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.

Study of the UV Light Conversion of Feruloyl Amides from Portulaca oleracea and Their Inhibitory Effect on IL-6-Induced STAT3 Activation.

Two new feruloyl amides, N-cis-hibiscusamide (5) and (7'S)-N-cis-feruloylnormetanephrine (9), and eight known feruloyl amides were isolated from Portulaca oleracea L. and the geometric conversion of the ten isolated feruloyl amides by UV light was verified. The structures of the feruloyl amides were determined based on spectroscopic data and comparison with literature data. The NMR data revealed that the structures of the isolated compounds showed cis/trans-isomerization under normal laboratory light conditions. Therefore, cis and trans-isomers of feruloyl amides were evaluated for their convertibility and stability by UV light of a wavelength of 254 nm. After 96 h of UV light exposure, 23.2%-35.0% of the cis and trans-isomers were converted to trans-isomers. Long-term stability tests did not show any significant changes. Among all compounds and conversion mixtures collected, compound 6 exhibited the strongest inhibition of IL-6-induced STAT3 activation in Hep3B cells, with an IC50 value of 0.2 µM. This study is the first verification of the conversion rates and an equilibrium ratio of feruloyl amides. These results indicate that this natural material might provide useful information for the treatment of various diseases involving IL-6 and STAT3.

Anti-osteoporotic and antioxidant activities of chemical constituents of the aerial parts of Ducrosia ismaelis.

A new pterocarpan glycoside, glycinol-3-O-ß-D-glucopyranoside (1), and a new dihydrochalcone glycoside, ismaeloside A (2), were isolated together with 13 known compounds, including several flavonoids (3-8), lignans (9-11), and phenolic compounds (12-15), from the methanol extract of the aerial parts of Ducrosia ismaelis. The chemical structures of these compounds were elucidated from spectroscopic data and by comparison of these data with previously published results. The anti-osteoporotic and antioxidant activities of the isolated compounds were assessed using tartrate-resistant acid phosphatase (TRAP), oxygen radical absorbance capacity (ORAC), and reducing capacity assays. Compound 15 exhibited a dose-dependent inhibition of osteoclastic TRAP activity with a TRAP value of 86.05±6.55% of the control at a concentration of 10 µM. Compounds 1, 3-5, and 8 showed potent peroxyl radical-scavenging capacities with ORAC values of 22.79±0.90, 25.57±0.49, 20.41±0.63, 26.55±0.42, and 24.83±0.12 µM Trolox equivalents (TE) at 10 µM, respectively. Only compound 9 was able to significantly reduce Cu(I) with 23.44 µM TE at a concentration of 10 µM. All of the aforementioned compounds were isolated for the first time from a Ducrosia species.

Assessment of nematicidal and plant growth-promoting effects of Burkholderia sp. JB-2 in root-knot nematode-infested soil.

Root-knot nematodes (RKN), Meloidogyne spp., are plant-parasitic nematodes that are responsible for considerable economic losses worldwide, because of the damage they cause to numerous plant species and the inadequate biological agents available to combat them. Therefore, developing novel and eco-friendly nematicides is necessary. In the present study, Burkholderia sp. JB-2, isolated from RKN-infested rhizosphere soil in South Korea, was evaluated to determine its nematicidal and plant growth-promoting effects under in vitro and in vivo conditions. Cell-free filtrates of the JB-2 strain showed high levels of nematicidal activity against second-stage juveniles (J2) of M. incognita, with 87.5% mortality following two days of treatment. In addition, the assessment of the activity against other six plant parasitic nematodes (M. javanica, M. hapla, M. arenaria, Ditylenchus destructor, Aphelenchoides subtenuis, and Heterodera trifolii) showed that the cell-free filtrates have a broad nematicidal spectrum. The three defense-responsive (MiMIF-2, MiDaf16-like1, and MiSkn1-like1) genes were activated, while Mi-cm-3 was downregulated when treated with cell-free filtrates of JB-2 cultures on J2. The greenhouse experiments suggested that the cell-free filtrates of the JB-2 strain efficiently controlled the nematode population in soil and egg mass formations of M. incognita in tomato (Solanum lycopersicum L., cv. Rutgers). An improvement in the host plant growth was observed, in which the shoot length and fresh weights of shoots and roots increased. The treatment with 10% of JB-2 cell-free filtrates significantly upregulated the expression levels of plant defenses (SlPR1, SlPR5, and SlPAL) and growth-promoting (ACO1, Exp18, and SlIAA1) genes compared with the corresponding parameters of the control group. Therefore, JB-2 could be a promising candidate for the sustainable management of RKN.

Dehydro-alpha-lapachone isolated from Catalpa ovata stems: activity against plant pathogenic fungi.

