Linagliptin attenuates thioacetamide-induced hepatic encephalopathy in rats: Modulation of C/EBP-ß and CX3CL1/Fractalkine, neuro-inflammation, oxidative stress and behavioral defects.

The degree of neuroinflammation is correlated mainly with cognitive and motor dysfunctions associated with hepatic encephalopathy (HE). The current study was conducted to explore the possible protective potential of the antidiabetic drug; linagliptin (LNG; 10 or 20 mg/kg) against HE induced by thioacetamide (TAA) in rats. Animals received two consecutive intraperitoneal injections of TAA (200 mg/kg) on alternate days. Neurobehavioral tests were performed 24 h after the last injection, and rats were sacrificed 24 h later (48 h). The higher LNG dose more effectively protected against TAA-induced changes. Administration of LNG for 15 days before TAA notably mitigated TAA-induced acute liver injury and HE, as verified by the marked improvement in motor coordination, locomotor activity, and cognition function. LNG maintained both brain and liver weight indices and retracted the hyperammonemia with a prominent suppression in liver transaminases. This was accompanied by an evident modulation of hepatic and hippocampal oxidative stress markers; GSH and MDA. LNG attenuated both liver and hippocampal pro-inflammatory cytokine; IL-1ß while augmented the anti-inflammatory one; IL-10. It noticeably reduced hepatic and hippocampal COX-2 and TNF-α and maintained hepatic and brain architectures. It also induced a marked decrease in the inflammation-regulated transcription factor, C/EBP-ß, with a profound increase in hippocampi's anti-inflammatory chemokine, CX3CL1/Fractalkine. LNG modulated TAA-induced disturbances in hippocampal amino acids; glutamate, and GABA with a significant increase in hippocampal BDNF. In conclusion, the regulatory effect of LNG on neuroinflammatory signaling underlines its neuroprotective effect against progressive encephalopathy accompanying acute liver injury.

Combination of pomegranate extract and curcumin ameliorates thioacetamide-induced liver fibrosis in rats: impact on TGF-ß/Smad3 and NF-κB signaling pathways.

Protection against liver injury and its consequences is considered an essential issue to minimize the number of annual deaths caused by liver diseases. The present study was designed to evaluate the potential role of pomegranate extract (PE) and/or curcumin in the regression of thioacetamide (TAA)-induced liver fibrosis, focusing on their modulatory effects on Nrf2/HO-1, NF-κB, and TGF-ß/Smad3 signaling pathways. Liver fibrosis was induced in male Wistar rats by intraperitoneal injection of TAA (100 mg/kg) three times a week, for 8 weeks. To assess the protective effects of PE and/or curcumin against TAA-induced liver fibrosis, rats were treated on a daily basis with oral doses of PE (200 mg/kg) and/or curcumin (200 mg/kg) for 8 weeks. The results indicated that PE and/or curcumin attenuated TAA-induced liver fibrogenesis, as evidenced by a significant improvement in the liver function tests (AST, ALT, ALP, and albumin), oxidative stress biomarkers (MDA, SOD, and GSH), and inflammatory biomarkers (NF-ĸB, TNF-α, IL-1ß, iNOS, TGF-ß, and MPO), compared to TAA group. Moreover, treatment with PE and/or curcumin exerted a significant upregulation of Nrf2/HO-1 gene expressions along with significant downregulation of NF-ĸB, TGF-ß, and phospho-Smad3 protein expressions, as well as α-SMA and collagen-1 gene expressions. The histopathological examination has corroborated these findings. In conclusion, hepatoprotective activities of PE and/or curcumin could be linked to their abilities to modulate Nrf2/HO-1, NF-κB, and TGF-ß/Smad3 signaling pathways. It is worth noting that the combination of PE and curcumin exerted superior hepatoprotective effects against TAA-induced liver fibrosis, as compared to monotherapy.

Saroglitazar Deactivates the Hepatic LPS/TLR4 Signaling Pathway and Ameliorates Adipocyte Dysfunction in Rats with High-Fat Emulsion/LPS Model-Induced Non-alcoholic Steatohepatitis.

