Compound of Cynanchum wilfordii and Humulus lupulus L. Ameliorates Menopausal Symptoms in Ovariectomized Mice.

Cynanchum wilfordii and Humulus lupulus L. have been used for their various pharmacological properties in South Korea as a traditional medicine or health functional food, respectively, and their intake may relieve menopausal symptoms. The purpose of current study was to determine the effect of compound of Cynanchum wilfordii and Humulus lupulus L. (CWHL) in menopausal symptoms of ovariectomized (OVX) mice. OVX mice received CWHL or caudatin (an active ingredient of CWHL) once daily for 7 weeks. Values for hypothalamic serotonin (5-HT), dopamine, norepinephrine, estrogen receptor (ER)-ß, 5-HT1A, and 5-HT2A were significantly enhanced, while value for hypothalamic monoamine oxidase A was reduced in CWHL and caudatin groups compared with the OVX group. CWHL and caudatin significantly reduced tail skin temperature and rectal temperature of OVX mice through partial recovering of the levels of serum estrogen, nitric oxide, follicle-stimulating hormone, luteinizing hormone, and receptor-activator of the NF-κB ligand (RANKL). Moreover, CWHL and caudatin improved bone mineral density via decreasing levels of serum RANKL, tartrate-resistant acid phosphatase, and collagen type 1 cross-linked N-telopeptide and improving levels of serum alkaline phosphatase, osteoprotegerin, and osteocalcin compared with the OVX group without adverse effects such as dyslipidemia. CWHL increased uterine ER-ß levels but did not change uterus and vaginal weights. Taken together, the results indicate that CWHL may relieve menopausal symptoms by controlling depression-, hot flashes-, and osteoporosis-associated biomarkers. Therefore, we propose that CWHL might be a safe and potential candidate for management of menopause as a health functional food.

Network Pharmacology-Based Investigation on Therapeutic Mechanisms of the Angelica dahurica Radix and Ligusticum chuanxiong Rhizoma Herb Pair for Anti-Migraine Effect.

Migraines are a common neurological disorder characterized by desperate throbbing unilateral headaches and are related to phonophobia, photophobia, nausea, and vomiting. The Angelica dahurica Radix and Ligusticum chuanxiong Rhizoma herb pair (ALHP) has been used to treat migraines for centuries in traditional Chinese medicine (TCM). However, the physiological mechanisms of migraine treatment have not yet been elucidated. In this study, a total of 50 hub targets related to the effect of 28 bioactive compounds in ALHP on anti-migraine were obtained through network pharmacology analysis. GO and KEGG analyses of the hub targets demonstrated that ALHP treatment of migraines significantly involved the G-protein-coupled receptor signaling pathway, chemical synaptic transmission, inflammatory response, and other biological processes. According to the degree of gene targets in the network, ACE, SLC3A6, NR3CI, MAPK1, PTGS2, PIK3CA, RELA, GRIN1, GRM5, IL1B, and DRD2 were found to be the core gene targets. The docking results showed a high affinity for docked conformations between compounds and predicted targets. The results of this study suggest that ALHP could treat migraines by regulating immunological functions, diminishing inflammation, and improving immunity through different physiological pathways, which contributes to the scientific base for more in-depth research as well as for a more widespread clinical application of ALHP.

Phenolic Profile and Fingerprint Analysis of Akebia quinata Leaves Extract with Endothelial Protective Activity.

In contrast to the stem and fruit of Akebia quinata, A. quinata leaves as a source rich in phenolic compounds with potentially beneficial pharmacological activities have been largely overlooked. To develop and use A. quinata leaves as a resource, we evaluated its potential as a cardiovascular-protective agent. Herein, we investigated the effects and potential mechanisms of A. quinata leaves extract on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells. We found that A. quinata leaves extract pretreatment of 10 µg/mL significantly attenuated LPS-induced protein expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1. Furthermore, this extract also suppressed LPS-induced phosphorylation of nuclear factor-κB p65. In order to elucidate the chemical profiles of the samples, the HPLC fingerprint was established, and prominent peaks were identified via HPLC-electrospray ionization-mass spectrometry. Multivariate statistical analyses, including hierarchical cluster analysis, principal component analysis, and partial least-squares discriminant analysis, were performed to evaluate the clustering of the samples. It was found that isochlorogenic acid C was a key marker for the classification of A. quinata leaves from the Gongju and Muju city in Korea. Collectively, this study not only suggested the potential of A. quinata leaves as a novel therapeutic candidate for inflammatory cardiovascular disease but also developed a quality control method for A. quinata leaves, which could help to expand the application of A. quinata.

