Yunnan Baiyao diminishes lipopolysaccharide-induced inflammation in osteoclasts

Abstract

Yunnan Baiyao (YNBY) has been refined for hundreds of years and has become a treasure of proprietary Chinese medicine that has significant curative effects in the field of hemostasis, blood circulation, and callus. In past years, YNBY has been demonstrated to play an anti-inflammatory role in bone-related diseases, such as rheumatoid arthritis and osteoporosis. However, the osteoclasts are multinucleated giant cells that resorb bone and participate in the occurrence, development, and progression of these bone-related diseases. Previous studies have reported that the inflammatory function is closely associated with arachidonic acid (AA) metabolism, as well as some inflammatory-related pathways, including the nuclear factor кB (NF-кB), mitogen-activated protein kinase (MAPK), and Wnt5a pathways. Therefore, we speculated that the anti-inflammatory effect of YNBY might be associated with the NF-кB, MAPK, and Wnt5a pathways. In order to further excavate the anti-inflammatory roles of YNBY, lipopolysaccharide (LPS) with an optimal concentration of 1,000 pg/ml was used to induce inflammation in osteoclasts. Our results showed that YNBY with a time- and dose-dependent method decreased the concentration of pro-inflammatory cytokines and the expression levels of cyclooxygenase-1 (COX-1), COX-2, 5-lipoxygenase, and prostaglandin E2. Moreover, it was found that COX-2 was the target gene regulated by YNBY. Finally, using NF-кB and MAPK pathway inhibitors or miRNA101b (involved in the Wnt5a pathway) in tandem with YNBY and the results exhibited that these groups caused a reduction in COX-1 and COX-2 expression, indicating that the anti-inflammatory function of YNBY might directly affect the NF-кB, MAPK, and Wnt5a pathways. PRACTICAL APPLICATIONS: Yunnan Baiyao (YNBY) is mainly extracted from precious Chinese medicines such as Panax notoginseng, borneol, musk, and yam and has a wide range of clinical applications. It is not only used to treat various types of traumatic injuries, but also used for upper gastrointestinal bleeding and wound ulcers, neonatal umbilitis, recurrent oral ulcers, esophagitis, bacterial dysentery, and so on. Although the detailed mechanism of action is not clear at present, it is believed that this is related to its anti-inflammatory, hemostatic, and immune-enhancing effects. Many bone-related diseases, such as rheumatoid arthritis and osteoporosis, are regarded to be intimately related to the inflammatory reaction. Thus, this study aimed to explore the underlying mechanisms of YNBY at anti-inflammatory roles. And our results suggested that YNBY directly affected the inflammatory cytokines and AA metabolic products which referred to the NF-кB, MAPK, and Wnt5a pathways, as well as AA metabolism, respectively. Hence, the practical applications of YNBY are the anti-inflammatory effects used to treat for bone-related diseases.

Keywords: Yunnan Baiyao (YNBY); arachidonic acid (AA); cyclooxygenase-1 (COX-1) or COX-2; lipopolysaccharide (LPS); osteoclasts.