Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale)

Ginger roots have been used to treat inflammation and have been reported to inhibit cyclooxygenase (COX). Ultrafiltration liquid chromatography mass spectrometry was used to screen a chloroform partition of a methanol extract of ginger roots for COX-2 ligands, and 10-gingerol, 12-gingerol, 8-shogaol, 10-shogaol, 6-gingerdione, 8-gingerdione, 10-gingerdione, 6-dehydro-10-gingerol, 6-paradol, and 8-paradol bound to the enzyme active site. Purified 10-gingerol, 8-shogaol and 10-shogaol inhibited COX-2 with IC₅₀ values of 32 μM, 17.5 μM and 7.5 μM, respectively. No inhibition of COX-1 was detected. Therefore, 10-gingerol, 8-shogaol and 10-shogaol inhibit COX-2 but not COX-1, which can explain, in part, the anti-inflammatory properties of ginger.     

Anti-gastric adenocarcinoma activity of 2-Methoxy-1,4-naphthoquinone,an anti-Helicobacter pylori compound from Impatiens balsamina L.

2-Methoxy-1,4-naphthoquinone (MeONQ) from Impatiens balsamina L. exhibited strong anti-H. pylori activity in our previous study. In this study, we investigated the cytotoxicity of MeONQ against gastric adenocarcinoma (MKN45 cell line) and propose the relevant mechanisms. MeONQ resulted in serious necrosis via superoxide anion catastrophe when the treatment doses were higher than 50 μM, whereas apoptosis occurred at low treatment doses (25–50 μM) through the caspase-dependent apoptosis pathway. Necrosis is the dominant mode of cell death. MeONQ exhibited high ability to induce gastric adenocarcinoma necrosis, showing good potential as a candidate agent for H. pylori infection related disease therapy.     

Cytochrome P450 1 enzyme inhibition and anticancer potential of chromene amides from Amyris plumieri

Cytochrome P450 (CYP) enzyme inhibitory properties of six chromenylated amide compounds (CAs) from Amyris plumieri are described. Inhibition of CYP microsomes (CYP1A1, CYP1A2, CYP1B1, CYP2D6, CYP3A4 and CYP2C19) was monitored using a fluorescent assay. Potent inhibition was found against CYP1A1 with IC₅₀ and K_i for CA1 (acetamide), being the lowest at 1.547 ± 1.0 μM and 0.37 μM respectively, displaying non-competitive kinetics. The selectivity for CYP1A1 was increased in CA3 (butanamide), which also exhibited cytotoxicity against breast cancer cells, MCF7 with an IC₅₀ of 47.46 ± 1.62 μM. Structure-activity relationship studies provide insight at a molecular level for CAs with implications in chemoprevention and chemotherapy.     

Pistagremic acid,a glucosidase inhibitor from Pistacia integerrima

Pistacia integerrima Stewart in traditionally used as folk remedy for various pathological conditions including diabetes. In order to identify the bioactive compound responsible for its folk use in diabetes, a phytochemical and biological study was conducted. Pistagremic acid (PA) was isolated from the dried galls extract of P. integerrima. Strong α-glucosidase inhibitory potential of PA was predicted using its molecular docking simulations against yeast α-glucosidase as a therapeutic target. Significant experimental α-glucosidase inhibitory activity of PA confirmed the computational predictions. PA showed potent enzyme inhibitory activity both against yeast (IC₅₀: 89.12 ± 0.12 μM) and rat intestinal (IC₅₀: 62.47 ± 0.09 μM) α-glucosidases. Interestingly, acarbose was found to be more than 12 times more potent an inhibitor against mammalian (rat intestinal) enzyme (having IC₅₀ value 62.47 ± 0.09 μM), as compared to the microbial (yeast) enzyme (with IC₅₀ value 780.21 μM). Molecular binding mode was explored via molecular docking simulations, which revealed hydrogen bonding interactions between PA and important amino acid residues (Asp60, Arg69 and Asp 70 (3.11 Å)), surrounding the catalytic site of the α-glucosidase. These interactions could be mainly responsible for their role in potent inhibitory activity of PA. PA has a strong potential to be further investigated as a new lead compound for better management of diabetes.     

