A systematic literature review of fenugreek seed toxicity by using ToxRTool: evidence from preclinical and clinical studies.

Fenugreek (Trigonella foenum graecum) seed extract is a bioactive ingredient of many food supplements. Hence, there is a need for systematic assessment of the quality of published toxicological studies for its use in human health, hazard consideration, and risk assessment. The aim of the present investigation was to determine the reliability of published toxicological studies of fenugreek seed by using ToxRTool (Toxicological data reliability assessment tool). A comprehensive systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, CPCI-S, ICTRP, Ovid, and Google Scholar till October 2018. Each identified study was evaluated for its quality using the ToxRTool with outcomes such as combined score, weighted score, and reliability category by three independent raters. Correlations of various criteria groups with the combined score were evaluated by Pearson correlation and Kendall rank correlation coefficient. Inter-rater consistency was measured by Cronbach's alpha coefficient. The database searches initially yielded 436 results, of which 391 (89.67%) studies were "not assignable". The remaining 45 studies were included for quantitative analysis by ToxRTool. Based on the weighted score, 17 in-vivo, and 3 in-vitro studies were determined to be "Reliable Without Restriction" which were conducted according to international guidelines such as GLP. These studies have a significant difference (p < 0.05) for the combined and weighted score as compared to non-GLP studies. Remaining 28 in-vivo and 2 in-vitro studies were determined to be "Not Reliable." The GLP studies conducted with "identified study material" have a significant difference (p < 0.0001) between combined and weighted score as compared to studies which used "non-identified study material". For criteria group of ToxRTool I, III and V, the Pearson correlation with the combined score was found to be 0.875, 0.734 and 0.905, respectively and Kendall rank correlation coefficient was found to be 0.764, 0.551 and 0.752, respectively. Cronbach's alpha coefficient for combined score and weighted score were 0.920 and 0.887, respectively. In conclusion, the ToxRTool was found useful to identify seventeen toxicity studies of fenugreek seeds as "Reliable without Restrictions". These studies showed a broad margin of safety for the standardized extract of fenugreek seeds and can form a basis for toxicological risk assessment with reasonable certainty.

Low molecular weight galactomannans-based standardized fenugreek seed extract ameliorates high-fat diet-induced obesity in mice via modulation of FASn, IL-6, leptin, and TRIP-Br2.

Background: Obesity is a complex, chronic metabolic disorder and its prevalence is increasing throughout most of the world. Low molecular weight galactomannans-based standardized fenugreek seed extract (LMWGAL-TF) has previously shown anti-diabetic and anti-hyperlipidemic potential. Aim: To evaluate the efficacy and mechanism of action of LMWGAL-TF in treating high fat diet (HFD)-induced obesity and hyperlipidemia in mice. Materials and methods: Male C57BL/6 mice were fed the HFD for 12 weeks and were co-administered with LMWGAL-TF (10, 30 and 100 mg kg-1, p.o.). Variables measured were behavioral, biochemical, molecular and histopathological. In a separate in vitro experiment, copper-ascorbate (Cu-As)-induced mitochondrial oxidative damage was evaluated. Results: The HFD-induced increase (p < 0.001) in body weight, fat mass, lean mass, adipose tissue (brown, mesenteric, epididymal and retroperitoneal) and liver weight was significantly attenuated (p < 0.001) by LMWGAL-TF (30 and 100 mg kg-1). The HFD-induced elevated levels of serum lipid, interleukins (ILs)-6 and leptin were significantly decreased (p < 0.001) by LMWGAL-TF (30 and 100 mg kg-1). Elevated fatty acid synthase (FASn), IL-6, leptin and transcriptional regulator interacting with the PHD-bromodomain 2 (TRIP-Br2) mRNA expression in brown adipose tissue (BAT), liver, and epididymal fat were significantly down-regulated (p < 0.001) by LMWGAL-TF (30 and 100 mg kg-1). Additionally, HFD-induced histological alterations in skeletal muscle, liver, white adipose tissue (WAT) and BAT were also reduced by LMWGAL-TF. Furthermore, the Cu-As-induced alteration in mitochondria oxidative stress (lipid peroxidation, protein carbonylation, glutathione, glutathione reductase, glutathione peroxidase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase) in skeletal muscle and BAT was significantly (p < 0.001) ameliorated by LMWGAL-TF (2, 4 and 6 mg mL-1) treatment. It also reduced the Cu-As-induced mitochondrial swelling. Conclusion: LMWGAL-TF showed its beneficial effect in reducing HFD-induced obesity via down-regulation of FASn, IL-6, leptin, and TRIP-Br2 in mice.

