efficacy remain unclear and essentially nothing is known about their potential immune-regulatory properties. As a result, NGE induced the differentiation of RAW264.7 macrophage cells. NGE-stimulated RAW264.7 macrophage cells elevated cytokines levels and NO production. NGE-stimulated RAW264.7 macrophage cells activated MAPKs and NF-κB signaling pathways. NGE encouraged the immuno-enhancing effects in immunosuppressed short-term treated with NGE mice model. NGE or Red ginseng encouraged the immuno-enhancing effects in immunosuppressed long-term treated with NGE mice model. Our data clearly show that NGE contains immune-enhancing activity and can be used to treat immunodeficiency.

Edible insects have been reported to produce metabolites showing various pharmacological activities, recently emerging as rich sources of health functional food. In particular, the larvae of Protaetia brevitarsis seulensis (Kolbe) have been used as traditional Korean medicines for treating diverse diseases, such as breast cancer, inflammatory disease, hepatic cancer, liver cirrhosis, and hepatitis. However, only few chemical investigations were reported on the insect larvae. Therefore, the aim of this study was to discover and identify biologically active chemical components of the larvae of P. brevitarsis seulensis. As a result, a quinoxaline-derived alkaloid (1) was isolated, which was not reported previously from natural sources. In addition, other related compounds (2, 4–10, 15, 16) were also encountered for the first time from the larvae. The structures of all the isolated compounds were established mainly by analysis of HRESIMS, NMR, and electronic circular dichroism data. Compound 5 exhibited inhibition of tyrosinase with IC50 value of 44.8 µM.

Blood stasis syndrome (BSS), additionally called Eohyul, is a basic pathological concept in Traditional Korean Medicine. Do In Seung Gi‑Tang (DISGT) is herbal medicine used for the treatment of BSS. It primarily treats metabolic diseases (MDs) including obesity, hypertension, diabetes mellitus and gynecological diseases, by promoting blood circulation. The present study aimed to investigate the anti‑adipogenesis effect of DISGT in 3T3‑L1 adipocytes using Oil Red O staining, and assessing levels of triglycerides (TGs) and leptin in adipocytes by ELISA and western blot analysis. The results demonstrated that DISGT treatment had inhibitory effects on fat droplet formation, TG accumulation, leptin production and cytokine content, during 3T3‑L1 adipocyte differentiation, without affecting cell viability. Additionally, DISGT treatment significantly suppressed the protein expression levels of peroxisome proliferator‑activated receptor γ and CAAT/enhancer binding protein α. These results provide evidence that DISGT has anti‑adipogenesis effects on preadipocytes and adipocytes by significantly blocking adipocyte differentiation and lipid accumulation, and suppressing adipogenic gene expression. Therefore, the present study demonstrated the potential of DISGT as a therapeutic agent for the treatment of MDs.

Background: Pestiviruses in general, and Bovine Viral Diarrhea (BVD) in particular, present several potential targets for directed antiviral therapy.Material and Methods: The antiviral effect of Cynanchum paniculatum (Bge.) Kitag (Dog strangling vine: DS) extract on the bovine viral diarrhea (BVD) virus was tested. First, a cytotoxicity test in MDBK (Madin-Darby bovine kidney) cells was done with all organic extract concentrations.Results: The cytotoxic concentration CC50 for the ethyl acetate (EA) extracts was 18.2 ug/ml. In the tissue culture, infectious dose (TCID50) assay, the BVD virus decreased when treated with 18.2 ug/ml of the ethyl acetate extracts.Conclusion: Ethyl acetate extracts and fractions of the DS extract could be used as a potential antiviral for BVD.Keywords: Antiviral, Bovine viral diarrhoea(BVD) virus, Cynanchum paniculatum (Bge.) Kitag.Ethly acetate extract

Background Yangkyuksanwha-tang (YST) is an herbal medicine based on Sasang constitutional medicine (SCM) and is widely used in Korean traditional medicine. The aim of the study was to evaluate the effect of YST on obesity in high-fat diet (HFD)-induced obese mice. Methods We induced obesity in C57bl/6 J mice using a HFD, and then orally administered 300 mg/kg YST for 6 weeks. We measured body weight, food efficiency, organ and fat weight, serum biochemical parameters, and obesity-related gene expression, and carried out histological analysis at the end of the experimental period. Results YST significantly reduced the absolute body weight and food efficiency ratio. The serum, aminotransferase, glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels were significantly lower in the YST-treated group than in the control group, whereas the high-density lipoprotein-cholesterol level in the YST-treated group was significantly higher. The YST-treated group also showed a significant reduction in regional fatty tissues and the absolute weight of various organs. We also observed a significantly reduced expression of AP2/FABP4, C/EBP-β, leptin, and SREBP1c/ADD1 mRNA, and significantly increased expression of UCP-2 and adiponectin mRNA in adipose tissue in the YST-treated group. YST also decreased the lipid droplet size and lipid accumulation in the liver, as well as adipocyte size in epididymal adipose tissue. At the dose tested, YST was non-toxic to the liver and kidneys of the mice. Conclusion The results imply that YST has anti-obesity effects in obesity-induced mice. Although the number of experimental animals was limited and the drug effects concern mice, rather than humans, which have different constitutions, the study has valuable implications with respect to the general effects of YST.

Sutaehwan (STH) has been used in Korean medicine for the treatment of abortus habitualis such as fetal restlessness in the uterus. Previously, we reported that a modified formulation of STH, Sutaehwan-Gami, has phytoestrogen-like properties in an ovariectomized menopausal rat model. However, the therapeutic effects of STH and the precise mechanisms by which STH affects various menopausal symptoms remain poorly understood. The current study was designed to explore the effects of a modified form of STH on menopausal anxiety, depression and heart hypertrophy and its mechanisms in 4-vinylcyclohexene diepoxide (VCD)-induced menopausal mouse models. VCD-induced menopausal model mice were fed a modified form of STH, which contained water extract of 3 herbs (called STH_KP17001) at a dose of 100 or 300 mg/kg/d or as a positive control, estradiol at a dose of 0.2 mg/kg/d with standard mouse pellets for 13 weeks. The results show that STH_KP17001 significantly restored the VCD-induced weight reduction of uterine and ovary through the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in the uterus and ovary. Moreover, STH_KP17001 showed slight proliferative effects and estrogen receptor α phosphorylation in MCF-7 cells. Treatment with STH_KP17001 reversed VCD-induced anxiety and depression through AMP-activated protein kinase (AMPK) activation and brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex, while improving heart hypertrophy through inactivation of inhibitor of kappaB α (IκBα) in the heart. The results indicate that STH_KP17001 improves menopause-induced anxiety, depression and heart hypertrophy, implying its protective role for the management of menopausal symptoms.

