Effects of genistein aglycone in glucocorticoid induced osteoporosis: A randomized clinical trial in comparison with alendronate.

Glucocorticoid-induced osteoporosis (GIO) complicates the clinical management of patients subjected to long-term glucocorticoid use. This study explored the effects of genistein on bone loss in a randomized double-blind alendronate-controlled trial in postmenopausal women with GIO. 200 postmenopausal women (taking at least 5 mg of prednisone equivalents) since 3 months, or more, and expected to continue for at least other 12 months, were randomized to receive genistein (54 mg/day daily) or alendronate (70 mg once a week) for 24 months. Both groups received also Calcium and Vitamin D3 supplementation. Median bone mineral density (BMD) at the antero-posterior lumbar spine significantly increased from 0.75 g/cm2 at baseline to 0.77 g/cm2 at 1 year and 0.79 g/cm2 at 2 years in alendronate-treated patients and from 0.77 g/cm2 at baseline to 0.79 g/cm2 at 12 months and to 0.80 g/cm2 at 24 months in genistein recipients. No difference was observed between the two treatments. Median BMD at the femoral neck increased from 0.67 g/cm2 at baseline to 0.68 g/cm2 at 1 year and 0.69 g/cm2 at 2 years in alendronate-treated patients and from 0.68 g/cm2 at baseline to 0.70 g/cm2 at 12 months and to 0.71 g/cm2 at 24 months in genistein recipients. No difference was observed between alendronate and genistein groups in BMD. Regarding bone markers genistein and alendronate statistically decreased c-terminal telopeptide, while osteocalcin, bone-ALP, and sclerostin showed greater changes in genistein treated patients. This randomized clinical trial suggests that genistein aglycone represents an additional therapeutic option for patients with GIO.

Rosmarinus officinalis and Skin: Antioxidant Activity and Possible Therapeutical Role in Cutaneous Diseases.

The rosemary plant, Rosmarinus officinalis L., one of the main members of the Lamiaceae family, is currently one of the most promising herbal medicines due to its pharmaceutical properties. This research aimed to evaluate the antioxidant role of Rosmarinus officinalis and its bioactive compounds on the skin, with a focus on the newly emerging molecular mechanisms involved, providing extensive scientific evidence of its anti-inflammatory, antimicrobial, wound-healing and anticancer activity in dermatological practice. The search was conducted on articles concerning in vitro and in vivo studies in both animals and humans. The results obtained confirm the antioxidant role of R. officinalis. This assumption derives the possibility of using R. officinalis or its bioactive elements for the treatment of inflammatory and infectious skin pathologies. However, although the use of rosemary in the treatment of skin diseases represents a fascinating line of research, future perspectives still require large and controlled clinical trials in order to definitively elucidate the real impact of this plant and its components in clinical practice.

Oxidative Stress and Phototherapy in Atopic Dermatitis: Mechanisms, Role, and Future Perspectives.

Atopic dermatitis is a chronic inflammatory skin disease in which the overproduction of reactive oxygen species plays a pivotal role in the pathogenesis and persistence of inflammatory lesions. Phototherapy represents one of the most used therapeutic options, with benefits in the clinical picture. Studies have demonstrated the immunomodulatory effect of phototherapy and its role in reducing molecule hallmarks of oxidative stress. In this review, we report the data present in literature dealing with the main signaling molecular pathways involved in oxidative stress after phototherapy to target atopic dermatitis-affected cells. Since oxidative stress plays a pivotal role in the pathogenesis of atopic dermatitis and its flare-up, new research lines could be opened to study new drugs that act on this mechanism, perhaps in concert with phototherapy.

Nodular-cystic eruption in course of sorafenib administration for hepatocarcinoma: An unconventional skin reaction requiring unconventional treatment.

Sorafenib is a multitargeted kinase inhibitor currently used in the treatment of advanced hepatocellular carcinoma (HCC). It is associated with a significant risk of skin toxicity, which nevertheless represents a clinical marker of good response to treatment. Hand-and-foot skin reaction, alopecia, mucositis, xerosis, skin discoloration, and nail involvement occur frequently in course of therapy. More rarely, sorafenib can target hair follicles. We report the case of a patient who developed painful inflamed nodular-cystic lesions in both pubic and axillary regions in course of treatment with sorafenib. Because of the limited therapeutic options, the patient underwent photodynamic therapy (PDT), a topical treatment which combines a photosensitizing drug applied on lesional skin and a source of light, and had no systemic side effects. At the end of the treatment period, the patient experienced progressive clinical improvement, with relief of the symptoms. PDT may be helpful to limit suffering in patients affected by recalcitrant skin toxicity of the pilosebaceous unit who are not candidates for, or not responsive to, standard therapies.

