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.

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.

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.

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.

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.

Clinical evaluation of the safety and efficacy of a timosaponin A-III-based antiwrinkle agent against skin aging.

BACKGROUND: Timosaponin A-III (TA-III) is known to exist in the medicinal herb of Anemarrhena asphodeloides as one of major chemical components. AIMS: The photoprotective properties of TA-III on UVB-exposed HaCaT cells were evaluated on the antiwrinkle effects and skin safety in terms of clinical trial. METHODS: The level of matrix metalloproteinase (MMP)-1, tissue inhibitor of metalloproteinases (TIMPs), and pro-inflammatory cytokines were measured in HaCaT cells following UVB irradiation. To evaluate the clinical safety of an agent containing 0.25% of TA-III for use on human skin. Female subjects (n = 21) between the ages of 43 and 55 who met the criteria for subject selection were selected. They were beginning to form or had already formed wrinkles. RESULTS: UVB irradiation increased MMP-1 expression and pro-inflammatory cytokines. These increases were attenuated by TA-III pretreatment of UVB-exposed HaCaT cells. We found that the agent containing 0.25% of TA-III ameliorated skin wrinkling. A comparison between groups showed that wrinkle parameters were significantly reduced after 12 weeks of product use (P < 0.05). According to skin safety result, TA-III showed no dermatological toxicity was found in participants. CONCLUSIONS: In conclusion, TA-III could provide protection against photoaging and daily application of TA-III for 12 weeks significantly reduced signs of facial aging by limiting wrinkle formation.

Assessment of the 4-week repeated-dose oral toxicity and genotoxicity of GHX02.

Herbal medicines are widely utilized for disease prevention and health promotion. GHX02 consists of mixtures including Gwaruin (Trichosanthes kirilowii), Haengin (Prunus armeniaca), Hwangryeon (Coptis japonica) and Hwangkeum (Scutellaria baicalensis). It has been purported to have therapeutic effectiveness in cases of severe bronchitis. Non-clinical safety testing comprised a single-dose oral toxicity study and a 28-day repeated-dose oral toxicity study with a 14-day recovery period, and genotoxicity was assessed by a bacterial reverse mutation test, in vitro chromosomal aberration test, in vivo mouse bone marrow micronucleus test and single cell gel electrophoresis assay (comet assay). In the single-dose oral toxicity study, the approximate lethal dosage is estimated to be higher than 5000 mg/kg in rats. Thus, the dosage levels were set at 0, 1250, 2500 and 5000 mg/kg/day in the 28-day repeated-dose oral toxicity study, and 10 male rats and 10 female rats/dose were administered GHX02. No clinical signs of toxicological significance were recorded in any animal during the dosing and the observation period in the single-dose study. The no-observed-adverse-effect level of GHX02 was 5000 mg/kg/day when administered orally for 28 days to male and female Sprague-Dawley rats. Despite increases in the frequencies of cells with numerical chromosomal aberration in the in vitro test, the increases were not considered relevant to the in vivo genetic risk. Except for the increase of in vitro numerical chromosomal aberration, clear negative results were obtained from other genetic toxicity studies.

Protective effects of Oxya chinensis sinuosa Mishchenko against ultraviolet B-induced photodamage in hairless mice.

BACKGROUND: Edible insects, including Oxya chinensis sinuosa Mishchenko (Oc), which is consumed as food in Asia, are considered as a human food shortage alternative, and also as a preventive measure against environmental destruction. Ultraviolet B (UVB) irradiation, which causes skin photodamage, is considered as an extrinsic skin aging factor. It reduces skin hydration, and increases wrinkle formation and reactive oxygen species (ROS) and inflammatory cytokine expression. Thus, the objective of this study was to investigate the anti-aging effects of an ethanol extract of Oc (Oc.Ex). METHODS: A UVB-irradiated hairless mouse model was used to examine relevant changes in skin hydration, wrinkle formation, and skin epidermal thickness. Also, antioxidant markers such as superoxide dismutase (SOD) and catalase (CAT) were analyzed, and Oc. Ex skin protective effects against UVB irradiation-induced photoaging were examined by determining the levels of skin hydration factors. RESULTS: Oc.Ex improved epidermal barrier dysfunctions such as increased transepidermal water loss (TEWL) and capacitance reduction in UVB-irradiated mice. It upregulated skin hydration-related markers, including hyaluronic acid (HA), transforming growth factor (TGF)-ß, and pro-collagen, in UVB-irradiated mice, compared with the vehicle control group. It also reduced UVB-induced wrinkle formation, collagen degradation, and epidermal thickness. Additionally, it remarkably suppressed the increased expression of matrix metalloproteinases (MMPs), and restored the activity of SOD and CAT in UVB-irradiated mice, compared with the vehicle control group. Furthermore, Oc. Ex treatment downregulated the production of inflammatory cytokines and phosphorylation of the mitogen-activated protein kinases (MAPKs) signaling pathway activated by UVB irradiation. CONCLUSION: This study revealed that Oc. Ex reduced skin thickness and the degradation of collagen fibers by increasing hydration markers and collagen-regulating factors in the skin of UVB-irradiated mice. It also inhibited UVB-induced antioxidant enzyme activity and inflammatory cytokine expression via MAPK signaling downregulation, suggesting that it prevents UVB-induced skin damage and photoaging, and has potential for clinical development in skin disease treatment.

