Evaluation of analgesic, anti-inflammatory and hepatoprotective effects of lycorine from Sternbergia fisheriana (Herbert) Rupr

The present study reports the potential antinociceptive, anti-inflammatory and hepatoprotective activities of lycorine from Sternbergia fischeriana (Herbert) Rupr. (Amaryllidaceae). Lycorine was evaluated on mice by using acetic-acid induced writhing and tail-flick tests. Lycorine exhibited stronger inhibition than aspirin in acetic-acid induced abdominal stretching at 1.0 mg/kg dose. Lycorine also showed antinociceptive activity at 1.0 mg/kg dose in tail-flick test. The anti-inflammatory activity of lycorine was not found to be significant at dose of 0.5 mg/kg. However, at doses of 1.0 mg/kg and 1.5 mg/kg, i.p. showed a significant reduction with 53.45% and 36.42%, respectively in rat paw oedema induced by carrageenan against the reference anti-inflammatory drug indomethacin (3 mg/kg, i.p.) (95.70%). The ED₅₀ of lycorine was determined as 0.514 mg/kg. Hepatoprotective activity of lycorine on carbon tetrachloride (CCl₄) induced acute liver toxicity following biochemical parameters were also evaluated. Rats were treated with lycorine at doses of 1.0 mg/kg and 2.0 mg/kg, i.p. Results of biochemical tests were confirmed by histopathological examination. Lycorine exhibited significant hepatoprotective effect at dose of 2.0 mg/kg i.p. dose.     

Ocotea quixos Lam. essential oil: In vitro and in vivo investigation on its anti-inflammatory properties

Here we investigated the anti-inflammatory properties of Ocotea quixos essential oil and of its main components, trans-cinnamaldehyde and methyl cinnamate, in in vitro and in vivo models. Ocotea essential oil and trans-cinnamaldehyde but not methyl cinnamate significantly reduced LPS-induced NO release from J774 macrophages at non-toxic concentrations, inhibited LPS-induced COX-2 expression and increased forskolin-induced cAMP production. The essential oil (30–100 mg/kg os) and trans-cinnamaldehyde (10 mg/kg os) in carrageenan-induced rat paw edema showed anti-inflammatory effect without damaging gastric mucosa. In conclusion we provide the first evidence of a significant anti-inflammatory gastro-sparing activity of O.quixos essential oil.     

Antinociceptive and antiplasmodial activities of cassane furanoditerpenes from Caesalpinia volkensii H. root bark

The chloroform and ethyl acetate extract (100 mg/kg) of Caesalpinia volkensii H. exhibited significant (P ≤ 0.05) antinociceptive activities using hot plate and writhing tests in mice while the later showed antiplasmodial activity (IC₅₀ 0.23 ± 0.07 and 4.39 ± 2.49 μg/ml) against chloroquine sensitive (D6) and chloroquine-resistant (W2), respectively. Two new furanoditerpenes [rel. 1β,5α-dihydroxyvoucapane (1) and rel. 1β,6β-dihydroxyvoucapane; 19β-methyl ester (2)] together with seven known compounds [voucapane (3), voucapan-5-ol (4), deoxycaesaldekarin C (5), caesaldekarin C (6), 5-hydroxyvinhaticoic acid (7), triacontanyl-(E)-ferulate (8), triacontanyl-(E)-caffaete (9) and 30′-hydroxytriacontanyl-(E)-ferulate (10)] were isolated from the two extracts. The administration of 3, 4, 5 and 6 (100 mg/kg i.p) caused a significant (P ≤ 0.05) reduction in the number of writhing episodes induced by acetic acid and (P ≤ 0.01) increased pain latency threshold in hot-plate test compared to control. However, the pure compounds indicated relatively (P ≤ 0.05) low antiplasmodial activity. The phytochemical constituents from the root bark of C. volkensii had better analgesic properties than antimalarial properties, justifying the use of the plant root bark as a remedy for pain.     

Theacrine,a purine alkaloid with anti-inflammatory and analgesic activities

The anti-inflammatory and analgesic effects of theacrine (1, 3, 7, 9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia kucha, were investigated. Xylene-induced ear edema, acetic acid-induced vascular permeability and λ-carrageenan-induced paw edema were used to investigate anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests were used to determine analgesic effect. Oral administration of theacrine (8–32 mg/kg) induced dose-related anti-inflammatory and analgesic effects. On the other hand, oral caffeine administration (8–32 mg/kg) did not show an inhibitory effect on the inhibition of inflammatory response or cause analgesia. Additionally, the result of the acute toxicity test showed that the LD₅₀ of theacrine was 810.6 mg/kg (769.5–858.0 mg/kg). The data obtained suggest theacrine possessed analgesic and anti-inflammatory activities.     

