Ozonated Sunflower Oil (OSO) Alleviates Inflammatory Responses in Oxazolone-Induced Atopic Dermatitis (AD)-Like Mice and LPS-Treated RAW 264.7 Cells.

Ozone, a highly reactive oxidant molecule, is widely used as a complementary therapy for various skin diseases, including wound healing, pressure ulcers, diabetic foot, and infections. However, there is limited research on the effectiveness of ozone for atopic dermatitis (AD). Ozonated sunflower oil (OSO) is an active ingredient obtained from partially ozonated sunflower oil (SO). OSO markedly reduced the LPS-induced increase in IL-1ß and nitric oxide (NO) levels in RAW 264.7 mouse macrophage cells. Oxazolone (OXZ) was applied to hairless mice to induce AD-like skin symptoms and immune response. OSO significantly alleviated the OXZ-induced increases in the number of infiltrating mast cells, epidermal thickness, AD symptoms, thymic stromal lymphopoietin (TSLP), and filaggrin, as well as the serum levels of NO, IgE, IL-1ß, and TNF-α. Furthermore, OSO inhibited the IL-4/STAT3/MAPK pathway and the expression of NF-κB. Our results suggest that OSO treatment could relieve AD-mediated skin damage through its anti-inflammatory and antioxidant activities. Therefore, it can be used as a therapeutic agent against AD-related skin diseases.

Effect of A. polygama APEE (Actinidia polygama ethanol extract) or APWE (Actinidia polygama water extract) on wrinkle formation in UVB-irradiated hairless mice.

BACKGROUND: Actinidia polygama (silver vine) is considered a medical plant which has been used in oriental medicine. It has been used for the treatment of pain, gout, rheumatoid arthritis, and inflammation. Few studies reported on the effect of Actinidia polygama (silver vine) on skin photoaging. OBJECTIVE: To evaluate the anti-photoaging effect of the ethanol and water extracts of A. polygama (APEE and APWE, respectively) in UVB-irradiated hairless mice. METHODS: SKH-1 hairless mice were exposed to UVB irradiation (30-60 mJ/cm2 ), following orally APEE or APWE oral administration for 10 weeks. We examined the effect on winkle improvement by a measuring Fullscope, PRIMOS, Craniometer, and Cutometer. Furthermore, we analyzed histological changes in mouse dorsal skin through hematoxylin and eosin (H&E) and Masson's trichrome (MT) staining. The expression of matrix metalloproteinase (1, 3, and 9) was analyzed by immunoblotting. RESULTS: Oral administration of APEE or APWE at 100 or 200 mg/kg in UVB-irradiated mice alleviated the symptoms of skin aging, such as wrinkling, epidermal hyperplasia, and water loss. In addition, the APEE or APWE oral administration increased skin elasticity by enhancing the production of type I collagen, elastin, and hyaluronic acid synthase and downregulating matrix metalloproteinase (1, 3, and 9) expression. CONCLUSION: Based on results for our study, APEE or APWE could protect the UVB-mediated skin wrinkle and is new target for the developing anti-wrinkle cosmetics.

Effects of Oral Administration of Lactiplantibacillus Plantarum APsulloc 331261 (GTB1TM) Isolated from Green Tea on Atopic Dermatitis (AD)-like Skin Lesion Mouse Models.

Background: Probiotics are known to improve atopic dermatitis (AD) by inhibiting T helper 2 (Th2)-related reactions, restoring the Th2/T helper1 (Th1) cytokine ratio. The most popular probiotic is Lactiplantibacillus plantarum (L. plantarum), which is widely used in the food and pharmaceutical industries. L. plantarum APsulloc 331261 (GTB1) used in this study was isolated from green tea. Materials and Methods: The effectiveness of oral GTB1 administration in improving AD was evaluated by visual evaluation, comparison of the lymph node sizes and spleen weights, histological evaluation, RT-qPCR, ELISA, and IHC analysis in the mouse model. Results: GTB1 improved AD symptoms, reduced epidermal thickness and mast cell numbers, decreased lymph node size and the spleen weight, increased filaggrin and loricrin protein levels, downregulated Th2 expression, and upregulated Th1 expression in a colony-forming unit-dependent manner. Conclusion: Oral administration of GTB1 isolated from green tea (Camellia sinensis) improved the AD symptoms, reduced hypersensitivity reaction, and increased the skin barrier function. Finally, it is involved in AD improvement by restoring the Th2/Th1 cytokine balance.

A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice.

