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1.  Hepatoprotective Activity of Cucumis trigonus Roxb. Fruitagainst CCl4 Inducesd Hepatic Damage in Rats 
In India, a number of medicinal plants and their formulations are used to cure hepatic disorders in traditional systems of medicine. No systemic study has been done on protective effect of Cucumis trigonus Roxb. (Cucurbitaceae) to treat hepatic diseases. Protective action of C. trigonus fruit extracts was evaluated in this study in animal model of hepatotoxicity, which was induced by carbon tetrachloride. Forty two healthy female albino Wistar rats weighing between 180 and 200 g were divided in to seven groups of 6. Group 1 was normal control group; Group 2, the hepatotoxic group was given CCl4; Group 3 was administered standard drug (Liv-52); Groups 4-7 received pet. ether, chloroform, alcohol and aqueous fruit extract (300 mg/kg) with CCl4. The parameters studied were alanine transaminase, aspartate transaminase, alkaline phosphatase and serum bilirubin activities. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Results of the biochemical studies of blood samples of CCl4 treated animals showed significant increase in the levels of serum enzyme activities, reflecting the liver injury caused by CCl4. Whereas blood samples from the animals treated with chloroform and aqueous fruit extracts showed significant and alcohol extract showed highly significant decrease in the levels of serum markers, indicating the protection of hepatic cells. The results revealed that alcoholic fruit extract of Cucumis trigonus could afford highly significant protection against CCl4 induced hepatocellular injury.
PMCID: PMC3828915  PMID: 24250357
Hepatoprotective; Hepatotoxicity; CCl4; Cucumis trigonus; Liver
2.  Antiurolithiatic and antioxidant activity of Hordeum vulgare seeds on ethylene glycol-induced urolithiasis in rats 
Indian Journal of Pharmacology  2012;44(6):672-677.
The objective was to investigate the antiurolithiatic and antioxidant activity of ethanolic extract of Hordeum vulgare seeds (EHV) on ethylene glycol-induced urolithiasis in Wistar albino rats.
Materials and Methods:
Urolithiasis was produced in Wistar albino rats by adding 0.75% v/v ethylene glycol (EG) to drinking water for 28 days. The ethanolic extract of Hordeum vulgare seeds (EHV) was assessed for its curative and preventive action in urolithiasis. In preventive treatment, the EHV given from 1st day to 28th day, while in the curative regimen, the EHV was given from 15th day to 28th day. Various renal functional and injury markers such as urine volume, calcium, phosphate, uric acid, magnesium, urea, and oxalate were evaluated using urine, serum, and kidney homogenate. Antioxidant parameters such as lipid peroxidation, superoxide dismutase, and catalase were also determined.
The EHV treatment (both preventive and curative) increased the urine output significantly compared to the control. The EHV treatment significantly reduced the urinary excretion of the calcium, phosphate, uric acid, magnesium, urea, and oxalate and increased the excretion of citrate compared to EG control. The increased deposition of stone forming constituents in the kidneys of calculogenic rats were significantly lowered by curative and preventive treatment with EHV. It was also observed that the treatment with EHV produced significant decrease in lipid peroxidation, and increased levels of superoxide dismutase and catalase.
These results suggest the usefulness of ethanolic extract of Hordeum vulgare seeds as an antiurolithiatic and antioxidant agent.
PMCID: PMC3523490  PMID: 23248392
Antioxidant; ethylene glycol; Hordeum vulgare; urolithiasis
3.  Inhibitory effect of rutin and curcumin on experimentally-induced calcium oxalate urolithiasis in rats 
Pharmacognosy Research  2010;2(6):388-392.
Renal epithelial cell injury by reactive oxygen species is pre-requisite step in the pathogenesis of urolithiasis. Rutin and curcumin are polyphenolic compounds known to have antioxidant and anti-inflammatory activities, but their effect on urolithiasis is yet to be elucidated. In the present study, we have investigated the inhibitory effect of rutin and curcumin on calcium oxalate urolithiasis in Wistar albino rats.
Calcium oxalate urolithiasis was induced experimentally by administration of 0.75% v/v ethylene glycol with 1% w/v ammonium chloride in drinking water for three days followed by only 0.75% v/v ethylene glycol for 25 days. Rutin (20 mg/kg body weight) and curcumin (60 mg/kg body weight) were given once daily for 28 days by oral route. After treatment period, calcium and oxalate levels in urine and kidney tissue homogenate were measured. Kidney was also used for histopathological examination.
Stone-induction with ethylene glycol and ammonium chloride resulted in elevated levels of calcium and oxalate in the urine and kidney sample, whereas supplementation of rutin and curcumin restored it near to normal. Histopathological study revealed minimum tissue damage and less number of calcium oxalate deposits in kidney of animal treated with rutin and curcumin as compared to calculi-induced animal.
The data suggest that the rutin and curcumin inhibits calcium oxalate urolithiasis. This effect is mediated possibly through a lowering of urinary concentration of stone forming constituents, anti-inflammatory and antioxidant effects.
PMCID: PMC3111700  PMID: 21713144
Calcium oxalate; curcumin; ethylene glycol; rutin; urolithiasis
4.  Antiurolithic activity of Origanum vulgare is mediated through multiple pathways 
Origanum vulgare Linn has traditionally been used in the treatment of urolithiasis. Therefore, we investigated the crude extract of Origanum vulgare for possible antiurolithic effect, to rationalize its medicinal use.