Bioactive flavones and biflavones from Selaginella moellendorffii Hieron

Three new flavones named 5-carboxymethyl-4′,7-dihydroxyflavone (1), its ethyl ester (2) and butyl ester (3) were isolated from the herb Selaginella moellendorffii Hieron., together with ten known compounds. Their structures were elucidated on the basis of spectroscopic and chemical analysis. Selected compounds were evaluated for their anti-HBV and cytotoxic activity. Among them, compounds 2 and 3 displayed inhibitory activity in vitro on hepatitis B virus (HBV) surface antigen (HBsAg) secretion of the Hep G2.2.15 cell line with IC₅₀ values of 0.17 mg/ml and 0.46 mg/ml, and on HBV e antigen (HBeAg) secretion with IC₅₀ values of 0.42 mg/ml and 0.42 mg/ml, respectively. Compounds 7, 8, 10 and 12 exhibited selective cytotoxicity against the three human cancer cell lines tested.     

Anti-diabetic effect of American ginseng may not be linked to antioxidant activity: Comparison between American ginseng and Scutellaria baicalensis using an ob/ob mice model

Antioxidants have been considered as a useful remedy in diabetes therapeutics, and thus, herbal medicines with antioxidant properties may play major role in treating diabetes. In this report, we performed a comparative study using American ginseng and Scutellaria baicalensis to test whether the anti-diabetic effect of American ginseng is associated with its antioxidant activity. We used a simple water extraction procedure to prepare American ginseng root extract (AGE) and S. baicalensis extract (SbE), and utilized these two antioxidant herbs to evaluate their anti-diabetic effect in obese diabetic ob/ob mice. HPLC analysis was used to identify major constituents in the AGE and SbE. After 12 days of daily intraperitoneal injection, AGE at 300 mg/kg showed significant effects on fasting blood glucose levels (P < 0.01) and glucose tolerance test (P < 0.01) compared to vehicle-treated mice. Animal body weights also reduced significantly after 12-day treatment (P < 0.01). However, SbE, a very strong antioxidant extract, administered at 5–50 mg/kg (based on our previous studies without adverse events) for 12 days did not show any significant effects on blood glucose and body weight changes. No effects were shown when baicalein, an effective antioxidant constituent in SbE, was administered at 1–5 mg/kg. It appears that the anti-diabetic effect of American ginseng may not be linked to its antioxidant actions. The mechanisms of American ginseng's effects on reducing high blood glucose levels and body weight remain to be investigated in future experiments.     

Optimizing dosage and preventing leaching of imidacloprid for management of hemlock woolly adelgid in forests

Hemlock woolly adelgid (Adelges tsugae Annand) threatens native hemlock (Tsuga canadensis and T. caroliniana) in the eastern United States. Imidacloprid used as a soil-applied systemic insecticide is effective against A. tsugae in natural forests and in landscapes. Non-target impacts are a special concern because hemlock is ecologically important; often growing next to streams which contain aquatic species that are sensitive to imidacloprid, some of which are protected or endangered fauna. Environmental risk can be mitigated by determining the minimum effective dosage in forests. Adelgid populations responded to imidacloprid dosage with approximately a linear relationship between the percent population reduction (probability scale) vs. log of dosage; 50% reduction in populations could be achieved with 0.15 g per 2.5 cm of trunk diameter at breast height (dbh), or 10% of the maximum labeled dosage. However, effectiveness was found to vary based on dbh; the dosage predicted to give ∼90% reductions in adelgid populations is given by the equation log(dosage) = 0.0153 × dbh − 1.074, where the dosage is g imidacloprid per 2.5 cm of trunk dbh, and dbh is measured as cm. For trees less than 82 cm dbh, these dosages are less than the typical 1.5 g imidacloprid per 2.5 cm dbh currently used. Formulation into tablets rather than as a wettable powder reduced the maximum imidacloprid concentration in soil solution at 5 cm depth from 80 to 1.6 ppm in columns constructed with the organic soil found beneath forest hemlocks. A combination of optimum dosing of trees and adoption of the tablet formulation when treating trees in sensitive habitats should minimize the risk of contaminating aquatic resources with imidacloprid.     

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.     

