Rotula aquatica Lour. mitigates oxidative stress and inflammation in acute pyelonephritic rats.

The current study evaluates the efficacy of methanolic extract of Rotula aquatica Lour. (MERA) against inflammatory changes associated with acute pyelonephritis. The antioxidant enzymes such as SOD, CAT, GPx, GR and oxidative stress markers like GSH content, malondialdehyde (MDA) level, nitrate level, reactive oxygen species (ROS) level and renal toxicity markers were evaluated in this study. The mRNA level expression of Toll-like receptor 4 (TLR-4), nuclear transcription factor kappa B (NF-κB), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and Tamm Horsfall protein (THP) were studied by RT-PCR analysis. The oral administration of MERA increases the antioxidant enzyme status in pyelonephritis rat. The elevated levels of oxidative stress markers in pyelonephritic rats were ameliorated by the administration of MERA at 100 mg/kg and 200 mg/kg bwt of the rat. The mRNA level expression of major genes were restored to normal level by MERA.

Methanolic Extract of Muntingia Calabura L. Mitigates 1,2-Dimethyl Hydrazine Induced Colon Carcinogenesis in Wistar Rats.

OBJECTIVE: The present study aimed to evaluate the efficacy of methanolic extract of Muntingia calabura L. leaves (MEMC) in ameliorating oxidative stress and inflammation associated with 1,2-dimethyl hydrazine (DMH) induced colon cancer. METHODS: The antioxidant enzymes, oxidative stress markers, liver and renal toxicity markers were evaluated. Histopathological examination of colon tissues was carried out with the aid of alcian blue stain and Hematoxylin and Eosin stain. RESULTS: MEMC supplementation at doses of 100 and 200 mg/kg body weight of rats causes the antioxidant enzymic levels to retain near to its normal range. Meanwhile the oxidative stress markers, which showed an elevation from its normal level upon DMH administration, gets significantly reduced on MEMC treatment. Histopathological observation also revealed that the severity of colorectal cancer was reduced by the supplementation of MEMC. CONCLUSION: The findings from the present study showed that MEMC can exert a potential role to ameliorate the oxidative stress and inflammation associated with colorectal cancer.

Ethyl acetate fraction of Muntingia calabura L. exerts anti-colorectal cancer potential via regulating apoptotic and inflammatory pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Muntingia calabura L. is a plant with traditional pharmacological relevance. The various plant parts are used by tribal communities for treating gastric ulcers, prostate gland swellings, headache, cold etc. Hence, an attempt was made to evaluate the anti-colorectal cancer potential of ethyl acetate fraction of M. calabura (EFMC). MATERIALS AND METHODS: HR LC-MS analysis was carried out for the identification of compounds present in EFMC. 1,2 Dimethylhydrazine (DMH) induced animal model was used for the evaluation of anti-CRC potential of EFMC. Antioxidant enzyme status, oxidative stress marker status, hepatic and renal function marker level were determined. Evaluation of mRNA level expression of inflammatory and apoptotic genes, hematological and histopathological examinations were also carried out to figure out the extent of colorectal cancer (CRC) and the beneficial role offered by EFMC. RESULTS: HR LC-MS analysis of EFMC revealed the presence of ten pharmacologically active compounds. EFMC treatment made the altered levels of antioxidant enzymes, oxidative stress markers, liver and renal function markers to retain near to its normal range. The hematological and histopathological evaluations also confirmed the anti-CRC effects exhibited by EFMC. EFMC offered a regulatory control over the inflammatory and apoptotic genes thereby mitigating the damaging effects of CRC. CONCLUSION: The present study depicted the presence of therapeutically active compounds exhibiting strong antioxidant, anti-inflammatory and anticancer potential. The beneficial role offered by these compounds could be responsible for the amelioration of DMH induced CRC. Hence, EFMC can be used as an anti-CRC agent in human subjects.

Acute oral toxicity and anti-inflammatory evaluation of methanolic extract of Rotula aquatica roots in Wistar rats.

