Psoriasis is a chronic inflammatory disease with complex etiology involving multiple factors. Current treatment methods are highly limited and there is a strong need for the development of safer and efficacious agents. We have previously shown that a water-soluble extract derived from hardy kiwifruit Actinidia arguta, called PG102, shows potent anti-inflammatory effects. Based on its reported biological activities, the effects of PG102 were examined on imiquimod-induced psoriasis-like skin inflammation. Our results showed that topical application of PG102 ameliorates clinical symptoms of psoriasis, reducing skin thickness and Interleukin (IL)-17A level in draining lymph nodes without causing any adverse effects. Treatment with PG102 on cytokine-stimulated HaCaT cells suppressed hyperproliferation and downregulated the expression of various chemokines and antimicrobial peptides known to induce neutrophil infiltration. These anti-inflammatory activities of PG102 were mediated via inhibition of NF-κB and signal transducer of activation (STAT) signaling. We also found decreased neutrophil chemotaxis both in vitro and in vivo. Taken together, PG102 has potential as a safe and effective reagent for the treatment of psoriasis.
Estrogen deficiency after menopause increases bone loss by activating RANKL-induced osteoclast differentiation. Dehydrodiconiferyl alcohol (DHCA), a lignan originally isolated from Cucurbita moschata, has been thought to be a phytoestrogen based on its structure. In this study, we tested whether DHCA could affect RANKL-induced osteoclastogenesis in vitro and ovariectomy-induced bone loss in vivo. In RAW264.7 cells, DHCA inhibited RANKL-induced differentiation of osteoclasts. Consistently, expression of the six osteoclastogenic genes induced by RANKL was down-regulated. DHCA was also shown to suppress the NF-κB and p38 MAPK signaling pathways by activating AMPK. Data from transient transfection assays suggested that DHCA might activate the estrogen receptor signaling pathway. Effects of DHCA on RANKL-induced osteoclastogenesis were reduced when cells were treated with specific siRNA to ERα, but not to ERβ. Interestingly, DHCA was predicted from molecular docking simulation to bind to both ERα and ERβ. Indeed, data from an estrogen receptor competition assay revealed that DHCA acted as an agonist on both estrogen receptors. In the ovariectomized (Ovx) mouse model, DHCA prevented Ovx-induced bone loss by inhibiting osteoclastogenesis. Taken together, our results suggest that DHCA may be developed as an efficient therapeutic for osteoporosis by regulating osteoclastogenesis through its estrogenic effects.
IL-37 is an immunomodulatory cytokine that suppresses inflammation in various cell types and disease models. However, its role in keratinocytes has not been clearly understood, and there has been no report on the agents that can increase the expression of IL-37 in keratinocytes. In this study, we investigated the effects of silencing IL37 in HaCaT keratinocytes and the molecular mechanisms involved in the upregulation of IL-37 by PG102, a water-soluble extract from Actinidia arguta. It was found that knockdown of IL37 resulted in the augmented expression of antimicrobial peptides (AMPs) in response to cytokine stimulation. PG102 increased the expression of IL-37 at both mRNA and protein levels presumably by enhancing the phosphorylation of Smad3, ERK, and p38. Indeed, when cells were treated with specific inhibitors for these signaling molecules, the expression level of IL-37 was reduced. PG102 also promoted colocalization of phospho-Smad3 and IL-37. Our results suggest that IL-37 inhibits the expression of AMPs and that PG102 upregulates IL-37 through p38, ERK, and Smad3 pathways in HaCaT cells.
Benign prostatic hyperplasia (BPH) is one of the most frequently observed diseases in the elderly male population worldwide. A variety of factors such as aging, hormonal imbalance, chronic inflammation, and oxidative stress play an important role in its pathogenesis. We have previously shown that HX109, an ethanol extract prepared from 3 plants (Taraxacum officinale, Cuscuta australis, and Nelumbo nucifera), alleviates prostate hyperplasia in the BPH rat model and suppresses AR signaling by upregulating Ca 2þ /CAMKKβ and ATF3. In this study, we used macrophage cell lines to examine the effects of HX109 on inflammation, which is considered an important causative factor in BPH pathogenesis. In the co-culture system involving macrophage-prostate epithelial cells, HX109 inhibited macrophage-induced cell proliferation, migration and epithelial-mesenchymal transition (EMT) by inhibiting the expression of CCL4 and the phosphorylation of STAT3. Furthermore, HX109 inhibited the expression of inflammatory cytokines and the phosphorylation of p65 NF-κB in a concentration dependent manner. Taken together, our results suggested that HX109 could regulate macrophage activation and its crosstalk with prostate cells, thereby inhibiting BPH.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.