Peripheral and central antinociceptive effects of the butanolic fraction of <Emphasis Type="Italic">Byrsonima verbascifolia</Emphasis> leaves on nociception-induced models in mice

Byrsonima verbascifolia (Malpighiaceae), commonly known as ‘murici’, is used in folk medicine, for example, in the treatment of inflammation. The anti-inflammatory activity of the butanolic fraction of B. verbascifolia leaves (BvBF) was previously reported by our group, and the present study was designed to evaluate their antinociceptive effects. BvBF (25, 50, and 100 mg/kg) administered intraperitoneally (i.p.) inhibited acetic acid induced abdominal writhing. In the formalin test, BvBF (10, 30 and 100 mg/kg, i.p.) caused a reduction in licking time in both the neurogenic and inflammatory phases. Moreover, we demonstrated that BvBF (30 and 100 mg/kg, i.p.) caused an increase in the latency to response in the hot-plate test. These results demonstrate that BvBF possesses marked peripheral and central antinociceptive activities. Pre-treatment with the non-selective receptor antagonist naloxone (5 mg/kg, i.p.) abolished the antinociceptive effects of BvBF (100 mg/kg, i.p.) in the neurogenic phase of the formalin and hot-plate tests. The anti-inflammatory activity of BvBF (previously reported) as well as the participation of the opioidergic system seems to be responsible, at least in part, for these antinociceptive effects. Finally, BvBF at the doses investigated (25, 50 and 100 mg/Kg) did not cause any toxicity signals, showing that the antinociceptive activity is devoid of sedative and hypomotility effects.     

Pharmacological reports about gastroprotective effects of methanolic extract from leaves of <Emphasis Type="Italic">Solidago chilensis</Emphasis> (Brazilian arnica) and its components quercitrin and afzelin in rodents

Solidago chilensis Meyenmost (Asteraceae), popularly known as “Brazilian arnica” or “arnica-do-campo,” is widely used in the folk medicine to treat gastric disorders. Based on this, the gastroprotective activity of S. chilensis methanolic extract was investigated. Besides, a phytochemical study allowed isolation of two flavonoids (quercitrin and afzelin). The gastroprotective effects were investigated in acute gastric ulcer models, and the antisecretory activity was assessed in vivo and in vitro. The adhered mucus levels, reduced glutathione (GSH) content and myeloperoxidase (MPO) activity were quantified in ulcerated tissues. The contribution of isolated compounds in extract effects was evaluated, and its doses were calculated according to its yield. To evaluate the in vivo healing properties of S. chilensis methanolic extract, a chronic gastric ulcer was induced in mice by 10 % acetic acid. Evaluation of tumor necrosis factor (TNF) levels was also performed at the site of the acetic acid-induced gastric ulcer. In parallel, effects on cell viability and cell proliferation of fibroblasts (L929 cells) were determined by in vitro trials. Firstly, the S. chilensis methanolic extract (100 or 300 mg/kg) reduced the ulcer area induced by ethanol/HCl in mice when compared to the vehicle group. Moreover, the S. chilensis extract (300 mg/kg) prevented the mucus depletion, the increase in MPO activity and the decrease in the GSH levels in the ulcerated gastric tissue. The S. chilensis extract also was able to decrease the indomethacin-induced gastric ulcer in rats at a dose of 100 mg/kg. The antisecretory effect of the extract (100 mg/kg, intraduodenal (i.d.)) was confirmed by the reduction in the volume and acidity in parallel to an increase in the pH of gastric content. In addition, quercitrin (1.38 mg/kg, but not 0.46 mg/kg) and afzelin (0.026 and 0.078 mg/kg) decreased the ethanol/HCl-induced gastric ulcer. In this model, quercitrin (1.38 mg/kg) prevented the depletion of gastric GSH content and both quercitrin (1.38 mg/kg) and afzelin (0.078 mg/kg) reduced the MPO activity. These compounds also inhibited the H⁺,K⁺-ATPase activity at a concentration of 1–100 μg/ml. In addition, the participation of quercitrin and afzelin in these effects also was confirmed. Furthermore, after 4 days of the treatment, an oral administration of S. chilensis methanolic extract (100 mg/kg) reduced the area of the gastric ulcer induced by acetic acid and the regeneration of the gastric mucosa was accompanied by a reduction in gastric TNF levels. The healing properties of the extract also were confirmed by enhancement of proliferation and coverage of scratched wounds in a fibroblast monolayer. Together, our results confirmed the gastroprotective effect of S. chilensis methanolic extract as well as its gastric healing potential and provided some support to the traditional use of S. chilensis for prevention and treatment of gastric lesions in complementation to its known anti-inflammatory properties.     