The most epidemic liver disorder non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis and inflammation with hepatocellular damage. Recently, it is predictable to be the extensive cause for liver transplantation. The absence of an approved therapeutic agent for NASH is the reason for investigating saroglitazar (SAR) which showed promising effects as a dual PPAR-α/γ agonist in recent studies on NASH. Here, we aimed to investigate the effect of SAR on NASH induced in rats by the administration of high-fat emulsion (HFE) and small doses of lipopolysaccharides (LPS) for 5 weeks. Rats were divided into three groups: negative control group (saline and standard rodent chow), model group (HFE(10 ml/kg/day, oral gavage) + LPS(0.5 mg/kg/week, i.p)), and SAR-treated group (HFE(10 ml/kg/day, oral gavage) + LPS(0.5 mg/kg/week, i.p.) + SAR(4 mg/kg/day, oral gavage) starting at week 3.Treatment with SAR successfully ameliorated the damaging effects of HFE with LPS, by counteracting body weight gain and biochemically by normalization of liver function parameters activity, glucose, insulin, homeostasis model of assessment (HOMA-IR) score, lipid profile levels, and histopathological examination. Significant changes in adipokine levels were perceived, resulting in a significant decline in serum leptin and tumor necrosis factor-α (TNF-α) level concurrent with adiponectin normalization. The positive effects observed for SAR on NASH are due to the downregulation of the LPS/TLR4 pathway, as indicated by the suppression of hepatic Toll-like receptor 4 (TLR4), NF-κB, TNF-α, and transforming growth factor-ß1 (TGF-ß1) expression. In conclusion, this work verified that SAR ameliorates NASH through deactivation of the hepatic LPS/TLR4 pathway and inhibition of adipocyte dysfunction.

Grape Seed Extract Alone or Combined with Atropine in Treatment of Malathion Induced Neuro- and Genotoxicity.

The aim of this study was to investigate the effect of treatment with grape seed extract (GSE) on the neurotoxic and genotoxic effects of acute malathion exposure. Rats received malathion (150 mg/kg by i.p. injection) for two successive days alone or combined with GSE at doses of 150 or 300 mg/kg, orally or with GSE at 300 mg/kg and atropine at a dose of 2 mg/kg, i.p. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase (PON1) were determined in cortex, striatum, and rest of brain tissue (subcortex). Interleukin-1ß (IL-1ß), and butyrylcholinesterase (BChE) activities were determined in brain regions. Cytogenetic analyses for chromosomal aberrations in somatic and germ cells, micronucleus test, Comet assay, DNA fragmentation of liver cells and histopathological examination of brain and liver sections were also performed. Malathion resulted in an increase in MDA, nitric oxide; a decrease in GSH and PON1 activity in different brain regions. IL-1ß increased, while BChE activity decreased in brain after the administration of malathion. The insecticide also caused marked structural and numerical chromosomal aberrations and increased liver DNA fragmentation. The Comet assay showed a significant increase in DNA damage of peripheral blood lymphocytes. These effects of malathion were alleviated with the administration of GSE alone or combined with atropine. Addition of atropine to treatment with GSE was associated with significant decrease in MDA, BChE and chromosomal aberrations compared with GSE only treatment. Our data indicate that GSE protects against malathion neurotoxic and genotoxic effects, most likely through reducing brain oxidative stress and inflammatory response.

Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A.

Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects. Docosahexaenoic acid (DHA) is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 µM. Dose-dependent treatments with 10-100 µM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%-98.8%. Similarly, dose-dependent treatments with 10-20 µM AST reversed the PA toxicity at its IC50 dose and raised these cells' survival to 61.7%-70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU), aspartate (ASP), and gamma amino butyric acid (GABA), with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels were abnormal, Nitric Oxide (NO) and Malondialdehyde (MDA) levels were significantly increased, and total antioxidant capacity (TAC) level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST treatments effectively counteracted the toxic effects of PA and normalized most biochemical parameters in rats. DHA and AST can be useful food additives to prevent and reverse PA food-induced toxicity.

Phenolic contents and bioactivities of pericarp and seeds of Pleiogynium solandri (Benth.) Engl. (Anacardiaceae).

