Star fruit extract and C-glycosylated flavonoid components have potential to prevent air pollutant-induced skin inflammation and premature aging.

Air pollution adversely affects skin, leading to skin inflammation and premature skin aging. Plant derived antioxidant compounds have been considered to be promising in discovery of effective agents for the protection of skin from the damage by air pollutants. Our previous studies demonstrated that Averrhoa carambola fruit (known as star fruit) is rich in flavonoid C-glycosides with unique structures and potent antioxidant activity. Thus, the star fruit extract (SFE) and main flavonoid C-glycoside components, carambolasides I, J, and P (1-3), carambolaflavone B (4), and isovitexin 2″-O-α-L-rhamnoside (5), were investigated for the activity against air pollutant stress in human epidermis. As a result, SFE and compounds 1-5 exhibited significant inhibitory activity against protein carbonylation in oxidative-stressed stratum corneum with the best activity being shown by compound 3. SFE and compounds 2-5 were also active against engine exhaust-induced protein carbonylation in stratum corneum. When further evaluated, SFE and compound 3 significantly inhibited gene expression of the key inflammation mediators IL-1α and COX-2 in PM-stressed keratinocytes. The results indicated that SFE and the flavonoid C-glycosides are potentially effective against air pollutant-induced skin inflammation and premature aging.

Decreased levels of endocytic collagen receptor Endo180 in dermal fibroblasts lead to decreased production of type I collagen and increased expression of matrix metalloproteinase-1.

BACKGROUND: Endo180 is involved in collagen remodeling by incorporating extracellular degraded collagen. Ultraviolet irradiation of dermal fibroblasts reduces Endo180 expression, which affects collagen fiber remodeling. However, it is unclear whether the decrease in Endo180 is directly related to the decrease in type I collagen fibers during photoaging. We aimed to clarify the relationship between Endo180 reduction and the decrease in type I collagen fibers observed in photoaged dermis. METHODS: Endo180 was reduced in normal human dermal fibroblasts using RNAi. Endo180 knockdown cells were inoculated into collagen gels. The influence of Endo180 knockdown was evaluated by measuring mRNA expression of collagen fiber remodeling-related factors and collagen gel contraction. The collagen state and oxidative stress in the collagen gels were also measured. RESULTS: Endo180 knockdown cells, which were confirmed by gelatin uptake inhibition, showed upregulation of matrix metalloproteinase-1 and downregulation of type I collagen mRNA expression when cultured in collagen gels. The contractility of the collagen gel was reduced by Endo180 knockdown. The collagen state in the extracellular matrix of the collagen gels containing Endo180 knockdown fibroblasts showed increased amounts of 3/4 fragmented collagen and denatured collagen and decreased type I collagen synthesis. In addition, an increase in intracellular oxidative stress was observed. CONCLUSIONS: This study confirmed that the decrease in Endo180 caused a failure in collagen fiber formation and a decrease in collagen production, reproducing the photoaging dermal structural changes. This suggests that the decrease in Endo180 may be involved in wrinkle formation, which is a characteristic of photoaged skin.

Interleukin-1 alpha derived from ultraviolet B-exposed keratinocytes is associated with a decrease of endocytic collagen receptor Endo180.

BACKGROUND: Endo180 contributes to the remodeling of the collagen fibers that comprise the dermal matrix due to the internalization of extracellular collagen fragments. In the sun-exposed elder skin, an accumulation of collagen fragments was observed in the dermal matrix which was associated with a reduction in Endo180 in the dermal fibroblasts. This suggests that the loss of Endo180 results in the accumulation of collagen fragments in the surrounding fibroblasts and causes interference with dermal matrix remodeling via collagen fibers. The purpose of the study was to identify a mechanism by which ultraviolet B (UVB) exposure induces a loss of Endo 180 with a specific focus on the crosstalk between keratinocytes and fibroblasts. METHODS: Endo180 from normal human dermal fibroblasts, which were cultured with a conditioned medium (CM) of UVB-exposed keratinocytes, was examined using mRNA expression, protein levels and collagen internalization by quantitative RT-PCR, ELISA, and flow cytometry, respectively. RESULTS: Although UVB irradiation to fibroblasts failed to reduce Endo180, the CM of UVB-exposed keratinocytes reduced Endo180 in the fibroblasts. Collagen internalization into the fibroblasts was decreased and was associated with a loss of Endo180. Among cytokines secreted from UVB-exposed keratinocytes, IL-1α solely reduced Endo180, and the reduction induced by the CM of UVB-exposed keratinocytes was abolished by the presence of IL-1RA. CONCLUSIONS: These results indicate that a substance secreted from UVB-exposed keratinocytes regulates Endo180 expression and that IL-1α may play an important role in the maintenance of Endo180.

