An Integrative Study of Scrophularia takesimensis Nakai in an Ovalbumin-Induced Murine Model of Asthma: The Effect on T Helper 2 Cell Activation.

Scrophularia have traditionally been used as herbal medicines to treat neuritis, sore throats, and laryngitis. In particular, S. takesimensis, a Korean endemic species with restricted distribution on Ulleung Island, holds significant resource and genetic value. However, its pharmacological properties have not been thoroughly evaluated. Thus, we provide detailed morphological characteristics and genomic information for S. takesimensis in this study. Moreover, its pharmacological activity was evaluated in an ovalbumin-induced asthma rat model, using extracts of S. takesimensis roots (100 or 200 mg/kg). The distinguishing features of S. takesimensis from related species include the presence or absence of stem wings, leaf shape, and habitat. The chloroplast (cp) genome of this species is 152,420 bp long and exhibits a conserved quadripartite structure. A total of 114 genes were identified, which included 80 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. The gene order, content, and orientation of the S. takesimensis cp genome was highly conserved and consistent with the general structure observed in S. buergeriana and S. ningpoensis cp genomes. Confirming the anti-inflammatory effects of S. takesimensis extract (STE) using an established mouse model of ovalbumin-induced asthma, we observed reduced asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and suppression of T helper 2 (Th2) cell. Furthermore, STE treatment reduced Th2 cell activation and differentiation. This study underscores the medicinal value of S. takesimensis. The importance of preserving S. takesimensis was revealed and crucial insights were provided for further research on its utilization as a medicinal resource.

Loranthus tanakae Franch. and Sav. Attenuates Respiratory Inflammation Caused by Asian Sand Dust.

Asian sand dust (ASD), generally produced in East Asia, including China, Japan, and Korea, directly leads to the development of pulmonary disease and exacerbates underlying pulmonary diseases. Loranthus tanakae Franch. and Sav. is a traditional herbal medicine applied to improve various inflammatory conditions. Here, we evaluated the curative properties of L. tanakae ethanol extract (LTE) against pulmonary inflammation caused by ASD. Additionally, to investigate the mechanism of action of LTE, we performed network pharmacological analysis. ASD was administrated on day 1, 3, and 5 by intranasal instillation, and LTE was orally administered for 6 days. Administration of LTE significantly decreased inflammatory cytokines and the number of inflammatory cells in bronchoalveolar lavage fluid, which was accompanied by a decrease in inflammatory cell accumulation in pulmonary tissue. Administration of LTE decreased the expression of cyclooxygenase2 and matrix metalloproteinase-9 in mice exposed to ASD with the decline in p65 phosphorylation. Additionally, administration of LTE significantly elevated hemeoxygenase (HO)-1 expression in the pulmonary tissue of mice exposed to ASD. These results were consistent with the data of network pharmacological analysis. This experiment showed that LTE attenuated pulmonary inflammation caused by ASD via inhibition of NF-κB and elevation of HO-1. Therefore, LTE may have potential as a therapeutic agent to treat pulmonary inflammation caused by ASD.

Anti-Atopic Effect of Scutellaria baicalensis and Raphanus sativus on Atopic Dermatitis-like Lesions in Mice by Experimental Verification and Compound-Target Prediction.

Scutellaria baicalensis Georgi and Raphanus Sativus Linne herbal mixture (SRE) is a Chinese herbal medicine. In this study, we aimed to evaluate the therapeutic efficacy of SRE as an active ingredient for 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) and to predict the underlying therapeutic mechanisms and involved pathways using network pharmacological analysis. Treatment with SRE accelerated the development of AD-like lesions, improving thickness and edema of the epidermis. Moreover, administering the SRE to AD-like mice suppressed immunoglobulin E and interleukin-4 cytokine and reduced T lymphocyte differentiation. In silico, network analysis was used to predict the exact genes, proteins, and pathways responsible for the therapeutic effect of the SRE against DNCB-induced AD. These results indicated that the SRE exerted protective effects on the DNCB-induced AD-like model by attenuating histopathological changes and suppressing the levels of inflammatory mediators. Therefore, the SRE can potentially be a new remedy for improving AD and other inflammatory diseases and predicting the intracellular signaling pathways and target genes involved. This therapeutic effect of the SRE on AD can be used to treat DNCB-induced AD and its associated symptoms.