Ethnopharmacological relevance Mahuang-Tang (MHT) has traditionally been used in Asia to treat a variety of diseases, such as fever without sweating, joint pain, lower back pain, asthma, and gynecological conditions. Polycystic ovary syndrome (PCOS) is a kind of gynecological disease that causes amenorrhea, infertility, and menopausal and urogenital disorders that could benefit from MHT treatment. Aim of the study In this study, we examined the effects of MHT on ovarian hormones and steroidogenic enzymes in female PCOS rats. Methods and results The PCOS rat model was induced by Letrozole, and an in vivo evaluation of whether the dietary consumption of MHT improved the PCOS-like symptoms was conducted. The luteinizing hormone (LH) level and luteinizing hormone/follicular-stimulating hormone (LH/FSH) ratio increased in PCOS rats but decreased following MHT treatment. In the PCOS rats, the reduced estrogen level was restored to that of normal controls with MHT treatment in serum. The transcription level(s) of gonadotropin receptors (Fshr and Lhr), steroid receptors (Pgr, and Esr1) and steroidogenic enzymes (Cyp19a1, Hsd3b1, Hsd17a1, and Cyp11a1) changed under the PCOS condition, and were regulated by MHT treatment in the ovaries of PCOS rats. The reproductive tissues of Letrozole-induced PCOS rats were restored into estrogenic condition from androgen environments. Conclusion These results suggest that MHT ameliorates the symptoms of PCOS by improving the dysregulation of ovarian steroids and steroidogenic enzymes in PCOS rats.

Ethnopharmacological relevance TADIOS is an herbal formulation prepared from a mixture of Taraxacum officinale (L.) Weber ex F.H.Wigg, Dioscorea batatas Decaisne and Schizonepeta tenuifolia (Benth.) Briquet. These plants have traditionally been used in Asia to treat a variety of respiratory diseases. A bulk of literature on traditional Korean medicine describe their activities and functions for respiratory problems. Therefore, we hypothesized that the combination of these plants might be effective in alleviating respiratory symptoms. Aim of the study In this study, we investigated whether TADIOS ameliorates LPS-induced acute lung injury via regulation of the Nrf2-HO-1 signaling pathway. Materials and methods The LPS-induced acute lung injury mouse model was used to determine the anti-inflammatory and anti-oxidative stress effects of TADIOS. The amount of marker compounds contained in TADIOS was quantified using high-performance liquid chromatography (HPLC) analysis. The protein level of pro-inflammatory cytokines in culture supernatant was measured by ELISA. Changes in the RNA level of pro-inflammatory cytokines in mice lungs and RAW264.7 cells were measured by quantitative RT-PCR. The relative amounts of reactive oxygen species (ROS) were measured by DCF-DA assay. Western blot analysis was used to evaluate expression of cellular proteins. Effects of TADIOS on antioxidant responsive elements (AREs) were determined by luciferase assay. The severity of acute lung injury was evaluated by Hematoxylin & Eosin (H&E) staining. To test the effects of TADIOS on LPS-induced oxidative stress, myeloperoxidase (MPO) activity and the total antioxidant capacity were measured. Results TADIOS was prepared by extraction of a blend of these three plants by ethanol, and quality control was performed through quantification of marker compounds by HPLC and measurement of bioactivities using cell-based bioassays. In the murine macrophage cell line RAW264.7, TADIOS effectively suppressed the production of pro-inflammatory cytokines such as IL-6 and IL-1β, and also ROS induced by LPS. When RAW264.7 cells were transfected with a luciferase reporter plasmid containing nucleotide sequences for AREs, TADIOS treatment increased the level of relative luciferase units in a dose-dependent manner. In the LPS-induced acute lung injury mouse model, orally administered TADIOS alleviated lung damage and neutrophil infiltration induced by LPS. Consistent with the in vitro data, treatment with TADIOS inhibited the LPS-mediated expression of pro-inflammatory cytokines and oxidative stress, and activated the Nrf2-HO-1 axis. Conclusion Our data suggest the potential for TADIOS to be developed as a safe and effective therapeutics for the treatment of acute respiratory distress syndrome., Graphical abstract Image 1

Muscle fatigue is induced by an acute or chronic physical performance inability after excessive physical activity often associated with lactate accumulation, the end-product of glycolysis. In this study, the water-extracted roots of Sanguisorba officinalis L., a herbal medicine traditionally used for inflammation and diarrhea, reduced the activities of lactate dehydrogenase A (LDHA) in in vitro enzyme assay myoblast C2C12 cells and murine muscle tissue. Physical performance measured by a treadmill test was improved in the S. officinalis-administrated group. The analysis of mouse serum and tissues showed significant changes in lactate levels. Among the proteins related to energy metabolism-related physical performance, phosphorylated-AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor-coactivator-1 alpha (PGC-1α) levels were enhanced, whereas the amount of LDHA was suppressed. Therefore, S. officinalis might be a candidate for improving physical performance via inhibiting LDHA and glycolysis.

