The miR-126-5p and miR-212-3p in the extracellular vesicles activate monocytes in the early stage of radiation-induced vascular inflammation implicated in atherosclerosis.

People exposed to radiation in cancer therapy and nuclear accidents are at increased risk of cardiovascular outcomes in long-term survivors. Extracellular vesicles (EVs) are involved in radiation-induced endothelial dysfunction, but their role in the early stage of vascular inflammation after radiation exposure remains to be fully understood. Herein, we demonstrate that endothelial cell-derived EVs containing miRNAs initiate monocyte activation in radiation-induced vascular inflammation. In vitro co-culture and in vivo experimental data showed that endothelial EVs can be sensitively increased by radiation exposure in a dose-dependent manner, and stimulate monocytes releasing monocytic EVs and adhesion to endothelial cells together with an increase in the expression of genes encoding specific ligands for cell-cell interaction. Small RNA sequencing and transfection using mimics and inhibitors explained that miR-126-5p and miR-212-3p enriched in endothelial EVs initiate vascular inflammation by monocyte activation after radiation exposure. Moreover, miR-126-5p could be detected in the circulating endothelial EVs of radiation-induced atherosclerosis model mice, which was found to be tightly correlated with the atherogenic index of plasma. In summary, our study showed that miR-126-5p and miR-212-3p present in the endothelial EVs mediate the inflammatory signals to activate monocytes in radiation-induced vascular injury. A better understanding of the circulating endothelial EVs content can promote their use as diagnostic and prognostic biomarkers for atherosclerosis after radiation exposure.

LDR-adapted liver-derived cytokines have potential to induce atherosclerosis.

PURPOSE: Atherosclerosis is a lipid-driven chronic inflammatory disease that causes cardiovascular diseases (CVD). The association between radiation and atherosclerosis has already been demonstrated; however, the effects of low-dose radiation (LDR) exposure on atherosclerosis have not been reported. Our study aims to propose that LDR may cause atherosclerosis phenotypes by the upregulation of plasminogen activator inhibitor-1 (PAI-1) and downregulation of androgen receptor (AR), which are cytokines secreted from the liver. METHODS: Low-density lipoprotein (LDL) receptor deficient (Ldlr-/-) mice were irradiated at 50 mGy, 100 mGy, and 1000 mGy. LDR irradiated Ldlr-/- mice serum was analyzed by cytokine array and proteomics with silver staining. Oil Red O staining and BODIPY staining were performed to determine lipid accumulation in Human umbilical vein endothelial cells (HUVECs). Foam cell formation and monocyte recruitment were assessed through co-culture system with HUVECs and THP-1 cells. RESULTS: After irradiation with LDR (100 mGy) the mice showed atherosclerotic phenotypes and through analysis results, we selected regulated cytokines, PAI-1 and AR, and found that these were changed in the liver. LDR-regulated cytokines have the potential to be transported to endothelial cells and induce lipid accumulation, inflammation of monocytes, increased oxidized low-density lipoprotein (oxLDL) and foam cells formation, that were series of phenotypes lead to plaque formation in endothelial cells and induces atherosclerosis. As a further aspect of this study, testosterone undecanoate (TU) was found to pharmacologically inhibit a series of atherosclerotic phenotypes exhibited by LDR. This study suggests a role for PAI-1 and AR in regulating the development of atherosclerosis after LDR exposure. Targeting PAI-1 and AR could serve as an attractive strategy for the management of atherosclerosis following LDR exposure.

The Current Safety Regulation for Radiation Emergency Medicine in Korea.

Radiation emergency medicine (REM) systems are operated around the world to provide specialized care for injured individuals who require immediate medical attention in accidents. This manuscript describes the current status of REM safety regulation in Korea and summarizes an assessment of the effects of this regulation. Responding to the requests of people for stronger safety regulations related to radiation exposure, a unique REM safety regulation for nuclear licensees, which is enforceable by laws, has been established and implemented. It is not found in other countries. It can provide a good example in practice for sustainable REM management including document reviews on medical response procedures and inspections of equipment and facilities. REM preparedness of nuclear or radiologic facilities has been improved with systematic implementation of processes contained in the regulation. In particular, the medical care system of licensees has become firmly coordinated in the REM network at the national level, which has enhanced their abilities by providing adequate medical personnel and facilities. This legal regulation service has contributed to preparing the actual medical emergency response for unexpected accidents and should ultimately secure the occupational safety for workers in radiation facilities.

