Hancornia speciosa Gomes induces hypotensive effect through inhibition of ACE and increase on NO

Ethnopharmacological relevance

The leaves of Hancornia speciosa Gomes are popularly used in Brazil to treat diabetes and hypertension. Cardiovascular diseases are the main cause of death worldwide and their incidences are increasing in Brazilian population. The present study aimed to investigate the hypotensive effect and the mechanism of action of Hancornia speciosa Gomes.

Methods

A fraction of the ethanolic extract of leaves from Hancornia speciosa (SFH) was obtained and standardized by its content on rutin, bornesitol and quinic acid. Systolic blood pressure (SBP) of normotensive mice was measured by tail pletismography. SFH was given orally and SBP was monitored for 5 h. Angiotensin-converting enzyme (ACE) inhibitor activity of SFH (1 mg/kg) or captopril (10 mg/kg) was measured by colorimetric methods. Serum nitrite levels were measured by spectrophotometry.

Results

SFH induced a dose-dependent hypotensive effect in normotensive mice. The serum activity of ACE and the level of angiotensin II were significantly reduced by SFH and by captopril. Administration of SFH induced a significant increase on plasmatic level of nitrites and the systemic inhibition of nitric oxide synthase by L-NAME (20 mg/kg) reduced the hypotensive effect of SFH.

Conclusions

The present work demonstrated that Hancornia speciosa has a potent hypotensive effect in normotensive mice. The inhibition of ACE leading to reduction on angiotensin II and increase on NO levels might account for the hypotensive effect. These results support the use of Hancornia speciosa by traditional medicine as antihypertensive.     

Effects of Black Raspberry on Lipid Profiles and Vascular Endothelial Function in Patients with Metabolic Syndrome

Black raspberry (Rubus occidentalis) has been known for its anti‐inflammatory and anti‐oxidant effects. However, short‐term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12‐week follow‐up. Lipid profiles, brachial artery flow‐mediated dilatation (baFMD), and inflammatory cytokines such as IL‐6, TNF‐α, C‐reactive protein, adiponectin, sICAM‐1, and sVCAM‐1 were measured at the baseline and at the 12‐week follow‐up. Decreases from the baseline in the total cholesterol level (?22.8 ± 30.4 mg/dL vs. ?1.9 ± 31.8 mg/dL, p < 0.05, respectively) and total cholesterol/HDL ratio (?0.31 ± 0.64 vs. 0.07 ± 0.58, p < 0.05, respectively) were significantly greater in the group with black raspberry than in the placebo group. Increases in baFMD at the 12‐week follow‐up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p < 0.05, respectively). Decreases from the baseline in IL‐6 (?0.4 ± 1.5 pg/mL vs. ?0.1 ± 1.0 pg/mL, p < 0.05, respectively) and TNF‐α (?2.9 ± 4.7 pg/mL vs. 0.1 ± 3.6 pg/mL, p < 0.05, respectively) were significantly greater in the group with black raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12‐week follow‐up. Copyright © 2014 John Wiley & Sons, Ltd.     

The Antiinflammatory Effect of an Extract of Tripterygium wilfordii Hook F on Adjuvant-induced Paw Oedema in Rats and Inflammatory Mediators Release

Tripterygium wilfordii Hook F (TWH), commonly known as the Thunder-God-Vine, is a popular remedy for rheumatism in southern China. In this study, we investigated the effect of T2 (an extract from TWH) on adjuvant-induced paw oedema in rats and inflammatory mediators. The results showed that an intraperitoneal injection of T2 could significantly decrease the adjuvant-induced paw oedema of rats. During in vitro study, lipopolysaccharide (LPS)-stimulated human mononuclear prostaglandin E₂ (PGE₂) in the culture supernatant was significantly inhibited by T2 at a concentration of 2 μg/mL compared with the control group without T2 treatment (22352±4725 vs 43433±9014 pg/mL, p <0.05). When rat neutrophils were treated with 3 μg/mL of T2, the superoxide production was significantly lower than that of the group without T2 treatment (0.72±0.07 vs 1.37±0.04 nmol, p <0.05). T2 failed to suppress the β-glucuronidase release from rat neutrophils but when the concentration was 30 μg/mL, it expressed a significant inhibition of lysozyme release (20.7±2.9 vs 38.2±4.0 in the control, p <0.05). The findings suggest this Chinese herb, like non-steroid antiinflammatory drugs, expresses a potential antiinflammatory effect through its inhibition of PGE₂ and superoxide function and lysozyme release. © 1997 by John Wiley & Sons, Ltd.     