Animal venoms, widespread throughout the world, are complex mixtures, the composition of which depends on the venom-producing species. The objective of this study was to contribute to the development of animal venom-based medicines by investigating the use of animal venom pharmacopuncture in Korean medicine (KM) institutions. We surveyed 256 public health centers from 1 through 31 October 2019 as guided by the Ministry of Health and Welfare (MoHW). A questionnaire developed by an expert group was distributed and collected for statistical analysis. The survey identified three types of animal venom-based pharmacopuncture: bee, snake, and toad venoms. The medications are based on a single animal venom ingredient and produced in 11 external herbal dispensaries (EHDs). Each animal venom is processed, refined, and freeze-dried in a cleanroom to produce a powder formulation that is later measured, diluted, filtered, filled, sealed, sterilized, and packaged as pharmacopuncture injections used in KM institutions. Bee venom therapy is effective in treating musculoskeletal pain, snake venom therapy is effective in controlling bleeding during surgery, and toad venom therapy is effective in cancer treatment. The study suggests that bee, snake, and toad venoms could be used in medical institutions and have the potential for drug development.

This research study explored the anti-cancer effects of natural materials in South Korea. Although South Korea has a long history of traditional medicine, many natural materials of South Korea have not yet been introduced to the rest of the world because of language barriers and inconsistent study conditions. In the past 3 years, 56 papers introducing 56 natural materials, which have anti-cancer effects, have been published by scientists in South Korea. Further, these studies have introduced five kinds of natural materials presented in research papers that were written in Korean and are therefore virtually unknown overseas. The anti-cancer effects were confirmed by 2-3 cancer markers in the majority of the studies, with the most common targets being breast cancer cells and gastric cancer cells. These cancers have the greatest incidence in South Korea. The natural materials studied not only exhibit anti-cancer activity but also display anti-inflammatory, anti-oxidative stress, and anti-diabetic activities. They have not yet been used for the direct treatment of disease but have potential as medicinal materials for alternative and complementary medicine for the treatment of many modern diseases. Many natural materials of South Korea are already known all over the world, and with this study, we hope to further future research to learn more about these natural medicines.

The protective effect of Phellinus linteus (ethanol extract) against osteoporosis was investigated using the Saos-2 human osteoblast-like cell line and osteoclasts. A nontoxic concentration of Ph. linteus (10-2 to 10-8 mg mL-1) increased alkaline phosphatase (ALP) (EC 3.1.3.1) activity to a larger extent than soy did. Ph. linteus also attenuated the number and the activity of tartrate-resistant acid phosphatase-positive multinucleated osteoclasts. These results indicate that Ph. linteus likely regulated both osteoblasts and osteoclasts, contributing to the protection against osteoporosis. The protective effect of Ph. linteus was examined in ovariectomized (OVX) rats. Histological analysis indicates that Ph. linteus improved trabecular bone mass and reduced osteoclast frequency without affecting lipid droplet accumulation in the femur of OVX rats. A Ph. linteus supplementation for 12 weeks also significantly increased serum ALP activity and reduced urinary deoxypyridinoline level in OVX rats. Ultimately, we found that 12-week Ph. linteus supplementation increased the bone accumulation of minerals, including calcium, magnesium, and phosphorus. Collectively, Ph. linteus protected against osteoporosis by balancing the number of osteoblasts and osteoclasts, which was particularly associated with increased ALP activity in vitro and in vivo and mineral accumulation in bone.

Agastache rugosa is used as a Korean traditional medicine to treat gastric diseases. However, the active ingredients and pharmacological targets of A. rugosa are unknown. In this study, we aimed to reveal the pharmacological effects of A. rugosa on gastritis by combining a mice model and a network pharmacology method. The macrophage and gastritis-induced models were used to evaluate the pharmacological effects of A. rugosa. The results show that A. rugosa relieved mucosal damage induced by HCl/EtOH in vivo. Network analysis identified 99 components in A. rugosa, six components were selected through systematic screening, and five components were linked to 45 gastritis-related genes. The main components were acacetin and luteolin, and the identified core genes were AKT serine/threonine kinase 1 (AKT1), nuclear factor kappa B inhibitor alpha (NFKBIA), and mitogen-activated protein kinase-3 (MAPK3) etc. in this network. The network of components, target genes, protein&ndash, protein interactions, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was closely connected with chemokines and with phosphoinositide 3-kinase-Akt (PI3K/AKT), tumor-necrosis-factor alpha (TNF&alpha, ), mitogen-activated protein kinase, nuclear factor kappa B, and Toll-like receptor (TLR) pathways. In conclusion, A. rugosa exerts gastro-protective effects through a multi-compound and multi-pathway regulatory network and holds potential for treating inflammatory gastric diseases.

Background In Traditional Korean and Chinese medicine, the herbal remedy Yijin (Erchen)-Tang (YJT) is widely used to treat obesity-related disorders, and its therapeutic potential has been demonstrated in numerous studies. However, the systemic effect of YJT on obesity status and change of lipid metabolism by YJT still remains unknown. Purpose This study aimed to investigate the therapeutic mechanism of the YJT on obesity by using lipidomics. Methods To evaluate the effects of treatment with YJT on obesity, C57BL/6 J mice were fed a high-fat and high-cholesterol (HFHC, 40% fat and 1% cholesterol) diet for 8 weeks and treated them with YJT for an additional 6 weeks. We then performed untargeted lipidomic analysis using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry mass spectroscopy coupled with multivariate statistical analysis. Results YJT ameliorated obesity induced systemic inflammation and improved insulin resistance. Additionally, YJT protected against HFHC-diet-induced hepatic inflammation. To explore specific changes in lipid metabolism associated with the therapeutic effects of YJT, we performed untargeted lipid profiling of the plasma. Partial least squares-discriminant analysis (PLS-DA) score plots showed that YJT altered the lipid metabolic pattern of HFHC mice. In particular, ceramides and triglycerides with saturated fatty acids and monounsaturated fatty acids were significantly changed by YJT, which were significantly associated with insulin resistance, the AGE-RAGE signaling pathway in diabetic complications and adipocytokine signaling pathway in pathway enrichment analysis. Thus, we analyzed the changes in adipocytes and adipokine caused by YJT, and confirmed that YJT alleviated adipocytes inflammation and macrophage infiltration, and reversed HFHC-induced alterations in leptin and adiponectin levels in adipose tissue and plasma. Conclusion These data suggest that YJT ameliorates obesity-induced systemic inflammation and insulin resistance by regulating lipid metabolism, and demonstrated that lipidomic profiling is a useful method to investigate the therapeutic effects of herbal decoctions in traditional Korean and Chinese medicine.