Sesquiterpenoids and norterpenoids from Vitex negundo

Chemical investigation on the seeds of Vitex negundo has afforded a new furan-containing sesquiterpenoid, negunfurol (1), a new norlabdane-type diterpenoid, negundoal (2), and two new norursane-type triterpenoids, negundonorins A (3) and B (4), together with two know compounds, 3-formyl-4,5-dimethyl-8-oxo-5H-6,7-dihydronaphtho[2,3-b]furan (5) and 3-epi-corosolic acid (6). Their structures and configurations were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Compound 3 was strongly cytotoxic against ZR-75-30 cell line with IC₅₀ value of 0.56 ± 0.19 μg/mL, whereas compound 1 was most active against HL-60 cell line with IC₅₀ value of 0.94 ± 0.26 μg/mL.     

Flavonols attenuate the immediate and late-phase asthmatic responses to aerosolized-ovalbumin exposure in the conscious guinea pig

We previously reported that quercetin and rutin have potent, anti-asthmatic activity, but the structure-activity relationships of flavonoids and anti-asthmatic agents are still poorly understood. In the current study, the effects of kaempferol, fisetin, and morin on the immediate-phase response (IAR) and late-phase response (LAR) caused by exposure to aerosolized-ovalbumin (OA) in OA-sensitized guinea pigs were evaluated by determining the specific airway resistance (sRaw), recruitment of leukocytes and chemical mediators in bronchoalveolar lavage fluid (BALF), histopathological surveys, and determination of neutrophil chemotaxis. Fisetin and kaempherol (30 mg/kg, p.o.) significantly (P < 0.01) inhibited sRaw by 47.93% and 30.05% in IAR, and 54.45% and 40.50% in LAR, when compared to vehicle control, respectively. Furthermore, all three studied flavonols (30 mg/kg, p.o.) significantly (P < 0.05) inhibited the recruitment of total, as well as subtypes of, leukocytes into the lung BALF. This recruitment inhibition corresponded to the inhibition of leukocyte infiltration, particularly of eosinophils and neutrophils, into the lung in pathological surveys and formly-methionyl-leucyl-phenylalanine (FMLP)-induced neutrophil chemotaxis studies. Kaempferol inhibited FMLP-induced neutrophil chemotaxis in a concentration-dependent manner in a tested range of 1–100 μM. Fisetin inhibited histamine content and peroxidase (EPO) activity in BALF in a dose-dependent manner. All three tested flavonols significantly (P < 0.01) inhibited histamine content at 10 mg/kg, and phospholipase A₂ (PLA₂) and EPO activities at 30 mg/kg (p.o.) in BALF. Kaempherol had a greater anti-asthmatic effect than other flavonols. Fisetin demonstrated the greatest inhibition of sRaw, whereas morin had lesser effects. These results indicate that the lower the molecular weight, the greater the anti-asthmatic activities of these compounds.     

Evaluation of central nervous system effects of iso-6-cassine isolated from Senna spectabilis var. excelsa (Schrad) in mice

The depressant and anticonvulsant activities of iso-6-cassine (ISO) from Senna spectabilis (0.5, 1.0 and 1.5 mg/kg) injected by oral route in mice caused a significant decrease in the motor activity of animals when compared with the control group, up to 30 days after the administration and at dose of 1.5 mg/kg, it reduced the remaining time of animals on Rota-rod apparatus. Additionally, ISO at doses tested was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole and picrotoxin. These results suggest possible depressant and anticonvulsant activities in mice that need further investigation.     

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).     

Isolation and free radical scavenging activities of a novel biflavonoid from the shells of Camellia oleifera Abel.

Oil production from the seeds of Camellia oleifera Abel. causes a great waste of shells which contain a lot of bioactive components. The aim of this research was to isolate flavonoid from the shells of C. oleifera Abel. and evaluate its uses. The shells were extracted by 70% methanol, hydrolyzed by 2 M hydrochloric acid, and further crystallized in acetone, the corresponding yield of flavonoid was up to 2.1% (purity: 93.8%). The procedure is concise, quick and proper for industrial utilization of the shells. Flavonoid was identified as bimolecular kaempferol structure by UV, MS, ¹H NMR and ¹³C NMR spectra, which is a new biflavonoid and first found in C. oleifera Abel. It showed stronger scavenging activity of DPPH and ABTS radicals than kaempferol. MDA decreased, and SOD and GSH-Px activities increased significantly in serum (P < 0.01) and brain tissue (P < 0.05) of mice after intragastric administration of biflavonoid at 200 mg/kg/d for 30 d. Its effects in vivo are superior to vitamin C and similar to kaempferol. Thus biflavonoid can be used as a prospective antioxidant to protect brain cells against damage from free radicals.     

