Antibacterial Sesquiterpene Lactones from Kaunia lasiophthalma.

Phytochemical study of the species Kaunia lasiophthalma enabled the isolation of three undescribed and three known guaianolide-type sesquiterpene lactones, and one new benzofuran. The bioguided fractionation methodology was successful in detecting antimicrobial metabolites against Staphylococcus aureus strains and permitted the description of undescribed guaianolide-type sesquiterpene lactones with substitution patterns matching all those described in the Oxylobinae subtribe.

Inhibitory Effect of Selected Guaianolide and Germacranolide Sesquiterpene Lactones on Nitric Oxide Production.

Trilobolide and its analogues belong to the guaianolide type of sesquiterpene lactones, which are characteristic and widely distributed within the families Asteraceae and Apiaceae. Certain guaianolides are receiving continuously increasing attention for their promising sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)-inhibitory activity. However, because of their alkylation capabilities, they are generally toxic. Therefore, the search for compounds with significant immunobiological properties but with decreased cytotoxicities suitable for use in immune-based pharmacotherapy is ongoing. Therefore, we extended our previous investigation of the immunobiological effects of trilobolide to a series of structurally related guaianolides and germacranolides. To evaluate the relationship, we tested a series of selected derivatives containing α-methyl lactone or exomethylene lactone ring. For a wider comparison, we also included some of their glycosidic derivatives. We assessed the in vitro immunobiological effects of the tested compounds on nitric oxide (NO) production, cytokine secretion, and prostaglandin E2 (PGE2) release by mouse peritoneal cells, activated primarily by lipopolysaccharide (LPS), and evaluated their viability. The inhibitory effects of the apparently most active substance, 8-deoxylactucin, seem to be the most promising.

Guaianolide Sesquiterpene Lactones from Centaurothamnus maximus.

Centaurothamnus maximus (family Asteraceae), is a leafy shrub indigenous to the southwestern Arabian Peninsula. With a paucity of phytochemical data on this species, we set out to chemically characterize the plant. From the aerial parts, two newly identified guaianolides were isolated: 3ß-hydroxy-4α(acetoxy)-4ß(hydroxymethyl)-8α-(4-hydroxy methacrylate)-1αH,5αH, 6αH-gual-10(14),11(13)-dien-6,12-olide (1) and 15-descarboxy picrolide A (2). Seven previously reported compounds were also isolated: 3ß, 4α, 8α-trihydroxy-4-(hydroxymethyl)-lαH, 5αH, 6ßH, 7αH-guai-10(14),11(13)-dien-6,12-olide (3), chlorohyssopifolin B (4), cynaropikrin (5), hydroxyjanerin (6), chlorojanerin (7), isorhamnetin (8), and quercetagetin-3,6-dimethyl ether-4'-O-ß-d-pyranoglucoside (9). Chemical structures were elucidated using spectroscopic techniques, including High Resolution Fast Atom Bombardment Mass Spectrometry (HR-FAB-MS), 1D NMR; 1H, 13C NMR, Distortionless Enhancement by Polarization Transfer (DEPT), and 2D NMR (1H-1H COSY, HMQC, HMBC) analyses. In addition, a biosynthetic pathway for compounds 1-9 is proposed. The chemotaxonomic significance of the reported sesquiterpenoids and flavonoids considering reports from other Centaurea species is examined.

The Effect of Different Ester Chain Modifications of Two Guaianolides for Inhibition of Colorectal Cancer Cell Growth.

Several sesquiterpene lactones (STLs) have been tested as lead drugs in cancer clinical trials. Salograviolide-A (Sal-A) and salograviolide-B (Sal-B) are two STLs that have been isolated from Centaurea ainetensis, an indigenous medicinal plant of the Middle Eastern region. The parent compounds Sal-A and Sal-B were modified and successfully prepared into eight novel guaianolide-type STLs (compounds 1-8) bearing ester groups of different geometries. Sal-A, Sal-B, and compounds 1-8 were tested against a human colorectal cancer cell line model with differing p53 status; HCT116 with wild-type p53 and HCT116 p53-/- null for p53, and the normal-like human colon mucosa cells with wild-type p53, NCM460. IC50 values indicated that derivatization of Sal-A and Sal-B resulted in potentiation of HCT116 cell growth inhibition by 97% and 66%, respectively. The effects of the different molecules on cancer cell growth were independent of p53 status. Interestingly, the derivatization of Sal-A and Sal-B molecules enhanced their anti-growth properties versus 5-Fluorouracil (5-FU), which is the drug of choice in colorectal cancer. Structure-activity analysis revealed that the enhanced molecule potencies were mainly attributed to the position and number of the hydroxy groups, the lipophilicity, and the superiority of ester groups over hydroxy substituents in terms of their branching and chain lengths. The favorable cytotoxicity and selectivity of the potent molecules, to cancer cells versus their normal counterparts, pointed them out as promising leads for anti-cancer drug design.

