## 4 Bioactive Properties
### Anti-Inflammatory Effects  
Inflammation is a complex biological response triggered by the immune system in response to harmful stimuli such as infections, injuries, or diseases. Many sesquiterpenes and their derivatives from _Ferula_ have anti-inflammatory properties, making them valuable for promoting overall health and potentially reducing the risk of chronic diseases associated with inflammation.  
Ferutinin (**18**) and referin (**21**) exhibit anti-inflammatory effects at a dose of 100 mg/kg using the in vivo carrageenan-induced edema model, which may be caused by the antagonistic effects of histamine and/or serotonin, and their anti-inflammatory effects may be directly related to the degree of oxidation of the benzene ring [226].  
The sesquiterpene coumarins methyl galbanate (**214**) and umbelliprenin (**150**) were reported to exert their anti-inflammatory effects by significantly inhibiting the LPS-induced production of nitric oxide (NO) and prostaglandin E\({}_{2}\) (PGE\({}_{2}\)), leading to a decrease in the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [227]. In another study, the anti-inflammatory effect of umbelliprenin (**150**) was evaluated in vitro and in vivo. It displayed a significant inhibitory effect on soybean lipoxygenase (a key enzyme in the process of inflammation), with an IC\({}_{50}\) value of 0.0725 uM, whereas the IC\({}_{50}\) value of the positive control, caffe acid, was 600 uM. Furthermore, it showed a significant anti-inflammatory effect (39%) in vivo, which was comparable to the positive control, indomethacin (47%), using the carrageenanin mouse-paw edema model [228]. In RAW264.7 cells stimulated by lipopolysaccharide-interferon-\(\gamma\) (IFN-\(\gamma\)), [PERSON] et al. [229] found that methyl galbanate (**214**) significantly reduced NO production. In the presence of methyl galbanate (**214**), the mRNA expression of iNOS stimulated by LPS/IFN-\(\gamma\) was reduced to 52% of the levels found with LPS/IFN-\(\gamma\) induction alone.  
Kellerin (**321**) is the major constituent (1.5%, \(w/w\)) of _F. sinkiangensis_, and its anti-inflammatory mechanism is to inhibit the mRNA expression of inflammatory cytokines such as NO, tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)), COX-2, interleukin-6 (IL-6), and interleukin-1\(\beta\) (IL-1\(\beta\)) [190]. [PERSON] et al. [190] found that kellerin (**321**) could transform microglia from a pro-inflammatory M1 phenotype into an anti-inflammatory M2 phenotype, and thus alleviate cognitive impairment in mice. In another research, kellerin (**321**) was found to decrease the levels of pro-inflammatory cytokines, inhibit the NF-kB signaling pathway, and reduce ROS production and NADPH oxidase activity to exert neuroprotective effects [27].  
[PERSON] et al. reported six new sesquiterpene counarins from _F fukanensis_, four of which (fukanefuromarin H-K) (**385**, **388**, **396**, and **397**) showed NO-inhibitory activities, with IC\({}_{50}\) values of 11.1-55.6 uM. In addition, fukanefuromarin H (**385**) and fukanefuromarin K (**397**) could inhibit the gene expression of iNOS, IL-6, and TNF-\(\alpha\) [156]. The sesquiterpene counarins fererbungeand B (**308**) (IC\({}_{50}\) 23.6 uM) and samarcandin acetate (**290**) (IC\({}_{50}\) 25.6 uM) from _F. bungeana_ were found to have a strong inhibitory effect on NO production in LPS-induced BV-2 microglia compared with the positive control, minocycline (IC\({}_{50}\) 25.6 uM) [137]. Episamarcandin acetate (**295**) from _Ferula sinkiangensis_ was also found to exert its anti-inflammatory activity by significantly decreasing NO production, with an IC\({}_{50}\) value of 2.3 uM, and inhibiting TNF-\(\alpha\), IL-1\(\beta\), and IL-6 expression [149].