Intestinal absorption of forsythoside A in different compositions of Shuang-Huang-Lian

Shuang-Huang-Lian (SHL), a traditional Chinese formula containing Lonicerae japonicae flos (LJF), Scutellariae radix (SR) and Forsythiae fructus (FF), is commonly used to treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. Forsythoside A is one of the main active ingredients in Forsythiae fructus, a key herb in SHL. In the present study, effects of different compositions in SHL on the intestinal absorption of forsythoside A were investigated. The observations from in situ intestinal circulation model showed that A/%(h^− 1) of forsythoside A in FF + LSF, FF + SR and SHL were all reduced greatly compared with that in FF. However, in pharmacokinetics study, C_max and AUC_0 → 1440 of forsythoside A all increased and T_1/2 prolonged in SHL, FF + LJF and FF + SR compared with FF. The results indicated that the different compositions of SHL decreased absorption but increased bioavailability of forsythoside A, which may be related to its metabolism inhibited in intestine or liver.     

Crown transparency, tree mortality and stem growth of Pinus sylvestris, and colonization of Tomicus piniperda after an outbreak of Gremmeniella abietina

In the year 2000, large areas of forest in Sweden, mainly 30-50 year old Pinus sylvestris (L.) stands, were attacked by the fungus Gremmeniella abietina (Lagerb.) Morelet. The aims of this study were to investigate: (i) the relationship between G. abietina-induced tree crown transparency (CT) and P. sylvestris (L.) tree mortality; (ii) the influence of CT levels on stem growth; (iii) the recovery of the crown; and (iv) the association of CT and colonization by Tomicus piniperda (L.). Thirty-five permanent sample plots were established in five P. sylvestris stands (38-46 years old), infested by G. abietina, and 23 plots in four reference stands, not obviously infested.During the 5 years following the attack, the total mortality amounted to 454 trees ha⁻¹ and 7.8 m² ha⁻¹, on average, in the five infested stands, corresponding to 42% of the trees and 34% of the basal area at the time of the attack. Most of the mortality occurred within 2 years of the attack. The mortality of individual trees (2002-2005) was found to be related to the crown transparency (CT), the position of needle loss within the crown and the tree diameter at breast height. Based on our modeling, the probability of mortality was substantially increased if the initial CT-value was higher than 85%.Growth reductions were detected for individual trees with an initial CT of >c. 40%. In contrast, trees with a low initial CT (<c. 40%) were not affected and even exhibited increased growth. In the five infested stands, the reductions in basal area and volume increment were estimated to be 26-58%, and, 42-73%, respectively, during the five growing seasons after the attacks.The trees in the infested stands that were still alive in spring 2005 had started to recover in terms of CT. Breeding of T. piniperda on the P. sylvestris (L.) stems occurred almost exclusively on stems with a CT > 90%.The data from this study suggest that when a P. sylvestris (L.) stand has been attacked by G. abietina, trees with a CT above 80% should be felled; the remaining trees will have a high probability of survival and resistance to successful breeding by the T. piniperda.     

Anti-inflammatory and analgesic properties of cis-mulberroside A from Ramulus mori

This study examined the analgesic and anti-inflammatory actions of cis-mulberroside A isolated from Ramulus mori in several models of inflammatory pain in mice. Cis-mulberroside A (25 and 50 mg/kg) given by p.o. route 30 min before challenge produced a dose-dependent inhibition of the acetic acid-induced pain and Evans blue leakage in mice. In addition, this compound exhibited significant systemic anti-inflammatory activity in carrageenan-induced mouse paw edema in a concentration-related manner (33.1–68.5% inhibition), and similar results were achieved in formalin test. Suppressive effects of cis-mulberroside A on the production of NO and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated macrophages were also assessed. Collectively, cis-mulberroside A showed high analgesic and anti-inflammatory activities. The above results will be the supporting evidence for the potential anti-rheumatoid activity of R.mori in Chinese traditional medicine.     

Antioxidant flavanes from Livistona chinensis

Three new flavanes and eight known flavonoids were isolated from the fruits of Livistona chinensis. The structure of the new flavanes were established as 2S,3S-3,5,7,3′,5′-pentahydroxyflavane (1), 2R,3R-3,5,6,7,8,4′-hexahydroxyflavane (2) and 2R,3R-3,5,6,7,8,3′,5′-heptahydroxyflavane (3), respectively, on the basis of chemical and spectroscopic data. The antiproliferative activity against four human tumor cell lines (HL-60, Mata, HepG2 and CNE-1) was evaluated. 1 had significantly antiproliferative effects against HL-60 and CNE-1 with the IC₅₀ of 0.2 ± 0.01 and 1.0 ± 0.1 μM, respectively, overpowering the reference compound in the assay (cisplatin). Most compounds also exhibited potent antioxidant activity.     