Antifilarial activity of Argyria speciosa against Setaria cervi in vitro

The effect of aqueous and alcoholic extracts of Argyria speciosa on the spontaneous movements of both the whole worm and a nerve/muscle preparation of Setaria cervi, and on the survival of microfilariae in vitro, was studied. Both extracts caused the inhibition of spontaneous movements of the whole worm and the nerve/muscle preparation of S. cervi, characterized by decrease in tone, amplitude and rate of contractions. The concentration required to inhibit the movements of the whole worm preparation was 150 μg/mL for the aqueous, and 75 μg/mL for the alcoholic extract. The concentration of A. speciosa extract required to produce an equivalent effect on the nerve/muscle preparation was 25 μg/mL for aqueous, and 50 ng/mL for the alcoholic extract.     

An In Vitro and Molecular Informatics Study to Evaluate the Antioxidative and β‐hydroxy‐β‐methylglutaryl‐CoA Reductase Inhibitory Property of Ficus virens Ait

The present study is initially intended to evaluate antioxidant and β‐hydroxy‐β‐methylglutaryl‐CoA reductase (HMGR) inhibitory property of Ficus virens Ait., first by in vitro analyses followed by a corroboratory molecular informatics study. Our results show that of all the sequentially extracted fraction of F. virens bark and leaves extract, F. virens bark methanol extract exhibits strong radical scavenging, antioxidant and oxidative DNA damage protective activity, which is well correlated with its total phenolic content. In addition, F. virens bark methanol extract, which is non‐cytotoxic, significantly and non‐covalently inhibit the HMGR activity (IC₅₀ = 3.45 ± 0.45 µg/ml) in comparison with other extracts. The mechanistic aspect of this inhibition activity is authenticated by molecular docking study of bioactive compounds as revealed from gas chromatography–mass spectrometry data, with HMGR. The analysis for the first time indicates that quinic acid (ΔG: ?8.11 kcal/mol) and paravastatin (ΔG: ?8.22 kcal/mol) exhibit almost same binding energy, while other compounds also showed good binding energy, suggesting that quinic acid alone or in combination with other major bioactive compound is probably responsible for HMGR inhibitory property of the extract and plausibly can be used in in vivo system for the management, prevention, and alleviation of hypercholesterolemia as well as hypercholesterolemia‐induced oxidative stress. Copyright © 2013 John Wiley & Sons, Ltd.     

Camellia sinensis Ameliorates the Efficacy of Last Line Antibiotics Against Carbapenem Resistant Escherichia coli

Aquo‐ethanolic extract of Camellia sinensis (PTRC‐31911‐A), standardized using Fourier transform infrared analysis, was found to have seven common functional groups in comparison with pre‐identified marker compound ‘quercetin’. Phyto‐chemical quantitation analysis revealed the presence of 10.65 µg/mg of flavonoids. The bioactivity fingerprint profile of PTRC‐31911‐A includes IC_{50 (Hydroxyl radical site specific scavenging)} = 11.36 ± 0.5 µg/mL, IC_{80 (Hydroxyl radical non‐site specific scavenging)} = 26.44 ± 0.5 µg/mL and IC_{50 (Superoxide ion scavenging)} = 10.141 ± 0.5 µg/mL. The drug combination analysis of PTRC‐31911‐A with five third‐line antibiotics was carried out against carbapenem‐resistant Escherichia coli. The analysis of combination of PTRC‐31911‐A (6.25–1000 µg/mL) and antibiotics (6.25–1000 µg/mL) revealed synergistic behaviour (fractional inhibitory concentration indices < 1) with tigecycline, ertapenem, meropenem, colistin and augmentin. The lead combination of PTRC‐31911‐A + ertapenem or meropenem showed maximum augmentative potential at 50 and 100 µg/mL, respectively, with nearly five‐fold decrease in minimum inhibitory concentrations as compared with respective antibiotics alone. The synergistic effects implied that the antibacterial combinations of PTRC‐31911‐A and ertapenem, meropenem, colistin, tigecycline or augmentin would be more effective than a single monotherapy with either of the antibacterial agent. Copyright © 2015 John Wiley & Sons, Ltd.     

