Eighteen iridoids from the roots and rhizomes of Valeriana jatamansi and their protective effects against α-hemolysin.

Thirteen previously undescribed iridoids (1-13), together with five known iridoids (14-18) were isolated from the roots and rhizomes of Valeriana jatamansi Jones. Their structures with absolute configurations were elucidated by analysis of MS, NMR, optical rotation and their experimental and calculated electronic circular dichroism spectra. All of the isolated compounds were tested for their protective effects against α-hemolysin-induced cell death in A549 cells. Compounds 14, 16 and 17 showed moderate protective effects, and compounds 15 and 18 showed weak protective effects.

Five undescribed abietane-type diterpenes of Callicarpa macrophylla.

A phytochemical investigation of the medicinal plant Callicarpa macrophylla resulted in the characterization of two rare rearrangement abietane-type diterpenoids, macrophypene F-G (1-2), and three abietane diterpenoids, named macrophypene H-J (3-5). Additionally, five known diterpenoids (6-10) were identified. The structures of the newly discovered compounds were fully established through extensive analysis of HRESIMS, 1D and 2D NMR data. The absolute configurations of the isolated compounds were determined using CD comparison, chemical methods, and X-ray crystal diffraction experiments. Subsequently, all isolated diterpenoids were evaluated for their inhibitory effects on extracellular PCSK9 protein levels by PCSK9 AlphaLISA screening. Jiadfenoic acid B (6, 56.80% inhibition at 20 µM) and holophyllin F (10, 43.18% inhibition at 20 µM) significantly decreased PCSK9 protein levels in medium of HepG2 cells.

Five undescribed guanidine alkaloids from Plumbago zeylanica.

Five undescribed guanidine alkaloids, plumbagines HK (1-4) and plumbagoside E (5), as well as five known analogues (6-10) were isolated from the roots of Plumbago zeylanica. Their structures were established by extensive spectroscopic analyses and chemical methods. In addition, 1-10 were accessed their anti-inflammatory activities by measuring nitric oxide (NO) concentrations in LPS-induced RAW 264.7 cells. However, all compounds especially 1 and 3-5 could not inhibit the secretion of NO but significant increase the secretion of NO. The result reminded us that 1-10 may become potential novel immune potentiators.

Neolinulicin A and B from Inula japonica and their anti-inflammatory activities.

A phytochemical study performed on Inula japonica led to isolation of a new 1,10-seco-sesquiterpene dimer Neolinulicin A (1) and 1,10-seco-sesquiterpene Neolinulicin B (2), together with nine known sesquiterpenes (3-11). Among them, Neolinulicin A (1), which has a new carbon skeleton, was a Diels-Alder [4 + 2] adduct of two sesquiterpene moieties. Their structures were established by extensive spectroscopic analysis. All of the isolated compounds showed inhibition of NO production in RAW 264.7 macrophages. The findings might supply information for the future design of anti-inflammatory agents from I. japonica.

Indole alkaloid from Nauclea latifolia promotes LDL uptake in HepG2 cells by inhibiting PCSK9.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been found to play a major role in atherosclerotic cardiovascular disease (ASCVD) by promoting hyperlipidemia. Its inhibition has therefore emerged as a viable drug target for improving the outcome of ASCVD. However, current monoclonal antibody PCSK9 inhibitors are considered cost ineffective and there is the need to discover new effective and cheaper small molecule alternatives. PURPOSE: The methanolic and ethanolic crude extracts of Nauclea latifolia have been shown to possess anti-hyperlipidemic activity, but the chemical component(s) responsible for this activity and the mechanism of action have remained unknown. The objective of this study was therefore to identify N. latifolia constituents with anti-hyperlipidemic activity and to investigate the inhibition of PCSK9 as a probable mechanism of action. METHOD: In the present study, compounds were isolated from the ethanolic extract of the stem of N. latifolia. The alkaloids were evaluated for their DiI-LDL uptake promoting activity in HepG2 cell. The most active compound was further assessed for its effect on low density lipoprotein receptor (LDLR) and PCSK9 protein expressions by western blot. RESULTS: 3R-3,14-dihydroangustoline (5), showed a relatively good activity in promoting LDL uptake (1.26-fold). It further increased LDLR protein expression and decreased the protein expression of PCSK9 in a dose dependent manner (1-50  µM). CONCLUSION: Alkaloids from N. latifolia may serve as a source of new PCSK9 inhibitors.

Jatrophane diterpenoids from Euphorbia helioscopia and their lipid-lowering activities.

The phytochemical study of Euphorbia helioscopia led to the isolation of 33 jatrophane diterpenoids (1-33), of which six (1-6) were new. This small jatrophane library was established to screen for potential lipid modulators. LDL-Uptake screening assay demonstrated that most of them improved LDL-Uptake rate in HepG2 cells, with compounds 16, 21 and 26 exhibiting more outstanding effects. Further exploration found that these three compounds could increase LDLR protein level in HepG2 cells dose-dependently. SAR studies suggested that substituted patterns of C-9, steric hindrance between C-14 and C-15, and the long conjugated fragment from C-5 to the carbonyl (C-9) were essential for the activity. Moreover, compound 21, a relatively abundant chemical in E. helioscopia, showed remarkable lipid-lowering effect in vivo, which makes it a promising lead for development of new lipid-lowering agents.

