Acyl atractyligenin and carboxyatractyligenin glycosides from Antennaria rosea subsp. confinis

Gou P., Xiao Y., Lv L., Xie H.

Three new glucosides of hydroquinone, monoterpene, and megastigmane, benzyl 2,5-dihydroxybenzoate 5-O-β-d-glucopyranoside (isotrichocarpin, 1), (2S,3R)-3,7-dimethyl-6-octene-1,2,3-triol 2-O-β-d-glucopyranoside (leontopodioside D, 4), and (6R,7R,8R,9S)-6,9-epoxy-7,8-dihydroxymegastigman-4-en-3-one 8-O-β-d-glucopyranoside (leontopodioside E, 7) were isolated from the whole herbs of Leontopodium leontopodioides (Willd.) Beauv. (Asteraceae), along with nebrodenside A (2), pungenin (3), betulalbuside A (5), geranyl O-β-d-glucopyranoside (6), and 3β-hydroxy-β-ionone 3-O-β-d-glucopyranoside (8). Their structure were determined by spectroscopic and chemical methods. All the known compounds were reported from this species for the first time. Compounds 2-6 showed potent in vitro pancreatic lipase inhibitory activity, suggesting their participation in the reductive effect of the herbs on triglyceride absorption.

Qi X., Zhang Y., Zhao P., Zhou L., Wang X., Huang X., Lin B., Song S.

Thirteen new ent-kaurane diterpenoids, stigmaydenes A-M (1-13), together with two known compounds (14, 15), were isolated from the crude extract of corn silk ( Zea mays). The structures of the compounds were confirmed by comprehensive spectroscopic analyses. The absolute configuration of compound 1 was defined by single-crystal X-ray diffraction. The absolute configurations of the compounds were also confirmed by comparison of experimental and calculated specific rotations. The compounds were evaluated for their neuroprotective effects against H2O2-induced SH-SY5Y cell injury, and compound 8 was active at 100 μM, as determined by flow cytometry (annexin V-FITC/PI staining) and Hoechst 33258 staining. The results suggested that compound 8 could protect neuronal cells from H2O2-induced injury by inhibiting apoptosis in SH-SY5Y cells.

Gu X., Shen X., Wang L., Wu Z., Li F., Chen B., Zhang G., Wang M.

The investigation of the fruits of Solanum nigrum led to the isolation of four previously undescribed steroidal alkaloids, named solanine A, 7α-OH khasianine, 7α-OH solamargine and 7α-OH solasonine, together with six known ones. The structures of the isolated compounds were elucidated unambiguously by spectroscopic data analyses and chemical methods. Solanine A represents an unusual steroidal alkaloid with an unprecedented 6/5/6/5/5/6 hexacyclic ring system, and its structure was confirmed by X-ray single crystal diffraction analysis. Compounds 2-4 were rare naturally occurring steroidal alkaloid glycosides bearing a hydroxyl group at C-7 position. Solanine A showed the most potent inhibitory activity against the LPS-induced NO production in murine RAW264.7 macrophages with an IC50 value of 3.85 ± 0.71 μM and significant cytotoxicity against MGC803, HepG2 and SW480 cancer cell lines with IC50 values of 6.00 ± 0.52 μM, 9.25 ± 0.49 μM and 6.23 ± 0.26 μM, respectively.

Zhang Y., Yang Y., Ruan J., Chen Q., Li J., Guo Y., Han L., Wang T.

A phytochemical investigation to obtain new triglyceride (TG) accumulation inhibitors resulted in the isolation of six new isobenzofuranones, leontopodiols A (1), B (2), leontopodiosides C (3), D (4), E (5), F (6), together with three known ones (7-9) from the aerial parts of Leontopodium leontopodioides (Willd.) Beauv. The structures of these isolates were identified by routine NMR experiments, optical rotation determination, electronic circular dichroism (ECD) calculation, along with chemical reaction. Moreover, compounds 1, 2, 5, and 7-9 displayed TG accumulation inhibitory effects on HepG2 cells.

Chen Q., Li J., Ruan J., Qu L., Wei H., Ma X., Zhang Y., Wang T.

Five new compounds, leontoaerialosides A (1), B (2), C (3), D (4), and E (5) were obtained from the 70% EtOH extract of the whole plants of Leontopodium leontopodioides (Wild.) Beauv. Their structures were elucidated by chemical and spectroscopic methods. Moreover, compounds 4 and 5 showed significant effects on stimulating the hepatic glucose uptake in HepG2 cells.