Herbal medicine Catuama induces endothelium-dependent and -independent vasorelaxant action on isolated vessels from rats,guinea-pigs and rabbits

The present study was designed to examine the vasorelaxant action of the herbal medicine Catuama and the hydroalcoholic extracts (HE) of each plant present in this product and to compare their effects with that caused by acetylcholine (ACh) in intact (⁺E) or in endothelium-rubbed (⁻E) rings of rat thoracic aorta (RA), guinea-pig pulmonary artery (GPPA), guinea-pig mesenteric artery (GPMA), rabbit pulmonary artery (RPA), rabbit mesenteric artery (RMA) precontracted with noradrenaline (NA) or phenylephrine (PE). The extract of Catuama (1-3000 μg/mL) produced graded relaxation of RA, ⁺E or ⁻E, with mean EC₅₀ of 430 μg/mL and ≊ 3000 μg/mL and E_max of 81 % ± 15 % and 47% ± 4 %, respectively. The nitric oxide (NO) synthase inhibitor, N^ω-nitro-L -arginine (L -NOARG, 100 μM ), inhibited in vasorelaxant action (p < 0.05) in RA (⁺E), while indomethacin (3 μM ), propranolol (1 μM ), glibenclamide (1 μM ), methylene blue (10 μM ) and apamin (0.1 μM ) had no significant effect. ACh (1-1000 μM ) caused graded relaxation in RA with ⁺E, these effects being markedly antagonized by L -NOARG (100 μM ), methylene blue (10 μM ) and partially by apamin (0.1 μM ), but not by indomethacin (3 μM ), glibenclamide (1 μM ) or propranolol (1 μM ). The Catuama extract (1-3000 μg/mL) produces partial relaxations in rings of RMA (mean EC₅₀ of 1073 μg7/ml and E_max of 56 % ± 13 %), an effect which was antagonized by L -NOARG (100 μM ). In RPA (⁺E) the extract produces partial relaxation followed by contraction (E_max 28 % ± 6 %), an effect which was abolished by L -NOARG (100 μM ) or methylene blue (10 μM ). The extract caused graded relaxation in rings of GPPA and GPMA with mean EC₅₀ values of 60 μg/mL and 1148 μg/mL and E_max 96% ± 2% and 88% ± 12%, respectively. L -NOARG (100 μM ) blocked the Catuama extract vasorelaxation in GPPA and only partially in GPMA, but markedly antagonized the vasorelaxations caused by ACh in both GPPA andRMA. The HE Paullinea cupana, Zinziber officinalis and Trichilia catigua (1-3000 μg/mL) caused a graded vasorelaxant effect ⁺E of RA with a mean EC₅₀ of 22, 55 and 1793 μg/mL and E_max 100%, 86% ± 7% 70% ± 2%, respectively. In addition the HE of P. cupana also caused graded relaxation in ⁻E of RA with EC₅₀ and E_max of 233 μg/mL and 100%, respectively, while T. catigua and Z. officinalis produced partial relaxation in RA ⁺E. In contrast the HE of Ptychopetalum olacoides caused little contraction (46% ± 14%). These results demonstrate that the medicinal herb Catuama produces significant vasorelaxation responses in vessels from different animal species, and show that its effects are in great part dependent on the release of NO or NO-derived substances. Our results also demonstrate that the vasorelaxant action of the product Catuama seems to be due to the action of the active principles present mainly in P. cupana; T. catigua and, to a lesser extent, in Z. officinalis. Such results may contribute to the explanation of its beneficial effect of Catuama herbal medicine in the management of cardiovascular disturbances. © 1997 John Wiley & Sons, Ltd.     

Triterpene acids isolated from Lagerstroemia speciosa leaves as α‐glucosidase inhibitors

The potential antidiabetic activity of ethyl acetate extract of the leaves of Lagerstroemia speciosa (LSL) was investigated by α‐amylase and α‐glucosidase inhibition assay. Six pentacyclic triterpenes (oleanolic acid, arjunolic acid, asiatic acid, maslinic acid, corosolic acid and 23‐hydroxyursolic acid) were isolated from LSL. Their structures were determined by spectroscopic analysis and their α‐glycosidase and α‐amylase inhibitory activities were investigated. They exhibited no or weak inhibitory activity against α‐amylase and middle α‐glucosidase inhibitory activities. Corosolic acid, which shows best bioactivity against α‐glucosidase (IC₅₀ = 3.53 µg/mL), contributes most to the α‐glucosidase inhibitory activity of EtOAc extract. The kinetics of inhibition of corosolic acid was also discussed. Results from this study might provide the scientific evidence for LSL for the treatment of diabetes in traditional medicine. Copyright © 2008 John Wiley & Sons, Ltd.     