OBJECTIVES: This study aimed to develop drugs from natural sources to overcome the side effects of many of synthetic drugs. Methanol extracts of both pericarp and seeds of Pleiogynium solandri were used to investigate antioxidant, hepatoprotective, and renal function protective, analgesic, and anti-inflammatory effects and to determine the chemical composition of the extract responsible for bioactivity. MATERIALS AND METHODS: Methanol (70%) extracts of the seeds and pericarps of P. solandri were prepared. Hot plate method was used to test analgesic activity, carrageenan-induced paw inflammation method was used to test anti-inflammatory activity, and colorimetric methods were used to test antioxidant, hepatoprotective (by determination of serum alanine and aspartate aminotransferase activities), and renal function protective effects (by measuring uric acid and creatinine levels). Chromatographic methods and means of (1)H-NMR, (13)C -NMR, and UV spectra were used for isolation and identification of the responsible compounds. RESULTS: In this study for the first time, four phenolic compounds were isolated from the pericarp of P. solandri which were identified as catechin, quercetin, quercetrin and rutin. Methanolic extract of both seeds and pericarp of P. solandri showed strong antioxidant effect, hepatoprotective, renal function protective, analgesic, and anti-inflammatory effects. However, seed extract had lower effect than pericarp in a dose dependent manner. CONCLUSION: This study showed that methanol extract of pericarp of P. solandri is more powerful than that of the seed regarding its antioxidant, hepato-protective; renal function protective, analgesic, and anti-inflammatory effects. The phenolic compounds isolated from the methanol extract of pericarp were responsible for bioactivity.

Therapeutic effect of Acacia nilotica pods extract on streptozotocin induced diabetic nephropathy in rat.

The aim of the present study was to examine the effect of aqueous methanol extract (150 and 300 mg/kg body weight) of Acacia nilotica pods in streptozotocin-induced diabetic rats for 60 days, and its biochemical, histopathological and histochemical study in the kidney tissues. Diabetic rats exhibited hyperglycemia, elevated of serum urea and creatinine. Significant increase in lipid peroxidation (LPO), superoxide dismutase (SOD) and reduced glutathione (GSH) was observed in diabetic kidney. Histopathological examination revealed infiltration of the lymphocytes in the interstitial spaces, glomerular hypertrophy, basement membrane thickening and tubular necrosis with loss of their brush border in some of the proximal convoluted tubules in diabetic rats. Acacia nilotica extract lowered blood glucose levels, restored serum urea and creatinine. In addition, Acacia nilotica extract attenuated the adverse effect of diabetes on LPO, SOD and GSH activity. Treatment with Acacia nilotica was found to almost restore the normal histopathological architecture of kidney of streptozotocin-induced diabetic rats. However, glomerular size and damaged area showed ameliorative effect after treatment with the extract. In conclusion, the antioxidant and antihyperglycemic properties of Acacia nilotica extract may offer a potential therapeutic source for the treatment of diabetes.

Chitosan induced hepato-nephrotoxicity in mice with special reference to gender effect in glycolytic enzymes activities.

Chitosan is an antilipidemic dietary supplement used as a diet aide. The present study investigated the effect of sex-toxicity relationship between male and female mice orally given two dose levels (150 and 300 mg/kg) for 35 days. Chitosan treatment caused significant elevation in transaminases (ALT, AST) and alkaline phosphatase (ALP) in liver and in serum urea and creatinine in dose dependent manner; no sex differences between-treated groups. Lipid profile parameters significantly decreased and significant increase in glycolytic enzymes activities in all treatment groups. Female mice treated with chitosan (300 mg/kg) had significant reduction in lipid profile parameters than the same dose of male group. Phosphofructokinase (PFK) and lactate dehydrogenase (LDH) activities significantly enhanced without sex differences, while glucose phosphate isomerase (GPI) and hexokinase (HK) significantly elevated in the higher dose of females than male. Histopathological study of liver and kidney tissues showed moderate to severe histopathological changes depend on the dose and gender difference. Image analysis resulted significant depletion in glycogen and protein contents especially in female more than male. These results indicated that female mice were more susceptible to the toxic effect of chitosan than males when administered with the higher dose for a long period.

Mushroom insoluble polysaccharides prevent carbon tetrachloride-induced hepatotoxicity in rat.