Camellia sinensis (L.) Kuntze Extract Attenuates Ovalbumin-Induced Allergic Asthma by Regulating Airway Inflammation and Mucus Hypersecretion.

Asthma is a pulmonary disease induced by the inhalation of aeroallergens and subsequent inappropriate immune responses. Camellia sinensis (L.) Kuntze has been evaluated as an effective antioxidant supplement produced from bioactive compounds, including flavonoids. In this study, we aimed to determine the effects of Camellia sinensis (L.) Kuntze extract (CE) on ovalbumin-induced allergic asthma. The components of CE were analyzed using high-performance liquid chromatography (HPLC) chromatogram patterns, and asthmatic animal models were induced via ovalbumin treatment. The antioxidant and anti-inflammatory effects of CE were evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), and nitric oxide (NO) assays. Seven compounds were detected in the CE chromatogram. In the ovalbumin-induced mouse model, CE treatment significantly decreased the inflammation index in the lung tissue. CE also significantly decreased eosinophilia and the production of inflammatory cytokines and OVA-specific IgE in animals with asthma. Collectively, our results indicate that CE has anti-inflammatory and antioxidant activities, and that CE treatment suppresses asthmatic progression, including mucin accumulation, inflammation, and OVA-specific IgE production.

Veronica persica Ethanol Extract Ameliorates Dinitrochlorobenzene-Induced Atopic Dermatitis-like Skin Inflammation in Mice, Likely by Inducing Nrf2/HO-1 Signaling.

Atopic dermatitis (AD) is chronic allergic contact dermatitis with immune dysregulation. Veronica persica has pharmacological activity that prevents asthmatic inflammation by ameliorating inflammatory cell activation. However, the potential effects of the ethanol extract of V. persica (EEVP) on AD remain elusive. This study evaluated the activity and underlying molecular pathway of EEVP in two AD models: dinitrochlorobenzene (DNCB)-induced mice and interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated human HaCaT keratinocytes. EEVP attenuated the DNCB-induced increase in serum immunoglobulin E and histamine levels, mast cell counts in toluidine-blue-stained dorsal skin, inflammatory cytokine (IFN-γ, interleukin [IL]-4, IL-5, and IL-13) levels in cultured splenocytes, and the mRNA expression of IL6, IL13, IL31 receptor, CCR-3, and TNFα in dorsal tissue. Additionally, EEVP inhibited the IFN-γ/TNF-α-induced mRNA expression of IL6, IL13, and CXCL10 in HaCaT cells. Furthermore, EEVP restored the IFN-γ/TNF-α-induced downregulation of heme oxygenase (HO)-1 in HaCaT cells by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. A molecular docking analysis demonstrated that EEVP components have a strong affinity to the Kelch-like ECH-associated protein 1 Kelch domain. In summary, EEVP inhibits inflammatory AD by attenuating immune cell activation and inducing the Nrf2/HO-1 signaling pathway in skin keratinocytes.

The Safety and Efficacy of 1-Monoeicosapentaenoin Isolated from the Trebouxiophyceae Micractinium on Anti-Wrinkle: A Split-Face Randomized, Double-Blind Placebo-Controlled Clinical Study.

The skin aging process is governed by intrinsic and extrinsic factors causing skin wrinkles, sagging, and loosening. The 1-monoeicosapentaenoin (1-MEST) is a component isolated from Micractinium, a genus of microalgae (Chlorophyta, Trebouxiophyceae). However, the anti-wrinkle effects of 1-MEST are not yet known. This study aimed to evaluate the anti-wrinkle effects of 1-MEST in vitro and in clinical trials. The cytotoxicity of 1-MEST was investigated in vitro using the MTS assay in human epidermal keratinocytes (HEKs). Expression of matrix metalloproteinase (MMP)-1 and MMP-9 was determined by ELISA in HEKs irradiated with UVB after treatment with 1-MEST. A split-face randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of 1-MEST. The study evaluated wrinkle parameters and visual assessment, self-efficacy and usability questionnaires, and adverse events. The study showed that the 1-MEST was not cytotoxic in HEKs, suppressed MMP-1 secretion and MMP-9 protein expression in HEKs irradiated with UVB. The wrinkle parameters and mean visual assessment score were significantly decreased in the test group after 12 weeks and differed from the control group. There were no significant differences in efficacy and usability. Adverse effects were also not observed. The 1-MEST showed anti-wrinkle properties to slow down or prevent skin aging.