Anti‐Inflammatory and Antinociceptive Activity of Urera aurantiaca

Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti‐inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti‐inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan‐induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose‐dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azinobis 3‐ethylbenzothiazoline 6‐sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED₅₀: 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity. Copyright © 2014 John Wiley & Sons, Ltd.     

Antihyperlipidemic Components of Cassia auriculata Aerial Parts: Identification Through In Vitro Studies

Cassia auriculata (Caesalpiniaceae) is a common Asian beverage and medicinal plant widely used in tradition medicine for diabetes, hyperlipidemia and various other disease conditions. Previous studies on crude extracts of C. auriculata have documented the scientific basis for some of its traditional medicinal uses. The present study investigates the antilipase activity of the ethanol extract of the aerial parts along with the previously isolated compounds (kaempferol‐3‐O‐rutinoside, rutin, kaempferol, quercetin and luteolin). The crude extract displayed inhibitory activity against pancreatic lipase with IC₅₀ of 6.0 ± 1.0 µg/mL. The most active antilipase compound was kaempferol‐3‐O‐rutinoside with IC₅₀ value (2.9 ± 0.50 μM) only about twice weaker than the standard antilipase drug, orlistat (IC₅₀ = 1.45 ± 0.26 μM). Luteolin, quercetin and rutin were found to be weak pancreatic lipase inhibitors (IC₅₀ over 100 μM), whereas kaempferol showed no activity up to 250 μM. The antihyperlipidemic effect of C. auriculata could be attributed to direct lipase inhibitory effect of the plant constituents. Copyright © 2012 John Wiley & Sons, Ltd.     

Medicinal Plants Traditionally Used for Treatment of Obesity and Diabetes Mellitus – Screening for Pancreatic Lipase and α‐Amylase Inhibition

In order to find new pancreatic lipase (PL) and α‐amylase inhibitors from natural sources for the treatment of obesity and related diseases as diabetes mellitus II, 23 medicinal plants with weight‐reducing, serum glucose‐reducing or related potential were investigated. Methanolic and water extracts of the plants were evaluated by using two in vitro test systems. Our findings have shown that the methanolic extract of Hibiscus sabdariffa L. (Malvaceae) showed high inhibitory activities to PL (IC₅₀: 35.8 ± 0.8 µg/mL) and α‐amylase (IC₅₀: 29.3 ± 0.5 µg/mL). Furthermore, the methanolic extract of Tamarindus indica L. (Leguminosae) showed a high anti‐lipase (IC₅₀: 152.0 ± 7.0 µg/mL) and the aqueous extract a high anti‐amylase (IC₅₀: 139.4 ± 9.0 µg/mL) activity. This work provides a priority list of interesting plants for further study with respect to the treatment of obesity and associated diseases. Copyright © 2015 John Wiley & Sons, Ltd.     

Regulation of insulin action by an extract of Artemisia dracunculus L. in primary human skeletal muscle culture: A proteomics approach

An ethanolic extract of Artemisia dracunculus L. (PMI 5011) has been observed to decrease glucose and insulin levels in animal models and enhance cellular signaling in cultured cells. To determine the mechanism of action of PMI‐5011, we have measured changes in protein expression in human primary skeletal muscle culture (HSMC) from subjects with Type 2 diabetes. After obtaining skeletal muscle biopsies, HSMCs were initiated, grown to confluence, and exposed to 10 µg/mL PMI 5011 overnight. Two‐dimensional difference in‐gel electrophoresis was used to separate proteins, and liquid chromatography mass spectrometry was used to identify differentially regulated proteins. Additionally, real‐time polymerase chain reaction (PCR) was used to confirm candidate proteins identified. These data demonstrate that a well characterized botanical extract of Artemisia dracunculus L. significantly modulates proteins involved in regulating inflammatory pathways, particularly the NFκB complex system. Copyright © 2010 John Wiley & Sons, Ltd.     

