Pyromeconic acid-enriched Erigeron annuus water extract as a cosmetic ingredient for itch relief and anti-inflammatory activity.

Erigeron annuus (EA), traditionally used to treat disorders such as diabetes and enteritis, contains a variety of chemicals, including caffeic acid, flavonoids, and coumarins, providing antifungal and antioxidative benefits. However, the ingredients of each part of the EA vary widely, and there are few reports on the functionality of water extracts in skin inflammation and barrier protection. We assessed the therapeutic properties of the extract of EA without roots (EEA) and its primary ingredient, pyromeconic acid (PA), focusing on their antihistamine, anti-inflammatory, and antioxidative capabilities using HMC-1(human mast cells) and human keratinocytes (HaCaT cells). Our findings revealed that histamine secretion, which is closely related to itching, was notably reduced in HMC-1 cells following pretreatment with EEA (0.1% and 0.2%) and PA (corresponding concentration, 4.7 of 9.4 µg/mL). Similarly, they led to a marked decrease in the levels of pro-inflammatory cytokines, including IL-1ß, IL-8, IL-6, and IFN-γ. Furthermore, EA and PA enhanced antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), reduced malondialdehyde (MDA) production, and showed reactive oxygen species (ROS) scavenging activity in HaCaT cells. Moreover, at the molecular level, elevated levels of the pro-inflammatory cytokines IL-1ß, IL-6, TARC, and MDC induced by TNF-α/IFN-γ in HaCaT cells were mitigated by treatment with EEA and PA. We also revealed the protective effects of EEA and PA against SDS-induced skin barrier dysfunction in HaCaT cells by enhancing the expression of barrier-related proteins. Using NanoString technology, a comprehensive analysis of gene expression changes indicated significant modulation of autoimmune and inflammatory genes by EEA and PA. In summary, this study suggests that EEA and the corresponding concentration of PA as an active ingredient have functional cosmetic applications to alleviate itching and improve skin health.

Induction of apoptosis in RL95-2 human endometrial cancer cells by combination treatment with docosahexaenoic acid and triacsin C.

Introduction: Docosahexaenoic acid (DHA) supplementation has been reported to negatively correlate with cancer cell proliferation and tumour development in many cancer types. Although cumulative evidence has demonstrated the apoptotic effect and cytotoxicity of DHA against tumour development in many cell types, the precise cellular and biochemical mechanisms of DHA-induced apoptosis in human endometrial cancer cells have not been investigated. Material and methods: MTT assay was performed to confirm the degree of apoptosis by combining treatment with DHA and triacsin C in endometrial cancer cell line. The synergistic effects of triacsin C and DHA were identified by performing flowcytometry and immunoblotting analysis. Results: Combined treatment with DHA and triacsin C significantly induced apoptosis in RL95-2 endometrial carcinoma cells. Combined treatment with 125 µM DHA and 5 µM triacsin C significantly increased the sub-G1 population and apoptotic fragments in endometrial carcinoma cells. It was also demonstrated that DHA and triacsin C induced apoptosis through mitochondrial pathways via caspases-9, -3, and -7 as well as through the extrinsic pathway by activation of caspase-8/BID. Conclusions: Further elucidation of the apoptotic mechanisms involving DHA treatment with ACS ablation could shed light on possible new treatment strategies for endometrial cancer. In addition, further research into the mechanisms of DHA and triacsin C-induced apoptotic mechanisms may lead to the development of therapeutic strategies for endometrial cancer.

Stimulatory effects of wavelength-dependent photobiomodulation on proliferation and angiogenesis of colorectal cancer.