[Guaianolides from aerial parts of Artemisia myriantha].

This study was performed to investigate the guaianolides from the aerial parts of Artemisia myriantha. The chemical constituents were isolated by chromatographic columns over silica gel, Sephadex LH-20, and ODS, as well as Semi-prep HPLC methods, and their structures were identified by NMR and MS data. Ten compounds were isolated and identified as follows: artemyriantholide E (1), tanaphillin (2), 1ß, 10ß-epoxydehydroleucodin (3), 5-hydroxyleucodin (4), dehydrocostuslactone (5), 3-O-methyl-iso-secotanapartholide (6), roxbughianin A (7), dehydroleucodin (8), arglabin (9), and 8α-acetoxyarglabin (10). Compound 1 was a new compound, and compounds 2-7 were isolated from this plant for the first time. Compound 3 exhibited selective cytotoxicity against human liver cancer (Bel-7402) with IC50 value of 5.35 µmol·L⁻¹, and 6 against human gastric cancer (BGC-823) with IC50 value of 2.68 µmol·L⁻¹, respectively.

Effect of guaianolides in the meiosis reinitiation of amphibian oocytes.

Sesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under stimulus with progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. There are previous records of the inhibitory effect of dehydroleucodin (DhL), a guaianolide lactone, on the progression of meiosis. It has been also shown that DhL and its 11,13-dihydroderivative (2H-DhL; a mixture of epimers at C-11) act as blockers of the resumption of meiosis in fully grown ovarian oocytes from the amphibian Rhinella arenarum (formerly classified as Bufo arenarum). The aim of this study was to analyze the effect of four closely related guaianolides, i.e., DhL, achillin, desacetoxymatricarin and estafietin as possible inhibitors of meiosis in oocytes of amphibians in vitro and discuss some structure-activity relationships. It was found that the inhibitory effect on meiosis resumption is greater when the lactone has two potentially reactive centres, either a α,ß-α',ß'-diunsaturated cyclopentanone moiety or an epoxide group plus an exo-methylene-γ-lactone function.

A Double Allylation Strategy for Gram-Scale Guaianolide Production: Total Synthesis of (+)-Mikanokryptin.

With over 5000 members isolated to date, sesquiterpene lactones represent a prolific source of medicinal agents with several derivatives in human clinical trials. The guaianolides, a major subset of this group, have been intensely investigated from both medicinal and chemical-synthesis perspectives for decades. To date, the myriad stereochemical permutations presented by this enormous family have precluded the synthesis of many unique members. Herein we report the total synthesis of the trans-fused 8,12-guaianolide (+)-mikanokryptin in 10 steps from (+)-carvone. Notably, this synthesis is the first gram-scale total synthesis of a guaianolide natural product.

Further amphoricarpolides from the surface extracts of Amphoricarpos complex from Montenegro.

Analysis of composition of sesquiterpene lactone fraction of leaf cuticular neutral lipids of Amphoricarpos complex from two different localities in north Montenegro, i.e., canyon of river Tara (A. autariatus ssp. autariatus) and mountain Zeletin (A. autariatus ssp. bertisceus) afforded sesquiterpene lactones with guaianolide skeletons (17 compounds), so called amphoricarpolides, typical for this genus. Nine of them, 9-17, were new compounds, and their structures were elucidated by detailed analyses of IR, NMR, and MS data.

Guaianolide sesquiterpenes and their activity from Artemisia mongolica.