Glycosides Based Standardized Fenugreek Seed Extract Ameliorates Bleomycin-induced Liver Fibrosis in Rats Via Modulation of Endogenous Enzymes.

BACKGROUND: Liver fibrosis a complex process of excess collagen deposition resulted in disturbance of hepatic cellar function. Glycosides based standardized fenugreek seed extract (SFSE-G) has potent anti-inflammatory, antioxidant, and anti-fibrotic properties. OBJECTIVE: The aim of this study is to evaluate the hepatoprotective potential of SFSE-G against bleomycin (BLM)-induced liver fibrosis in laboratory animals. MATERIALS AND METHODS: Sprague-Dawley rats (180-220 g) were assigned to various groups, namely, normal, sham, BLM control, SFSE-G (5, 10, 20, and 40 mg/kg, p.o.), methylprednisolone (10 mg/kg, p.o.), and sildenafil (25 mg/kg, p.o.). Liver fibrosis was induced in various groups (except normal and sham) by single intratracheal BLM (6 IU/kg) injection. Various biochemical, molecular (reverse transcription polymerase chain reaction) and histological parameters were evaluated. RESULTS: Intratracheal BLM administration caused significant induction (P < 0.001) of hepatotoxicity and liver fibrosis reflected by elevated levels of serum aspartate transaminase (AST), alanine transaminase (ALT), total as well as direct bilirubin, and gamma-glutamyl transferase (GGT). Administration of SFSE-G (20 and 40 mg/kg, p.o.) significantly reduced (P < 0.001) levels of AST, ALT, and GGT and significantly increased (P < 0.001) the level of serum albumin. BLM-induced elevated liver oxidative stress and decreased total antioxidant capacity was significantly restored (P < 0.001) by SFSE-G (20 and 40 mg/kg) treatment. It also significantly inhibited BLM-induced alteration in liver Farnesoid X receptor (FXR) mRNA expression. SFSE-G treatment reduced histopathological alteration induced by BLM in liver. CONCLUSION: SFSE-G exerts its hepatoprotective potential via inhibition of oxido-nitrosative stress and modulation of FXR mRNA expression thus ameliorates BLM-induced liver fibrosis.

Prenatal Developmental Toxicity Study of Glycosides-based Standardized Fenugreek Seed Extract in Rats.

CONTEXT: Glycoside-based standardized fenugreek seed extract (SFSE-G) demonstrated promising efficacy in animal models of immune-inflammatory conditions. AIM: The present study was aimed at embryo-fetal development toxicity evaluation of SFSE-G in Wistar rats as per guideline No. 414 of the Organization for Economic Co-operation and Development (OECD). MATERIAL AND METHODS: Mated female rats were randomized into four groups of 30 each and received oral doses of either SFSE-G at 250, 500, and 1000 mg/kg or vehicle (water) during the period of gestation (postconception) from gestational day 5 (GD5, an implantation day) until 1 day before cesarean sections (GD19). Maternal food consumption, body weights, and clinical signs were monitored throughout gestation. Cesarean sections were performed on GD20 and fetal observations (gravid uterine weight, implantation sites, early and late resorptions, live and dead fetuses) were recorded. Live fetuses were weighed and examined for external, visceral, and skeletal variations and malformations. RESULTS: None of the SFSE-G-treated groups showed maternal and embryo-fetal toxicity. Occasional and incidental skeletal and visceral malformations were observed and found to be spontaneous and unrelated to the treatment. CONCLUSION: Oral exposure of SFSE-G during the prenatal period did not show significant maternal and embryo-fetal toxicity up to a dose of 1000 mg/kg in rats. Therefore, the no-observed-adverse-effect level for SFSE-G for prenatal oral exposure was considered to be 1000 mg/kg. SUMMARY: Prenatal toxicity of glycoside-based standardized fenugreek seed extract (SFSE-G) was evaluated.SFSE-G was orally gavaged to rats on gestational days 5-19 with a limit dose of 1000 mg/kg.SFSE-G did not show maternal or developmental toxicity.SFSE-G showed NOAEL of 1000 mg/kg for prenatal exposure in female rats. Abbreviations used: CPCSEA: Committee for the Purpose of Control and Supervision of Experiments on Animals; GD: Gestational day; GRAS: Generally recognized as safe; HED: Human equivalent dose; NOAEL: No-observed adverse effect levels; OECD: Organization for Economic Co-operation and Development; SFSE-G: glycoside-based standardized fenugreek seed extract.

