Effect of GHX02 on an Asthma-Rhinitis Mouse Model Induced by Ovalbumin and Diesel Particulate Matter.

Fine dust concentrations come in direct contact with the human respiratory system, thereby reducing lung function and causing respiratory diseases such as asthma and rhinitis. The aim of this study was to evaluate the efficacy of GHX02 (combination of four herbs [Trichosanthes kirilowii, Prunus armeniaca, Coptis japonica, and Scutellaria baicalensis]), a herbal extract with established efficacy against bronchitis and pulmonary disease, in the treatment of asthma accompanied by rhinitis aggravated by fine dust. Therefore, we constructed an asthma-rhinitis mouse model of Balb/c mice challenged with ovalbumin (OVA) and fine diesel particulate matter, which were administered with three concentrations of GHX02. GHX02 significantly inhibited the increase of total cells and immune cells in bronchoalveolar lavage fluid, lung tissue, and nasal ductal lymphoid tissue (NALT). GHX02 also reduced the severity of histological lung injury and the expression of interleukin (IL)-1α and nuclear factor kappa B (NF-κB), which regulate inflammatory responses. The results indicate that GHX02 inhibited the inflammatory immune response in mice. Therefore, this study highlights the potential of GHX02 as a treatment for patients with asthma accompanied by rhinitis. Balb/c mice were challenged with OVA and PM10D, and then treated with three concentration of GHX02. GHX02 significantly inhibited the increase of total cells, immune cells lymphocytes, neutrophils, and macrophages, as well as their expression in lung tissue. GHX02 significantly inhibited the increase of total cells and immune cells in NALT. GHX02 decreased the severity of histological lung injury, expression of IL-1α and NF-κB. This study suggests the probability that GHX02 is effective for asthma patients with rhinitis by inhibiting inflammatory immune response.

Photoprotective Effects of Processed Ginseng Leaf Administration against UVB-Induced Skin Damage in Hairless Mice.

Although ginseng leaves contain a larger amount of ginsenosides than the roots, studies on the protective effect of oral administration of ginseng leaves against photoaging are lacking. Processed ginseng leaves (PGL) prepared by acid reaction to increase effective ginsenoside content showed higher levels of Rg3 (29.35 mg/g) and Rk1 (35.16 mg/g) than ginseng leaves (Rg3 (2.14 mg/g) and Rk1 (ND)), and ginsenosides Rg3 and Rk1 were evaluated as active ingredients that protected human keratinocytes against UVB-induced cell damage by increasing cell proliferation and decreasing matrix metalloproteinase (MMP)-2 and 9 secretion. Herein, the effect of oral PGL administration (50, 100, or 200 mg/kg, daily) against photoaging in HR-1 hairless mice was assessed by measuring wrinkle depth, epidermal thickness, and trans-epidermal water loss for 16 weeks. The PGL treatment group showed reduced skin wrinkles, inhibited MMP-2 and MMP-9 expression, and decreased IL-6 and cyclooxygenase-2 levels. These data suggest that oral PGL administration inhibits photoaging by inhibiting the expression of MMPs, which degrade collagen, and inhibiting cytokines, which induce inflammatory responses. These results reveal that ginseng leaves processed by acid reaction may serve as potential functional materials with anti-photoaging activities.

Efficacy and Safety of Yukmijihwang-Tang in the Treatment of Cough-Variant Asthma: Study Protocol for a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