Cytotoxic and other withanolides from aeroponically grown Physalis philadelphica.

Eleven withanolides including six previously undescribed compounds, 16ß-hydroxyixocarpanolide, 24,25-dihydroexodeconolide C, 16,17-dehydro-24-epi-dioscorolide A, 17-epi-philadelphicalactone A, 16-deoxyphiladelphicalactone C, and 4-deoxyixocarpalactone A were isolated from aeroponically grown Physalis philadelphica. Structures of these withanolides were elucidated by the analysis of their spectroscopic (HRMS, 1D and 2D NMR, ECD) data and comparison with published data for related withanolides. Cytotoxic activity of all isolated compounds was evaluated against a panel of five human tumor cell lines (LNCaP, ACHN, UO-31, M14 and SK-MEL-28), and normal (HFF) cells. Of these, 17-epi-philadelphicalactone A, withaphysacarpin, philadelphicalactone C, and ixocarpalactone A exhibited cytotoxicity against ACHN, UO-31, M14 and SK-MEL-28, but showed no toxicity to HFF cells.

Resin glycosides from the seeds of Ipomoea muricata and their multidrug resistance reversal activities.

Resin glycosides represent an important chemotaxonomic marker of the Convolvulaceae family and possess multidrug resistance (MDR) reversal activity. In our recent study, nine previously undescribed resin glycosides, Calonyctins B-J, were isolated from the seeds of Ipomoea muricata. Their structures with the absolute configuration were established on the basis of comprehensive spectroscopic analysis and chemical methods. Among these, Calonyctins F-I possessed a skeleton in which the aglycone moiety and the oligosaccharide core were linked by a 3-hydroxy-2-methylbutanoic acid moiety to form a 25-membered macrocyclic structure. Calonyctins E, J, and muricatic acid C methyl ester were non-cytotoxic but enhanced the cytotoxicity of vincristine by 2.5-407.1 fold at 25 µM in KB/VCR cells. Calonyctin E was the most active one.

Serratene-type triterpenoids from Palhinhaea cernua.

Phytochemical investigation of the 95% ethanol extract of the whole plant of Palhinhaea cernua afforded five new serratene-type triterpenoids (1-5) together with four known analogues (6-9). The structures of the new compounds were elucidated by extensive spectroscopic analysis and X-ray crystallographic data. Compounds 1-3 triggered apoptosis of Hela-/- cell with EC50 values of 3.49 ±â€¯0.05, 0.28 ±â€¯0.13 and 7.98 ±â€¯0.03 µM, respectively.

Jatrophanes as promising multidrug resistance modulators: Advances of structure-activity relationships.

The phytochemical study of Euphorbia helioscopia afforded euphornin (1) in a large amount. Alkaline hydrolysis of 1 using potassium carbonate yielded the main product monodeacetyleuphornin (2), whose structural modification at 14-OH gave rise to 21 acylated derivatives euphornoate A-U (3-23). Thus, a mini compound library of jatrophanes was established to screen for MDR modulators. Biological studies clearly demonstrated the effect of C-14 pattern modification in MDR reversal activity and several compounds with RF values over 300 fold at 20 µM (6, 16, 20, 22, 23) were thought to be promising MDR modulators. The SARs are discussed, which reveal that introduction of an alkyl acyl group bearing 4 carbons at C-14 or an aryl acyl group with electron donating groups is favorable for the activity.

Halimane-type diterpenoids from Vitex rotundifolia and their anti-hyperlipidemia activities.

Vitex rotundifolia is the variant of the traditional Chinese medicine (TCM) Vitex trifolia. Diterpenoids from V. trifolia have shown anti-hyperlipidemia activity. As part of a continuous research program of searching for anti-hyperlipidemia constituents from TCM, 95% alcohol extract of the fruits of V. rotundifolia was fully studied, and 18 diterpenoids were isolated, including eight previously undescribed compounds (viterofolins A-H). Among them, viterofolins A-B were previously undescribed rearranged halimane-type diterpenoids, viterofolins CH were previously undescribed halimane-type diterpenoids. These compounds were then firstly evaluated in lipid (Dil-LDL) uptake assay in HepG2 cells. Viterofolin H, (5S, 6R, 8R, 9R, 10S)-6-acetoxy-9-hydroxy-13 (14)-labden-16,15-olide and previtexilactone showed moderate activities in promoting LDL uptake (1.27-1.35 fold). This work laid the foundation for searching anti-hyperlipidemia natural products.

(19αH)-lupane and (9ßH)-lanostane triterpenes from Euphorbia helioscopia trigger apoptosis of tumor cell.

Chemical investigation of Euphorbia helioscopia resulted in the identification of seven new triterpenes named euphorbatrine A-G (1-7), including two (19αH)-lupane (1-2) and three (9ßH)-lanostane (4-6), which are very rare metabolites from plants. Their structures were elucidated by extensive spectroscopic analysis, X-ray crystallography and chemical methods. Compounds 5 and 6 triggered apoptosis of Hela-/- cell with EC50 values of 1.59±0.25 and 26.48±0.78µM, respectively.