In recent decades, the laser treatment of cancer has been introduced as a promising treatment option. Because of the maldistribution of optical energy and an ambiguous boundary between the normal and tumor tissues, laser irradiation can stimulate residual cancer cells, leading to a cancer regrowth. As photobiomodulation (PBM) is involved in an extensive range of cellular responses, profound comprehension of photo-stimulated mechanisms against the cancer cells is required to establish a safety margin for PBM. Therefore, we aimed to identify the stimulant effects of PBM at various wavelengths against the tumor cells to establish a safety margin for the laser treatment. CT26 murine colon cancer cells were exposed to either 405 (BL), 635 (VIS), or 808 (NIR) nm laser lights at the fluences of 0, 10, 30, and 50 J/cm2. In addition, CT26 tumor-bearing mice were irradiated with BL, VIS, or NIR at a fluence of 30 J/cm2. Both the proliferation and angiogenesis potential of the CT26 cells and tumors were evaluated using the MTT assay, western blot, and immunohistochemistry (IHC) staining analyses. Although cell viability was not statistically significant, BL significantly induced p-ERK upregulation in the CT26 cells, indicating that PBM with BL can stimulate proliferation. In vivo tests showed that the NIR group exhibited the maximum relative tumor volume, and BL yielded a slight increase compared to the control. In the IHC staining and western blot analyses, both BL and NIR increased the expression of EGFR, VEGF, MMP-9, and HIF-1α, which are related to the proliferation and angiogenesis-related factors. Further investigations will be pursued to clarify the molecular pathways that depend on the cancer cell types and laser wavelengths for the establishment of safety guidelines in clinical environments.

Ultraviolet B-irradiated mushroom supplementation increased the Ca++ uptake and ameliorated the LPS-induced inflammatory responses in zebrafish larvae.

The harmful effects of excessive ultraviolet (UV) exposure are well known. However, moderate exposure to UV radiation is beneficial and required for active vitamin D synthesis in our body. People living in the coldest regions on the earth are unable to expose their skin to the solar UV radiation and, therefore, additional supplementation of Vitamin D2 is recommended. Mushrooms are one such consumable macrofungi, which has high vitamin content and therefore used in various traditional medicines. Particularly, UVB-irradiated mushrooms are rich in active vitamin D content and that is why recommended to include in the daily diets for the patients suffering from the problems associated with bone mineralization. In the present study, we evaluated the cytotoxic effect of mushroom extract (UVB-ME) (Lentinus edodes) treatment against MG-63 cells, HepG2 cells, and CCD 841 CoN cells. Furthermore, we elucidated the potential of UVB-ME on Ca++ uptake in osteoblast-like MG-63 cells. Next, we validated the response of Ca++ uptake on the growth and development of zebrafish larvae. In addition, the anti-inflammatory and immunomodulatory potential of UVB-ME treatment against lipopolysaccharide-induced inflammatory response was also analyzed in vivo. Collectively, the study suggested that dietary supplementation of UVB-irradiated mushroom is beneficial for bone calcification and could modulate the host immune system.

Synergistic Effect of Methyl Jasmonate and Abscisic Acid Co-Treatment on Avenanthramide Production in Germinating Oats.

The oat (Avena sativa L.) is a grain of the Poaceae grass family and contains many powerful anti-oxidants, including avenanthramides as phenolic alkaloids with anti-inflammatory, anti-oxidant, anti-itch, anti-irritant, and anti-atherogenic activities. Here, the treatment of germinating oats with methyl jasmonate (MeJA) or abscisic acid (ABA) resulted in 2.5-fold (582.9 mg/kg FW) and 2.8-fold (642.9 mg/kg FW) increase in avenanthramide content, respectively, relative to untreated controls (232.6 mg/kg FW). Moreover, MeJA and ABA co-treatment synergistically increased avenanthramide production in germinating oats to 1505 mg/kg FW. Individual or combined MeJA and ABA treatment increased the expression of genes encoding key catalytic enzymes in the avenanthramide-biosynthesis pathway, including hydroxycinnamoyl-CoA:hydrocyanthranilate N-hydroxycinnamoyl transferase (HHT). Further analyses showed that six AsHHT genes were effectively upregulated by MeJA or ABA treatment, especially AsHHT4 for MeJA and AsHHT5 for ABA, thereby enhancing the production of all three avenanthramides in germinating oats. Specifically, AsHHT5 exhibited the highest expression following MeJA and ABA co-treatment, indicating that AsHHT5 played a more crucial role in avenanthramide biosynthesis in response to MeJA and ABA co-treatment of germinating oats. These findings suggest that elicitor-mediated metabolite farming using MeJA and ABA could be a valuable method for avenanthramide production in germinating oats.