Qi C., Wang E., Jin L., Yan M., Zhang X., Wang H., Ye W.

Two new ent-kaurene diterpenoids, 13α,15α-dihydroxy-18-carboxy-19-nor-ent-kaur-16-ene-2β-O-(2′-angelate)-β- d -glucopyranoside (leontocin A, 1), 13α,15α-dihydroxy-18-carboxy-19-nor-ent-kaur-16-ene-2β-O-(2′-angelate-6′-acetyl)-β- d -glucopyranoside (leontocin B, 2), and one new lignan, 2,3-bis[(3,4-di-hydroxyphenyl)methylene]-monoethyl ester-butanedioic acid (leontolignan A, 3), together with three known phenolic acids (4-6) were isolated from the aerial parts of Leontopodium leontopodioides (Asteraceae). Their structures were elucidated by chemical and spectroscopic methods. All isolates were evaluated for their anti-inflammatory activities by measuring their inhibitory effects against cyclooxygenase-1 and 2 in vitro.

Jia X., Yang D., Xie H., Jiang Y., Wei X.

The fruit of Averrhoa carambola L. (Oxalidaceae) is a commercially important fruit. Our study on the chemical constituents present in the fresh sweet fruit led to the isolation of eleven non-flavonoid phenolic compounds. Their structures were identified by analyses of spectroscopic data. They were two new alkyl phenol diglucosides, carambolasides K (1) and L (2), four phenylpropanoids, (+)-isolariciresinol 9-O-β- d -glucoside (3), (+)-lyoniresinol 9-O-β- d -glucoside (4), (−)-lyoniresinol 9-O-β- d -glucoside (5), and 1-O-feruloyl-β- d -glucose (6), three benzoic acids, protocatechuic acid (7), 1-O-vanilloyl-β- d -glucose (8), and tecomin (9), a simple phenol, koaburaside (10), and a naphthoquinone, (+)-cryptosporin (11). All of them were reported from A. carambola fruit for the first time. Compounds 1–8 and 10 showed 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation scavenging activity comparable to l -ascorbic acid, while compounds 3, 5, and 7 exhibited potent ferric reducing antioxidant power (FRAP). In addition, compounds 6 and 11 demonstrated weak porcine pancreatic lipase inhibitory activity.

Xiao Y., Xie H., Zhao L., Gou P.

Two new acyl flavone glucosides, luteolin-4⿲-O-(6-p-hydroxybenzoyl)-β- d -glucopyranoside (leontopodioside A, 1) and luteolin-4⿲-O-[6-(2-methylbutyryl)]-β- d -glucopyranoside (leontopodioside B, 2), and a new acyl lignan glucoside, lariciresinol-9-angeloyl-4-O-β- d -glucopyranoside (leontopodioside C, 3) were isolated from the whole plants of Leontopodium leontopodioides (Asteraceae). Their structures were determined by spectroscopic and chemical methods. Compounds 1⿿3 exhibited α-glucosidase inhibitory activity with the half maximal inhibitory concentration (IC50) values of 55.6, 39.7, and 474.9 μM, respectively, in comparison with acarbose (626.3 μM).

Ercan P., El S.N.

The total saponin content and its in vitro bioaccessibilities in Tribulus terrestris and chickpea were determined by a static in vitro digestion method (COST FA1005 Action INFOGEST). Also, in vitro inhibitory effects of the chosen food samples on lipid and starch digestive enzymes were determined by evaluating the lipase, α-amylase and α-glucosidase activities. The tested T. terrestris and chickpea showed inhibitory activity against α-glucosidase (IC50 6967 ± 343 and 2885 ± 85.4 μg/ml, respectively) and α-amylase (IC50 343 ± 26.2 and 167 ± 6.12 μg/ml, respectively). The inhibitory activities of T. terrestris and chickpea against lipase were 15.3 ± 2.03 and 9.74 ± 1.09 μg/ml, respectively. The present study provides the first evidence that these food samples (T. terrestris, chickpea) are potent inhibitors of key enzymes in digestion of carbohydrates and lipids in vitro.

Lang R., Fromme T., Beusch A., Wahl A., Klingenspor M., Hofmann T.

