In the present study, we demonstrate an inhibitory effect of (+)-catechin on oxidative stress-induced apoptosis in fibroblasts, accompanied by amelioration of the phosphorylation of p38 and JNK induced by oxidative stress.
We focused on fibroblasts because they participate in skin maintenance and renewal. In the skin, fibroblasts play a key role in the production of extracellular matrix components, including collagen, elastin, and hyaluronic acid. In clinical aesthetic medicine, epidermal or intradermal injection of hyaluronic acid is performed to obtain glossy and healthy skin (microinjections of hyaluronic acid, vitamins, minerals, and amino acids into the superficial layer of the skin)
. Other techniques, such as implanting activated fibroblasts in the skin, are also known to revive the skin to be glossy and healthy (intradermal injection of cultivated skin fibroblasts into wrinkles)
[16–18]. However, these therapies are associated with a high cost and may provoke adverse events, including misplacement, allergy, nodules, necrosis, abscesses, and rejection. In contrast, the use of health supplements, such as green tea and food-derived active substances, is a safer and beneficial anti-aging method.
The integrity and functions of the skin barrier may be impaired by excessive exposure to allergens, chemicals, ultraviolet light, and dehydration. Failure of the skin barrier would subsequently lead to infections with pathogens and result in inflammatory responses. Locally produced reactive oxygen species are also known to inhibit the growth of epithelial cells and fibroblasts by inducing apoptosis and inhibiting collagen and hyaluronic acid production, all of which have been implicated in aging processes leading to skin wrinkles and sagging. Our present study suggests that (+)-catechin is a potential candidate for suppressing oxidative stress-induced apoptosis of skin fibroblasts, which may in turn reverse the reduction of fibroblast-derived production of collagen and hyaluronic acid. Other reports suggest that EGCG, another type of catechin, is also a potential candidate for suppressing oxidative stress-induced apoptosis of skin fibroblasts
; however, our present study showed that (+)-catechin is less cytotoxic than EGCG, suggesting that for therapeutic and preventive purposes (+)-catechin may be superior to EGCG.
To elucidate the underlying mechanisms by which (+)-catechin inhibits oxidative stress-induced apoptosis in fibroblasts, we focused on the effects of (+)-catechin on the phosphorylation of p38 and JNK, both of which are key molecules for oxidative stress-induced apoptosis
. JNK and p38 belong to the family of stress kinases and have been shown to be required for biological stress responses, such as apoptosis induced by UV, radiation, oxidative stress, heat shock, and tumor necrosis factor (TNF)-α stimulation. It has been reported that H2O2 signaling through TNF receptor 1 selectively activates JNK and p38
[20, 21]. JNK plays an important role in controlling cell death and is known to affect the function of Bcl-2 family molecules, which suppress apoptosis. Specifically, phosphorylation of Bcl-2 by JNK results in the inhibition of Bcl-2 function and therefore induces the activation of apoptosis
[20, 21]. In contrast, p38 MAPK is known to be involved in the activation of apoptosis-modulating proteins, such as Fas and Bax
. Collectively, our present study suggests that (+)-catechin exerts anti-apoptotic effects against oxidative stress by inhibiting the phosphorylation of p38 and JNK. The precise mechanisms by which (+)-catechin suppresses the phosphorylation of JNK and p38 will be a future research topic.
Although (+)-catechin was found to exert anti-apoptotic effects in the present study, previous reports have shown both pro-apoptotic and anti-apoptotic effects of catechins. In particular, EGCG, a molecule in the same catechin group, was suggested to play a role in growth inhibition and apoptosis induction in a variety of cancer cells
. In contrast, EGCG was reported to have an anti-apoptotic effect in renal mesangial cells
 and endothelial cells
, similar to our results in the present study. Therefore, we speculate that the effect of catechins on apoptosis may vary according to cell type and the nature of pathogenesis. Given the different cell-specific responses of catechins, it is important to establish an appropriate strategy for using catechins for treatment and prevention of various diseases. It would be ideal for catechins have suppressive actions against cancers and protective effects for organs such as the kidneys and cardiovascular system. Accumulating evidence on the preventive effect of catechins and green tea against various systemic diseases, including cancers, diabetes, and hypertension, suggests little potential harm to human health from high consumption of catechins and green tea for maintenance of skin beauty.