Annual Prevalence, Health Expenditures, and Co-Morbidities Trend of Iron Deficiency Anemia in Korea: National Health Insurance Service Data from 2002 to 2013.

Despite improvements in nutritional status, iron deficiency anemia (IDA) remains a debilitating nutritional problem worldwide. We estimate annual IDA prevalence rates by sex and age and the trends therein in Korea. We also calculate the health expenditures of IDA and its co-morbidities by analyzing claims data in the National Health Information Database from 2002 to 2013. All analyses were performed based on diagnosis codes of IDA (D50, D50.0, D50.8, and D50.9) regardless of whether IDA was the principal or a coexisting disease. Trends in IDA prevalence rates were evaluated by calculating annual percent changes (APCs) in prevalence. The health expenditures of IDA were calculated based on the direct medical costs (outpatient and hospitalization costs, pharmaceutical costs) and direct non-medical costs (travel costs). The overall IDA prevalence in both sexes increased approximately 2.3-fold from 2002 to 2013; the APC was +7.6%. In females, the prevalence of IDA was highest in aged 30-39 and 40-49 years. The APC was highest in those aged <10 years (+18.2%), followed by those aged ≥80 (+14.7%) and 70-79 (+9.8%) years. In males, the prevalence rates were highest in aged <10 years, followed by those aged ≥60 years. The APC was highest in those aged <10 years (+19.1%), followed by those aged ≥80 years (+10.5%). The total health expenditures increased 2.8-fold during 12 years. Diseases of the respiratory or gastrointestinal tract were the most prevalent co-morbidities in both males and females. The annual prevalence of IDA continues to rise in association with adverse health expenditures and co-morbidities in spite of improvements in nutritional status. Most importantly, infants and young children, the elderly, and females aged 30-49 years are at highest risk of IDA. A national, prospective, and well-organized effort to improve iron status and to manage IDA is required.

Anti-obesity effects of red seaweed, Plocamium telfairiae, in C57BL/6 mice fed a high-fat diet.

This study aimed to demonstrate the anti-obesity effect of Plocamium telfairiae (PT), a red seaweed. Different percentages of ethanol (0%, 20%, 40%, 60%, 80%, and 100%) were used for the preparation of PT extract. Furthermore, 3T3-L1 cells were used to determine the percentage of ethanol for optimal anti-adipogenesis of PT, and the anti-obesity properties of the optimized extract of PT (PTE) (40%) was assessed in obese mice. The results indicate that 40% ethanol extract (40 PTE) significantly decreased fat accumulation and suppressed the expression of major adipogenesis factors such as peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein 1 (SREBP-1), CCAAT/enhancer-binding protein (C/EBP)-α, and phosphorylated ACC (pACC) in 3T3-L1 cells. Furthermore, in the high-fat diet-induced obese mice, 40 PTE significantly reduced the weights of white adipose tissue, as well as the levels of triglyceride, total cholesterol, adiponectin, and insulin in the serum. Liver histopathology showed that steatosis decreased in all the PTE treatment groups. The adipogenesis-related proteins, PPAR-γ and SREBP-1, were also significantly decreased in PTE treatment groups. Additionally, 40 PTE increased mRNA expression of mitochondrial uncoupling proteins (UCP)-1 and UCP-3 in brown adipose tissue. These findings provide evidence that 40 PTE can alleviate lipid droplet accumulation in 3T3-L1 adipocytes and obese C57BL/6 mice, indicating that PTE has strong anti-obesity effects and could be used as a therapeutic agent or a component of pharmaceutical drugs and functional foods.

Anti-Obesity Effects of Grateloupia elliptica, a Red Seaweed, in Mice with High-Fat Diet-Induced Obesity via Suppression of Adipogenic Factors in White Adipose Tissue and Increased Thermogenic Factors in Brown Adipose Tissue.