The crude aqueous-methanolic extract of Origanum vulgare (Ov.Cr) was studied using the in vitro and in vivo methods. In the in vitro experiments, supersaturated solution of calcium and oxalate, kidney epithelial cell lines (MDCK) and urinary bladder of rabbits were used, whereas, in the in vivo studies, rat model of urolithiasis was used for the study of preventive and curative effect.
In the in vitro experiments, Ov.Cr exhibited a concentration-dependent (0.25-4 mg/ml) inhibitory effect on the slope of nucleation and aggregation and also decreased the number of calcium oxalate monohydrate crystals (COM) produced in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against DPPH free radical and lipid peroxidation induced in rat kidney tissue homogenate. Ov.Cr reduced the cell toxicity using MTT assay and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 μg/cm2) crystals. Ov.Cr relaxed high K+ (80 mM) induced contraction in rabbit urinary bladder strips, and shifted the calcium concentration-response curves (CRCs) towards right with suppression of the maximum response similar to that of verapamil, a standard calcium channel blocker. In male Wistar rats receiving lithogenic treatment comprising of 0.75% ethylene glycol in drinking water given for 3 weeks along with ammonium chloride (NH4Cl) for the first 5 days, Ov.Cr treatment (10-30 mg/kg) prevented as well as reversed toxic changes including loss of body weight, polyurea, crystalluria, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls.
These data indicating the antiurolithic activity in Ov.Cr, possibly mediated through inhibition of CaOx crystallization, antioxidant, renal epithelial cell protective and antispasmodic activities, rationalizes its medicinal use in urolithiasis.
PMCID: PMC3222619  PMID: 22004514
5.  Antiurolithiatic and antioxidant activity of Mimusops elengi on ethylene glycol-induced urolithiasis in rats 
Indian Journal of Pharmacology  2010;42(6):380-383.
To evaluate the potential of Mimusops elengi in the treatment of renal calculi.
Materials and Methods:
Petroleum ether, chloroform, and alcohol extracts of Mimusops elengi bark were evaluated for antiurolithiatic and antioxidant activity in male albino Wistar rats. Ethylene glycol (0.75%) in drinking water was fed to all the groups (Groups II–IX) except normal control (Group I) for 28 days to induce urolithiasis for curative (CR) and preventive (PR) regimen. Groups IV, V, and VI served as CR, and groups VII, VIII, and IX as PR were treated with different extracts of M. elengi bark. Groups I, II, and III served as normal control, positive control (hyperurolithiatic), and standard (cystone 750 mg/kg), respectively. Oxalate, calcium, and phosphate were monitored in the urine and kidney. Serum BUN, creatinine, and uric acid were also recorded. In vivo antioxidant parameters such as lipid peroxidation (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were also monitored.
All the extracts of M. elengi were safe orally and exhibited no gross behavioral changes in the rats. In hypercalculi animals, the oxalate, calcium, and phosphate excretion grossly increased. However, the increased deposition of stone forming constituents in the kidneys of calculogenic rats were significantly (P < 0.001) lowered by curative and preventive treatment with alcohol extract (AlE) of M. elengi. It was also observed that alcoholic extract of M. elengi produced significant (P < 0.001) decrease in MDA, and increased GSH, SOD, and CAT. These results confirm that AlE of M. elengi possess potent antiurolithiatic activity.
The results obtained suggest potential usefulness of the AlE of M. elengi bark as an antiurolithiatic agent.
PMCID: PMC2991697  PMID: 21189910
Antiurolithiatic activity; BUN; creatinine; Mimusops elengi
6.  Study of antiurolithiatic activity of Asparagus racemosus on albino rats 
Indian Journal of Pharmacology  2012;44(5):576-579.
The aim of this study was to investigate the effect of ethanolic extract of Asparagus racemosus on urolithiasis in rats.
Materials and Methods:
Thirty-six male Wistar albino rats were randomly divided into six groups (n = 6). Ethylene glycol (EG) 0.75% and ammonium chloride (AC) 2% in drinking water were fed to all groups (Groups II–VI) except normal control (Group I) rats for 10 days to induce urolithiasis. Group III–VI rats were treated with ethanolic extract of Asparagus racemosus at doses 200, 400, 800, and 1600 mg/kg, respectively, for 10 days. Positive control (Group II) rats were treated with EG/AC alone. Group I rats were administered drinking water and distilled water (6 μl/g) by gavage. After 10 days, blood samples were collected and analyzed for serum concentrations of calcium, phosphorus, urea, and creatinine. The kidneys were removed and sectioned for histopathological examination. The data were presented as mean ± standard error of mean and analyzed using one-way analysis of variance and Student's “t”-test. P < 0.05 was considered statistically significant. Conventional windows software was used for statistical analysis.
The rats treated with ethanolic extract of A. racemosus at doses 800 and 1600 mg/ kg significantly (P < 0.05) reduced the serum concentrations of calcium, phosphorus, urea, and creatinine. Histopathology of the kidneys in Groups V and VI revealed less tissue damage and were almost similar to Group I rats.
