Probiotics, prebiotics and synbiotics- a review.

The health benefits imparted by probiotics and prebiotics as well as synbiotics have been the subject of extensive research in the past few decades. These food supplements termed as functional foods have been demonstrated to alter, modify and reinstate the pre-existing intestinal flora. They also facilitate smooth functions of the intestinal environment. Most commonly used probiotic strains are: Bifidobacterium, Lactobacilli, S. boulardii, B. coagulans. Prebiotics like FOS, GOS, XOS, Inulin; fructans are the most commonly used fibers which when used together with probiotics are termed synbiotics and are able to improve the viability of the probiotics. Present review focuses on composition and roles of Probiotics, Prebiotics and Synbiotics in human health. Furthermore, additional health benefits like immune-modulation, cancer prevention, inflammatory bowel disease etc. are also discussed. Graphical abstractPictorial summary of health benefits imparted by probiotics, prebiotics and synbiotics.

Hydroalcohol extract of Trigonella foenum-graecum seed attenuates markers of inflammation and oxidative stress while improving exocrine function in diabetic rats.

CONTEXT AND OBJECTIVE: The herb fenugreek, Trigonella foenum-graecum Linn (Fabaceae), seeds have been traditionally used in the treatment of diabetes but its effect on oxidative stress and pro-inflammatory cytokines in the improvement of exocrine function of diabetes has not been studied. The effect of hydroalcoholic extract of Trigonella foenum-graecum seeds (HEF) on alloxan-induced type-II diabetic rat model was investigated. MATERIALS AND METHODS: Effect of HEF (500, 1000, and 2000 mg/kg), glimepiride (4 mg/kg), and combination of HEF (500 mg/kg) + glimepiride (2 mg/kg), on alloxan-induced diabetic rats was evaluated by assaying (blood glucose, serum protein, glycosylated hemoglobin, muscle and liver glycogen, glucose uptake by diaphragm, liver glucose transport, serum pancreatic enzymes (α-amylase, lipase), pro-inflammatory cytokines (TNF-α, IL-6), antioxidant enzymes [glutathione (GSH), superoxide dismutase (SOD)], lipid peroxides (liver and pancreas), and histoarchitecture (liver, pancreas). RESULTS: Treatment with HEF (at different doses), glimepiride, and HEF + glimepiride increased body weight and glucose uptake, reduced plasma glucose, glycosylated hemoglobin, liver glucose transport, pro-inflammatory cytokines, pancreatic enzymes and restored depleted glycogen (muscle, liver) and total protein significantly (p < 0.01) and dose dependently, including prevention of lipid peroxidation and restoration of GSH and SOD (liver and pancreas). Treatment with HEF + glimepiride potentiated hypoglycemic activity of glimepiride. Histoarchitecture of liver and pancreas showed marked improvement. CONCLUSION: Present experimental findings suggest that HEF possesses promising hypoglycemic activity, presumably by amelioration of oxidative stress and pro-inflammatory cytokines. HEF may be useful as an adjuvant with clinically effective antidiabetic drugs in the management of type-II diabetes.

Ameliorative effects of Tricholepis glaberrima in experimentally induced hepatic damage in rats: modulation of cytokines functions.

ETHNOPHARMACOLOGICAL RELEVANCE: Tricholepis glaberrima belonging to family Asteraceae is popularly known as "Brahmadandi" in Indian system of medicine and is claimed to be effective in the treatment of various ailments such as neurological disorders, hepatic disorders, sexual dysfunction, skin disease etc. The present study was undertaken to investigate the possible role of Tricholepis glaberrima in rifampicin and Bacillus Calmette-Guerin/lipopolysaccharides (BCG/LPS) induced hepatotoxicity in rats and its possible mechanism of actions. MATERIALS AND METHODS: Hepatotoxicity was induced in rats by administration of rifampicin for 30 days and in another experiment BCG on day 1 and LPS on day 11. In both the experiments, hepatotoxicity was assessed by alteration of serum marker enzymes (AST, ALT, and LDH), total proteins, MDA and NO formation, cytokines mainly IL-6 and TNF-α and histoarchitecture alterations. The IL-6 and TNF-α level in liver homogenates were determined by ELISA technique. RESULTS: Administration of both rifampicin and BCG-LPS elicited hepatic damage reflected in significantly (p<0.01) increased serum marker enzymes AST, ALT, ALP, GGT, LDH and decreased total proteins, increased MDA and NO formation in liver homogenate. Furthermore, IL-6 and TNF-α increased significantly in both the experimental conditions. Pretreatment with METg and silymarin attenuated significantly (p<0.01) marker enzymes, TP, MDA and NO formation as well as IL-6 and TNF-α production in liver homogenates. Prophylactic treatment with METg exhibits significant improvement in liver damage as compared to therapeutic treatment. CONCLUSION: The hepatoprotective activity of METg may be correlated with the amelioration of oxidative stress due to immunological insult, by improving antioxidant defense ability of hepatocytes and also by reducing the cytokines (TNF-α, IL-6 and NO) production.