Antibacterial activity of essential oils from Psidium and Pilocarpus species of plants

The antibacterial activity of six essential oils obtained from the leaves of Pilocarpus and Psidium species of plants have been studied. The leaf oils of Psidium guyanensis, Psidium pohlianum and Pilocarpus spicatus showed the most potent antibacterial activity (MIC 52.5–75.0 μg/mL) against Gram-negative Pseudomonas aeruginosa. Against Gram-positive Staphylococcus aereus, P. guyanensis demonstrated marked activity (MIC 75.0±15.0 μg/mL) followed by P. spicatus and Pilocarpus pauciflorus (MIC 100.0±28.9 μg/mL). The efficacy of some tested oils against P. aeruginosa, the most resistant organism may have significant clinical implication. © 1997 John Wiley & Sons, Ltd.     

Antihyperglycemic Activity of Extracts from Boldoa purpurascens Leaves in Alloxan‐Induced Diabetic Rats

In order to investigate the potential use of Boldoa purpurascens against diabetes, the antihyperglycemic effect of an ethanol extract obtained from its leaves was evaluated at doses of 50, 100 and 200 mg/kg in rats after induction of hyperglycemia by alloxan. Insulin 5 IU/kg was used as positive control and NaCl 0.9% as negative control. A similar experiment was performed with the aqueous extract used at doses of 50 and 100 mg/kg using metformin at a dose of 50mg/kg as positive control. Statistical analysis was carried using the Kruskal–Wallis test with an interval of trust of 99%. The ethanolic and aqueous extract of B. purpurascens showed a significant decrease of blood glucose levels 72 h after administration. Phytochemical analysis of the ethanol extract showed the presence of D‐pinitol, a compound known for its hypoglycemic properties. In conclusion, ethanolic as well as aqueous extracts of B. purpurascens leaves show antihyperglycemic activity, possibly due to the presence of D‐pinitol and flavonoids. Copyright © 2012 John Wiley & Sons, Ltd.     

Chemical compounds as well as antioxidant and litholytic activities of Arbutus unedo L. leaves against calcium oxalate stones

ObjectiveThe present study aimed to quantify and identify the bioactive compounds of the Arbutus unedo L. leaves in order to evaluate both their antioxidant properties and litholytic activities against calcium oxalate stones.MethodsThis survey was carried out using hydroalcoholic extract (E.FA) and infusion (I.FA) of A. unedo leaves. The quantification of phenolic compounds, flavonoids, flavonols and anthocyanins was done by spectrophotometric methods and identification of chemical components was performed by ultra-performance liquid chromatography with photodiode array and electrospray ionization tandem mass spectrometry. Antioxidant activity was measured using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and by the ferric reducing/antioxidant power (FRAP) assay. Litholytic activity of E.FA and I.FA was studied using a special model that resembles circuitry of the urinary system.ResultsE.FA showed greater antioxidant efficacy than I.FA (P < 0.05). Its higher efficiency was shown via the values of median inhibitory concentration, which was close to (76.14 ± 0.91) µg/mL for E.FA versus (202.64 ± 5.77) μg/mL for I.FA using the DPPH method, and (53.77 ± 0.81) μg/mL for E.FA versus (236.86 ± 31.90) μg/mL for I.FA, using FRAP method. I.FA exhibited significantly higher litholytic activity compared to E.FA (P < 0.05), with dissolution values of 31.03% ± 0.63% versus 14.55% ± 0.65%, respectively.ConclusionOverall, the results suggest that the A. unedo is rich in bioactive compounds, and possesses antioxidant and litholitic abilities that are worthy of further study.     

Anti‐Leishmanial,Anti‐Inflammatory and Antimicrobial Activities of Phenolic Derivatives from Tibouchina paratropica

A new phenolic derivative, 2,8‐dihydroxy‐7H‐furo[2,3‐f]chromen‐7‐one ( 1 ), together with isoquercitrin ( 2 ), was isolated from the aerial parts of Tibouchina paratropica. Compound structures were elucidated by spectroscopic methods. Both compounds show antimicrobial activit y towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti‐parasitic activity against Leishmania donovani (IC₅₀ = 0.809 µg/mL). In addition, an 85% reduction in the secretion of the pro‐inflammatory cytokine IL‐6 was recorded when macrophages challenged with lipopolysaccharide were exposed to compound 1 , but no effect on the anti‐inflammatory IL‐10 was observed. Compound 2 showed neither anti‐parasitic nor anti‐inflammatory properties. In addition, no cytotoxic activities were observed against the human‐derived macrophage THP‐1 cells. Copyright © 2014 John Wiley & Sons, Ltd.     

