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Various diabetic drugs have been developed as the number of patients with type 2 diabetes has increased. Sodium-glucose cotransporter (SGLT)-2 inhibitors have been developed as novel therapeutic agents. However, SGLT-2 inhibitors cause skin dryness. The mechanism through which SGLT-2 inhibitors cause skin dryness is unknown. The purpose of this study was to investigate the mechanism through which dapagliflozin, a SGLT-2 inhibitor, induces skin dryness. Specific pathogen-free KK-Ay/TaJcl (type 2 diabetes model) mice were orally administered with SGLT-2 inhibitor (dapagliflozin) daily for 4 weeks at a dose of 1 mg/kg/d. Skin dryness induced in KK-Ay/TaJcl mice became severe after dapagliflozin administration. Dapagliflozin treatment decreased collagen type I and hyaluronic acid levels in mice; additionally, it affected the transforming growth factor (TGF)-β/hyaluronan synthase pathway, further reducing hyaluronic acid levels. The results indicate that the reduction in hyaluronic acid levels plays an important role in the occurrence of dry skin in diabetes.

Cyclooxygenase (COX)-1-selective inhibitors have side effects such as itching and dryness of the skin. In this study, the degree of skin dryness and the onset mechanism of this condition were investigated by comparing the effects of three non-steroidal anti-inflammatory drugs (NSAIDs) in mice. Mice were orally administered either indomethacin, loxoprofen sodium, or celecoxib (n = 5 per group) once daily for four consecutive days, and blood samples as well as skin and jejunal tissues were isolated on day 5. In the mice treated with indomethacin, transepidermal water loss was significantly increased, and dry skin was observed. In addition, the expression of matrix metalloproteinase (MMP)-I, mast cells, CD163, CD23, CD21, histamine, and peroxisome proliferation-activated receptor (PPAR)γ in the skin and jejunum was increased, and the blood levels of interleukin-10 and immunoglobulin E were also increased. In contrast, the expression of collagen type I in the skin was decreased. These results show that indomethacin activates PPARγ in the skin and jejunum, changes the polarity of macrophages, increases the secretion of MMP-1 from mast cells, and decomposes collagen type I, leading to dry skin.

Various side effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in analgesia have been reported. Among the NSAIDs, celecoxib has fewer side effects and is often used in therapeutic applications. However, the effect of celecoxib on aged skin is unknown. In this study, we investigated the effects of celecoxib administration on the skin of aged mice. We analyzed a 40-week-old mouse model and a 10-week-old mouse as the control group. The animals were orally administered celecoxib for four consecutive days and then killed and dissected the day after the last dose. In aged mice treated with celecoxib, the water content of the stratum corneum, which is one of the markers of dry skin, was lower than that in the control and young mice groups. In addition, serum hyaluronic acid, creatinine, and inflammatory cytokines in the collected blood samples of aged mice were elevated compared to those in other mice groups, suggesting the onset of acute renal injury. Therefore, it was considered that acute renal injury occurred from the administration of celecoxib to aged mice, whereas dry skin developed by the promotion of inflammatory cytokine secretion and release into the bloodstream in this group.

Metastasis, which accounts for the majority of all cancer-related deaths, occurs through several steps, namely, local invasion, intravasation, transport, extravasation, and colonization. Glycyrrhizin has been reported to inhibit pulmonary metastasis in mice inoculated with B16 melanoma. This study aimed to identify the mechanism through which glycyrrhizin ameliorates the extravasation of melanoma cells into mouse lungs. Following B16 melanoma cell injection, mice were orally administered glycyrrhizin once every two days over 2 weeks; lung samples were then obtained and analyzed. Blood samples were collected on the final day, and cytokine plasma levels were determined. We found that glycyrrhizin ameliorated the extravasation of melanoma cells into the lungs and suppressed the plasma levels of interleukin-6, tumor necrosis factor-α, and transforming growth factor-β. Furthermore, glycyrrhizin ameliorated the lung tissue expression of high mobility group box-1 protein (HMGB1), receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)-4, RAS, extracellular signal-related kinase, NF-κB, myeloid differentiation primary response 88, IκB kinase complex, epithelial-mesenchymal transition markers, and vascular endothelial growth factor-A. Our study demonstrates that glycyrrhizin ameliorates melanoma metastasis by regulating the HMGB1/RAGE and HMGB1/TLR-4 signal transduction pathways.

