Acertannin Prevented Dextran Sulfate Sodium-induced Colitis by Inhibiting the Colonic Expression of IL-23 and TNF-α in C57BL/6J Mice.

The present study investigates the effects of acertannin on colitis induced by dextran sulfate sodium (DSS) and changes in the colonic levels of the cytokines interleukin (IL)-1ß, IL-6, IL-10, IL-23, tumor necrosis factor (TNF)-α, the chemokine monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF).We examine the following: inflammatory colitis was induced in mice by 2% DSS drinking water given ad libitum for 7 days. Red blood cell, platelets, and leukocyte counts and hematocrit (Ht), hemoglobin (Hb), and colonic cytokine and chemokine levels were measured. The disease activity index (DAI) was lower in DSS-treated mice orally administered acertannin (30 and 100 mg/kg) than in DSS-treated mice. Acertannin (100 mg/kg) inhibited reductions in the red blood cell count and Hb and Ht levels in DSS-treated mice. Acertannin prevented DDS-induced mucosal membrane ulceration of the colon and significantly inhibited the increased colonic levels of IL-23 and TNF-α. Our findings suggest that acertannin has potential as a treatment for inflammatory bowel disease (IBD).

Two hydroxyflavanones isolated from Scutellaria baicalensis roots prevent colitis-associated colon cancer in C57BL/6 J mice by inhibiting programmed cell death-1, interleukin 10, and thymocyte selection-associated high mobility group box proteins TOX/TOX2.

BACKGROUND: Colorectal cancer was the second leading cause of mortality in 2019 and the number of new colorectal cancer cases was the highest in 2018 and 2019 in Japan. PURPOSE: The present study investigated the inhibitory effects of 2(S)-2',5,6',7-tetrahydroxyflavanone and 2 (R), 3(R)-2',3,5,6'-7-pentahydroxyflavanone on the incidence and growth of tumors in azoxymethane (AOM) plus dextran sulfate sodium (DSS)-treated mice. METHODS: The intraperitoneal administration of AOM (10 mg/kg) on day 0 induced colorectal carcinogenesis. Mice were given free and unlimited access to drinking water containing 1.5% (w/v) DSS on days 5 - 8, 30 - 33, and 56 - 57. They were orally administered tetra- and penta-hydroxyflavanones (10 and 30 mg/kg) for 10, 11, and 14 days followed by discontinuation intervals of 20 and 15 days. Cytokine, chemokine, programmed cell death-1 (PD-1), cyclooxygenase (COX)-2, and thymocyte selection-associated high mobility group box protein (TOX)/TOX2 expression levels were measured using their respective ELISA kits and an immunohistochemical analysis. RESULTS: The number and area of tumors decreased by 60.6 and 72.9% in mice administered 10 mg/kg tetra- and pentahydroxyflavanones, respectively, with reductions of 95.0 and 87.0% in Ki-67-positive cells, 91.7 and 92.7% in COX-2-postive cells, and 83.1 and 93.8% in TOX/TOX2-positive cells, respectively, in the colon. On the other hand, two tera- and pentahydroxyflavanone had no effect on p53 (a tumor suppressor by cell cycle arrest and apoptosis)-positive cells. The administration of 10 mg/kg tetra- and pentahydroxyflavanones to AOM/DSS-treated mice also resulted in decreases of 59.5 and 42.5% in IL-10 levels and 58.1 and 93.9% in PD-1 levels, respectively, in the colon. CONCLUSION: The inhibitory effects of tetra- and pentahydroxyflavanones on the growth of colon tumors in AOM/DSS-treated mice appear to be associated with decreases in the colon levels of IL-10 and PD-1 through the down-regulated expression of COX-2 and CD8+ T-cell exhaustion by TOX/TOX2 in the tumor microenvironment.

Antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin isolated from Angelica keiskei roots through the inhibited activation and differentiation of M2 macrophages.