Ethnopharmacological relevance A promising approach to treat a variety of diseases are considered as complementary and alternative herbal medicines. Prunus serrulata var. spontanea L. (Rosaceae) is used as herbal medicine to treat allergic diseases according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea. Aim of the study We prepared the aqueous extract of the bark of P. serrulata (AEBPS) and aimed to investigate the effects in mouse anaphylaxis models and various types of mast cells, including RBL-2H3, primary cultured peritoneal and bone marrow-derived mast cells. Materials and methods We used ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models, in vivo. The control drug dexamethasone (10 mg/kg) was used to compare the effectiveness of AEBPS (1–100 mg/kg). In vitro, IgE-stimulated mast cells were used to confirm the role of AEBPS (1–100 μg/mL). For statistical analyses, p values less than 0.05 were considered to be significant. Results In ASA model, oral administration of AEBPS suppressed the hypothermia and increased level of serum histamine in a dose-dependent manner. AEBPS attenuated the serum IgE, OVA-specific IgE, and interleukin (IL)-4. Oral administration of AEBPS also blocked mast cell-dependent PCA. AEBPS suppressed degranulation of mast cells by reducing intracellular calcium level in mast cells. AEBPS inhibited tumor necrosis factor-α and IL-4 expression and secretion in a concentration-dependent manner through the reduction of nuclear factor-κB. Conclusions On the basis of these findings, AEBPS could serve as a potential therapeutic target for the management of mast cell-mediated allergic inflammation and as a regulator of mast cell activation.

Ethnopharmacological relevance Korean Red ginseng extract (RG) is one of the most widely used traditional health functional food in Asia, which invigorates immunity and vital energy. RG have been suggested to inhibit proliferation, invasion, and inflammation in several cancer cell lines. Correspondingly, clinical studies have raised the possibility that RG could augment therapeutic efficacy in cancer patients. However, little is known about the anti-cancer effects of RG in glioblastoma (GBM), the most common and aggressive brain tumor for which effective therapeutic regimens need to be developed. Aim of this study: Here, we assessed the in vivo and in vitro anti-cancer properties of RG in a patient-derived xenograft mouse model and GBM stem cell (GSC) line. Materials and methods We evaluated the anti-cancer effects of RG in patient-derived GBM xenograft mice with and without combined concurrent chemo- and radiation therapy (CCRT). Furthermore, we verified the in vitro effects of RG on the proliferation, cell death, and stem cell-like self-renewal capacity of cancer cells. Finally, we investigated the signaling pathway affected by RG, via which its anti-cancer effects were mediated. Results When combined with CCRT, RG impeded GBM progression by reducing cancer cell proliferation and ionized calcium-binding adapter molecule 1 (IBA1)-positive immune cell recruitment. The anti-cancer effects of RG were mediated by Rg3 and Rh2 ginsenosides. Rg3 promoted cell death while Rh2 did not. Furthermore, both Rg3 and Rh2 reduced cell viability and self-renewal capacity of GSCs by inhibiting Wnt/β-catenin signaling. Conclusion Therefore, our observations imply that RG could be applied to the GBM patients in parallel with CCRT to enhance therapeutic efficacy.

Cervus nippon mantchuricus extract, known as nok‑gol (NGE) in Korean, is useful for the treatment of various inflammatory diseases, including bone resorption and neutropenia. However, NGE has not been widely investigated, and its efficacy and safety remain to be fully elucidated. In the present study, histological analysis, blood analysis, reverse transcription‑semi-quantitative polymerase chain reaction analysis and enzyme‑linked immunosorbent assays were performed to verify the inhibitory effect of NGE on atopic dermatitis (AD) in BALB/c mice and on inflammatory effects in HMC‑1 human mast cells. NGE suppressed the development of AD in mice, and decreased the infiltration of inflammatory cells, mast cells and CD4+ T cells into AD skin lesions. NGE also decreased leukocyte levels induced by 2,4‑dinitrochlorobenzene (DNCB). NGE alleviated AD‑like inflammatory symptoms in mice by suppressing the production of CD4+ T cells. NGE downregulated the mRNA expression of inflammatory cytokines induced by DNCB. It also decreased the serum immunoglobulin E concentration and inflammatory cytokine levels in DNCB‑treated BALB/c mice. The in vitro experiments demonstrated that NGE reduced the phorbol 12‑myristate 13‑acetate + ionomycin‑induced expression of pro‑inflammatory cytokines interleukin (IL)‑4, IL‑13, tumor necrosis factor‑α, and IL‑6 in HMC‑1 cells. Taken together, the results of the present study indicated that NGE suppressed the progression of DNCB‑induced AD in BALB/c mice and reduced inflammatory effects in HMC‑1 cells. This suggests that NGE may be a useful drug for the treatment of AD.

Ethnopharmacological relevance According to traditional Korean medicine theory in which children's growth retardation is attributed to blood deficiency, Siwu decoction (SWD), a representative treatment for blood deficiency, was chosen as a sample. Aim of the study: To evaluate the effects of SWD on chondrocyte proliferation of growth plate in adolescent female rats. Materials and methods Female adolescent rats were allocated to one of the following four groups; SWD 100 and 300 mg/kg, recombinant human growth hormone, and vehicle for 4 days. Tetracycline was intraperitoneally injected at 48 h before sacrifice to obtain a band exhibiting fluorescence by binding newly formed bone. Bromodeoxyuridine was injected at day 2–4 to mark proliferating chondrocytes. To evaluate possible mechanisms of SWD, expressions of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate were examined by immunohistochemistry. Results Treatment with SWD significantly increased the number of BrdU-positive chondrocytes and the new bone formation in the proximal growth plate of tibia compared to the vehicle treated control group. SWD also increased the expression of IGF-1 and BMP-2 in the proliferative and hypertrophic zones of the growth plate. Conclusions SWD 300 mg/kg stimulates chondrocyte proliferation and new bone formation in the growth plate. Immunohistochemical studies indicate that the effects of SWD may be due to upregulation of local IGF-1 and BMP-2 expression in the growth plate, which may be considered as a GH-dependent paracrine-autocrine pathway.