Obesity is a serious metabolic syndrome characterized by high levels of cholesterol, lipids in the blood, and intracellular fat accumulation in adipose tissues. It is known that the suppression of adipogenic protein expression is an effective approach for the treatment of obesity, and regulates fatty acid storage and transportation in adipose tissues. The 60% ethanol extract of Grateloupia elliptica (GEE), a red seaweed from Jeju Island in Korea, was shown to exert anti-adipogenic activity in 3T3-L1 cells and in mice with high-fat diet (HFD)-induced obesity. GEE inhibited intracellular lipid accumulation in 3T3-L1 cells, and significantly reduced expression of adipogenic proteins. In vivo experiments indicated a significant reduction in body weight, as well as white adipose tissue (WAT) weight, including fatty liver, serum triglycerides, total cholesterol, and leptin contents. The expression of the adipogenic proteins, SREBP-1 and PPAR-γ, was significantly decreased by GEE, and the expression of the metabolic regulator protein was increased in WAT. The potential of GEE was shown in WAT, with the downregulation of PPAR-γ and C/EBP-α mRNA; in contrast, in brown adipose tissue (BAT), the thermogenic proteins were increased. Collectively, these research findings suggest the potential of GEE as an effective candidate for the treatment of obesity-related issues via functional foods or pharmaceutical agents.

Feasibility of Ultrasound-Guided Trigger Point Injection in Patients with Myofascial Pain Syndrome.

We compared the feasibility of ultrasound (US)-guided myofascial trigger point (MTrP) injection with that of a blind injection technique following the use of shear wave elastography (SWE) for the measurement of stiffness at the MTrPs in patients with trapezius myofascial pain syndrome (MPS). A total of 41 patients (n = 41) were randomized to either the trial group (n = 21, SWE combined with US-guided injection) or the control group (n = 20, SWE combined with blind injection). At baseline and four weeks, they were evaluated for the manual muscle test (MMT), the range of motion (ROM), pain visual analogue scale (VAS) scores, Shoulder Pain and Disability Index (SPADI) scores and Neck Disability Index (NDI) scores during the abduction, adduction, flexion, extension, external rotation and internal rotation of the shoulder joint. Differences in changes in pain VAS scores, NDI scores and SPADI scores at four weeks from baseline between the two groups reached statistical significance (p = 0.003, 0.012, and 0.018, respectively). US-guided MTrP injection is a more useful modality as compared with a blind injection in patients with MPS.

Ulmus macrocarpa Hance modulates lipid metabolism in hyperlipidemia via activation of AMPK pathway.

Ulmus macrocarpa Hance as an oriental medicinal plant has shown enormous potential for the treatment of several metabolic disorders in Korea. Hyperlipidemia, which is characterized by the excess accumulation of lipid contents in the bloodstream, may lead to several cardiovascular diseases. Therefore, in this study, anti-hyperlipidemic potential of U. macrocarpa water extract (UME) was examined in vitro and in vivo using HepG2 cells and experimental rats, respectively. The hyperlipidemia in experimental rats was induced by the high-cholesterol diet (HCD) followed by oral administration of various concentrations (25, 50 and 100 mg/kg) of UME for 6 weeks. As a result, the UME significantly improved the biochemical parameters such as increased the level of triglyceride, total cholesterol, and low-density lipoprotein cholesterol as well as reduced the high-density lipoprotein cholesterol in the HCD-fed rats. In addition, UME also prevented lipid accumulation through regulating AMPK activity and lipid metabolism proteins (ACC, SREBP1 and HMGCR) in the HCD-fed rats as compared to the controls. Moreover, similar pattern of gene expression levels was confirmed in oleic acid (OA)-treated HepG2 cells. Taken together, our results indicate that UME prevents hyperlipidemia via activating the AMPK pathway and regulates lipid metabolism. Thus, based on the above findings, it is estimated that UME could be a potential therapeutic agent for preventing the hyperlipidemia.

Improvement in neurogenesis and memory function by administration of Passiflora incarnata L. extract applied to sleep disorder in rodent models.