Expansion of monocytic myeloid-derived suppressor cells ameliorated intestinal inflammatory response by radiation through SOCS3 expression.

Radiation-induced colitis is a common clinical problem after radiation therapy and accidental radiation exposure. Myeloid-derived suppressor cells (MDSCs) have immunosuppressive functions that use a variety of mechanisms to alter both the innate and the adaptive immune systems. Here, we demonstrated that radiation exposure in mice promoted the expansion of splenic and intestinal MDSCs and caused intestinal inflammation due to the increased secretion of cytokines. Depletion of monocytic MDSCs using anti-Ly6C exacerbated radiation-induced colitis and altered the expression of inflammatory cytokine IL10. Adoptive transfers of 0.5 Gy-derived MDSCs ameliorated this radiation-induced colitis through the production IL10 and activation of both STAT3 and SOCS3 signaling. Intestinal-inflammation recovery using 0.5 Gy-induced MDSCs was assessed using histological grading of colitis, colon length, body weight, and survival rate. Using in vitro co-cultures, we found that 0.5 Gy-induced MDSCs had higher expression levels of IL10 and SOCS3 compared with 5 Gy-induced MDSCs. In addition, IL10 expression was not enhanced in SOCS3-depleted cells, even in the presence of 0.5 Gy-induced monocytic MDSCs. Collectively, the results indicate that 0.5 Gy-induced MDSCs play an important immunoregulatory role in this radiation-induced colitis mouse model by releasing anti-inflammatory cytokines and suggest that IL10-overexpressing mMDSCs may be potential immune-therapy targets for treating colitis.

Chronic radiation exposure aggravates atherosclerosis by stimulating neutrophil infiltration.

BACKGROUND: Radiation exposure is known to increase the risk of chronic inflammatory diseases, such as atherosclerosis, by modulating inflammation. METHODS: To investigate the infiltration of leukocytes in radiation-aggravated atherosclerosis, we examined low-density lipoprotein receptor-deficient (Ldlr-/-) mice and C57BL/6j mice after exposure to 0.5 or 1 Gy radiation over 16 weeks. RESULTS: We found that radiation exposure induced atherosclerosis development in Ldlr-/- mice, as demonstrated by increased lipid-laden plaque size, reactive oxygen species levels, and levels of the pro-inflammatory cytokines, IL-1ß and TNF-α, in the aortas and spleens. Total plasma cholesterol, triglyceride, and LDL cholesterol levels were also increased by radiation exposure, along with cardiovascular risk. We also showed dose-dependent increases in neutrophils and monocytes that coincided with a reduction in lymphocytes in the spleens of Ldlr-/- mice. The correlation between the infiltration of leukocytes and cytokine production was also confirmed in the hearts and spleens of these mice. CONCLUSIONS: We concluded that chronic radiation exposure increased the production of pro-inflammatory mediators, which was associated with the migration of neutrophils and inflammatory monocytes into sites of atherosclerosis. Thus, our data suggest that the accumulation of neutrophils and inflammatory monocytes, together with the reduction of lymphocytes, contribute to aggravated atherosclerosis in Ldlr-/- mice under prolonged exposure to radiation.

Assessment of an Emergency Medicine System for Radiation Accidents in Korea: A State Survey of the Workers Involved the Medical Response to Radiation Accidents.

Radiation emergency medicine systems are operated around the world to provide special care for the injured that require immediate medical attention in accidents. The objective of this survey was to evaluate people's perception of those who design the emergency medical plan for radiation accidents and those who supervise it in Korea. A questionnaire survey was conducted on the people involved in a regulatory system for medical response in a radiation emergency. Of 150 survey recipients, 133 (88.7%) completed the survey, including 92 workers and 41 inspectors. The respondents expressed the view that the national emergency medical plan is prepared above the average level using a Likert-style scale of 1 to 5 (mean = 3.55, SD = 0.74). Interestingly, using the Mann-Whitney U test, it could be shown that inspectors evaluated the emergency medical system for radiation accidents more strictly in all of the questions than the licensee workers, especially on radiation medical emergency preparedness (p = 0.004) and the governmental regulatory policy for radiation safety (p = 0.007). For a more efficient system of radiation emergency medicine, licensee workers prioritized the workforce, whereas inspectors favored laws and regulations for safety. The survey results show different perspectives between inspectors and licensee workers, which stem from the actual properties of each occupational role in the regulatory system for radiation medical emergency. These data could be utilized for communication and interaction with relevant people to improve the medical response preparedness against radiation accidents.

Risk perception of radiation emergency medical staff on low-dose radiation exposure: Knowledge is a critical factor.