Strong inhibition of deoxyschizandrin and schisantherin A toward UDP-glucuronosyltransferase (UGT) 1A3 indicating UGT inhibition-based herb–drug interaction

Deoxyschizandrin and schisantherin A are major bioactive lignans isolated from Fructus schisandrae which has been widely used as a tonic in traditional Chinese medicine for many years. Inhibition of UDP-glucuronosyltransferases (UGTs) by herbal components might be an important reason for clinical herb–drug interaction. The aim of the present study is to investigate the inhibitory effect of deoxyschizandrin and schisantherin A on major UGT isoforms. Recombinant UGT isoforms were used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 μM of deoxyschizandrin and schisantherin A exhibited strong inhibition on UGT1A3, and negligible inhibition on other tested UGT isoforms. Furthermore, deoxyschizandrin and schisantherin A were demonstrated to inhibit UGT1A3 in a concentration-dependent manner, with IC₅₀ value of 10.8 ± 0.4 μM and 12.5 ± 0.5 μM, respectively. Dixon and Lineweaver–Burk plots showed that inhibition of UGT1A3 by deoxyschizandrin was best fit to competitive inhibition type, and inhibition kinetic parameter (K_i) was calculated to be 0.48 μM. Inhibition of UGT1A3 by schisantherin A gave the best fit for types of noncompetitive inhibition, and the results showed K_i to be 11.3 μM. All these experimental data suggested that herb–drug interaction might occur when deoxyschizandrin or schisantherin A containing herbs were co-administered with drugs which mainly undergo UGT1A3-mediated metabolism. However, given that many in vivo factors could influence the in vitro–in vivo extrapolation (IVIVE), these in vitro inhibitory parameters should be considered with caution.     

Effects of resveratrol on the ultrastructure of Botrytis cinerea conidia and biological significance in plant/pathogen interactions

Many roles have been ascribed to stilbenes, namely as antimicrobial, deterrent or repellent compounds in plants, protecting them from attacks by fungi, bacteria, nematodes or herbivores, acting both as constitutive and active defense (phytoalexin) compounds. More recently, stilbenes (especially resveratrol and its derivatives) were acclaimed for their wondrous effects and wide range of purported healing and preventive powers as cardioprotective, antitumor, neuroprotective and antioxidant agents. Although there is a huge number of works concerning the role of resveratrol in human health, reports on the antifungal activity of this compound are still scarce. This study was thus conducted in order to investigate the toxicity of resveratrol at an ultra- structural level to dormant conidia of Botrytis cinerea, the causal microorganism for gray mold. In grapevine particularly, this disease can affect all the green organs but is particularly damaging for ripening berries. Observations using transmission electron microscopy showed the occurrence of damages on conidia treated with sub-lethal doses, that is, 60 μg/mL (2.6 × 10^− 4 M) of resveratrol, a concentration usually reached in grapevine leaves and grape berries challenged by this pathogen. These results provide further data about the overall mode of action of this phytoalexin and its role in the B. cinerea/grapevine interaction.     

Hydrolysable tannins depress cardiac papillary muscle contraction and propranolol-induced negative inotropism

We studied effects of hydrolysable tannins on rat papillary muscle contractions induced by propranolol. The developed force of papillary muscle was measured isometrically with an inductive force transducer. The IC₅₀ values for digallic acid, gallic acid, germin D, praecoxin A and 1-desgalloyl rugosin F were 4.2 × 10^− 5 M, 1.3 × 10^− 4 M, 1,4 × 10^− 4 M, 1.5 × 10^− 4 and 1.7 × 10^− 4 M, respectively. Incubation with tannins significantly attenuated the propranolol-induced negative inotropic contractile response. These results show that hydrolysable tannins depress muscle contractions and potentiate the activities of β-adrenergic blocker.     

Novel indole C-glycosides from Isatis indigotica and their potential cytotoxic activity

Two novel indole C-glycosides, which were the first reported alkaloids C-glycosides from Isatis indigotica, together with five known alkaloids were isolated. The novel alkaloids were elucidated to be indole-3-acetonitrile-4-methoxy-2-C-β-D-glucopyranoside (1) and N-methoxy-indole-3-acetonitrile-2-C-β-D-glucopyranoside (2) on the basis of spectroscopic analysis. 1 exhibited significant cytotoxic activities against human myeloid leukemia HL-60 and human liver cancer HepG2 cells with the IC₅₀ of 1.3 ± 0.1 and 2.1 ± 0.3 μM, respectively. 2 showed potential cytotoxic activities against HL-60 and human myeloid leukemia Mata cells with the IC₅₀ of 5.1 ± 0.4 and 12.1 ± 0.8 μM, respectively.     

Two novel biphenyl dimers from the heartwood of Caesalpinia sappan

Two novel biphenyl dimers, caesappanin A (1) and B (2), were isolated from the ethanol extract of the heartwood of Caesalpinia sappan. Their structures were elucidated on the basis of spectroscopic data including IR, HRESIMS, 1D and 2D NMR. Preliminary bioassays showed that compound 1 possessed potent cytotoxic effects against 4 cell lines including HCT-8, BGC-823, A549 and A2780 with IC₅₀ between 1.67 μM and 4.88 μM.     

