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[Display omitted] • Four unusual sesquilignans compounds were isolated from the resin of Ferula sinkiangensis. • Hypothetic biosynthetic pathways of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. • Biological assay revealed that 2a and 2b could inhibit IL-6 and TNF-α production in LPS induced RAW264.7 cells in a dose-dependent manner. Sinkianlignans A − D (1 – 4), four new sesquilignans with an unusual architectures was characterized with a rarely α-γ′, β-γ′, and γ-γ′ linkage pattern, and sinkianlignans E − F (5 and 6), two lignans, were isolated from the Ferula sinkiangensis. Hypothetic biosynthetic pathway of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. The structures of isolates were established by spectroscopic techniques and computational methods. Biological evaluation of all the isolated compounds revealed that compounds 2a and 2b could inhibit IL-6 and TNF-α production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

• 16 New diarylheptanoid-chalcone hybrids were isolated from A. katsumadai. • Compounds 1 – 3 , 5 – 7 , 11 – 14 , 21 – 25 , and 27 showed PTP1B selective inhibition. • All compounds showed obvious inhibition on α -glucosidase. • Compounds 1 , 3 , and 12 were α -glucosidase and PTP1B mixed-type inhibitors. The EtOH extracts of the dried seeds of Alpinia katsumadai were revealed with hypoglycemic effects on db/db mice at the concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 16 new diarylheptanoid-chalcone hybrids, katsumadainols A 1 −A 16 (1 – 16), together with 13 known analogues (17 – 29), were isolated from A. katsumadai under the guidance of bioassay. Most of the compounds showed α -glucosidase and PTP1B dual inhibition, among which compounds 1 – 3 , 5 – 7 , 11 – 14 , 21 – 25 , and 27 showed PTP1B/TCPTP selective inhibition with IC 50 values ranging from 22.0 to 96.7 μM, which were 2–10 times more active than sodium orthovanadate (IC 50 , 215.7 μM). All compounds exhibited obvious inhibition against α -glucosidase with IC 50 values of 2.9–29.5 μM, indicating 6–59 times more active than acarbose (IC 50 , 170.9 μM). Study of enzyme kinetics indicated compounds 1 , 3 , and 12 were PTP1B and α -glucosidase mixed-type inhibitors with K i values of 13.1, 12.9, 21.6 μM, and 4.9, 7.4, 3.4 μM, respectively. [ABSTRACT FROM AUTHOR]

• Eleven new ent -labdane diterpenoids were isolated from C. odontochila. • Their absolute configurations were established by ECD, [ α ] D and X-ray methods. • One ent -labdane and four ent- kauranes showed α -glucosidase inhibitory activity. • Compounds 12 and 16 were mixed-type inhibitors with K i of 334.1 and 589.2 μM. • Docking study disclosed the importance of the carboxyl group at C-4 position. Eleven new ent -labdane diterpenoids, cheodontoins A-K (1 – 11), and thirteen known diterpenoids involving two ent -labdanes (12 – 13) and eleven ent- kauranes (14 – 24), were isolated from the active part of Chelonopsis odontochila (Lamiaceae) under the guidance of bioassay. The structures of cheodontoins A-K (1 – 11) were elucidated by extensive HRESIMS, 1D and 2D NMR, [ α ] D and ECD experiments, X-ray diffraction and quantum calculation. Interestingly, five nor- ent- labdanes (9 – 13) were obtained from this genus for the first time. One ent -labdane diterpenoid (12) and four ent- kaurane diterpenoids (16 , 19 , 23 , and 24) showed α -glucosidase inhibitory activity with IC 50 values of 326.5 ± 3.5, 599.1 ± 13.8, 620.1 ± 16.1, 185.0 ± 4.2, and 190.7 ± 11.6 μM, respectively. Compounds 12 and 16 were α -glucosidase mixed-type inhibitors with K i values of 334.1 and 589.2 μM according to the enzyme kinetics using Lineweaver-Burk and Dixon plots. Docking study manifested that compounds 12 and 23 well located in the catalytic pocket of α -glucosidase by hydrophobic effects with Trp1355, Trp1369, Phe1427, Phe1559, and Phe1560 residues. This study provides new insights for the antidiabetic effects of C. odontochila with ent -labdane and ent -kaurane diterpenoids as the active constituents. [ABSTRACT FROM AUTHOR]

