Protective skin aging effects of cherry blossom extract (Prunus Yedoensis) on oxidative stress and apoptosis in UVB-irradiated HaCaT cells.

Extracts of the cherry blossom plant have been reported to exert various biological effects on human cells. However, no previous investigations have examined the antioxidant and anti-apoptotic effects of these extracts on ultraviolet B (UVB) radiation-induced skin aging. This study explores the underlying mechanisms of the antioxidant and anti-apoptotic effects of cherry blossom extract (CBE) in human keratinocyte (HaCaT) cells. HaCaT cells were treated with CBE at concentrations of 0.5, 1.0, and 2.0% for 24 h and then irradiated with UVB (40 mJ/cm2). CBE effectively and dose-dependently decreased the levels of reactive oxygen species and malondialdehyde, while increasing the activities of superoxide dismutase and glutathione peroxidase. Pretreatment with 1 and 2% CBE attenuated UVB-induced DNA damage by reducing the formation of cyclobutane pyrimidine dimers and 8-hydroxy-20-deoxyguanosine. Furthermore, CBE also prevented UVB-induced apoptosis and significantly downregulated B cell lymphoma 2 (Bcl-2)-associated X, cytochrome-c, and caspase-3 expression, while upregulating Bcl-2 expression. Taken together, these results indicate that CBE protects HaCaT cells from UVB-induced oxidative stress and apoptosis and suggest that CBE could be a potent antioxidant against skin aging.

PM2.5 Exposure Elicits Oxidative Stress Responses and Mitochondrial Apoptosis Pathway Activation in HaCaT Keratinocytes.

BACKGROUND:: PM2.5 (aerodynamic diameter ≤ 2.5 µm) is a dominant and ubiquitous air pollutant that has become a global concern as PM2.5 exposure has been linked to many adverse health effects including cardiovascular and pulmonary diseases. Emerging evidence supports a correlation between increased air PM2.5 levels and skin disorders although reports on the underlying pathophysiological mechanisms are limited. Oxidative stress is the most common mechanism of PM2.5-induced adverse health effects. This study aimed to investigate PM2.5-induced oxidative damage and apoptosis in immortalized human keratinocyte (HaCaT) cells. METHODS:: HaCaT cells were exposed to 0, 25, 50, 100, or 200 µg/ml PM2.5 for 24 h. Reactive oxygen species (ROS) generation, lipid peroxidation products, antioxidant activity, DNA damage, apoptotic protein expression, and cell apoptosis were measured. RESULTS:: PM2.5 exposure (0-200 µg/ml) for 24 h resulted in increased ROS levels (arbitrary unit: 201.00 ± 19.28, 264.50 ± 17.91, 305.05 ± 19.57, 427.95 ± 18.32, and 436.70 ± 17.77) and malondialdehyde production (0.54 ± 0.05 nmol/mg prot, 0.61 ± 0.06 nmol/mg prot, 0.68 ± 0.05 nmol/mg prot, 0.70 ± 0.05 nmol/mg prot, and 0.76 ± 0.05 nmol/mg prot), diminished superoxide dismutase activity (6.47 ± 0.28 NU/mg prot, 5.97 ± 0.30 NU/mg prot, 5.15 ± 0.42 NU/mg prot, 4.08 ± 0.20 NU/mg prot, and 3.76 ± 0.37 NU/mg prot), and increased DNA damage and apoptosis in a dose-dependent manner in HaCaT cells. Moreover, cytochrome-c, caspase-3, and caspase-9 expression also increased proportionately with PM2.5 dosing. CONCLUSION:: PM2.5 might elicit oxidative stress and mitochondria-dependent apoptosis that likely manifests as skin irritation and damage.

Zinc(II)-curcumin accelerates the healing of acetic acid-induced chronic gastric ulcers in rats by decreasing oxidative stress and downregulation of matrix metalloproteinase-9.

Gastric ulcers form as a result of a multifaceted process which includes acid secretion, reactive oxygen species generation and extracellular matrix (ECM) degradation. The aim of this study was to investigate the possible mechanisms underlying the anti-ulcerogenic effects of the Zn(II)-curcumin complex, a curcumin derivative, on the healing of acetic acid-induced gastric ulcers in rats. The severely ulcerated gastric mucosa of control animals had a lower glutathione level (GSH) and superoxide dismutase activity (SOD), and increased malondialdehyde (MDA) content compared to sham operated rats (P<0.001). Zn(II)-curcumin solid dispersions (equivalent to 12, 24 and 48 mg/kg) dose-dependently reduced the gastric ulcer index, significantly increased SOD activity and GSH levels, and reduced the MDA content and matrix metalloproteinase-9 (MMP-9) mRNA expression in the gastric mucosa (P<0.05, compared to control animals). Zn(II)-curcumin exerted a greater anti-ulcerogenic effect than curcumin at the same dose (24 mg/kg), leading to a reduced severity of gastric ulcers, lower MDA content, and increased SOD activity and GSH levels (P<0.05). In conclusion, these results confirm that the Zn(II)-curcumin complex possesses an enhanced mucosal barrier defense activity compared to curcumin alone, due to its synergistic ability to decrease oxidative stress and attenuate MMP-9-mediated inflammation.