Puqienine E: An angiotensin converting enzyme inhibitory steroidal alkaloid from Fritillaria puqiensis

Eight steroidal alkaloids, puqienine A, puqienine B, puqienine C, puqienine D, puqienine E, puqietinone, puqiedine and peimisine were isolated from Fritillaria puqiensis G. D. Yu et. G. Y. Chen, and their anti-hypertensive effect were assessed in vitro based on the inhibition of the purified angiotensin converting enzyme (ACE) using high-performance liquid chromatography assay. The results showed that puqienine E, puqienine B and puqienine A exhibited better inhibitory activity against ACE than others, with inhibition ratios of 70.2 ± 0.5%, 24.7 ± 0.5% and 20.4 ± 2.8%, respectively at the concentration of 200 μM. The 50% inhibiting concentration of puqienine E was determined to be 68 µM.     

Chemical constituents from endophytic fungus Fusarium oxysporum

A new oxysporidinone analogue (1) and a new 3-hydroxyl-2-piperidinone derivative (2), along with the known compounds (−)-4,6′-anhydrooxysporidinone (3), (+)-fusarinolic acid (4), gibepyrone D (5), beauvercin (6),cerevisterol (7), fusaruside (8), and (2S,2′R,3R,3′E,4E,8E)-1-O-D-glucopyranosyl-2-N-(2′-hydroxy-3′-octadecenoyl)-3-hydroxy-9-methyl-4,8-sphingadienine (9) were isolated from Fusarium oxysporum. Compounds 1-9 were evaluated for cytotoxicity using the MTT method against cancer cell lines, PC-3, PANC-1, and A549. Beauvericin showed cytotoxicity against PC-3, PANC-1, and A549 with IC₅₀ value of 49.5 ± 3.8, 47.2 ± 2.9, and 10.4 ± 1.6 μM, respectively. Beauvericin also exhibited anti-bacterial activity towards methicillin-resistant Staphylococcus aureus (MIC = 3.125 μg/mL) and Bacillus subtilis (MIC = 3.125 μg/mL).     

The influence of land-use change on the organic carbon distribution and microbial respiration in a volcanic soil of the Chilean Patagonia

Land-use changes can modify soil carbon contents. Depending on the rate of soil organic matter (SOM) formation and decomposition, soil-vegetation systems can be a source or sink of CO₂. The objective of this study was to determine the influence of land-use change on SOM distribution, and microbial biomass and respiration in an Andisol of the Chilean Patagonia. Treatments consisted of degraded natural prairie (DNP), thinned and pruned Pinus ponderosa plantations (PPP), and unmanaged second-growth Nothofagus pumilio forest (NPF). The soil was classified as medial, amorphic, mesic Typic Hapludands. Soil microbial respiration and microbial biomass were determined in the laboratory from soil samples taken at 0–5, 5–10, 10–20 and 20–40 cm depths obtained from three pits excavated in each treatment. Physical fractionation of SOM was performed in soil of the upper 40 cm of each treatment to obtain the three following aggregate-size classes: macroaggregates (>212 μm), mesoaggregates (212–53 μm) and microaggregates (<53 μm). Plant C content was 68% higher in PPP than in DNP and 635% higher in NPF than in PPP. Total soil and vegetation C content in both DNP and PPP were less than half of that in NPF. Total SOC at 0–10 cm depth decreased in the order DNP (7.82%) > NPF (6.16%) > PPP (4.41%), showing that land-use practices affected significantly (P < 0.01) SOC stocks. In all treatments, microbial biomass C and respiration were significantly higher (P < 0.05) in the upper 5 cm. Soil microbial respiration was also correlated positively with microbial biomass C and SOC. The different land uses affect the formation of organic matter, SOC and microbial biomass C, which in turn will affect soil microbial respiration. Conversion of DNP to PPP resulted in a 44% decrease of SOC stocks in 0–10 cm mineral soil. The largest amount of SOC was stabilized within the mesoaggregate fraction of the less disturbed system, NPF, followed by PPP. In the long term, formation of stable mesoaggregates in soils protected from erosion can behave as C sinks.     

Anticholinesterase activity of standardized extract of Illicium verum Hook. f. fruits

Illicium verum is a well known spice in traditional Indian system for its therapeutic potential. The present study was aimed to evaluate the acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory (BChE) activity of standardized extracts of I. verum and its oil. Present study confirmed that anethole contributed to the anticholinesterase activity of I. verum, with more specificity towards AChE. IC₅₀ for AChE and BChE inhibitory activity of anethole was 39.89 ± 0.32 μg/mL and 75.35 ± 1.47 μg/mL, whereas for the oil, 36.00 ± 0.44 μg/mL and 70.65 ± 0.96 μg/mL respectively. Therefore I. verum can be a good lead as anti-cholinesterase agent from natural resources.     