BACKGROUND: Tumor growth and metastasis have been closely associated with the M2 macrophage-induced activation of tumor-associated macrophages (TAMs). PURPOSE: The antitumor and antimetastatic actions of xanthangelol and 4-hydroxyderricin on the role of M2 macrophages in the TAMs of highly metastatic osteosarcoma LM8-bearing mice have not yet been fully elucidated. In order to clarify the mechanisms underlying the antitumor and antimetastatic actions of the above chalcones, we performed in vivo and in vitro studies. STUDY DESIGN: The antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin were examined in vivo and the effects on M2 macrophage differentiation and activation were examined in vitro. METHODS: We examined the antitumor and antimetastatic effects of xanthoangelol and 4-hydroxyderricin on highly metastatic osteosarcoma LM8-bearing mice (in vivo). Further, we examined their effects on the differentiation of interleukin (IL)-4 plus IL-13-induced M2 macrophages and activation of IL-4 plus IL13-induced M2 macrophages (in vitro). We also investigated the expression and phosphorylation of signal transducer and activator of transcript 3 (Stat 3) in the differentiation process of M2-polarized macrophages (in vitro). RESULTS: Xanthoangelol or 4-hydroxyderricin (25 or 50 mg/kg, twice daily) inhibited tumor growth, metastasis to the lung and liver, and TAM expression in tumors. In addition, xanthoangelol (10, 25 or 50 µM) and 4-hydroxyderricin (5, 10, 25 or 50 µM) inhibited the production of IL-10 and monocyte chemoattractant protein (MCP)-1 in M2-polarized macrophages. This result indicated that xanthoangelol and 4-hydroxyderricin inhibited the activation of M2 macrophages. Furthermore, xanthoangelol (5-50 µM) inhibited the phosphorylation of Stat 3 without affecting the expression of the Stat 3 protein in the differentiation process of M2 macrophages, which indicated that these chalcones inhibited the differentiation of M2 macrophages. CONCLUSION: These findings suggested that the antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderrcin might be attributed to the regulated activated TAMs through the inhibition of activation and differentiation of M2 macrophages in the tumor microenvironment.

Anti-tumor effects of various furocoumarins isolated from the roots, seeds and fruits of Angelica and Cnidium species under ultraviolet A irradiation.

We examined the effects on cell proliferation of 10 methoxyfurocoumarins and 7 dihydrofurocumarins isolated from Umbelliferae medicinal plants, and their mechanisms of action against B16F10 melanoma cells or in melanin-possessing hairless mice implanted with B16F10 melanoma cells, under UVA irradiation. Furocoumarins having a methoxy group, such as bergapten (1), xanthotoxin (2), phellopterin (4), byakangelicin (6), neobyakangelicin (8), isobergapten (9) and sphondin (10), showed anti-proliferative activity and caused G2/M arrest at concentrations of 0.05-15.0 µM. The 7 dihydrofurocoumarins had no effect. UVA plus 1, 2, 4, 6 and sec-O-acetylbyakagelicin (7), having one methoxy group at the C-5 position and a linear-type conformation, reduced tumor growth and final tumor weight in B16F10-bearing mice at 0.5 or 1.0 mg/kg (intraperitoneal injection). UVA plus 1 and 2 increased Chk1 phosphorylation and decreased cdc2 (Thr 161) phosphorylation in the melanoma cells. The anti-tumor actions of UVA plus furocoumarins having a methoxy group might be due to the arrest of the cell cycle at G2/M through an increase in phospho-Chk1 and reduction in phospho-cdc2.

Whey peptides prevent chronic ultraviolet B radiation-induced skin aging in melanin-possessing male hairless mice.

Whey proteins or peptides exhibit various actions, including an antioxidant action, an anticancer action, and a protective action against childhood asthma and atopic syndrome. The effects of orally administered whey peptides (WPs) on chronic ultraviolet B (UVB) radiation-induced cutaneous changes, including changes in cutaneous thickness, elasticity, wrinkle formation, etc., have not been examined. In this study, we studied the preventive effects of WPs on cutaneous aging induced by chronic UVB irradiation in melanin-possessing male hairless mice (HRM). UVB (36-180 mJ/cm(2)) was irradiated to the dorsal area for 17 wk in HRM, and the measurements of cutaneous thickness and elasticity in UVB irradiated mice were performed every week. WPs (200 and 400 mg/kg, twice daily) were administered orally for 17 wk. WPs inhibited the increase in cutaneous thickness, wrinkle formation, and melanin granules and the reduction in cutaneous elasticity associated with photoaging. Furthermore, it has been reported that UVB irradiation-induced skin aging is closely associated with the increase in expression of matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), Ki-67-, and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. WPs also prevented increases in the expression of MMP-2 and pro-MMP-9, VEGF, and Ki-67- and 8-OHdG-positive cells induced by chronic UVB irradiation. It was found that WPs prevent type IV collagen degradation, angiogenesis, proliferation, and DNA damage caused by UVB irradiation. Overall, these results demonstrate the considerable benefit of WPs for protection against solar UV-irradiated skin aging as a supplemental nutrient.