Ameliorative effects of type-A procyanidins polyphenols from cinnamon bark in compound 48/80-induced mast cell degranulation.

Allergic diseases are a significant health concern in developing countries. Type-A procyanidin polyphenols from cinnamon (Cinnamomum zeylanicum Blume) bark (TAPP-CZ) possesses antiasthmatic and antiallergic potential. The present study was aimed at the possible anti-allergic mechanism of TAPP-CZ against the compound 48/80 (C48/80)-induced mast cell degranulation in isolated rat peritoneal mast cells (RPMCs). TAPP-CZ (1, 3, 10, and 30 µg/ml) was incubated for 3 hours with isolated, purified RPMCs. The C48/80 (1 µg/ml) was used to induce mast cell degranulation. The mast cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay whereas histamine, ß-hexosaminidase (ß-HEX), and interleukin-4 (IL-4) levels were determined in RPMCs. TAPP-CZ (3, 10, and 30 µg/ml) showed significant and dose-dependent decrease in a number of degranulated cells and levels of markers (histamine, ß-HEX, and IL-4) as compared with C48/80 control. In conclusion, TAPP-CZ stabilizes mast cell and cause inhibition of the allergic markers such as histamine, IL-4, and ß-HEX in IgE-mediated manner. The present study supports mast cell stabilization as a possible mechanism of action of TAPP-CZ against immune respiratory disorders such as asthma and allergic rhinitis.

Acute and repeated doses (28 days) oral toxicity study of Vicenin-1, a flavonoid glycoside isolated from fenugreek seeds in laboratory mice.

Vicenin-1 (fenugreek glycoside) has been proven to possess potent anti-inflammatory and anti-oxidant activity. The objective of the present investigation was to determine in-vivo acute and subacute (28-days repeated dose) oral toxicity of Vicenin-1 isolated from fenugreek seed. Vicenin-1 (93%) was isolated from a hydroalcoholic extract of fenugreek seed and characterized using HPLC, TLC, 1H NMR and 13C NMR. Acute oral toxicity (AOT) and subacute toxicity studies of Vicenin-1 were carried out according to OECD 425 (up-and-down procedure) and OCED 407 guidelines in Swiss albino mice. In AOT, Vicenin-1 showed 10% mortality when administered at a dose of 5000 mg/kg. However, when vicenin-1 was administered for at doses of 37.5, 75, or 150 mg/kg 28-days it did not show any mortality at the administered doses. Vicenin-1 (75 mg/kg) did not show observational, behavioral, biochemical or histopathological toxic effects. There were minor alterations in body weight, hematology, and histopathology of mice administered with Vicenin-1 (150 mg/kg), but these changes were within normal laboratory ranges. The highest concentration of Venicin-1 was found in liver (3.46%) followed by lung (0.65%). In conclusion, Vicenin-1 showed median lethal dose (LD50) of 4837.5 mg/kg with no-observed-adverse-effect levels (NOAEL) at 75 mg/kg and lowest adverse effect levels (LOAEL) at 150 mg/kg for both sexes of mice during AOT and sub-acute toxicity study, respectively.

Development and validation of HPLC method for vicenin-1 isolated from fenugreek seeds in rat plasma: application to pharmacokinetic, tissue distribution and excretion studies.