Protective Effect of Bojungikki-Tang against Radiation-Induced Intestinal Injury in Mice: Experimental Verification and Compound-Target Prediction.

Bojungikki-tang (BJIT) is a traditional herbal medicine used in Korea, Japan, and China to treat gastrointestinal disorders. In this study, we aimed to investigate whether BJIT has protective effects against radiation-induced intestinal injury and to predict the underlying therapeutic mechanisms and related pathways via network pharmacological analyses. BJIT was injected intraperitoneally (50 mg/kg body weight) to C3H/HeN mice at 36 and 12 h before exposure to partial abdominal irradiation (5 Gy and 13 Gy) to evaluate the apoptotic changes and the histological changes and variations in inflammatory cytokine mRNA levels in the jejunum, respectively. Through in silico network analysis, we predicted the mechanisms underlying BJIT-mediated regulation of radiation-induced intestinal injury. BJIT reduced the level of apoptosis in the jejunal crypts 12 h post 5-Gy irradiation. Histological assessment revealed intestinal morphological changes in irradiated mice 3.5 days post 13-Gy irradiation. Furthermore, BJIT decreased inflammatory cytokine levels following radiation exposure. Apoptosis, TNF, p53, VEGF, toll-like receptor, PPAR, PI3K-Akt, and MAPK signaling pathways, as well as inflammatory bowel disease (IBD), were found to be linked to the radioprotective effects of BJIT against intestinal injury. According to our results, BJIT exerted its potential protective effects by attenuating histopathological changes in jejunal crypts and suppressing inflammatory mediator levels. Therefore, BJIT is a potential therapeutic agent that can treat radiation-induced intestinal injury and its associated symptoms.

Loranthus tanakae Franch. & Sav. Suppresses Inflammatory Response in Cigarette Smoke Condensate Exposed Bronchial Epithelial Cells and Mice.

Loranthus tanakae Franch. & Sav. found in China, Japan, and Korea is traditionally used for managing arthritis and respiratory diseases. In this study, we analyzed the components of L. tanakae 70% ethanol extract (LTE) and investigated the therapeutic effects of LTE on pulmonary inflammation using cells exposed to cigarette smoke condensate (CSC) and lipopolysaccharide (LPS) in vitro and in vivo in mice and performed a network analysis between components and genes based on a public database. We detected quercitrin, afzelin, rhamnetin 3-rhamnoside, and rhamnocitrin 3-rhamnoside in LTE, which induced a significant reduction in inflammatory mediators including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and inflammatory cells in CSC exposed H292 cells and in mice, accompanied by a reduction in inflammatory cell infiltration into lung tissue. In addition, LTE increased translocation into the nuclei of nuclear factor erythroid-2-related factor 2 (Nrf2). By contrast, the activation of nuclear factor (NF)-κB, induced by CSC exposure, decreased after LTE application. These results were consistent with the network pharmacological analysis. In conclusion, LTE effectively attenuated pulmonary inflammation caused by CSC+LPS exposure, which was closely involved in the enhancement of Nrf2 expression and suppression of NF-κB activation. Therefore, LTE may be a potential treatment option for pulmonary inflammatory diseases including chronic obstructive pulmonary disease (COPD).

Ethanol extract of Veronica persica ameliorates house dust mite-induced asthmatic inflammation by inhibiting STAT-3 and STAT-6 activation.

