Medicinal Plant Research 2024, Vol.14, No.3, 126-136 http://hortherbpublisher.com/index.php/mpr 133 Importantly, the c-fos/NFATc1 pathway of chrysanthemum extract indicates significant potential in the treatment of osteoporosis and related diseases through osteoclast differentiation (Yang et al., 2019). 7.2 Interaction with cellular targets Chrysanthemum extract interacts with various cellular targets to exert its effects. For instance, in neuroblastoma cells, CM extract has been shown to inhibit oxidative stress-induced cytotoxicity by modulating the expression of apoptotic proteins such as Bcl-2 and Bax, and by preventing the cleavage of caspase-3 andPARP. In the context of obesity and dyslipidemia, CM leaf extract and its constituent luteolin have been demonstrated to normalize lipid profiles by affecting lipidomic biomarkers such as cholesteryl esters, lysophosphatidylcholines, andsphingomyelins (Shon et al., 2020). Moreover, CM's anti-inflammatory properties are partly attributed to its ability to inhibit the production of pro-inflammatory cytokines and enzymes, such as TNF-α, IL-1β, IL-6, and iNOS, through the inactivation of MAPKs and NF-κBpathways (Zhang et al., 2019). 7.3 Synergistic effects with other compounds When chrysanthemum is combined with other Chinese herbs, its therapeutic effect can be enhanced. For example, a combination of chrysanthemum and wolfberry (Lycium barbarum) has shown synergistic antioxidant and anti-inflammatory effects. This combination significantly reduced oxidative stress and inflammation in macrophages, with the most potent effects observed at a 1:1 ratio of chrysanthemum to wolfberry. Additionally, the flavonoids apigenin and luteolin, which are abundant in CM, have been found to work synergistically to inhibit the expression of adhesion molecules and oxidative stress markers in endothelial cells, further enhancing CM's cardiovascular protective effects (Lii et al., 2010). These findings suggest that CM's bioactive compounds can interact synergistically with other natural products to amplify its therapeutic benefits. 8 Safety and Toxicology 8.1 Toxicological studies and safety profile Chrysanthemum morifolium, commonly used in traditional Chinese medicine, has been extensively studied for its therapeutic benefits. However, its safety profile is equally important. Toxicological studies have shown that extracts from Chrysanthemum morifolium are generally safe and exhibit low toxicity. A study on the neuroprotective effects of Chrysanthemum morifolium extract demonstrated it effectively inhibited cytotoxicity and improved cell viability without adverse effects. Additionally, the flower extract has been shown to ameliorate obesity-induced inflammation in rats without causing significant toxicity (Lee et al., 2021). These findings suggest that Chrysanthemum morifoliumis safe for use in both traditional and modern medicinal applications. 8.2 Potential side effects and contraindications Despite its general safety, some potential side effects and contraindications of Chrysanthemum morifoliumshould be noted. Chrysanthemum extract can cause mild gastrointestinal disorders in some populations. Due to the strong bioactive components of chrysanthemum, it may interfere with the action sites of certain drugs. For example, chrysanthemum has been shown to interfere with other drugs targeting the PI3K/Akt signaling pathway when regulating it (Feng et al., 2022). In addition, some people are allergic to Asteraceae plants, and taking chrysanthemum related drugs may cause allergic reactions (Yang et al., 2019). 8.3 Guidelines for safe usage To ensure the safe use of Chrysanthemum morifolium, several guidelines should be followed: Adhere to recommended dosages as excessive intake may lead to adverse effects. The use of specific concentrations (0.2% and 0.4% CE) of chrysanthemum has a good therapeutic effect on obesity and is non-toxic. It is important to follow traditional formulas and consult a professional doctor when taking chrysanthemum and its combination drugs (Zhang et al., 2019). Individuals with chrysanthemum allergy should undergo patch testing or consult a professional doctor before using chrysanthemum products (Ojha et al., 2023). There is limited data on the safety of using chrysanthemums in pregnant and lactating women. Therefore, it is recommended that pregnant and lactating women use it with caution and consult a professional doctor.
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