Carotane sesquiterpenes from Peperomia pellucida and their anti-infective activities.

Owing to the challenges of antimicrobial resistance, investigations of new antibiotics from medicinal plants are continuously being conducted. Peperomia pellucida is a pantropical plant used in traditional medicine for the treatment of various disorders. From the ethanol extract of a whole P. pellucida plant, one previously undescribed carotane sesquiterpene (pellucarotine), one known carotane sesquiterpene (daucol), and one phenylpropanoid (dillapiol) were isolated and structurally elucidated. Their structures were determined based on 1D and 2D NMR, HR-ESI-Mass, experimental, and computational electronic circular dichroism spectroscopic data and compared with those reported in the literature. Antimicrobial assay results showed that pellucarotine had an anti-infective effect on Candida albicans with an MIC of 512 µg/mL.

Structures and antiosteoclastogenic activity of compounds isolated from edible lotus (Nelumbo nucifera Gaertn.) leaves and stems.

One new 1,4-bis-phenyl-1,4-butanedione glycoside (14), one new eudesmane-type sesquiterpenoid (16), and 16 known compounds were isolated from the leaves and stems of Nelumbo nucifera Gaertn. The structures of the isolated compounds were elucidated by interpretation of their 1D and 2D NMR spectroscopic and HRESIMS data. Time-dependent density functional theory calculations and Electronic Circular Dichroism (ECD) spectroscopy was used to determine absolute configurations of the new eudesmane-type sesquiterpenoid (16). All the isolated compounds were examined for their antiosteoclastogenic activity. Preliminarily results of the TRAP staining on RAW 264.7 cells indicated that compounds 1 and 11 possess potential inhibitory effects on RANKL-induced osteoclast formation. Further bioassay investigation was carried out to reveal that compounds 1 and 11 suppressed RANKL-induced osteoclast formation in a concentration-dependent manner with the inhibition up to 55% and 78% at the concentration of 10 µM, respectively. In addition, the structure-activity relationship analysis showed that the 1,3-dioxole substitute and the double bond at C-6a/C-7 in the aporphine skeleton may be responsible for the antiosteoclastogenic activity. The findings provided valuable insights for the discovery and structural modification of aporphine alkaloids as the antiosteoclastogenic lead compounds.

Antioxidant and Antidiabetic Activities of Flavonoid Derivatives from the Outer Skins of Allium cepa L.

The onion, known as the bulb onion or common onion, is not only a key ingredient in many tasty and healthy vegetarian meals but also many traditional medicines. Nine new flavonoids [cepaflavas A, B (5, 6), cepadials A-D (7-9 and 14), and cepabiflas A-C (10-12)] and six known compounds (1-4, 13, 15) were obtained from the outer skins of Allium cepa L. Among them, compounds 5, 6, and 9 might be artificial products formed during extraction and isolation. New compounds were structurally elucidated using various spectroscopy/spectrometry techniques, including NMR and HRMS, and computational methods. Their absolute configurations were determined using time-dependent density functional theory calculations, combined with ECD spectroscopy, optical rotation calculation, and statistical procedures (CP3 and DP4 analysis). The free radical scavenging assays revealed that the new compounds 10-12 possessed considerable antioxidant activities with IC50 values of 4.25-8.88 and 7.12-8.14 µM against DPPH and ABTS•+, respectively. Compounds 13-15 showed substantial inhibitory activities against both α-glucosidase and protein tyrosine phosphatase 1B (PTP1B), with IC50 values of 0.89-6.80 and 1.13-6.82 µM, respectively. On the basis of molecular docking studies, 13 and 15 were predicted to have high binding capacity and strong affinity toward the active site of PTP1B.

The Effects of 2',4'-Dihydroxy-6'-methoxy-3',5'- dimethylchalcone from Cleistocalyx operculatus Buds on Human Pancreatic Cancer Cell Lines.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a principal natural chalcone of Cleistocalyx operculatus buds, suppresses the growth of many types of cancer cells. However, the effects of this compound on pancreatic cancer cells have not been evaluated. In our experiments, we explored the effects of this chalcone on two human pancreatic cancer cell lines. A cell proliferation assay revealed that DMC exhibited concentration-dependent cytotoxicity against PANC-1 and MIA PACA2 cells, with IC50 values of 10.5 ± 0.8 and 12.2 ± 0.9 µM, respectively. Treatment of DMC led to the apoptosis of PANC-1 by caspase-3 activation as revealed by annexin-V/propidium iodide double-staining. Western blotting indicated that DMC induced proteolytic activation of caspase-3 and -9, degradation of caspase-3 substrate proteins (including poly[ADP-ribose] polymerase [PARP]), augmented bak protein level, while attenuating the expression of bcl-2 in PANC-1 cells. Taken together, our results provide experimental evidence to support that DMC may serve as a useful chemotherapeutic agent for control of human pancreatic cancer cells.

Lactones from the pericarps of Litsea japonica and their anti-inflammatory activities.