BAY 11-7082 inhibits the NF-κB and NLRP3 inflammasome pathways and protects against IMQ-induced psoriasis.

BAY 11-7082 antagonizes I-κB kinase-ß preventing nuclear translocation of nuclear factor-κB (NF-κB); it also inhibits NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation. NF-κB is involved in psoriasis, whereas the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod (IMQ) cream (62.5 mg/day) on the shaved back skin of C57BL/6 and NLRP3 knockout (KO) mice for 7 consecutive days. Sham psoriasis animals were challenged with Vaseline cream. Sham and IMQ animals were randomized to receive BAY 11-7082 (20 mg/kg/i.p.) or its vehicle (100 µl/i.p of 0.9% NaCl). Skin of IMQ animals developed erythema, scales, thickening and epidermal acanthosis. IMQ skin samples showed increased expression of pNF-κB and NLRP3 activation. BAY 11-7082 blunted epidermal thickness, acanthosis and inflammatory infiltrate. BAY 11-7082 reduced pNF-κB, NLRP3, tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß expression, blunted the phosphorylation of signal transducer and activators of transcription 3 (STAT3) and decreased IL-23 levels. In addition, BAY 11-7082 reawakened the apoptotic machinery. NLRP3 KO animals showed a reduced total histological score but persistent mild acanthosis, dermal thickness and expression of pNF-κB and pSTAT3, following IMQ application. Our data suggest that BAY 11-7082 might represent an interesting approach for the management of psoriasis-like dermatitis depending on the dual inhibition of NF-κB and NLRP3.

Genistein aglycone, a soy-derived isoflavone, improves skin changes induced by ovariectomy in rats.

BACKGROUND AND PURPOSE: Ovariectomy accelerates age-related skin changes as adequate oestrogen levels are required to control structural integrity and functional capacity of skin. Genistein, a soy-derived isoflavone, has been tested in anti-ageing cosmetic preparations with interesting results on skin elasticity, photoaging and skin cancer prevention. We investigated the effects of genistein aglycone and compared them with systemic raloxifene hydrochloride and 17-α-ethinyloestradiol on skin changes in aged, ovariectomized (OVX) rats. EXPERIMENTAL APPROACH: Six months after ovariectomy, rats were randomly allocated to different groups and treated, daily, with genistein aglycone (1 and 10mg·kg(-1) s.c.), raloxifene hydrochloride (0.05 and 0.5mg·kg(-1) s.c.) or 17-α-ethinyloestradiol (0.003 and 0.03mg·kg(-1) s.c.) for 12 weeks. Controls were untreated OVX and sham OVX rats. At the end of the treatment period, a skin biopsy was carried out and skin samples were assessed for molecular, histological and functional changes. KEY RESULTS: Skin samples of untreated OVX rats showed a decrease in TGF-ß1, VEGF, MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 compared with sham OVX rats. All the treatments significantly restored this depressed molecular profile revealed in OVX rats. Genistein aglycone, 1mg·kg(-1) , also significantly increased the thickness of collagen and breaking strength of skin in the OVX rats. CONCLUSIONS AND IMPLICATIONS: Relatively long-term, systemic treatment with genistein aglycone shows comparable efficacy to oestrogen in reversing some molecular, histological and functional changes of the skin associated with ovariectomy in aged rats. This suggests that genistein aglycone might be an effective alternative therapy for the management of age-related skin changes in postmenopausal women.

Anti-inflammatory effects of the methanol extract of Sedum telephium ssp. maximum in lipopolysaccharide- stimulated rat peritoneal macrophages.

Sedum telephium ssp. maximum is a medicinal plant that possesses anti-inflammatory, analgesic and keratolytic properties. We investigated the anti-inflammatory activity of its methanolic extract (STME) in rat peritoneal macrophages (MPhis) stimulated with lipopolysaccharide from Salmonella enteritidis. After stimulation with 10 microg/ml of LPS, MPhis were coincubated with different doses of STME (8, 16 and 32 microg/ml) or RPMI medium alone using different times of incubation. STME reduced levels of tumor necrosis factor-alpha, both mRNA and its protein, and significantly decreased IL-1beta and IL-6 production. Moreover, STME inhibited inducible nitric oxide synthase expression and blunted nitrite release and inhibited both extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase activation in lipopolysaccharide-stimulated MPhis. Data show that STME might be useful as a potential anti-inflammatory agent.