Seven undescribed sesquiterpenes, including three dimeric guaianolide sesquiterpenes artemongolides G-I (1-3) and four sesquiterpene lactones artemanomalide D-G (16-19), along with seventeen known compounds isoabsinthin (4), absinthin (5), 11-eptabsinthin (6), 11, 11'-bis-epiabsinthin (7), 10', 11'- epiabsinthin (8), anabsinthin (9), isoanabsinthin (10), absinthin D (11), anabsin (12), caruifolin D (13), gnapholide (14), caruifolin C (15), 1ß(R),10ß(S)-dihydroxy-3-oxo-11ß (S)H-4,11(13)-guaien-6α(S),12-olide (20), 1α,6α,8α-trihydroxy-5α,7ßH-guaia-3,10(14),11(13)-trien-12-oic acid (21), 1α,6α,8α-trihydroxy-5α,7ßH-guaia-3,9,11(13)-trien-12-oic acid (22), argyinolide J (23), artabsinolide A (24) were isolated from the plant Artemisia mongolica. The structures were determined by interpreting NMR, HRESIMS and ECD data. The X-ray crystal structure of 4, 7 and 8 were reported for the first time. In the anti-vitiligo activity test, compounds 2, 7, 12, 23 and 24 demonstrated activity in promoting melanogenesis at a concentration of 50 µM in B16 cells, with 8-methoxypsoralan (8-MOP) as a positive control. Further research on the mechanism revealed that artemongolides H (2) enhance the expression of MITF and TRPs by upregulating p-Akt and p-GSK-3ß, leading to an increase in ß-catenin content in the cell cytoplasm. Subsequently, ß-catenin translocates into the nucleus, resulting in melanogenesis. The results supported the regulation of melanogenesis by artemongolide H (2) through the Akt/GSK3ß/ß-catenin signaling pathway. The anti-inflammatory results demonstrated that compounds 4, 5, 6, 9 and 14 can inhibit the upregulation of IL-6 mRNA and CCL2 mRNA expression. Compound 12 specifically inhibited the upregulation of IL-6 mRNA expression. These compounds exhibited significant anti-inflammatory activities. The activity results revealed that these sesquiterpene compounds have the potential to become lead compounds for the treatment of vitiligo and inflammatory diseases.

Contact sensitization to calocephalin, a sesquiterpene lactone of the guaianolide type from cushion bush (Leucophyta brownii, Compositae).

BACKGROUND: Cushion bush [Leucophyta brownii Cass. = Calocephalus brownii (Cass.) F. Muell.] is an Australian Compositae shrub that has been introduced into Scandinavia as a pot plant. The first case of sensitization occurred in a gardener, and the main allergen was identified as the guaianolide calocephalin. OBJECTIVE: To present the identification of the main allergen, and to assess the prevalence of sensitization to calocephalin in Compositae-allergic patients. MATERIALS AND METHODS: Calocephalin was isolated from a dichloromethane extract of aerial parts of cushion bush. Calocephalin 0.1% ethanol was included in the plant series in Malmö, Sweden, and Odense, Denmark. RESULTS: Nuclear magnetic resonance (NMR) analysis of calocephalin resulted in a revision of its chemical structure to 4α-acetoxy-1α,2α-epoxy-5α,10αH-guai-11(13)-en-12,8ß-olide. The prevalence of patch test positivity was up to 28% in aimed patch testing. Despite strongly positive patch test reactions, the relevance was unknown in the majority of cases, and only 1 person was occupationally sensitized. CONCLUSION: Calocephalin is a potent contact allergen, but, as cushion bush is a low-maintenance pot plant, primary sensitization is most likely to occur through occupational exposure. Positive reactions in Compositae-sensitive persons probably occur because of cross-reactivity, and patients should be warned about contact with cushion bush plants.

Non-Volatile Terpenoids and Lipophilic Flavonoids from Achillea erba-rotta Subsp. moschata (Wulfen) I. Richardson.