Veronica persica is a flowering plant belonging to the family Scrophulariaceae. Here, we aimed to evaluate the pharmacological activity of the ethanol extract of Veronica persica (EEVP) in an airway inflammation model. We examined airway responsiveness to aerosolized methacholine, serum immunoglobulin (Ig)E levels, and total cell numbers in the lung and bronchoalveolar lavage fluid (BALF). Histological analysis of the lung tissue was performed using hematoxylin-eosin, Masson trichrome, or periodic acid-Schiff staining. Fluorescence-activated cell sorting analysis in the lung and BALF was applied to clarify the changes in immune cell types. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were applied to investigate cytokine levels and gene expression related to airway inflammation. STAT-3/6 phosphorylation was examined in primary bronchial/tracheal epithelial cells using western blot analysis. EEVP significantly suppressed total IgE levels and methacholine-induced increase of Penh value in the HDM-challenged mouse model. EEVP also attenuated the severity of airway remodeling in lung tissues and decreased eosinophil and neutrophil infiltration in the lungs and BALF. EEVP significantly reduced the production of cytokines in BAL and splenocyte culture medium, and the expression of mRNAs related to airway inflammation in the lung tissue. EEVP suppressed IL-4/13-induced STAT-3/6 phosphorylation in the epithelial cells. We showed for the first time that EEVP effectively inhibits eosinophilic airway inflammation by suppressing the expression of inflammatory factors for T cell activation and polarization, and inhibits MCP-1 production of bronchial/tracheal epithelial cells by suppressing STAT-3/6 activation. EEVP may be a potential pharmacological agent to prevent inflammatory airway diseases.

Wrinkle reduction using a Sasang constitutional medicine-based topical herbal cream in So-eum subjects: A split-face randomized double-blind placebo-controlled study.

BACKGROUND: Skin aging is caused by exogenous and endogenous factors and is commonly manifested as wrinkling, sagging, and looseness of the skin. The herbal extract including Zingiber officinale Roscoe, Atractylodes chinensis (Bunge) Kodiz, Curcuma longa L., and Cinnamomum cassia (L.) J.Presl (ZACC extract), is widely used for So-eum (SE) Sasang constitutional type individuals. This study aimed to examine the protective effects of the ZACC extract against skin aging in 21 SE type subjects. METHODS: The safety and clinical efficacy of herbal cream were evaluated after application on human skin in a split-face randomized, double-blind, placebo-controlled study. The Sasang Constitution Analysis Tool (SCAT) was used to select 21 SE type subjects, who applied herbal cream and placebo cream for 12 weeks. Visual assessment, wrinkle parameters, questionnaires, and skin safety were evaluated. RESULTS: The visual assessment score was decreased by using of the herbal cream, but there were no significant differences between groups. Among the wrinkle parameters, R1 (skin roughness) and R4 (smoothness depth) values were significantly improved after the application of the herbal cream compared to those observed after application of the placebo cream for 12 weeks. No significant differences were observed in evaluation of the product efficacy and usability by questionnaires. There were no adverse dermatologic reactions in the SE type subjects during the evaluation period. CONCLUSION: The ZACC herbal cream may be used to prevent or slow skin aging, including wrinkle formation, in SE type individuals.

Hesperidin Inhibits UVB-Induced VEGF Production and Angiogenesis via the Inhibition of PI3K/Akt Pathway in HR-1 Hairless Mice.

Hesperidin is a citrus flavanone glycoside with potent anti-inflammatory effects that interferes with UVB-stimulated angiogenesis in skin, but its molecular mechanisms of action remain unclear. Here, we investigated the effects of hesperidin on UVB-induced angiogenesis in HR-1 hairless mice. We found hesperidin treatment inhibited skin neovascularization skin induced by repetitive UVB light exposure. Exposure to UVB radiation induces the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-13 (MMP-13), and MMP-9, but we found all of these were inhibited by treatment with hesperidin. Using immunohistochemistry and Western blotting, we also found hesperidin inhibited the increase in hypoxia inducible factor-1 (HIF-1)α expression induced by UVB exposure. After discovering that UVB induces VEGF expression via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways, we found hesperidin reduces UVB-induced VEGF expression by inhibiting UVB-induced PI3K activity. This, in turn, reduces the UVB-induced Akt/p70S6K phosphorylation in human primary keratinocytes and fibroblast cells. Because it affects the mediators of angiogenesis, our data suggest hesperidin has an anti-angiogenic effect on the pathologic skin neovascularization induced by UVB light. Thus, hesperidin may prove useful in the treatment of skin injuries caused by UVB light exposure.