The Nardostachys jatamansi DC (NJ) root has been used as a sedative or analgesic to treat neurological symptoms and pain in traditional Korean medicine. Here, we investigate the potential effects of NJ on Alzheimer's disease (AD) and reveal the molecular mechanism through which NJ exerts its effects. The neuroprotective effect of the NJ root ethanol extract against β amyloid (Aβ) toxicity was examined in vitro using a cell culture system and in vivo using a Drosophila AD model. The NJ extract and chlorogenic acid, a major component of NJ, inhibited Aβ-induced cell death in SH-SY5Y cells. Moreover, the NJ extract rescued the neurological phenotypes of the Aβ42-expressing flies (decreased survival and pupariation rate and a locomotor defect) and suppressed Aβ42-induced cell death in the brain. We also found that NJ extract intake reduced glial cell number, reactive oxygen species level, extracellular-signal-regulated kinase (ERK) phosphorylation, and nitric oxide level in Aβ42-expressing flies, without affecting Aβ accumulation. These data suggest that the neuroprotective activity of NJ might be associated with its antioxidant and anti-inflammatory properties, as well as its inhibitory action against ERK signaling; thus, NJ is a promising medicinal plant for the development of AD treatment.

The fruit of Stauntonia hexaphylla is commonly used as a traditional anthelmintic in Korea, Japan, and China. However, its anti-inflammatory activity and the underlying mechanisms have not been studied systematically. In the present study, we examined the anti-inflammatory activities of an aqueous extract of S. hexaphylla fruit (SHF) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The SHF extract contained anti-inflammatory compounds, such as neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid. The extract inhibited protein levels of inducible nitric oxide synthase and the activity of cyclooxygenase enzyme, with concomitant reductions in the production of nitric oxide and prostaglandin E2 in LPS-activated RAW 264.7 cells. Additionally, the SHF extract reduced the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The SHF extract attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing the phosphorylation of its inhibitor, IκBα. Furthermore, the SHF extract showed a significant anti-inflammatory effect in vivo by reducing the volume of carrageenan-induced paw edema in rats. Our results suggest that the SHF extract exerts potential anti-inflammatory properties against LPS-activated RAW 254.7 cells, and in an animal model of inflammation.

Amomum tsao-ko (A. tsao-ko) has been used as a traditional medicine for the treatment of infectious and digestive disorders. In the present study, we report the anti-inflammatory activity and molecular mechanism of 2,8-decadiene-1,10-diol (DDO) isolated from the extract of A. tsao-ko in lipopolysaccharide-stimulated RAW 264.7 cells. DDO treatment inhibited the production of nitric oxide and prostaglandin E2 by downregulating inducible nitric oxide synthase and cyclooxygenase-2 expression, respectively. Moreover, DDO suppressed the production of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. These inhibitory effects of DDO on the expression of inflammatory proteins were found to be mediated through the inactivation of mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase and p38(MAPK), and inhibition of nuclear factor-κB (NF-κB) pathways including degradation of inhibitor of κB-α and nuclear localization of NF-κB. Taken together, these findings demonstrate the pharmacological roles and molecular mechanisms of DDO in regulating inflammatory responses, and suggest further evaluation and development of DDO as a potent therapeutic agent for the treatment of inflammatory disorders.

To prove whether dietary intervention can prevent Helicobacter pylori-induced atrophic gastritis and gastric cancer, we developed cancer preventive kimchi (cpKimchi) through special recipe and administered to chronic H. pylori-initiated, high salt diet-promoted, gastric tumorigenesis mice model. H. pylori-infected C57BL/6 mice were administered with cpKimchi mixed in drinking water up to 36 weeks. Gross and pathological gastric lesions were evaluated after 24 and 36 weeks, respectively and explored underlying molecular changes to explain efficacies. Cancer preventive actions of anti-inflammation and anti-mutagenesis were compared between standard recipe kimchi (sKimchi) and special recipe cpKimchi in in vitro H. pylori-infected cell model. The erythematous and nodular changes, mucosal ulcerative and erosive lesions in the stomach were noted at 24th weeks, but cpKimchi administration significantly ameliorated. After 36th weeks, scattered nodular masses, some ulcers, and thin nodular gastric mucosa were noted in H. pylori-infected mice, whereas these gross lesions were significantly attenuated in cpKimchi group. On molecular analysis, significant expressions of COX-2 and IL-6, activated NF-κB and STAT3, increased apoptosis, and marked oxidative stresses were noted in H. pylori-infected group relevant to tumorigenesis, but these were all significantly attenuated in cpKimchi group. cpKimchi extracts imparted significant selective induction of apoptosis only in cancer cells, led to inhibition of H. pylori-induced proliferation, while no cytotoxicity through significant HO-1 induction in non-transformed gastric cells. In conclusion, daily dietary intake of cpKimchi can be an effective way either to rejuvenate H. pylori-atrophic gastritis or to prevent tumorigenesis supported with the concerted actions of anti-oxidative, anti-inflammatory, and anti-mutagenic mechanisms.