Several studies have been conducted to explore the anticancer effects of vitamin C (VC). However, the effect of high-dose VC administration on melanoma is still unknown. Therefore, in this study, we investigated the effects of high-dose VC (4 g/kg) on the invasion and proliferation of melanoma cells in various organs of mice. B16 melanoma cells (1 × 106 cells/100 µL) were intravenously injected into the tails of female mice, and VC solution (4 g/kg) was orally administered once a day for 14 d. On the 15th day, samples from the liver, lungs, jejunum, and ovaries were collected and analyzed for invasion and proliferation of melanoma cells. Oral VC administration decreased the number of dihydroxyphenylalanine (DOPA)-positive cells and gp100-positive melanoma cells in the ovaries and suppressed the invasion and proliferation of melanoma. Compared to melanoma-administered mice, macrophage inflammatory protein-2 levels and number of neutrophils were increased in the VC + melanoma-administered mice. Furthermore, the concentrations of VC, iron, and hydrogen peroxide, and the number of terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly increased in the ovaries of VC + melanoma-administered mice compared to those of melanoma-administered mice. These results suggest that VC can reduce the invasion and proliferation of melanoma cells in the ovaries, and neutrophils in the ovaries play an important role in achieving this melanoma-suppressive effect.

Purpose Although the onset mechanism of Alzheimer's disease, which co-occurs with aging, has been extensively studied, no effective methods that improve the decline in memory and learning abilities following aging have been developed. Tranexamic acid provided promising results for ameliorating photo-aging and extending the natural lifespan. However, it is unknown whether it affects the decline in memory and learning abilities due to aging. In this study, we examined the effect of tranexamic acid on memory and learning abilities of naturally aging mice. Methods ICR mice were orally administered with tranexamic acid (12 mg/kg/day) three times weekly for 2 years, and their memory and learning abilities were compared between the tranexamic acid-treated and non-treated groups. Results The decline in memory and learning abilities due to aging was ameliorated by tranexamic acid administration. The expression of plasmin and amyloid-β decreased following the treatment with tranexamic acid. Furthermore, the number of M1-type brain macrophages diminished and that of M2 macrophages increased. In addition, administration of tranexamic acid decreased the concentrations of interleukin (IL)-1β and tumor necrosis factor-α, while it increased the levels of IL-10 and transforming growth factor-α in the brain. Conclusion These results indicated that tranexamic acid suppressed the secretion of the inflammatory cytokines aging M1-type macrophages, thereby improving age-related memory and learning abilities.

Sparassis crispa (SC; Japanese name: Hanabiratake) is a mushroom with high β(1-3)-glucan content. We here studied the effects of SC and lactic acid bacteria-fermented SC (SCL) on innate immunity. In in vivo studies using mice, oral administration of SC or SCL enhanced the accumulation of macrophages, neutrophils, natural killer (NK) cells, and C-C chemokine receptor type 2- or phospho-Syk-expressing cells in the jejunum epithelial villi and spleen, with significantly higher cell numbers in the SCL group than in the SC group. In addition, mRNA levels of genes encoding tissue factor (TF) and tumor necrosis factor (TNF)-α were increased in monocytes/macrophages from the peritoneal cavity of mice orally administered SCL. In in vitro studies using cultured human monocytes, SC and SCL enhanced the expression of gees involved in blood coagulation and inflammation, as well as those encoding various innate immune-related factors, such as TF, TNF-α, plasminogen activator inhibitor (PAI)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1β, IL-8, IL-12β, and IL-17, in a dose-dependent manner. In particular, the expression levels of all these factors in monocytes were significantly higher with SCL treatment than with SC treatment. SCL significantly enhanced the phagocytosis of pH-sensitive fluorescent dye-labeled Escherichia coli by human monocytes compared to SC. The effect of SCL on phagocytosis was significantly reduced to approximately 30% by pre-digestion of SCL with β-glucanase, suggesting that β(1-3)-glucan in SCL is a major contributor to the effect. These data suggest that oral administration of SCL significantly enhances innate immunity in mice and possibly humans.