Radiation emergency medical (REM) staff respond to many types of disasters such as radiological and nuclear accidents as well as environmental radioactivity exposure. The objective of this study was to evaluate the risk perception of REM staff on radiation exposure in various situations and to analyze the factors that affect their risk perception. A questionnaire was given to 284 REM staff affiliated with various organizations, including nuclear power generation, nuclear fuel manufacturing, large-scale irradiation, and radiation-waste disposal facilities, as well as research and development institutions. To determine the substantially influential factors for risk perception, we analyzed the questionnaire responses using ordinal logistic regression, Kruskal-Wallis, and Spearman correlation analyses. It was generally perceived by REM staff that low-dose radiation exposure in daily life and work environments does not pose any health risks. A higher level of radiation knowledge was tightly associated with a lower risk perception of REM staff on extremely low-dose (several mSv) radiation exposure, thus exhibiting an inverse correlation. In contrast to radiation researchers, the work experience of REM staff was not a contributing factor to their risk perception. In our study, REM staff with a high level of radiation knowledge did not have any health concerns in their work environments. Efforts to enhance the radiation knowledge of REM staff through proper education and training would result in analytical risk evaluation, which may also improve their willingness to help meet surge capacity needs in large-scale radiological events.

Inhibition of EphA2 by Dasatinib Suppresses Radiation-Induced Intestinal Injury.

Radiation-induced multiorgan dysfunction is thought to result primarily from damage to the endothelial system, leading to a systemic inflammatory response that is mediated by the recruitment of leukocytes. The Eph-ephrin signaling pathway in the vascular system participates in various disease developmental processes, including cancer and inflammation. In this study, we demonstrate that radiation exposure increased intestinal inflammation via endothelial dysfunction, caused by the radiation-induced activation of EphA2, an Eph receptor tyrosine kinase, and its ligand ephrinA1. Barrier dysfunction in endothelial and epithelial cells was aggravated by vascular endothelial-cadherin disruption and leukocyte adhesion in radiation-induced inflammation both in vitro and in vivo. Among all Eph receptors and their ligands, EphA2 and ephrinA1 were required for barrier destabilization and leukocyte adhesion. Knockdown of EphA2 in endothelial cells reduced radiation-induced endothelial dysfunction. Furthermore, pharmacological inhibition of EphA2-ephrinA1 by the tyrosine kinase inhibitor dasatinib attenuated the loss of vascular integrity and leukocyte adhesion in vitro. Mice administered dasatinib exhibited resistance to radiation injury characterized by reduced barrier leakage and decreased leukocyte infiltration into the intestine. Taken together, these data suggest that dasatinib therapy represents a potential approach for the protection of radiation-mediated intestinal damage by targeting the EphA2-ephrinA1 complex.

(R)-(+)-pulegone suppresses allergic and inflammation responses on 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice model.

BACKGROUND: (R)-(+)-pulegone (PLG), a biotransformation of monoterpene ketones, is one of essential oils of Labiatae family. Although PLG was reported to have anti-inflammatory and anti-histamine effects, the therapeutic effects of PLG on atopic dermatitis (AD) have not been reported yet. OBJECTIVE: This study investigated the anti-AD effects and underlying mechanisms of PLG in AD-induced mice. METHODS: BALB/c male mice were challenged with 2, 4-dinitrochlorobenzene (DNCB, 1%) to induce AD. After 4 days of rest, PLG (0.1, 1 and 10 µM) were topically applied to dorsal skin for 2 weeks with secondary elicitation using 0.5% DNCB. Histological changes were identified by H&E staining and mast cells were evaluated by toluidine blue staining. Pro-inflammatory cytokines and serum IgE levels were analyzed by ELISA. Inflammatory mediators were measured by western blotting assay. RESULTS: Topical treatment with PLG significantly suppressed skin thickness and scratching behavior compared with control group. Expression of nerve growth factor was also decreased by PLG treatment. PLG administration decreased serum IgE levels and the number of mast cells in mice model of DNCB-induced AD. The levels of IL-4, IFN-γ, IL-6, TNF-α and IL-1ß in dorsal skin of PLG-treated group were lower than those in the control group. PLG inhibited the phosphorylation of MAPKs, as well as IκBα degradation and NF-κB activation. CONCLUSIONS: PLG attenuated the symptoms of AD by suppressing cytokines production, the phosphorylation of MAPKs and the activation of NF-κB signaling. These data suggest that PLG may be an effective natural compound for the treatment of inflammatory skin diseases.

