Phytochemical profiling of polyphenols and thyroid stimulatory activity of Ficus religiosa leaf extract in 6-propyl-thiouracil-induced hypothyroid rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant, Ficus religiosa (L.) from the family Moraceae, has been extensively used in Ayurveda and Unani. Traditionally this plant is known for the treatment of constipation, liver diseases and neurological disorders that are related to hypothyroidism. AIM OF THE STUDY: This study was primarily designed to evaluate the effect of Ficus religiosa leaf (FL) extract in ameliorating hypothyroidism in rats and to identify the major bioactive compounds in the test extract that might be responsible for the thyroid-altering activity. In addition, the probable mechanism underlying the thyroid regulation of the main FL constituents were analyzed by molecular docking. MATERIALS AND METHODS: Adult female Wistar rats were used. LC-ESI-MS/MS was performed to identify the compounds present in the extract. HPLC analysis of FL extract was also performed. A pilot study was made using 3 doses of FL extract. Out of 50, 100, and 200 mg/kg, 100 mg/kg appeared to be the most effective one as it could increase thyroid hormones and decreased TSH levels. In the final experiment, propyl-thiouracil (PTU)-induced hypothyroid rats were orally treated with FL extract (100 mg/kg) or L-thyroxine (100 µg/kg, i.p.) daily for 28 consecutive days. On 29th day, all rats were sacrificed and the serum levels of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and hepatic 5' deiodinase-1(5'D1) were estimated by ELISA. Liver marker enzymes (alanine aminotransferase, ALT and aspartate aminotransferase, AST); total cholesterol (TC) and triglycerides (TG); hepatic lipid peroxidation (LPO) and the activities of antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) content were estimated in liver tissues. RESULTS: LC-MS-MS analyses of the leaf extract identified 11 compounds including the three major compounds, betulinic acid (BA), chlorogenic acid (CGA), and quinic acid (QA). While the PTU treatment decreased the levels of thyroid hormones and 5'D1 activity, it increased the TSH, ALT, AST, TNF-α, IL-6, TC, and TG levels. Furthermore, hepatic LPO significantly increased with a decrease in reduced GSH, SOD, CAT, and GPx. However, FL treatment in PTU-induced animals nearly reversed these adverse effects and improved liver function by decreasing ALT, AST, hepatic LPO and increasing the levels of antioxidants. FL not only improved the liver histology, but also suppressed the inflammatory cytokines, TNF-α and IL-6 in PTU-induced animals. A molecular docking study towards the understanding of the thyroid stimulatory mechanism of action revealed that BA, CGA, and QA might have augmented thyroid hormones by interacting with the thyroid hormone receptor (TRß1) and TSH receptor (TSHR). CONCLUSION: For the first time, we report the pro-thyroidal potential of Ficus religiosa leaf extract. We postulate that its main bioactive compounds, BA, CGA, and QA involved in this action may serve as novel thyroid agonists in ameliorating hypothyroidism.

Co-administration of Pterocarpus marsupium Extract and Glibenclamide Exhibits Better Effects in Regulating Hyperglycemia and Associated Changes in Alloxan-induced Diabetic Mice.

BACKGROUND: Diabetes mellitus (DM) is a well-known global metabolic disorder. For its treatment, glibenclamide (GLB) is very often prescribed. However, herbal drugs are considered effective and better alternatives due to their low risk of side effects. This study was conducted to determine the combined effects of GLB and Pterocarpus marsupium (PM, a commonly available Indian herb) extract for the effective and safe treatment of hyperglycemia in the mouse model. METHODS: Healthy adult male mice were distributed into five groups (n=7 in each group). Group I acted as the control, whereas groups II, III, IV, and V were considered experimental groups which received a single dosage (150 mg/kg body weight) of alloxan (ALX) intraperitoneally (i.p.). In addition, groups III, IV, and V received a pre-standardized dose of GLB (500 µg/kg body weight), PM extract (150 mg/kg body weight), and GLB+PM, respectively, at the same doses as used in individual treatment, after the seventh day of ALX administration for 15 days and the alterations in different DM related parameters were evaluated. RESULTS: ALX-induced hyperglycemia and other adverse effects were nearly normalized by GLB and PM co-treatment as evidenced by marked suppression in glucose, triglyceride, total-cholesterol, lipid-peroxidation, and lipid-hydroperoxides with an increase in antioxidants status and liver glycogen content. The positive effects were more pronounced when both GLB and PM were given, as compared to that of either of the drugs, administered alone. Liver ultra-structure, analyzed through histology and transmission electron microscopy revealed normalization of the ALX-induced damaged hepatocytes. The presence of epicatechin, the major phytoconstituent of the PM extract, as confirmed by high-performance liquid chromatography (HPLC), is responsible for its antioxidative and glucose-lowering activities. CONCLUSION: These findings reveal that PM, along with GLB, exhibits synergistic and better effects than the individual drug in regulating hyperglycemia and associated changes in alloxan-induced mice.

