Structurally Diverse Sesquiterpenoids from the Genus of Ainsliaea.

The genus of Ainsliaea embraces approximately 70 recognized species, many of which have been used to treat various diseases in folklore medicines. As the main metabolites of Ainsliaea plants, Ainsliaea sesquiterpenoids have drawn considerable attention in related scientific communities due to their intriguing structures and a variety of bioactivities. In this review, we intend to provide a full-aspect coverage of sesquiterpenoids reported from the genus of Ainsliaea, including 145 monomeric sesquiterpenoids and 30 oligomeric ones. Multiple aspects will be summarized, including their classification, distributions, structures, bioactivities, and biomimetic syntheses. In addition, their possible biosynthetic pathway will be discussed in detail.

[Research progress on chemical structures and pharmacological effects of natural cytisine and its derivatives].

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.

Purification, Structural Analysis and Cardio-Protective Activity of Polysaccharides from Radix Astragali.

Two polysaccharides, named APS2-I and APS3-I, were purified from the water extract of Radix Astragali. The average molecular weight of APS2-I was 1.96 × 106 Da and composed of Man, Rha, GlcA, GalA, Glc, Gal, Xyl, and Ara in a molar ratio of 2.3:4.8:1.7:14.0:5.8:11.7:2.8:12.6, while the average molecular weight of APS3-I was 3.91 × 106 Da and composed of Rha, GalA, Glc, Gal, and Ara in a molar ratio of 0.8:2.3:0.8:2.3:4.1. Biological evaluation showed APS2-I and APS3-I had significant antioxidant activity and myocardial protection activity. Furthermore, total polysaccharide treatment could significantly enhance hemodynamic parameters and improve cardiac function in rat ischemia and reperfusion isolated heart models. These results provided important information for the clinical application of APS in the field of cardiovascular disease and implied that Astragalus polysaccharides (APS) could be considered as a reference for the quality control of Radix Astragali.

α-Glucosidase and Bacterial ß-Glucuronidase Inhibitors from the Stems of Schisandra sphaerandra Staph.

α-Glucosidase (AGS) is a therapeutic target for Type 2 diabetes mellitus (T2DM) that tends to complicate with other diseases. Some medications for the treatment of T2DM complications have the risk of inducing severe adverse reactions such as diarrhea via the metabolism of intestinal bacterial ß-glucuronidase (BGUS). The development of new AGS and/or BGUS inhibitors may improve the therapeutic effects of T2DM and its complications. The present work focused on the isolation and characterization of AGS and/or BGUS inhibitors from the medicinal plant Schisandra sphaerandra. A total of eight compounds were isolated and identified. Sphaerandralide A (1) was obtained as a previously undescribed triterpenoid, which may have chemotaxonomy significance in the authentication of the genus Schisandra and Kadsura. 2'-acetyl-4',4-dimethoxybiphenyl-2-carbaldehyde (8) was obtained from a plant source for the first time, while compounds 2-7 were isolated from S. sphaerandra for the first time. In the in vitro assay, compounds 1-5 showed potent to moderate activity against AGS. Interestingly, compound 3 also exhibited significant BGUS inhibitory activity, demonstrating the potential of being developed as a bifunctional inhibitor that may find application in the therapy of T2DM and/or the diarrhea induced by medications for the treatment of T2DM complications.

Lignans and sesquiterpenes from Schisandra tomentella A. C. Smith.

This is the first phytochemical investigation of Schisandra tomentella A. C. Smith. 11 lignans and 8 sesquiterpenoids, were isolated from the stems of S. tomentella, including two undescribed lignans, tomentaschinins A-B (1-2), and two new sesquiterpenoids, tomentaschinnes A-B (3-4). Their structures were elucidated based on the interpretation of their spectroscopic data. Cytotoxicity and MDR reversal effect of these compounds were screened on multidrug resistance cancer cell line MCF-7/ADR, and results showed gomisin M2 (7) could promote the efficacy of adriamycin against MCF-7/ADR.

Dibenzocyclooctadiene lignans from the stems of Schisandra sphaerandra.