Anti-hyperglycemic activity of rutin in streptozotocin-induced diabetic rats: an effect mediated through cytokines, antioxidants and lipid biomarkers.

Administration of rutin (50 and 100 mg/kg) and pioglitazone (10 mg/kg) orally for 3 weeks treatment significantly improved body weight, reduced plasma glucose and glycosylated hemoglobin, pro-inflammatory cytokines (IL-6 and TNF-alpha), restored the depleted liver antioxidant status and serum lipid profile in high fat diet + streptozotocin induced type 2 diabetic rats. Rutin treatment also improved histo-architecture of beta islets and reversed hypertrophy of hepatocytes. Rutin exhibited significant antidiabetic activity, presumably by inhibiting inflammatory cytokines, improving antioxidant and plasma lipid profiles in High fat diet + streptozotocin induced type 2 diabetic model and may be useful as a diabetic modulator along with standard antidiabetic drugs. However, such effects need to be confirmed on human subjects in clinical condition.

Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism(s): a critical discussion.

Liver is a primary organ involved in biotransformation of food and drugs. Hepatic diseases are a major worldwide problem. Hepatic disorders are mainly caused by toxic chemicals (alcohol), xenobiotics (carbon tetrachloride, chlorinated hydrocarbons and gases CO2 and O2) anticancer (azathioprine, doxorubicin, cisplatin), immunosuppressant (cyclosporine), analgesic anti-inflammatory (paracetamol, thioacetamide), anti-tubercular (isoniazid, rifampicin) drugs, biologicals (Bacillus-Calmette-Guerin vaccine), radiations (gamma radiations), heavy metals (cadmium, arsenic), mycotoxin (aflatoxin), galactosamine, lipopolysaccharides, etc. Various risk factors for hepatic injury include concomitant hepatic diseases, age, gender, alcoholism, nutrition and genetic polymorphisms of cytochrome P450 enzymes have also been emphasized. The present review enumerates various in vivo animal models and in vitro methods of hepatic injury using diverse toxicants, their probable metabolic pathways, and numerous biochemical changes viz. serum biomarkers enzymes, liver function, oxidative stress associated events like free radicals formation, lipid peroxidation, enzyme antioxidants and participation of cytokines (tumour necrosis factor-α, transforming growth factor-ß, tumour necrosis factor-related apoptosis inducing ligand), and other biomolecules (Fas and C-jun N-terminal kinase) are also discussed. The underlying cellular, molecular, immunological, and biochemical mechanism(s) of action responsible for liver damage (toxicity) are also been discussed. This review should be immensely useful for researchers especially for phytochemists, pharmacologists and toxicologists working on hepatotoxicity, hepatotoxic chemicals and drugs, hepatoprotective agents and drug research organizations involved especially in phytopharmaceuticals and other natural products.

Evaluation of anti-allergic and anti-anaphylactic activity of ethanolic extract of Zizyphus jujuba fruits in rodents

The present study reports the anti-allergic activity of ethanolic extract of Zizyphus jujuba Mill., Rhamnaceae, and its possible mode of action. The effect of extract of Z. jujuba at different doses (250, 500 and 1000 mg/kg, orally) was simulated on studied animal models of asthma and allergy: a) milk induced eosinophilia and leukocytosis; b) compound 48/80 induced mast cell degranulation; and, c) active and passive cutaneous anaphylaxis. In addition, extract of Z. jujuba's effect on sensitized guinea pig ileum (ex vivo) and tracheal chain preparations (in vitro) were investigated.Treatment with extract of Z. jujuba at all doses significantly: prevented the milk-induced eosinophilia and compound 48/80 induced degranulation of mesenteric mast cells; decreased passive cutaneous and active anaphylactic reactions. In addition, extract of Z. jujuba inhibited acetylcholine as well as histamine induced tracheal chain contraction, and also antigen induced contraction of sensitized guinea pig ileum (Shultz-Dale inhibition test). Furthermore, it exhibited also free radicals scavenging activity (in vitro). The observed anti-allergic and anti-anaphylactic activity of extract of Z. jujuba may be largely through the stabilization of mast cells by the membrane presence of phytoconstituents (steroidal saponins and flavonoids).

