Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health.
Indran Inthrani Raja,Liang Ryan Lim Zhen,Min Tan Ee,Yong Eu-Leong
Pharmacology & therapeutics
The morbidity and mortality associated with fractures due to osteoporosis or "porous bone" contributes significantly to global healthcare costs and will increase exponentially with ageing populations. In menopausal women, the onset of menopause and rapid estrogen withdrawal leads to osteoporotic fractures. Healthy bone requires the coordinated remodeling function of osteoclasts, osteoblasts, and osteocytes in the basic bone multicellular unit, regulated by estrogen, RANKL/OPG, ROS, growth factors, and other kinase signaling pathways. Anti-osteoporotic drugs in current use such as hormone replacement therapy, selective estrogen receptor modulators, and bisphosphonates are designed to target these pathways, but all have their limitations. Extracts of the dried aerial parts of the traditional Chinese medicinal plant Epimedium (Berberidaceae) has long been used for bone health. Some nine Epimedium prenylflavonoid compounds have been reported to target estrogen signaling and other bone morphogenesis pathways in mesenchymal stem cell, osteoblast, and osteoclast cell lineages. Epimedium prenylflavonoids and enriched extracts can exert beneficial effects on bone health in estrogen-deficient and other osteoporosis animal models. The development of sensitive and rapid mass chromatographic techniques to quantify compounds extracted from Epimedium, including icariin and icaritin, has been used to standardize production and to study the pharmacokinetics and metabolism of Epimedium in animal models and humans. Recent clinical trials have reported positive effects on bone health, suggesting that compounds or extracts of Epimedium have the potential to be developed as agents, alone or in combination with other drugs, to prevent or delay the onset of osteoporosis and reduce the risk of hip fractures.
Anti-inflammatory chemical constituents of Flos Chrysanthemi Indici determined by UPLC-MS/MS integrated with network pharmacology.
Tian Dong,Yang Yong,Yu Meng,Han Zheng-Zhou,Wei Min,Zhang Hong-Wu,Jia Hong-Mei,Zou Zhong-Mei
Food & function
Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum indicum L., is a common functional food and a well-known traditional Chinese medicine (TCM) for the treatment of inflammatory diseases. Previous studies have revealed that FCI has anti-inflammatory activity, but little is known about its anti-inflammatory chemical profile. In this study, the potential anti-inflammatory constituents of FCI were investigated by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with the network pharmacology approach, and further confirmed on a LPS activated RAW264.7 macrophage model. As a result, a total of forty-two compounds, including thirty-two flavonoids, nine phenolic acids and one sesquiterpene, were identified. Among them, fourteen compounds including eight flavonoids (11, 17, 24, 28, 32, 39, 41 and 42) and six caffeoylquinic acids (3, 4, 5, 13, 15 and 20) were recognized as potential key anti-inflammatory constituents of FCI through network pharmacology analysis, because they accounted for 92% of the relative peak area in the UPLC-Q-TOF/MS chromatogram and acted on 87 of 97 the inflammatory targets of FCI. However, only 16 targets were shared between the flavonoids and caffeoylquinic acids, indicative of both acting on more different targets. Further the anti-inflammatory effects of the fourteen constituents were validated with the decreased levels of NO, TNF-α, IL-6 and PGE2 in RAW264.7 macrophage cells treated with LPS. Our results indicated that both flavonoids and caffeoylquinic acids were responsible for the anti-inflammatory effect of FCI through synergetic actions on multi-targets. Moreover, 3,5-dicaffeoylquinic acid (15), luteolin (24) and linarin (28) were the most important active constituents of FCI and could be selected as chemical markers for quality control of FCI. Overall, the findings not only explore the anti-inflammatory chemical constituents of FCI, but also provide novel insights into the effective constituents and mechanism of TCMs.
Integrated Phytochemical Analysis Based on UPLC-Q-TOF-MS/MS, Network Pharmacology, and Experiment Verification to Explore the Potential Mechanism of for Chronic Bronchitis.
Deng Yaling,Ren Hongmin,Ye Xianwen,Xia Lanting,Liu Minmin,Liu Ying,Yang Ming,Yang Songhong,Ye Xide,Zhang Jinlian
Frontiers in pharmacology
Background and Aim: (PG) has been widely used for treating chronic bronchitis (CB). However, the material basis and underlying mechanism of action of PG against CB have not yet been elucidated. Methods:To analyze the ingredients in PG, ultraperformance liquid chromatography-quadrupole-time-of-flight tandem mass (UPLC-Q-TOF-MS/MS) technology was performed. Subsequently, using data mining and network pharmacology methodology, combined with Discovery Studio 2016 (DS), Cytoscape v3.7.1, and other software, active ingredients, drug-disease targets, and key pathways of PG in the treatment of CB were evaluated. Finally, the reliability of the core targets was evaluated using molecular docking technology and studies. Results:A total of 36 compounds were identified in PG. According to the basic properties of the compounds, 10 major active ingredients, including platycodin D, were obtained. Based on the data mining approach, the Traditional Chinese Medicine Systems Pharmacology Database, and the Analysis Platform (TCMSP), GeneCards, and other databases were used to obtain targets related to the active ingredients of PG and CB. Network analysis was performed on 144 overlapping gene symbols, and twenty core targets, including interleukin-6 (IL-6) and tumor necrosis factor (TNF), which indicated that the potential signaling pathway that was most relevant to the treatment of CB was the IL-17 signaling pathway. Conclusion:In this study, ingredient analysis, network pharmacology analysis, and experiment verification were combined, and revealed that PG can be used to treat CB by reducing inflammation. Our findings provide novel insight into the mechanism of action of Chinese medicine. Furthermore, our data are of value for the research and development of novel drugs and the application thereof.