BACKGROUND: The plant Rotula aquatica Lour. was traditionally well known due to its large number of pharmacological action and medicinal uses. The plant is a necessary component of many Ayurvedic drug preparations since historical times. It is widely used as a crucial ancient drug for kidney and bladder stones. OBJECTIVES: The main objective of the study was to evaluate the acute toxicity and anti inflammatory efficacy of methanolic extract of R.aquatica Lour. in in vivo models. MATERIALS AND METHODS: The qualitative phytochemical analysis and invitro antioxidant activity of the roots of methanolic extract of R.aquatica Lour. (MERA) was evaluated. The acute toxicity effect of MERA was evaluated with two different doses (550, 2000 mg/kg body weight), were administrated orally to Wistar rats. The rats were observed for sign and symptoms of toxicity and mortality for 14 days. The parameters measured including relative organ weight, blood, biochemical and histopathological parameters of hepatic and renal toxicity. The anti-inflammatory effect of MERA was also evaluated in carrageenan and dextran-induced paw edema models. RESULTS: The phytochemical evaluation of MERA shows the presence of secondary metabolites like alkaloids, flavonoids, phenolics and tannins, phytosterols, reducing sugars, proteins and terpenoids. The results of in-vitro antioxidant evaluation of MERA reveal its capability to scavenging free radical at a lower concentration. The MERA did not show any visible signs of toxicity up to the dose of 2000 mg/kg body weight. The results obtained from our carrageenan and dextran-induced paw edema model study also proved the anti-inflammatory effect of MERA in rat model. CONCLUSION: The result shows the potential of MERA as an anti-inflammatory drug to reduce the signs of inflammation devoid of any toxic effect.

Protective Role of Terminalia bellirica (Gaertn.) Roxb Fruits Against CCl4 Induced Oxidative Stress and Liver Injury in Rodent Model.

ABSTRACT: The medicinal plant, Terminalia bellirica (Gaertn.) Roxb. is widely used in the traditional Indian system of medicine like Ayurveda for centuries in the treatment of various ailments owing to it's rejuvenating as well as health promoting effects. The present study evaluates protective role of aqueous acetone extract of T. bellirica fruits (AATB) against CCl4 induced liver toxicity in animal model. The liver damage was assessed by liver function markers including ALT, AST, ALP, GGT, LDH, total bilirubin, total protein, albumin, globulin and albumin-globulin ratio. The levels of MDA, ROS, and NO along with the tissue antioxidants were evaluated to assess hepatic oxidative stress and level of lipid peroxidation. Treatment with AATB prior to the exposure of CCl4 significantly reduced the damage when compared to the control rats. The outcome of the present study advocates the traditional use of the plant as ethnic food and health tonic.

Protective effect of Rotula aquatica Lour against gentamicin induced oxidative stress and nephrotoxicity in Wistar rats.

Gentamicin is an aminoglycoside antibiotic widely used for the treatment of life-threatening infections caused by Gram-negative bacteria. The use of gentamicin was limited due to its ototoxic and nephrotoxic adverse effects. The current study was designed to evaluate the protective effect of ethyl acetate fraction from Rotula aquatica (EFRA) against gentamicin induced nephrotoxicity. The antioxidant enzymes status, lipid peroxidation, nitrate and ROS level, serum markers like creatinine, Urea, BUN were estimated in the present study. The histopathological analysis of renal tissues was done by H&E and PAS staining. The mRNA level expression of KIM-1, NF-κB, TNF- α, and IL-6 were measured by semi-quantitative reverse transcription-polymerase chain reaction. The changes in antioxidant parameters were restored by the treatment of EFRA at different dose (50 mg/kg bwt, 100 mg/kg bwt). The serum parameters, ROS, MDA and nitrate level were decreased by administration of EFRA. The EFRA ameliorates histological changes associated with gentamicin induced nephrotoxicity. The mRNA level expression of KIM-1, NF-κB, TNF- α, and IL-6 were downregulated in EFRA treated groups. The results from present study reveals the role of EFRA as good anti-inflammatory and nephro protective drug.

Rotula aquatica Lour attenuates secretion of proinflammatory mediators and cytokines in lipopolysaccharide-induced inflammatory responses in murine RAW 264.7 macrophages.