UNLABELLED: The aim of the present study was to investigate the effect of mushroom insoluble non-starch polysaccharides (MINSP) on the carbon tetrachloride (CCl(4))-induced hepatic damage in rat. MINSP (100 and 200 mg/kg) administered daily orally for 15 days before CCl(4) (1.5 ml/kg). The effect of MINSP treatment was also examined in normal rats. Normal groups treated with MINSP showed significant decrease in serum activities of the liver enzymes, lipid peroxides and nitric oxide (NO) in the liver. Reduced glutathione (GSH) and total proteins (TP) contents in liver homogenate also increased after treatment with only MINSP for 15 days. In CCl(4)-treated rats, significant elevation in serum liver enzymes, increased lipid peroxides and NO in the liver, and depletion of hepatic-GSH level were observed. Pre-treatment with MINSP significantly ameliorated the tested parameters when compared with CCl(4)-treated group. It improved the antioxidant activity of the liver in a dose-dependent manner. Histopathological examination of hepatic tissue revealed that MINSP administration alone protected hepatocytes from the damage induced by CCl(4). CONCLUSION: MINSP are safe; it could be used as fat replacer in processing low fat diet. MINSP represents a good functional food and liver supporter for patient suffering from various liver diseases.

Synthesis, anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives.

The action of the coumarin-type drugs and related compounds is reviewed to their VKOR antagonistic effects. In our study, twenty 3-pyridinyl, pyrimidinyl and pyrazolyl-4-hydroxycoumarin derivatives were synthesized. A comparative in vivo (CT, PT determination) and in vitro (measurement of PIVKA-II levels) anticoagulant study with respect to warfarin showed that the synthesized compounds have different anticoagulant activities, the most prospective compounds were the 3-pyrazolyl-4-hydroxycoumarin derivatives.

Immunological studies on Amaranth, Sunset Yellow and Curcumin as food colouring agents in albino rats.

The use of food dyes is at least controversial because they are only of essential role. Moreover many of them have been related to health problems mainly in children that are considered a very vulnerable group. This study was carried out to investigate the effect of oral administration of Amaranth, Sunset Yellow and Curcumin for 4 weeks at doses of 47, 315 and 157.5 mg/kg b. wt. and after 2 weeks all animals were immunostimulated by intra peritoneal injection of sheep RBCs 10% (1 ml/rat). Body weight, relative body weight, total and differential leukocytes count, mononuclear cell count, delayed hypersensitivity, total protein and serum fractions were determined. Results revealed that oral administration of Amaranth, Sunset Yellow and Curcumin did not affect the body weight gain or the spleen weight. On the other hand Sunset Yellow and Curcumin significantly decreased the weight of thymus gland of the rats. Total leukocyte count were not affected while Amaranth and Curcumin-treated rats revealed a significant decrease in neutrophiles and monocytes and a compensatory increase in lymphocytes. Moreover, oral administration of Sunset Yellow revealed a significant decrease in monocyte percent. Amaranth, Sunset Yellow and Curcumin significantly decreased the delayed hyper sensitivity. Total serum protein, albumin, total globulin and albumin/globulin (A/G) ratio were not affected by administration of the colouring agents. Oral administration of Amaranth increases the density of albumin band. On the other hand oral administration of Curcumin decreases the density of the albumin band. Oral administration of any of the tested colouring agents did not change the density of globulin region as compared to control group. In conclusion we found that both synthetic (Amaranth and Sunset Yellow) and natural (Curcumin) colouring agents used at doses up to 10 times the acceptable daily intake exerted a depressing effect on the cellular but not humoral immune response.

Effect of spironolactone on pain responses in mice.

The effects of spironolactone, a non-selective aldosterone antagonist, were examined on thermally-induced pain using the hot-plate and tail-flick tests, on chemogenic pain induced by intraplantar capsaicin, on electrically-induced pain, on visceral nociception induced by intraperitoneal acetic acid injection and on haloperidol-induced catalepsy in mice. Spironolactone significantly shortened response latency in the mouse tail-flick test but produced modest decreases in response latencies in the mouse hot plate test. The drug reduced the antinociceptive effect of tramadol in the hot plate test. Spironolactone in addition decreased nociceptive thresholds of electrically-induced pain in mice. In contrast, spironolactone elicited significant antinociceptive actions in the mouse acetic-acid-induced writhing assay and at doses of 20-160 mg/kg decreased capsaicin-induced chemogenic pain. Spironolactone at doses of 40 or 80 mg/kg reduced spontaneous activity and produced a significant impairment on the rotarod test in mice. The drug (10-80 mg/kg) increased the duration of catalepsy induced by haloperidol by 56.3-188.5 %. In conclusion, spironolactone increased pain behavior in a dose-dependent manner in models of thermal and electrical pain, but decreased inflammatory visceral pain due to intraperitoneal acetic acid and chemogenic pain due to intraplantar capsaicin. The effect of spironolactone on various types of pain needs further evaluation.