The pharmacokinetical study of plant alkaloid tetrandrine with a simple HPLC method in rabbits

A simple HPLC method was developed to quantify rabbit plasma tetrandrine (Tet) with propranolol (Pro) as internal standard. Based on the established method Tet and Pro were eluted at 7.1 and 12.0 min, respectively. It was shown that the concentration-time data of Tet fit the classical two-compartment model, no matter the drug was administered intravenously or orally to rabbits. The values of AUC_0 → ∞, clearance (Cl_0 → ∞), volume of distribution (Vd), and elimination half-life (t_1/2β) of Tet were 59861.149 ± 26962.196 μg/L ? min, 0.503 ± 0.173 L/min/kg, 179 ± 76.185 L/kg, and 283.808 ± 162.937 min for intravenous injection of 5 mg/kg, or 18986.217 ± 7462.308 μg/L ? min, 0.805 ± 0.267 L/min/kg, 110.284 ± 94.176 L/kg, and 732.919 ± 847.32 min for gavage administration of 10 mg/kg , respectively. The results indicate that Tet displays a limited absorption in intestinal tract, even though it has a favorable pharmacokinetic profile after oral or intravenous administration.     

Impacts of selective logging on above-ground forest biomass in the Monts de Cristal in Gabon

Selective logging is an important socio-economic activity in the Congo Basin but one with associated environmental costs, some of which are avoidable through the use of reduced-impact logging (RIL) practices. With increased global concerns about biodiversity losses and emissions of carbon from forest in the region, more information is needed about the effects of logging on forest structure, composition, and carbon balance. We assessed the consequences of low-intensity RIL on above-ground biomass and tree species richness in a 50 ha area in northwestern Gabon. We assessed logging impacts principally in 10 randomly located 1-ha plots in which all trees ?10 cm dbh were measured, identified to species, marked, and tagged prior to harvesting. After logging, damage to these trees was recorded as being due to felling or skidding (i.e., log yarding) and skid trails were mapped in the entire 50-ha study area. Allometric equations based on tree diameter and wood density were used to transform tree diameter into biomass.Logging was light with only 0.82 trees (8.11 m³) per hectare extracted. For each tree felled, an average of 11 trees ?10 cm dbh suffered crown, bole, or root damage. Skid trails covered 2.8% of the soil surface and skidding logs to the roadside caused damage to an average of 15.6 trees ?10 cm dbh per hectare. No effect of logging was observed on tree species richness and pre-logging above-ground forest biomass (420.4 Mg ha⁻¹) declined by only 8.1% (34.2 Mg ha⁻¹). We conclude from these data that with harvest planning, worker training in RIL techniques, and low logging intensities, substantial carbon stocks and tree species richness were retained in this selectively logged forest in Gabon.     

Post-fire soil respiration in relation to burnt wood management in a Mediterranean mountain ecosystem

After a wildfire, the management of burnt wood may determine microclimatic conditions and microbiological activity with the potential to affect soil respiration. To experimentally analyze the effect on soil respiration, we manipulated a recently burned pine forest in a Mediterranean mountain (Sierra Nevada National and Natural Park, SE Spain). Three representative treatments of post-fire burnt wood management were established at two elevations: (1) “salvage logging” (SL), where all trees were cut, trunks removed, and branches chipped; (2) “non-intervention” (NI), leaving all burnt trees standing; and (3) “cut plus lopping” (CL), a treatment where burnt trees were felled, with the main branches lopped off, but left in situ partially covering the ground surface. Seasonal measurements were carried out over the course of two years. In addition, we performed continuous diurnal campaigns and an irrigation experiment to ascertain the roles of soil temperature and moisture in determining CO₂ fluxes across treatments. Soil CO₂ fluxes were highest in CL (average of 3.34 ± 0.19 μmol m⁻² s⁻¹) and the lowest in SL (2.21 ± 0.11 μmol m⁻² s⁻¹). Across seasons, basal values were registered during summer (average of 1.46 ± 0.04 μmol m⁻² s⁻¹), but increased during the humid seasons (up to 10.07 ± 1.08 μmol m⁻² s⁻¹ in spring in CL). Seasonal and treatment patterns were consistent at the two elevations (1477 and 2317 m a.s.l.), although respiration was half as high at the higher altitude.Respiration was mainly controlled by soil moisture. Watering during the summer drought boosted CO₂ effluxes (up to 37 ± 6 μmol m⁻² s⁻¹ just after water addition), which then decreased to basal values as the soil dried. About 64% of CO₂ emissions during the first 24 h could be attributed to the degasification of soil pores, with the rest likely related to biological processes. The patterns of CO₂ effluxes under experimental watering were similar to the seasonal tendencies, with the highest pulse in CL. Temperature, however, had a weak effect on soil respiration, with Q₁₀ values of ca. 1 across seasons and soil moisture conditions. These results represent a first step towards illustrating the effects of post-fire burnt wood management on soil respiration, and eventually carbon sequestration.     