Liposomes as potential carrier system for targeted delivery of polyene antibiotics.

The development of new therapeutic modalities involves the use of drug carrier, such as liposomes, which can modify pharmacokinetic and bio-distribution of drug profile. Polyene antibiotics incorporation into liposomes improves its availability at the site, bio-distribution and therapeutic index mainly through the engulfment of liposomes by circulating monocytes/macrophages and transportation to the site of infection. Polyene antibiotics (AmB, SJA-95, HA-1-92) and other antibiotics (streptomycin, tobramycin, quinolones, anti-tubercular and anti-cancer drugs), liposomal preparations are described with possible advantages from therapeutic efficacy and toxicity point of view. The polyene macrolide antibiotics liposomal preparations proved to be more effective in the treatment of systemic mycosis. The AmB-cyclodextrin derivatives inclusion complex is a major breakthrough in liposomal preparation which can be converted into aqueous phase of liposome. Liposomal drug incorporated preparation has been one of the important areas of research for developing the existing polyene antibiotics into useful chemotherapeutic agents in clinical medicine. In recent past other antibiotics have also been incorporated into liposomes using wide variety of materials, phosphatidylethanolamine derivatives (pegylated liposomes, enzyme sensitive conjugates, fluidosomes of anti-cancer drugs and poly lactic/glycolic acid microspheres for anti-tuberculosis drugs). In addition, attempts were also made to extend the receptor mediated drug targeting and to review some relevant patents.

Amelioration of cognitive, motor and endogenous defense functions with silymarin, piracetam and protocatechuic acid in the cerebral global ischemic rat model.

AIMS: The neuroprotective activities of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) on cerebral global ischemic/reperfusion were evaluated in a rat model. MAIN METHODS: A midline ventral incision was made in the throat region. The right and left common carotid arteries were located and a bilateral common carotid artery occlusion (BCCAO) was performed for 30min using atraumatic clamps followed by a 24h period of reperfusion. Neurological/behavioral functions (cognitive and motor), endogenous defense systems (lipid peroxidation, glutathione, catalase, and superoxide dismutase), reduced water content and infarct size and histopathological alterations were then studied. KEY FINDINGS: Silymarin and PCA treatments significantly improved cognitive, motor and endogenous defense functions, histopathological alterations, and, reduced both water content and infarct size compared to the vehicle-treated ischemic control group. Piracetam treatment improved neurological and histopathological alterations, reduced water content and infarct size, but failed to restore/prevent the impaired endogenous defense functions significantly. SIGNIFICANCE: Silymarin showed better neuroprotection than piracetam and PCA in experimentally induced global ischemic/reperfusion and was able to facilitate mnemonic performance.

Anti-diabetic activity of embelin: involvement of cellular inflammatory mediators, oxidative stress and other biomarkers.

Embelin (benzoquinone), an active constituent of methanolic extracts of the fruit of Embelia basal (Myrsinaceae), was studied in high fat diet (HFD)+streptozotocin (STZ) diabetic rats. Treatment of embelin (25 and 50 mg/kg/day, p.o.) for 3 weeks to HFD+STZ diabetic rats elicited insignificant increase in body weight, reduced the elevated plasma glucose, glycosylated haemoglobin and pro-inflammatory mediators (interleukin 6 and tumour necrosis factor α) significantly. Furthermore, embelin treatment at both the doses significantly decreased the elevated malondialdehyde, restored depleted glutathione, antioxidant enzymes, superoxide dismutase and catalase in liver. The increased lipid profiles in HFD+STZ diabetic rats were also reduced by embelin treatment significantly. Embelin treatment to HFD+STZ diabetic rats also improved the altered histoarchitecture of ß-islets of pancreas and hepatocytes. The embelin effect on progression of type 2 diabetes mellitus in rats appears to be through the inhibition of intracellular pro-inflammatory mediators, lowering of lipid profile and amelioration of oxidative stress. Considering the pharmacological activity profile of embelin, it is suggested that embelin be a useful diabetic modulator or adjuvant along with clinically effective anti-diabetic drugs in the treatment of type 2 diabetes mellitus and needs to be clinically evaluated on human subjects.