[Display omitted] • 15 new compounds were isolated from the whole bodies of Blaps japanensis. • Compounds 1–3 are novel spiroindole alkaloids with a unique spiro[ chromane -4,3′- indoline ]-2,2′-dione motif. • Biological assay revealed that compounds could inhibit human cancer cells (A549, Huh-7, and K562), JAK3, ROCK1, COX-2, and extracellular matrix in rat renal proximal tubular cells. Blapspirooxindoles A–C (1 – 3), three novel spirooxindole alkaloids with a unique spiro[ chromane -4,3′- indoline ]-2,2′-dione motif, blapcumaranons A and B (4 and 5), two new 2-cumaranon derivatives, blapoxindoles A–J (6 – 15), ten new oxindole alkaloid derivatives, along with one known compound (16), were isolated from the whole bodies of Blaps japanensis. Their structures including absolute configurations were determined by using spectroscopic, X-ray crystallographic, and computational methods. Compounds 1 – 11 and 13 exist as racemic mixtures in nature, and their (–)- and (+)-antipodes were separated by chiral HPLC. Biological evaluations of these compounds were determined with multiple assays including anti-tumor, anti-inflammatory, and renal protection activities in vitro. Several compounds displayed effective activity in one or more assays. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ten new diarylheptanoid dimers were isolated from A. katsumadai. • Compounds 1 – 5 and 7 – 10 significantly stimulated GLP-1 secretion. • Compounds 1 – 4 showed obvious inhibition on GPa. • Compounds 1 – 5 and 10 were PTP1B selective inhibitors. • Compounds 1 – 4 were GLP-1 secretagogues and multiple-enzyme inhibitors. Ten new diarylheptanoid dimers, katsumadainols C 1 − C 10 (1 – 10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, α -glucosidase, PTP1B, and DPP4. Compounds 1 – 5 and 7 – 10 significantly stimulated GLP-1 secretion by 267.5–433.1% (25.0 μM) and 117.8–348.2% (12.5 μM). Compounds 1 – 4 exhibited significant inhibition on GPa with IC 50 values of 18.0–31.3 μM; compounds 1 – 5 showed obvious inhibition on α -glucosidase with IC 50 values of 6.9–18.2 μM; compounds 1 – 5 and 10 possessed PTP1B inhibitory activity with IC 50 values ranging from 35.5 to 80.1 μM. This investigation first disclosed compounds 1 – 4 as intriguing GLP-1 secretagogues and GPa, α -glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants. [ABSTRACT FROM AUTHOR]

[Display omitted] • 51 artemyrianolide H derivatives were synthesized and evaluated for cytotoxicity against human hepatoma cells. • 34 compounds were more active than artemyrianolide H and sorafenib. • Compound 25 induced G2/M phase arrest, apoptosis and bound to PDGFRA and MAP2K2. Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha , and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC 50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure−activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC 50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 μM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25 , and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with K D value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate. [ABSTRACT FROM AUTHOR]

[Display omitted] • Twenty-one new guaianolide dimers were isolated from Artemisia zhongdianensis. • Nine compounds exhibited cytotoxicity against HSC-LX2. • Compounds 2, 6 and 13 displayed inhibitory activity on the deposition of Col Ⅰ, HA and HL. • This study provides more evidence for understanding of antihepatic fibrosis potency of Artemisia zhongdianensis. In the search for new antihepatic fibrosis candidates, it was observed that the EtOH extract of Artemisia zhongdianensis and EtOAc fraction had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with the inhibitory ratios of 85.7 % and 83.9 % at 400 μg/mL. 21 new guaianolide dimers, artemzhongdianolides A1 − A21 (1 – 21) were isolated from the active fractions under the guidance of bioassay, and elucidated by spectral analyses (HRESIMS, 1D and 2D NMR, IR, ECD). The absolute stereochemistry of compounds 1 , 13 , and 14 was determined by single-crystal X-ray diffraction analyses. Cytotoxicity evaluation suggested that nine compounds exhibited activity against HSC-LX2 with IC 50 values ranging from 14.0 to 95.2 μM. Of them, compounds 2 , 6 , and 13 displayed significant cytotoxicity against HSC-LX2 with IC 50 values of 22.1, 24.3 and 14.0 μM, which were 6 to 10 times more active than the positive drug silybin (IC 50 , 148.6 μM). Preliminary mechanism study revealed that compounds 2 , 6 , and 13 could markedly inhibited the deposition of human collagen type Ⅰ (Col Ⅰ), human hyaluronic acid (HA), and human laminin (HL) with IC 50 values of 37.9, 54.8, and 28.0 μM (Col Ⅰ), 29.5, 25.3, and 42.9 μM (HL), 31.2, 94.6, and 12.4 μM (HA), which were 1.5 to 13-fold more potent than silybin. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fourteen new coumaric acid analogues were isolated from Artemisia capillaris. • Twelve compounds exhibited cytotoxicity against HSC-LX2. • Compound 2 displayed potent inhibitory activity on the deposition of Col Ⅰ, HL and HA. • This study provides more evidence for the traditional use of Artemisia capillaris against hepatic fibrosis. Under the guidance of bioassay against HSC-LX2, the EtOH extract and the EtOAc fraction of Artemisia capillaris (Yin-Chen) exhibited cytotoxic activity against HSC-LX2 with inhibitory ratios of 39.7% and 68.7% at the concentration of 400.0 μg/mL. Bioassay-guided investigation of Fr. D (the active fraction) yielded 14 new coumaric acid analogues, artemicapillasins A–N (1 – 14). The structures of the isolates were elucidated by spectroscopic analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. Cytotoxic activity against HSC-LX2 cells of these isolates was performed to reveal that 12 compounds demonstrated cytotoxicity with inhibitory ratios more than 50% at 400 μM. The most active artemicapillasin B (2) gave an IC 50 value of 24.5 μM, which was about 7 times more toxic than the positive drug silybin (IC 50 , 162.3 μM). Importantly, artemicapillasin B (2) showed significant inhibition on the deposition of human collagen type I (Col I), human laminin (HL) and human hyaluronic acid (HA) with IC 50 values of 11.0, 14.4 and 13.8 μM, which was about 7, 11 and 5 times more active than silybin. Artemicapillasin B (2) as an interesting antihepatic fibrosis candidate is worth in-depth study. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sixteen new guaiane-type sesquiterpenoids were isolated from A. atrovirens. • The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. • Compounds 3 and 5 displayed cytotoxicity with IC 50 values of 8.0 and 16.0 μM (HepG2), 18.2 and 32.2 μM (Huh7). Random screening revealed that the EtOH extract of Artemisia atrovirens showed significant cytotoxicity against two human hepatoma cell lines (HepG2 and Huh7) with the inhibitory ratio of 98.9% and 99.7% at the concentration of 100 μg/mL. Further bioactivity-guided isolation of active fraction led to 16 new guaiane-type sesquiterpenoids, artematrovirenins A–P (1 – 16). Their structures were elucidated by extensive spectroscopic data. The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. Pharmacological evaluation suggested that five compounds (3 , 5 , 8 , 10 , and 15) exhibited cytotoxicity, compounds 3 and 5 displayed cytotoxicity against HepG2 cell line with an IC 50 values of 8.0 and 16.0 μM, as well as against Huh7 cell line with values of 18.2 and 32.2 μM. [ABSTRACT FROM AUTHOR]