CONTEXT: Vicenin-1, a flavonol glycoside, has potent platelet aggregation inhibition, antioxidant, radioprotectants and anti-inflammatory activities. OBJECTIVE: To establish a rapid, simple, precise and sensitive high-performance liquid chromatography (HPLC) method for determination of vicenin-1 in rat plasma, and to investigate the pharmacokinetics, tissue distribution and excretion after a single 60 mg/kg oral dose in rats. MATERIALS AND METHODS: Vicenin-1 was extracted by solid-liquid extraction through Tulsicon® ADS-400 (0.40-1.2 mm). Chromatographic separation was achieved by HPLC with a C18 column with a mobile phase composed of water and acetonitrile (75:25 v/v) and a flow rate of 1 mL/min along with UV detection at 210 nm. RESULTS: Good linearity of calibration curve was found between 10.5 and 100.5 µg/mL (R2 = 0.995) for plasma and tissue, whereas 2.5-500 µg/mL (R2 = 0.999) for the urine and stool samples. The extraction recoveries were 98.51-99.58% for vicenin-1 in plasma, whereas intra-day and inter-day precision were validated by relative standard deviation (%RSD), that came in the ranges of 1.16-1.79% and 1.28-1.73%, respectively. The pharmacokinetics results showed Cmax (7.039 µg/mL) and Tmax (2 h) after oral administration of vicenin-1. Tissue distribution study showed that the highest concentration of vicenin-1 was achieved in the liver followed by the lung. Approximately 24.2% of its administered dose was excreted via urinary excretion route. CONCLUSION: The first-pass metabolism, poor solubility and presence of reducing sugar moiety in vicenin-1 may decrease its bioavailability. The developed method is sensitive, specific and was successfully applied to the pharmacokinetics, tissue distribution and excretion studies of vicenin-1 in rats.

Pharmacokinetics, tissue distribution and excretion study of a furostanol glycoside-based standardized fenugreek seed extract in rats.

The furostanol glycoside isolated from the seed of fenugreek (SFSE-G) has an array of pharmacological activities. To date, no validated high-performance liquid chromatography (HPLC) method has been reported for quantification of SFSE-G in biological samples. Hence, the aim of the present study was to study the pharmacokinetics, tissue distribution and excretion profiles of SFSE-G after oral administration in rats. A rapid, sensitive, selective, robust and reproducible HPLC method has been developed for determination of SFSE-G in the rat biological samples. The chromatographic separation was accomplished on a reversed-phase C18 column using formic acid and acetonitrile (80:20) as mobile phase at a flow rate of 1.0 mL/min and 274 nm as a detection wavelength. The assay was linear for SFSE-G with the correlation coefficients (R(2)) >0.996. The analytes were stable during samples storage and handling, and no matrix effects were observed. After oral dosing of SFSE-G at a dose of 200 mg/kg, the elimination half-life was app. 40.10 h. It showed relatively slowly distribution and eliminated in urine and feces after 24 h, and could be detected until 108 h post-dosing. Following oral single dose (200 mg/kg), SFSE-G was detected in lung and brain which indicated that it could cross the blood-brain barrier. It is a major route of elimination is excretion through urine and feces. In conclusion, oral administration of SFSE-G showed slow distribution to tissues, such as lung and brain, but showed fast renal elimination.