The enhancing immune response and anti-inflammatory effects of Anemarrhena asphodeloides extract in RAW 264.7 cells.

BACKGROUND: Anemarrhena asphodeloides has been widely used in traditional medicine for thousands of years; it has been reported to improve learning and memory, and to reduce inflammation. However, the role of A. asphodeloides in enhancing the immune response has remained unclear. PURPOSE: This study aimed to evaluate the effect of A. asphodeloides extract (AA-Ex) on enhancing the immune response in macrophages and to identify the active compounds causing these effects. STUDY DESIGN/METHODS: To determine the enhancing immune response of AA-Ex and its active compounds, cell proliferation and cell cycle of RAW 264.7 cells were analyzed by MTS assay and flow cytometry. The gene expression of p53, p27, cyclin D2, and cyclin E2 was measured by real-time PCR. To evaluate the anti-inflammatory effects of AA-Ex and its active compounds, the production of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory cytokines was analyzed by Griess reagent, flow cytometry, and real-time PCR. The phosphorylation of p38, c-Jun N-terminal kinase, inhibitory kappa B alpha, and p65 was examined by western blot analysis. RESULTS: AA-Ex increased cell proliferation by extending the cell cycle S-phase; timosaponin B and timosaponin B-II affected cell proliferation and the cell cycle as active compounds of A. asphodeloides. Next, we determined that A. asphodeloides displayed anti-inflammatory effects, including the inhibition of the production of NO, ROS, and pro-inflammatory cytokines through the suppression of mitogen-activated protein kinase and nuclear factor kappa B phosphorylation downstream of the toll-like receptor 4 signaling pathway. Moreover, we identified that timosaponin B and timosaponin B-II were the active compounds for these effects. CONCLUSION: Our results suggest that A. asphodeloides promotes the immune response and has anti-inflammatory effects. Moreover, timosaponin B and B-II played important roles as the active compounds of A. asphodeloides in enhancing the immune and anti-inflammatory responses in this model.

Skin Moisturizing and Antiphotodamage Effects of Tyndallized Lactobacillus acidophilus IDCC 3302.

Photoaging is generally the result of chronic exposure to the sun and ultraviolet (UV) radiation, which causes skin damage. In this study, we developed a UVB-induced hairless mouse model to determine whether Lactobacillus acidophilus IDCC 3302 tyndallizate (ACT3302) can enhance photodamaged skin repair. Mice (6 weeks old) were divided into six groups containing normal, UVB-treated vehicle, and UVB-treated ACT3302 (1 × 105, 1 × 106, 1 × 107, and 1 × 108 cells). Epidermal thickness was increased by UVB, but the thickening was lessened by ACT3302 as was the transepidermal water loss (TEWL). However, ACT3302 increased capacitance and decreased TEWL. Skin tissue staining to evaluate skin collagen increases in the number of skin collagen bundles in UVB-treated ACT3302 mice. UVB irradiation increased matrix metalloproteinase (MMP) and proinflammatory cytokine expression and activated mitogen-activated protein kinases in hairless mice; these changes were also attenuated by ACT3302. We conclude that ACT3302 effectively suppressed wrinkle formation induced by UVB irradiation through MMP downregulation. Therefore, ACT3302 potentially prevents skin photoaging and wrinkle formation.

Hepatoprotective Effects of Insect Extracts in an Animal Model of Nonalcoholic Fatty Liver Disease.

Insects represent the largest and most diverse group of organisms on earth and are potential food and drug resources. Recently, we have demonstrated that a Forsythia viridissima extract prevented free fatty acid-induced lipid accumulation in an in vitro cellular nonalcoholic fatty liver disease (NAFLD) model. In this study, we aimed to evaluate the hepatoprotective effects of extracts of the insects Protaetia brevitarsis seulensis Kolbe, 1886 (PB), Oxya chinensis sinuosa Mishchenko, 1951 (OC), and Gryllus bimaculatus De Geer, 1773 (GB) in a high-fat diet (HFD)-induced NAFLD animal model, as well as to elucidate the underlying mechanisms. The effects of the supplementation with PB, OC, and GB extracts were evaluated histopathologically and histochemically. PB, OC, and GB extract supplementation inhibited the HFD-induced increase in body weight and body fat mass and ameliorated other adverse changes, resulting in decreased liver function parameters, lower serum triglyceride and cholesterol levels, and increased serum adiponectin levels. The expression of hepatic genes involved in lipid droplet accumulation and in fatty acid uptake also decreased upon treatment of HFD-fed mice with the extracts. These results provide evidence of the protective effects of the PB, OC, and GB extracts against HFD-induced fatty liver disease in an animal model.