Scutellaria baicalensis ameliorates the destruction of periodontal ligament via inhibition of inflammatory cytokine expression.

BACKGROUND: Scutellaria baicalensis (SB) is widely used as a medicinal plant to treat various inflammatory diseases. In the present study, we investigated the effects of SB on periodontitis in ligature-induced experimental rat model. METHODS: Rats were subjected to a ligature placement around the first molar of the mandible to induce periodontitis. 100 mg/kg SB extracts were orally administered for 14 days. The molar tissues were stained with 1% methylene blue. Histopathological changes of the periodontium were observed by hematoxylin and eosin staining. The levels of cytokines were measured in the gingival tissue. RESULTS: Alveolar bone resorption was statistically lower in the SB group compared to the ligatured group. SB inhibited the mineralization of cementum. In addition, SB reduced the production of IL-1ß, 6, -8 and TNF-α cytokine mRNA expression in gingival tissues. CONCLUSION: These results suggest that SB showed ameliorative effects in the ligature-induced periodontitis by inhibition of inflammatory cytokine expression.

Effects of Cynanchum wilfordii on osteoporosis with inhibition of bone resorption and induction of bone formation.

Cynanchum wilfordii Hemsley has been used for the treatment of musculoskeletal diseases in traditional Republic of Korean medicine. The present study investigated the effects of C. wilfordii water extract (CW) on postmenopausal osteoporosis. Female mice were used and randomly assigned into a normal group and three ovariectomized (OVX) groups: OVX with vehicle (OVX + vehicle); OVX with 17ß­estradiol (E2; 10 µg/kg/day); and OVX with CW (1 mg/kg/day). Oral administration of CW or E2 intraperitoneal injection began 9 weeks after OVX and continued for 3 weeks. Following sacrifice, bone histology, bone mineral density (BMD) and bone mineral content (BMC) of the femur were observed. Serum osteocalcin concentration was analyzed. In addition, the expression levels of osteoprotegerin (OPG) and osterix were evaluated in human osteoblast­like Saos­2 cells. In the lateral and medial epicondyles of the CW­administrated group, dense and well­formed bone marrow cells with reduced bone marrow pores were observed. CW decreased the number of tartrate resistant acid phosphatase­positive multinucleated osteoclasts. BMD and BMC were increased following increased serum osteocalcin levels by CW treatment. The expression levels of OPG and osterix were upregulated by CW treatment in vitro. The results suggested that C. wilfordii has an advantageous effect on osteoporosis and possesses the potential to be used in osteoporosis treatment.

Cynanchum atratum inhibits the development of atopic dermatitis in 2,4-dinitrochlorobenzene-induced mice.

Cynanchum atratum Bunge (Apocynaceae) is a folk medicine to treat skin inflammatory diseases. However, the effects of C. atratum on atopic dermatitis have not been elucidated. In this study, we evaluate the effects of aqueous extract of C. atratum (CA) and its molecular mechanism on atopic dermatitis (AD). 1 and 100mg/mL CA were topically applied to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions for 11 days. The number of scratching behavior was evaluated for 20min. AD-like symptoms including elevated serum IgE, skin hyperplasia and mast cell infiltration were investigated. The expressions of pro-inflammatory cytokines and mediators were analyzed in AD-like skin legions. In addition, pro-inflammatory cytokine production was confirmed in human mast cells (HMC)-1 stimulated with PMA plus A23187 (PMACI). Topical application of CA attenuated total serum IgE level and scratching behavior. Skin hyperplasia including epidermis and dermis was ameliorated in CA-treated skin legions. The number of infiltrated mast cells was significantly decreased by CA treatment. In addition, CA reduced pro-inflammatory cytokines, such as IL-6, IL-1ß and TNF-α and Th2 cytokine, IL-4, in both of AD-like skin lesions and PMACI-sensitized HMC-1 cells. Furthermore, CA decreased the expressions of NF-κB, phospho-IκBα and MAP kinase. These results suggest the inhibitory effects of CA on the development of AD by regulating pro-inflammatory cytokines and mediators. CA could be an effective substance for the treatment of AD.