In vitro and in vivo antiproliferative effect of a combination of ultraviolet-A and alkoxy furocoumarins isolated from Umbelliferae medicinal plants, in melanoma cells.

We examined the effects of six furocoumarins with alkoxy groups at the C-5 or C-8 position isolated from Umbelliferae medicinal plants on cell proliferation, and their mechanisms of action against B16F10 melanoma cells or in melanin-possessing hairless mice implanted with B16F10 cells, under UVA irradiation. Three furocoumarins with an alkoxy group at C-5, isoimperatorin (1), oxypeucedanin (2) and oxypeucedanin hydrate (3), showed antiproliferative activity and caused G2/M arrest at concentrations of 0.1-10.0 µm. Furthermore, three furocoumarins with an alkoxy group at C-8, imperatorin (4), heraclenin (5) and heraclenol (6), inhibited the proliferation of melanoma cells and cell cycle at G2/M at concentrations of 0.1-1.0 µm. UVA plus 1, 2, 3, 4 and 6 reduced tumor growth and final tumor weight in B16F10-bearing mice at a dose of 0.3, 0.5 or 1.0 mg kg(-1) (intraperitoneal injection). UVA plus 1, 3 and 6 increased Chk1 phosphorylation and reduced cdc2 (Thr 161) phosphorylation in melanoma cells. We suggest that the antitumor actions of UVA plus furocoumarins with an alkoxy group at C-5 or C-8 were due to G2/M arrest of the cell cycle by an increase in phosphor-Chk1 and decrease in phospho-cdc2.

Hop (Humulus lupulus L.) extract inhibits obesity in mice fed a high-fat diet over the long term.

Hops (Humulus lupulus L.) are traditionally used to add bitterness and flavour to beer. Although the isomerised hop extracts produced by the brewing process have been thought to ameliorate lipid and glucose metabolism, the influence of untreated hop extracts on high-fat (HF) diet-induced obesity is unclear. The present study examined the anti-obesity effects of a hop extract in male C57BL/6J mice fed a HF diet, or HF diet plus 2 or 5 % hop extract for 20 weeks. The oral glucose tolerance test was performed at week 19. Furthermore, water excretion was evaluated in water-loaded Balb/c male mice. The effects of the extract on lipid accumulation and PPARγ expression in 3T3-L1 adipocytes were examined. The hop extract inhibited the increase in body and adipose tissue weight, adipose cell diameter and liver lipids induced by the HF diet. Furthermore, it improved glucose intolerance. The extract enhanced water excretion in water-loaded mice. Various fractions of the hop extract inhibited lipid accumulation and PPARγ expression in 3T3-L1 adipocytes. Hop extracts might be useful for preventing obesity and glucose intolerance caused by a HF diet.

Anti-tumor and anti-metastatic actions of wogonin isolated from Scutellaria baicalensis roots through anti-lymphangiogenesis.