Chemical investigation into the stems of the medicinal plant Schisandra sphaerandra led to the isolation and identification of a new dibenzocyclooctadiene lignan sphaerandrin A (1) and 11 known ones gomisin B (2), schirubrisin B (3), kadsuphilin B (4), schizandrin (5), benzoylgomisin Q (6), angeloylgomisin Q (7), gomisin G (8), schisanwilsonin O (9), isogomisin O (10), schisantherin D (11), and wuweizisu C (12). The structure of the new compound was elucidated by comprehensive spectroscopic methods including 1 D/2D NMR, HRESIMS, and CD spectrometry. To the best of our knowledge, compounds 2 - 11 were obtained from this species for the first time. All the compounds were evaluated for the cytotoxic activity against the triple-negative breast cancer cell lines MDA-MB-231 and HCC-1937.

Biotransformation of Huperzine A by Irpex lacteus-A fungal endophyte of Huperzia serrata.

The biotransformation of huperzine A (hupA), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. Two previously undescribed compounds 1-2, along with a known analog 8α,15α-epoxyhuperzine A (3), were isolated and identified. The structures of all the isolates were established by spectroscopic methods including NMR, MS, IR, and UV spectra. In particular, the absolute configurations of 1 and 2 were elucidated by CD spectra comparison and theoretic NOE strength calculation. In the LPS-induced neuro-inflammation injury assay, 1-3 exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with EC50 values of 35.3 ±â€¯0.9, 32.1 ±â€¯0.9, and 50.3 ±â€¯0.8 nM, respectively.

Biotransformation of Huperzine B by a Fungal Endophyte of Huperzia serrata.

The biotransformation of huperzine B (hupB), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. One new compound, 8α,15α-epoxyhuperzine B (1), along with two known oxygenated hupB analogs, 16-hydroxyhuperzine B (2) and carinatumin B (3), was isolated and identified. The structures of all the isolates were deduced by spectroscopic methods including NMR, MS, IR, and UV spectra. The known compounds 2 and 3 were obtained from a microbial source for the first time. To the best of our knowledge, it is the first report on the microbial transformation of hupB and would facilitate further structural modification of hupB by chemo-enzymatic method. In the LPS-induced neuro-inflammation injury assay, 8α,15α-epoxyhuperzine B (1) exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with an EC50 of 40.1 nm.

New Eudesmane Sesquiterpenoids from Salvia plebeia R. Br.

Three new sesquiterpenoids, salplebeones A - C (1 - 3), were isolated from the ethanol-soluble extract of the aerial part of Salvia plebeia R. Br. Their structures were established by detailed analysis of NMR and MS spectra. Salplebeone A was an eudesmane lactone, while salplebeones B and C were rare eudesmane sesquiterpenoids, containing 12,8-lactam groups. Antiproliferative activities of salplebeones A - C to myeloid leukemia cell lines were evaluated.

New cytotoxic phloroglucinol derivatives from Agrimonia pilosa.

Three new phloroglucinol derivatives, namely agripinol A-C (1-3), were isolated from Agrimonia pilosa Ledeb, along with two known ones (4-5). Their structures were characterized by spectroscopic methods, including MS and NMR spectroscopic techniques. The absolute configurations of the new compounds were unambiguously established by single crystal X-ray diffraction analyses. In the cytotoxicity assay, all compounds exhibited more potent cytotoxic activities against HCT-116, MDA-MB-231 and PC-3, as compared with the positive control fluorouracil.

C21 steroid-enriched fraction refined from Marsdenia tenacissima inhibits hepatocellular carcinoma through the coordination of Hippo-Yap and PTEN-PI3K/AKT signaling pathways.

