Dysmenorrhea is a common gynecological complaint in adolescent and young females. The purpose of this study is to assess the efficacy of Shaofu Zhuyu (SFZY) decoctions as treatments for primary dysmenorrhea.

Tongqiaohuoxue decoction (THD), a water extract of a mixture of eight species of medicinal herbs, has been used for the treatment of blood stasis and hypercoagulation in traditional East Asian medicine since 18th century.

Gomisin N (GN), a lignan derived from Schisandra chinensis, has been shown to possess antioxidant, anti-inflammatory, and anticancer properties. In the present study, we investigated the protective effect of GN against ethanol-induced liver injury using in vivo and in vitro experiments. Histopathological examination revealed that GN administration to chronic-binge ethanol exposure mice significantly reduced ethanol-induced hepatic steatosis through reducing lipogenesis gene expression and increasing fatty acid oxidation gene expression, and prevented liver injury by lowering the serum levels of aspartate transaminase and alanine transaminase. Further, it significantly inhibited cytochrome P450 2E1 (CYP2E1) gene expression and enzyme activity, and enhanced antioxidant genes and glutathione level in hepatic tissues, which led to decreased hepatic malondialdehyde levels. It also lowered inflammation gene expression. Finally, GN administration promoted hepatic sirtuin1 (SIRT1)-AMP-activated protein kinase (AMPK) signaling in ethanol-fed mice. Consistent with in vivo data, treatment with GN decreased lipogenesis gene expression and increased fatty acid oxidation gene expression in ethanol-treated HepG2 cells, thereby preventing ethanol-induced triglyceride accumulation. Furthermore, it inhibited reactive oxygen species generation by downregulating CYP2E1 and upregulating antioxidant gene expression, and suppressed inflammatory gene expression. Moreover, GN prevented ethanol-mediated reduction in SIRT1 and phosphorylated AMPK. These findings indicate that GN has therapeutic potential against alcoholic liver disease through inhibiting hepatic steatosis, oxidative stress and inflammation.

Acute hepatitis A (AHA) involves severe CD8+ T cell-mediated liver injury. Here we showed during AHA, CD8+ T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8+ T cells. TCR-independent activation of non-HAV-specific CD8+ T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8+ T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV-unrelated virus-specific CD8+ T cells and the innate-like cytolytic activity of CD8+ T cells, but not the activation of HAV-specific T cells. Thus, host injury in AHA is associated with innate-like cytotoxicity of bystander-activated CD8+ T cells, a result with implications for acute viral diseases.

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.

Improvement of endometrial receptivity is necessary for successful embryo implantation, and its impairment is associated with female infertility. In this study, we investigated the effect of the roots of Cnidium officinale Makino (CoM) on endometrial receptivity in both in vitro and in vivo model of embryo implantation. We found that CoM enhanced the adhesion of JAr cells to Ishikawa cells by stimulating expression of leukemia inhibitory factor (LIF) and integrins. In addition, blocking of LIFR using hLA or neutralization of integrins αV, β3, and β5 using antibodies significantly reduced the enhanced adhesion between JAr cell and CoM-treated Ishikawa cells, indicating that LIF and integrin play an important role in trophoblast-endometrium adhesion for embryo implantation. Furthermore, we identified that CoM significantly improved the implantation rate of blastocysts in the mouse model of RU-induced implantation failure. By collecting these results, here, we suggest that CoM has a therapeutic potential against female infertility associated with decreased endometrial receptivity.

Dried ginger (Zingiberis Processum Rhizoma (ZR)) is frequently used to prevent or treat common cold and flu. This study aimed to investigate the influence of ZR extracts on influenza-specific antibody production in cyclophosphamide (Cy)-induced immunocompromised mice. Female BALB/c mice were injected three times with saline or Cy. To investigate the effect of ZR, either distilled water or ZR was administered orally to mice daily for 10 days after Cy injection. After ZR administration, the mice were immunized with the 2017/2018 influenza vaccine. Pretreatment with ZR extracts enhanced influenza-specific antibody production in Cy-induced immunocompromised mice after flu vaccination and restored the influenza antigen-specific T helper (Th) type 1/Th2 balance to the normal state. Further, ZR suppressed the eosinophil enrichment caused by Cy injection in the spleen. We demonstrated that ZR can be used to increase antibody production in immunocompromised individuals before vaccination.