Tumor growth and metastasis are associated with angiogenesis and lymphangiogenesis through the production of vascular endothelial growth factor (VEGF) or VEGF-C in tumors, and the phosphorylation of VEGF receptor (VEGFR)-2 or VEGFR-3 in vascular endothelial cells or lymphatic endothelial cells (LECs). Tumor-associated macrophages (TAMs) play an important role in tumor lymphangiogenesis, and consequently stimulate metastasis through the lymphatic system to lymph nodes. We examined the effects of wogonin isolated from Scutellaria baicalensis roots on tumor growth and metastasis using a highly metastatic model in osteosarcoma LM8-bearing mice. Wogonin (25 and 50 mg/kg, twice daily) reduced tumor growth and metastasis to the lung, liver and kidney, angiogenesis (CD31-positive cells), lymphangiogenesis (LYVE-1-positive cells), and TAM (F4/80-positive cell) numbers in the tumors of LM8-bearing mice. Wogonin (10-100 µM) also inhibited increases in IL-1ß production and cyclooxygenase (COX)-2 expression induced by lipopolysaccharide in THP-1 macrophages. Wogonin had no effect on VEGF-C production in LM8 cells, or VEGFR-3 expression in human lymphatic endothelial cells (HLECs), however, it inhibited VEGF-C-induced VEGFR-3 phosphorylation in HLECs. The anti-tumor and anti-metastatic actions of wogonin may be associated with the inhibition of VEGF-C-induced lymphangiogenesis through a reduction in VEGF-C-induced VEGFR-3 phosphorylation by the inhibition of COX-2 expression and IL-1ß production in TAMs.

Effects of the extracts and an active compound curcumenone isolated from Curcuma zedoaria rhizomes on alcohol-induced drunkenness in mice.

The Curcuma zedoaria rhizome has been used traditionally to treat gastrointestinal diseases as an aromatic stomachic drug, and this is currently used to treat alcohol-induced loss of appetite and nausea in Japan. We examined the effects of various fractions and isolated compounds on alcohol-induced drunkenness and blood alcohol concentrations in mice. The 30% ethanol-extract (1000mg/kg) of C. zedoaria rhizome prevented drunkenness 60 and 120min after 40% alcohol administration. The n-hexane-soluble fraction (300mg/kg) and an isolated compound (3, 10 or 30mg/kg) prevented drunkenness at 30, 60 or 120min. The extract, n-hexane-soluble fraction and isolated compound reduced the elevation in blood alcohol concentrations 30 and 60min after 40% alcohol administration. The isolated compound (10 and 30mg/kg) enhanced liver ADH activity 30 and 60min after 40% alcohol administration. The compound was identified as curcumenone by a direct comparison of (1)H- and (13)C-NMR spectral data. In conclusion, the protective effect of the C. zedoaria extract on drunkenness might be due to an active substance, curcumenone, and decreases in the elevation of blood alcohol concentrations through increased liver alcohol dehydrogenase activity.

Effects of ginsenoside Rb1 on skin changes.

Ginseng roots (Panax ginseng CA Meyer) have been used traditionally for the treatment, especially prevention, of various diseases in China, Korea, and Japan. Both experimental and clinical studies suggest ginseng roots to have pharmacological effects in patients with life-style-related diseases such as non-insulin-dependent diabetic mellitus, atherosclerosis, hyperlipidemia, and hypertension. The topical use of ginseng roots to treat skin complaints including atopic suppurative dermatitis, wounds, and inflammation is also described in ancient Chinese texts; however, there have been relatively few studies in this area. In the present paper, we describe introduce the biological and pharmacological effects of ginsenoside Rb1 isolated from Red ginseng roots on skin damage caused by burn-wounds using male Balb/c mice (in vivo) and by ultraviolet B irradiation using male C57BL/6J and albino hairless (HR-1) mice (in vivo). Furthermore, to clarify the mechanisms behind these pharmacological actions, human primary keratinocytes and the human keratinocyte cell line HaCaT were used in experiments in vitro.

Effects of an Atractylodes lancea rhizome extract and a volatile component ß-eudesmol on gastrointestinal motility in mice.