Objective: Atopic dermatitis (AD) symptoms are altered with exercise. However, no study has investigated the association between testosterone and AD. The aim of this study was to investigate the role of testosterone by which the strength and weakness of exercise affects the skin symptoms of AD. Methods: Specific pathogen-free (SPF) and conventional NC/Nga mice were used. NC/Nga mice spontaneously developed dermal symptoms similar to AD patients. Two exercises, mild (20 m/min, 60 min) and rigorous (25 m/min, 90 min), were carried out using a treadmill four times every alternate day. Furthermore, we administered testosterone (0, 5, 50, 500, and 5000 pg/mice) to non-exercised conventional NC/Nga mice. On the final day of this experiment, we analyzed the plasma levels of immunoglobulin E (IgE), interleukin (IL)-6, IL-4, IL-13, testosterone and α-melanocyte-stimulating hormone (α-MSH) by ELISA kit. Results: Symptoms manifested by NC/Nga mice were strongly exacerbated upon severe exercise but were ameliorated during mild exercise. Between mild and severe exercised conventional mice, the plasma level of IgE was not changed. On administering an equivalent amount of testosterone, depending on the exercise, AD-like symptoms in non-exercising NC/Nga mice were ameliorated with mild exercise and exacerbated through rigorous exercise. Plasma IL-6, IL-4, and IL-13 levels remained unchanged between +50 pg (mild) and +500 pg (severe) testosterone administration. Plasma α-MSH levels were elevated with +500 pg testosterone but decreased with +50 pg testosterone administration. Conclusion: The present results suggest that exercise largely mimics AD symptoms depending on the α-MSH and testosterone levels.

Long-term eye exposure to ultraviolet (UV)A can effect memory and learning ability. However, the underlying mechanism behind these effects remain unknown. In this study, we used HR-1 mice to study effects of long-term UVA eye irradiation. The eyes or dorsal skin of the mice were exposed to UVA at the dose of 110kj/m2 using an FL20SBLB-A lamp three times a week over 12 months. We measured the levels of reactive oxygen species, corticotropin-releasing hormone (CRH), urocortin 2, and CRH type 2 receptor (CRHR-2) in the brain of treated and control animals. Their memory and learning ability following exposure to UVA was analyzed by the standard water maze test. Our results showed that the levels of reactive oxygen species, CRH, urocortin 2, and CRHR-2 increased significantly following long-term UVA irradiation, and the effects were more pronounced in animals subjected to eye irradiation than those subjected to dorsal skin irradiation. Furthermore, the UVA exposure led to an increase in the levels of β-amyloid and microglia in the brain. These results indicated that UVA eye irradiation potentially mediated a decline in memory and learning ability via enhancing levels of urocortin 2, microglia, and β-amyloid in the brain.

Introduction: In a rapidly aging society, the number of people suffering from osteoporosis keeps increasing. However, effective prevention strategies for osteoporosis are not yet currently available. Objective: In this study, we examined the ameliorative effects of tranexamic acid on osteoporosis in 24-month-old mice. Methods: During the study period, mice were orally administered tranexamic acid 3 times per week. Results: Bone mineral density, which is a parameter of osteoporosis, was improved following tranexamic acid administration. In addition, female mice evidenced a stronger phenotypic improvement than male mice. In female mice treated with tranexamic acid, ovary abnormalities were reduced. Furthermore, the levels of transforming growth factor-β, hyaluronic acid, CD44, reactive oxygen species, and apoptosis, as well as the number of infiltrated neutrophils and macrophages in the ovary were lower than those in the control or solvent-administered mice. In addition, 17β-estradiol levels in blood increased when compared with the control or solvent-treated mice. In addition, administration of tranexamic acid to 24-month-old male mice decreased the level of apoptosis in the testis. However, the levels of 17β-estradiol and testosterone in blood increased compared with the control or solvent-administered mice. Conclusions: The use of tranexamic acid had an ameliorative effect on osteoporosis, possibly by protecting ovaries and testes.

