Effects of Psidium guajava Linn. leaf extract in Japanese subjects with knee pain: a randomized, double-blind, placebo-controlled, parallel pilot study.

The extract of Psidium guajava Linn. (guava) leaf was recently revealed to suppress the advance of osteoarthritis (OA) in rat anterior cruciate ligament-transection models. To investigate the efficacy of guava leaf extract in improving knee pain, which is a common symptom of OA, we conducted a double-blind parallel pilot clinical study in Japanese subjects with knee pain. The subjects, who had no medical history of knee treatment, were randomly assigned to two groups with similar total Japanese Knee Osteoarthritis Measure (JKOM) scores. During the 12-week intake period, the subjects in each group ingested 1 g of guava leaf extract (the guava group) or placebo (the placebo group) daily. At week 12, pain and stiffness in knees (one subcategory of JKOM score) in the guava group was significantly lower than that in the placebo group. Using the visual analogue scale (VAS) for knee pain, a significant association between treatment effect and test period was shown, and the guava group had a lower VAS score at week 12 than the placebo group. In conclusion, continuous intake of guava leaf extract might relieve knee pain, suggesting a potential preventive effect against OA symptoms.

Expression of steroidogenic enzymes in human sebaceous glands.

Androgens are well known to influence sebum synthesis and secretion. Various factors related to androgen biosynthesis are expressed in human sebaceous glands. In this study, immunohistochemical analysis of human skin specimens from 43 subjects indicated that various androgen-producing and -metabolizing enzymes were functionally localized to sebocytes accumulating lipid droplets and that the exclusive expression of 17ß-hydroxysteroid dehydrogenase type 2 (17ß-HSD2 (HSD17B2)) in sebaceous glands was negatively correlated with that of peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), which also significantly changed in an age-dependent manner. We also demonstrated that the changes of 17ß-HSD2 expression in human immortalized sebocytes (SZ95) influenced the expressions of sebogenesis-related factors. In addition, the overexpression of 17ß-HSD2 in SZ95 significantly increased the androstenedione production and markedly decreased the amounts of testosterone and dihydrotestosterone when DHEA was added externally. On the other hand, the phosphorylation of mammalian target of rapamycin, which is well known to induce sebum secretion and the onset and/or aggravation of acne, was increased by the addition of testosterone in the presence of IGF1 in hamster sebocytes. These results all indicated that local androgen biosynthesis and metabolism in human sebaceous glands could play a pivotal role in sebum synthesis and secretion.

Sex steroid synthesis in human skin in situ: the roles of aromatase and steroidogenic acute regulatory protein in the homeostasis of human skin.

Sex steroids have been known to play important roles in the homeostasis of human skin, but little is known about their biosyntheses in that tissue. In this study, we characterized the correlation between the concentrations of sex steroids and the expression levels of the factors involved in their synthesis or metabolism in human skin. The expression levels of aromatase (ARO) and steroidogenic acute regulatory protein (StAR) were positively correlated with estrogens and testosterone concentrations, respectively. We demonstrated that estrogen synthesis was markedly decreased by ARO inhibitor and that skins with higher ARO expression had thicker elastic fibers than those with lower ARO expression. While pregnenolone and testosterone concentrations were increased by cholesterol administration to epidermal keratinocytes. Scalp skin with higher StAR expression was cleared to have significantly fewer hair follicles than that with lower expression. Our results suggest that the status of ARO and StAR contribute to estrogen synthesis in situ, especially for the regulation of elastic fiber formation, and to testosterone synthesis, which may be associated with hair growth, respectively.

The role of estrogen-metabolizing enzymes and estrogen receptors in human epidermis.

Local estrogen metabolism and its sensitivities in the skin have been also suggested to contribute to skin homeostasis in addition to age- and/or gender-dependent circulating estrogen, even though their local mechanisms have been largely unknown. To characterize their potential correlations, age- and gender-dependencies were evaluated focusing on 5 pivotal estrogen-metabolizing enzymes including aromatase, estrogen sulfotransferase, steroid sulfatase, and 17ß-hydroxysteroid dehydrogenases and estrogen receptors (ERα and ERß) using immunohistochemistry of 100 human skin specimens. When their epidermal expression levels were compared among 7 age groups, ranging from the teens to the seventies, the highest expression in the teens group and the lowest expression in the seventies group were found in the expression of aromatase and ERß, respectively, while no significant differences between the male and the female groups were found in the immunoreactivities of our interested proteins. Our results suggest that age-related differences in aromatase and ERß expressions impact epidermal homeostasis.

The characteristics of aromatase deficient hairless mice indicate important roles of extragonadal estrogen in the skin.

The roles of extragonadal estrogen in the skin are poorly understood, due to the lack of proper animal models. We examined the skin phenotypes of aromatase-knockout hairless (ArKO) mice and wild-type hairless (WT) mice, both of which were obtained through crossbreeding of Ar+/- mice and hairless mice. Differences in the skins of ArKO and WT mice were compared with those of ovariectomized (OVX) and control (Sham) mice. A difference was observed in the skin tone of ArKO mice, which is pale white and differs from the pinkish tone of all other mice. However, both ArKO and OVX mice similarly exhibited deteriorations of skin properties as compared to their respective controls. Furthermore, all the deteriorations were similarly amplified by chronic UVB irradiation in both ArKO and OVX mice as compared to their respective controls. The unique skin phenotype of ArKO mice was observed in sunburn reactions. Specifically, skins of ArKO mice showed no reaction after an acute UVB irradiation at dose intensities caused sunburn in others. However, follow-up observation found delayed reactions associated with brownish skin color and swelling only in ArKO mice, thereby suggesting that the role of extragonadal estrogen may be connected with the protective reactions of skin.