AIM OF THE STUDY: The rhizomes of Atractylodes lancea DC (Compositae) are used clinically to treat gastrointestinal symptoms, including functional dyspepsia and gastroparesis, in China and Japan, but their influence and mechanism on gastrointestinal motility are not yet proven in detail. MATERIALS AND METHODS: This study examined the effects of an Atractylodes lancea extract, and isolated ß-eudesmol, on gastric emptying and small intestinal motility in atropine-, dopamine-, and 5-hydroxytryptamine (5-HT)-treated mice. RESULTS AND CONCLUSIONS: The extract (500 or 1000mg/kg) and ß-eudesmol (50 or 100mg/kg), as well as itopride hydrochloride (a dopamine D(2) receptor antagonist, 10 or 50mg/kg), stimulated small intestinal motility in normal mice. They inhibited reductions in gastric emptying and gastrointestinal motility induced by dopamine (1mg/kg, intraperitoneal injection, ip). The extract (1000mg/kg) and ß-eudesmol (100mg/kg) inhibited the atropine-induced decrease in small intestinal motility, but not gastric emptying. Furthermore, the extract (500 or 1000mg/kg) and ß-eudesmol (25, 50, or 100mg/kg) inhibited reductions in gastric emptying and small intestinal motility caused by 5-HT (4mg/kg, ip) or the 5-HT(3) receptor agonist 1-(3-chlorophenyl) biguanide (0.5mg/kg, ip), but not a 5-HT(2C) receptor agonist. These findings suggest that the extract of Atractylodes lancea and ß-eudesmol may stimulate gastric emptying or small intestinal motility by inhibiting the dopamine D(2) receptor and 5-HT(3) receptor.

Effects of Swertia japonica extract and its main compound swertiamarin on gastric emptying and gastrointestinal motility in mice.

The Swertia japonica is used clinically as a remedy for gastrointestinal symptoms in Japan. We examined the effects of a S. japonica and swertiamarin on gastric emptying and gastrointestinal motility in atropine-, dopamine-, and 5-hydroxytryptamine (5-HT)-treated mice. All three preparations inhibited reductions in gastric emptying and gastrointestinal motility induced by dopamine (1mg/kg, intraperitoneal injection, ip). Neither the powder, swertiamarin, nor itopride had any effect on the reductions in gastric emptying and gastrointestinal motility caused by 5-HT (4 mg/kg, ip). These findings suggest that the powder and swertiamarin stimulate gastric emptying and gastrointestinal motility by inhibiting the dopamine D(2) receptor.

Effects of Red Ginseng extract on allergic reactions to food in Balb/c mice.

AIM OF THE STUDY: Red Ginseng roots (Panax ginseng C.A. Meyer) have traditionally been thought to have anti-allergic effects, but their influence on food-induced allergic responses is unclear. MATERIALS AND METHODS: This study examined the effects of a Red Ginseng extract on an ova-albumin (OVA)-evoked allergic reaction in mice. RESULTS AND CONCLUSIONS: The orally administered extract significantly inhibited the increase in OVA-specific IgG(1) (Th(2)) levels in OVA-sensitized mice, but had no effect on OVA-specific IgE (Th(2)) levels. The extract prevented a reduction in IL-12 production and the ratio of IFN-γ (Th(1)) to IL-4 (Th(2)) in splenocytes, and enhanced small intestinal CD8-, IFN-γ-, and IgA-positive cell numbers in the OVA-sensitized mice. These findings suggest that Red Ginseng inhibits allergic reactions to food by preventing reductions in the ratio of IFN-γ to IL-4 and in IL-12 production induced by dietary antigens in spleen cells, and/or increasing the expression of CD8 and IFN-γ in the small intestine. It may also protect against sensitization to antigens as an immunomodulator by increasing intestinal IgA secretion without affecting antigen-specific IgE levels. In conclusion, Red Ginseng roots may be a natural preventative of food allergies.

Anti-Obesity effects of protopanaxdiol types of Ginsenosides isolated from the leaves of American ginseng (Panax quinquefolius L.) in mice fed with a high-fat diet.

Effects of protopanaxdiol (PDG) and protopanaxatriol (PTG) types of ginsenosides isolated from the leaves of American ginseng on porcine pancreatic lipase activity were determined in vitro. PDG inhibited the pancreatic lipase activity in a dose-dependent manner at the concentrations of 0.25-1mg/ml. It inhibited hydrolysis of about 83.2% of triolein at about 1mg/ml of PDG. However, PTG showed no inhibitory activity. Therefore, anti-obesity activity of PDG was evaluated in mice fed a high-fat diet. The results demonstrated that PDG was effective in preventing and healing obesity, fatty liver and hypertriglyceridemia in mice fed with a high-fat diet.

French maritime pine bark (Pinus maritima Lam.) extract (Flavangenol) prevents chronic UVB radiation-induced skin damage and carcinogenesis in melanin-possessing hairless mice.