The ethanolic extract of A. racemosus has protective effect against urolithiasis.
PMCID: PMC3480787  PMID: 23112416
Ammonium chloride; antiurolithiatic activity; Asparagus racemosus; ethylene glycol
7.  Antiurolithiatic Effects of Solanum xanthocarpum Fruit Extract on Ethylene-Glycol-Induced Nephrolithiasis in Rats 
This study was designed to evaluate the effects of Solanum xanthocarpum fruit extract in ethylene-glycol-induced urolithiasis in the male Wistar rats. Nephrolithiasis was induced in male Wistar rats by adding ethylene glycol (0.75%) in drinking water for 28 days. Animals were divided into six groups, each containing six viz. Vehicle control, model control, S. xanthocarpum methanol extract in different doses of 100, 200, and 400 mg/kg p.o., Cystone (750 mg/kg, p.o.) served as a standard. Hyperoxaluria as well as an increase in the excretion of calcium, phosphate, uric acid and decrease in citrate and magnesium in urine, impairment of renal function and oxidative imbalance in kidney were observed in the calculi-induced group. Treatment with S. xanthocarpum decreases hyperoxaluria, calcium, and uric acid, improves renal function, and also produces antioxidant effects. Crystalluria was characterized by excretion calcium oxalate (CaOX) crystals, which were enormous in the lithogenic group but smaller in the drug-treated group. The histology showed that the calculi-induced group had a large deposition of CaOX crystals in kidney while the treated group had trivial and fewer deposits. The result indicates the antiurolithiatic activity of S. xanthocarpum mediated possibly by CaOX crystal inhibition, diuretic, antioxidant and maintaining balance between stone promoter and inhibitor constituents, and this study rationalized its medicinal use in urolithiasis.
PMCID: PMC3483526  PMID: 23112535
Calcium oxalate; ethylene glycol; Solanum xanthocarpum; urolithiasis
8.  Biopotency of Acalypha indica Linn on Membrane Bound ATPases and Marker Enzymes urolithic Rats 
Ancient Science of Life  2011;31(1):3-9.
The ethanolic extract of Acalypha indica was tested for its biopotency on membrane bound enzymes and marker enzymes in urolithiasis in male wistar albino rats. Calcium oxalate urolithiasis was induced by 0.75% ethylene glycol in drinking water for 30 days. There was a significant decrease in membrane bound enzymes such as Ca2+ ATPase, Mg2+ ATPase, Na+K+ ATPase and marker enzymes Aspartate Transaminase (AST), Alanine Transaminase (ALT), Acid phosphatase (ACP) and Alkaline Phosphatase (ALP) in liver and kidney. The AST, ALT, ACP and ALP were increased in serum and urine of rats. Therapeutic treatment with plant extract (200mg/kg b.wt.dose-1 day-1 oral-1) has significantly ameliorated to near normalcy in the curative group. These results of the present study concluded that A. indica can play an important role in the prevention of disorders associated with kidney stone formation.
PMCID: PMC3377040  PMID: 22736883
Marker enzymes; membrane bound enzymes; Urolithiasis; ethylene glycol; Acalypha indica
9.  Studies on the in vitro and in vivo antiurolithic activity of Holarrhena antidysenterica 
Urological research  2012;40(6):671-681.
Holarrhena antidysenterica has a traditional use in the treatment of urolithiasis, therefore, its crude extract has been investigated for possible antiurolithic effect.
Materials and methods
The crude aqueous-methanolic extract of Holarrhena antidysenterica (Ha.Cr) was studied using the in vitro and in vivo methods.
In the in vitro experiments, Ha.Cr demonstrated a concentration-dependent (0.25–4 mg/ml) inhibitory effect on the slope of aggregation. It decreased the size of crystals and transformed the calcium oxalate monohydrate (COM) to calcium oxalate dehydrate (COD) crystals, in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) free radicals and lipid peroxidation induced in rat kidney tissue homogenate. Ha.Cr (0.3 mg/ml) reduced (p < 0.05) the cell toxicity and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 μg/cm2) crystals. In male Wistar rats, receiving 0.75% ethylene glycol (EG) for 21 days along with 1% ammonium chloride (AC) in drinking water, Ha.Cr treatment (30–100 mg/kg) prevented the toxic changes caused by lithogenic agents; EG and AC, like loss of body weight, polyurea, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls.
These data indicate that Holarrhena antidysenterica possesses antiurolithic activity, possibly mediated through inhibition of CaOx crystal aggregation, antioxidant and renal epithelial cell protective activities and may provide base for designing future studies to establish its efficacy and safety for clinical use.