Anti-Wrinkle Effect of Isatis indigotica Leaf Extract: Evaluation of Antioxidant, Anti-Inflammation, and Clinical Activity.

Isatis indigotica leaf is an oriental herbal medicine that has been known for various pharmacological effects. However, its anti-wrinkle activity has not been fully evaluated. Therefore, we evaluated the anti-wrinkle effect of I. indigotica leaf extract on human skin. The purified extract inhibited 85.4% of 2,2-diphenyl-1-1picrylhydrazyl and 72.2% of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radicals at a concentration of 1 mg/mL. Nitrite production was reduced by 30% after treatment with 50 µg/mL of extract. Three fractions from the extract downregulated the mRNA expression of matrix metalloproteinase-1 and -3 and upregulated the expression of interleukin 4. Among the three fractions, fraction 2 exhibited the highest activity. The major component of the extract was identified as 3,4,5-trimethoxycinnamic acid by liquid chromatography coupled with mass spectrometry. Molecular docking was conducted to predict the binding mechanism of 3,4,5-trimethoxycinnamic with matrix metalloproteinase-1 and -3, and their binding energies were -5.20 and -4.89 kcal/mol, respectively. In a clinical trial, five roughness values of visiometer and visual score were significantly reduced in treated groups compared with the placebo group after 8 weeks. I. indigotica leaf extract inhibits wrinkle formation, and could be a potential anti-wrinkle agent. This is the first clinical trial demonstrating its anti-wrinkle activity.

Evaluation of Anti-Melanogenesis Activity of Enriched Pueraria lobata Stem Extracts and Characterization of Its Phytochemical Components Using HPLC-PDA-ESI-MS/MS.

The root of Pueraria lobata (Willd.) is a widely used herbal medicine worldwide, whereas the stem of the plant is discarded or used as feed for livestock. To reuse and exploit the stem of P. lobata as a resource, we investigated its potential as a skin-whitening agent. We found that the developed, enriched P. lobata stem (PLS) extract significantly inhibited melanin production in the 3-isobutyl-1-methylxanthine-induced B16/F10 cells at a concentration of 50 µg/mL. To further confirm the mechanism of the antimelanogenic effect of the enriched PLS extracts, we examined the mRNA expression of tyrosinase, which was suppressed by the extracts. To standardize and implement effective quality control of the enriched PLS extracts, its major chemical constituents were identified by high-performance liquid chromatography-photodiode array-electrospray ionization-mass spectrometry. In total, 12 constituents were identified. In silico analysis showed that the main constituents, puerarin and daidzin, had excellent binding affinities for human tyrosinase. Collectively, our results suggest that the PLS extracts could be used as anti-pigmentation agents.

An anti-cancer effect of Sambou bamboo saltTM in melanoma skin cancer both in vivo and in vitro models.

Bamboo salt has anti-allergic, anti-inflammatory, anti-oxidant, diabetics, anti-aging, and immune-enhancing effects, which are closely related to anti-cancer effect. The aim of this study was to investigate the anti-cancer effects of Sambou bamboo saltTM (SBS) in melanoma skin cancer in vivo and in vitro models. SBS-administered mice effectively reduced tumor growth and increased survival rate compared with B16F10 cell-inoculated mice without tissue damage, hepatotoxicity, and nephrotoxicity. SBS enhanced levels of immune-enhancing mediators, such as interferon-γ, interleukin (IL)-2, IL-6, IL-12, tumor necrosis factor-α, and IgE in serum and melanoma tissues. Furthermore, SBS enhanced activities of caspases and levels of Bax and p53, whereas decreased levels of Bcl-2. This reduction was a consequence of apoptosis signaling pathway. In conclusion, these results suggest that SBS is a potential substance for cancer therapy. SBS has the potential to be developed either as Korean traditional medicine or as a health functional food for cancer therapy. PRACTICAL APPLICATIONS: In these days cancer is one of the world's largest health problems. Bamboo salt is used as a Korean traditional food or medicine and has beneficial effect on inflammation. We have identified Sambou bamboo saltTM (SBS) is a potential substance for cancer therapy. These insights suggest that SBS can potentially be utilized for health functional foods for cancer treatment as well as improve various cancer diseases such as melanoma skin cancer.