Angelica dahurica ameliorates the inflammation of gingival tissue via regulation of pro-inflammatory mediators in experimental model for periodontitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Anti-inflammatory effects of Angelica dahurica (AD) have been reported in previous studies. In this study, we investigated the anti-inflammatory effects of AD on periodontitis. MATERIALS AND METHODS: Male Sprague-Dawley rats aged 7 weeks (n=7) were subjected to ligature around bilateral mandibular first molars. 1 and 100mg/mL of AD were topically applied to first molars for 14 days. Histological changes were observed in gingival epithelial layer, and the thickness of the gingival epithelial layer as well as the number of epithelial cells were quantified. To investigate the mRNA expression of pro-inflammatory cytokines in gingival tissues, reverse transcriptase polymerase chain reaction was performed. To confirm the anti-inflammatory effects of AD, pro-inflammatory mediators including cytokines and NF-kB, COX-2, and iNOS were analyzed in LPS-stimulated Raw 264.7 cells. RESULTS: Topical application of AD attenuated not only the thickness of epithelial layer, also the number of epithelial cells in gingival tissue. The expressions of IL-1ß, IL-6, IL-8, and IFN-γ in gingiva were significantly reduced by AD treatment. Additionally, the expressions of IL-1ß, IL-6, IL-8 and IFN-γ mRNA were inhibited by AD in LPS-treated RAW264.7 macrophage cells. Furthermore, AD treatment decreased LPS-induced elevation of NF-κB, COX-2 and iNOS protein levels in RAW264.7 cells. CONCLUSION: Taken together, AD application ameliorated the hyperplasia of gingival epithelial layer by down-regulating pro-inflammatory mediators. AD might have therapeutic potentials for periodontal diseases.

Lycium chinense Improves Post-Menopausal Obesity via Regulation of PPAR-γ and Estrogen Receptor-α/ß Expressions.

The fruit of Lycium chinense Miller (Solanaceae) is used as a functional food and a medicinal herb for treating many specific health concerns. Weight gain induced by estrogen deficiency is a problem for post-menopausal women around the globe. The present study investigates the effects of aqueous extract of L. chinense (LC) on post-menopausal obesity. Female C57BL/6 mice were ovariectomized and fed on high-fat diet (HFD) for 12 weeks to induce post-menopausal obesity. LC extract (1[Formula: see text]mg/kg and 10[Formula: see text]mg/kg) was orally administrated for 6 weeks with continuous HFD feeding. Ovarian adipose tissues and uterus were weighed. Serum triglyceride, cholesterol, LDL-cholesterol and fasting glucose levels were analyzed. The expressions of adipocyte-specific factors and estrogen receptors (ERs) were investigated. Additionally, lipid accumulation was confirmed in differentiated 3T3-L1 adipocytes. Increased body weight due to post-menopausal obesity was ameliorated about 14.7% and 17.76% by treatment of 1[Formula: see text]mg/kg and 10[Formula: see text]mg/kg LC, respectively. LC treatment reduced both of serum lipid and fasting blood glucose levels. Adipocyte hypertrophy and fatty liver were ameliorated in LC-treated groups. In LC-treated adipocyte cells, lipid accumulation was significantly inhibited. The expression of perilipin in adipose tissues was decreased by LC. In addition, expression of PPAR-[Formula: see text] protein was down-regulated in adipose tissues and differentiated adipocytes, while GLUT4 expression was increased in adipose tissues by LC treatment. Moreover, LC treatment up-regulated the expressions of ER-[Formula: see text]/[Formula: see text] accompanied with increased uterine weight. These results showed the ameliorative effects of LC on overweight after menopause. Post-menopausal obesity may be improved by LC treatment.

Immunomodulatory effects of Pseudostellaria heterophylla (Miquel) Pax on regulation of Th1/Th2 levels in mice with atopic dermatitis.

Pseudostellaria heterophylla (PH) has various pharmacological effects that include immunologic enhancement and anti­oxidation. However, it remains unclear whether PH exerts beneficial effects in dermatological diseases. The present study examined the effects of PH on a 2,4-dinitrochlorobenzene (DNCB)­induced atopic dermatitis (AD) mouse model and elucidated its underlying mechanism of action. PH extract (1 and 100 mg/ml) was applied topically to DNCB-treated dorsal skin of mice every day for 11 days. The immunomodulatory effects of PH were evaluated by measuring skin thickness, mast cell infiltration, serum levels of immunoglobulin E (IgE), and mRNA expression levels of T helper (h)1/Th2 and pro­inflammatory cytokines in dorsal skin. In addition, cluster of differentiation (CD)4+ T cells were detected in dorsal skin by immunohistochemistry. Topical application of PH significantly reduced the thickness of dermis, epidermis and serum IgE production compared with the DNCB group. PH treatment inhibited infiltration of inflammatory cells, including mast cells and CD4+ T cells, and suppressed the mRNA expression levels of cytokines (interferon­Î³, interleukin­4, ­6, ­8 and ­1ß, and tumor necrosis factor­α) associated with the immune response. Furthermore, PH treatment significantly downregulated the protein expression levels of nuclear factor­κB, phosphorylated inhibitor of κBα and mitogen­activated protein kinases. The results suggested that PH may be a potential therapeutic strategy for the treatment of AD via the modulation of Th1 and Th2 levels.