• Eleven new sesquiterpenoids were isolated from A. lavandulaefolia. • Fourteen compounds exhibited cytotoxicity against HSC-LX2 with IC 50 values ranging from 16.5 to 337.2 μM. • Compounds 14 , 15 and 18 displayed inhibitory activity on the deposition of Col I and HL. The preliminary assay suggested that the EtOH extract of Artemisia lavandulaefolia had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with an inhibitory ratio of 94.1% at 400 μg/mL. Bioassay-guided investigation led to eleven new sesquiterpenoids, artemilavanolides C–F (1 – 4) and artemlavandulolides A–G (5 – 11), as well as thirteen known compounds (12 – 24). Their structures were elucidated by extensive spectroscopic data and X-ray crystallographic analysis. Cytotoxicity evaluation suggested that fourteen compounds exhibited activity against HSC-LX2; compounds 22 , 23 and 24 were comparable to the positive control, silybin (IC 50 , 162.3 μM); compounds 6 , 9 and 16 showed moderate activity with IC 50 values of 109.3, 114.0 and 124.2 μM. Importantly, compounds 14 , 15 and 18 displayed significant cytotoxicity against HSC-LX2 with IC 50 values of 52.1, 16.5 and 21.3 μM, and inhibitory activity on the deposition of human collagen type I (Col I) and human laminin (HL) with IC 50 values ranging from 7.3 to 71.6 μM and from 18.6 to 72.9 μM. [ABSTRACT FROM AUTHOR]

• Thirteen new 2,6-epoxydiarylheptanoids were isolated from A. tsao-ko. • Eight diarylheptanoids showed obvious α -glucosidase inhibitory activity. • Compounds 12 and 13 were noncompetitive inhibitors of α -glucosidase. • The K i values of compounds 12 and 13 on α -glucosidase were 539.6 and 385.2 μM. The dried fruits of Amomum tsao-ko are well-known dietary spices and traditional Chinese medicines. The random screen revealed that 50% ethanol-water extract of A. tsao-ko demonstrated significant α -glucosidase inhibitory activity with an IC 50 value of 38.6 μg/mL. Bioactivity-guided isolation on the active fraction afforded 13 new 2,6-epoxy diarylheptanoids, tsaokopyranols A–M (1 – 13), and four known ones (14–17). Their structures featuring a 2,6-epoxy pyran ring were established by extensively spectroscopic analyses (HRESIMS, IR, UV, 1D and 2D NMR) and ECD calculations. Seven new (4 – 6 , 8 – 11) and one known (16) compounds showed obvious α -glucosidase inhibitory activity with IC 50 values ranging from 59.4 to 116.5 μM, higher than acarbose (IC 50 : 219.0 μM). An enzyme kinetic analysis indicated that compounds 12 and 13 were noncompetitive-type inhibitors of α -glucosidase with K i values of 539.6 and 385.2 μM. This result provided new insights for the usage of A. tsao-ko , and 2,6-epoxydiarylheptanoids as new anti-diabetic candidates. [ABSTRACT FROM AUTHOR]