Marsdenia tenacissimae extraction (MTE), a traditional herbal medicine, has exhibited anti-tumor effects on a variety of cancers. However, its effectiveness and the mechanism of action in Hepatocellular carcinoma (HCC) has not been fully understood. In the present study, we demonstrate that C21 steroid-enriched fraction from MTE, which contains five main C21 steroids (FR5) exhibits obvious pharmacological activities on HCC cells in vitro and in vivo. FR5 induces apoptosis and inhibits proliferation and migration of HepG2 and Bel7402 cells in a dose and time dependent manner. Furthermore, in HCC cells, we found that FR5 inhibits Hippo pathway, leading to inactivation of YAP and increase of PTEN. Enhanced PTEN results in the inhibition of PI3K/AKT signaling pathway, inhibiting cell proliferation by FR5 and FR5-induced apoptosis. Moreover, it was proved that FR5 treatment could inhibit tumor growth in a HCC xenograft mouse model, and immunohistochemistry results showed FR5 treatment resulted in down-regulation of Bcl-2 and YAP, and up-regulation of PTEN and PI3K. Taken together, we found that FR5 effectively inhibits proliferation and induces apoptosis of HCC cells through coordinated inhibition of YAP in the Hippo pathway and AKT in the PI3K-PTEN-mTOR pathway, and suggest FR5 as a potential therapy for HCC.

Natural friedelanes.

This review covers the occurrence and biological activities of all natural friedelane triterpenoids found between 1977 and March 2011. The biogeneses of dimeric friedelanes and several rearranged friedelanes are discussed. The pharmacological properties of representative compounds, including celastrol and correolide, have also been compiled, on the basis of 344 references.

Ceriponols A-K, tremulane sesquitepenes from Ceriporia lacerate HS-ZJUT-C13A, a fungal endophyte of Huperzia serrata.

Tremulane sesquiterpenes ceriponols A-K, together with three known ones tremulenediol A, 11,12-dihydroxy-1-tremulen-5-one and conocenol B, were isolated from the cultures of Ceriporia lacerate, a fungal endophyte residing in the stems of the medicinal plant Huperzia serrata. Among these isolates, ceriponol B possessed an unprecedent 12-nortremulane skeleton. The structures of all isolates were elucidated by spectroscopic methods, including MS and NMR (1D and 2D) spectroscopic techniques. The cytotoxic activities of ceriponols A-K were evaluated against three human tumor cell lines (HeLa, HepG2, and SGC 7901). Ceriponols F and K exhibited moderate cytotoxicity against all the tested human cancer cell lines with IC50 values ranging from 32.3 ± 0.4 to 173.2 ± 1.5 µM, while ceriponol G showed slightly better cytotoxicity against a HeLa cell line.

Natural disesquiterpenoids.

This review covers the isolation, structural determination, biological activities and biomimetic synthesis of all natural dimeric sesquiterpenoids, along with a detailed discussion of the biogenesis of these metabolites. Syntheses leading to the revision of structures have also been included, and 368 references are cited.

Analysis and determination of diterpenoids in unprocessed and processed Euphorbia lathyris seeds by HPLC-ESI-MS.

Euphorbia lathyris (Caper spurge) is a toxic and potent Chinese materia medica (T/PCMM). This study sought a method for identifying five diterpenoids (Euphorbia factors L1-L3, L7a and L8) with the spectra of UV and mass, quantifying three diterpenoids L1, L2, and L8 in crude extracts of unprocessed and processed E. lathyris seeds by liquid chromatography/electrospray ionization mass spectrometry (LC-ESI-MS). The analysis was achieved on an Agilent Eclipse XDB-C18 column (4.6 mm×150 mm i.d., 5 µm) with an isocratic elution with a mobile phase consisting of water and acetonitrile at a flow rate of 0.25 mL/min at column temperature of 30 °C and UV detection was set at 272 nm. An ESI source was used with a positive ionization mode. The calibration curve was linear in the ranges of 9.9-79 µg/mL for Euphorbia factor L1, 3.8-30.5 µg/mL for Euphorbia factor L2, and 1.0-20.6 µg/mL for Euphorbia factor L8. The average recoveries (n=6) of three diterpenoids were 98.39%, 91.10% and 96.94%, respectively, with RSD of 2.5%, 2.4% and 2.1%, respectively. The contents of the three diterpenoids in processed E. lathyris seeds were 3.435, 1.367 and 0.286 mg/g, respectively, which decreased more sharply than those in unprocessed E. lathyris seeds which were 4.915, 1.944 and 0.425 mg/g, respectively. The method is simple, accurate, reliable and reproducible, and it can be applied to control the quality of unprocessed and processed E. lathyris seeds.