Plastid Phylogenomic Data Offers Novel Insights Into the Taxonomic Status of the Trichosanthes kirilowii Complex (Cucurbitaceae) in South Korea.

Trichosanthes is a genus in Cucurbitaceae comprising 90-100 species. Trichosanthes species are valuable as herbaceous medicinal ingredients. The fruits, seeds, and roots of species such as T. kirilowii and T. rosthornii are used in Korean traditional herbal medicines. T. rosthornii is only found in China, whereas in South Korea two varieties, T. kirilowii var. kirilowii and T. kirilowii var. japonica, are distributed. T. kirilowii var. kirilowii and T. kirilowii var. japonica have different fruit and leaf shapes but are recognized as belonging to the same species. Furthermore, although its members have herbal medicine applications, genomic information of the genus is still limited. The broad goals of this study were (i) to evaluate the taxonomy of Trichosanthes using plastid phylogenomic data and (ii) provide molecular markers specific for T. kirilowii var. kirilowii and T. kirilowii var. japonica, as these have differences in their pharmacological effectiveness and thus should not be confused and adulterated. Comparison of five Trichosanthes plastid genomes revealed locally divergent regions, mainly within intergenic spacer regions (trnT-UGU-trnL-UAA: marker name Tri, rrn4.5-rrn5: TRr, trnE-UUC-trnT-GGU: TRtt). Using these three markers as DNA-barcodes for important herbal medicine species in Trichosanthes, the identity of Trichosanthes material in commercial medicinal products in South Korea could be successfully determined. Phylogenetic analysis of the five Trichosanthes species revealed that the species are clustered within tribe Sicyoeae. T. kirilowii var. kirilowii and T. rosthornii formed a clade with T. kirilowii var. japonica as their sister group. As T. kirilowii in its current circumscription is paraphyletic and as the two varieties can be readily distinguished morphologically (e.g., in leaf shape), T. kirilowii var. japonica should be treated (again) as an independent species, T. japonica.

Extract of Curcuma zedoaria R. prevents atherosclerosis in apolipoprotein E-deficient mice.

BACKGROUND/OBJECTIVES: Curcuma zedoaria R. (Zingiberaceae) has been used to treat headache, fever, and hypertension-related symptoms in Asian countries, including Korea, China, and Japan. We investigated whether dietary intake of a C. zedoaria extract (CzE) affected atherosclerosis in vivo. MATERIALS/METHODS: Apolipoprotein E-deficient (ApoE-/-) mice (n = 32) were fed a normal diet (ND), a high-cholesterol diet (HCD), an HCD containing CzE (100 mg/kg/day), or an HCD containing simvastatin (10 mg/kg/day) for 12 weeks. The anti-atherosclerotic effects were evaluated by observing changes in fatty streak lesions, immunohistochemical analysis, ex vivo fluorescence imaging, lipid profiles, and western blot analysis. RESULTS: The CzE-fed group showed a 41.6% reduction of atherosclerosis. Furthermore, CzE significantly reduced the levels of serum triglyceride, high-density lipoprotein, the chemokine (C-X3-C-motif) ligand 1, the adhesion molecules vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin; down-regulation of tumor necrosis factor-α, interleukin-6, high mobility group box-1, and cathepsin levels in the aortic sinuses and aortas of ApoE-/- mice were also observed. CONCLUSIONS: The results suggest that the inclusion of a water extract of C. zedoaria in a HCD is closely correlated with reducing the risk of vascular inflammatory diseases in an ApoE mouse model.

Serum Starvation Sensitizes Anticancer Effect of Anemarrhena asphodeloides via p38/JNK-Induced Cell Cycle Arrest and Apoptosis in Colorectal Cancer Cells.