Rotula aquatica belongs to the family Boraginaceae, and is reported to contain baunerol, steroids and alkaloids. In Ayurveda, R. aquatica has been used for the treatment of various diseases such as diabetes, treatment of piles, venereal disease, and cancer. The current study aims to investigate the anti-inflammatory effect of methanolic extract of R. aquatica (MERA) in RAW 264.7 cells. The cytotoxicity of MERA was analyzed by MTT assay. The total cyclooxygenase (COX) activity, 5-lipoxygenase (5-LOX) activity, myeloperoxidase activity, inducible nitric oxide synthase activity, nitrate level and reactive oxygen species production were studied in LPS-stimulated RAW 264.7 cells. The gene level expression of cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were also evaluated in this study. The MERA did not show any cytotoxicity at different concentrations (6.25-100 µg/ml). MERA (100 µg/ml) inhibited total COX and 5-LOX activity at 50.53 and 62.03%, respectively, besides significantly (p < 0.05) diminished nitrate and ROS generation, when compared with LPS control. Moreover, MERA down-regulated the mRNA expressions of inflammatory marker genes like TNF-α, IL-6, and COX-2 against LPS stimulation. Our results demonstrate that MERA is able to attenuate inflammatory response, possibly via ROS and NO suppression, inhibiting the production of arachidonic acid metabolites and modulation of proinflammatory mediators and cytokines release.

Ethyl acetate fraction of Terminalia bellirica (Gaertn.) Roxb. fruits inhibits proinflammatory mediators via down regulating nuclear factor-κB in LPS stimulated Raw 264.7 cells.

Inflammation has been considered as a major risk factor for various kinds of human diseases. Macrophages play substantial roles in host defense against infection. It can be activated by lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria. The current study aims to investigate the anti-inflammatory effects of ethyl acetate fraction isolated from T. bellerica (EFTB) in LPS stimulated RAW 264.7 macrophage cell lines. The inhibitory effects of EFTB on total cyclooxygenase (COX), 5-lipoxygenase (5-LOX) activity, nitrate and inducible nitric oxide synthase (iNOS) level, reactive oxygen species (ROS) production were studied. The gene level expression of COX-2, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and Nuclear factor-κB (NF-κB) were also studied in LPS stimulated RAW 264.7 cells. EFTB (100µg/mL) inhibited all inflammatory markers in dose dependent manner. Moreover, EFTB down regulated the mRNA expression of TNF-α, IL-6, COX-2 and NF-κB against LPS stimulation. Our results demonstrated that EFTB is able to attenuate inflammatory response possibly via suppression of ROS and NO species, inhibiting the production of arachidonic acid metabolites, proinflammatory mediators and cytokines release.

In vivo toxicity evaluation of aqueous acetone extract of Terminalia bellirica (Gaertn.) Roxb. fruit.

Terminalia bellirica (Gaertn.) Roxb. (Family: Combretaceae), known as Bhibhitaki in Sanskrit and locally known as Behera in India is one of the oldest medicinal plants which has widely been used in the traditional system of medicine, especially in Ayurveda for centuries. The dried fruit of Terminalia bellirica is used for treating various ailments. Aqueous acetone extract of Terminalia bellirica (Gaertn.) Roxb fruits (AATB), showed antioxidant potential in our screening study is selected for the present in vivo toxicity evaluation. Acute administration of AATB was done in female Wistar Albino rats as a single dose up to 2000 mg/kg body weight. At the end of the study, Blood was collected for biochemical and hematological analyses, while histological examinations were performed on liver and kidney. There was no alteration in the behavioral pattern, food and water intake in the treated animals. The relative organ weight, biochemical parameters, hematological parameters and histopathological analysis were also found normal. All the parameters of the toxicity evaluation were found to be normal and the data suggests aqueous acetone extract of Terminalia bellirica fruit is safe, to be used as a traditional herbal formulation for its antioxidant potential and other health benefits.

Methanolic extract of Woodfordia fruticosa Kurz flowers ameliorates carbon tetrachloride-induced chronic hepatic fibrosis in rats.