Reverse Na(+)/Ca(2+)-exchange mediated Ca(2+)-entry and noradrenaline release in Na(+)-loaded peripheral sympathetic nerves.

[(3)H]noradrenaline ([(3)H]NA) released from sympathetic nerves in the isolated main pulmonary artery of the rabbit was measured in response to field stimulation (2Hz, 1ms, 60V for 3min) in the presence of uptake blockers (cocaine, 3 x10(-5)M and corticosterone, 5 x10(-5)M). The [(3)H]NA-release was fully blocked by the combined application of the selective and irreversible 'N-type' voltage-sensitive Ca(2+)-channel (VSCC)-blocker omega-conotoxin (omega-CgTx) GVIA (10(-8)M) and the 'non-selective' VSCC-blocker aminoglycoside antibiotic neomycin (3x10(-3)M). Na(+)-loading (Na(+)-pump inhibition by K(+)-free perfusion) was required to elicit further NA-release after blockade of VSCCs (omega-CgTx GVIA+neomycin). In K(+)-free solution, in the absence of functioning VSCCs (omega-CgTx GVIA+neomycin), the fast Na(+)-channel activator veratridine (10(-5)M) further potentiated the nerve-evoked release of [(3)H]NA. This NA-release was significantly inhibited by KB-R7943, and fully blocked by Ca(o)(2+)-removal. However, Li(+)-substitution was surprisingly ineffective. The non-selective K(+)-channel blocker 4-aminopyridine (4-AP, 10(-4)M) also further potentiated the nerve-evoked release of NA in K(+)-free solution. This potentiated release was concentration-dependently inhibited by KB-R7943, significantly inhibited by Li(+)-substitution and abolished by Ca(o)(2+)-removal. It is concluded that in Na(+)-loaded sympathetic nerves, in which the VSCCs are blocked, the reverse Na(+)/Ca(2+)-exchange-mediated Ca(2+)-entry is responsible for transmitter release on nerve-stimulation. Theoretically we suppose that the fast Na(+)-channel and the exchanger proteins are close to the vesicle docking sites.

Zizyphus spina-christi extract protects against aflatoxin B1-initiated hepatic carcinogenicity.

Aflatoxins (AF), a group of closely related, extremely toxic mycotoxins, produced by Aspergillus flavus and A. parasiticus can occur as natural contaminants of foods and feeds. Aflatoxins have been shown to be hepatotoxic, carcinogenic, mutagenic, and teratogenic to different animal species. Zizyphus spina-christi L. extract was investigated for its antifungal and antimicrobial activities. The aim of the present work was to evaluate the antioxidant activity of the methanol extract of Z. spina-christi L. leaves against the oxidative stress of aflatoxin in rats. Fourty male Sprague-Dawley male rats were divided into four groups including the control group, the group fed aflatoxin-contaminated diet (3 mg/kg diet) and the groups treated with Zizyphus extract (5 mg/kg b.w) alone or in combination with AF for 15 days. Biochemical analysis revealed that treatment with AF resulted in a significant increase in ALT, AST, cholesterol, triglycerides, uric acid, TNFa, LPO, NO and CEA, whereas it decrease significantly GPX and SOD. The histopathological examination of the liver, kidney and testis showed sever histological changes typical to those reported for aflatoxicosis. Animals treated with Zizyphus extract alone or plus AF showed a significant improvement in all biochemical parameters and histological picture of liver, kidney and testis. It could be concluded that Zizyphus extract have a power protective role against aflatoxicosis.

Presynaptic alpha2-receptors regulate reverse Na+/Ca2+-exchange and transmitter release in Na+-loaded peripheral sympathetic nerves.