BACKGROUND: Cough-variant asthma (CVA), a precursor of typical asthma, is the main cause of chronic cough. We hypothesize that yukmijihwang-tang (YJT), which has been used for chronic cough in traditional medicine and has been reported to have an anti-inflammatory effect, could be an adjuvant to asthma treatment. METHODS: We plan a randomized, double-blind, placebo-controlled, multicenter, phase 2 trial to investigate the efficacy and safety of YJT in CVA patients. A total of 60 patients with CVA will be recruited and randomly assigned to either a high-dose YJT group, standard-dose YJT group, or control group (placebo) in a 1:1:1 allocation ratio after a 2-week run-in period. For the run-in period, only inhaled corticosteroids (ICSs) will be used, and the investigational drug will be administered once a day with concomitant ICS for 6 weeks. Data will be collected at baseline, week 3, and week 6, and the primary outcome measure will be the mean cough symptom score (CSS) change before and after medication. The secondary outcome measures will include the Leicester cough questionnaire-Korean version (LCQ-K) score, eosinophil count and eosinophil cationic protein level, pulmonary function test, and the number of uses of rescue medication, and so on. CONCLUSION: This study aimed to evaluate the efficacy and safety of YJT in concomitant treatment with ICS in patients with CVA and to determine the optimal dosage of YJT. The results are expected to provide evidence for the use of YJT as an adjuvant treatment for CVA.Cough-Variant-Asthma (CVA), eine Frühform von typischem Asthma, ist die Hauptursache von chronischem Husten. Unserer Vermutung nach könnte Yukmijihwang-Tang (YJT), das in der traditionellen Medizin zur Behandlung von chronischem Husten eingesetzt wird und das Berichten zufolge einen entzündungshemmenden Effekt hat, unterstützend in der Asthma-Therapie wirken.en: Wir planen eine randomisierte, doppelblinde, placebokontrollierte, multizentrische Phase-2-Studie, um die Wirksamkeit und Sicherheit von YJT bei Patienten mit CVA zu untersuchen. Insgesamt werden 60 CVA-Patienten für die Studie rekrutiert und nach einer zweiwöchigen Run-in-Phase randomisiert im Verhältnis 1:1:1 einer Gruppe mit hochdosiertem YJT, einer Gruppe, die YJT in der Standarddosierung erhält oder einer Kontrollgruppe (Placebo) zugewiesen. Während der Run-in-Phase werden nur inhalative Corticosteroide (ICS) verwendet, und das Prüfpräparat wird über 6 Wochen einmal täglich gleichzeitig mit den ICS angewendet. Die Datenerhebung erfolgt bei Studienbeginn, in Woche 3 sowie in Woche 6, und das primäre Zielkriterium ist die Änderung des mittleren Hustenscores (cough symptom score, CSS) vor und nach der Anwendung der Medikamente. Zu den sekundären Zielkriterien gehören der Score des Leicester Hustenfragebogens - koreanische Version (LCQ-K), die Eosinophilenzahl und der Spiegel an eosinophilem kationischen Protein, Lungenfunktionstests sowie die Anzahl der Anwendungen von Bedarfsmedikation usw.Ziel dieser Studie ist es, die Wirksamkeit und Sicherheit von YJT bei gleichzeitiger Behandlung mit ICS bei Patienten mit CVA zu bewerten und die optimale YJT-Dosis zu ermitteln. Es wird erwartet, dass die Ergebnisse Belege für die Anwendung von YJT als adjuvante Therapie bei CVA liefern werden.WHO International Clinical Trials Registry Platform, Clinical Research Information Service (CRIS), KCT0006994, registriert am 10. Februar 2022, https://cris.nih.go.kr/cris/search/detailSearch.do/21743.

Protective Effects of Glycine soja Leaf and Stem Extract against Chondrocyte Inflammation and Osteoarthritis.

Wild soybean, also known as Glycine soja Sieb. et Zucc. (GS), has long been known for its various health benefits. Although various pharmacological effects of G. soja have been studied, the effects of GS leaf and stem (GSLS) on osteoarthritis (OA) have not been evaluated. Here, we examined the anti-inflammatory effects of GSLS in interleukin-1ß (IL-1ß)-stimulated SW1353 human chondrocytes. GSLS inhibited the expression of inflammatory cytokines and matrix metalloproteinases and ameliorated the degradation of collagen type II in IL-1ß-stimulated chondrocytes. Furthermore, GSLS played a protective role in chondrocytes by inhibiting the activation of NF-κB. In addition, our in vivo study demonstrated that GSLS ameliorated pain and reversed cartilage degeneration in joints by inhibiting inflammatory responses in a monosodium iodoacetate (MIA)-induced OA rat model. GSLS remarkably reduced the MIA-induced OA symptoms, such as joint pain, and decreased the serum levels of proinflammatory mediators, cytokines, and matrix metalloproteinases (MMPs). Our findings show that GSLS exerts anti-osteoarthritic effects and reduces pain and cartilage degeneration by downregulating inflammation, suggesting that it is a useful therapeutic candidate for OA.