Recently, there have been reports that chronic insomnia acts as an insult in the brain, causing memory loss through the production of ROS, inflammation, and, Alzheimer's disease if persistent. Insomnia remains the leading cause of sleep disturbance and as such has serious implications for public health. Patients with Alzheimer's disease are also known to suffer from severe sleep disturbance. Meanwhile, vitexin is a key ingredient in Passiflora incarnata L (passion flower, PF) extract, which is known to help with sleep. This medicinal plant has been used as a folk remedy for sedation, anxiety and sleep since centuries ago, but the standardization work has not been done and the extent of the effect has not been clearly demonstrated. For this reason, we tried to test the possibility that repeated administration of PF could improve the memory by promoting hippocampal neurogenesis at the DBA/2 mice known have inherited sleep disorders, as well as preventive effects of Alzheimer's disease. Here, we found that vitexin, which is the main bioactive component of ethanol extracts from leaves and fruits (ratio; 8:2) of PF, confirmed the improvement of neurogenesis (DCX) of DBA/2 mice repeated PF oral administration by immunohistochemistry (IHC) and western blot analysis. PF-treated group showed increased the neurotrophic factor (BDNF) in the hippocampus compared with that of vehicle-treated group, but the inflammation markers Iba-1 (microglial marker) and COX-2 were inconsistent between the groups. However, we found COX-2 signal is essential for hippocampal neurogenesis according to the additional IHC experiments using COX-2 inhibitor and pIkappaB have shown. In addition, although prescription sleeping pills have been reported to show significant changes in appetite and metabolic rate from time to time, no changes in the feeding behavior, body weight, metabolic rate and body composition of the animals were observed by administration of PF. Interestingly, we found that short-term oral administration of PF displayed improved memory according to the water maze test. Quantitative analysis of Tau protein, which is a marker of Alzheimer's disease, was performed in the SD rats and DBA/2 mice by repeated PF oral administration and pTau/Tau values were significantly decreased in PF-treated group than vehicle-treated group. In conclusion, our results suggest that PF lead high hippocampal neurogenesis in the animals even in inherited sleep-disturbed animals. The increased hippocampal neurogenesis functionally enhanced memory and learning functions by repeated PF oral administration. These results identify PF as a potential therapy for enhancing memory functions and prevention of Alzheimer's disease through actions on the hippocampus.

The Clinical Effects of Dendropanax Morbifera on Postmenopausal Symptoms: Review Article.

Postmenopausal women aged 50s generally experience gradual changes in body such as decline in antioxidant and estrogen levels as the body ages. To overcome these aging-associated changes, the needs for health functional foods are increasing. Dendropanax morbifera (DM) have antioxidant effects, anti-inflammatory against cancer cells, antidiabetic, and antiatherogenic effect which are associated with postmenopausal symptoms. We analyzed clinical effects of DM on aging-related symptoms by reporting their antioxidant, anticancer and inflammatory activity, etc. and their bioactivity. Data sources EMBASE, SCOPUS, PubMed, Web of Science, and Google Scholar databases were searched up to August 2016 for studies investigating medicinal plants in prevention and treatment of diabetes. The search terms were "Dendropanax morbifera". The reference lists of articles were also reviewed for additional relevant studies. Extracts of DM have various efficacy such as antioxidant, anti-cancer, anti-inflammatory activity and anti-thrombotic effect.

Role Identification of Passiflora Incarnata Linnaeus: A Mini Review.

Some species of traditional herbal medicine has a history of use, most traditional natural herbs have been used for various diseases such as diabetes, hypertension, and obesity. Among them, Passiflora incarnata L. is a traditional natural medicine, flowers as well as berries, roots, and leaves have been used as a medicine. It has been used as a natural medicine for the treatment of insomnia and anxiety for a longtime in Europe, and it has been used primarily for sedation tea in North America. Moreover, Passiflora incarnata L. is widely used anti-asthmatic, analgesic and sedation in Brazil. In other words, Passiflora incarnata L. has been used to treat a sedative, dysmenorrhea, insomnia, cancer, etc. in many countries. Present review of the plants showed a wide range of pharmacological activity in anxiolytic relax the clinical disease, such as anti-inflammatory, anxiety and antioxidant. In addition, Passiflora incarnata L. affects menopause symptoms such as vasomotor symptoms, insomnia, and depression. This review aims to provide the latest information on specific functional components of Passiflora incarnata L. especially the results of clinical trials will provide new insights into opportunities for the future development of natural medicines and doors will be used for purposes of analysis.