Musk yarrow (Achillea erba-rotta subsp. moschata (Wulfen) I. Richardson) is endemic to the Central Alps, and is used to flavour alcoholic beverages. Despite its popularity as aromatizing agent and its alleged beneficial effects on digestion, the phytochemical profile of the plant is still largely unknown and undiscovered. As a consequence, its authentication in aromatized products is impossible beyond sensory analysis allowing forgery. To address these issues, we phytochemically characterized a sample of musk yarrow from the Italian Eastern Alps, identifying, in addition to widespread phytochemicals (taraxasterol, apigenin), the guaianolides 3, 8, 9; the seco-caryophyllane 6; and the polymethoxylated lipophilic flavonoids 1, 4, and 5. The flavonoid xanthomicrol 1, a major constituent of the plant, was cytotoxic to HeLa cells, but only modestly affected primary 3T3 fibroblasts. On account of their stability, detectability by UV absorption, and concentration, the oxygenated flavonoids qualify as markers to validate the supply chain of the plant growers to consumers.

Guaianolides from Achillea millefolium L. and their anti-inflammatory activity.

Seven previously undescribed guaianolides, millefolactons A-G, and three known analogues, millefoliumins A-C, were isolated from the whole plant of Achillea millefolium L. growing in Xinjiang, China. Their structures were elucidated using the HR-ESI-MS and NMR data analyses. The absolute configurations of millefolactons A-G were determined by single-crystal X-ray crystallography, ECD data analysis, and quantum-chemical ECD calculations. Millefolactons A-E are rare 3-oxa-guaianolides. Millefolacton C, millefolacton E, millefoliumin A and millefoliumin B exhibited enzymatic inhibition of 15-LOX. Molecular docking simulations were conducted to visualize interactions between the four active compounds and 15-LOX and determine binding mechanisms. Moreover, a LPS-induced BV2 cell model was used to further investigate the anti-inflammatory mechanism of millefolacton C. As a result, millefolacton C significantly inhibited NO release, repressed levels of pro-inflammatory cytokines including TNF-α, IL-18, PGE2 and IL-6, and inhibited the protein expression of iNOS and COX2 proteins. In addition, millefolacton C could potently decreased the expression of NLRP3, ASC, and IL-1ß proteins in LPS-stimulated BV2 cells. These results indicate that the 3-oxa-guaianolides from A. millefolium L. offer great potential as leads for anti-inflammatory drug development.

Identification and characterization of CYP71 subclade cytochrome P450 enzymes involved in the biosynthesis of bitterness compounds in Cichorium intybus.

Industrial chicory (Cichorium intybus var. sativum) and witloof (C. intybus var. foliosum) are crops with an important economic value, mainly cultivated for inulin production and as a leafy vegetable, respectively. Both crops are rich in nutritionally relevant specialized metabolites with beneficial effects for human health. However, their bitter taste, caused by the sesquiterpene lactones (SLs) produced in leaves and taproot, limits wider applications in the food industry. Changing the bitterness would thus create new opportunities with a great economic impact. Known genes encoding enzymes involved in the SL biosynthetic pathway are GERMACRENE A SYNTHASE (GAS), GERMACRENE A OXIDASE (GAO), COSTUNOLIDE SYNTHASE (COS) and KAUNIOLIDE SYNTHASE (KLS). In this study, we integrated genome and transcriptome mining to further unravel SL biosynthesis. We found that C. intybus SL biosynthesis is controlled by the phytohormone methyl jasmonate (MeJA). Gene family annotation and MeJA inducibility enabled the pinpointing of candidate genes related with the SL biosynthetic pathway. We specifically focused on members of subclade CYP71 of the cytochrome P450 family. We verified the biochemical activity of 14 C. intybus CYP71 enzymes transiently produced in Nicotiana benthamiana and identified several functional paralogs for each of the GAO, COS and KLS genes, pointing to redundancy in and robustness of the SL biosynthetic pathway. Gene functionality was further analyzed using CRISPR/Cas9 genome editing in C. intybus. Metabolite profiling of mutant C. intybus lines demonstrated a successful reduction in SL metabolite production. Together, this study increases our insights into the C. intybus SL biosynthetic pathway and paves the way for the engineering of C. intybus bitterness.

Phytochemical investigation of Volutaria lippii and evaluation of the antioxidant activity.