Efficacy and Safety of Bojungikgi-Tang for Persistent Allergic Rhinitis: A Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

Background: Allergic rhinitis (AR) is a common disease, and conventional medications are often insufficient for treatment. Bojungikgi-tang (BJIGT) is an herbal medicine widely used in traditional medicine and has anti-inflammatory and immunoregulatory effects. We hypothesize that BJIGT would improve nasal symptoms in patients with persistent AR (PAR). Methods: This is a randomized, double-blind, placebo-controlled, phase II trial. A total of 105 patients, identified with perennial allergens, with a history of PAR and a mean total nasal symptom score (TNSS) ≥ 5 during the run-in period will be recruited from Daejeon Korean Medicine Hospital. Participants will be randomly assigned to a high-dose BJIGT group, standard-dose BJIGT group, or control group (placebo) in a 1 : 1 : 1 allocation ratio after a week run-in period. The treatment medication will be taken three times per day for 4 weeks. The primary outcome measure is the mean change in the TNSS before and after medication. The secondary outcome measures include the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, total IgE and eosinophil count, overall assessment of AR, pattern identification questionnaire for AR, and Sasang constitution. Discussion. The aim of this study is to investigate the efficacy and safety of BJIGT in the treatment of PAR and to determine the suitable dosage of BJIGT. Therefore, we planned a randomized, controlled, phase II trial of two different doses of BJIGT compared with placebo, and the results of this study are expected to provide evidence for the use of BJIGT as a treatment of PAR. Trial Registration. The National Clinical Trial Registry Clinical Research Information Service, CRIS, KCT0006616, https://cris.nih.go.kr/cris/search/detailSearch.do/20706.

Herbal Medicines for the Treatment of Chronic Obstructive Airway Diseases (Asthma or Chronic Obstructive Pulmonary Disease): A Prospective Observational Study.

Background: Obstructive airway disease is a major health problem and has a great impact on global socioeconomic burden. Despite therapeutic advances in recent decades, there is still a need for effective and safe therapeutic agents for patients with asthma or chronic obstructive pulmonary disease (COPD). Methods: This prospective observational study explored the effects of herbal medicines in patients with asthma and COPD. All participants visited the hospital at least every 4 weeks for 12 weeks to receive their herbal medicines based on their pattern identification and to evaluate safety and efficacy endpoints. We followed the diagnostic criteria used by Korean medicine doctors to prescribe herbal medicines, explored variations in prescribed herbal medicines, and explored a number of clinical features in patients with asthma or COPD. Results: A total of 24 patients were enrolled: 14 were diagnosed with asthma and 10 with COPD and 19 completed the study. After 12 weeks of herbal medicine treatment, herbal medicines significantly improved the modified Clinical Asthma Measurement Scale in Oriental Medicine-V in asthma patients and the modified Medical Research Council Dyspnoea Scale and St. George's Respiratory Questionnaire in COPD patients. For all patients, modified Medical Research Council Dyspnoea Scale score and interleukin-13 were found to be significantly different after treatment. Additionally, the majority of patients were satisfied with our herbal medicine treatments, and no severe adverse events were reported during the study. Conclusions: Our study provides preliminary clinical data on the safety and efficacy of herbal medicines in patients with asthma and COPD.

Anti-Inflammatory and Analgesic Effects of Schisandra chinensis Leaf Extracts and Monosodium Iodoacetate-Induced Osteoarthritis in Rats and Acetic Acid-Induced Writhing in Mice.