Aim of the study Previous studies in our laboratory revealed the neuroprotective effect of modified Yeoldahanso-tang (MYH) in models of Parkinson׳s disease (PD). In this study, we investigated another traditional Korean herbal formula, modified Chungsimyeolda-tang (termed DG), as a potential treatment for PD. Chungsimyeolda-tang has been used in Korea to treat cerebrovascular diseases, such as stroke. Here, we verify the neuroprotective and autophagy-inducing effects of DG to evaluate any potential anti-parkinsonian properties. Materials and methods 1-Methyl-4-phenylpyridinium (MPP + ) and rotenone were used to induce cytotoxicity in nerve growth factor (NGF)-differentiated rat pheochromocytoma (PC12) cells. Cell viability was measured using an MTT assay. Induction of autophagy by DG in NGF-differentiated PC12 cells was measured using an immunoblotting assay with an LC3 antibody. The proteasomal inhibitor lactacystin was used to induce ubiquitin-proteasome system (UPS) dysfunction in NGF-differentiated PC12 cells. DG-mediated clearance of aggregated proteins was measured using an immunoblotting assay with a ubiquitin antibody. Results and conclusions Our findings indicate that DG robustly protects NGF-differentiated PC12 cells against the neurotoxic effects of MPP + and rotenone in an in vitro model. Furthermore, DG protects NGF-differentiated PC12 cells against lactacystin-induced cell death. This effect is partially mediated by an increased autophagy associated with the enhanced degradation of aggregated proteins. This study suggests that DG is an attractive candidate drug for inducing autophagy and, therefore, may represent a promising strategy to prevent diseases associated with misfolded/aggregated proteins in various neurodegenerative disorders, including Parkinson׳s disease.

As a treatment for allergic asthma, inhaled treatments such as bronchodilators that contain β2-agonists have an immediate effect, which attenuates airway obstructions and decreases airway hypersensitivity. However, bronchodilators only perform on a one off basis, but not consistently. Asthma is defined as a chronic inflammatory disease of the airways accompanying the overproduction of mucus, airway wall remodeling, bronchial hyperreactivity and airway obstruction. Liriope platyphylla radix extract (LPP), a traditional Korean medicine, has been thoroughly studied and found to be an effective anti-inflammatory medicine. Here, we demonstrate that an inhaled treatment of LPP can attenuate airway hyperresponsiveness (AHR) in an ovalbumin-induced asthmatic mouse model, compared to the saline-treated group (p < 0.01). Moreover, LPP decreases inflammatory cytokine levels, such as eotaxin (p < 0.05), IL-5 (p < 0.05), IL-13 (p < 0.001), RANTES (p < 0.01), and TNF-α (p < 0.05) in the bronchoalveolar lavage (BAL) fluid of asthmatic mice. A histopathological study was carried out to determine the effects of LPP inhalation on mice lung tissue. We performed UPLC/ESI-QTOF-MS, LC/MS, and GC/MS analyses to analyze the chemical constituents of LPP, finding that these are ophiopogonin D, spicatoside A, spicatoside B, benzyl alcohol, and 5-hydroxymethylfurfural. This study demonstrates the effect of an inhaled LPP treatment both on airway AHR and on the inflammatory response in an asthmatic mouse model. Hence, LPP holds significant promise as a nasal inhalant for the treatment of asthmatic airway disease.

The methanol extract of the roots and stems of Daphne genkwa and its constituents yuanhuacin (1) and genkwanine N were previously reported to have Nurr1 activating effects and neuroprotective effects in an animal model of Parkinson's disease (PD). In this study, four more daphnane-type diterpenes (acutilonine F (2), wikstroemia factor M

Background Blood stasis syndrome (BSS) is a general pattern identification and refers to pathological stagnation of blood circulation, dysfunction of endothelial cells or metabolic disorder in traditional Korean medicine (TKM). Dohongsamul-Tang (DHSMT) is a well-known traditional herbal formula which used for treatment and prevention of BSS by promoting blood circulation in TKM. Methods Cytotoxicity of DHSMT was examined by cell counting kit-8 (CCK-8). We also investigated the anti-adipogenesis effect of DHSMT by using Oil Red O staining, intracellular triglyceride assay leptin ELISA and western blot analysis in 3T3-L1 adipocytes. In addition, the accumulation of adiponectin, resistin and plasminogen activator inhibitor-1 (PAI-1) were measured by magnetic bead panel kit. Results Oil Red O staining showed that DHSMT markedly reduced fat accumulation without affecting cell cytotoxicity. DHSMT also significantly decreased accumulation of triglyceride and adipokines such as leptin, adiponectin, resistin and PAI-1 compared with fully differentiated adipocytes. Furthermore, our results found that DHSMT significantly suppressed the adipocyte differentiation by downregulating adipogenic-specific transcriptional factors such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding proteins alpha (C/EBPα) and fatty acid binding protein 4 (FABP4) in adipocytes. Conclusions Taken together, our findings provide that DHSMT has potential for treatment and prevention of obesity or MS related to BSS.

Angelica gigas Nakai (AGN) is a crucial oriental medicinal herb that grows especially in Korea and the Far-East countries. It contains chemically active compounds like pyranocoumarins, polyacetylenes and essential oils, which might be useful for treatment of several chronic diseases. It has been used for centuries as a traditional medicine in Southeast Asia, but in Western countries is used as a functional food and a major ingredient of several herbal products. The genus Angelica is also known as ‘female ginseng’ due to its critical therapeutic role in female afflictions, such as gynecological problems. However, it is well-documented that the AGN pyranocoumarins may play vital beneficial roles against cancer, neurodisorders, inflammation, osteoporosis, amnesia, allergies, depression, fungi, diabetes, ischemia, dermatitis, reactive oxygen species (ROS) and androgen. Though numerous studies revealed the role of AGN pyranocoumarins as therapeutic agents, none of the reviews have published their molecular mechanism of action. To the best of our knowledge, this would be the first review that aims to appraise the biosynthesis of AGN’s major active pyranocoumarins, discuss effective extraction and formulation methods, and detail the molecular action mechanism of decursin (D), decursinol angelate (DA) and decursinol (DOH) in chronic diseases, which would further help extension of research in this area.