The molecular mechanism underlying the anticancer effects of Anemarrhena asphodeloides (A. asphodeloides) on colon cancer is unknown. This is the first study evaluating the anticancer effect of A. asphodeloides extract (AA-Ex) in serum-starved colorectal cancer cells. Changes in cell proliferation and morphology in serum-starved MC38 and HCT116 colorectal cancer cells were investigated using MTS assay. Cell cycle and apoptosis were investigated using flow cytometry, and cell cycle regulator expression was determined using qRT-PCR. Apoptosis regulator protein levels and mitogen-activated protein kinase (MAPK) phosphorylation were assessed using western blotting. AA-Ex sensitively suppressed proliferation of serum-starved colorectal cancer cells, with MC38 and HCT116 cells showing greater changes in proliferation after treatment with AA-Ex under serum starvation than HaCaT and RAW 264.7 cells. AA-Ex inhibited cell cycle progression in serum-starved MC38 and HCT116 cells and increased the expression of cell cycle inhibitors (p53, p21, and p27). Furthermore, AA-Ex induced apoptosis in serum-starved MC38 and HCT116 cells. Consistently, AA-Ex suppressed the expression of the anti-apoptotic molecule Bcl-2 and upregulated pro-apoptotic molecules (cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved-PARP) in serum-starved cells. AA-Ex treatment under serum starvation decreased AKT and ERK1/2 phosphorylation in the cell survival signaling pathway but increased p38 and JNK phosphorylation. Furthermore, AA-Ex treatment with serum starvation increased the levels of the transcription factors of the p38 and JNK pathway. Serum starvation sensitizes colorectal cancer cells to the anticancer effect of A. asphodeloidesvia p38/JNK-induced cell cycle arrest and apoptosis. Hence, AA-Ex possesses therapeutic potential for colon cancer treatment.

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].

Protective effects of Sosihotang extract against ultraviolet B-induced skin photoageing in hairless mice.

OBJECTIVES: Sosihotang (SSH) is an herbal medicine traditionally used against the common cold, and hepatic and gastric diseases, in Northeast Asia. In this study, we investigated whether SSH extract can protect against UVB-induced skin damage and photoageing. METHODS: HaCaT cells were treated with SSH extract and exposed UVB irradiation at 20 mJ/cm2 . Hairless mice were orally administered SSH extract (100 mg/kg per mouse) as UVB irradiation was increased from 60 to 120 mJ/cm2 over the course of 12 weeks. KEY FINDINGS: Treatment with SSH extract inhibited the upregulation of MMP-1 and MMP-9 expression in UVB-irradiated HaCaT cells. In UVB-irradiated hairless mice, treatment with SSH extract restored the levels of factors instrumental in skin hydration (TEWL, capacitance, HA and TGF-ß) and those regulating collagen content (procollagen, MMP-1 and MMP-9). This activity inhibited epidermal thickening and disorganization of collagen fibres. Administration of SSH extract also ameliorated the expression of UVB-induced pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) and phosphorylation of MAPK family members (MEK, JNK, ERK and p38) by upregulating the activity of antioxidant enzymes (SOD, CAT, Nrf-2, HO-1 and NQO-1). CONCLUSIONS: These results indicate that SSH extract can be used therapeutically for the treatment of UVB-induced skin damage and photoageing.

Beneficial Effects of Insect Extracts on Nonalcoholic Fatty Liver Disease.

It is well known that nonalcoholic fatty liver disease (NAFLD) is a common disease worldwide because of unhealthy changes in dietary habits. In this study, we determined the effects of Tenebrio molitor Linnaeus, 1758 extract (TML) and Allomyrina dichotoma Linnaeus, 1771 larvae extract (ADL) in cellular and animal models. In vitro, TML and ADL treatments did not cause cytotoxicity, but attenuated the accumulation of lipid in HepG2 cells induced by free fatty acids. In vivo, mice were orally treated with TML and ADL for 10 weeks during high-fat diet feeding. TML and ADL administration significantly reduced the weight of body, liver tissue, and adipose tissue. Serum lipid profiles, hepatic functional parameters, and glucose levels were ameliorated by TML and ADL. Moreover, TML and ADL suppressed increased lipogenesis and inflammation-related makers, and improved antioxidant enzyme activity. In liver tissue, the decreased lipid accumulation by administration of TML and ADL was observed using Oil Red O and Hematoxylin and Eosin staining. Therefore, we suggest that TML and ADL may be having a therapeutic potential and is used to develop a therapeutic agent for NAFLD.