PMCID: PMC3666572  PMID: 22622371
Urolithiasis; Holarrhena antidysenterica; In vitro; In-vivo; MDCK cell line; Rats
10.  Exploring Antiurolithic Effects of Gokshuradi Polyherbal Ayurvedic Formulation in Ethylene-Glycol-Induced Urolithic Rats 
Gokshuradi Yog (GY) is a polyherbal ayurvedic formulation used traditionally for several decades in India for the treatment of urolithiasis. The aim of the present study was to determine the underlying mechanism of GY action in the management of calcium oxalate urolithiasis. The effect of Gokshuradi polyherbal aqueous extracts (GPAEs) was studied on various biochemical parameters involved in calcium oxalate formation by employing in vitro and in vivo methods. GPAE exhibited significant antioxidant activity against 1, 1-diphenyl-2-picrylhydrazyl free radical and inhibited lipid peroxidation in the in vitro experiments. The rat model of urolithiasis induced by 0.75% ethylene glycol (EG) and 1% ammonium chloride (AC) in water caused polyuria, weight loss, impairment of renal function, and oxidative stress and decreased antioxidant enzyme activities in untreated control groups. However, GPAE- (25, 50, and 100 mg/kg) treated groups caused diuresis accompanied by a saluretic effect and revealed significant increase in antioxidant enzyme activities along with decreased oxalate synthesizing biochemical parameters at higher doses. This study revealed the antiurolithic effect of GPAE mediated possibly through inhibiting biochemical parameters involved in calcium oxalate formation, along with its diuretic and antioxidant effects, hence supporting its use in the treatment of calcium oxalate urolithiasis.
PMCID: PMC3608183  PMID: 23554833
11.  Evalution of Antiurolithic Activity of Alcoholic Extract of Roots of Cissampelos Pareira in Albino Rats 
Background: In ayurvedic system of medicine a vast number of medicinal plants are reported to possess with antiurolithic activity.
Aim: To study the antiurolithic activity of alcoholic extract of roots of Cissampelos pareira (AERCP) in chemicals induced urolithiasis in albino rats.
Materials and Methods: Nine Groups of albino rats (n=6) were used to evaluate the antiurolithic activity of alcoholic extract of roots of C.Pareira. Group I received with rat chow diet, Group II with 2% Ammonium chloride (AC) and 0.75% Ethylene glycol (EG) Group III with EG plus AC and cystone (5 ml/kg), Groups IV, V, VI with low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses of root extract, Groups VII, VIII, IX with EG plus AC and low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses of root extract respectively for 10 days. Urolithiasis was induced by supplying drinking water mixed with 2% Ammonium chloride and 0.75% Ethylene glycol for 10 days. On 11th day three rats from each Group were kept in one metabolic cage and urine (pooled) collected for 24h was subjected for estimation of biochemical parameters like urinary calcium, uric acid and magnesium. Blood was collected on the same day and analysed for various parameters. Kidneys were observed for the histopathological changes.
Results: The rats treated with alcoholic extract of roots of C. pareira at 03 different doses significantly (p≤ 0.05) reduced urinary calcium, uric acid and increased urinary magnesium levels, reduced serum calcium, creatinine and increased serum magnesium. Rats treated with 200 mg/kg and 400 mg/kg doses revealed less tissue damage and the cytology of the nephrotic tissue was almost similar to normal control Group I rats.
Conclusion: Results showed that alcoholic extract of roots of C. pareira has exhibited a significant antiurolithic effect against urolithiasis in experimental rats.
PMCID: PMC4149086  PMID: 25177580
Ammonium chloride; Ethylene glycol; Urolithiasis
12.  Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats 
Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague–Dawley strain weighting (120–150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury.
PMCID: PMC3730730  PMID: 23961190
AbM, Agaricus blazei Murill; CCl4, carbon tetrachloride; AST, aspartate transaminase; ALT, alanine transaminase; LDH, lactate dehydrogenase; GR, glutathione reductase; GSH, glutathione; MDA, malondialdehyde; vit. C, vitamin C; vit. E, vitamin E; Agaricus blazei Murill; Carbon tetrachloride; Hepatoprotective; Antioxidant; Liver
13.  Protective effects of Cornus mas fruit extract on carbon tetrachloride induced nephrotoxicity in rats 
Indian Journal of Nephrology  2014;24(5):291-296.
Oxidative damage is implicated in the pathogenesis of kidney injury. Cornus mas is used for in renal aliments traditionally in Iran. The present study was aimed to investigate the antioxidant activity of C. mas fruit extract (CMFE) on carbon tetrachloride (CCl4) treated oxidative stress in Wistar albino rats. Forty two male albino rats were divided into seven groups. Group I served as a sham; Group II served as a normal control; Group III served as a toxic control, with CCl4 (1 ml/kg body weight; 80% in olive oil); Groups IV and V received CMFE at doses of 300 and 700 mg/kg before CCl4 injection; Groups VI and VII received extract at same doses orally at 2, 6, 12, 24 and 48 h after CCl4 intoxication. CCl4 injection produced a significant rise in serum markers of oxidative stress and lipid peroxidation product malondialdehyde along with the reduction of antioxidant enzymes such as superoxide dismuta, catalase and glutathion peroxidase. Serum creatinine, urea and uric acid concentrations were increased whereas level of protein and albumin were reduced. Treatment of rats with different doses of fruit extract (300 and 700 mg/kg) significantly (P < 0.05) ameliorated the alterations induced with CCl4 in lipid peroxidation, antioxidant defenses, biochemical and renal lesions. Based on these results, we conclude that CMFE protects kidney from oxidative stress induced by CCl4.
