Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking

Abstract

Kaempferol (KP), as a natural anti-inflammatory compound, has been reported to have curative effects on alleviating senile osteoporosis (SOP), which is an inflammation-related musculoskeletal disease, but the molecular mechanisms remain unclear due to scanty relevant studies. We predicted the targets of KP and SOP, and the common targets of them were subsequently used to carry out PPI analysis. Moreover, we adopted GO and KEGG enrichment analysis and molecular docking to explore potential mechanisms of KP against SOP. There were totally 152 KP-related targets and 978 SOP-related targets, and their overlapped targets comprised 68 intersection targets. GO enrichment analysis showed 1529 biological processes ( p < 0.05 ), which involved regulation of inflammatory response, oxidative stress, regulation of bone resorption and remodeling, osteoblast and osteoclast differentiation, etc. Moreover, KEGG analysis revealed 146 items including 44 signaling pathways ( p < 0.05 ), which were closely linked to TNF, IL-17, NF-kappa B, PI3K-Akt, MAPK, estrogen, p53, prolactin, VEGF, and HIF-1 signaling pathways. By means of molecular docking, we found that kaempferol is bound with the key targets’ active pockets through some connections such as hydrogen bond, pi-alkyl, pi-sigma, pi-pi Stacked, pi-pi T-shaped, and van der Waals, illustrating that kaempferol has close combination with the key targets. Collectively, various targets and pathways involve in the process of kaempferol treatment against SOP through regulating inflammatory response, oxidative stress, bone homeostasis, etc. Moreover, our study first reported that kaempferol may regulate core targets’ expression with involvement of inflammatory response, oxidative stress, and bone homeostasis, thus treating SOP.

A Comparison of the Antiosteoporotic Effects of Cornelian Cherry (Cornus mas L.) Extracts from Red and Yellow Fruits Containing Different Constituents of Polyphenols and Iridoids in Osteoblasts and Osteoclasts

“…They decreased osteoclastogenesis, mainly through RANKL-related pathways, and promoted osteoblast differentiation [ 7 , 52 ]. Proposed mechanisms responsible for the benefits of kaempferol in senile osteoporosis include also anti-inflammatory and antioxidative properties and regulation of osteoblasts' and osteoclasts' apoptosis [ 53 ]. Kaempferol and quercetin in the forms of 3- O -glucuronide, 3- O -galactoside, or O -glucoside were found in small amounts in RED EXT1, but their potential contribution to the antiosteoporotic effect is difficult to elucidate.…”

Transcriptomics-based Exploration of the Mechanism of Kaempferol in the Treatment of Osteoporosis in Ovariectomized Rats

“…3 Some experiments proved that kaempferol can regulate bone metabolism balance and improve bone density by increasing osteoblast activity while decreasing osteoclast activity. [4][5][6][7][8] Our preliminary experiments found that RPN1 may serve as a new target for kaempferol to improve osteoporosis. 9 Therefore, kaempferol which may be a more investigative antiosteoporotic herbal monomer can be used as a complementary and alternative drug with promising clinical applications in the treatment of osteoporosis.…”

Bioactivity, Molecular Mechanism, and Targeted Delivery of Flavonoids for Bone Loss

“…Additionally, the role of Kaempferol in curing senile osteoporosis was also confirmed by performing molecular docking studies. The study revealed that Kaempferol is a potent curative agent against this musculoskeletal disease as it can regulate oxidative stress, various inflammatory pathways, and bone homeostasis [ 250 ]. For the first time, molecular docking investigations performed by Yu X. et al revealed that Naringin might treat osteoporotic fracture, presumably via modulating a variety of signaling pathways and targets associated with the development of osteoclasts and oxidative stress.…”