Hepatic fibrosis, characterized by extracellular matrix accumulation, is the common cause of chronic liver failure and is a leading cause of morbidity and mortality worldwide. The aim of the present study was to evaluate the effect of dried flowers of Woodfordia fruticosa on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rat model. Hepatic fibrosis was induced in male Wistar rats by CCl4 administration (150 µl/100 g rat weight, oral) twice a week for 10 weeks. In preventive model, administration of daily doses of methanolic extract of W. fruticosa (MEWF) at two different doses (100 mg/kg, body weight (b.w.) and 200 mg/kg, b.w.) was started 1 week before the onset of CCl4 administration and continued for 10 weeks. In curative model, MEWF at 100 and 200 mg/kg were given for last 2 weeks after the establishment of fibrosis. MEWF at a dose of 200 mg/kg was able to exert a more pronounced effect as evidenced histologically by significant reduction in fibrotic septa formation in liver tissue, immunohistochemically by abridged expression of collagen III, and also biochemically by serum and tissue antioxidant status, lipid peroxidation, and hydroxyproline level. Liquid chromatography-mass spectrometry analysis revealed the presence of confertin, quercetin methyl ether, ellagic acid, and stigmasterol in MEWF, which could be responsible for its antifibrotic activity. These results indicate the effective protection exerted by MEWF against CCl4-induced hepatic fibrosis in a dose-dependent manner.

Dose-response effects of Elephantopus scaber methanolic extract on N-nitrosodiethylamine-induced hepatotoxicity in rats.

AIM: A decoction of Elephantopus scaber (Asteraceae) root is used to treat liver disorders in Indian and Chinese traditional medicine. The study was designed to examine the dose response effects of E. scaber methanolic extract on rats exposed to N-nitrosodiethylamine (NDEA) induced hepatotoxicity (0.02% NDEA in water five days per week, per oral) in preventive and curative models. METHODS: In preventive groups, NDEA was administered for six weeks. Daily doses of E. scaber methanolic extract (200 and 100 mg·kg-1) started one week before the onset of NDEA intoxication and continued for six weeks. In curative animals, NDEA was administered for six weeks followed by treatment with the methanolic n-hexane extract of E. scaber (200 and 100 mg·kg-1) for ten days. RESULTS: E. scaber extract treatment significantly (P ≤ 0.05) reduced the levels of AST, ALT, and MDA in both experimental groups. The extract also enhanced the antioxidant enzyme and protein levels in rats intoxicated with NDEA. Treatment with the extract dose dependently protected the liver from NDEA-induced hepatotoxicity with normal hepatocytes and uniform sinusoids, but in some areas showed degenerating hepatic cells in both treatment groups. CONCLUSION: E. scaber methanolic extract dose dependently prevented and reversed the hepatotoxicity induced by NDEA in both experimental models.

Antioxidant activity of Albizzia lebbeck (Linn.) Benth. in alloxan diabetic rats.

There is an increasing demand for natural anti-diabetic drugs, as continuous oral administration of insulin can culminate in many side effects and toxicity. In our endeavour to formulate some cost-effective herbal medicines for diabetes, we undertook this study to evaluate the antioxidant potential of aqueous extract of Albizzia lebbeck (ALL) in diabetic rats. The oxidative stress in alloxan-induced diabetic rats was determined by estimating the levels of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and reduced glutathione (GSH) in liver and kidneys. Activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S transferase (GST) were assessed in diabetic as well as rats co-administered with ALL. Oxidative damage in the liver and kidneys of diabetic rats as evidenced by a marked increment in the levels of TBARS and CD, and also a distinct diminution in GSH content was nullified by ALL, as these parameters showed a tendency to retrieve towards normalcy on co-administration of the herbal drug. The antioxidant enzymes registered a decline in activity in diabetic rats thus revealing the damaging effects of free radicals generated due to alloxan exposure. The activities of these enzymes returned to normalcy in ALL-administered rats indicating the antioxidant efficacy of the drug in resisting oxidative insult. The findings provide a rationale for further studies on isolation of active principles and pharmacological evaluation.

Probing the anti-hyperlipidemic efficacy of the allspice (Pimenta officinalis Lindl.) in rats fed with high fat diet.