Lindera obtusiloba extract (LOE), a traditional herbal medicine used to enhance blood circulation and to reduce inflammation, induced NO-mediated endothelium-dependent relaxation, and reduced the formation of reactive oxygen species (ROS). The study investigated whether LOE improves endothelial dysfunction and reduces plaque inflammation and progression by inhibiting ROS generation in a mouse model of atherosclerosis. Eight-week-old apolipoprotein E-deficient (apoE-/-) mice fed with a western diet (WD) were randomized into different groups by administering vehicle (0.5% carboxymethylcellulose (CMC)), LOE (100 mg/kg/day), or losartan (30 mg/kg/day) by gavage until the age of 28 weeks. Fourteen male C57BL/6 mice that were fed normal chow and treated with CMC were used as negative controls. Similar to losartan treatment, LOE treatment induced the concentration-dependent relaxation of aorta rings in WD-fed apoE-/- mice. LOE treatment significantly reduced the vascular ROS formation and expression of NADPH oxidase subunits, including p22phox and p47phox. Compared with WD-fed apoE-/- mice, mice exposed to chronic LOE treatment exhibited reductions in plaque inflammation-related fluorescence signals and atherosclerotic lesions. These effects were greater than those of losartan treatment. In conclusion, LOE treatment improves endothelial dysfunction and reduces plaque inflammation as well as lesion areas by reducing vascular NADPH oxidase-induced ROS generation in a mouse model of atherosclerosis.

The Redox-sensitive Induction of the Local Angiotensin System Promotes Both Premature and Replicative Endothelial Senescence: Preventive Effect of a Standardized Crataegus Extract.

Endothelial senescence, characterized by an irreversible cell cycle arrest, oxidative stress, and downregulation of endothelial nitric oxide synthase (eNOS), has been shown to promote endothelial dysfunction leading to the development of age-related vascular disorders. This study has assessed the possibility that the local angiotensin system promotes endothelial senescence in coronary artery endothelial cells and also the protective effect of the Crataegus extract WS1442, a quantified hawthorn extract. Serial passaging from P1 to P4 (replicative senescence) and treatment of P1 endothelial cells with the eNOS inhibitor L-NAME (premature senescence) promoted acquisition of markers of senescence, enhanced ROS formation, decreased eNOS expression, and upregulation of angiotensin-converting enzyme (ACE) and AT1 receptors. Increased SA-ß-gal activity and the upregulation of ACE and AT1R in senescent cells were prevented by antioxidants, an ACE inhibitor, and by an AT1 receptor blocker. WS1442 prevented SA-ß-gal activity, the downregulation of eNOS, and oxidative stress in P3 cells. These findings indicate that the impairment of eNOS-derived nitric oxide formation favors a pro-oxidant response triggering the local angiotensin system, which, in turn, promotes endothelial senescence. Such a sequence of events can be effectively inhibited by a standardized polyphenol-rich extract mainly by targeting the oxidative stress.

Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated protein kinase (AMPK)-mediated glucose uptake and adipogenesis pathways.

Dibenzoylmethane (DBM) has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK) and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor). DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4) was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS), was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

Rhus verniciflua extract modulates survival of MCF-7 breast cancer cells through the modulation of AMPK-pathway.

Rhus verniciflua STOKES (RVS) is used as an anti-cancer agent in traditional herbal medicine. However, the underlying molecular mechanism of its action is poorly understood. Here, we elucidated the mechanism of the anti-cancer mechanism of RVS in MCF-7 human breast cancer cells. We found that RVS increased the phosphorylation of AMP-activated protein kinase (AMPK) and downstream acetyl-CoA carboxylase (ACC) and suppressed cell viability in an AMPK-dependent fashion. RVS also induced an increase in reactive oxygen species (ROS) levels. RVS-induced AMPK phosphorylation was not observed in the presence of N-acetyl-cysteine (NAC), which indicated that ROS is associated with RVS-induced AMPK phosphorylation. In addition, fluorescent staining (Annexin V/propidium iodide) revealed that RVS increased the expression of Annexin V, which indicates that RVS leads to cancer-induced apoptosis. Moreover, RVS increased the phosphorylation of p53 and the expression of Bax. The inhibition of AMPK blocked RVS-induced p53 phosphorylation and Bax expression, which suggests that AMPK is involved in RVS-induced cancer apoptosis. Taken together, these results demonstrate that RVS has anti-tumor effects on MCF-7 cells through an AMPK-signaling pathway.