Silymarin improves the behavioural, biochemical and histoarchitecture alterations in focal ischemic rats: a comparative evaluation with piracetam and protocatachuic acid.

Comparative neuroprotective potential of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) was evaluated in focal ischemic rats. Various pharmacological, biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite content, brain water content) and behavioural (memory impairment, motor control, neurological score) including infarct size and histopathological alterations were evaluated. Silymarin (200mg/kg) and PCA treatment significantly improved behavioural, biochemical and histopathological changes, and reduced water content and infarct size. However, piracetam only improved behavioural and histopathological changes, reduced water content and infarct size. The findings indicate that silymarin exhibits neuroprotective activity better than PCA and piracetam in focal ischemia/reperfusion reflected by its better restoration of behavioural and antioxidant profile.

Anti-inflammatory and analgesic activity of protocatechuic acid in rats and mice.

Anti-inflammatory and analgesic activity of protocatechuic acid (PCA), a natural product, was evaluated in different rat models (viz., carrageenan-induced paw oedema, cotton pellet-induced granuloma and Freund's adjuvant arthritis) of inflammation and chemical and heat induced mouse models of pain. Treatment with PCA inhibited significantly different biological parameters like hind paw oedema, granuloma exudates formation and arthritis index in carrageenan oedema, cotton pellet granuloma and Freund's adjuvant arthritis, respectively. The biochemical changes viz., glutathione, superoxide dismutase, catalase, lipid peroxidation and NO in oedematous or in liver tissues and serum alanine aminotransferase and lactic dehydrogenase occurred during different types of inflammation were either significantly restored or inhibited with PCA pretreatment. Present experimental findings demonstrate promising anti-inflammatory and analgesic activity of PCA which is comparable with that of standard drugs used.

Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: evidence of its antioxidant property.

The present study investigates the protective effects of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity using various animal models with biochemical parameters like serum marker enzymes and antioxidants in target tissues. In addition, liver and cardiac histoarchitecture changes were also studied. Curcumin treatment inhibited carrageenin and albumin induced edema, cotton pellet granuloma formation. The increased relative weight of liver and heart in CCl(4) induced liver injury and isoproterenol induced cardiac necrosis were also reduced by curcumin treatment. Elevated serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) increased lipid peroxidation, decreased gluthione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in edematous, granulomatus, liver and heart tissues during inflammation, liver injury and cardiac necrosis, respectively. Curcumin treatment reversed all these above mentioned biochemical changes significantly in all animal models studied. Even histoarchitecture alterations observed in liver injury and cardiac necrosis observed were partially reversed (improved) by curcumin treatments. In in vitro experiments too curcumin inhibited iron catalyzed lipid peroxidation in liver homogenates, scavenged nitric oxide spontaneously generated from nitroprusside and inhibited heat induced hemolysis of rat erythrocytes. The present in vitro and in vivo experimental findings suggest the protective effect of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity in rats.

Stem bark extraction of Ficus bengalensis Linn for anti-inflammatory and analgesic activity in animal models.

In the present study, anti-inflammatory and analgesic effect of aqueous extract of Ficus bengalensis (AEFB) and methanolic extract of F. bengalensis (MEFB) was evaluated in animal models. Preliminary results indicated that MEFB treatment possesses significant anti-inflammatory potential as compared to AEFB. The anti-inflammatory activity of MEFB exhibited in both acute (carrageenan induced hind paw edema and acetic acid induced vascular permeability) and subchronic (cotton pellet-induced granuloma) models of inflammation was found to be significant. In addition, the extract also showed significant analgesic activity in acetic acid induced writhing. Pretreatment with MEFB during inflammatory condition (both acute and sub-chronic) prevented increase in malondialdehyde (MDA) formation and myeloperoxidase activity in edematous as well as granulomatous tissue. Further, serum marker enzymes (AST, ALT and ALP) increased in inflammatory conditions were also inhibited with MEFB treatment. Hence, the anti-inflammatory activity observed in the present study with MEFB could be attributed largely to its antioxidant and lysosomal membrane stabilizing effects.