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.

An Herbal Formula CGplus Ameliorates Stress-Induced Hepatic Injury in a BALB/c Mouse Model.

INTRODUCTION: Stress is a well-known factor for inflammation in diverse organs/tissues. Stress also leads to liver injury, which was supported by clinical observations and animal studies. We herein investigated the hepatoprotective property of an herbal formula (called as CGplus) consisting of Artemisia gmelinii Weber ex Stechm. (syn, Artemisia iwayomogi Kitamura), Wurfbainia villosa var. xanthioides (Wall. ex Baker) Skornick. & A.D.Poulsen (syn, Amomum xanthioides Wallich), and Salvia miltiorrhiza Bunge against stress-induced hepatic damage. METHODS: Male BALB/c mice were orally administered water extract of CGplus (0, 50, 100, or 200 mg/kg) daily for 5 days, and then subjected to immobilization stress for 6 h on the 5th day. RESULTS: Acute immobilization stress elevated remarkably serum concentrations of stress hormones (corticosterone and adrenaline) and two hepatic injury parameters (ALT and AST), while these alterations were significantly attenuated by the administration of CGplus. The increases of oxidative parameters (ROS, NO, lipid peroxidation, and protein carbonyl) and deviation of IL-1ß and IL-10 in opposite directions in hepatic tissues were significantly normalized by CGplus. Pre-treatment with CGplus also notably ameliorated the abnormal activation of toll-like receptor 4 (TLR4), CD14, and lipopolysaccharide-binding protein (LPB) as well as infiltration of neutrophils in hepatic tissues. CONCLUSION: These results suggest that an herbal formula (CGplus) derived from traditional pharmaceutical theory has a potent protective effect against stress-induced hepatic injury via regulation of pro- (IL-1ß) and anti-inflammatory (IL-10) cytokines.

Skin Hydration Effects of Scale-Up Fermented Cyclopia intermedia against Ultraviolet B-Induced Damage in Keratinocyte Cells and Hairless Mice.

Photoaging occurs by chronic skin exposure to the sun and ultraviolet irradiation and leads to skin aging accompanied by a lack of skin hydration. We previously demonstrated the photoprotective effect of fermented Cyclopia intermedia (honeybush) extract on the skin. In this study, we evaluated the skin hydration effects of scaled-up fermented honeybush extract (HU-018) against ultraviolet B (UVB) radiation in HaCaT immortalized human keratinocytes and hairless mice. Pretreating HaCaT cells with HU-018 attenuated the decreased hyaluronic acid (HA) levels and mRNA expression of genes encoding involucrin, filaggrin, and loricrin by UVB irradiation. HU-018 treatment also ameliorated the decreased stratum corneum (SC) hydration and the increased levels of transepidermal water loss (TEWL) and erythema index (EI) in hairless mice after UVB exposure. Microarray analysis revealed changes in gene expression patterns of hyaluronan synthase 2 (Has2), transforming growth factor-beta 3 (TGF-ß3), and elastin induced by HU-018 in UVB-irradiated mice. Consistently, the mRNA expression of Has2, TGF-ß3, and elastin was increased by HU-018 treatment. Moreover, HU-018 restored the increased epidermal thickness and collagen disorganization in skin tissue of UVB-irradiated mice. HU-018 treatment also decreased matrix metalloproteinase-1 (MMP-1) expression and increased procollagen type-1, elastin, and TGF-ß1 expression. In conclusion, we found that HU-018 promoted skin hydration processes in UVB-irradiated keratinocytes and hairless mice by modulating involucrin, filaggrin, loricrin, and HA expression and ameliorating visible signs of photoaging. Thus, HU-018 may be a good skin hydration agent for skin care.