2- O -β- d -Glucopyranosyl-carboxyatractyligenin isolated from raw coffee beans inhibits ATP-production in isolated mitochondria by blockage of adenine nucleotide translocase. UPLC-ToF-MS quantification revealed high levels of this phytochemical in lyophilized raw coffee extracts but complete degradation during coffee roasting. • Glucosides of atractyligenin derivatives were isolated from coffee. • Carboxyatractyligenin-glcp inhibits mitochondrial adenine nucleotide translocase. • A quantitation method was developed for atractyligenin glucoside derivatives. • Carboxyatractyligenin-glcp is degraded upon coffee roasting. Atractyloside ( 1 ) and carboxyatractyloside ( 2 ) are well-known inhibitors of the adenine nucleotide translocase (ANT) in mitochondria, thus effectively blocking oxidative phosphorylation. Structurally related derivatives atractyligenin ( 3 ), 2- O -β- d -glucopyranosyl-atractyligenin ( 4 ), 3′- O -β- d -glucopyranosyl-2′- O -isovaleryl-2β-(2-desoxy-atractyligenin)-β- d -glucopyranoside ( 5 ), and 2- O -β- d -glucopyranosyl-carboxyatractyligenin ( 6 ) were isolated from raw beans of Coffea L. and the impact of 1 – 6 on ANT activity was evaluated in isolated mitochondria. Among the coffee components, 6 significantly inhibited ANT activity leading to reduced respiration. Quantitative analysis in commercial coffees, experimental roastings of coffee, and model experiments using purified compound 6 consistently revealed a complete degradation during thermal treatment. In comparison, raw coffee extracts were found to contain high levels of 6 , which are therefore expected to be present in food products enriched with raw coffee extracts. This implies the necessity of analytically controlling the levels of 6 in raw coffee extracts when used as additives for food products.

Xie H., Yoshikawa M.

Further investigation on the whole herbs of Sinocrassula indica (Crassulaceae) led to the isolation of four new acylated flavonol bisdesmosides, sinocrassosides A₁₃, B₆, B₇, and D₄, together with kaempferol 3-O-β-D-(6-O-acetyl)glucopyranosyl-7-O-α-L-rhamnopyranoside. Their structures were established by spectral and chemical methods.

Li X., Luo J., Wang X., Luo J., Wang J., Kong L.

Two new compounds, a neolignan (1), and a benzofuran derivative (2), along with 6 known compounds (3-8), were isolated from the aerial parts of Leontopodium leontopodioides. The structures of the new compounds were elucidated as (7R,8S)-3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol (1) and (2R)-12-hydoxy-4-methoxy-tremeton (2) on the basis of their spectroscopic data, respectively. All of the isolates were evaluated for their effects on the inhibition of nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 macrophages and compounds 1 and 8 exhibited inhibitory activity with IC(50) values of 35.80 and 24.41 μM, respectively.

Brucoli F., Borrello M.T., Stapleton P., Parkinson G.N., Gibbons S.

We report the first complete structure elucidation of the ent-kaurane diterpenoid glycoside atractyloside (1) by means of NMR and X-ray diffractometry techniques. Extensive one- and two-dimensional NMR experiments were employed to assign the proton and carbon signals of 1, and crystallography experiments established the configurations of all stereogenic centers. Furthermore, we present a novel semisynthetic route for the preparation of the highly cytotoxic aglycone derivative of 1, 15-didehydroatractyligenin methyl ester (3). All compounds were tested for their antibiotic activity against Enterococcus faecalis, Escherichia coli, and several strains of Staphylococcus aureus, including fluoroquinolone-resistant (SA1199B) and two epidemic MRSA (EMRSA-15 and -16) strains. Compound 3 exhibited moderate activity against all of the Staph. aureus strains with an MIC value of 128 mg/L.

Lanzotti V., Termolino P., Dolci M., Curir P.

A phytochemical analysis of Aesculus pavia has led to the isolation of eight novel triterpenoid saponins, based on oleane type skeleton and named paviosides A-H (1a, 1b-4a, 4b). On the basis of chemical, and 2D NMR and mass spectrometry data, the structures of the new compounds were elucidated as 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-d-glucopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-tigloyl-22-acetyl barringtogenol C (1a), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-glucopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-angeloyl-22-acetyl barringtogenol C (1b), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-galactopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-tigloyl-22-acetyl barringtogenol C (2a), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-galactopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-angeloyl-22-acetyl barringtogenol C (2b), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-xylopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-tigloyl-22-acetyl barringtogenol C (3a), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-xylopyranosyl (1 → 4)]-β-d-glucopyranosiduronic acid 21-angeloyl-22-acetyl barringtogenol C (3b), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-xylopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-tigloyl-22-acetyl protoaescigenin (4a), and 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-xylopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-angeloyl-22-acetyl protoaescigenin (4b). The compounds showed cytotoxic activity on J-774, murine monocyte/macrophage, and WEHI-164, murine fibrosarcoma, cell lines. Among them, paviosides E-H (3a, 3b and 4a, 4b) showed higher activity with values ranging from 2.1 to 3.6 μg/mL. Structure-activity relationship studies indicated the positive effect on the activity of xylose unit in the place of glucose, while a little detrimental effect is observed when glucose is substituted by galactose. The aglycone structure and the presence of a tigloyl or an angeloyl group at C-21 do not affect significantly the inhibitory activity on both tested cell lines.