Effect of Dangguibohyul-Tang, a Mixed Extract of Astragalus membranaceus and Angelica sinensis, on Allergic and Inflammatory Skin Reaction Compared with Single Extracts of Astragalus membranaceus or Angelica sinensis.

Dangguibohyul-tang (DBT), herbal formula composed of Astragalus membranaceus (AM) and Angelica sinensis (AS) at a ratio of 5 : 1, has been used for the treatment of various skin diseases in traditional medicine. We investigated the effect of DBT on allergic and inflammatory skin reaction in atopic dermatitis-like model compared to the single extract of AM or AS. DBT treatment showed the remission of clinical symptoms, including decreased skin thickness and scratching behavior, the total serum IgE level, and the number of mast cells compared to DNCB group as well as the single extract of AM- or AS-treated group. Levels of cytokines (IL-4, IL-6, IFN-γ, TNF-α, and IL-1ß) and inflammatory mediators (NF-κB, phospho-IκBα, and phospho-MAPKs) were significantly decreased in AM, AS, and DBT groups. These results demonstrated that AM, AS, and DBT may have the therapeutic property on atopic dermatitis by inhibition of allergic and inflammatory mediators and DBT formula; a mixed extract of AM and AS based on the herb pairs theory especially might be more effective on antiallergic reaction as compared with the single extract of AM or AS.

Inhibitory effects of Leonurus sibiricus on weight gain after menopause in ovariectomized and high-fat diet-fed mice.

Leonurus sibiricus, also called motherwort, is a well-known functional food and medicinal herb. It has been known to possess beneficial properties for women's health, especially for aged women. Estrogen deficiency in the menopause could induce lipid metabolic abnormalities in body fat, resulting in obesity. In this study, the inhibitory effects of L. sibiricus on obesity after the menopause were investigated. Female C57BL/6 mice were ovariectomized and fed high-fat diet (HFD) for 12 weeks. Following an induction period, aqueous extracts of L. sibiricus (LS) were orally administrated for 6 weeks. The body, uterine, and visceral fat weights were measured immediately after the animals were killed. Histological analysis was performed to monitor fat and liver. Serum levels of glucose, triglyceride, total cholesterol, and LDL-cholesterol were evaluated. In addition, the expression of lipases was analyzed. Total body weight was significantly decreased by LS treatment. Histological changes in adipocyte size were shown along with a decrease of visceral fat weight in the LS-treated group. In addition, the fat infiltration of liver was reduced by LS administration. LS-treated mice experienced decreases of serum triglyceride, total cholesterol, and LDL-cholesterol levels. The expression of HSL and ATGL was significantly increased by LS treatment. These results suggest that LS could regulate the lipid metabolism via an increase of lipases expression in ovariectomized and HFD-fed mice. LS might be a novel candidate for a functional food to inhibit weight gain after the menopause.

Topical Treatment of Hair Loss with Formononetin by Modulating Apoptosis.

Formononetin is one of the main components of red clover plants and its role on hair regrowth against hair loss has not been established yet. In the present study, we assessed the potential effects of formononetin on alopecia, along with impaired hair cycles by induction of apoptosis-regression.Depilated C57BL/6 mice were used for monitoring the hair cycles. Formononetin (1 and 100 µM) was topically treated to the dorsal skin for 14 days. Topical formononetin treatment induced miniaturized hair follicles to recover to normal sizes. Tapering hair shaft began to grow newly, emerging from the hair follicles by formononetin. In addition, formononetin inhibited the activation of caspase-8 and decreased the procaspase-9 expression. As a result of formononetin treatment, anti-apoptotic Bcl-2 was up-regulated, whereas pro-apoptotic Bax and p53 were down-regulated, resulting in a decrease of caspase-3 activation. Formononetin showed the obvious inhibition of apoptosis under terminal deoxynucleotidyl transferase dUTP nick end labeling staining thereafter.Taken together, our findings demonstrate that formononetin exerted the hair regrowth effect on hair loss, in which the underlying mechanisms were associated with Fas/Fas L-induced caspase activation, thus inhibiting apoptosis.