PMCID: PMC4165053  PMID: 25249718
Carbon tetrachloride; Cornus mas; lipid paroxidation; nephrotoxicity; oxidative stress
14.  Effect of Commiphora mukul gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats 
To study the antioxidant efficacy of Commiphora mukul (C. mukul) gum resin ethanolic extract in streptozotocin (STZ) induced diabetic rats.
The male Wistar albino rats were randomly divided into four groups of eight animals each: Control group (C), CM-treated control group (C+CMEE), Diabetic control group (D), CM- treated diabetic group (D+CMEE). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg/ bwt). After being confirmed the diabetic rats were treated with C. mukul gum resin ethanolic extract (CMEE) for 60 days. The biochemical estimations like antioxidant, oxidative stress marker enzymes and hepatic marker enzymes of tissues were performed.
The diabetic rats showed increased level of enzymatic activities aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) in liver and kidney and oxidative markers like lipid peroxidation (LPO) and protein oxidation (PO) in pancreas and heart. Antioxidant enzyme activities were significantly decreased in the pancreas and heart compared to control group. Administration of CMEE (200 mg/kg bw) to diabetic rats for 60 days significantly reversed the above parameters towards normalcy.
In conclusion, our data indicate the preventive role of C. mukul against STZ-induced diabetic oxidative stress; hence this plant could be used as an adjuvant therapy for the prevention and/or management of diabetes and aggravated antioxidant status.
PMCID: PMC3609238  PMID: 23569867
Commiphora mukul; Antioxidants; Lipid peroxidation; Streptozotocin
15.  Influence of Momordica charantia on oxidative stress-induced perturbations in brain monoamines and plasma corticosterone in albino rats 
Indian Journal of Pharmacology  2011;43(4):424-428.
The objective of this study was to evaluate the antistress activity of Momordica charantia (MC) fruit extract on stress-induced changes in albino rats and also to explore attenuating effects of MC on in vitro lipid peroxidation in rat brain.
Materials and Methods:
In this study, Wistar albino rats (180–200 g) were used. Plasma corticosterone and monoamines—5-hydroxy tryptamine (5-HT), norepinephrine (NE), epinephrine (E) and dopamine (DA) in cortex, hypothalamus and hippocampus regions of brain were determined in animals under different stressful conditions. Ethanolic fruit extract of MC, at doses of 200 and 400 mg/kg, was used. The oxidative stress paradigms used in in vivo models were acute stress (AS) and chronic unpredictable stress (CUS). Panax quinquefolium (PQ) was used as a standard in in vivo models and ascorbic acid was used as a reference standard in the in vitro method.
Subjecting the animals to AS (immobilization for 150 min once only) resulted in significant elevation of plasma corticosterone levels and brain monoamine levels. Pretreatment with MC at doses of 200 and 400 mg/kg p.o. significantly countered AS-induced changes and a similar effect was exhibited by PQ at 100 mg/kg p.o. In the CUS regimen (different stressors for 7 days), plasma corticosterone levels were significantly elevated whereas the levels of 5-HT, NE, E, and DA were depleted significantly. Pretreatment with MC (200 and 400 mg/kg) attenuated the CUS-induced changes in the levels of above monoamines in cortex, hypothalamus, and hippocampus regions of brain and plasma corticosterone in a dose-dependent manner. Furthermore, MC extract (1000–5000 μg/mL) exhibited a significant quenching effect on in vitro lipid peroxidation indicating its strong antioxidant activity which was compared with ascorbic acid.
This study reveals the antistress activity of MC as it significantly reverted the stress-induced changes, and the activity might be attributed to its antioxidant activity since stress is known to involve several oxidative mechanisms.
PMCID: PMC3153706  PMID: 21844998
Corticosterone; lipid peroxidation; Momordica charantia; monoamines; oxidative stress
Acta Informatica Medica  2012;20(3):180-185.
The present study was conducted to evaluate the antioxidant and immunostimulant effects of The Carica papaya fruit aqueous extract (CPF, Caricaceae) against acrylamide induced oxidative stress and improvement of Immune functions which affected by free radicals liberating acrylamide in rats.
Material and methods:
Sixty male wistar albino rats (195-230g) were assigned to four groups, (fifteen/group). The first group used as control group and received normal physiological saline orally daily. The second group was supplemented with acrylamide 0.05% in drinking water. The third group was gastro-gavaged with 250 mg/kg of papaya fruit extract orally on daily basis. The fourth group was supplemented with acrylamide 0.05% in drinking water and gastro-gavaged with 250 mg/kg of papaya fruit extract orally on daily basis. The chosen dose of papaya fruit extract was based on the active pharmacological dose range obtained from the orientation study earlier conducted. The experimental period was extended to forty day. At the expiration of the experimental period and night fasting, blood samples were collected from the orbital venous sinus. The sera were separated and used for determining of IgG and IgM and the stomach, liver and kidney homogenates for estimation of MDA, GSH level, SOD and CAT activity as a biomarker of lipid peroxidation and antioxidative stress.
Results and discussion:
The obtained results revealed that, acrylamide caused significant increases in MDA and decrease of GSH level, SOD and CAT activity due to the oxidative stress induced by acrylamide on membrane polyunsaturated fatty acids in rat’s stomach, liver and kidney while administration of CPF aqueous extract, was significantly ameliorated the increased levels of MDA and decline of GSH, SOD and CAT activity in the stomach, liver and kidney tissues caused by acrylamide toxicity. Meanwhile, CPF aqueous extract significantly increased immune functions (IgG and IgM) while acrylamide significantly decrease it specially IgG. Thus, this study suggests that acrylamide-induced oxidative stress in rats can be ameliorated by administration of CPF aqueous extract.