Research Quality-Based Multivariate Modeling for Comparison of the Pharmacological Effects of Black and Red Ginseng.

Black ginseng has various pharmacological activities, but only few studies have compared its pharmacological effects with those of red ginseng. We conducted an integrative systematic literature evaluation and developed a non-inferiority test based on the multivariate modeling approach to compare the pharmacological effects of red ginseng and black ginseng. We searched reported studies on the pharmaceutical effects and composition of ginsenosides and assigned numeric scores using nonlinear principal component analysis, based on discretization measures for the included publications. Downstream weighted linear regression models were constructed to study the eight major biological activities that are generally known to be exhibited by red ginseng. Our statistical model, based on available ordinal information gathered from previous literature, helped in comparing the overlapping effects of black ginseng. Black ginseng showed antioxidant effects comparable to those of red ginseng; however, this variant was inferior to red ginseng in enhancing immunity, relieving fatigue, alleviating depression/anxiety, decreasing body fat, and reducing blood pressure. We have showed a cost-efficient method to indirectly evaluate the biological effects of ginseng products using data from published articles. This method can also be used to compare the nutritional and medicinal value of herbal medicines that share similar compositions of bioactive compounds.

Characterization and Antioxidant Activity Determination of Neutral and Acidic Polysaccharides from Panax Ginseng C. A. Meyer.

Panax ginseng (P. ginseng) is the most widely consumed herbal plant in Asia and is well-known for its various pharmacological properties. Many studies have been devoted to this natural product. However, polysaccharide's components of ginseng and their biological effects have not been widely studied. In this study, white ginseng neutral polysaccharide (WGNP) and white ginseng acidic polysaccharide (WGAP) fractions were purified from P. ginseng roots. The chemical properties of WGNP and WGAP were investigated using various chromatography and spectroscopy techniques, including high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, and high-performance liquid chromatography with an ultra-violet detector. The antioxidant, anti-radical, and hydrogen peroxide scavenging activities were evaluated in vitro and in vivo using Caenorhabditis elegans as the model organism. Our in vitro data by ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid), reducing power, ferrous ion chelating, and hydroxyl radical scavenging activity suggested that the WGAP with significantly higher uronic acid content and higher molecular weight exhibits a much stronger antioxidant effect as compared to that of WGNP. Similar antioxidant activity of WGAP was also confirmed in vivo by evaluating internal reactive oxygen species (ROS) concentration and lipid peroxidation. In conclusion, WGAP may be used as a natural antioxidant with potent scavenging and metal chelation properties.

Ginger on Human Health: A Comprehensive Systematic Review of 109 Randomized Controlled Trials.

Clinical applications of ginger with an expectation of clinical benefits are receiving significant attention. This systematic review aims to provide a comprehensive discussion in terms of the clinical effects of ginger in all reported areas. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline, randomized controlled trials on the effects of ginger were investigated. Accordingly, 109 eligible papers were fully extracted in terms of study design, population characteristics, evaluation systems, adverse effects, and main outcomes. The reporting quality of the included studies was assessed based on the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials and integrated together with studies that investigated the same subjects. The included studies that examined the improvement of nausea and vomiting in pregnancy, inflammation, metabolic syndromes, digestive function, and colorectal cancer's markers were consistently supported, whereas other expected functions were relatively controversial. Nevertheless, only 43 clinical trials (39.4%) met the criterion of having a 'high quality of evidence.' In addition to the quality assessment result, small populations and unstandardized evaluation systems were the observed shortcomings in ginger clinical trials. Further studies with adequate designs are warranted to validate the reported clinical functions of ginger.

Increase in Protective Effect of Panax vietnamensis by Heat Processing on Cisplatin-Induced Kidney Cell Toxicity.