In this study, we aimed to determine the anti-inflammatory and antinociceptive activities of Schisandra chinensis leaf extracts (SCLE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, an acetic acid-induced mouse model of writhing, and a monosodium iodoacetate (MIA)-induced rat model of osteoarthritis (OA). In LPS-stimulated RAW264.7 cells, a 100 µg/mL dose of SCLE significantly reduced the production of nitric oxide (NO), interleukin-1ß (IL-1ß), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2). Acetic acid-induced writhing responses in mice that quantitatively determine pain were significantly inhibited by SCLE treatment. In addition, SCLE significantly decreased the MIA-induced elevation in OA symptoms, the expression levels of pro-inflammatory mediators/cytokines and matrix metalloproteinases, and cartilage damage in the serum and joint tissues. Our data demonstrated that SCLE exerts anti-osteoarthritic effects by regulating inflammation and pain and can be a useful therapeutic candidate against OA.

Inhibitory effects of modified gamgil-tang in a particulate matter-induced lung injury mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The modified gamgil-tang (GGX) is a mixture of four herbal medicine including Platycodi Radix, Glycyrrhizae Radix, Lonicerae Flos and Mori Radicis Cortex which has been traditionally used to treat lung and airway diseases to relieve symptoms like sore throat, cough, and sputum in Korea. Its major component chlorogenic acid had been reported to have antioxidant, antibacterial, hepatoprotective, cardioprotective, anti-inflammatory, antiviral, and anti-microbial activity. AIM OF THE STUDY: To identify the inhibitory effect of GGX in a particulate matter (PM) induced lung injury mouse model. MATERIALS AND METHODS: We evaluated NO production, the release of TNF-α and IFN-γ in PM-induced MH-S cells, and the number of neutrophils, immune cell subtypes, and the secretion of TNF-α, IL-17, CXCL-1, MIP-2 in the PM-stimulated mouse model to assess the inhibitory effect of GGX against PM. In addition, as exposure to PM increases respiratory symptoms, typically cough and sputum, we attempted to evaluate the antitussive and expectorant activities of GGX. RESULTS: Our study provided evidence that GGX has inhibitory effects in PM-induced lung injury by inhibiting the increase in neutrophil and inflammatory mediators, deactivating T cells, and ameliorating lung tissue damage. Notably, GGX reduced PM-induced neutrophilic inflammation by attenuating the number of neutrophils and regulating the secretion of neutrophil-related cytokines and chemokines, such as TNF-α, IL-17, MIP2, and CXCL-1. In addition, GGX demonstrated an antitussive activity by significantly reducing citric acid-induced cough frequency and delaying the latent period and expectorant activities by the increased phenol red secretion compared to the control group. CONCLUSIONS: GGX is expected to be an effective herbal remedy to prevent PM-induced respiratory disease.

Extracts of Phyllostachys pubescens Leaves Represses Human Steroid 5-Alpha Reductase Type 2 Promoter Activity in BHP-1 Cells and Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rat Model.

Benign prostatic hyperplasia (BPH) is the most common symptomatic abnormality of the human prostate characterized by uncontrolled proliferation of the prostate gland. In this study, we investigated the effect of bamboo, Phyllostachys pubescens, leaves extract (PPE) on human 5α-reductase type 2 (SRD5A2) gene promoter activity in human prostate cell lines and the protective effect of PPE on a testosterone-induced BPH rat model. PPE repressed human SRD5A2 promoter activity and its mRNA expression. The rats treated with PPE for 4 weeks showed a significantly attenuated prostate weight compared to vehicle control. PPE-treated rats also showed reduced serum dihydrotestosterone, testosterone, prostate-specific antigen, and SRD5A2 levels by testosterone injection. Quantitative real-time polymerase chain reaction showed that PPE treatment significantly decreased mRNA expression of SRD5A2, androgen receptor (AR), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor 2 compared with the vehicle-treated, testosterone-injected rats in the prostate. Furthermore, PPE treatment showed reduced AR, PCNA, and tumor necrosis factor alpha expression in the prostate via immunohistofluorescence staining. In conclusion, oral administration of PPE prevented and inhibited the development and progression of enlarged prostate lesions in testosterone-induced animal models through various anti-proliferative and anti-inflammatory pharmacological effects and induced suppression of SRD5A2 gene expression.

Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase.