A positive growth response to NaCl applications in Eucalyptus plantations established on K-deficient soils

Contrasting responses of Eucalyptus trees to K fertilizer applications have been reported on soils with low K contents. A complete randomized block experiment was set up in Brazil to test the hypothesis that large atmospheric deposits of NaCl in coastal regions might lead to a partial substitution of K by Na in Eucalyptus physiology and enhance tree growth. Treatments with application of 1.5, 3.0, 4.5 kmol K ha⁻¹ (K_1.5, K_3.0, K_4.5, respectively) as KCl, 3.0 kmol K ha⁻¹ applied as K₂SO₄, 3.0 kmol Na ha⁻¹ (Na_3.0) as NaCl commercialized for cattle feeding, and a mixture of 1.5 kmol K + 1.5 kmol Na ha⁻¹ (K_1.5 + Na_1.5) were compared to a control treatment (C) with no K and Na applications. All the plots were fertilized with large amounts of the other nutrients.     

Soil–atmosphere CO2, CH4 and N2O fluxes in boreal forestry-drained peatlands

Greenhouse gas emissions from managed peatlands are annually reported to the UNFCCC. For the estimation of greenhouse gas (GHG) balances on a country-wide basis, it is necessary to know how soil–atmosphere fluxes are associated with variables that are available for spatial upscaling. We measured momentary soil–atmosphere CO₂ (heterotrophic and total soil respiration), CH₄ and N₂O fluxes at 68 forestry-drained peatland sites in Finland over two growing seasons. We estimated annual CO₂ effluxes for the sites using site-specific temperature regressions and simulations in half-hourly time steps. Annual CH₄ and N₂O fluxes were interpolated from the measurements. We then tested how well climate and site variables derived from forest inventory results and weather statistics could be used to explain between-site variation in the annual fluxes. The estimated annual CO₂ effluxes ranged from 1165 to 4437 g m⁻² year⁻¹ (total soil respiration) and from 534 to 2455 g m⁻² year⁻¹ (heterotrophic soil respiration). Means of 95% confidence intervals were ±12% of total and ±22% of heterotrophic soil respiration. Estimated annual CO₂ efflux was strongly correlated with soil respiration at the reference temperature (10 °C) and with summer mean air temperature. Temperature sensitivity had little effect on the estimated annual fluxes. Models with tree stand stem volume, site type and summer mean air temperature as independent variables explained 56% of total and 57% of heterotrophic annual CO₂ effluxes. Adding summer mean water table depth to the models raised the explanatory power to 66% and 64% respectively. Most of the sites were small CH₄ sinks and N₂O sources. The interpolated annual CH₄ flux (range: −0.97 to 12.50 g m⁻² year⁻¹) was best explained by summer mean water table depth (r² = 64%) and rather weakly by tree stand stem volume (r² = 22%) and mire vegetation cover (r² = 15%). N₂O flux (range: −0.03 to 0.92 g m⁻² year⁻¹) was best explained by peat CN ratio (r² = 35%). Site type explained 13% of annual N₂O flux. We suggest that water table depth should be measured in national land-use inventories for improving the estimation of country-level GHG fluxes for peatlands.     

The phenylpropanoids of Aster flaccidus

Aster flaccidus bge has been used as traditional medicine in northwestern China. Two new phenylpropanoids (1–2) including one lignan: (7′R, 8S)-9′-lariciresinol-(α-methyl)-butanoate (1), 5,9-dimethoxyl-7-(α-methyl)-butanoxyl-phenyl-2E-propenol-(α-methyl)-butanoate (2) isolated from the chloroform extract of the root of Aster flaccidus bge were identified by means of extensive spectroscopic studies: 1D and 2D NMR spectra as well as HRMS analysis. They have not obvious anti-HIV-1 therapeutic activity (TI = 1.0–1.1) compared with AZT (TI = 55,556) as the result of the determination of their in vitro anti-HIV-1 activity while compound 2 displays strong antitumor activity against BEL 7402 (human liver carcinoma) with cisplatin as a positive control and the effect increases with the measuring-time going on (24 h, IC₅₀: 106.67 ± 8.47 µM — 72 h, IC₅₀: 50.51 ± 6.11 µM).