Volutaria lippii (L.) Cass. ex Maire, syn. Centaurea lippii (L.), (Asteraceae) is a plant from the central region of Algeria, considerably distributed in all Mediterranean areas. Herein, the antioxidant activity of the three derived fractions [chloroform (CHCl3), ethyl acetate (EtOAc) and n-butanol (n-BuOH)] of the 70% methanol extract of the aerial parts (leaves and flowers), was assessed by using CUPRAC, ABTS, DPPH free radical scavenging, and ß-carotene bleaching methods. The results obtained allowed to guide the fractionation of EtOAc and n-BuOH fractions by CC followed by purification by TLC and reverse phase HPLC. A guaianolide glucoside, 3ß-hydroxy-11ß,13-dihydrodehydrocostuslactone 8α-O-(6'-acetyl-ß-glucopyranoside) (1), never reported in the literature, was isolated together with other known compounds (2-14). Their structures were elucidated by the extensive use of 1 D- and 2 D-NMR experiments along with ESI-MS analyses and with comparison with literature data.

Guaianolides and unusual 3-oxa-guaianolides from Artemisia macrocephala.

Eight undescribed guaianolides (macrocephalolides A-H) and two known analogues (parishin C, artabsinolide E) were isolated from the whole plant of Artemisia macrocephala growing in Xinjiang, China. Their structures were determined on the basis of extensive spectroscopic analysis, with absolute configurations established by comparison of experimental and calculated ECD data, as well as confirmation of single-crystal X-ray diffraction crystallography. Macrocephalolides A-B featured an unusual type of 3-oxa-guaianolide with a cyclopentenone moiety. Macrocephalolides C-E possessed a dihydro-2H-pyran acetal segment, representing an unprecedented 2, 3-secoguaianolide skeleton with 6/7/5 tricyclic ring system in natural sesquiterpenes. The X-ray crystal structures of parishin C and artabsinolide E were reported for the first time.

Essential Oil and Non-Volatile Metabolites from Kaunia longipetiolata (Sch.Bip. ex Rusby) R. M. King and H. Rob., an Andean Plant Native to Southern Ecuador.

Kaunia longipetiolata (Sch.Bip. ex Rusby) R. M. King and H. Rob. (Asteraceae) is a plant native to southern Ecuador. The dry leaves afforded, by steam distillation, an essential oil that was qualitatively and quantitatively analyzed by GC-MS and GC-FID, respectively, on two orthogonal columns of different polarity. Sesquiterpenes predominated in the volatile fraction, among which α-zingiberene (19.7-19.1%), ar-curcumene (17.3-18.1%), caryophyllene oxide (5.1-5.3%), (Z)-ß-caryophyllene (3.0-3.1%), (2Z,6Z)-farnesal (2.6-3.6%), and spathulenol (2.0-2.1%) were the major components. In addition to the identified compounds, two main unidentified constituents (possibly oxygenated sesquiterpenes) with probable molecular masses of 292 and 230, respectively, were detected. They constituted about 5% and 8% (w/w), respectively, of the whole essential oil. The oil chemical composition was complemented with the enantioselective analysis of ten chiral components. Four scalemic mixtures and six enantiomerically pure terpenes were identified. An enantiomeric excess (ee) was determined for (1R,5R)-(+)-ß-pinene (65.0%), (R)-(-)-α-phellandrene (94.6%), (S)-(+)-linalool (15.0%), and (R)-(-)-terpinen-4-ol (33.8%). On the other hand, (1R,5R)-(+)-α-pinene, (1R,5R)-(+)-sabinene, (S)-(-)-limonene, (S)-(+)-ß-phellandrene, (1R,2S,6S,7S,8S)-(-)-α-copaene, and (R)-(+)-germacrene D were enantiomerically pure. Finally, the non-volatile fraction obtained by extraction of the leaves with MeOH was investigated. Eight known compounds were isolated by liquid column chromatographic separations. Their structures were determined by NMR spectroscopy as dehydroleucodine, kauniolide, (3S,3aR,4aR,6aS,9aS,9bR)-3-hydroxy-1,4a-dimethyl-7-methylene-5,6,6a,7,9a,9b-hexahydro-3H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one, novanin, bisabola-1,10-diene-3,4-trans-diol, (R)-2-(2-(acetoxymethyl)oxiran-2-yl)-5-methylphenyl isobutyrate, eupalitin-3-O-glucoside, and 3,5-di-O-caffeoylquinic acid. Literature data about the identified metabolites indicate that K. longipetiolata is a rich source of biologically active natural products.