PMCID: PMC3508853  PMID: 23322975
Carica papaya fruit; Acrylamide; Oxidative stress; Immunoglobulin.
17.  Effect of Unex on ethylene glycol-induced urolithiasis in rats 
Indian Journal of Pharmacology  2011;43(4):466-468.
This study was aimed to evaluate the effectiveness of the Unex capsule on albino rats as a preventive agent against the development of kidney stones. The Unex capsule is a marketed product of Unijules Life Sciences, Nagpur, containing the extracts of Boerhaavia diffusa and Tribulus terrestris. Activity of Unex was studied using the ethylene glycol-induced urolithiasis model. Standard drug used was Cystone. Several parameters were used including urinary volume, urine pH, urine analysis, and serum analysis to assess the activity. The results indicated that the administration of Unex to rats with ethylene glycol-induced lithiasis significantly reduced and prevented the growth of urinary stones (P < 0.01). Also, the treatment of lithiasis-induced rats by Unex restored all the elevated biochemical parameters (creatinine, uric acid, and blood urea nitrogen), restored the urine pH to normal, and increased the urine volume significantly (P < 0.01) when compared to the model control drug. This study supports the usage of Unex in urolithiasis and the utility could further be confirmed in other animal models.
PMCID: PMC3153716  PMID: 21845008
Boerhaavia diffusa; ethylene glycol; Tribulus terrestris; unex; urolithiasis
18.  Evaluation of anti-urolithiatic activity of Pashanabhedadi Ghrita against experimentally induced renal calculi in rats 
Ayu  2012;33(3):429-434.
Population in an industrialized world is afflicted by urinary stone disease. Kidney stones are common in all kinds of urolithiasis. One distinguished formulation mentioned by Sushruta for management of Ashmari (urolithiasis) is Pashanabhedadi Ghrita (PBG), which is in clinical practice since centuries. Validation of drug is the requirement of time through the experimental study. In this study, trial of PBG has been made against ammonium oxalate rich diet and gentamicin injection induced renal calculi in albino rats. The calculi were induced by gentamicin injection and ammonium oxalate rich diet. Test drug was administered concomitantly in the dose of 900 mg/kg for 15 consecutive days. Rats were sacrificed on the 16th day. Parameters like kidney weight, serum biochemical, kidney tissue and histopathology of kidney were studied. Concomitant treatment of PBG attenuates blood biochemical parameters non-significantly, where as it significantly attenuated lipid peroxidation and enhanced glutathione and glutathione peroxidase activities. It also decreased crystal deposition markedly into the renal tubules in number as well as size and prevented damage to the renal tubules. The findings showed that PBG is having significant anti-urolithiatic activities against ammonium oxalate rich diet plus gentamicine injection induced urolithiasis in rats.
PMCID: PMC3665093  PMID: 23723654
Ammonium oxalate; Ashmari; gentamicin; Pashanabhedadi Ghrita; urolithiasis
19.  Lemon juice has protective activity in a rat urolithiasis model 
BMC Urology  2007;7:18.
The use of herbal medicines (medicinal plants or phytotherapy) has recently gained popularity in Europe and the United States. Nevertheless the exact mechanism of the preventive effects of these products is still far to be clearly established, being its knowledge necessary to successfully apply these therapies to avoid stone formation.
The effect of oral lemon juice administration on calcium oxalate urolithiasis was studied in male Wistar rats. Rats were rendered nephrolithic by providing drinking water containing 0.75% ethylene glycol [v/v] (EG) and 2% ammonium chloride [w/v] (AC) for 10 days. In addition to EG/AC treatment, three groups of rats were also gavage-administered solutions containing 100%, 75% or 50% lemon juice [v/v] (6 μl solution/g body weight). Positive control rats were treated with EG/AC but not lemon juice. Negative control rats were provided with normal drinking water, and were administered normal water by gavage. Each group contained 6 rats. After 10 days, serum samples were collected for analysis, the left kidney was removed and assessed for calcium levels using flame spectroscopy, and the right kidney was sectioned for histopathological analysis using light microscopy.
Analysis showed that the rats treated with EG/AC alone had higher amounts of calcium in the kidneys compared to negative control rats. This EG/AC-induced increase in kidney calcium levels was inhibited by the administration of lemon juice. Histology showed that rats treated with EG/AC alone had large deposits of calcium oxalate crystals in all parts of the kidney, and that such deposits were not present in rats also treated with either 100% or 75% lemon juice.
These data suggest that lemon juice has a protective activity against urolithiasis.
PMCID: PMC2194764  PMID: 17919315
20.  PA01.16.Effect of sheetaprabha tablets on ethylene glycol induced urolithiasis in rats 
Ancient Science of Life  2012;32(Suppl 1):S65.