Sanchez J., Kauffmann B., Grélard A., Sanchez C., Trézéguet V., Huc I., Lauquin G.J.

Atractyloside (ATR) was characterized in 1868 and until now structural studies on diterpenic moiety had been done through the characterization of ATR derivatives; while the glycosidic moiety seemed to be a β-D-glucopyranose a recent crystal structure of the mitochondrial ATP/ADP carrier in complex with CATR showed an α-D-glucopyranose. We decided to re-examine the ATR and CATR structures by crystallographic study of ATR.

Bülbül M., Çokdinleyen S.

AbstractObesity is a condition caused by abnormal fat accumulation. The prevalence of obesity and related diseases is increasing globally, and efforts to find solutions are ongoing. In addition to diet, exercise, and surgery, drug therapy is recommended for individuals seeking a solution. Current anti‐obesity drugs target central and peripheral pathways. However, drugs targeting the central nervous system have serious side effects. Therefore, one of the approaches in the treatment of obesity is to inhibit pancreatic lipase (PL), which acts on peripheral pathways. Currently, the only clinically approved PL inhibitor is Orlistat, but this semi‐synthetic drug has also been associated with unwanted side effects. Recently, there has been extensive research on natural sources and natural products derived from these sources as potential lipase inhibitors with fewer side effects. This article reviews recent in vitro studies on inhibiting the PL enzyme by extracts from plants, fungi, and algae, as well as natural products derived from these extracts. In addition, the review presents recent molecular docking and in vivo studies demonstrating potential natural PL inhibitors.

Liu M., Jia Y., Xie H.

Michelia champaca L. (Magnoliaceae) was cultivated in large scale for flowers as cosmetic raw materials, whereas the value of its leaves remains to be discovered. Our chemical study on the leaves yielded four new flavonol diglycosides, champaflavosides A–D (1–4), together with twenty-three known flavonoid glycosides (5–27). Their structures were determined by spectroscopic and chemical methods. Compounds 5–21 and 23–27 were not previously reported from the genus Michelia, and kaempferol 3-O-rutinoside (22) was obtained from this species for the first time. All the compounds were evaluated for antioxidant activity by four in vitro assays. Compounds 3–12 and 20 showed more potent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity than l-ascorbic acid (l-AA). Compounds 2–23, 25, and 27 exhibited 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation scavenging activity superior to l-AA. The ferric reducing antioxidant powers (FRAP) of compounds 2–13, 17, and 19 were higher than l-AA. Further, eighteen compounds demonstrated cellular reactive oxygen species (ROS) scavenging activity, of which champaflavoside D (4), rhamnetin 3-O-neohesperidoside (8), quercetin 3-O-(6-O-E-p-coumaroyl)-neohesperidoside (9), and liquiritin (27) were more potent than curcumin. The results revealed that the renewable leaves of M. champaca are a rich source of flavonoids and antioxidants.

Chen Y., Dong Y., Song L., Bai C., Wang B., Sa C.