Effect of glycosides based standardized fenugreek seed extract in bleomycin-induced pulmonary fibrosis in rats: Decisive role of Bax, Nrf2, NF-κB, Muc5ac, TNF-α and IL-1ß.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive multifactorial disease with limited therapeutic options. Glycosides based standardized fenugreek seed extract (SFSE-G) possesses potent anti-inflammatory and anti-oxidant property. AIM: To evaluate the efficacy of SFSE-G against bleomycin (BLM) induced pulmonary fibrosis by assessing behavioral, biochemical, molecular and ultrastructural changes in the laboratory rats. MATERIALS AND METHODS: IPF was induced in male Sprague-Dawley rats by single intratracheal BLM (6IU/kg) injection followed by SFSE-G (5, 10, 20 and 40mg/kg, p.o.) or methylprednisolone (10mg/kg, p.o.) treatment for 28day. Various parameters were analyzed in lung and bronchoalveolar lavage fluid (BALF) after 14 and 28days of the drug treatment. RESULTS: SFSE-G (20 and 40mg/kg, p.o.) administration significantly prevented the BLM induced alteration in body weight, lung index, lung function test and hematology. The altered total and differential cell count in BALF and blood was significantly prevented by SFSE-G treatment. The decreased peripheral blood oxygen content after BLM instillation was significantly increased by SFSE-G treatment. SFSE-G significantly enhanced the BALF and lung antioxidant status, through modulating the SOD, GSH, T-AOC, MDA, NO level and Nrf2, HO-1 mRNA expression. There was a significant reduction in lung 5-HT level by SFSE-G treatment. The altered mRNA expression of biomarkers of lung inflammation (TNF-α, IL-1ß, IL-6 and IL-8), fibrosis (TGF-ß, collagen-1, ET-1, Muc5ac, NF-κB, VEGF, Smad-3) and apoptosis (Bax, Bcl-2 and Caspase-3) were significantly prevented by SFSE-G treatment. BLM induced histological inflammatory and fibrotic insult in the lung were reduced by SFSE-G treatment. It also ameliorated BLM induced lung ultrastructural changes as observed by transmission electron microscopic studies. However, administration of SFSE-G (5mg/kg, p.o.) failed to show any protective effect against BLM-induced PF whereas SFSE-G (10mg/kg, p.o.) showed significant amelioration in BLM-induced PF except lung function test, BALF and lung antioxidant level. CONCLUSION: SFSE-G showed anti-fibrotic efficacy executed through induction of Nrf2, which in turn may modulate anti-inflammatory molecules, inhibit fibrogenic molecules and decreased apoptosis to ameliorate BLM induced pulmonary fibrosis.

Acute and repeated doses (28 days) oral toxicity study of glycosides based standardized fenugreek seed extract in laboratory mice.

The objective of the present work was to study acute and subacute (28-days repeated dose) oral toxicity effect of glycosides based standardized fenugreek seed extract (SFSE-G) in vivo. SFSE-G was prepared by resin-based chromatography and standardized to glycosides namely trigoneoside Ib (76%) and vicenin 1 (15%). The acute oral toxicity (AOT) and subacute toxicity studies were performed in Swiss albino mice (5 mice/sex/group) as per OECD 425 (up-and-down procedure) and OCED 407 guidelines respectively. Acute oral administration of 5000mg/kg of SFSE-G showed 40% mortality with no mortality in lower dosages. The subacute oral administration of SFSE-G did not show observational or toxicological effects on the body or organ weights, food consumption, ophthalmic effects, locomotor activity, hematology, blood biochemistry, urinalysis, or histopathology at dose 250mg/kg. However, SFSE-G (1000mg/kg) showed mortality and minor alterations to body weight, relative liver weights, hematology and blood chemistry parameters related to treatment but it was within normal laboratory ranges. In conclusion, SFSE-G showed median lethal dose (LD50) more than 4350mg/kg and no-observed adverse effect levels (NOAEL) of 250mg/kg for both sexes during AOT and sub-acute toxicity study, respectively.

Anti-allergic effect of intranasal administration of type-A procyanidin polyphenols based standardized extract of cinnamon bark in ovalbumin sensitized BALB/c mice.

The objective of the present work was to evaluate anti-allergic effects of intranasal administration of type-A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP-CZ) in ovalbumin (OVA)-induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1-G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2-G6) were sensitized with OVA (500 µL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14-21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 µL/nostril) and G4-G6 received TAPP-CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 µL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP-CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA-induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP-CZ showed anti-allergic efficacy in animal model of AR.

Protective effect of Hygrophila spinosa against cisplatin induced nephrotoxicity in rats.