In this study, the anti-hyperlipidemic effect of aqueous extract of Pimenta officinalis (APO) was investigated in experimental rats fed with high fat diet (HFD). Hyperlipidemia in experimental rats was evidenced by a significant enhancement in the level of glycerol, triglycerides and phopholipids in serum, and also in liver and kidney tissues. HFD caused oxidative stress in these animals as shown by marked increment in the levels of thiobarbituric acid reactive substances (TBARS) and diene conjugates (CD), and a distinct diminution in reduced glutathione (GSH) content in liver and kidneys. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) showed reduced activity in hyperlipidemic rats. All these biochemical parameters showed reliable signs of retrieving towards near-normalcy in APO-administered HFD fed rats. This study unveiled the anti-hyperlipidemic as well as antioxidant activity of APO.

Effect of Coscinium fenestratum on hepatotoxicity in rats.

Anti-hepatotoxic activity of methanol extract of Coscinium fenestratum stem (MEC) was investigated against carbon tetrachloride-induced hepatopathy in rats. Hepatotoxic rats were treated with MEC for a period of 90 days (60mg/kg body weight, daily, orally by intubation). Anti-hepatotoxic effect was studied by assaying the activities of serum marker enzymes like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase, lactate dehydrogenase etc. and glucose (6) phosphate dehydrogenase in liver. We also estimated the concentrations of total proteins, total lipids, triglycerides, phospholipids and cholesterol in serum, liver and kidney. The activities of all the marker enzymes registered a significant elevation in carbon tetrachloride-treated rats, which were significantly recovered towards an almost normal level in animals co-administered with MEC. Other biochemical changes induced by carbon tetrachloride too showed reliable signs of retrieving towards the normalcy. Histopathological analysis confirmed the biochemical investigations. This study unravels the anti-hepatotoxic activity of MEC.

Preliminary evaluation of the antihepatotoxic activity of Kamilari, a polyherbal formulation.

Hepatoprotective efficacy of Kamilari, a polyherbal preparation was studied in carbon tetrachloride (CCl4)-induced liver dysfunction in albino rats by determining different biochemical parameters in serum and tissues. In serum, the activities of enzymes like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and the concentrations of protein and bilirubin were evaluated. The concentrations of total lipids, cholesterol, triglycerides (TG) and phospholipids were studied in serum and different tissues. Here, a dose-dependent study was conducted and oral administration of Kamilari at a dose of 750 mg/kg body weight significantly reduced the toxic effects of CCl4. From the observations, the conclusion drawn is that Kamilari stabilized the hepatic frame against the toxicity of CCl4.

Antioxidant effect of Coscinium fenestratum in carbon tetrachloride treated rats.

Antioxidant effect of methanol extract of Coscinium fenestratum stem powder was examined using carbon tetrachloride-intoxicated rat liver as the experimental model. Hepatotoxic rats were treated with the methanol extract for 90 days (daily, orally at the dose of 60 mg/kg body weight). Lipid peroxidation in carbon tetrachloride-administered rats was evidenced by a marked elevation in the levels of thiobarbituric acid reactive substances and diene conjugates, and also a profound diminution in glutathione content in the liver. Rats co-administered with the methanol extract retained an almost normal level of these constituents. The decreased activities of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in carbon tetrachloride-intoxicated rats, and its retrieval towards near-normalcy in the methanol extract co-administered animals revealed the effectiveness of Coscinium fenestratum in combating oxidative stress due to hepatic damage. The findings provide a rationale for further studies on isolation of active principles and its pharmacological evaluation.

Hepatoprotection by Elephantopus scaber Linn. in CCl4-induced liver injury.

The efficacy of the medicinal plant Elephantopus scaber Linn. (Asteraceae), to prevent carbon teterachloride (CCI4)-induced chronic liver dysfunction in the rats was examined by determining different biochemical markers in serum and tissues. In serum, liver function marker enzymes like aspartate aminotrasferase (AST), alanine aminotrasferase (ALT), alkaline phosphatase (ALP) and also protein were evaluated. The concentrations of total lipid, cholesterol and phospholipids were studied in serum and the different tissues. The concentration of serum triglycerides was also studied. The biochemical changes induced by CCI4 in different tissues particularly in the liver tissue improved following treatment with E. scaber Linn. The results suggest the hepatoprotective effect of this medicinal plant.