An ethanolic extract of Lindera obtusiloba stems, YJP-14, improves endothelial dysfunction, metabolic parameters and physical performance in diabetic db/db mice.

Lindera obtusiloba is a medicinal herb traditionally used in Asia for improvement of blood circulation, treatment of inflammation, and prevention of liver damage. A previous study has shown that an ethanolic extract of Lindera obtusiloba stems (LOE) has vasoprotective and antihypertensive effects. The possibility that Lindera obtusiloba improves endothelial function and metabolic parameters in type 2 diabetes mellitus (T2DM) remains to be examined. Therefore, the aim of the present study was to determine the potential of LOE to prevent the development of an endothelial dysfunction, and improve metabolic parameters including hyperglycemia, albuminuria and physical exercise capacity in db/db mice, an experimental model of T2DM. The effect of LOE (100 mg/kg/day by gavage for 8 weeks) on these parameters was compared to that of an oral antidiabetic drug, pioglitazone (30 mg/kg/day by gavage). Reduced blood glucose level, body weight and albumin-creatinine ratio were observed in the group receiving LOE compared to the control db/db group. The LOE treatment improved endothelium-dependent relaxations, abolished endothelium-dependent contractions to acetylcholine in the aorta, and normalized the increased vascular oxidative stress and expression of NADPH oxidase, cyclooxygenases, angiotensin II, angiotensin type 1 receptors and peroxynitrite and the decreased expression of endothelial NO synthase in db/db mice. The angiotensin-converting enzyme (ACE) activity was reduced in the LOE group compared to that in the control db/db group. LOE also inhibited the activity of purified ACE, COX-1 and COX-2 in a dose-dependent manner. In addition, LOE improved physical exercise capacity. Thus, the present findings indicate that LOE has a beneficial effect on the vascular system in db/db mice by improving endothelium-dependent relaxations and vascular oxidative stress most likely by normalizing the angiotensin system, and also on metabolic parameters, and these effects are associated with an enhanced physical exercise capacity.

Decaffeinated green tea extract improves hypertension and insulin resistance in a rat model of metabolic syndrome.

BACKGROUND: Oxidative stress and endothelial dysfunction are closely associated with hypertension and insulin resistance (IR) in metabolic syndrome (MetS). It is still controversial whether green tea extract (GTE) may have blood pressure (BP) lowering effect. Decaffeinated GTE might be presumed to have strong antioxidative effect and BP-lowering effect as compared with catechins. Thus we investigated whether decaffeinated-GTE could attenuate hypertension and IR by improving endothelial dysfunction and reducing oxidative stress in a rat model of MetS. METHODS AND RESULTS: 20 Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 13 weeks old, MetS rats, were randomized into a saline treated group (OLETF; n = 10) and a group treated with decaffeinated-GTE (25 mg/kg/day) (GTE-OLETF; n = 10). Intraperitoneal glucose tolerance tests and BP measurements were performed at 13 and 25 weeks. Decaffeinated-GTE significantly reduced BP (OLETF vs. GTE-OLETF; 130 ± 7 vs. 121 ± 3 mmHg, p = 0.01), fasting/postprandial 2 h glucose (141 ± 18/159 ± 13 vs. 115 ± 7/132 ± 16 mg/dL, p = 0.009/0.002) and insulin levels (4.8 ± 2.3 vs. 2.4 ± 1.3 ng/mL, p < 0.001). Decaffeinated-GTE significantly reduced vascular reactive oxygen species (ROS) formation and NADPH oxidase activity, and improved endothelium dependent relaxation in the thoracic aorta of OLETF rats. Decaffeinated-GTE also suppressed the expression of p47 and p22phox (NADPH oxidase subunits) in the immunohistochemical staining, and stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) and Akt in the immunoblotting of aortas. CONCLUSIONS: Decaffeinated-GTE reduced the formation of ROS and NADPH oxidase activity and stimulated phosphorylation of eNOS and Akt in the aorta of a rat model of MetS, which resulted in improved endothelial dysfunction and IR, and eventually lowered BP.

An ethanolic extract of Lindera obtusiloba stems causes NO-mediated endothelium-dependent relaxations in rat aortic rings and prevents angiotensin II-induced hypertension and endothelial dysfunction in rats.