Novel phenanthridine (PHE-4i) derivative inhibits carrageenan-induced rat hind paw oedema through suppression of hydrogen sulfide

This study was conducted to assess the anti-inflammatory effect of a novel synthesized phenanthridine alkaloid (PHE-4i) and to examine the possible involvement of hydrogen sulfide (H₂S) in anti-inflammatory mechanism. The synthesized phenanthridine derivative PHE-4i (2, 5, and 10 mg/kg) was administered intraperitoneally to rats. One hour following treatment, inflammation was induced by intraplantar injection of carrageenan (1 %), in the hind paw. Paw volume as the index of inflammation was measured before and after carrageenan injection. Neutrophil sequestration into the hind paw was quantified by measuring tissue myeloperoxidase (MPO) activity and was compared for the inhibition of H₂S production. Pretreatment with PHE-4i significantly reduced carrageenan-induced hind paw weight, MPO activity, leukocyte infiltration, and H₂S production in a dose-dependent manner (p < 0.001). These results indicate that the anti-inflammatory effect of PHE-4i on carrageenan-induced rat paw oedema could be via the inhibition of the gaseous mediator H₂S.     

Mixed effects of caffeic acid phenethyl ester (CAPE) on joint inflammation,bone loss and gastrointestinal inflammation in a murine model of collagen antibody-induced arthritis

Objective

To investigate the effect of caffeic acid phenethyl ester (CAPE) on local and systemic inflammation and bone loss in collagen antibody-induced arthritis (CAIA) mice.

Methods

Four groups of mice (n = 8 per group) were allocated; control, CAPE (1 mg/kg), CAIA and CAIA + CAPE (1 mg/kg). Local inflammation and bone loss were evaluated using clinical paw scores, in vivo micro-computed tomography (micro-CT), histological assessment and tartrate-resistant acid phosphatase (TRAP) staining. Serum levels of C-reactive protein (CRP) and C-terminal telopeptide (CTX-1) were measured by ELISA. Jejunum and colon sections were evaluated histopathologically for damage and toxicity.

Results

Greater paw scores and percentage change in paw volume were observed in CAIA + CAPE compared to the control groups (p < 0.05). Bone volume over time remained unchanged (p = 0.94) and the number of multinucleated TRAP-positive cells was greatest in CAIA + CAPE mice (p < 0.05). CRP and CTX-1 levels did not differ between groups. CAIA + CAPE mice exhibited lower colon toxicity scores and a reduced percentage of cavitated goblet cells in the colon crypts compared with CAIA mice (p = 0.026 and p = 0.003, respectively). Histopathology in the jejunum was not altered.

Conclusion

CAPE did not reduce paw inflammation or bone loss in CAIA mice. CAPE reduced histopathological changes in the colon of CAIA mice.

     

Evaluation of the protective effect of pentoxifylline on carrageenan-induced chronic non-bacterial prostatitis in rats

