Potential skin health promoting benefits of costunolide: a therapeutic strategy to improve skin inflammation in imiquimod-induced psoriasis.

Psoriasis is a recurrent inflammatory skin disease. IL-36-related cytokines are overexpressed in psoriasis, but the mechanism is not yet clear. Costunolide (Cos) is a sesquiterpenoid compound derived from the root of the traditional Chinese medicine Aucklandia lappa Decne. This study aimed to explore the mechanism of Cos on improving psoriasis-like skin inflammation. An in vivo model was established by applying imiquimod treatment to the back skin of mice, and an in vitro model was established by using polyinosinic-polycytidylic acid (Poly(I:C)) stimulated-mouse primary dermal fibroblasts to induce inflammation. The results showed that Cos improved the pathological changes of psoriasis-like skin inflammation. In addition, Cos could inhibit epidermal damage and inflammation-related expression and improve the occurrence of skin-related inflammation in both in vivo and in vitro experiments. The improvement of psoriasis-like skin inflammatory response might be through the P2X7R/IL-36 signaling pathway. Collectively, Cos has an inhibitory effect on the expression of psoriasis-like skin inflammation. This showed that Cos has potential skin health promoting benefits by preventing psoriasis-like skin inflammation.

Low frequency pulsed electromagnetic fields exposure alleviate the abnormal subchondral bone remodeling at the early stage of temporomandibular joint osteoarthritis.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is characterized by abnormal subchondral bone remodeling and cartilage degeneration. As a non-invasive biophysical technology, pulsed electromagnetic field (PEMF) treatment has been proven to be efficient in promoting osteogenesis. However, the potential bone protective effect and mechanism of PEMF on abnormal subchondral bone remodeling in TMJOA are unknown. METHODS: Unilateral anterior crossbite (UAC) was used to create TMJOA model in rats, and 17ß-estradiol (E2) were injected daily to mimic patients with high-physiological levels of estrogen. Mouse osteoblast-like MC3T3-E1 cells treated with recombinant murine IL-1ß was used to establish inflammatory environment in vitro. The treatment group were subjected to PEMF (2.0mT, 15 Hz, 2 h/d). Micro-CT scanning, histological staining, real-time PCR and western blotting assays were preformed to observe the changes in the subchondral bone. RESULTS: Abnormal resorption of subchondral bone induced by UAC, characterized by decreased bone mineral density, increased osteoclast activity and expression of osteoclast-related factors (RANKL) and down-regulated expression of osteogenesis-related factors (OPG, ALP, Runx2 and OCN) at the early stage, could be reversed by PEMF exposure, which was similar to the effect of estrogen. In addition, PEMF exposure and E2 supplement may have a synergistic effect to some extent. Moreover, PEMF exposure could promote the ALP activity and osteogenic mineralization ability of MC3T3-E1 cells. PEMF promoted the expression of factors related to Wnt/ß-Catenin signal pathway both in vivo and in vitro. CONCLUSIONS: Appropriate PEMF exposure have a protective effect on subchondral bone in TMJOA at early stage, in which canonical Wnt/ß-Catenin pathway may be involved. PEMF may be a promising biophysical approach for early intervention of TMJOA in clinic.

Aqueous extract of Scrophularia ningpoensis improves insulin sensitivity through AMPK-mediated inhibition of the NLRP3 inflammasome.