Sheetaprabha tablets, Ayurvedic proprietary medicine, contain Sweta Parpati & Hajrul hahood bhasma as active ingredients. Sweta parpati is mainly indicated in mootravaha srotovikara & hajrul hahood bhasma is having mootrala and ashmari bhedana actions. A survey of the literature showed that no pharmacology study was made on the sweta parpati and sheetaprabha tablets. In the present study we investigated the effect of Sheetaprabha tablets in ethylene glycol induced urolithiasis in rats.
Urolithiasis was induced in male wistar rats by adding ethylene glycol (0.75%) in drinking water. Protective (130mg/kg & 260mg/kg) and curative effect (130mg/kg & 260mg/kg) of Sheetaprabha was studied in experimental animal models.
Ethylene glycol induced urolithiatic rats showed significant increase in blood urea nitrogen (P<0.001), creatinine & phosphorus (P<0.05) and also significant increase in SGOT, SGPT & ALP levels in serum, which were prevented by Sheetaprabha treated rats in protective groups and decreased in curative groups. Histopathologies of kidneys were prevented calcium oxalate formation and tubular degeneration, and increase in tubular regeneration was observed in protective (130mg/kg, 260mg/kg) group.
The present study findings indicate that treatment with Sheetaprabha tablets, which decreases and also prevents the growth of the calcium oxalate crystals in urinary tract. It also seems that the preventive effect is more effective than its curative effect. Hence, this study confirms the traditional use of Sheetaprabha tablets in urolithiasis.
PMCID: PMC3800946
21.  Camellia sinensis (L.) Kuntze Extract Ameliorates Chronic Ethanol-Induced Hepatotoxicity in Albino Rats 
The goal of this study was to investigate the hepatoprotective effects of aqueous extract of Camellia sinensis or green tea extract (AQGTE) in chronic ethanol-induced albino rats. All animals were divided into 4 groups in the study for a 5-week duration. 50% ethanol was given orally to the rats with two doses (5 mg/kg bw and 10 mg/kg bw) of AQGTE. Ethanol administration caused a significant increase in the levels of plasma and serum enzymatic markers, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), and nonenzymatic markers (cholesterol and triglycerides), lipid peroxidation contents, malondialdehyde (MDA), and glutathione-S-transferase (GST), and decreased the activities of total proteins, albumin, and cellular antioxidant defense enzymes such as superoxide dismutase (SOD). The elevation and reduction in these biochemical enzymes caused the damage in hepatocytes histologically due to the high production of ROS, which retards the antioxidant defense capacity of cell. AQGTE was capable of recovering the level of these markers and the damaged hepatocytes to their normal structures. These results support the suggestion that AQGTE was able to enhance hepatoprotective and antioxidant effects in vivo against ethanol-induced toxicity.
PMCID: PMC4164262  PMID: 25254057
22.  Antioxidant, Antihyperlipidaemic and Antidiabetic Activity of Eugenia Floccosa Bedd Leaves in Alloxan Induced Diabetic Rats 
The ethanol extract of Eugenia floccosa Bedd (Family: Myrtaceae) leaf was investigated for its antioxidant, antihyperlipidaemic and antidiabetic effect in Wistar Albino rats. Diabetes was induced in Albino rats by administration of alloxan monohydrate (150mg/kg, i.p). The ethanol extracts of E. floccosa at a dose of 150 and 300mg/kg of body weight were administered at single dose per day to diabetes induced rats for a period of 14 days. The effect of ethanol extract of E. floccosa leaf extract on blood glucose, plasma insulin, creatinine, glycosylated haemoglobin, urea serum lipid profile [total cholesterol (TR), triglycerides (TG), low density lipoprotein – cholesterol (LDL-C), very low density lipoprotein – cholesterol (VLDL-C), high density lipoprotein – cholesterol (HDL-C) and phospholipid (PL)] serum protein, albumin, globulin, serum enzymes [serum glutamate pyruvate transaminases (SGPT) and serum glutamate oxaloacetate transaminases (SGOT), and alkaline phosphatase (ALP)], lipoprotein peroxidation (LPO) antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPx) were measured in the diabetic rats. The ethanol extract of Eugenia floccosa leaf elicited significant reductions of blood glucose (P<0.05), lipid parameters except HDL-C, serum enzymes and significantly increased HDL-C and antioxidant enzymes. The extracts also caused significant increase in plasma insulin (P<0.05) in the diabetic rats. From the above results, it is concluded that ethanol extract of Eugenia floccosa possesses significant antidiabetic, antihyperlipidaemic and antioxidant effects in alloxan induced diabetic rats.
PMCID: PMC3979240  PMID: 24826030
Antioxidant; antihyperlipidaemic; antidiabetic; E. floccosa; alloxan
23.  Antioxidant and anticancer evaluation of Scindapsus officinalis (Roxb.) Schott fruits 
Ayu  2011;32(3):388-394.