Chronic non-bacterial prostatitis (CNP) is the most common type of prostatitis and oxidative stress (OS) was shown to be highly elevated in prostatitis patients. This study aimed to investigate the protective effect of pentoxifylline (PTX) on CNP induced by carrageenan in rats. Male adult Wistar rats (n = 30) were divided into control, CNP and three treatment groups (n = 6) including CNP + cernilton and CNP + PTX groups. CNP was induced by single intraprostatic injection of 1% carrageenan (100 µl). Rats in treatment groups received orally cernilton 100 mg/kg and PTX at 50 and 100 mg/kg 1 week after CNP induction for 21 days. Prostatic index (PI), prostatic specific antigen (PSA), tumor-necrosis factor alpha (TNF-α), serum lipid peroxidation (MDA), blood urea nitrogen, creatinine and histopathological changes were compared between groups. There were significant increase of PI, serum levels of PSA, TNF-α and MDA in CNP group at 29 day. In treatment groups, significant reduction in PI, serum levels of PSA, TNF-α, MDA and creatinine was observed especially in rats treated with dose of 50 mg/kg of PTX. In CNP group, histopathological changes of the prostate such as leucocyte infiltration, large involutions and projection into the lumen and reducing the volume of the lumen were observed as well. Whereas PTX, especially at dose of 50 mg/kg, could improve the above-mentioned changes remarkably in CNP treated rats. For the first time, our findings indicated that PTX improved CNP induced by carrageenan in rats.     

Anti-inflammatory effect of <Emphasis Type="Italic">Naravelia zeylanica</Emphasis> DC via suppression of inflammatory mediators in carrageenan-induced abdominal oedema in zebrafish model

The traditional herbal medicines are receiving great importance in the health care sector, especially in Indian system of medicine, i.e, Ayurveda. The present study focused on the standardization of Naravelia zeylanica (L.) DC in terms of its active phytochemicals and to evaluate the anti-inflammatory activity of ethanol extract of N. zeylanica (ENZ). An analytical method was developed by high-performance liquid chromatography for simultaneous determination of β-sitosterol, lupeol and oleanolic acid in ENZ. The cell viability of ENZ was investigated using MTT assay. IC₅₀ value of ENZ on cell viability was found to be 653.01 µg/mL. To determine the anti-inflammatory activity of ENZ by in vitro method, LPS was added to the macrophage cells to induce activation and ENZ was further added to observe the recovery of inflamed cells. These cells when treated with ENZ, the percentage of viable cells were considerably increased to 74.68%. Loss of mitochondrial membrane potential on treatment with LPS and its recovery by ENZ was studied and found that the number of cells that were damaged on treatment with ENZ + LPS was comparatively lesser than treatment with LPS only. An in vivo anti-inflammatory study was carried out in carrageenan-induced abdominal oedema method in adult zebrafish which revealed the percentage inhibition of inflammation at graded dose levels of ENZ as 23.5% at 100 mg/kg, 62.4% at 200 mg/kg and 87.05% at 350 mg/kg when compared with standard of diclofenac which showed 85% inhibition at 100 mg/kg. The PCR amplification of DNA extracted from adult zebrafish showed that increased concentration of ENZ considerably downregulates the expression of TNF-α and iNOS, the mediators of inflammation.     

Effect of Gastric Fluid Volume on the <Emphasis Type="Italic">In Vitro</Emphasis> Dissolution and <Emphasis Type="Italic">In Vivo</Emphasis> Absorption of BCS Class II Drugs: a Case Study with Nifedipine

Nifedipine is a BCS Class II drug used for treatment of hypertension and preterm labor. Large inter-patient variability in nifedipine absorption results in variable exposure among different patients. We conducted in vitro dissolution studies to compare nifedipine dissolution from immediate release (IR) capsules with different volumes of dissolution media. Results from dissolution studies were used to design a crossover study in healthy volunteers to evaluate the effect of coadministered water volume with nifedipine 10 mg IR capsules on nifedipine pharmacokinetics, especially absorption (C _max, t _max, and AUC_0-6). Dissolution studies demonstrated that larger gastric fluid volumes result in enhanced nifedipine dissolution from 10 mg IR cosolvent capsules (73 vs. 17% in 200 and 100 mL simulated gastric fluid, respectively, at 30 min). The pharmacokinetic crossover study in healthy volunteers (N?=?6) did not show a significant effect of the water volume administered with the capsule (50 vs. 250 mL) on C _max, t _max, or AUC_0-6 of orally administered nifedipine IR capsules (10 mg). However, administration of large water volumes resulted in lower variability in nifedipine C _max (47 vs. 70% for 250 and 50 mL, respectively). Administration of large water volumes with nifedipine 10 mg IR cosolvent capsules may reduce inter-individual variability in plasma exposure. Evaluation of similar effects in other BCS Class II drugs is recommended.     

