Signaling pathways related to kaempferol active monomers in the treatment of osteoporosis
Yang Qipei1, Chen Feng2, Cui Wei2, Zhang Chi2, Wu Ruiqi1, Song Zhenheng1, Meng Xin1
1Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; 2Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
Abstract: BACKGROUND: Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level, and the mechanism of related signaling pathways is an important way to further understand osteoporosis. At present, traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis. Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action.
OBJECTIVE: To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature.
METHODS: “Kaempferol, osteoporosis, osteoblasts, osteoclasts, bone marrow mesenchymal stem cells, signaling pathways” were used as Chinese and English search terms to search CNKI, WanFang, VIP, PubMed, Web of Science and Embase databases for relevant literature published from database inception to February 2023.
RESULTS AND CONCLUSION: Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation, proliferation and apoptosis of bone marrow mesenchymal stem cells, osteoblasts and osteoclasts. Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways. Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex. Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis. Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification. Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway. Kaempferol inhibits the expression of ERK, JNK, p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway, thus protecting osteogenesis. Kaempferol enhances the expression of osteogenic factors, bone morphogenetic protein-2, p-Smad1/5/8, β-catenin and Runx2, inhibits the expression of Peroxisome proliferation-activated receptor, and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.
Key words: kaempferol, osteoporosis, osteoblast, osteoclast, bone marrow mesenchymal stem cell, signaling pathway