Colorectal cancer (CRC) is a malignancy of the colon or rectum. It is ranked as the third most common cancer in both men and women worldwide. Early resection permitted by early detection is the best treatment, and chemotherapy is another main treatment, particularly for patients with advanced CRC. A well-known thymidylate synthase (TS) inhibitor, 5-fluorouracil (5-FU), is frequently prescribed to CRC patients; however, drug resistance is a critical limitation of its clinical application. Based on the hypothesis that Coptidis Rhizoma extract (CRE) can abolish this 5-FU resistance, we explored the efficacy and underlying mechanisms of CRE in 5-FU-resistant (HCT116/R) and parental HCT116 (HCT116/WT) cells. Compared to treatment with 5-FU alone, combination treatment with CRE and 5-FU drastically reduced the viability of HCT116/R cells. The cell cycle distribution assay showed significant induction of the G0/G1 phase arrest by co-treatment with CRE and 5-FU. In addition, the combination of CRE and 5-FU notably suppressed the activity of TS, which was overexpressed in HCT116/R cells, as compared to HCT116/WT cells. Our findings support the potential of CRE as an adjuvant agent against 5-FU-resistant colorectal cancers and indicate that the underlying mechanisms might involve inhibition of TS expression.

Cryptotympana pustulata Extract and Its Main Active Component, Oleic Acid, Inhibit Ovalbumin-Induced Allergic Airway Inflammation through Inhibition of Th2/GATA-3 and Interleukin-17/RORγt Signaling Pathways in Asthmatic Mice.

Cicadae Periostracum (CP), derived from the slough of Cryptotympana pustulata, has been used as traditional medicine in Korea and China because of its diaphoretic, antipyretic, anti-inflammatory, antioxidant, and antianaphylactic activities. The major bioactive compounds include oleic acid (OA), palmitic acid, and linoleic acid. However, the precise therapeutic mechanisms underlying its action in asthma remain unclear. The objective of this study was to determine the antiasthmatic effects of CP in an ovalbumin (OVA)-induced asthmatic mouse model. CP and OA inhibited the inflammatory cell infiltration, airway hyperresponsiveness (AHR), and production of interleukin (IL)7 and Th2 cytokines (IL-5) in the bronchoalveolar lavage fluid and OVA-specific imunoglobin E (IgE) in the serum. The gene expression of IL-5, IL-13, CCR3, MUC5AC, and COX-2 was attenuated in lung tissues. CP and OA might inhibit the nuclear translocation of GATA-binding protein 3 (GATA-3) and retinoic acid receptor-related orphan receptor γt (RORγt) via the upregulation of forkhead box p3 (Foxp3), thereby preventing the activation of GATA-3 and RORγt. In the in vitro experiment, a similar result was observed for Th2 and GATA-3. These results suggest that CP has the potential for the treatment of asthma via the inhibition of the GATA-3/Th2 and IL-17/RORγt signaling pathways.

A combination of Olea europaea leaf extract and Spirodela polyrhiza extract alleviates atopic dermatitis by modulating immune balance and skin barrier function in a 1-chloro-2,4-dinitrobenzene-induced murine model.