Chemical composition and bioactivities of the essential oil from different organs of <Emphasis Type="Italic">Ferula communis</Emphasis> L. growing in Tunisia

The essential oils obtained by the hydrodistillation from the fresh flowers, leaves, stems, and roots of Ferula communis L., growing in Tunisia were analyzed by GC and GC/MS. Thirty-two components were identified in the oil of flowers with camphor (18.3 %), α-pinene (15.3 %), and β-eudesmol (9.3 %) as the main constituents. Twenty-nine compounds were identified in the oil of stems with β-eudesmol (28.1 %), δ-eudesmol (11.1 %), and α-eudesmol (9.6 %) as the main compounds. Twenty compounds were characterized in the oil of roots with dillapiole (7.9 %), guaiol (7.3 %), and spathulenol (6.8 %). In the oil of leaves, α-eudesmol (25.2 %), β-eudesmol (20.7 %), δ-eudesmol (10.1 %), and caryophyllene oxide (7.2 %) were found as the main constituents. This study was undertaken to evaluate the antioxidant activity using DPPH (2,2′-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid), reducing power, and catalase activity. We tested also the antibacterial, cytotoxic, and cholinesterase inhibition properties of the essential oil of different organs of F. communis. The essential oil of the stems showed the highest antioxidant activity (IC₅₀ = 0.03 ± 0.001 mg mL^?1), in DPPH assay and the important result of catalase (303.03 µmol H₂O₂ degraded/min/protein) of F. communis. The antibacterial activity of the oil was determined by micro-well dilution assay. The best results (MIC = 0.156 ± 0.02 mg mL^?1) were exhibited by the essential oil of the leaves of F. Communis against Pseudomonas aeruginosa. Besides, the strongest cytotoxic activity against Hela cells was shown with essential oils’ leaves with an inhibition percentage of 79.05 % at the concentration of 500 µg mL^?1. However, the best inhibition percentage of A 549 cells was detected for essential oils’ leaves with an inhibition percentage of 54.56 % at 250 µg mL^?1. Our finding showed that the essential oil of the flowers was the most active, with 64.623 % of inhibition against butyrylcholinesterase at 10 mg mL^?1 from the incubation time of 30 min.     

<Emphasis Type="Italic">p</Emphasis>-Hydroxyacetophenone suppresses nuclear factor-κB-related inflammation in nociceptive and inflammatory animal models

p-Hydroxyacetophenone (HAP) is a crucial chemical compound present in plants of the genus Artemisia, which are used in traditional therapies for treating jaundice, hepatitis, and inflammatory diseases. Nevertheless, the bioactivity of HAP remains to be identified in order to prove its importance in the plants of genus Artemisia. This study investigated the antioxidative, antinociceptive, and anti-inflammatory effects of HAP, and probed its possible molecular mechanisms. Our results revealed that HAP (80 mg/kg, intraperitoneally) in vivo reduced the acetic acid-induced writhing response and formalin-induced licking time. Moreover, in the λ-carrageenan-induced acute-inflammatory paw edema model in mice, HAP significantly improved hind paw swelling and neutrophil infiltration. In a homogenized paw tissue examination, HAP attenuated pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. Simultaneously, HAP also inhibited the production of nuclear factor kappa B, cyclooxygenase-2, and nitric oxide (NO). Another examination revealed that HAP exerted anti-inflammatory activity by decreasing malondialdehyde levels in the edematous paw through increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase in the liver. These findings may be beneficial in understanding the therapeutic effects of some plants of the genus Artemisia in the pretreatment of inflammation-associated diseases.     