A French maritime pine bark extract, Flavangenol, is widely used as a nutritional supplement for protection against atherosclerosis, hypertension, diabetes, etc. Chronic exposure to solar UV radiation damages skin, increasing cutaneous thickness, wrinkling and pigmentation, as well as reducing elasticity, and causes skin cancer. The aim of this study was to examine the effects of flavangenol on skin damage and the incidence of skin tumors caused by long-term UVB irradiation in melanin-possessing hairless mice. The oral administration of flavangenol (60, 200 or 600 mg kg(-1), twice daily) significantly inhibited increases in skin thickness, and the formation of wrinkles and melanin granules, as well as increases in the diameter and length of skin blood vessels. Furthermore, it prevented increases in numbers of apoptotic, Ki-67-positive and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells, and the expression of skin vascular endothelial growth factor (VEGF) induced by chronic UVB irradiation. The effect on these biomarkers was associated with a reduction in the incidence of tumors in mice. The antiphotoaging and anticarcinogenetic activities of flavangenol may be due to inhibition of the expression of Ki-67, 8-OHdG and VEGF through a scavenging effect on reactive oxygen species.

Enhancing effects of a chromone glycoside, eucryphin, isolated from Astilbe rhizomes on burn wound repair and its mechanism.

We previously reported that three compounds isolated from Astilbe thunbergii rhizomes accelerated burn wound healing. Among the three substances, eucryphin enhanced burn wound healing most strongly; however, the biological mechanisms of eucryphin are not yet well understood and here we examined the effects on chemokine, growth factor, and cytokine productions in in vivo and in vitro experiments. We have set burn wounds on the backs of mice and topically applied either vehicle alone or vehicle containing low doses of eucryphin to the burn wound. We examined the effects of eucryphin on chemokine, cytokine, and growth factor production at the wound site and in various cells. Eucryphin (10(-4) to 10(-8)% ointment) facilitated burn wound repair compared to the vehicle control. Eucryphin (100 ng per wound) increased IL-1beta, MCP-1, VEGF, and TGF-beta1 levels in the exudates from the wound area. Eucryphin increased VEGF, TGF-beta1, and HIF-1alpha expression levels in keratinocytes. These findings suggest that the enhancement of burn wound healing by eucryphin might be due to promotional angiogenesis during skin wound repair as a result of the stimulation of VEGF and TGF-beta1 production caused by the increase in HIF-1alpha expression in keratinocytes.

Increased spontaneous electrical activity at a latent myofascial trigger point after nociceptive stimulation of another latent trigger point.

OBJECTIVE: To investigate the changes in surface and intramuscular electromyographic (EMG) activity at latent trigger points (TrPs) in the extensor carpi radialis brevis muscle after injection of either glutamate or isotonic saline into latent TrPs in the infraspinatus muscle. METHOD: Nociceptive muscle stimulation was obtained by a bolus injection of glutamate (0.2 mL, 0.5 M) into a latent TrP located in the right infraspinatus muscle in 12 healthy volunteers. A bolus of isotonic saline (0.9%, 0.2 mL) injection served as control. Injections were guided by intramuscular EMG showing resting spontaneous electrical activity at the latent myofascial TrP in the infraspinatus muscle. Intramuscular (at the TrP) and surface EMG activities of both infraspinatus and extensor carpi radialis brevis muscles were recorded before, during, and after injection for a period of 6 minutes to monitor changes produced in EMG activity. RESULTS: Glutamate injection into latent TrPs induced higher pain intensity than isotonic saline injection (P<0.001). The analysis of variance showed a significant increase in root mean square score of intramuscular EMG activity at TrP in the extensor carpi radialis brevis after glutamate (mean+/-SD: 212.0+/-215.6 microV) but not isotonic saline (mean+/-SD: 74.2+/-72.2 microV) injections (P<0.001). No changes in surface EMG activity were found. No significant changes in root mean square of intramuscular and surface EMG activity in the infraspinatus muscle were found. CONCLUSIONS: Our results show that an increased nociceptive activity at latent TrPs in the infraspinatus muscle may increase motor activity and sensitivity of a TrP in distant muscles at a same segmental level.