A new triterpene saponin from Androsace integra

A new triterpene saponin, androsacin (1), along with two known compounds, ardisiacrispin A (2) and saxifragifolin A (3), were isolated from the whole plants of Androsace integra. The chemical structure of the new compound was elucidated as 3β-O-{β-D-glucopyranosyl-(1 → 4)-O-β-D-xylopyranosyl-(1 → 2)-O-β-D-glucopyranosyl-(1 → 4)-[O-β-D-glucopyranosyl-(1 → 2)]-α-L-arabinopyranosyl}-16α-hydroxy-13β,28-epoxy-olean-30-al on the basis of spectral evidence. Ardisiacrispin A (2) was cytotoxic toward HepG2 cancer cell with the GI₅₀ value of 1.56 μM.     

A secoiridoid with quinone reductase inducing activity from Cortex fraxini

A new secoiridoid named chinensisol (1) along with twenty known compounds were isolated from the 95% ethanol extract of Cortex fraxini. Their structures were elucidated on the basis of NMR, MS, IR and UV spectral evidences. The quinone reductase (QR) inducing activities of the compounds were evaluated and the results showed that compounds 1, 9 and 14 had moderate QR inducing activities with CD values (concentration required to double the specific activity of QR) of 72.4 ± 7.7, 34.3 ± 3.3 and 42.0 ± 0.4 μM respectively.     

Polyketides with antimicrobial activity from the solid culture of an endolichenic fungus Ulocladium sp

Two new polyketides, 7-hydroxy-3, 5-dimethyl-isochromen-1-one (1) and 6-hydroxy-8-methoxy-3a-methyl-3a,9b-dihydro-3H-furo[3,2-c]isochromene-2,5-dione (2), along with eleven known compounds, 5′-methoxy-6-methyl-biphenyl-3,4,3′-triol (3), 7-hydroxy-3-(2-hydroxy-propyl)-5-methyl-isochromen-1-one (4), rubralactone (5), isoaltenuene (6), altenuene (7), dihydroaltenuenes A (8), altenusin (9), alterlactone (10), 6-O-methylnorlichexanthone (11), norlichexanthone (12), and griseoxanthone C (13) were isolated from the culture of the endolichenic fungus Ulocladium sp. Compound 2 was obtained as a racemate with an unprecedented chemical skeleton. The NMR data assignments for 3 and 4 were achieved for the first time. Compounds 1-13 were screened for their antimicrobial and radical scavenging activities. Compound 1 showed some antifungal activity against Candida albicans SC 5314 with IC₅₀ of 97.93 ± 1.12 μM. Compounds 11-13 showed strong activity against Bacillus subtilis with IC₅₀ in the range of 1-5 μM. Compound 12 significantly inhibited the growth of methicillin-resistant Staphylococcus aureus with IC₅₀ of 20.95 ± 1.56 μM. Compounds 9 and 10 showed strong radical scavenging activity in comparison with vitamin C. The plausible biosynthetic pathways for compounds 1, 2, and 4-8 were discussed.     

Antioxidant flavonoids from Epimedium wushanense

Two new flavonoids, wushanicaritin (1) and wushankaempferol (2), along with 24 known flavonoids were isolated from the whole herb of Epimedium wushanense T.S. Ying (Berberidaceae). On the basis of NMR and ESI-MS spectroscopic analysis, structures of compounds 1 and 2 were elucidated as 8-γ-hydroxy-γ,γ-dimethylpropyl-3,5,7-trihydroxy-4′- methoxyflavone and kaempferol 3-O-α-l-[2,3-di-O-β-d-(6-E-p-coumaroyl) glucopyranosyl]-rhamnopyranosyl-7-O-α-l-rhamnopyranoside, respectively. DPPH radical scavenging activity tests indicated that 1 (IC₅₀ 35.3 μM) exhibited antioxidant activity comparable to Vitamin C (IC₅₀ 32.0 μM), while 2 (IC₅₀ 443.7 μM) showed weak activity.