Lindera obtusiloba is a medical herb traditionally used in Asia for the improvement of blood circulation, treatment of inflammation, and prevention of liver damage. The possibility that L. obtusiloba affects vascular reactivity remains to be examined. Therefore, the aim of the present study was to evaluate both the in vitro and in vivo vascular effects of an ethanolic extract of L. obtusiloba stems (LOE). Vascular reactivity was assessed in organ chambers using rat aortic rings and the activation of endothelial NO synthase (eNOS) in cultured bovine aortic endothelial cells. LOE induced endothelium-dependent relaxations, which were abolished by inhibitors of nitric oxide synthase (N (ω)-nitro-L: -arginine) and guanylyl cyclase (1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-L-one), significantly reduced by inhibitors of PI3 kinase (wortmannin and LY294002), and not affected by inhibitors of cyclooxygenase (indomethacin) and endothelium-derived hyperpolarizing factor-mediated responses (charybdotoxin plus apamin). LOE prevented contractile responses to phenylephrine and angiotensin II in rings with endothelium, but not in those without endothelium. LOE caused a concentration-dependent phosphorylation of Akt at Serine473 and eNOS at Serine1177 in endothelial cells. Thereafter, the vasoprotective effect of LOE was investigated in an experimental model of hypertension in rats. Intake of LOE prevented the angiotensin II-induced increase in systolic blood pressure, and endothelial dysfunction to acetylcholine and oxidative stress as assessed using dihydroethidine in aortic rings. The present findings indicate that LOE has vasoprotective and antihypertensive properties most likely by stimulating the endothelial formation of NO and inhibiting oxidative stress.

Clinical evaluation of the depigmenting effect of Glechoma Hederacea extract by topical treatment for 8 weeks on UV-induced pigmentation in Asian skin.

UV is a major environmental factor inducing and worsening the symptoms of hyperpigmentation disorders such as freckles, melasma and solar lentigines. During UV-induced skin inflammatory reactions, pro-inflammatory mediators initiate the production of various paracrine melanogenic factors (α-MSH, SCF, ET-1, bFGF and NO) in keratinocytes. These paracrine factors activate melanin synthase in melanocytes through the paracrine network between melanocytes and keratinocytes. Glechoma hederacea (GH) is a herbal plant used in oriental medicine to treat inflammation. Its anti-inflammatory effects, through inhibition of NO synthesis (NOS) as well as the pro-inflammatory cytokine TNF-α, have been reported. However, there has not yet been any report of a depigmenting effect. In this study of placebo-controlled, 8 week topical treatment with a 1% GH extract lotion on UV-induced pigmented spots in female Asian subjects, significant effects of anti-inflammation and depigmenting were proven. The depigmenting effect of GH seems to be related to inhibiting the secretion of pro-inflammatory cytokines and melanogenic paracrine factors from keratinocytes, rather than to direct inhibition of melanogenic activities in melanocytes.

Lysimachia clethroides extract promote vascular relaxation via endothelium-dependent mechanism.

Lysimachia clethroides is widely used in traditional herbal medicine for many purposes, especially for blood vessel-related diseases in Korea and East Asia. Experiments were undertaken to determine whether hydro-alcoholic extract obtained from L. clethroides (LCE) has vasorelaxant activity in the rat aorta rings and, if so, to elucidate the underlying mechanism. Rat aorta rings were suspended in organ chambers for the measurement of changes in isometric tension in the presence or absence of several inhibitors. LCE induced endothelium-dependent vasodilation (ED50 = 6.1 mug/mL) and that was abolished by nitric oxide synthase inhibitor, N-nitro-L-arginine, and guanylyl cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one, PI3-kinase inhibitor, wortmannin, and cell permeable superoxide dismutase. In addition, LCE decreased vessels contraction by phenylephrine. Prostaglandin synthesis inhibitor, indometacin, and inhibitors of endothelium-derived hyperpolarizing factor, charybdotoxin plus apamin, did not affect vasodilatory effect of LCE. In cultured endothelial cells, LCE-induced phosphorylation of serine 1177-endothelial nitric oxide synthase and serine 473-Akt. LCE inhibited strongly nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in smooth muscle cells and angiotensin II-induced contraction of rat aorta. Finally, increased oxidative stress in rat aorta-induced by angiotensin II is ameliorated by LCE. Taken together, LCE induces an endothelium-dependent vasodilation and might be involved, at least in part, the activation of the nitric oxide-cyclic guanosine monophosphate pathway. In addition, LCE decreases oxidative stress in aorta by inhibition of NADPH oxidase activity. The present findings indicate that LCE could be a candidate of herbal medicine for cardiovascular diseases associated with disturbed NO production and endothelial dysfunction.