OBJECTIVE: To evaluate the nephroprotective effect of methanolic extract of Hygrophila spinosa (HSME) (Acanthaceae) in (CP)-induced acute renal failure in rats. MATERIALS AND METHODS: HSME (250 mg/kg and 500 mg/kg body weight), were administered orally to male wistar albino rats.CP was used to induce acute renal failure. The parameters studied included blood urea and serum creatinine and malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and GSH peroxidase activities. Histopathological examination was also carried out. RESULTS: The results revealed that HSME pretreatment signiûcantly reduced blood urea and serum creatinine levels elevated by CP administration. Furthermore, HSME signiûcantly attenuated CP-induced increase in MDA and decrease in reduced GSH, and CAT and SOD and GSH peroxidase activities in renal cortical homogenates. Additionally, histopathological examination showed that HSME markedly ameliorated CP-induced renal tubular necrosis. CONCLUSION: The results indicate that the aerial parts of H. spinosa are endowed with nephroprotective activity.

Neurobehavioral assessment of hydroalcoholic extract of Trigonella foenum-graecum seeds in rodent models of Parkinson's disease.

CONTEXT: Neuroprotective therapy to rescue dopaminergic neurons is an important trait in the management of Parkinson's disease (PD). OBJECTIVE: The present study identified and evaluated SFSE-T, a standardized hydroalcoholic extract of Trigonella foenum-graecum L. seeds (Fabaceae), in animal models of PD. MATERIALS AND METHODS: The identification of SFSE-T was carried out by high-performance liquid chromatography for the marker compound trigonelline (TGN). The effects of single dose oral treatment of SFSE-T (10, 30 or 100 mg/kg) were studied using animal models of PD, namely, 6-hydroxydopamine (6-OHDA)-induced unilateral lesions in rats, and 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in C57BL/6 mice. The effects of SFSE-T on monoamino oxidase (MAO) enzyme in vitro as well as possible side effects of SFSE-T in vivo were also evaluated. RESULTS: The concentration of TGN in a test sample of SFSE-T was found to be 82%. SFSE-T (30 mg/kg, oral) showed a significant increase in the number of ipsilateral rotations (45.67 rotations in 30-min period) as compared with vehicle control group (no rotations) when tested in 6-OHDA-induced unilateral lesioned rats. SFSE-T (30 mg/kg, oral) showed significant reversal of motor dysfunction (spontaneous motor activity scores, speed, distance traveled and number of square crossed) caused by MPTP induced lesions in C57BL/6 mice in pretreatment (1 h) schedule but not in post-treatment (1 h) schedule. SFSE-T neither showed anticholinergic effects nor showed selective MAO-B enzyme inhibition in vitro. DISCUSSION AND CONCLUSION: SFSE-T showed reversal of motor symptoms in an animal model of PD probably through neuroprotective properties.

Effect of Hygrophila spinosa in ethylene glycol induced nephrolithiasis in rats.

OBJECTIVE: Hygrophila spinosa (Acanthaceae) is traditionally used to treat urinary calculi. The present study aimed to evaluate the antiurolithiatic activity of methanolic extract of Hygrophila spinosa (Acanthaceae) in ethylene glycol induced nephrolithiasic rats. MATERIALS AND METHODS: Methanolic extract of Hygrophila spinosa (HSME) (250 and 500 mg/ kg body weight) was administered orally to male Wistar albino rats. Ethylene glycol (EG) was used to induce nephrolithiasis. The parameters studied included water intake, urinary volume, urinary pH, urinary and kidney oxalate and calcium, urinary magnesium and serum uric acid. RESULTS: Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and serum uric acid along with decreased excretion of urinary magnesium. Treatment with HSME significantly reduced the elevated urinary oxalate, urinary calcium and serum uric acid with increase in reduced urinary magnesium. Ethylene glycol feeding also resulted in increased levels of calcium and oxalate in kidney which was decreased after the treatment with HSME. The increased deposition of stone forming constituents in the kidneys of ethylene glycol treated rats was significantly lowered by treatment with HSME. CONCLUSION: The results indicate that the aerial parts of Hygrophila spinosa are endowed with antiurolithiatic activity, thereby justifying its traditional claim.

Ameliorative effects of standardized extract from Trigonella foenum-graecum L. seeds on painful peripheral neuropathy in rats.