Cisplatin is a platinum-based anticancer agent used for treating a wide range of solid cancers. One of the side effects of this drug is its severe nephrotoxicity, limiting the safe dose of cisplatin. Therefore, many natural products have been studied and applied to attenuate the toxicity of this compound. In this study, we found that steamed Vietnamese ginseng (Panax vietnamensis) could significantly reduce the kidney damage of cisplatin in an in vitro model using porcine proximal tubular LLC-PK1 kidney cells. From processed ginseng under optimized conditions (120 °C, 12 h), we isolated seven compounds (20(R,S)-ginsenoside Rh2, 20(R,S)-ginsenoside Rg3, ginsenoside Rk1, ginsenoside-Rg5, and ocotillol genin) that showed kidney-protective potential against cisplatin toxicity. By comparing the 50% recovery concentration (RC50), the R form of ginsenoside, Rh2 and Rg3, had RC50 values of 6.67 ± 0.42 µM and 8.39 ± 0.3 µM, respectively, while the S forms of ginsenoside, Rh2 and Rg3, and Rk1, had weaker protective effects, with RC50 ranging from 46.15 to 88.4 µM. G-Rg5 and ocotillol, the typical saponin of Vietnamese ginseng, had the highest RC50 (180.83 ± 33.27; 226.19 ± 66.16, respectively). Our results suggest that processed Vietnamese gingseng (PVG), as well as those compounds, has the potential to improve kidney damage due to cisplatin toxicity.

Potential anti-inflammatory effect of Madi-Ryuk and its active ingredient tannic acid on allergic rhinitis.

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

Sasa Quelpaertensis Nakai Induced Antidepressant-Like Effect in Ovariectomized Rats.

BACKGROUND: Sasa quelpaertensis Nakai extract (SQE) or dwarf bamboo has been extensively investigated for its antioxidant and anti-inflammatory effects; however, no previous study assessed its effect as an antidepressant agent. Therefore, this study was designed to examine the effect of oral SQE administration in ameliorating menopausal depressive symptoms and to evaluate its mechanisms in ovariectomized rats with repeated stress. METHODS: All experimental groups except normal group underwent ovariectomy and then immobilization for 14 consecutive days. During these 2 weeks, two rat groups received SQE (100 and 300 mg/kg orally) and their cutaneous body temperature was measured. The tail suspension test (TST) and forced swim test (FST) were performed in order to evaluate depression-like behavior. Additionally, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were carried out to evaluate the central monoaminergic neurotransmitter levels and activity. RESULTS: Oral SQE (100 mg/kg) administration had reduced immobility time in TST and FST. Additionally, the SQE 100 and 300 mg/kg administration had decreased the cutaneous body temperature in the rats compared to those without treatment. In ELISA analysis, the SQE 100 group expressed elevated levels of serotonin and dopamine in the hypothalamus, prefrontal cortex, and hippocampus. Antityrosine hydroxylase (anti-TH) antibodies showed a tremendous increase in the density of TH positive cells in the locus coeruleus (LC) region of the SQE 100 group. Likewise, the SQE 100 elevated the number of tryptophan hydroxylase (TPH) and protein kinase C (PKC) immunoreactive cell counts and density in the hypothalamic region. CONCLUSION: These results suggested that the oral SQE administration induced the antidepressant-like effect in the ovariectomized rats with repeated stress via upregulating the levels of serotonin and dopamine through enhancing the expression of TH, TPH, and PKC in many brain areas.

The ameliorative effect of AST2017-01 in an ovalbumin-induced allergic rhinitis animal model.

OBJECTIVE: AST2017-01 is developed to be used for treatment and prevention of allergic diseases and composed of processed-Cordyceps militaris and processed-Rumex crispus. But, effect of AST2017-01 remains unclear in an allergic rhinitis (AR). So, this study aimed to explore the effects of AST2017-01 in ovalbumin (OVA)-induced AR animal model. METHODS: OVA-induced AR animals were orally administered AST2017-01 and chrysophanol, an active component of AST2017-01 for 10 days. RESULTS: In mice with AR, AST2017-01 and chrysophanol markedly decreased number of rubs, IgE, histamine, thymic stromal lymphopoietin, tumor necrosis factor-α, interleukin (IL)-1ß, IL-4, IL-5, and IL-13 in serum or nasal mucosa tissues. Moreover, activities and protein levels of caspase-1 were markedly diminished by oral administration of AST2017-01 and chrysophanol. Declines of macrophage inflammatory protein-2, intercellular adhesion molecules-1, eosinophil, and mast cells were also noted in nasal mucosa tissues of AST2017-01 and chrysophanol groups. CONCLUSIONS: Taken together, these findings indicate that AST2017-01 has an anti-allergic effect as a therapeutic agent or functional food for treating and preventing AR.