Poligoni Multiflori Radix (PMR) is a traditional Korean medicinal herb that is known to have various pharmacological effects, including antihyperlipidemic, anticancer, and anti‑inflammatory effects. However, the effects of PMR on bone metabolism have not been elucidated to date. The present study aimed to investigate the in vitro and in vivo effect of PMR water extract on the regulation of osteoblast and osteoclast activity. Effects of PMR water extract on receptor activator of nuclear factor‑kB ligand (RANKL)‑induced osteoclast differentiation and survival of mouse bone marrow macrophages (BMMs) obtained from femurs were investigated by tartrate‑acid resistant acid phosphatase (TRAP)‑positive cells and XTT assay. Expression of osteoclast‑related genes was assayed by western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Additionally, the effects of PMR water extract on osteoblastic proliferation and differentiation were investigated by alkaline phosphatase (ALP) activity assay, alizarin red staining, and levels of mRNA encoding known osteoblast markers. Furthermore, the effects of PMR water extract on lipopolysaccharide (LPS)‑induced bone loss were examined in a mouse model. PMR inhibited RANKL‑induced osteoclast differentiation of BMMs in a dose‑dependent manner without significant cytotoxicity, and suppressed expression of the main osteoclast differentiation markers Fos proto‑oncogene and nuclear factor of activated T‑cell. In addition, PMR decreased the mRNA expression levels of NFATc1 target genes, including TRAP, osteoclast‑associated receptor, ATPase H+ transporting, lysosomal 38 kDa V0 subunit d2, and Cathepsin K. These inhibitory effects were mediated by the p38 and extracellular signal‑regulated kinase/nuclear factor‑κB pathway. Simultaneously, PMR enhanced the differentiation of primary osteoblasts, and increased the mRNA expression of runt‑related transcription factor 2, ALP, osterix, and osteocalcin. Notably, PMR improved LPS‑induced trabecular bone loss in mice. Collectively, the present findings demonstrated that PMR may regulate bone remodeling by reducing osteoclast differentiation and stimulating osteoblast formation. These results suggest that PMR may be used for the treatment of bone diseases, such as osteoporosis and rheumatoid arthritis.

Background So-ochim-tang-gamibang (SOCG) is a traditional Korean medicine frequently used for depression in the clinical field. In this study, we evaluated the potential genotoxicity of SOCG using three standard batteries of tests as part of a safety evaluation. Methods SOCG was evaluated for potential genotoxic effects using the standard three tests recommended by the Ministry of Food and Drug Safety (MFDS) of Korea. These tests were the bacterial reverse mutation test (Ames test), in vitro mammalian chromosomal aberration test using Chinese hamster lung cells, and in vivo micronucleus test using ICR mice. Results The Ames test with Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and the Escherichia coli strain WP2uvrA(pKM101) showed that SOCG did not induce gene mutations at any dose level in all of the strains. SOCG did not induce any chromosomal aberrations in the in vitro chromosomal aberration test (for both the 6 and 24 h test) and the in vivo micronucleus test. Conclusions Based on the results of these tests, it was concluded that SOCG does not exhibit any genotoxic risk under the experimental conditions of this study.

OBJECTIVE This experimental study investigated the efficacy of Korean Red Ginseng (KRG) extract in reducing the partial losses of random flaps. METHOD Forty Wistar Albino rats were randomly distributed into 4 groups as (A) control group, (B) stress group, (C) oral KRG group, and (D) intraperitoneal KRG group. The modified McFarlane flap of 9 × 3 cm with a caudal pedicle was harvested from the back of the rats in all the groups. Korean Red Ginseng was administered to groups C and D at standard doses for 10 days. After 10 days, the flaps were removed in all groups and were examined macroscopically, histopathologically, histochemically, and biochemically. The results were statistically analyzed and compared among the groups. RESULTS The flap necrosis rates were significantly lower in groups C and D compared with groups A and B (P < 0.05). The vascular density, antioxidant activity, and hypoxia-inducible factor-1α levels were significantly higher in the groups C and D compared with the groups A and B (P < 0.05). Although vascular density, hypoxia-inducible factor-1α, and catalase levels were negatively correlated with the flap necrosis rates, there was a significantly positive correlation between malondialdehyde and necrosis rates. CONCLUSIONS Korean Red Ginseng increases the viability of random pattern skin flaps, resulting in reduced rates of distal necrosis. Korean Red Ginseng has antioxidant activity and increases neovascularization.

Objective: To study the anti-inflammatory properties of OJ. Context: Ojayeonjonghwan (OJ) is a traditional Korean prescription, which has been widely used for the treatment of prostatitis. However, no scientific study has been performed of the anti-inflammatory effects of OJ. Materials and methods: Peritoneal macrophages were isolated 3–4 days after injecting a C57BL/6J mouse with thioglycollate. They were then treated with OJ water extract (0.01, 0.1, and 1 mg/mL) for 1 h and stimulated with lipopolysaccharide (LPS) for different times. Nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and proinflammatory cytokine levels were determined by NO assay, Western blotting, RT-PCR and ELISA. Results: NO generation and iNOS induction were increased in the LPS-activated mouse peritoneal macrophages. However, NO generation and iNOS induction by LPS were suppressed by treatment with OJ for the first time. The IC50 value of OJ with respect to NO production was 0.09 mg/mL. OJ did not influence LPS-stimulated COX-2 induction, but did significantly decrease LPS-stimulated secretions and mRNA expressions of tumour necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Inhibition rates of TNF-α, IL-6, and IL-1β at an OJ concentration of 1 mg/mL were 77%, 88%, and 50%, respectively. OJ also suppressed the LPS-induced nuclear translocation of NF-κB. High-performance liquid chromatography showed schizandrin and gomisin A are major components of OJ. Conclusions: OJ reduces inflammatory response, and this probably explains its positive impact on the prostatitis associated inflammation.