Electrical depolarisation-(2 Hz, 1 ms)-induced [3H]noradrenaline ([3H]NA) release has been measured from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3 x 10(-5) M; corticosterone, 5 x 10(-5) M). Substitution of most of the external Na+ by Li+ (113 mM; [Na+]0: 25 mM) slightly potentiated the axonal stimulation-evoked release of [3H]NA in a tetrodotoxin (TTX, 10(-7) M) sensitive manner. The reverse Na+/Ca2+-exchange inhibitor KB-R7943 (3 x 10(-5) M) failed to inhibit the stimulation-evoked release of [3H]NA, but increased the resting outflow of neurotransmitter. The 'N-type' voltage-sensitive Ca2+-channel (VSCC) blocker omega-conotoxin (omega-CgTx) GVIA (10(-8) M) significantly and irreversibly inhibited the release of [3H]NA on stimulation (approximately 60-70%). The 'residual release' of NA was abolished either by TTX or by reducing external Ca2+ from 2.5 to 0.25 mM. The 'residual release' of NA was also blocked by the non-selective VSCC-blocker neomycin (3 x 10(-3) M). Correlation was obtained between the extent of VSCC-inhibition and the transmitter release-enhancing effect of presynaptic alpha2-receptor blocker yohimbine (3 x 10(-7) M). When the release of [3H]NA was blocked by omega-CgTx GVIA plus neomycin, yohimbine was ineffective. Inhibition of the Na+-pump by removal of K+ from the external medium increased both the resting and the axonal stimulation-evoked release of [3H]NA in the absence of functioning VSCCs (i.e., in the presence of neomycin and after omega-CgTx treatment). Under these conditions the stimulation-evoked release of NA was abolished either by TTX or by external Ca2+-removal (+1 mM EGTA). Similarly, external Li+ (113 mM) or the reverse Na+/Ca2+ exchange blocker KB-R7943 (3 x 10(-5) M) significantly inhibited the stimulation-induced transmitter release in 'K+-free' solution. KB-R7943 decreased the resting outflow of NA as well. Under conditions in which the Na+-pump was inhibited in the absence of functioning VSCCs, yohimbine (3 x 10(-7) M) further enhanced the release of neurotransmitter, while l-noradrenaline (l-NA, 10(-6) M), an agonist of presynaptic alpha2-receptors, inhibited it. The yohimbine-induced enhancement of NA-release was abolished by Li+-substitution and significantly inhibited by KB-R7943 application. It is concluded that after blockade of VSCCs brief depolarising pulses may reverse Na+/Ca2+-exchange and release neurotransmitter in Na+-loaded sympathetic nerves. Further, similar to that of VSCCs, the reverse Na+/Ca2+-exchange may also be regulated by presynaptic alpha2-receptors.

The effect of ginseng on bile-pancreatic secretion in the rat. Increase in proteins and inhibition of total lipids and cholesterol secretion.

Ginseng is one of the most popular herbal remedies. Studies were performed in anaesthetized rats to examine the effect of ginseng on bile secretion. Male Sprague-Dawley rats were anaesthetized with intraperitoneal (i.p.) urethane (1.25 g kg(-1)) and equipped with biliary cannulas inserted into the bile duct through the sphincter of Oddi. Rats were treated with a single i.p. injection of ginseng at 25, 50 or 100 mg kg(-1) (1 ml(-1)) 30 min before bile collection; the control group received i.p. saline only at 1 ml(-1)volume. The effect of multiple doses of ginseng on bile volume and biliary composition was also studied. Ginseng was given in the higher dose of 100 mg kg(-1) (1 ml(-1), i.p.) every 12 hours for 2 days. Bile was collected in 15 min fractions for 90 min. Bile flow (bile-pancreatic juice), biliary excretion of total proteins, cholesterol and total lipids were measured. The single administration of different doses (25, 50 and 100 mg kg (-1)) of ginseng reduced basal bile secretion in a dose-dependent manner. Single-dose administration of ginseng at 100 mg kg(-1) caused 32.9% reduction in basal bile flow. Meanwhile, mean basal bile flow was reduced by 15.1% in rats treated with multiple doses of ginseng at 100 mg kg(-1) for two days. Biliary protein concentrations were significantly increased after single- or multiple-dose administration of ginseng, but protein output was only significantly increased (33%) in rats treated with ginseng (100 mg kg(-1)) twice a day for 2 days. Biliary total lipids and cholesterol concentration and outputs were significantly reduced after single or multiple administration of ginseng. In conclusion, administration of ginseng in the rat resulted in a reduction of bile flow and in bile secretion of total lipids and cholesterol, while it increased the secretion of proteins in a dose-dependent manner. The precise mechanisms underlying these effects remain to be elucidated. The findings indicate the need for clinical trials for the effect of this herb on bile composition and flow in man in view of a possible modulatory effect for the herb on gallstone formation.