Scubatines A-F, new cytotoxic neo-clerodane diterpenoids from Scutellaria barbata D. Don.

Phytochemical investigation of the 70% acetone extract of the whole plant of Scutellaria barbata D. Don afforded six new neo-clerodane diterpenoids, scubatines A-F (1-6), and four known analogues (7-10). Their structures were elucidated on the basis of extensive spectroscopic analyses. Cytotoxic activity against the HL-60 and A549 cell lines was assessed for all isolated compounds. Compound 9 exhibited moderate activity against HL-60 with an IC50 value of 5.6µM. Compound 6 showed weak cytotoxic activity against A549 and HL-60 with IC50 values of 10.4 and 15.3µM, respectively.

Crassins A-H, Diterpenoids from the Roots of Croton crassifolius.

Phytochemical investigation of the 70% acetone extract of Croton crassifolius roots afforded eight new diterpenoids, crassins A-H (1-8), and 19 known compounds. The structures of the new compounds were determined by spectroscopic methods, and their absolute configurations were determined by electronic circular dichroism, single-crystal X-ray diffraction analysis, comparison with literature data, and biogenetic considerations. Crassins A (1) and B (2) are new ring B-rearranged diterpenoids, whereas crassin C (3) is a new ring A-rearranged diterpenoid. Crassin H (8) exhibited selective cytotoxicity against A549 cells (IC50 5.2 µM) compared with HL-60 cells (IC50 11.8 µM). The known compound chettaphanin-II exhibited moderate activity against the A549 and HL-60 cell lines (IC50 8.4 and 10.5 µM, respectively).

Merremins A-G, resin glycosides from Merremia hederacea with multidrug resistance reversal activity.

Five new pentasaccharide resin glycosides, named merremins A-E (1-5), two new pentasaccharide resin glycoside methyl esters, named merremins F and G (6, 7), and four known resin glycosides, murucoidin IV, murucoidin V, stoloniferin IV, and murucoidin XVII, were obtained from the aerial parts of Merremia hederacea. This is the first report of resin glycosides obtained from M. hederacea. In addition, the new compounds can be divided into three types: those possessing an 18-membered ring (1-4), compound 5 with a 20-membered ring, and those with an acyclic core (6, 7). Furthermore, the different types of resin glycosides were evaluated for their multidrug resistance reversal activities. Compounds 1, 5, 6, and murucoidin V were noncytotoxic and enhanced the cytotoxicity of vinblastine by 2.3-142.5-fold at 25 µM. Compound 5 and murucoidin V, with 20-membered rings, were more active than compound 1, with an 18-membered ring.

Dammarane-type triterpenoids from Gentianella azurea.

Thirteen new dammarane-type triterpenoids (1-13) and four known analogues, gentirigenic acid (14) and the gentirigeosides A, B, and E (15-17), were isolated from Gentianella azurea. Their structures were elucidated by detailed analysis of the NMR, MS, and X-ray crystallographic data. This is the first report of dammarane-type triterpenoids in the Gentianella genus. In addition, the known structures of gentirigenic acid (14) and the gentirigeosides A, B, and E (15-17) were revised based on the X-ray diffraction analysis. Gentirigeoside A (15) was found to inhibit nitric oxide production in RAW 264.7 macrophages with an IC50 value of 6.6 ± 2.1 µM.

Guanidine alkaloids from Plumbago zeylanica.

Eleven new guanidine alkaloids, plumbagines A-G (2-8) and plumbagosides A-D (9-12), as well as two known analogues (1, 13), were isolated from the aerial parts of Plumbago zeylanica. Their structures were elucidated by spectroscopic analyses including 1D and 2D NMR, MS, IR, and CD methods. The absolute configuration of 1 was determined by single-crystal X-ray diffraction of its derivative (1a).

[Comparative studies on the amount of ginsenosides between the crown galls and Chinese medicinal materials of Panax quinquefolium].

OBJECTIVE: To provide theoretical basis for the production of ginsenosides by using modern biotechnologies, the comparative studies of the amount of ginsenosides between the crown galls and Chinese medicinal materials of Panax quinquefolium were carried out. METHODS: Total ginsenosides were determined by spectrophotometry, and the contents of ginsenoside Rb1, Rb3, Rc, Re were determined by HPLC. RESULTS: (1) The total ginsenosides in the crown galls of Panax quinquefolium (aftert 27 days' cultivation) was almost as much as that of Chinese medicinal material of Panax quinquefolium. (2) The contents of ginsenoside Rb1, Re in the crown galls were about half of that in Chinese medicinal materials of Panax quinquefolium, and ginsenoside Rc was about 80%. But the amount of ginsenoside Rb3 in the crown galls of Panax quinquefolium was much more than that in Chinese medicinal materials of Panax quinquefolium as almost 15 times higher. CONCLUSION: The crown galls of Panax quinquefolium may be a new potential resource for large-scale production of ginsenosides.