## 2 Sesquietpene Lactones with Significant In Vivo Activity
### Arglabin  
Arglabin (**2**) (Figure 3), is a guaianolide sesquiterpene lactone with the chemical formula C\({}_{15}\)H\({}_{18}\)O\({}_{3}\), isolated from several species including _Artemisia myriantha_ Wall. ex [PERSON] [62; 63], _Artemisia jacutica_ [PERSON] [64], and _Artemisia glabella_ [PERSON] and Kir. species [65] where the extraction yield was 0.27% [66]. Fortunately, several synthetic and hemisynthetic methods for preparing compound **2** have been reported [67; 68; 69; 70], allowing it to be provided in the quantities necessary for research and medicinal applications.  
The arglabin (**2**) molecule contains a 5,7,5-tricyclic ring structure with contiguous stereo centers [70]. Furthermore, it contains both an epoxide and an \(\alpha\),\(\beta\)-unsaturated Michael acceptor, two functional groups that have important roles in its pharmacological activities [71]. There are many research lines advancing towards more effective drugs on the basis of the arglabin (**2**) molecule. New arglabin (**2**) derivatives have been obtained by chemical modification, the most successful being obtained via amination followed by treatment with gaseous hydrochloric acid. This converts arglabin (**2**) into the hydrochloride salt of the dimethyl amino adduct, which is very soluble in water [66; 72]. This arglabin (**2**) salt form was used in the therapy of several cancer types such as breast, lung, liver and esophageal tumors in oncological clinics of Kazakhstan [73; 74; 75]. Treatment of an esophageal carcinoma patient with compound 2 contributed to a significant reduction in tumor volume, favoring its regression and a lower incidence of leucopenia [75].  
In terms of mechanism of action, arglabin (**2**) inhibits farnesyl protein transferase enzyme [65; 72]. It influences DNA synthesis in murine P388 lymphocytic leukemia cells [74]. Recently, [PERSON] and co-authors [76] have reported that compound **2** inhibits T-cell receptor activation and anti-CD3-induced movement of intercellular Ca\({}^{2+}\) ions ([Ca\({}^{2+}\)],), blocks ERK1/2 phosphorylation and depletes [GSH] in Jurkat T cells.  
The anticancer effect of Arglabin (**2**) was also demonstrated by [PERSON] and colleagues [77] on xenografted oral squamous cell carcinomas. They elucidated that tumor growth is inhibited via  
Figure 3: Structure of arglabin (**2**).  
downregulation of relevant protein expression in the mTOR/PI3K/Akt signaling pathway and impairment of mitochondrial membrane potential, leading to apoptosis.  
Recently, the pharmacokinetic properties of arglabin (**2**) have been reviewed [72], highlighting that it mainly accumulates in the liver, quickly reaches peripheral tissues and penetrates the blood-brain barrier. Furthermore, according to the literature, arglabin (**2**) has no described adverse effects, since it does not affect normal liver and kidney function or cause local irritative/allergenic reactions, nor mutagenic or embryotoxic effects [66; 72; 78].  
Besides anticancer activity, arglabin (**2**) demonstrated in vivo anti-arthritis activity in a rat model. Arglabin (**2**) lowers the levels of inflammatory mediators and cytokines, and reduces expression of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), COX-2 (cyclooxygenase-2) and iNOS (inducible nitric oxide synthase) [79]. [PERSON] and co-authors [80] suggest that arglabin (**2**) is a compound with great potential in inflammation and atherosclerosis therapy. Using a high-fat diet ApoE2.Ki mouse model, experimental results [80] showed that arglabin (2) reduces inflammation by decreasing IL-18 and IL-18 levels and increases autophagy apoptosis [81].  
Studies carried out with arglabin (**2**) show its potential for developing new anticancer and/or anti-inflammatory drugs, the main limiting factor being its low bioavailability. The preparation of soluble active versions of compound 2, and/or new delivery systems may attract further interest in this sesquiterpene lactone.