The methanol extract of stems of Catalpa ovata G Don exhibits potent in vivo antifungal activity against Magnaporthe grisea (Hebert) Barr (rice blast) on rice plants, Botrytis cinerea Pers ex Fr (tomato grey mould) and Phytophthora infestans (Mont) de Bary (tomato late blight) on tomato plants, Puccinia recondita Rob ex Desm (wheat leaf rust) on wheat plants and Blumeria graminis (DC) Speer f. sp. hordei Marchal (barley powdery mildew) on barley plants. An antifungal substance was isolated and identified as dehydro-alpha-lapachone from mass and nuclear magnetic resonance spectral data. It completely inhibited the mycelial growth of B. cinerea, Colletotrichum acutatum Simmonds, Colletotrichum gloeosporioides Simmonds, M. grisea and Pythium ultimum Trow over a range of 0.4-33.3 mg litre(-1). It also controlled the development of rice blast, tomato late blight, wheat leaf rust, barley powdery mildew and red pepper anthracnose (Colletotrichum coccodes (Wallr) S Hughes). The chemical was particularly effective in suppressing red pepper anthracnose by 95% at a concentration of 125 mg litre(-1).

Nematicidal and antifungal activities of annonaceous acetogenins from Annona squamosa against various plant pathogens.

The methanol extract of Annona squamosa seeds was highly active against two phytoparasitic nematodes, Bursaphelenchus xylophilus and Meloidogyne incognita. It efficiently suppressed plant diseases, caused by Phytophthora infestans and Puccinia recondita. Ten annonaceous acetogenins (AAs) were isolated, and their chemical structures were identified by mass and nuclear magnetic resonance spectral data. Out of 10 substances, eight displayed strong in vitro nematicidal activity against B. xylophilus with LD(50) values ranging 0.006 to 0.048 µg/mL. Squamocin-G showed potent nematicidal activity against M. incognita. Squamocin, squamocin-G, and squamostatin-A also displayed potent in vitro and in vivo antifungal activities against P. infestans causing tomato late blight. In addition, squamostatin-A effectively controlled the development of wheat leaf rust caused by P. recondita. Our findings suggested that A. squamosa seeds and its bioactive AAs can be an alternative resource of a promising botanical nematicide and fungicide to control various plant diseases.

Anti-human rhinovirus activity of raoulic acid from Raoulia australis.

Human rhinoviruses (HRVs), members of the Picornaviridae family, are composed of over 100 different virus serotypes. Until now there is no recorded clinically effective antiviral chemotherapeutic agent for treatment of diseases caused by HRVs. Our previous study of raoulic acid tested against serotype human rhinoviruses showed anti-HRV2 (species A) and -3 (species B) activities. In this study, raoulic acid was found to possess broad-spectrum antiviral activity against six HRVs with a 50% inhibition concentration of less than 9.5 microg/mL through inhibition of the cellular absorption of the HRV particles. Furthermore, the effect of raoulic acid on resistance of HRV5 exhibited to pleconaril was more pronounced than the effect on HRV1b, -6, -14, -15, and -40. However, ribavirin did possess weak antiviral activity against HRVs. Collectively, the results demonstrate that raoulic acid is a novel therapeutic candidate for two different groups of human rhinovirus.

Phytotoxic sesterterpene, 11-epiterpestacin, from Bipolaris sorokiniana NSDR-011.

The structure of siccanol, a phytotoxic sesterterpene of fungal origin, was analyzed after chemical conversion by NMR spectroscopy. Siccanol was found to be an epimer of terpestacin that has been isolated from Arthrinium sp., and was thus renamed 11-epiterpestacin. Its stereochemistry was also identical with that of fusaproliferin, a structurally related mycotoxin from Fusarium proliferatum. Therefore, this sesterterpene may also be referred to as 24-deacetyl fusaproliferin. The phytotoxicity of 11-epiterpestacin was almost equal to that of terpestacin, but significantly higher than that of fusaproliferin.

Cochlioquinone A1, a new anti-angiogenic agent from Bipolaris zeicola.

Cochlioquinone A1 (CoA1) was newly isolated from the culture extract of Bipolaris zeicola as a potent anti-angiogenic agent. CoA1 inhibited in vitro angiogenesis of bovine aortic endothelial cells (BAECs) such as bFGF-induced tube formation and invasion at the concentration (1 microg/mL) without cytotoxicity. Notably, CoA1 exhibited more potent inhibition activity for the growth of BAECs than that of normal and cancer cell lines investigated in this study. These results demonstrate that CoA1 is a new anti-angiogenic agent and can be developed as a new therapeutic agent for angiogenesis-related diseases.