Suppression of P2X7/NF-κB pathways by Schisandrin B contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury

The aim of the present study was to assess the effects and mechanisms of Schisandrin B (SchB) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg), and SchB (25, 50, and 75 mg/kg) was injected 1 h before LPS challenge by gavage. After 12 h, bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected. Histological studies demonstrated that SchB attenuated LPS-induced interstitial edema, hemorrhage, and infiltration of neutrophils in the lung tissue. SchB pretreatment at doses of 25, 50, and 75 mg/kg was shown to reduce LPS-induced lung wet-to-dry weight ratio and lung myeloperoxidase activity. In addition, pretreatment with SchB lowered the number of inflammatory cells and pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. The mRNA and protein expression levels of nuclear factor kappa B (NF-κB) signaling-related molecules activated by P2X7 were investigated to determine the molecular mechanism of SchB. The findings presented here suggest that the protective mechanism of SchB may be attributed partly to the decreased production of pro-inflammatory cytokines through the inhibition of P2X7/NF-κB activation.     

Lipid-based Formulations for Danazol Containing a Digestible Surfactant,Labrafil M2125CS: <Emphasis Type="BoldItalic">In Vivo</Emphasis> Bioavailability and Dynamic <Emphasis Type="BoldItalic">In Vitro</Emphasis> Lipolysis

Purpose

To evaluate the use of Labrafil® M2125CS as a lipid vehicle for danazol. Further, the possibility of predicting the in vivo behavior with a dynamic in vitro lipolysis model was evaluated.

Methods

Danazol (28 mg/kg) was administered orally to rats in four formulations: an aqueous suspension, two suspensions in Labrafil® M2125CS (1 and 2 ml/kg) and a solution in Labrafil® M2125CS (4 ml/kg).

Results

The obtained absolute bioavailabilities of danazol were 1.5?±?0.8%; 7.1?±?0.6%; 13.6?±?1.4% and 13.3?±?3.4% for the aqueous suspension, 1, 2 and 4 ml Labrafil® M2125CS per kg respectively. Thus administration of danazol with Labrafil® M2125CS resulted in up to a ninefold increase in the bioavailability, and the bioavailability was dependent on the Labrafil® M2125CS dose. In vitro lipolysis of the formulations was able to predict the rank order of the bioavailability from the formulations, but not the absorption profile of the in vivo study.

Conclusions

The bioavailability of danazol increased when Labrafil® M2125CS was used as a vehicle, both when danazol was suspended and solubilized in the vehicle. The dynamic in vitro lipolysis model could be used to rank the bioavailabilities of the in vivo data.

     

Gender-Dependent Pharmacokinetics of Veratramine in Rats: <Emphasis Type="Italic">In Vivo</Emphasis> and <Emphasis Type="Italic">In Vitro</Emphasis> Evidence

Veratramine, a major alkaloid from Veratrum nigrum L., has distinct anti-tumor and anti-hypertension effects. Our previous study indicated that veratramine had severe toxicity toward male rats. In order to elucidate the underling mechanism, in vivo pharmacokinetic experiments and in vitro mechanistic studies have been conducted. Veratramine was administrated to male and female rats intravenously via the jugular vein at a dose of 50 μg/kg or orally via gavage at 20 mg/kg. As a result, significant pharmacokinetic differences were observed between male and female rats after oral administration with much lower concentrations of veratramine and 7-hydroxyl-veratramine and higher concentrations of veratramine-3-O-sulfate found in the plasma and urine of female rats. The absolute bioavailability of veratramine was 0.9% in female rats and 22.5% in male rats. Further experiments of veratramine on Caco-2 cell monolayer model and in vitro incubation with GI content or rat intestinal subcellular fractions demonstrated that its efficient passive diffusion mediated absorption with minimal intestinal metabolism, suggesting no gender-related difference during its absorption process. When veratramine was incubated with male or female rat liver microsomes/cytosols, significant male-predominant formation of 7-hydroxyl-veratramine and female-predominant formation of veratramine-3-O-sulfate were observed. In conclusion, the significant gender-dependent hepatic metabolism of veratramine could be the major contributor to its gender-dependent pharmacokinetics.     

Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene <Emphasis Type="BoldItalic">FCGRT</Emphasis> by MicroRNA-3181

Purpose

FCGRT encodes the alpha-chain component of the neonatal Fc receptor (FcRn). FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn by two microRNAs (hsa-miR-3181 and hsa-miR-3136-3p) acting on FCGRT.