In this data file, the synthetic procedures for the preparation of a series of anticancer tetrazolato-bridged dinuclear platinum(II) complexes ([{cis-Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)]n+ (n = 1 or 2, tetrazolato-bridged complexes)) and of the bridging ligands of 5-substituted 1H-tetrazoles (5-R-1H-tetrazoles) are described. These compounds were characterized by 1H-, 13C-, 19F- and 195Pt-NMR spectroscopy and mass spectrometry.

Cyclooxygenase (COX)-1-selective inhibitors have side effects such as itching and dryness of the skin. In this study, the degree of skin dryness and the onset mechanism of this condition were investigated by comparing the effects of three non-steroidal anti-inflammatory drugs (NSAIDs) in mice. Mice were orally administered either indomethacin, loxoprofen sodium, or celecoxib (n = 5 per group) once daily for four consecutive days, and blood samples as well as skin and jejunal tissues were isolated on day 5. In the mice treated with indomethacin, transepidermal water loss was significantly increased, and dry skin was observed. In addition, the expression of matrix metalloproteinase (MMP)-I, mast cells, CD163, CD23, CD21, histamine, and peroxisome proliferation-activated receptor (PPAR)γ in the skin and jejunum was increased, and the blood levels of interleukin-10 and immunoglobulin E were also increased. In contrast, the expression of collagen type I in the skin was decreased. These results show that indomethacin activates PPARγ in the skin and jejunum, changes the polarity of macrophages, increases the secretion of MMP-1 from mast cells, and decomposes collagen type I, leading to dry skin.

Tranexamic acid (TA) has been reported to exhibit antitumor effects in various mouse models of cancer. However, the mechanism underlying its antitumor effects against endometrial cancer remains to be elucidated. This study was aimed at investigating the efficacy of TA against chronic inflammation-associated endometrial cancer induced by

Introduction: Although it is beneficial to protect the skin from natural aging, especially in an aging society, the approach by which this can be achieved is still not well known. Hochu-ekki-to, a Chinese natural medicine, has various advantageous effects; however, there is no report about its influence on skin aging. Objective: Therefore, we examined the effect of hochu-ekki-to against natural aging. Methods: Hairless mice, bred without ultraviolet ray irradiation and physical stress, were orally administered huchu-ekki-to 3 times per week for 2 years. After that period, degree of skin hydration and permeability were measured. Furthermore, hematoxylin and eosin histochemistry was performed to determine the morphology and condition of the tissues. Lastly, levels of vitamin A, vitamin C, and reactive oxygen species (ROS) in plasma and skin, as well as concentration of hyaluronic acid in the skin, were measured. Results: Signs of skin aging were ameliorated by administration of hochu-ekki-to, such as moisture retention, skin hydration, and the generation of wrinkles. Furthermore, vitamin A, vitamin C, collagen type I, collagen type III, fibroblasts, and hyaluronic acid levels in the skin increased, while levels of ROS decreased after hochu-ekki-to treatment. Conclusion: These results indicated that natural skin aging was ameliorated by treatment with hochu-ekki-to, specifically moisture retention, and skin hydration, and thickening, via the regulation of the vitamin C/fibroblast, collagen type III/collagen type I, and vitamin A/hyaluronic acid signaling pathways.

Background Vitamin C plays a part in various roles in the human body. In this study, we examined the effect of oral administration of high-dose vitamin C on the skin dryness induced by irinotecan. Methods To establish the experimental model of irinotecan-induced skin dryness, the drug was intraperitoneally administered for four consecutive days. Simultaneously, oral administration of high-dose vitamin C (4 g/kg) was continued for 4 days. Results High-dose vitamin C administration ameliorated the skin dryness induced by irinotecan. The expression of caspase-3 and caspase-9, reactive oxygen species, and the number of TUNEL-positive cells increased in the skin of irinotecan-treated mice but were lowered by high-dose vitamin C administration. In contrast, fibroblasts and collagen type I decreased in the skin of the irinotecan-treated mice but was increased by high-dose vitamin C administration. Conclusion These results suggested that high-dose vitamin C administration can improve the skin dryness induced by irinotecan.