BACKGROUND: Scrophularia ningpoensis Hemsl. is a commonly used medicinal plant in China for the treatment of diabetes mellitus (DM), but its mechanism of action remains poorly described. Type 2 diabetes mellitus (T2DM) accounts for > 90% of all DM cases and is characterized by insulin resistance. PURPOSE: The aim of this study was to investigate whether the insulin sensitivity can be improved by treatment with aqueous extract of S. ningpoensis (AESN) and further explore its mechanism(s) of activity. METHODS: Primary mouse hepatocytes and human HepG2 hepatocytes were used to investigate the effects of AESN on cell viability, AMP-activated protein kinase (AMPK) activation and glucose output under normal culture conditions. To mimic hyperglycemia and insulin resistance in vitro, hepatocytes were exposed to high glucose (HG), and the influences of AESN on AMPK phosphorylation, NLRP3 inflammation activation, insulin signaling, lipid accumulation and glucose output were investigated. Increasing doses of AESN (50, 100 and 200 mg/kg/day) were administered by gavage to db/db mice for 8 weeks, and then biochemical analysis and histopathological examinations were performed. RESULTS: AESN significantly activated AMPK and inhibited glucose output in hepatocytes, but did not impact cell viability under normal culture conditions. Moreover, in HG-treated hepatocytes, AESN protected against aberrant AMPK activity, NLRP3 inflammasome activation, insulin signaling, and lipid accumulation. AMPK inhibition abolished the regulatory effects of AESN on the NLRP3 inflammasome, insulin signaling, lipid accumulation, and glucose output of hepatocytes following HG exposure. Furthermore, AESN administration reduced blood glucose and serum insulin levels, improved lipid profiles and insulin resistance, and corrected the aberrant AMPK activity and NLRP3 inflammasome activation in liver tissues. CONCLUSION: AESN improves insulin sensitivity via AMPK-mediated NLRP3 inflammasome inhibition.

Thymoquinone Attenuates Acetaminophen Overdose-Induced Acute Liver Injury and Inflammation Via Regulation of JNK and AMPK Signaling Pathway.

Thymoquinone (TQ) is a main aromatic component of Nigella sativa L. seeds or Agastache rugosa (Fisch. & C.A.Mey.) Kuntze. The protective mechanism of TQ against acute liver injury induced by acetaminophen (APAP), however, remains unclear. We aimed to investigated the hepato-protective mechanism of TQ on the development of APAP-induced acute liver injury. Male kunming mice were pretreated with TQ or N-acetylcysteine (NAC) before a single APAP injection. Human Chang liver cells were incubated with TQ, SP600125 or AICAR in presence of APAP for 24 h. TQ pretreatment reduced levels of serum aminotransferases and increased hepatic glutathione and glutathione peroxidase activities via inhibiting CYP2E1 expression. TQ inhibited JNK, ERK and P38 phosphorylation induced by APAP. Meanwhile, TQ inhibited PI3K/mTOR signaling activation and activated AMPK phosphorylation. Moreover, TQ prevented APAP-induced hepatocytes apoptosis regulated by Bcl-2 and Bax. Furthermore, TQ inhibited STAT3 phosphorylation on APAP-induced acute liver injury. In addition, TQ significantly inhibited P2X7R protein expression and IL-1 ß release. APAP-enhanced JNK phosphorylation and APAP-suppressed AMPK phosphorylation were also observed in Chang liver cells, and these changes were recovered by pretreatment with TQ, SP600125 and AICAR. Our findings suggest that TQ may actively prevent APAP-induced acute liver injury, and the effect may be mediated by JNK and AMPK signaling pathways.

Differential effects of high-physiological oestrogen on the degeneration of mandibular condylar cartilage and subchondral bone.

The striking predilection of temporomandibular disorders (TMD) in women, especially during gonad-intact puberty or reproductive years, indicates that oestrogen plays an important role in the progression of TMD, but the underlying mechanism remains unclear. In this study, unilateral anterior crossbite (UAC) was used to create temporomandibular joint osteoarthritis (TMJ OA) models in rats, while 17ß-estradiol (E2) injections were applied to mimic patients with high-physiological levels of oestrogen. Micro-CT scanning, histological staining and real-time PCR assays were preformed to observe the degenerative changes in the mandibular condylar cartilage and subchondral bone. The results showed that obvious degradation was found in the condylar cartilage and subchondral bone of rats with UAC procedure, including decreased cartilage thickness, loss of extracellular matrix, increased apoptotic chondrocytes and expression of pro-inflammatory and catabolic factors, decreased bone mineral density and increased osteoclast activity. E2 supplements aggravated the condylar cartilage degradation but reversed the abnormal bone resorption in the subchondral bone induced by UAC. Our results revealed that high-physiological oestrogen plays a destructive role in condylar cartilage but a protective role in subchondral bone at the early stage of TMJ OA. These dual and distinct effects should be given serious consideration in future OA treatments.