Chongmyungtang (CMT) is a famous Korean herbal medicine for improving learning and memory, which has been reported to have anti-cholinergic and neuroprotective effects. Therefore, drug-drug interactions were examined between CMT and donepezil as a first screening of combination therapy for cognitive deficits. Rats received oral co-administration of donepezil with distilled water as a control or donepezil with CMT as a combination. The distilled water or CMT was co-administered at intervals within 5min after donepezil or 1.5h intervals. The plasma samples were analyzed for donepezil concentration and its pharmacokinetic parameters of T

Oryeong-san is a traditional herbal formula that is used for the treatment of common genitourinary diseases in Korea and other Asian countries. However, little is known about its safety and influence on drug metabolism. In the present study, we investigated the subacute toxicity of an Oryeong-san water extract (OSWE) in rats and its effects on activities of drug-metabolizing enzymes. Subacute toxicity was modeled in animals exposed to treatment with the extract at multiple doses. Rats were given OSWE by oral gavage at 0, 1000, 2000 and 5000 mg/kg/day for 4 weeks. We checked general observations and investigated any changes of body/organ weight, food consumption, hematology, serum biochemistry, and urinalysis in vivo; and the activities of human microsomal cytochrome P450s (CYP450s) and UDP-glucuronosyltransferase (UGT) isozymes in vitro. We found that OSWE caused no significant toxicological changes at the doses tested. Therefore, the no observed adverse effect level of OSWE was more than 5000 mg/kg/day for male and female rats. OSWE inhibited the activities of CYP2C19 (IC50: 737.69 μg/mL) and CYP2E1 (IC50: 177.77 μg/mL). These results indicate that OSWE may be safe with no drug-related toxicity for up to 4 weeks and provide useful information concerning its potential to interact with conventional drugs or other herbal medicines.

Background Yukmijihwangtang (YJT) is a traditional Korean medicine that has been used to treat kidney-yin deficiency symptoms such as dizziness and tinnitus. In addition, because it is also thought to nourish kidney-yin, it has been used to treat short stature from congenital deficiency. This study evaluated the effects of YJT on longitudinal bone growth in rats. Methods Female adolescent rats were randomly assigned to groups that received distilled water (per os [p.o.] twice a day; control), recombinant human growth hormone (rhGH; 20 μg/kg, subcutaneous [s.c.] once a day), or two different doses of YJT (100 or 300 mg/kg, p.o. twice a day). In each group, treatment was maintained for 4 days. Rats were injected intraperitoneally with 5-bromo-2’-deoxyuridine (BrdU; 50 mg/kg) to label proliferating chondrocytes on days 2 – 4. Tetracycline hydrochloride (20 mg/kg) was injected intraperitoneally to form fluorescent bands on the growth plates on day 3 for measuring the longitudinal bone growth rate. Expression of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate was identified using immunohistochemistry. Results There was a significant increase in the rate of bone growth in the 300 mg/kg YJT group (523.8 ± 23.7 μm/day; P

Only a few osteological reports describe bone injuries thought to have been caused by falls from horses. Nevertheless, anthropological study alone is insufficient for establishing the correlates of such equestrian accidents. We therefore reviewed the records in Seungjeongwon ilgi (Diaries of the Royal Secretariat) and Joseon wangjo silrok (Annals of the Joseon Dynasty) of the Korea's Joseon period (1392-1910 CE). Although the mechanisms of trauma were diverse, the Joseon documents recorded many injuries caused by horse-riding accidents. During 1625-1872 CE, equestrian-related accidents occurred almost every year, overwhelming other causes of trauma. In all horse-riding accidents (n=142), 37.77% of the records offer detailed data about the traumatic mechanism. Injuries occurred most frequently to the extremities (79.58%), which were followed by the trunk (34.5%) and head (4.92%). Although we do not think that this attempt can explain every paleopathological case, our historical review shows that equestrian-related injuries could be considered as one of the major causes for the bone trauma observed among ancient equestrian people.

The hepatic anti-inflammatory potential of hexane extracts of Dioscorea batatas Decne edible part (EDH-1e) and bark (EDH-2b) were investigated in Western-type diet-fed apolipoprotein E null [ApoE (-/-)] mice and HepG2 cells. EDH-1e and EDH-2b suppressed the increased levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transforming growth factor beta 1 (TGF-β1), vascular cell adhesion protein 1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), and reduced infiltration of monocytes into liver tissue. The protein levels of Toll-like receptor 4 (TLR4) were also downregulated by EDH-1e and EDH-2b treatment as were the levels of activator protein 1 (AP-1), c-fos, and c-jun in the livers from Western-type diet-fed ApoE (-/-) mice and in lipopolysaccharide-stimulated HepG2 cells. Taken together, EDH-1e and EDH-2b attenuated hepatic inflammation and fibrosis via suppression of the TLR4-AP1-mediated signaling pathway.

Background SC-E1 is a novel herbal formula consisting of five oriental medicinal herbs used frequently in traditional herbal medicine for the treatment of inflammatory diseases in Korea. This study examined the effects of SC-E1 on lipopolysaccharide (LPS)-stimulated macrophages and the molecular mechanism involved. Methods The cytotoxic effect of the SC-E1 extract was evaluated in RAW 264.7 cells by MTT assay. The effects of SC-E1 on the free radical scavenging and generation of intracellular reactive oxygen species were measured using DPPH and DCFH-DA, respectively. The effects of SC-E1 on the production of pro-inflammatory cytokines, inflammatory mediators, and related products were determined by ELISA and western blotting. The molecular mechanism and the nuclear translocation of nuclear factor-kappa B (NF-κB) and NF-E2-related factor 2 (Nrf2) were examined by western blot analysis and immunocytochemistry. Results SC-E1 exhibited strong anti-oxidant activity and inhibited LPS-induced NO secretion as well as iNOS expression and the production of pro-inflammatory cytokines, without affecting the cell viability. SC-E1 also suppressed the LPS-induced NF-κB activation and the mitogen-activated protein kinase (MAPK) pathway. Moreover, SC-E1 induced heme oxygenase-1 (HO-1) expression via the nuclear translocation of Nrf2. The inhibitory effects of SC-E1 on the production of pro-inflammatory cytokines were abrogated by treatment with SnPP, an HO-1 inhibitor. Conclusion These results suggest that SC-E1 exerts its anti-oxidant and anti-inflammatory effects through the inhibition of NF-κB and MAPK as well as Nrf2-mediated HO-1 induction in macrophages. These findings provide evidences for SC-E1 to be considered as a new prescription for treating inflammatory diseases.