Several methods exist for the treatment of cancer in modern medicine. These include chemotherapy, radiotherapy, and surgery; most cancer chemotherapeutants severely affect the host normal cells. Hence the use of natural products now has been contemplated of exceptional value in the control of cancer. Plant-derived natural products such as flavonoids, terpenes, alkaloids, etc., have received considerable attention in recent years due to their diverse pharmacological properties including cytotoxic and cancer chemopreventive effects. Looking into this, the antioxidant and anticancer evaluation of Scindapsus officinalis (Roxb.) Schott fruits has been attempted to investigate its antitumor activity. The collection and authentication of the plant material mainly fruits and their various extractions was done. Identification of plant's active constituents by preliminary phytochemical screening was carried out. An in-vitro cytotoxic assay using the brine shrimp lethality assay with brine shrimp eggs (Artemia salina) at a dose of 1–10 μg/ml with the fruit extract was performed by the method described by Mayer et al. Cell viability using the Trypan blue dye exclusion test at a dose of 20, 40, 80, 120, and 160 μg/ml dissolved in DMSO (final concentration 0.1%), and cytotoxicity using the MTT assay where viable cells convert MTT into a formazan salt were performed. All pharmacological screening for acute toxicity and anti tumour studies using EAC 1 × 106 cells/mouse treated Swiss albino mice at a dose of 100 and 200 mg/kg/day orally was carried out. Biochemical and antioxidants predictions from various parameters like hematological, RBC, WBC count, PVC, total protein, Tissue Lipid Peroxidation, SOD, CATALASE, GPx, GST levels and anti tumour activity of Scindapsus officinalis were observed. The data was statistically analyzed by one-way ANOVA followed by Dunnett's and Tukey's multiple comparison test. The antitumor effect of the extract is evident from the increase in mean survival time (MST) lifespan, reduction in the solid tumor volume, and also the reversal of altered hematological parameters almost equal to normal. The methanolic extract (100–200 mg/kg/day orally) was found to be cytotoxic on human cancer cell lines. In addition, the methanolic extract had an antioxidant effect as reflected by a decrease in LPO, GST, and GPx (oxidant enzymes), and an increase in SOD and catalase.
PMCID: PMC3326889  PMID: 22529657
Antioxidant; Ehrlich's ascites carcinoma; hematological parameter; mean survival time; solid tumor volume; Scindapsus officinalis
24.  Prevention of renal crystal deposition by an extract of Ammi visnaga L. and its constituents khellin and visnagin in hyperoxaluric rats 
Urological research  2010;39(3):189-195.
In Egypt, teas prepared from the fruits of Ammi visnaga L. (syn. “Khella”) are traditionally used by patients with urolithiasis. The aim of this study was to evaluate whether oral administration of an aqueous extract prepared from the fruits of Ammi visnaga as well as two major constituents khellin and visnagin could prevent crystal deposition in stone-forming rats. Hyperoxaluria was induced in male Sprague-Dawley rats by giving 0.75% ethylene glycol (EG) and 1% ammonium chloride (NH4Cl) via the drinking water. The Khella extract (KE; 125, 250 or 500 mg/kg) was orally administered for 14 days. The histopathological examination of the kidneys revealed that KE significantly reduced the incidence of calcium oxalate (CaOx) crystal deposition. In addition, KE significantly increased urinary excretion of citrate along with a decrease of oxalate excretion. Comparable to the extract, khellin and visnagin significantly reduced the incidence of calcium oxalate deposition in the kidneys. However, both compounds did not affect urinary citrate or oxalate excretion indicating a mechanism of action that differs from that of the extract. For KE, a reasonably good correlation was observed between the incidence of crystal deposition, the increase in citrate excretion and urine pH suggesting a mechanisms that may interfere with citrate reabsorption. In conclusion, our data suggest that KE and its compounds, khellin and visnagin, may be beneficial in the management of kidney stone disease caused by hyperoxaluria but that it is likely that different mechanism of action are involved in mediating these effects.
PMCID: PMC3663934  PMID: 21069311
Ammi visnaga; Apiaceae; nephrolithiasis; hyperoxaluria; calcium oxalate; khellin; visnagin
25.  Amelioration of nitrobenzene-induced nephrotoxicity by the ethanol extract of the herb Euphorbia hirta 
Pharmacognosy Research  2011;3(3):201-207.
Euphorbia hirta (L.) (Euphorbiaceae) is a very popular herb amongst practitioners of traditional medicine and used in the treatment of female disorders, respiratory ailments, tumors, jaundice, digestive problems, wounds, etc. We aimed to evaluate the protective effect of E. hirta against nitrobenzene-induced nephrotoxicity in albino rats.
Materials and Methods:
The nephroprotective activity of the ethanol extract of E. hirta (400 mg/kg body weight) was studied in nitrobenzene-induced albino rats (1000 mg/kg body weight). The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and the levels of reduced glutathione (GSH), total thiols and vitamin C in the kidney tissues were determined. Histopathologic investigation was performed in the kidney tissue samples.
Nitrobenzene administration significantly (P < 0.01) enhanced the lipid peroxidation and significantly (P < 0.05) depleted the levels of SOD, CAT, GPx, GST, GSH, total thiols and vitamin C. Treatment with the ethanol extract of E. hirta significantly normalized the antioxidant levels. The nephroprotective activity was also supported by histopathologic studies of kidney tissue.
The results indicate that the ethanol extract of E. hirta ameliorates renal dysfunction and could be used as an effective protector against nitrobenzene-induced nephrotoxicity, primarily through its antioxidant capacity.
PMCID: PMC3193622  PMID: 22022170
Antioxidant; Euphorbia hirta; histopathology; nephrotoxicity; nitrobenzene

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