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease in humans. Although Olea europaea leaf extract (OLE) and Spirodela polyrhiza extract (SPE) have been used to protect against skin damage, the effects of their combined administration on atopic dermatitis have yet to studied. PURPOSE: In this study, we evaluated the potential therapeutic effects of an OLE and SPE combination on the progression of atopic dermatitis and the possible mechanisms underlying these effects in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. METHODS: Atopic dermatitis was induced by topical application of 0.2% w/v DNCB prepared in an olive oil:acetone solution (1:3), and thereafter OLE, SPE and OLE + SPE were administered orally for 5 weeks. We determined atopic dermatitis symptoms, serum IgE levels, and levels of cytokine- and gene expression in the dorsal skin and splenocytes, and performed histological and immune cell subtype analyses. The expression of skin barrier-related proteins (filaggrin, sirtuin 1, and claudin 1) was also evaluated. RESULTS: The OLE + SPE combination significantly ameliorated atopic dermatitis symptoms, including dermatitis scores, and reduced epidermal thickness and infiltration of different inflammatory cells in mice with DNCB-induced atopic dermatitis. It also significantly reduced the number of CD4+, CD8+, and CD4+/CD69+ T cells; immunoglobulin E-producing B cells (CD23+/B220+) in the axillary lymph nodes; CD3+ T-cell eosinophils (chemokine-chemokine receptor 3+/CD11b+) in the skin; and CD3+ T cells, immunoglobulin E-producing B cells (CD23+/B220+), and eosinophils in peripheral blood mononuclear cells. Additionally, the experimental combination lowered levels of serum immunoglobulin E and histamine, as well as Th2-mediated cytokines, and interleukin-4, -5, and -13, whereas it increased the levels of Th1-mediated cytokine interferon-γ in splenocytes. Furthermore, the preparation significantly restored expression of the skin barrier-related proteins filaggrin, sirtuin 1, and claudin 1, and also reduced the expression of the inflammatory cytokine interleukin-6 and chemokine-chemokine receptor 3, as well as the pruritus-related cytokine interleukin-31 and interleukin-31 receptor, in atopic dermatitis skin lesions. CONCLUSION: Taken together, our findings indicate that administration of a combination of OLE and SPE can alleviate atopic dermatitis symptoms by regulating immune balance and skin barrier function and may be an effective therapeutic option for the treatment of atopic dermatitis.

Efficacy and Safety of GHX02 in the Treatment of Acute Bronchitis and Acute Exacerbation of Chronic Bronchitis: A Phase â ¡, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

Acute bronchitis and acute exacerbations of chronic bronchitis (AECB) have cough and sputum as the main symptoms with a high prevalence and substantial economic burden. Although the demand for bronchitis treatment increases due to causes, such as air pollution, the appropriateness of antibiotic prescriptions and the effects of current symptomatic treatments for bronchitis are unclear. GHX02, which is a combined formulation containing four herbs, and has been clinically used for bronchitis in South Korea. We conducted a phase II, randomized, double-blind, and placebo-controlled, multicenter trial to evaluate its efficacy and safety. Patients with acute bronchitis or AECB were recruited and randomized to receive high-dose GHX02 (1920 mg/day), standard-dose GHX02 (960 mg/day), or placebo for 7 days. The primary outcome measure was the change in Bronchitis Severity Score (BSS) from baseline to Day 7. The secondary outcomes were the frequency of coughing fits, Questionnaire of Clinical Symptoms of Cough and Sputum (QCSCS), Leicester Cough Questionnaire (LCQ), Integrative Medicine Outcome Scale (IMOS), and Integrative Medicine Patient Satisfaction Scale (IMPSS). A total of 117 patients were randomized to parallel groups (38 in the high-dose GHX02, 41 in the standard-dose GHX02 group, and 38 in the placebo group). The mean differences in BSS from baseline to Day 7 in the treatment groups (4.2 ± 2.0 and 4.5 ± 1.8 in the high-dose GHX02 and standard-dose GHX02 groups, respectively) were higher than the placebo group (3.8 ± 2.1), p = 0.028. The mean differences in the frequency of coughing fits from baseline to Day 7 and IMPSS were better in the GHX02 treatment group than in the placebo group (standard-dose GHX02 group vs placebo group, p = 0.036). The QCSCS, LCQ, IMOS, and GHX02 of the treatment groups also showed more improvement than the placebo group, but there were no statistically significant differences between the groups. There were no severe adverse effects during the trial. This study supports that GHX02 is effective and safe for patients with bronchitis and provides the basis for progression to a phase III study. Clinical Trial Registration: [https://cris.nih.go.kr] WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003665].

Hypericum ascyron L. extract reduces particulate matter-induced airway inflammation in mice.