The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways.

BACKGROUND: Hesperidin is a flavonoid with antioxidant, anti-inflammatory, and immune modulatory activities. Photoaging is a consequence of chronic exposure to the sun and ultraviolet (UV) radiation. This study was designed to evaluate the efficacy of hesperidin against photoaging of dorsal skin in hairless mice. METHODS: Hairless male mice (6-week-old) were divided into three groups (n = 7): control, UVB-treated vehicle, and UVB-treated hesperidin groups. UVB-irradiated mice from hesperidin group were orally administered 0.1 mL of water containing 100 mg/kg body weight per day hesperidin. RESULTS: The mean length and depth of wrinkles in the UVB-treated hesperidin group significantly improved after the oral administration of hesperidin, which significantly inhibited the increase in epidermal thickness and epidermal hypertrophy (P < 0.05). UVB irradiation of mice induced epidermal barrier dysfunction including an increase in the transepidermal water loss (TEWL); however, hesperidin decreased the TEWL. UVB irradiation increased the expression of MMP-9 and pro-inflammatory cytokines whereas UVB-treated hesperidin group showed reduced expression. These results indicate that hesperidin showed anti-photoaging activity in the UVB-irradiated hairless mice. In conclusion, hesperidin inhibited the UVB-induced increase in skin thickness, wrinkle formation, and collagen fiber loss in male hairless mice. CONCLUSIONS: These results suggest that hesperidin shows potent anti-photoaging activity by regulating MMP-9 expression through the suppression of MAPK-dependent signaling pathways.

Protective effects of compounds from Garcinia mangostana L. (mangosteen) against UVB damage in HaCaT cells and hairless mice.

Ultraviolet B (UVB) radiation causes alterations in the skin, such as epidermal thickening, wrinkle formation and inflammation. Therefore, preventing UVB-induced skin damage can promote general health among the human population. Garcinia mangostana L. (mangosteen) is a fruit that has become a popular botanical dietary supplement because of its perceived role in promoting overall health. The present study investigated the photoprotective effects of α-, ß-, γ-mangostins and gartanin against UVB radiation using the HaCaT immortalized human keratinocyte cell line as an in vitro model and hairless mice as an in vivo model. UVB radiation increased the expression of matrix metalloproteinase (MMP)­1 and ­9 and decreased the mRNA expression levels of involucrin, filaggrin and loricrin in HaCaT cells; however, these changes were attenuated by pretreating the cells with α-, ß-, γ-mangostins and gartanin. Among these compounds, α-mangostin exhibited the greatest effects in reducing UVB-induced skin wrinkles, inhibited epidermal thickening in hairless mice in vivo. Exposure to UVB radiation increased the expression of MMPs and pro-inflammatory cytokines and activated mitogen-activated protein kinases in hairless mice, but these changes were attenuated by α-mangostin. The authors suggested that α-mangostin exerts anti-wrinkle and anti-aging properties.

Dual Protective Effects of Flavonoids from Petasites japonicus against UVB-Induced Apoptosis Mediated via HSF-1 Activated Heat Shock Proteins and Nrf2-Activated Heme Oxygenase-1 Pathways.

The leaves of Petasites japonicus are used for their anti-allergic properties in traditional Korean, Japanese, and Chinese medicine. This study aimed to identify bioactive compounds isolated from P. japonicus leaves. All compounds were assessed for their ability of transcriptional activation, induction of phase 2 enzymes and heat shock proteins (HSPs), as well as protection against the UVB-induced apoptotic cell death. Bioactive compounds were isolated from P. japonicus leaves. All compounds were evaluated for their protective effect using human dermal fibroblasts (HDF) and human epidermal keratinocyte cells (HEKC) treated with UVB radiation. Four flavonoids were isolated from the leaves of P. japonicus and identified as kaempferol-3-O-(6″-acetyl)-ß-D-glucoside (1), quercetin-3-O-(6″-acetyl)-ß-D-glucoside (2), kaempferol-3-O-ß-D-glucoside (3), and quercetin-3-O-ß-D-glucoside (4). These compounds activated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heat-shock response transcription elements (HSE) that resulted in the induction of heme oxygenase-1 (HO-1) and HSP70, respectively. Activation of these pathways provided protection to the skin cells against UVB radiation. The isolated compounds activated the Nrf2 and HSE pathways and could protect against UVB-induced apoptosis.