Methods

The binding of candidate microRNAs to the 3′-untranslated region of FCGRT was evaluated using luciferase reporter constructs in CHO cells. The effect of microRNAs on FCGRT mRNA and FcRn protein expression was evaluated using specific microRNA mimics and inhibitor transfections in A549, HEK293 and HepG2 cells.

Results

Hsa-miR-3181 mimic reduced luciferase reporter activity by 70.1% (10 nM, P <?0.0001). In A549, HEK293 and HepG2 cells, hsa-miR-3181 decreased FCGRT mRNA expression (48.6%, 51.3% and 43.5% respectively, 25 nM, P <?0.05). The hsa-miR-3181 mimic decreased the expression of FcRn protein by 40% after 48 h (25 nM, P <?0.001). The mature form of hsa-miR-3181 was detected in samples of human liver.

Conclusions

These data suggest that hsa-miR-3181 is an epigenetic regulator of FCGRT expression. The identification of this regulator of FCGRT may provide insights into a potential determinant of interindividual variability in FcRn expression.

     

Anti-inflammatory, analgesic and antipyretic effects of friedelin isolated from Azima tetracantha Lam. in mouse and rat models

Objectives Friedelin was isolated from Azima tetracantha Lam. leaves collected from Kallakurichi, Villuppuram district, Tamil Nadu, India. The anti‐inflammatory, analgesic and antipyretic activities of friedelin have been investigated in Wistar rats and mice. Methods Friedelin was isolated from the hexane extract of leaves of A. tetracantha using column chromatography. The effects of friedelin on inflammation were studied by using carrageenan‐induced hind paw oedema, croton oil‐induced ear oedema, acetic acid‐induced vascular permeability, cotton pellet‐induced granuloma and adjuvant‐induced arthritis. The analgesic effect of friedelin was evaluated using the acetic acid‐induced abdominal constriction response, formalin‐induced paw licking response and the hot‐plate test. The antipyretic effect of friedelin was evaluated using the yeast‐induced hyperthermia test in rats. Key findings In the acute phase of inflammation, maximum inhibitions of 52.5 and 68.7% (P < 0.05) were noted with 40 mg/kg friedelin in carrageenan‐induced paw oedema and croton oil‐induced ear oedema, respectively. Administration of friedelin (40 mg/kg) significantly (P < 0.05) decreased the formation of granuloma tissue induced by cotton pellet at a rate of 36.3%. In the adjuvant‐induced arthritis test friedelin inhibited 54.5% of paw thickness. Friedelin inhibited acetic acid‐induced vascular permeability in mice. Friedelin also produced significant (P < 0.05) analgesic activity in the acetic acid‐induced abdominal constriction response and formalin‐induced paw licking response. In the hot‐plate test, friedelin did not show any significant results when compared with control. Treatment with friedelin showed a significant (P < 0.05) dose‐dependent reduction in pyrexia in rats. Conclusions The results suggested that friedelin possessed potent anti‐inflammatory, analgesic and antipyretic activities.     

Effect of Cd<Superscript>+2</Superscript> on phosphate solubilizing abilities and hydrogen peroxide production of soil-borne micromycetes isolated from <Emphasis Type="Italic">Phragmites australis</Emphasis>-rhizosphere

The aims of this work were to evaluate the phosphate-solubilization and hydrogen peroxide (H₂O₂) production by the soil-borne micromycetes, Aspergillus japonicus, Penicillium italicum and Penicillium dipodomyicola, isolated from Phragmites australis rhizosphere and to study the effect of several concentrations of Cadmium (Cd²⁺) on both variables. Our results showed that P. italicum achieved a higher P-solubilization and H₂O₂ production than A. japonicus and P. dipodomyicola, as only P. italicum showed a positive correlation (R² = 0.71) between P-solubilization and H₂O₂ production. In dose–response assays, P. italicum was also more tolerant to Cd²⁺ (0.31 mM) in comparison to A. japonicus (0.26 mM). Analysis of the 2⁴ factorial experimental design showed that P-solubilization by P. italicum was negatively affected by increases in Cd²⁺ (p = 0.04) and yeast extract (p = 0.02) in the culture medium. The production of H₂O₂ was positively affected only by glucose (p = 0.002). Fungal biomass production was reduced significantly (p = 0.0009) by Cd²⁺ and increased (p = 0.0003) by high glucose concentration in the culture medium. The tolerance and correlation between P-solubilization and H₂O₂ production in the presence of Cd²⁺ was strain and species dependent. The effects of Cd²⁺, glucose, ammonium sulfate and yeast extract on those variables were evaluated through a two-level factorial design. P. italicum is promising for P-solubilization in soils contaminated with Cd²⁺ and may be an alternative for manufacture of biofertilizers to replace chemical fertilizers.     

