BACKGROUND:Morinda has been reported to promote the proliferation, the secretion of alkaline phosphatase and osteocalcin, and mRNA expression of transforming growth factor of osteoblasts. However, little information is available addressing the effects of Morinda on receptor activator of nuclear factor-κB expression in osteoclasts in rats with osteoporosis. OBJECTIVE:To study the effects of Morinda on receptor activator of nuclear factor-κB expression in osteoclastsofosteoporosis rats. METHODS:Thirty Sprague-Dawley rats were equaly and randomly divided into Morinda and 17β-estradiol groups. Rat models of osteoporosis were established by bilateral ovariectomy, and then 5 mL of Morinda decocta(1.0mmol/L)and 17β-estradiol (1×10-6mmol/L) were administered intragastricaly to rats in Morinda and 17β-estradiol groups for 3 consecutive months, respectively. Primary osteoclasts were isolated from rats in both groups, andthen cultured for 3, 6 and 9 days folowed by TRAP staining andcelcounting. Bone mineral density of the proximal and distal femur, urine and serum levels of Ca2+and progesterone, and receptor activator of nuclear factor-κB expression in osteoclasts ofrats in both groups were determined. RESULTS AND CONCLUSION:Osteoclast fusion was reduced in Morinda group. In contrast, number of osteoclastswas increased andcels becamemore maturein the17β-estradiol group. Bone mineral density of the proximal and distal femur bilateraly, urine and serum levels of Ca2+and progesterone were significantly increased, while receptor activator of nuclear factor-κB expression was significantly decreased in osteoclasts in Morinda group compared with 17β-estradiol group (P< 0.05). These results indicate that Morinda reduces receptor activator of nuclear factor-κB expression in osteoclasts in osteoporosis rats, thereby inhibiting the development and progression of osteoporosis.

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is un-known.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the acti-vation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphory-lation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by acti-vating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.