Five new lactones, litsenolide F1 (1), lisealactone H1 (10), lisealactone H2 (11), akolactone D (13), and akolactone E (14), along with thirteen known compounds were isolated from the pericarps of Litsea japonica (Thunb.) Jussieu. Their chemical structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, HRMS, and chemical methods. The isolated compounds were evaluated for their inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among them, 2-alkylidene-3-hydroxy-4-methylbutanolide derivatives (compounds 1-9) exhibited the most potent activity, with IC50 values in the range of 2.9-12.8 µM. In additon, compounds 1, 3, 4, and 6 showed inhibition of iNOS and COX-2 expression in concentration-dependent manner. Compound 3 suppresses mRNA expression of iNOS, COX-2, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells. Based on these evidence, the isolated lactones from L. japonica could be promissing candidates for the development of new anti-inflammatory agents.

Cholinesterase inhibitory alkaloids from the rhizomes of Coptis chinensis.

Coptis chinensis has been used as a medicinal herb in traditional oriental medicine. In this study, chemical investigation of a water extract of C. chinensis identified two new quaternary protoberberines (1, 2), a new tricyclic amide (3), together with five known compounds. Their chemical structures were elucidated by analysis with 1D and 2D NMR and high-resolution mass spectroscopy, as well as by comparison with those reported in the literature. Compounds 4, 5, and 7 showed potent inhibition against acetylcholinesterase (AChE) with IC50 values of 1.1, 5.6, and 12.9 µM, respectively. Compounds 2 and 4 showed inhibition of butyrylcholinesterase (BChE) with IC50 values of 11.5 and 27.8 µM, respectively. The kinetic activities were investigated to find out the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 5 and 7 were noncompetitive; BChE inhibition by compound 2 was also noncompetitive.

Chemical constituents from the fruits of Ligustrum japonicum and their inhibitory effects on T cell activation.

A previously undescribed nor-dammarane, 3ß,20,23-trihydroxy-24,25,26,27-tetranordammarane; three previously undescribed secoiridoid glycosides, ligujaponosides A-B, and iso-oleonuzhenide; and twenty three known compounds, were isolated from the fruits of Ligustrum japonicum Thunb. Their chemical structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, and HRMS. The isolated compounds were screened for immunosuppressive effects on T activated cells by evaluating interleukin-2 (IL-2) production. Among them, sesamin inhibited IL-2 production in Jurkat T cells with an IC50 value of 38 ± 2 µM. In addition, sesamin inhibited the phosphorylation of extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase (MAPK) family, in phorbol 12-myristate 13-acetate (PMA)/A23187-stimulated T cells. Therefore, sesamin was demonstrated to inhibit T cell activation via regulation of MAPK phosphorylation pathway.

Alkaloids from Piper nigrum Exhibit Antiinflammatory Activity via Activating the Nrf2/HO-1 Pathway.

In the present study, ten alkaloids, namely chabamide (1), pellitorine (2), retrofractamide A (3), pyrroperine (4), isopiperolein B (5), piperamide C9:1 (8E) (6), 6,7-dehydrobrachyamide B (7), 4,5-dihydropiperine (8), dehydropipernonaline (9), and piperine (10), were isolated from the fruits of Piper nigrum. Among these, chabamide (1), pellitorine (2), retrofractamide A (3), isopiperolein B (5), and 6,7-dehydrobrachyamide B (7) exhibited significant inhibitory activity on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, with IC50 values of 6.8, 14.5, 30.2, 23.7, and 38.5 µM, respectively. Furthermore, compound 1 inhibited lipopolysaccharide-induced NO production in bone marrow-derived macrophages with IC50 value of 9.5 µM. Consistent with NO inhibition, treatment of RAW264.7 cells with chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) suppressed expression of inducible NO synthase and cyclooxygenase-2. Chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) induced heme-oxygenase-1 expression at the transcriptional level. In addition, compound 1 induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and upregulated the expression of Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 and γ-glutamyl cysteine synthetase catalytic subunit, in a concentration-dependent manner in RAW264.7 cells. These findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme-oxygenase-1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases. Copyright © 2017 John Wiley & Sons, Ltd.

Isolation of a New Homomonoterpene from Madhuca pasquieri and Effect of Isolated Compounds on NO Production.

A new homomonoterpene, 1,3,3-trimethyl-7-oxabicyclo[3.1.1]hexa-9-en-10-oic acid, named madhusic acid A (1), together with ten known compounds (2-11) were isolated from the methanolic extract of the dried leaves of Madhuca pasquieri (Dubard) H. J. Lam. The structure of the new compound was elucidated on the basis of 1D, 2D NMR (COSY, HMQC, and HMBC) and mass spectral analyses. We examined the effects of the isolated compounds against LPS-induced NO production in macrophage RAW264.7 cells and compound 2 showed effective activity with an IC50 value of 14.5 µM.

Inflammatory Inhibitory Activity of Sesquiterpenoids from Atractylodes macrocephala Rhizomes.

Three new sesquiterpenoids, 13-hydroxyl-atractylenolide II (1), 4-ketone-atractylenolide III (2), and eudesm-4(15)-ene-7ß,11-diol (3), along with eleven known compounds (4-14), were isolated from the rhizomes of Atractylodes macrocephala. The structures and relative configurations of 1-3 were determined by analysis of the spectroscopic data, and the absolute configurations of 1 and 2 were assigned by circular dichroism technique. The anti-inflammatory activities of these isolates were evaluated against lipopolysaccharide-induced nitric oxide production in macrophage RAW264.7 cells; compounds 4, 7, and 8 exhibited moderate efficacy with IC50 values of 48.6±0.5, 46.4±3.2, and 32.3±2.9 µM, respectively.