Scientists are using artificial intelligence to swiftly scan current medicines for new uses or forecast which compounds could alleviate diseases.
Osteoporotic mice treated with dihydroartemisinin (DHA) had significantly improved bone density (bottom) compared to controls (top). Image Credit: ACS Central Science, 2023, DOI: 10.1021/acscentsci.3c00794
Using one such deep learning system, researchers discovered that dihydroartemisinin (DHA), an antimalarial drug and a byproduct of traditional Chinese medicine, could also be utilized to treat osteoporosis. Their findings were published in ACS Central Science. The group demonstrated how DHA successfully stopped bone loss caused by osteoporosis in mice.
Osteoblasts, which create new bone, and osteoclasts, which break down existing bone, coexist in balance in healthy individuals. However, excessive activity on the part of the “demolition crew” could lead to bone loss and osteoporosis, a condition that primarily affects elderly people. The primary objective of current osteoporosis treatment is to reduce osteoclast activity.
However, osteoblasts, or more precisely, bone marrow mesenchymal stem cells (BMMSCs), their progenitors, could act as the foundation for an alternative strategy. These multipotent cells often become fat-producing cells during osteoporosis, but they can be reprogrammed to aid in treating the disease.
In the past, Zhengwei Xie and associates created a deep learning system that could forecast how well specific small-molecule medications would restore disease-related alterations to gene expression. This time, Yan Liu and Weiran Li joined them, and their objective was to apply the algorithm to discover a novel osteoporosis treatment plan that centered on BMMSCs.
The algorithm was run on a profile of differentially expressed genes in adult and newborn mice by the researchers. One of the most highly ranked compounds found was DHA, an artemisinin derivative that is essential to the treatment of malaria.
Mice with induced osteoporosis showed virtually complete preservation of bone integrity and a considerable reduction in bone loss in their femurs after receiving DHA extract for six weeks. The group created a more reliable technique using injected, DHA-loaded nanoparticles to enhance delivery.
The bones of mice with osteoporosis who got the medicine matched those of the control group, and there was no sign of harm. Further research revealed that DHA interacted with BMMSCs to retain their stemness and, as a result, create more osteoblasts. According to the researchers, this study shows that DHA is a prospective treatment agent for osteoporosis.
The authors gratefully acknowledge funding from the National Natural Science Foundations of China, the Beijing International Science and Technology Cooperation, the Beijing Natural Science Foundation, Peking University Clinical Medicine Plus X - Young Scholars Project, the Ten-Thousand Talents Program, the Key R & D Plan of Ningxia Hui Autonomous Region, the Innovative Research Team of High-Level Local Universities in Shanghai, the Beijing Nova Program, the China National Postdoctoral Program for Innovative Talents, the China Postdoctoral Science Foundation, and the Peking University Medicine Sailing Program for Young Scholars’ Scientific & Technological Innovation.
Journal Reference:
Wang, R., et al. (2023) Deep Learning-Predicted Dihydroartemisinin Rescues Osteoporosis by Maintaining Mesenchymal Stem Cell Stemness through Activating Histone 3 Lys 9 Acetylation. ACS Central Science. doi:10.1021/acscentsci.3c00794