An effective method to protect the skin from natural aging is unknown. Therefore, in this study, we examined the ameliorative effects of tranexamic acid on natural skin aging. In addition, we examined the sex difference in the effect exhibited by tranexamic acid. We bred hairless mice without ultraviolet ray irradiation and physical stress for 2 years. During the study period, mice were orally administered tranexamic acid (12 mg/kg/day) three times per week. Development of signs of skin aging was found to be ameliorated by tranexamic acid. Furthermore, synthetic inhibition of plasmin was observed following tranexamic acid treatment. The synthetic reinforcement of hyaluronic acid by an increase in the number of epidermal cells and the degradative inhibition of extracellular matrix (ECM) by matrix metalloproteinase (MMP) suppression were observed. These results indicate that natural skin aging was ameliorated by tranexamic acid via the regulation of the plasmin/TGF-β/epidermal cells/hyaluronic acid and plasmin/MMPs/ECM signal transmission pathways. Taken together, sex difference was observed for the ameliorative effect of tranexamic acid on skin aging, with a stronger effect observed in females than in males. More importantly, we found that the synthesis of hyaluronic acid was stronger in female mice than in male mice.

Skin dryness is a characteristic of rheumatoid arthritis (RA) model mice. However, the mechanism underlying the induction of dry skin by RA is unclear. We hypothesized that T helper (Th)2 and Th17 cells mediate this process. A mouse model of DBA/1JJmsSlc collagen-induced arthritis was treated with Th2 or Th17 cell inhibitor, and transepidermal water loss (TEWL) and the expression of markers associated with allergic reaction and inflammation were evaluated. TEWL and plasma levels of thymic stromal lymphopoietin, interleukin (IL)-6 and -17, and tumor necrosis factor (TNF)-α were increased in the arthritis mouse model compared to that in control mice. Administration of Th2 cell inhibitor abolished the increase in TEWL, IL-6, and TNF-α levels, whereas Th17 cell inhibitor reversed TEWL and decreased IL-17 level. Th2 and Th17 cells contribute to the induction of dry skin, but via distinct mechanisms.

Several studies have been conducted to investigate the anti-cancer effects of vitamin C (VC). However, the effect of high-dose VC administration on tumor angiogenesis remains unclear. Focusing on our high-dose VC, our study investigated the effect of high-dose VC (4 g/kg) on vascular endothelial growth in mice with xenografts of a rectal cancer cell line referred to as Colon 26. Male mice harboring Colon 26 tumors were established, and high-dose VC solution was orally administered once daily for 14 d. On the final day of the study, the lower limb tumor tissues and serum samples were collected and analyzed for the expression of tumor angiogenesis related proteins as well as the levels of reactive oxygen species (ROS). Oral VC administration decreased tumor volumes and increased p53 and endostatin levels. In addition, plasma and in tumor part ROS levels and tissue hypoxia inducible factor-1α (HIF-1α) were reduced by VC administration. In addition, the levels of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor D (VEGFD) were decreased by VC administration. These results suggest that VC exerts its anti-cancer effects by suppressing angiogenesis.

Long-term ultraviolet A (UVA) eye irradiation decreases memory and learning ability in mice. However, the underlying mechanism is still unclear. In this study, ICR mice were used to study the effects of long-term UVA eye irradiation. The eyes of mice were exposed to UVA from an FL20SBLB-A lamp three times a week for 1 year. Then, we analyzed memory and learning ability in the mice using water maze and step-through passive avoidance tests, and measured the levels of p53, Period2 (Per2), Clock, brain and muscle Arnt-like protein-1 (Bmal1), nicotinamide mononucleotide adenylyltransferase (NMNAT) activity, nicotinamide phosphoribosyltransferase (NAMPT) activity, nicotinamide adenine dinucleotide (NAD+), and sirtuin 1 (Sirt1) in the brains of treated and control animals. The results showed that the p53 level increased significantly following long-term UVA eye irradiation, whereas the levels of Period2, Bmal1, Clock, NMNAT and NAMPT activities, NAD+, and Sirt1 decreased significantly. Furthermore, we found that p53 inhibition ameliorated the UVA eye irradiation-induced depression of memory and learning ability. These results indicate that long-term UVA eye irradiation stimulates p53, inhibits the clock gene, and reduces Sirt1 production in the NAD+ constructional system, resulting in reduced memory and learning ability.