Anti‐TNF‐α Activity of Brazilian Medicinal Plants and Compounds from Ouratea semiserrata

Several plant species are used in Brazil to treat inflammatory diseases and associated conditions. TNF‐α plays a pivotal role on inflammation, and several plant extracts have been assayed against this target, both in vitro and in vivo. The effect of 11 Brazilian medicinal plants on TNF‐α release by LPS‐activated THP‐1 cells was evaluated. The plant materials were percolated with different solvents to afford 15 crude extracts, whose effect on TNF‐α release was determined by ELISA. Among the evaluated extracts, only Jacaranda caroba (Bignoniaceae) presented strong toxicity to THP‐1 cells. Considering the 14 non‐toxic extracts, TNF‐α release was significantly reduced by seven of them (inhibition > 80%), originating from six plants, namely Cuphea carthagenensis (Lythraceae), Echinodorus grandiflorus (Alismataceae), Mansoa hirsuta (Bignoniaceae), Ouratea semiserrata (Ochnaceae), Ouratea spectabilis and Remijia ferruginea (Rubiaceae). The ethanol extract from O. semiserrata leaves was fractionated over Sephadex LH‐20 and RP‐HPLC to give three compounds previously reported for the species, along with agathisflavone and epicatechin, here described for the first time in the plant. Epicatechin and lanceoloside A elicited significant inhibition of TNF‐α release, indicating that they may account for the effect produced by O. semiserrata crude extract. Copyright © 2015 John Wiley & Sons, Ltd.     

The effect of garlic consumption on Th1/Th2 cytokines in phytohemagglutinin (PHA) activated rat spleen lymphocytes

The balance and regulation of T helper 1 (Th1) and Th2‐type cytokines are important in the effective immune response to different diseases. To clarify the effect of garlic (Allium sativum L.) consumption on the Th1/Th2 balance, the secretion of gamma interferon (IFN‐γ) and interleukin‐4 (IL‐4), as two prototypes of Th1/Th2 cytokines, were compared in serum and supernatant of in vitro phytohemagglutinin activated rat spleen lymphocytes. Thirty male rats were divided equally into two groups. The treatment group received garlic solution in water (600 mg/kg/4 mL) and controls received distilled water by gavage. After 1 month, serum and supernatant of PHA activated spleen lymphocytes were analysed for IFN‐γ and IL‐4 by the enzyme‐linked immunosorbent assay test and thymus and spleen weights were measured. The garlic treatment group showed significantly decreased production of IFN‐γ from 101.73 ± 4.62 to 74.64 ± 4.64 pg/mL and significantly increased IL‐4 production from 26.75 ± 3.35 to 83.92 ± 6.56 pg/mL (p < 0.001) in the supernatant of PHA induced spleen lymphocytes. The serum level of these cytokines was undetectable. The mean weight of thymuses in the garlic fed animals was significantly reduced from 0.456 ± 0.016 to 0.368 ± 0.023g compared with the control group (p < 0.005). There were no significant differences between the spleen weights in the two groups. In conclusion, oral garlic treatment may favor a Th2 or humoral immune response. Copyright © 2008 John Wiley & Sons, Ltd.     

Protein tyrosine phosphatase 1B inhibitory activity of 24‐norursane triterpenes isolated from Weigela subsessilis

During the screening effort to discover new types of protein tyrosine phosphatase 1B (PTP1B) inhibitors, it was found that a MeOH extract of the leaves and stems of Weigela subsessilis (Caprifoliaceae) inhibited the enzyme activity. By means of an in vitro bioassay‐guided fractionation on the MeOH extract, two 24‐norursane triterpenes, ilekudinol A (1) and ilekudinol B (2), were isolated as active metabolites. Compounds 1 and 2 inhibited PTP1B with IC₅₀ values of 29.1 ± 2.8 and 5.3 ± 0.5 μM, respectively. Kinetic studies suggest that both 1 and 2 are non‐competitive inhibitors of PTP1B. The findings indicate that the free carboxyl group at C‐28 in this type of triterpenes plays a critical role in the inhibition of PTP1B. Copyright © 2010 John Wiley & Sons, Ltd.