Targeted isolation of sesquiterpene lactone dimers from Aucklandia lappa guided by LC-HRMS/MS-based molecular networking.

An LC-HRMS/MS-based molecular networking strategy was applied to investigate the potential sesquiterpene dimers of Aucklandia lappa, leading to the isolation of three undescribed guaiane-guaiane dimers and one guaiane-eudesmane dimer together with six known sesquiterpenes. The structures were determined by analyzing their 1D, 2D NMR, and HRESIMS data as well as ECD calculations. The biogenetic pathway of the sesquiterpene dimers was postulated to involve the Diels-Alder cycloaddition as the key step. All compounds exhibited their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values ranging from 0.3 to 25.1 μM.

Han JS ，Kim JG ，Linh Le TP ，Cho YB ，Lee D ，Hong JT ，Lee MK ，Hwang BY ... -  《-》

Targeted isolation of dimeric sesquiterpene lactones and sesquiterpene derivatives from the roots of Inula helenium.

LC-HRMS/MS-based molecular networking was applied to investigate the bioactive sesquiterpene lactones and their analogs contained in Inula helenium, enabling the isolation of four undescribed eudesmane-eudesmane sesquiterpene dimers (1-4), a sesquiterpene-amino acid adduct (5), and 17 known sesquiterpenes (6-22). The structures were determined based on 1D, 2D NMR, and HRESIMS data analysis, as well as DP4+ probability analyses and ECD calculations. The biosynthetic pathway of the sesquiterpene dimers is postulated to proceed via the Diels-Alder reaction as the key step. The inhibitory activity of all isolates on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages was evaluated. Compounds 4, 17, and 20 exhibited significant inhibitory activity against NO production, with IC50 values of 8.4, 5.5, and 9.1 μM, respectively.

Han JS ，Kim JG ，Cho YB ，An BK ，Lee D ，Lee MK ，Hwang BY ... -  《-》

Sesquiterpenoids from the roots of Aucklandia costus and their anti-inflammatory activities.

Five undescribed sesquiterpenoid dimers, aucklandiolides A-E (1-5), one new sesquiterpenoid glycoside, β-cyclocostunolide-15-β-D-glucopyranoside (6), and seventeen known analogues (7-23) were isolated from the roots of Aucklandia costus. Their structures were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, and their configurations were confirmed by the computational calculations of ECD and NMR chemical shifts. Aucklandiolides A and B are the first examples of dimeric sesquiterpenoids with a unique 6/6/6/5/6/6 ring system originated from a proposed Diels-Alder cycloaddition between two eudesmane sesquiterpenoids. Besides, compounds 9-11, 20, and 22 showed significant inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells at a concentration of 20 μM.

Lyu HY ，Bao MY ，Io CC ，Xiong HM ，Chen FL ，Bai LP ，Zhang W ，Jiang ZH ，Zhu GY ... -  《-》

Undescribed amino acid-sesquiterpene lactone adducts and sesquiterpene glycosides from the roots of Saussurea lappa and their anti-HBV activity.

Saussurea lappa (Asteraceae family), a traditional Chinese medicine, has been found to possess anti-inflammatory, immune-promoting, antibacterial, antitumor, anti-HBV, cholestatic, and hepatoprotective activities. Herein, two undescribed amino acid-sesquiterpene lactone adducts, saussureamines G and H (1 and 2), and two new sesquiterpene glycosides, saussunosids F and G (3 and 4), along with 26 known sesquiterpenoids (5-30) have been isolated from the roots of S. lappa. Their structures and absolute configurations of these compounds were established by physical data analyses such as HRESIMS, IR, 1D and 2D NMR and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (5, 6, 12, 13, 17, 19, 23, 26, 29, and 30) exhibited activities against the secretions of HBsAg and HBeAg. In particular, compound 6 showed inhibition of HBsAg and HBeAg secretion with IC50 values of 11.24 and 15.12 μM, with SI values of 1.25 and 0.93, respectively. Molecular docking studies were also conducted on the anti-HBV compounds. Overall, this study provides insights into the potential therapeutic uses of the compounds found in the roots of S. lappa, particularly in the treatment of hepatitis B virus infections.

Cong XY ，He JY ，Shu TY ，Chen H ，Feng Y ，Su LH ，Xu M ... -  《-》

Sesquiterpene lactone dimers from Artemisia lavandulifolia inhibit interleukin-1β production in macrophages through activating autophagy.

Twelve new sesquiterpene lactone dimers, lavandiolides A-L (1-12), were isolated from the whole plants of Artemisia lavandulifolia. Among them, compounds 1-6 are 1,3-linked Diels-Alder adducts between two guaianolide monomers, and 7-12 are 2,4-linked sesquiterpene lactone dimers. Their structures were elucidated by comprehensive analysis of HRESIMS, 1D and 2D NMR spectra. Their absolute configurations were determined by ECD spectra and single-crystal X-ray diffraction analyses with Cu Kα radiation. The nitric oxide (NO) inhibitory effect of all the isolates was assessed on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compounds 1, 3, 7 and 9 showed potent inhibitory effects on NO production, with IC50 values of 0.61 ± 0.15, 1.64 ± 0.04, 1.89 ± 0.16, and 1.40 ± 0.23 μM, respectively. Furthermore, compound 1 inhibited NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome-mediated interleukin-1β (IL-1β) production through activating autophagy.

Wang Q ，Zhang T ，Ke CQ ，Tang C ，Yao S ，Lin L ，Ye Y ... -  《-》