The consequences of increased industrialization increased the risk of asthma and breathing difficulties due to increased particulate matter in the air. We aim to investigate the therapeutic properties of Hypericum ascyron L. extract (HAE) in airway inflammation and unravel its mechanism of action. We conducted nitric oxide and cell viability assay, real-time PCR and western blot analyses along with in vitro studies. in vivo studies include a model of coal fly ash and diesel exhaust particle (CFD)-induced airway inflammation in mice. HAE reduced coal fly ash (CFA)-induced nitric oxide secretion without exhibiting cytotoxicity in MH-S cells. HAE also reduced the mRNA expression of pro-inflammatory cytokines and reduced the expression of proteins in the NFκB and MAPK pathways. In a mice model of CFD-induced airway inflammation, HAE effectively reduced neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and increased the amount of T cells in the BALF, lungs, and blood while reducing all other immune cell subtypes to reduce airway inflammatory response. CXCL-1, IL-17, MIP-2, and TNF-α expression in the BALF were also reduced. HAE effectively reduced MIP-2 and TNF-α mRNA expression in the lung tissue of mice. In a nutshell, HAE is effective in preventing airway inflammation induced by CFA in MH-S cells, as well as inflammation induced by CFD in mice.

Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality.

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.

Anti-Melanogenic Effects of Korean Red Ginseng Oil in an Ultraviolet B-Induced Hairless Mouse Model.

A 'remedy for all' natural product widely known in the Korean Peninsula is called Panax Ginseng Meyer. Globalization represents a persistent risk to the ozone layer, leading to bountiful amounts of Ultra-Violet B beams (UVB). The variety in human skin hues is ascribed to the characteristic color called Melanin. However, Melanin overproduction due to UVB beams promotes skin staining and tumorigenesis, a process called photo aging, which damages skin quality. To assess the effects of Korean Red Ginseng Oil (KGO) on photo aging, the murine melanoma cell lines B16/F10 were used in vitro and HRM-2 hairless mice exposed to UVB were studied in vivo. Our results revealed that KGO reduced tyrosinase activity and melanin production in B16/F10 cells along with the suppression of upstream factors involved in the melanin production pathway, both transcriptionally and transitionally. In the in vivo studies, KGO suppressed the expression of Matrix Metalloproteinase (MMP) and Interleukins along with a reduction of depth in wrinkle formation and reduced collagen degradation. Moreover, the feed intake and feed efficiency ratio that decreased as a result of UVB exposure was also improved by KGO treatment. In light of our results, we conclude that KGO can have considerable benefits due to its various properties of natural skin enhancement.

Dietary Epigallocatechin-3-Gallate Alters the Gut Microbiota of Obese Diabetic db/db Mice: Lactobacillus Is a Putative Target.

Obesity results in the progression of metabolic disorders, and especially type 2 diabetes mellitus (T2DM), and the gut microbiota have been implicated in the development of T2DM. This study investigated the effect of epigallocatechin-3-gallate (EGCG) on structural changes to the gut microbiota of obese diabetic db/db mice. db/db mice were subjected to a control and EGCG (10, 50, and 100 mg/kg) diet for 8 weeks. Glucose homeostasis and the structure and composition of the gut microbiota were measured. EGCG inhibited the increases in body weight and fasting blood glucose levels. Similarly, it resulted in remarkable improvements in glucose tolerance. Based on lipid profiles, EGCG decreased serum cholesterol and low-density lipoprotein (LDL) levels, and increased the high-density lipoprotein/LDL ratio. In addition, upon fecal microbiota analysis, this compound significantly increased the Firmicutes:Bacteroidetes ratio at the phylum level and increased Lactobacillus abundance at the genus level. Especially, its administration increased abundances of the Lactobacillus gasseri, Lactobacillus intestinalis, and Lactobacillus reuteri. We also found that EGCG increased Christensenellaceae abundance and decreased Enterobacteriaceae and Proteobacteria abundance at the family level. EGCG improves glucose homeostasis in diabetic mice. Its beneficial effects on glucose homeostasis are likely associated with alterations to the gut microbiota. Furthermore, the enrichment of probiotics (Lactobacillus) might be a potential mechanism underlying the effects of EGCG on glucose homeostasis.

Effects of a herbal formulation, KGC3P, and its individual component, nepetin, on coal fly dust-induced airway inflammation.