Effects of olive leaf extract and its main component oleuroepin on acute ultraviolet B irradiation-induced skin changes in C57BL/6J mice.

Olive (Olea europaea L.) leaves have long been used in folk medicine and herbal tea in Europe and the Mediterranean area. The Mediterranean climate is characterized by high temperatures, and by strong ultraviolet B (UVB) radiation causing the skin to age, increasing wrinkling, pigmentation and skin thickness. The aim of this study was to examine the effects of an olive leaf extract and its component oleuropein on skin damage caused by acute UVB irradiation in C57BL/6J mice. The extract (300 or 1000 mg/kg) and oleuropein (25 or 85 mg/kg) were administered orally twice daily for 14 days. UVB was administered daily at a dose of 120 mJ/cm(2) for the first 5 days and then every other day for 9 days. Both treatments inhibited the increases in skin thickness induced by radiation. They also inhibited increases in the Ki-67- and 8-hydroxy-2'-deoxyguanosine-positive cell numbers, melanin granule area and matrix metalloproteinase-13 (MMP-13) expression. These preventive effects on UVB-induced skin damage might be caused in part by inhibiting the degradation of extracellular matrixes in the corium, and by the proliferation of epidermal cells through the inhibition of increases in MMP-13 levels and reactive oxygen species induced by irradiation.

Olive leaf extract and its main component oleuropein prevent chronic ultraviolet B radiation-induced skin damage and carcinogenesis in hairless mice.

Chronic exposure to solar UV radiation damages skin, increasing its thickness and reducing its elasticity, and causes skin cancer. Our aim in this study was to examine the effects of an olive leaf extract and its component oleuropein on skin damage and the incidence of skin tumors caused by long-term UVB irradiation in hairless mice. Male hairless mice (5 wk old) were divided into 6 groups, including a non-UVB group, a vehicle-treated UVB group (control), 2 olive leaf extract-treated UVB groups, and 2 oleuropein-treated UVB groups. Five groups were UVB irradiated (36-180 mJ/cm(2)) 3 times each week for 30 wk and skin thickness and elasticity after UVB irradiation were measured every week. Olive leaf extract (300 and 1000 mg/kg) and oleuropein (10 and 25 mg/kg) were administered orally twice daily every day for 30 wk. The extract and oleuropein significantly inhibited increases in skin thickness and reductions in skin elasticity, and skin carcinogenesis and tumor growth. Furthermore, they prevented increases in the expression of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13 as well as in levels of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in the skin. Based on histological evaluation, they prevented increases in the expression of Ki-67 and CD31-positive cells induced by the irradiation. These results suggest that the preventative effects of the olive leaf extract and oleuropein on chronic UVB-induced skin damage and carcinogenesis and tumor growth may be due to inhibition of the expression of VEGF, MMP-2, MMP-9, and MMP-13 through a reduction in COX-2 levels.

Effects of a turmeric extract (Curcuma longa) on chronic ultraviolet B irradiation-induced skin damage in melanin-possessing hairless mice.

Turmeric (the rhizomes of Curcuma longa L., Zingiberacease) is widely used as a dietary pigment and spice, and has been traditionally used for the treatment of inflammation, skin wounds and hepatic disorders in Ayurvedic, Unani and Chinese medicine. Although the topical application or oral administration of turmeric is used to improve skin trouble, there is no evidence to support this effect. The aim of this study was to clarify whether turmeric prevents chronic ultraviolet B (UVB)-irradiated skin damage. We examined the effects of a turmeric extract on skin damage including changes in skin thickness and elasticity, pigmentation and wrinkling caused by long-term, low-dose ultraviolet B irradiation in melanin-possessing hairless mice. The extract (at 300 or 1000 mg/kg, twice daily) prevented an increase in skin thickness and a reduction in skin elasticity induced by chronic UVB exposure. It also prevented the formation of wrinkles and melanin (at 1000 mg/kg, twice daily) as well as increases in the diameter and length of skin blood vessels and in the expression of matrix metalloproteinase-2 (MMP-2). Prevention of UVB-induced skin aging by turmeric may be due to the inhibition of increases in MMP-2 expression caused by chronic irradiation.