Clinical efficacy of herbal extract cream on the skin hydration, elasticity, thickness, and dermis density for aged skin: A randomized controlled double-blind study.

BACKGROUND: Traditional medicine herbal prescriptions used for the treatment of skin disease have been developed into cosmetics. Sang-Hyul-Yun-Boo-Em (SHYBE) is a mixed herbal formula prescribed for patients with yin or blood deficiency patterns of skin disease. A previous study reported that SHYBE exercises anti-allergic and anti-inflammatory effects. To date, no study has reported the efficacy of cosmetics containing the SHYBE extract. AIMS: To observe the efficacy of SHYBE extract cream on hydration, elasticity, thickness, and dermis density in aged skin. METHODS: This was a double-blind randomized placebo-controlled parallel-group trial. The trial consisted of an 8-week topical application of the test or placebo products with two visits at 4-week intervals. A total of 46 healthy Korean females, aged 40-59, were enrolled in this study. Objective skin assessments for hydration, elasticity, thickness and dermis density, self-assessment, and safety assessment were conducted. RESULTS: Sang-Hyul-Yun-Boo-Em extract cream improved skin hydration, elasticity, and dermal density in Asian middle-aged females compared with placebo cream, which excluded SHYBE extract and contained other cosmetic materials. CONCLUSIONS: Sang-Hyul-Yun-Boo-Em extract cream showed anti-aging properties in middle-aged women. It could be recommended for aging skin with dryness, and loss of elasticity and density.

Regulatory effects of chrysophanol, a bioactive compound of AST2017-01 in a mouse model of 2,4-dinitrofluorobenzene-induced atopic dermatitis.

The aim of this study is to determine whether AST2017-01 which consists of Rumex crispus and Cordyceps militaris would improve atopic dermatitis (AD). We analyzed anti-AD effects of AST2017-01 and chrysophanol, a bioactive compound of AST2017-01, using a 2,4-dinitrofluorobenzene-induced AD murine model. AST2017-01 and chrysophanol relieved clinical severity in AD-like skin lesions and significantly decreased scratching behavior. The thickness of epidermis and infiltration of inflammatory cells in AD-like skin lesions were reduced by AST2017-01 or chrysophanol. AST2017-01 and chrysophanol significantly suppressed the levels of histamine, immunoglobulin E, thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-6, and tumor necrosis factor-α in serum of AD mice. The protein levels of TSLP, intercellular adhesion molecule-1, and macrophage inflammatory protein 2 were significantly inhibited in the skin lesions. The mRNA expressions of TSLP, thymus and activation-regulated chemokine/CCL17, and C-C chemokine receptor 3 were inhibited in the skin lesions by AST2017-01 or chrysophanol. In addition, AST2017-01 and chrysophanol significantly suppressed the expressions and activities of caspase-1 in the skin lesions. Taken together, these results suggest that AST2017-01 has beneficial effects on AD and may be used as a health functional food in AD.

Improvement effects of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich on postmenopausal symptoms of ovariectomized mice.

BACKGROUND: Menopausal hot flushes occur frequently in postmenopausal women. In the present study, we investigated a regulatory effect of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich (PCE17), an extract of flowers of Pueraria thomsonii Benth. (PE), an extract of peels of Citrus unshiu Markovich (CE), a mixture of tectorigenin 7-O-xylosylglucoside, tectoridin, and tectorigenin (Tec, the active compounds of PE), and hesperidin (Hes, an active compound of CE) on menopausal hot flushes. METHODS: We examined the anti-hot flushes properties of PCE17, PE, CE, Tec, or Hes using a mouse model of ovariectomy-induced hot flushes. RESULTS: The ovariectomy-induced rise in the tail skin temperature was significantly prevented by PCE17, PE, CE, Tec, or Hes. PCE17, PE, CE, Tec, or Hes significantly enhanced 5-HT levels and attenuated RANKL levels in the hypothalamus of ovariectomized (OVX) mice. Treatment with PCE17, PE, CE, Tec, or Hes significantly enhanced the levels of estrogen receptor (ER)-ß, 5-HT1A, 5-HT2A, and tryptophan hydroxylase mRNA expression in the hypothalamus of OVX mice. PCE17, PE, or CE decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, but did not increase estrogen levels in the serum of OVX mice. Tec or Hes decreased FSH or LH levels and increased estrogen levels. Treatment with PCE17, PE, CE, or Tec ameliorated vaginal atrophy in OVX mice. Finally, PCE17, PE, CE, Tec, or Hes significantly increased norepinephrine and dopamine levels in the hypothalamus of OVX mice. CONCLUSION: Thus, these results imply that PCE17 has protective effects against hot flushes.