Leontopodium leontopodioides (Willd.) Beauv. (L. leontopodioides.) has been used to treat lung diseases in traditional Chinese medicine (TCM). However, a systematic analysis of its chemical components has not been reported so far. In this study, UPLC-Q-Orbitrap MS and GC-MS were applied to investigate the chemical composition of the water extracts and essential oils of L. leontopodioides. UPLC-Q-Orbitrap MS adopts a heating electrospray ionization source, collecting primary and secondary mass spectrometry data in positive and negative ions, respectively, and uses Compound Discoverer 3.2 software to analyze the collected raw data. As a result, a total of 39 compounds were identified from their high-resolution mass spectra in both positive and negative ionization modes, including 13 flavonoids and their glycosides, 15 phenolic acids, 4 oligosaccharides and glycosides, 4 pentacyclic triterpenoids, and 3 other compounds. Among them, 18 chemical components have not been reported in L. leontopodioides. In the GC-MS section, two common organic solvents (n-hexane and diethyl ether) were used to extract essential oils, and the mass spectra were recorded at 70 eV (electron impact) and scanned in the range of 35∼450 m/z. Compounds were identified using NIST (version 2017), and the peak area normalization method was used to calculate their relative amounts. Finally, 17 components were identified in the volatile oil extracted with n-hexane, accounting for 80.38% of the total volatile oil, including monoterpenoids, phenylpropene, fatty acids, and aliphatic hydrocarbons. In the volatile oil extracted with diethyl ether, 16 components were identified, accounting for 73.50% of the total volatile oil, including phenylpropene, aliphatic hydrocarbons, monoterpenoids, fatty acids, and esters. This study was the first to conduct a comprehensive analysis of the chemical composition of the L. leontopodioides water extract and its essential oil, and a comprehensive chemical composition spectrum was constructed, to lay a foundation for its further pharmacodynamic material basis and quality evaluation.

Badalamenti N., Bruno M., Pavela R., Maggi F., Benelli G.

AbstractPlant-borne secondary metabolites are attracting high interest for their potential use in agricultural applications, with special reference to the control of arthropod pests. In the present work, the structural elucidation of glycosylated diterpenoid carboxyatractyloside (2) isolated from the roots of Chamaeleon gummifer Cass. (Asteraceae) is reported by means of spectroscopic and spectrometric techniques. Complete identification occurred thanks to one- and two-dimensional NMR experiments, assigning the single protons and carbons, and the stereochemistry by the NOESY correlations. Carboxyatractyloside (2), together with two ent-kaurenes atractyloside (1) and atractyligenin (3), extracted from the roots of C. gummifer, have been tested for their acaricidal and oviposition inhibition activity against the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae) Notably, compounds 1–3 were toxic to T. urticae, leading to significant mortality, oviposition inhibition, reduced hatchability of eggs, and natality inhibition. However, at the lowest dose (12.5 µg cm−2) compound 2 was the most effective, leading to mortality > 60% after 5 days exposure, inhibiting oviposition by > 70% and egg hatching by 33%; it also reduced natality by 80%. Overall, these compounds represent valuable candidates to develop novel acaricides for crop protection. Further research on how to develop stable formulations for field use, as well as on non-target effects of these compounds on pollinators and mite biocontrol agents, is ongoing.

Rocha S., Rufino A.T., Freitas M., Silva A.M., Carvalho F., Fernandes E.

Badalamenti N., Vaglica A., Maggio A., Bruno M., Quassinti L., Bramucci M., Maggi F.

Atractyloside, carboxyatractyloside, their aglycon atractyligenin, and several synthetic derivatives were tested and found to be active against a panel of human tumor cell lines. Atractyligenin was subjected to oxidation, bromination, and elimination reactions, obtaining several compounds. A singular skeleton was synthesized by chemical rearrangement starting from 3β-bromo-2,15-diketoatractyligenin methyl ester. The synthesized compounds resulted active against all cell lines tested. In particular, 15-ketoatractyligenin methyl ester and 3β-bromo-2,15-diketoatractyligenin methyl ester resulted the most active with IC50 values of 0.427 and 0.723 μM against A375 melanoma cell line. Excellent results were also obtained against the colon cancer cell line CaCo2, with slightly lower antiproliferative activity. An interesting extension of the study should be to analyze the atractyligenin derivatives also as target for human melanoma and human colon cancer cells.

Wang S., Yu M., Li H., Zhang G.

Sixteen new (1-16) and three known (17-19) polyacylated ent-kaurane diterpenoid glycosides were isolated from the aerial parts of Inula hupehensis. The planar structures of 1-16 and their relative configurations were established on the basis of extensive spectroscopic analysis. The absolute configurations of all stereogenic centers for compounds 1 and 6 were determined by single-crystal X-ray diffraction experiments, and the absolute configurations of the other new compounds were assigned by chemical degradation and experimental ECD data. Antineuroinflammatory testing of all the isolates showed that compound 5 inhibited lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells with an IC50 value of 15.6 μM. In an α-glucosidase inhibitory assay, compound 13 exhibited a strong inhibitory effect with an IC50 value of 32.8 μM, whereas the IC50 value of the positive control, acarbose, was 387.8 μM.