Flavonoids from the aerial parts of <Emphasis Type="Italic">Houttuynia cordata</Emphasis> attenuate lung inflammation in mice

The aerial parts of Houttuynia cordata used for treating inflammation-related disorders contain flavonoids as major constituents. Since certain flavonoids possess anti-inflammatory activity, especially in the lung, the pharmacological activities of H. cordata and the flavonoid constituents were evaluated using in vitro and in vivo models of lung inflammation. The 70 % ethanol extract of the aerial parts of H. cordata inhibited the production of inflammatory biomarkers IL-6 and NO in lung epithelial cells (A549) and alveolar macrophages (MH-S), respectively. And the same plant material, administered orally (100 and 400 mg/kg), significantly inhibited lung inflammatory response in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury. From the extract, major flavonoids including afzelin, hyperoside and quercitrin were successfully isolated and they also attenuated LPS-induced lung inflammation in mice by oral administration. In particular, quercitrin showed most potent activity at 100 mg/kg. These results demonstrate for the first time that H. cordata and three flavonoid constituents have a therapeutic potential for treating lung inflammatory disorders.     

Design,synthesis, and evaluation of the anticonvulsant and antidepressant activities of pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine derivatives

A series of pyrido[2,3-d]pyrimidine derivatives (4a–4n, 5a–5n, 6, and 7) were designed and synthesized as potential anticonvulsants and antidepressants. Their pharmacological activities were evaluated by maximal electroshock test, forced swimming test, and tail suspension test in mice. Pharmacological analyses showed that compounds 4-benzyl-6,8-dimethylpyrido[3,2-e]tetrazolo[1,5-a]pyrimidin-5(4H)-one (4a) and 4-(3-fluorobenzyl)-6,8-dimethylpyrido[3,2-e]tetrazolo[1,5-a]pyrimidin-5(4H)-one (4e) exhibited the greatest anticonvulsant activity (PI 12.02 and 12.25, respectively, 30 min after intraperitoneal injection), and were more efficient than the reference drug, carbamazepine. In addition, 4-(4-fluorobenzyl)-6,8-dimethylpyrido[3,2-e]tetrazolo[1,5-a]pyrimidin-5(4H)-one (4f) and 6-(4-fluorobenzyl)-2,4-dimethylpyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(6H)-one (5f) possessed potent antidepressant properties that lead to significant reduction in the duration of the immobility time than did the control (P < 0.001), which possessed activities similar to those of fluoxetine. 4f showed obvious antidepressant activity at doses of 10 mg/kg.     

Synthesis and biological evaluation of quinolines,thiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidines,thiadiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidines and triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazepines as antimicrobial agents

Series of quinolines, thiazolo[3,2-a]pyrimidines, thiadiazolo[3,2-a]pyrimidines and triazolo[3,4-b][1,3,4]thiadiazepines were synthesized by the reaction of amino compound, aromatic aldehyde and malononitrile/ethyl cyanoacetate, using 2-[5-(4-methoxyphenyl)-4H-1,2,4-triazol-3-ylthio]acetic acid as an organocatalyst in water–ethanol mixture. Synthesized compounds were evaluated for in vitro antibacterial and antifungal activities against three fungal and five bacterial strains. Some of them exhibited good activity in comparison with the standard fluconazole and streptomycin such as compound 16h has shown best antifungal activity with MIC value of 60 µg/mL against A. niger and 12g exhibited best antibacterial activity with MIC value of 50 µg/mL against E. coli.