Coal fly dust (CFD)-induced asthma model is used as an ambient particulate matter model of serious pulmonary damage. We aimed to evaluate the effects of a combination of ginseng and Salvia plebeia R. Br extract (KGC-03-PS; KG3P) and its individual components (hispidulin, nepetin and rosmarinic acid) in a CFD-induced mouse model of airway inflammation (asthma). We also evaluated signal transduction by KG3P and its individual components in the alveolar macrophage cell line, MH-S cells. In vitro, KG3P and its individual components inhibited nitric oxide production and expression of pro-inflammatory mediators and cytokines (iNOS, COX-2, IL-1ß, IL-6 and TNF-α) through the NF-κB and MAPK pathways in coal fly ash (CFA)-induced inflammation in MH-S cells. Moreover, in the CFD-induced asthma model in mice, KG3P and its predominant individual component, nepetin, inhibited Asymmetric Dimethyl arginine (ADMA) and Symmetric Dimethyl arginine (SDMA) in serum, and decreased the histopathologic score in the lungs. A significant reduction in the neutrophils and immune cells in BALF and lung tissue was demonstrated, with significant reduction in the expression of the pro-inflammatory cytokines. Finally, IRAK-1 localization was also potently inhibited by KG3P and nepetin. Thus, KG3P extract can be considered as a potent candidate for amelioration of airway inflammation.

The effect of lung-conduction exercise in chronic obstructive pulmonary disease: Study protocol for randomized, assessor-blind, multicenter trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an irreversible disease characterized by cough, sputum production, and dyspnea, and has a high prevalence and mortality. Pulmonary rehabilitation (PR) is a management that improves the quality of life for COPD patients; however, PR is not readily accessible. Therefore, we developed lung-conduction exercises (LCE) that can be performed without any limitations. LCE consists of breathing, stretching, and tapping to relieve dyspnea in COPD patients. METHODS/DESIGN: This randomized, assessor-blind, multicenter trial aims to recruit 54 patients with moderate and severe COPD. Subjects will be randomly allocated to a control group (only medication), an LCE group (medication + LCE, 5 times a week), or a PR group (medication + PR, 5 times a week). The 6-minute walk distance, pulmonary function tests (forced expiratory volume at 1 second, forced vital capacity, and forced expiratory volume at 1 second/forced vital capacity), modified Borg scale, modified medical research council dyspnea scale, COPD assessment test, and St. George respiratory questionnaire will be measured before starting the trial and after the 4th and 8th weeks to determine motor performance, lung function, and dyspnea. CONCLUSION: We aim to demonstrate that LCE is effective in improving symptoms and psychosomatic stability in COPD patients. Therefore, this trial will play an important role in fortifying the foundation of clinical application.

Protective Effect of GHX02 Extract on Particulate Matter-Induced Lung Injury.

Industrial development, along with the rapid growth of the economy, has greatly improved the quality of life in humans. Moreover, advancements in medical technology have increased life expectancy. Small particles increase airway inflammation when they penetrate the alveoli. We observed that GHX02 decreased the frequency and delayed the onset time of citric acid-induced coughing in guinea pigs. A phenol red secretion assay indicated that the GHX02 extract exhibits potent expectorant activity. The GHX02 extract also greatly reduced leukocyte levels. Our results indicate that GHX02 inhibits airway inflammation, reduces sputum production, and relieves cough. The GHX02 extract suppressed histamine release from mast cells resulting from compound 48/80-induced degranulation. The extract exhibited antimicrobial activity against Streptococcus pneumoniae and significantly inhibited the formation of LTC4. At high concentrations, the GHX02 extract suppressed the formation of PGE2 (prostaglandin E2). Interleukin (IL)-4 and IL-13 levels decreased with an increasing dosage of GHX02. Oral administration of the GHX02 extract suppressed PM10D-induced inflammatory symptoms in the lung, including increased alveolar wall thickness, accumulation of collagen fibers, and cytokine release. Treatment with the GHX02 extract also resulted in lower levels of inflammatory cells, in bronchoalveolar lavage fluid and lung tissue. Our results indicate that GHX02 may be a useful therapeutic agent for treatment of respiratory diseases.