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.

Inflammation is a primary risk factor for cancer. Epidemiological studies previously demonstrated that aspirin decreased the incidence of cancer and specifically reduced the risk of colorectal cancer. However, the number of animal studies that have confirmed the efficacy of aspirin remains limited. Therefore, the purpose of the present study was to investigate the mechanisms by which aspirin prevents colorectal cancer in mice. ICR mice were treated with azoxymethane and the ulcerative colitis inducer, dextran sodium sulfate, to induce colorectal tumors. Aspirin was orally administered three times per week for 12 weeks. Aspirin significantly reduced the number and size of colorectal tumors. Aspirin also significantly decreased tumor necrosis factor alpha and reactive oxygen species (ROS) levels in the plasma. Immunohistochemical analyses and western blots showed that cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), and the active form of Yes-associated protein 1 (YAP1), and cytosolic high mobility group box 1 (HMGB1) were strongly expressed at colorectal tumor sites and clearly suppressed by aspirin. An indicator of inflammation-related DNA damage, 8-nitroguanine, also accumulated in the colorectal tissues and was suppressed by aspirin. The present results suggest that the ingestion of aspirin suppressed carcinogenesis caused by inflammation through decreases in COX2 and ROS levels, resulting in reductions in DNA damage and oncogenic YAP1.

Dry eye syndrome is known to develop from several systemic inflammatory diseases. Although dry eye may develop due to extraintestinal complications of ulcerative colitis (UC), the pathogenesis is not well-known. This study aimed to investigate whether there was decrease in the tear secretion volume in a mice model with UC; the difference between the control and dextran sodium sulphate (DSS)-treated group was also determined.This study included a mice model with UC induced by the oral administration of 5.0% DSS for 7 days. Following the DSS treatment, the tear volume was measured using the Schirmer's test. The colon and ocular tissues, including the lacrimal gland, were evaluated using histological and protein analyses. Additionally, tumour necrosis factor (TNF)-α and interleukin (IL)-6 in the plasma were determined. Differences between groups (DSS-treated versus control mice) were determined using Student'sThe tear volume in DSS-treated mice was decreased compared to that in the control mice. Plasma levels of TNF-α and IL-6 in DSS-treated mice was higher than that of control. Morphological change was observed with the invasion of the inflammatory cell in the lacrimal gland of DSS-treated mice. Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL)-positive cells were increased in the lacrimal glands of DSS-treated mice compared with control group. The distribution of aquaporin-5 expressed in the lacrimal gland of DSS-treated mice was decreased compared to that in the control group.These findings suggest that a decrease in the tear volume in UC was associated with a functional decline in the inflamed lacrimal gland. This result therefore provides useful information that could contribute to the development of treatment approaches for dry eye associated with UC.

Ultraviolet (UV) irradiation to the eye induces photoimmunosuppression. In here, we examined the effect of green odor against immunosuppression of contact hypersensitivity in the eye induced by ultraviolet B (UVB) irradiation. Systemic immunosuppression was induced in ICR mice sensitized with 0.5% oxazolone through the skin by a single exposure to UVB. Consecutive green odor treatment significantly counteracted UVB irradiation-induced immunosuppression of the contact hypersensitivity (CHS) response. The green odor treatment increased dopamine and β-endorphin levels in the brain and the plasma, respectively, and decreased the plasma corticosterone concentration in the oxazolone-sensitized mice after UVB irradiation to the eye, in contrast with that in acetone-treated mice (treatment negative control). Green odor prevented UVB irradiation-induced photoimmunosuppression of the CHS response by regulating the dopamine/β-endorphin/corticosterone pathway.