Bamboo salt suppresses skin inflammation in mice with 2, 4-dinitrofluorobenzene-induced atopic dermatitis.

Bamboo salt (BS) is a traditional Korean food, and has been reported to have anti-cancer, anti-inflammatory, and anti-metastatic effects. However, the anti-atopic dermatitis (AD) activity of BS has not been described yet. In the present study, we examined the preventive effect of BS on AD. The effect of oral administration of BS was tested in a 2, 4-dinitrofluorobenzene (DNFB)-induced AD animal model, by histological analysis, enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, caspase-1 assay, and Western blotting analysis. BS administration reduced the total clinical severity and scratching frequencies, compared with the AD group. In the serum of DNFB-induced AD mice, the levels of IgE, histamine, thymic stromal lymphopoietin (TSLP), interleukin (IL)-5, and IL-13 were significantly reduced by BS treatment. BS significantly reduced the protein and mRNA expression of TSLP, IL-6, and tumor necrosis factor-α in the AD skin lesions. BS markedly reduced the infiltration of inflammatory cells. Furthermore, the activation of caspase-1 was reduced by BS in the AD skin lesions. Our results suggested that BS should be considered as a candidate treatment for allergic inflammatory diseases including AD.

The new therapeutic herbal drug HM0601 and its bioactive compound rutin exert potent antiproliferative activities in mast cells.

HM0601 consists of Allium hookeri and Lycium chinense fruit and contains a lot of rutin. Here, we ascertained whether HM0601 and its major compound rutin reduce proliferation of human mast cell line, HMC-1, under thymic stromal lymphopoietin (TSLP) stimulation. Therapeutic rutin or HM0601 treatment considerably reduced proliferation of mast cells without exposing activated HMC-1 cells to any cytotoxicity. Reduced levels of mouse double minute 2 and phosphorylated signal transducers and activators of transcription 6 were accompanied by treatment with rutin or HM0601. In TSLP-stimulated cells, rutin or HM0601 treatment significantly impaired levels of interleukin (IL)-13 and Bcl2 expression. Notably, rutin or HM0601 treatment returned Bax and phosphorylated p53 protein levels and caspase-3 activities impaired by TSLP. In addition, levels of inflammatory cytokine were considerably reduced by treatment with rutin or HM0601 on TSLP-stimulated cells. In conclusion, these results indicate that HM0601 can be used as a new therapeutic herbal drug for prevention and therapeutic intervention of allergic inflammatory diseases.

Molecular mechanisms of anti-inflammatory effect of chrysophanol, an active component of AST2017-01 on atopic dermatitis in vitro models.

AST2017-01 mainly consists of Rumex crispus and -Cordyceps militaris and has been widely consumed as an herbal medicine or functional food in Korea. Here we investigated the influences of AST2017-01 and its active component, chrysophanol on human mast cell (HMC-1 cell) and human keratinocyte (HaCaT cell)-mediated inflammatory reactions. Pretreatment with AST2017-01 or chrysophanol suppressed intracellular calcium levels and histamine release in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-treated HMC-1 cells. Levels of phosphorylated-mitogen-activated protein kinase increased by PMACI stimulation were reduced by AST2017-01 or chrysophanol pretreatment. Protein levels of IκB kinaseß and receptor-interacting protein 2 in PMACI-treated HMC-1 cells were decreased by AST2017-01 or chrysophanol pretreatment. Pretreatment with AST2017-01 or chrysophanol significantly blocked PMACI-induced activation of caspase-1 and nuclear factor-κB. In addition, pretreatment with AST2017-01 or chrysophanol significantly decreased the PMACI-induced levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and thymic stromal lymphopoietin (TSLP) on HMC-1 cells. In activated HaCaT cells, pretreatment with AST2017-01 or chrysophanol significantly reduced production of TSLP and activation of caspase-1. In conclusion, these findings indicate that chrysophanol is an active component of AST2017-01 and AST2017-01 acts as a novel potent anti-inflammatory herbal medicine or functional food.