Premenstrual syndrome: A mini review.

Premenstrual syndrome (PMS) is characterized by recurrent, moderate-to-severe affective, physical, and behavioral symptoms that develop during the luteal menstrual cycle and disappear within a few days of menstruation. Premenstrual dysphoric disorder (PMDD) is a severe and disabling condition that can affect personal relationships and occupational activities. PMS occurs in 30-40% of reproductive-age females; PMDD affects 3-8% of this population. Although the etiology of PMS is unclear, several theories suggest increased sensitivity to normal hormonal changes and neurotransmitter abnormalities. The diagnostic method of PMS is the Daily Record of Severity of Problems, which women with PMS can use to self-report several symptoms and their severity. Although combined oral contraceptives and serotonergic antidepressants are effective drugs, each is a different option for treating PMS/PMDD. Serotonergic antidepressants are the drugs of choice for improving both physical and mood symptoms. Combined oral contraceptives appear to primarily improve physical symptoms. Clinicians should consider each patient's situation individually. Other treatment options include lifestyle modification, cognitive behavioral therapy, and herbal medicine (e.g., chasteberry).

Anti-obesity phenotypic screening looking to increase OBR cell surface expression.

The leptin receptor, OBR, is involved in the regulation of whole-body energy homeostasis. Most obese people are resistant to leptin and do not respond to the hormone. The prevention and reversal of leptin resistance is one of the major current goals of obesity research. We showed previously that increased OBR cell surface expression concomitantly increases cellular leptin signaling and prevents obesity development in mice. Improvement of OBR cell surface expression can thus be considered as an interesting anti-obesity therapeutic strategy. To identify compounds that increase the surface expression of OBR, we developed a cell-based, phenotypic assay to perform a high-content screen (HCS) against a library of 50,000 chemical compounds. We identified 67 compounds that increased OBR cell surface expression with AC50 values in the low micromolar range and no effect on total OBR expression and cellular toxicity. Compounds were classified into 16 chemical clusters, of which 4 potentiated leptin-promoted signaling through the JAK2/STAT3 pathway. In conclusion, development of a robust phenotypic screening approach resulted in the discovery of four new scaffolds that demonstrate the desired biological activity and could constitute an original therapeutic solution against obesity and associated disorders.

Identification of two HIV inhibitors that also inhibit human RNaseH2.

A total of 140,000 compounds were screened in a targetfree cell-based high throughput assay against HIV-1 infection, and a subset of 81 promising compounds was identified. Secondary screening of these 81 compounds revealed two putative human RNaseH2 inhibitors, RHI001 and RHI002, with IC50 value of 6.8 µM and 16 µM, respectively. RHI002 showed selective activity against human RNaseH2 while RHI001 inhibited HIV-RNaseH, E. coli RNaseH, and human RNaseH1 with IC50 value of 28.5 µM, 7.9 µM, and 31.7 µM, respectively. Kinetic analysis revealed that both inhibitors had non-competitive inhibitor-like properties. Because RNaseH2 is involved in the etiology of Aicardi-Goutier syndrome and has been suggested as an anticancer drug target, small molecule inhibitors modulating its activity would be useful for investigating the cellular function of this molecule.

Identification of a novel sulfonamide non-nucleoside reverse transcriptase inhibitor by a phenotypic HIV-1 full replication assay.

Classical target-based, high-throughput screening has been useful for the identification of inhibitors for known molecular mechanisms involved in the HIV life cycle. In this study, the development of a cell-based assay that uses a phenotypic drug discovery approach based on automated high-content screening is described. Using this screening approach, the antiviral activity of 26,500 small molecules from a relevant chemical scaffold library was evaluated. Among the selected hits, one sulfonamide compound showed strong anti-HIV activity against wild-type and clinically relevant multidrug resistant HIV strains. The biochemical inhibition, point resistance mutations and the activity of structural analogs allowed us to understand the mode of action and propose a binding model for this compound with HIV-1 reverse transcriptase.