OBJECTIVE: To evaluate the effects of the standardized extract of fenugreek (Trigonella foenum-graecum L. Family: Leguminasae) seed (IND01) in animal models of peripheral neuropathy. METHODS: IND01 was prepared from fenugreek seeds and standardized by high performance liquid chromatography to a marker compound, trigonelline. The effects of daily oral administration of IND01 (50, 100 and 200 mg/kg) were studied in rats after partial sciatic nerve ligation (PSNL) and sciatic nerve crush injury (SNCI) during 30-days period. The measurements on thermal hyperalgesia (TH), motor function test (MFT) score and motor nerve conduction velocity (MNCV) were recorded. RESULTS: IND01 offered sustained protection against TH and deranged MFT scores in both models from 7-day onwards. Fifteen days of daily oral administration of IND01 restored MNCV reduction in rats with SNCI but not with PSNL. CONCLUSIONS: IND01 was found to be effective in rat models of painful peripheral neuropathy.

H. Spinosa T. Anders ameliorates diabetic neuropathy in Wistar albino rats.

Diabetic neuropathic pain, an important microvascular complication in diabetes, is recognised as one of the most difficult types of pain to treat. The development of tolerance, inadequate relief, and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. Reactive oxygen/nitrogen species, increased oxidative stress, cytokines, and apoptosis are implicated in the pathogenesis of diabetic neuropathy. The aim of the present study was to explore the effect of methanolic extract of aerial parts of H. spinosa (HSME) on alloxan induced diabetic neuropathy in Wistar rats. Diabetic rats developed neuropathy after the third week of diabetes induction. Chronic treatment with HSME (250, 500, and 750 mg/kg body weight; p.o.) for 6 weeks starting from the 3rd week of alloxan injection showed significant increase in the pain threshold levels as compared to diabetic rats. HSME treated diabetic animals showed significant decrease in blood glucose level and increase in body weight as compared to diabetic control animals. The changes in lipid peroxidation status and antioxidant enzymes levels observed in sciatic nerve of diabetic rats were significantly restored by HSME treatment. Thus, the results suggest therapeutic potential of H. spinosa in treatment of diabetic neuropathy.

Protective effect of aqueous extract of Feronia elephantum correa leaves on thioacetamide induced liver necrosis in diabetic rats.

OBJECTIVE: To evalueate hepatoprotective effects Feronia elephantum (F. elephantum) correa against thioacetamide (TA) induced liver necrosis in diabetic rats. METHODS: Male wistar rats were made diabetic with alloxan (160 mg/kg) on day 0 of the study. They were intoxicated with hepatotoxicant (thioacetamide, 300 mg/kg, ip) on day 9 of study to produce liver necrosis. Effects of 7 day daily once administration (day 2 to day 9) of EF (400 and 800 mg/kg, po) were evaluated on necorosis of liver in terms of mortality, liver volume, liver weight, serum aspartate aminotransferase (AST) and serum alanine transaminase (ALT), and histopathology of liver sections (for signs of necorosis and inflammation) on day-9 of the study. Separate groups of rats with treated only with alloxan (DA control), thioacetamide (TA control) and both (TA+DA control) were maintained. RESULTS: FE significantly lowered the mortality rate and showed improvement in liver function parameters in TA-induced diabetic rats without change in liver weight, volume and serum glucose levels. CONCLUSIONS: FE showed promising activity against TA-induced liver necorsis in diabetic rats and so might be useful for prevention of liver complications in DM.

Anti-asthmatic potential of chrysin on ovalbumin-induced bronchoalveolar hyperresponsiveness in rats.