Inhibitory effects of α-mangostin on mammalian DNA polymerase, topoisomerase, and human cancer cell proliferation.

We found that the ethanol extract of mangosteen (Garcinia mangostana L.) fruit rind had a strong inhibitory effect on mammalian DNA polymerase (pol) activity and isolated α-mangostin as a potent pol inhibitor from the extract. In this study, the inhibitory activities against mammalian pols by α-mangostin and its related five compounds, 3-isomangostin, xanthone, 9,10-anthraquinone, 9-anthracenecarboxylic acid, and anthracene, were investigated. α-Mangostin was the most potent inhibitor of the mammalian pol species among the tested compounds, with IC50 values of 14.8-25.6 µM. This compound also inhibited human DNA topoisomerases (topos) I and II activities with IC50 values of 15.0 and 7.5 µM, respectively, but did not inhibit the activities of other DNA metabolic enzymes tested. α-Mangostin also did not directly bind to double-stranded DNA as determined by thermal transition analysis. α-Mangostin was found to suppress human colon HCT116 carcinoma cell proliferation with an LC50 of 18.5 µM, inhibit the activity of cellular topos, halt cell cycle in the G2/M phase, and induce apoptosis. These results suggest that decreased proliferation by α-mangostin may be a result of the inhibition of cellular topos rather than pols, and α-mangostin might be an anticancer chemotherapeutic agent.

Effect of oral Kohki tea on bladder dysfunction induced by severe partial outlet obstruction.

PURPOSE: Extracts of the leaves of Engelhardtia chrysolepis, a subtropical plant that grows wild in southern China, have been used medicinally in east Asia for hundreds of years. A standard extract named Kohki tea (Maruzen Pharmaceuticals, Onomichi City, Japan) is sold over the counter in Japan as a sweet tea shown to confer many beneficial effects on general health and well-being. The tea contains strong antioxidants, including several dihydroflavonol glycosides. The results of previous studies show that natural products with antioxidant activities provide protective effects on the bladder of rabbits with partial outlet obstruction. We determined in vivo and in vitro whether oral pretreatment of rabbits with Kohki tea protects the bladder from dysfunction induced by partial outlet obstruction. MATERIALS AND METHODS: A total of 28 New Zealand White rabbits were separated into 4 groups of 7 each. Rabbits in groups 1 and 2 were treated by gavage with 100 mg./kg. Kohki tea daily in distilled water, while those in groups 3 and 4 were given distilled water. After 4 weeks of daily oral administration each rabbit was sedated, the bladder was catheterized and cystometry was performed at a filling rate of 1 ml. per minute. At the completion of cystometry the rabbits were immediately anesthetized. Moderate outlet obstruction was created in groups 1 and 3, and sham surgery was performed in groups 2 and 4. Treatment was continued for an additional 4 weeks, when each rabbit was sedated and cystometry was repeated. After cystometry the bladder was exposed through a midline incision, excised, weighed and 4 strips of bladder body were cut for contractility studies. The balance of the bladder was separated between smooth muscle and mucosa by blunt dissection, frozen in liquid nitrogen and stored at -70C for biochemical analyses. RESULTS: Partial outlet obstruction stimulated similar increases in the bladder weight of all obstructed rabbits. Partial outlet obstruction resulted in a significant decrease in bladder compliance in all obstructed animals. However, the bladder of obstructed rabbits given Kohki tea were significantly more compliant than those given water. Voiding pressures in the control group and the obstructed group given distilled water were approximately equal, while obstructed rabbits given Kohki tea showed significantly higher maximal voiding pressure. The contractile responses to all forms of stimulation were reduced by obstruction to a significantly greater degree in the rabbits not given tea than in those given tea. Sarcoplasmic reticulum Ca2+-adenosine triphosphatase enzyme activity of the bladder was significantly reduced in obstructed rabbits given vehicle but activity was not reduced in obstructed rabbits given Kohki tea. CONCLUSIONS: Kohki tea had a significant protective effect on bladder function, contractile responses and bladder biochemistry in rabbits with moderate to severe partial outlet obstruction.