Subsets of the human CD8+ T cell population express inhibitory NK cell receptors, such as killer immunoglobulin-like receptors (KIRs) and NKG2A. In the present study, we examine the phenotypic and functional characteristics of KIR+CD8+ T cells and NKG2A+CD8+ T cells. KIRs and NKG2A tend to be expressed by human CD8+ T cells in a mutually exclusive manner. In addition, TCR clonotypes of KIR+CD8+ T cells barely overlap with those of NKG2A+CD8+ T cells, and KIR+CD8+ T cells are more terminally differentiated and replicative senescent than NKG2A+CD8+ T cells. Among cytokine receptors, IL12Rβ1, IL12Rβ2, and IL18Rβ are highly expressed by NKG2A+CD8+ T cells, whereas IL2Rβ is expressed by KIR+CD8+ T cells. IL-12/IL-18-induced production of IFN-γ is prominent in NKG2A+CD8+ T cells, whereas IL-15-induced NK-like cytotoxicity is prominent in KIR+CD8+ T cells. These findings suggest that KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations with different cytokine responsiveness.

Morus alba, a medicinal plant in Asia, has been used traditionally to treat diabetes mellitus and hypoglycemia. However, the effects of M. alba extract (MAE) on atopic dermatitis have not been verified scientifically. We investigated the effects of MAE on atopic dermatitis through in vitro and in vivo experiments.

Artemisia capillaries Thunb. (AC) has been used to treat inflammatory and hepatic disorders such as hepatic injury, hepatic fibrosis and hepatitis. However, the efficacy of AC against atopic dermatitis (AD), an inflammatory disease, has not been examined. In the present study, AC was evaluated for anti-inflammatory and anti-AD effects using both in vitro and in vivo systems.

Sobokchukeo-Tang (ST) is a well-known formula that is used for treating primary dysmenorrhea caused by blood stasis syndrome (BSS) in Korea and China. The current study investigated the anti‑inflammatory and anti‑adipogenesis effects of ST on adipocytes and macrophages. The anti‑inflammatory efficacy of ST was evaluated in RAW 264.7 cells and differentiated THP‑1 cells. To induce inflammation, the cells were treated with lipopolysaccharide (LPS; 1 µg/ml). Following the induction of inflammation, the levels of proinflammatory cytokines, interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α) in the cell supernatant were detected using enzyme‑linked immunosorbent assay. 3T3‑L1 preadipocytes differentiated into adipocytes in response to insulin, isobutyl‑1‑methylxanthine and dexamethasone (MDI). To confirm the anti‑adipogenesis efficacy of ST, we investigated Oil Red O staining was performed, triglyceride (TG) and leptin secretion were measured, and the protein expression of lipid metabolism‑associated factors was determined. ST significantly inhibited TNF‑α and IL‑6 production in the LPS‑treated RAW 264.7 cells compared with LPS stimulation alone. In addition, the concentrations of IL‑6 and TNF‑α were significantly inhibited by ST in LPS‑treated THP‑1 cells. Lipid accumulation was reduced by ST, similarly to the positive control treatment, SB203580. In the ST‑treated group, the TG and leptin concentrations were inhibited by up to 50 and 83%, respectively, compared with MDI induction only. The ST‑treated group reduced the protein expression of peroxisome proliferator‑activated receptor‑γ and CCAAT/enhancer‑binding protein α compared with MDI induction only. The results of the present study demonstrated that ST exerts anti‑inflammatory effects on LPS‑treated mouse and human macrophage cell lines. ST inhibited adipogenesis in MDI‑induced 3T3‑L1 adipocytes, as indicated by the significant reduction in TG and leptin concentrations without cytotoxicity. Thus, ST may be useful as a therapeutic agent for preventing lipid‑associated diseases, including obesity and atherosclerosis.

We evaluated the effects of Alpinia katsumadai Hayata (AKH, Zingiberaceae) extract on the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in RAW 264.7 cells, thymus- and-activation-regulated chemokine (TARC/CCL17) in HaCaT cells, and histamine level in HMC-1 cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for 4 weeks, and the protective effects of AKH was investigated by measuring the severity of the skin reaction on the back and ears, and plasma levels of immunoglobulin E (IgE) and histamine. AKH extract suppressed the production of NO and PGE(2) in RAW 264.7 cells, TARC in HaCaT cells, and histamine in HMC-1 cells in a dose-dependent manner. In in vivo experiments, the severity of dermatitis, including erythema/hemorrhage, edema, erosion and scaling, and plasma levels of IgE, and histamine were lower in NC/Nga mice with atopic dermatitis, treated with AKH extract than in untreated mice. AKH extract reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration on the skin of the back and ear. These results suggest that AKH inhibits the development of house dust mite-induced atopic dermatitis in NC/Nga mice.