CONTEXT: Chrysin, a flavonoid obtained from various natural sources, has been reported to act as an anti-inflammatory and antioxidant agent. However, its anti-allergic action is not fully understood. OBJECTIVE: In this study, we investigated the in vivo anti-asthmatic activity of chrysin. MATERIALS AND METHODS: The effects of chrysin were evaluated using ovalbumin (OVA) (two subcutaneous 1 mL injections of 20 µg) to induce bronchoalveolar hyperresponsiveness in rats. Chrysin, when administered at 3, 10, and 30 mg/kg, p.o., respectively, before OVA challenge, reduced inflammatory cell (total and differential cell count) infiltration into the lungs measured from bronchoalveolar lavage fluid as supported by lung histology. RESULTS: The total lung injury score was reduced in a dose-dependent manner, evaluated in six different categories (infiltration of leucocytes, type of inflammatory exudates, status of bronchi, perivascular status of lung blood vessels, integrity of alveoli and activation of alveolar macrophages). Various cellular injury parameters such as alkaline phosphatase, lactate dehydrogenase, and total protein were estimated and found to be reduced by chrysin pretreatment. Further, chrysin was found to reduce nitrite concentration (NO) and lipid peroxidation, suggesting its antioxidant activity. DISCUSSION AND CONCLUSION: Chrysin showed anti-asthmatic potential, probably due to the alteration of Th1/Th2 polarization via the suppression of inducible nitric oxide synthase, nuclear factor-κB, and activation protein.

beta-adrenoreceptor blocking and antihypertensive activity of PP-24, a newly synthesized aryloxypropanolamine derivative.

PP-24 is a newly synthesized putative beta-adrenoceptor antagonist. The objective of the study was to the evaluate beta-adrenoceptor blocking activity of PP-24 on isolated rat preparations: right atria, uterus and colon. Effects on the rat ECG and renal hypertension (induced by left renal artery ligation) were also investigated. Treatment with PP-24 (3 and 10 mg kg(-1)) for 7 days in rats with renal hypertension significantly reduced the mean atrial blood pressure. Single i.v. injections of isoprenaline (0.3, 1 and 3 microg kg(-1)) alone in normal anaesthetized rat caused hypotension and tachycardia, while PP-24 alone produced dose-dependent falls in mean aterial pressure and bradycardia. Pretreatment of anaesthetized rats with test compounds significantly blocked the hypotension response but not the tachycardia induced by isoprenaline (0.3, 1 and 3 microg kg(-1)). The pA(2) of PP-24 to beta(1)-, beta(2)- and beta(3)-adrenoceptors was 7.72 +/- 0.082, 7.40 +/- 0.082 and 6.39 +/- 0.16, respectively. The beta(1)/beta(2) selectivity ratio was 2.08, compared with 1.27 for propranolol and 39.17 for atenolol. It is concluded that PP-24 possesses beta-adrenoceptor blockade activity but with non-specific affinity for beta(1)- and beta(2)-adrenoceptor subtypes. The rank order of potency of the antagonists for beta(1)-adrenoceptors was atenolol > PP-24 > propranolol. The antihypertensive activity of PP-24 in rats with renal hypertension appears to be due to blockade of beta-adrenoceptors.

Interaction of Aqueous Extract of Pleurotus pulmonarius (Fr.) Quel-Champ. with Glyburide in Alloxan Induced Diabetic Mice.

Mushrooms are low calorie food with very little fat and are highly suitable for obese persons. With no starch and very low sugars, they are the 'delight of the diabetics'. Combination of herbal drugs (or isolated phytochemicals) is found to be beneficial in certain diseases when given along with conventional drugs. The aim of the present study was to evaluate the effects of aqueous extract of Pleurotus pulmonarius (Lentinaceae) (called as PP-aqu) and its interaction with glyburide in alloxan induced diabetic mice. The diabetic mice treated were with PP-aqu (500 mg/kg, p.o.) alone or combination with glyburide (10 mg/kg, p.o.) for 28 days. Blood samples were collected by orbital sinus puncture using heparinized capillary glass tubes and were analyzed for serum glucose on 0, 7th, 14th, 21st and 28th days. Body weights and mortality were noted during the study period. In oral glucose tolerance test (OGTT), glucose (2.5 g/kg, p.o.) was administered with either vehicle, PP-aqu alone or in combination with glyburide and serum glucose level analyzed at 0, 30, 60 and 120 min after drug administration. Administration of PP-aqu (500 mg/kg) and its combination with glyburide (10 mg/kg) significantly (P < 0.001) decreased serum glucose level in diabetic mice. In OGTT, glyburide or PP-aqu treatment alone or their combination produced significant (P < 0.001) increase in glucose threshold. Thus we suggest that P. pulmonarius showed potent and synergistic antihyperglycemic effect in combination with glyburide.