Although various methods for improving the natural aging of skin have been examined, an effective method is currently unavailable. Therefore, in this study, we investigated the effects of Momordica charantia on the natural aging of skin of mice and how sex differences influenced these effects. To this end, we bred female and male hairless mice without ultraviolet ray irradiation and physical stress for 2 years. During the study period, mice were orally administered 50 mg/kg/day Momordica charantia fruit extract, three times per week. The characteristics of naturally aging skin, in terms of moisture retention, hydration, thickness, and reduced wrinkle score, improved after Momordica charantia treatment in both male and female mice. Furthermore, reduced cell apoptosis was observed in the female ovaries and male testes, and the levels of testosterone and 17β-estradiol in blood were maintained. After treatment with Momordica charantia, the expression of matrix metalloprotease (MMP)-1 and hyaluronidase (HAYL)2 decreased in the skin of female mice, whereas the serum levels of interleukin (IL)-33 increased in the male mice. These results indicated that the natural aging of the skin was decelerated by Momordica charantia via regulation of the 17β-estradiol/mast cell/MMP-1/HAYL2 and testosterone/mast cell/IL-33 signaling pathways in female and male mice, respectively.

High-dose vitamin C administration has been reported to exhibit antitumor effect in various mouse models of cancer. However, the underlying mechanism of antitumor effect against colorectal cancer remains to be elucidated. In this study, we investigated the antitumor effect of high-dose vitamin C in a mouse model of chronic inflammation-associated colorectal cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). After cancer induction, the mice were administered vitamin C and/or irinotecan. Because irinotecan is a key drug in colorectal cancer treatment, it was used for comparison in this study. We examined reactive oxygen species (ROS) and interleukin-6 (IL-6) levels in the plasma of mice, as well as collagen type I and caspase-1 expression and neutrophil and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cell counts in the colon tissue. Vitamin C and/or irinotecan administration decreased the plasma level of ROS and IL-6 and increased the expression of collagen type I and caspase-1. Furthermore, it increased neutrophil and TUNEL-positive cell counts. The most significant changes in the parameters analyzed were observed when both vitamin C and irinotecan were administered.

Photoaging can be induced by long-term ultraviolet (UV)A eye irradiation, but an ameliorating method for such photoaging is not known. In this study, we examined the effects of tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) on photoaging of the skin induced by UVA eye irradiation. We used the C57BL/6 j female mice and locally exposed their eyes to UVA at a dose of 110 kJ/m2 using an FL20SBLB-A lamp multiple times a week for one year. The plasma urocortin 2, β-endorphin, methionine enkephalin (OGF), and histamine content, as well as the expression of the corticotropin-releasing hormone receptor (CRHR) type 2, μ-opioid receptor, opioid growth factor receptor (OGFR), T-bet, and GATA3 increased in the mice subjected to UVA eye irradiation. However, the increased levels of urocortin 2, methionine enkephalin, histamine, OGFR, T-bet, and GATA3 were suppressed by tranexamic acid treatment. Conversely, the levels of β-endorphin and μ-opioid receptor increased with tranexamic acid treatment. In addition, the expression of the estrogen receptor-β on the surface of mast cells was increased by tranexamic acid. These results indicate that photoaging induced by UVA eye irradiation can be ameliorated by tranexamic acid through the regulation of hypothalamo-pituitary hormones. Furthermore, this ameliorative effect on photoaging may be due to an increase in estrogen receptor-β after tranexamic acid treatment.

Ultraviolet (UV) irradiation is a well known photo-immunosuppressant. To determine the effect of Eucommia ulmoides leaf extract (ELE) components (chlorogenic acid, geniposidic acid, and asperuloside) on UVB induced immunosuppression, we examined mice that were contact hypersensitized. Systemic immunosuppression was induced in the C57BL/6j mice that were sensitized with 0.5% oxazolone through the skin by a single exposure to UVB. Consecutive oral administration of ELE, chlorogenic acid, or geniposidic acid significantly reduced UVB-induced suppression of the contact hypersensitivity (CHS) response. The treatment with chlorogenic acid or geniposidic acid decreased the serum interleukin-10 levels in the sensitized mice after UVB irradiation. Additionally, the level of plasma reactive oxygen species and the expression of skin mast cells decreased in the chlorogenic acid-treated mice. Contrarily, the expression of regulatory T cell in the skin decreased in the geniposidic acid-treated mice. These results suggest that chlorogenic and geniposidic acids prevent the photo-immunosuppression of the CHS response.