The Chung Hun Wha Dam Tang (CHWDT) herbal combination was reported to cease dizziness and phlegm. However, the effect of CHWDT in obesity has not yet been known mechanically. Therefore, we investigated whether this CHWDT could protect the cells from lipogenesis, gluconeogenesis, and inflammation in both in vivo and in vitro. CHWDT significantly decreased body weight, epididymal and perirenal fat content without affecting feed intake in high-fat diet-induced obese mice model. Additionally, CHWDT inhibited obesity-induced SREBP1, FAS, PGC1α, G6Pase, PEPCK and increased CPT1, ACO, and LCAD genes expression in vivo and in vitro. Proinflammatory cytokines like TNF-α and iNOS expression were reduced by CHWDT in both Raw264.7 macrophages and HepG2 cells. In addition, NO production was also significantly decreased by CHWDT in LPS-stimulated macrophages. Furthermore, AMPKα activation by CHWDT was involved in inhibition of obesity by reducing triglycerides production and increasing CPT1 expression. Based on all of the results, we suggest that CHWDT has inhibitory effects on obesity-induced lipogenesis, gluconeogenesis, and inflammation via AMPKα activation.

We examined whether Angelicae Dahuricae Radix (AR) suppresses the development of atopic dermatitis (AD)-like skin lesions induced by Dermatophagoides farinae in NC/Nga mice. To investigate the effect of AR, we measured the AD severity score, measured plasma levels of IgE and histamine, and performed histological analysis in NC/Nga mice. We also confirmed the anti-inflammatory effects of AR by measuring TARC/CCL17 production from LPS-treated RAW 264.7 cells and mRNA levels of TARC and MDC/CCL22 in TNF-α/IFN-γ-treated HaCaT cells. 10 mg/day of AR extract was applied for 4 weeks to NC/Nga mice. Both the AR extract and 0.1% tacrolimus suppressed the development of AD-like skin lesions and reduced dermatitis scores of the back and ear skin. AR extracts caused an inhibition of histological changes induced by repeated application of D. farinae and a reduction of IgE and histamine levels in plasma (P < 0.05). Furthermore, NO production in LPS-treated RAW 264.7 cells was diminished in a dose-dependent manner, and hTARC production and TARC and MDC mRNA levels in TNF-α/IFN-γ-treated HaCaT cells were diminished by AR. The inhibitory effect of AR on NO, TARC and MDC production may be associated with the suppression of AD-like skin lesions in D. farinae-induced NC/Nga mice.

To explore plastic changes in the red nucleus (RN) of stroke patients with severe corticospinal tract (CST) injury as a compensatory mechanism for recovery of hand function.

Aims. Artemisia iwayomogi (AI) has been used for fever reduction, diuresis, and hepatoprotection in Korea. The present study was performed to evaluate the anti-inflammatory and antiatopic dermatitis effects of AI using both in vitro and in vivo systems. Methods. The compositions in AI were analyzed by HPLC. To determine the anti-inflammatory effects of AI, the production of nitric oxide (NO) was measured in lipopolysaccharide treated RAW264.7 cells. Histamine levels were assayed to evaluate the antiallergic effects on MC/9 cells stimulated with phorbol-12 myristate 13-acetate and A23187. Finally, AI (10 mg/mouse/day) was topically applied onto the backs and ears of Dermatophagoides farinae-sensitized Nc/Nga mice for four weeks. Results. Isochlorogenic acid A (20.63 ± 0.26 mg/g), chlorogenic acid (9.04 ± 0.08 mg/g), and scopoletin (8.23 ± 0.01 mg/g) were among the major components of AI. AI inhibited the NO and histamine productions in RAW264.7 and MC/9 cells, respectively. In the mice, the topical application of AI reduced the dermatitis scores in the dorsal skin and ears and reduced the plasma levels of IgE. Conclusions. These results suggest that AI might be explored as a potential therapeutic agent to treat AD, and that the analytic method using HPLC will facilitate the development of quality control for AI.

Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1β-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.

Our understanding of adaptive immune responses in patients with coronavirus disease 2019 (COVID-19) is rapidly evolving, but information on the innate immune responses by natural killer (NK) cells is still insufficient.

Gomisin N (GN) is a lignan derived from Schisandra chinensis. AMP-activated kinase (AMPK) has gained attention as a therapeutic target for the treatment of metabolic syndrome. Previously, we reported that GN activated the AMPK pathway and ameliorated high-fat diet (HFD)-induced hepatic steatosis. In this study, we investigated the anti-diabetic effects of GN in C2C12 myotubes and HFD obese mice. GN enhanced the phosphorylation of AMPK/acetyl-CoA carboxylase (ACC) and Akt. In addition, GN promoted glucose uptake in C2C12 myotubes, which was accompanied by the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Treatment with compound C, an AMPK inhibitor, suppressed GN-mediated stimulation of glucose uptake. Furthermore, GN increased the expression of mitochondria biogenesis and fatty acid oxidation genes in C2C12 myotubes. In the in vivo study, administration of GN to HFD mice decreased the levels of fasting blood glucose and insulin, and improved glucose tolerance in HFD obese mice. GN administration rescued the decreased phosphorylation of AMPK and Akt and stimulated the expression of mitochondria biogenesis genes in the skeletal muscle of HFD mice. These findings suggested that GN exerted anti-hyperglycemic effects through AMPK activation.

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.