Novel role of Zn(II)-curcumin in enhancing cell proliferation and adjusting proinflammatory cytokine-mediated oxidative damage of ethanol-induced acute gastric ulcers.

Alcohol consumption can induce gastric ulcers and zinc deficiency. Zinc complexes were reported to have anti-ulcer activity as it acts as an anti-inflammatory and antioxidant. Zn(II)-curcumin complex and its solid dispersions (SDs) were synthesized and evaluated for its gastroprotective activity and mechanism against ethanol-induced ulcer. The Swiss murine fibroblast cell line (3T3) was used as an alternative in vitro model to evaluate the effects of Zn(II)-curcumin on cell proliferation. Zn(II)-curcumin were administered orally for seven consecutive days prior to induction of ulcers using ethanol. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that solid dispersions (SDs) of Zn(II)-curcumin (2.5-20 µM) enhanced the proliferation of 3T3 cells more significantly than curcumin at the same concentrations (P<0.01). Oral administration of Zn(II)-curcumin (12, 24 and 48 mg/kg) SDs dose-dependently prevented formation of ulcer lesions induced by ethanol. The levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and oxidative stress superoxide dismutase (SOD), glutathione peroxidase (GPX-Px), malonaldehyde (MDA) and H(+)-K(+)-ATPase were in the rats exposed to ethanol in ulceration have been altered. Zn(II)-curcumin prevented formation of ulcer lesions, significantly inhibited TNF-α and IL-6 mRNA expression, increased the activity of SOD and GSH-Px, reduced MDA levels and H(+)-K(+)-ATPase in mucosa of rats compared to controls (P<0.05). These findings suggest that the gastroprotective activity of Zn(II)-curcumin complex might contribute in stimulating cell proliferation and adjusting the proinflammatory cytokine-mediated oxidative damage to the gastric mucosa.

Gastroprotective and antidepressant effects of a new zinc(II)-curcumin complex in rodent models of gastric ulcer and depression induced by stresses.

Curcumin, a yellow pigment found in the rhizome of Curcuma loga, has been used to treat a variety of digestive and neuropsychiatric disorders since ancient times in China. Curcumin can chelate various metal ions to form metallocomplexes of curcumin which show greater effects than curcumin alone. This study investigated the antiulcerogenic and antidepressant effects of a Zn(II)-curcumin complex on cold-restraint stress (CRS)-induced gastric ulcers in rats, and on the forced swimming test (FST), tail suspension test (TST) and 5-hydroxy-l-tryptophan (5-HTP)-induced head twitch test in mice. CRS disrupted the rat mucosal barrier and induced gastric ulcers by decreasing the activities of the antioxidant enzymes, and increasing H(+)-K(+)-ATPase activity and malondialdehyde (MDA) level. Pretreatment with Zn(II)-curcumin (12, 24, and 48mg/kg) dose-dependently reversed these trends, reduced gastric lesions and H(+)-K(+)-ATPase activity, and increased antioxidant activities compared with control groups. Zn(II)-curcumin significantly increased HSP70 mRNA, and attenuated increased iNOS mRNA in the mucosa. Zn(II)-curcumin (17, 34, and 68mg/kg) also significantly decreased immobility time in the FST and TST, and enhanced 5-HTP-induced head twitches in mice. These results demonstrate that the Zn(II)-curcumin complex showed significant gastroprotective and antidepressant effects compared with curcumin alone via a synergistic effect between curcumin and zinc.

Gastroprotective effects of a new zinc(II)-curcumin complex against pylorus-ligature-induced gastric ulcer in rats.

Zn(II)-curcumin, a mononuclear (1:1) zinc complex of curcumin was synthesized and examined for its antiulcer activities against pylorus-ligature-induced gastric ulcer in rats. The structure of Zn(II)-curcumin was identified by elemental analysis, NMR and TG-DTA analysis. It was found that a zinc atom was coordinated through the keto-enol group of curcumin along with one acetate group and one water molecule. Zn(II)-curcumin (12, 24 and 48 mg/kg) dose-dependently blocked gastric lesions, significantly reduced gastric volume, free acidity, total acidity and pepsin, compared with control group (P<0.001) and curcumin alone (24 mg/kg, P<0.05). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that Zn(II)-curcumin markedly inhibited the induction of nuclear factor-kappa B (NF-kappaB), transforming growth factor beta(1) (TGF-beta(1)) and interleukin-8 (IL-8), compared with control group (P<0.05). These findings suggested that Zn(II)-curcumin prevented pylorus-ligation-induced lesions in rat by inhibiting NF-kappaB activation and the subsequent production of proinflammatory cytokines, indicating a synergistic effect between curcumin and zinc. An acute toxicity study showed that mice treated with SDs of Zn(II)-curcumin (2 g/kg) manifested no abnormal signs.