Alisol C 23-acetate from the rhizome of Alisma orientale.

THE TITLE COMPOUND [SYSTEMATIC NAME: 11ß-hydr-oxy-24,25-ep-oxy-3,16-oxo-protost-13 (17)-en-23-yl acetate], C(32)H(48)O(6), a protostane-type triterpenoid, was isolated from the Chinese herbal medicine alismatis rhizoma (the rhizome of Alisma orientalis Juzep). The mol-ecule contains four trans-fused rings, viz. three six-membered and one five-membered ring. Two of the six-membered rings have slightly distorted half-chair conformations, while the third exhibits a chair conformation. The five-membered ring is almost planar. An inter-molecular O-H⋯O hydrogen bond between the hydr-oxy and ep-oxy groups and intra- and intermolecular C-H⋯O hydrogen bonds are observed.

Lignans from Saussurea conica and their NO production suppressing activity.

Three new lignan derivatives, conicaols A and B and conicaoside, together with seven known compounds were identified from Saussurea conica. Their structures were elucidated by spectral methods including 1D and 2D NMR techniques. Six 2,3-dibenzylbutyrolactone-type lignans were biologically evaluated, and two of them, arctigenin and matairesinol, showed potent activity to suppress NO production in vitro in LPS-activated macrophages of SD rat.

Sesquiterpene lactones with potent cytotoxic activities from Vernonia chinensis.

Five new sesquiterpene lactones, namely vernchinilides A-E (1-5), along with five known compounds, 8 beta-(2-methylacryloyloxy)hirsutinolide 13-O-acetate (6), 8 alpha-(2-methylacryloyloxy)-1beta,4beta-epoxy-1alpha-methoxy-13-O-acetate-10 betaH-germacra-5 E,7(11)-dien-12,6-olide (7), 8 beta-(2-hydroxymethylacryloyloxy)hirsutinolide 13-O-acetate (8), 8 alpha-tigloyloxyhirsutinolide 13-O-acetate ( 9) and vernolide-B (10) were isolated from Vernonia chinensis. The structures of these new compounds were elucidated on the basis of spectral data, especially 2D-NMR techniques. Compounds 2, 5 and 6 exhibited potent cytotoxic activities against P-388 and A-549 tumor cell lines.

Lathyranoic acid A: first secolathyrane diterpenoid in nature from Euphorbia lathyris.

[structures: see text] Lathyranoic acid A (1), the first secolathyrane diterpenoid with an unprecedented skeleton, and a new diterpenoid Euphorbia factor L11 (2) were isolated from the seeds of Euphorbia lathyris. Their structures were elucidated by spectroscopic analysis and chemical methods. A biogenetic route involving an enzymatic Baeyer-Villiger oxidation as the key step was postulated for the transformation of 2 to 1 and mimicked by an unusual chemical Baeyer-Villiger oxidation.

Novel diterpenoids with potent inhibitory activity against endothelium cell HMEC and cytotoxic activities from a well-known TCM plant Daphne genkwa.

Twelve highly oxygenated novel daphnane-type diterpenoids genkwanines A-L (1-12), together with four known diterpenes (13-16), were isolated from the bud of Daphne genkwa, a well-known traditional Chinese medicine (TCM). The new structures were elucidated on the basis of spectral methods, especially 2D NMR spectra (HMQC, HMBC, NOESY). Inhibitory activity against endothelium cell HMEC proliferation and cytotoxic activities against two tumor cell lines were assessed for all the compounds 1-16, and found to be significant and structure related. A number of compounds showed very potent cytotoxic activities against two tumor cell lines at the IC50 levels of 0.15-8.40 microM, and most interestingly, five of the compounds 4, 8, 10, 13, and 14 exhibited strong activity to inhibit the endothelium cell HMEC at the IC50 levels of 2.90-15.0 microM.