Sesquiterpenes from Artemisia Sieversiana and their anti-inflammatory activities.

Eight undescribed sesquiterpenes, including three dimeric guaianolides and five sesquiterpens, together with ten known ones, were isolated from the aerial parts of Artemisia sieversiana. Their structures were elucidated by extensive spectroscopic techniques and ECD calculation. The isolated compounds were tested for their anti-inflammatory effects against IL-1ß, IL-6 and TNF-α in LPS-induced RAW 264.7 cells. Compounds 4, 9, 12, 15, 16 and 17 showed potent anti-inflammatory activities.

Guaianolides from Artemisia codonocephala suppress interleukine-1ß secretion in macrophages.

Sesquiterpene lactones supply a variety of scaffolds for the development of anti-inflammatory drugs. In this study, eight undescribed guaianolides, i.e., lavandolides A‒H, were isolated from the whole plants of Artemisia codonocephala, together with five known analogues. Their planar structures and relative configurations were elucidated by spectroscopic measurements, and their absolute configurations were determined by electronic circulardichroism spectra and single crystal X-ray diffraction experiments. The nitric oxide inhibitory effect of all the isolates was assessed on lipopolysaccharide stimulated THP-1 macrophages. Lavandolide D showed a potent inhibitory effect on NO production, with IC50 values of 3.31 ± 0.74 µM. Furthermore, lavandolide D inhibited NOD-, LRR- and pyrin domain-containing protein 3 inflammasome-mediated interleukin-1ß production through activating autophagy.

Sesquiterpene Lactones from Cotula cinerea with Antibiotic Activity against Clinical Isolates of Enterococcus faecalis.

Cotula cinerea, belonging to the tribe Anthemideae, is a plant widespread in the Southern hemisphere. It is frequently used in folk medicine in North African countries for several of its medical properties, shown by its extracts and essential oils. The dichloromethane extract obtained from its aerial parts demonstrated antibiotic activity against Enterococcus faecalis and was fractionated by bioguided purification procedures affording five main sesquiterpene lactones. They were identified by spectroscopic methods (NMR and ESIMS data) as guaiantrienolides, i.e., 6-acetoxy-1ß-,6-acetoxy-1α-, and 6-acetoxy-10-ß-hydroxyguaiantrienolide (1-3), and germacrenolides, i.e., haagenolide and 1,10-epoxyhaagenolide (4 and 5). The absolute configuration was assigned by applying the advanced Mosher's method to haagenolide and by X-ray diffraction analysis to 1,10-epoxyhaagenolide. The specific antibiotic and antibiofilm activities were tested toward the clinical isolates of Enterococcus faecalis. The results showed that compounds 3-5 have antibacterial activity against all the strains of E. faecalis, while compound 2 exhibited activity only toward some strains. Compound 1 did not show this activity but had only antibiofilm properties. Thus, these metabolites have potential as new antibiotics and antibiofilm against drug resistant opportunistic pathogens.

Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation.

Inflammation is a crucial and complex process that reestablishes the physiological state after a noxious stimulus. In pathological conditions the inflammatory state may persist, leading to chronic inflammation and causing tissue damage. Sesquiterpene lactones (SLs) are composed of a large and diverse group of highly bioactive plant secondary metabolites, characterized by a 15-carbon backbone structure. In recent years, the interest in SLs has risen due to their vast array of biological activities beneficial for human health. The anti-inflammatory potential of these compounds results from their ability to target and inhibit various key pro-inflammatory molecules enrolled in diverse inflammatory pathways, and prevent or reduce the inflammatory damage on tissues. Research on the anti-inflammatory mechanisms of SLs has thrived over the last years, and numerous compounds from diverse plants have been studied, using in silico, in vitro, and in vivo assays. Besides their anti-inflammatory potential, their cytotoxicity, structure-activity relationships, and pharmacokinetics have been investigated. This review aims to gather the most relevant results and insights concerning the anti-inflammatory potential of SL-rich extracts and pure SLs, focusing on their effects in different inflammatory pathways and on different molecular players.