Syringic acid, a novel thyroid hormone receptor-ß agonist, ameliorates propylthiouracil-induced thyroid toxicity in rats.

The aim of this study was to evaluate the potential of syringic acid (SA) against propylthiouracil (PTU)-induced hypothyroidism in rats. SA at a prestandardized dose, 50 mg/kg/day, was orally administered to PTU-induced hypothyroid rats for 30 days, and alterations in the levels of serum triiodothyronine (T3 ), thyroxine (T4 ), thyrotropin (TSH), alanine transaminase (ALT), and aspartate transaminase (AST); tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); total cholesterol (CHOL) and triglycerides (TG); hepatic lipid peroxidation (LPO) and antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione content), as well as histological changes in liver and thyroid were examined. The molecular interactions of the ligand, SA, with thyroid-related protein targets, such as human thyroid hormone receptor ß (hTRß), and thyroid peroxidase (TPO) protein, were studied using molecular docking. Whereas in hypothyroid animals, T4 , T3 , and antioxidants were decreased, there was an increase in TSH, TNF-α, IL-6, ALT, AST, and hepatic LPO; administration of SA in PTU-induced animals reversed all these indices to near normal levels. SA also improved the histological features of liver and thyroid gland. Our study clearly demonstrates SA as a novel thyroid agonist for augmenting the thyroid functions in rats. Molecular docking analysis reveals that SA possesses good binding affinity toward both the targets, hTRß and TPO. Through this approach, for the first time we provide the evidence for SA as a novel thyroid agonist and suggest a receptor-mediated mechanism for its thyroid stimulatory potential.

Plasma Proteome Profiling of Coronary Artery Disease Patients: Downregulation of Transthyretin-An Important Event.

Coronary artery disease (CAD) is a prevalent chronic inflammatory cardiac disorder. An early diagnosis is likely to help in the prevention and proper management of this disease. As the study of proteomics provides the potential markers for detection of a disease, in the present investigation, attempt has been made to identify disease-associated differential proteins involved in CAD pathogenesis. For this study, a total of 200 selected CAD patients were considered, who were recruited for percutaneous coronary intervention (PCI) treatment. The proteomic analysis was performed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF MS/MS. Samples were also subjected to Western blot analysis, enzyme-linked immunosorbent assay (ELISA), peripheral blood mononuclear cells isolation immunofluorescence (IF) analysis, analytical screening by fluorescence-activated cell sorting (FACS), and in silico analysis. The representative data were shown as mean ± SD of at least three experiments. A total of 19 proteins were identified. Among them, the most abundant five proteins (serotransferrin, talin-1, alpha-2HS glycoprotein, transthyretin (TTR), fibrinogen-α chain) were found to have altered level in CAD. Serotransferrin, talin-1, alpha-2HS glycoprotein, and transthyretin (TTR) were found to have lower level, whereas fibrinogen-α chain was found to have higher level in CAD plasma compared to healthy, confirmed by Western blot analysis. TTR, an important acute phase transport protein, was validated low level in 200 CAD patients who confirmed to undergo PCI treatment. Further, in silico and in vitro studies of TTR indicated a downexpression of CAD in plasma as compared to the plasma of healthy individuals. Lower level of plasma TTR was determined to be an important risk marker in the atherosclerotic-approved CAD patients. We suggest that the TTR lower level predicts disease severity and hence may serve as an important marker tool for CAD screening. However, further large-scale studies are required to determine the clinical significance of TTR.

Evaluation of antithyroid potential of Luffa acutangula peel extract and its chemical constituents as identified by HR-LC/MS.

Although some reports are there indicating the medicinal values of fruit peels, on vegetable peels investigations are meager. The present study is an attempt to explore the hitherto unknown potential of Luffa acutangula peel extract in T4-induced hyperthyroid female mice. Animals were made hyperthyroid by administering pre-standardized dose of l-thyroxin (l-T4 at 0.5 mg/kg/day) for 12 consecutive days and then the effects of the test peel extract at 25 and 50 mg/kg for 15 days were studied on the changes in serum thyroid hormones, glucose, different lipids; hepatic lipid peroxidation (LPO); enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and in reduced glutathione. The main chemical constituents of the extract were identified by high resolution liquid chromatography mass spectrometry. Administration of the test peel extract to the hyperthyroid mice at both the test doses decreased the levels of serum thyroid hormones, glucose and tissue LPO suggesting its antithyroid, antihyperglycemic and antiperoxidative potential. These positive effects were also supported by an improved lipid profile as well as liver histology. LC-MS analyses revealed the presence of kaempferol-3-O-rutinoside, kameferol-O-neohesporoside, quercetin, cinnamic acid ethyl ester, caffeic acid derivatives such as 4-O-caffeyol quinic acid, 3-sinapoylquinic acid and 4,5-dihydroxyprenyl caffeate, orientin and sinapic acid. It is presumed that the antithyroid and anti-hyperglycemic actions of the test plant extract could be the result of antioxidative properties of these phytochemicals.

Ameliorative effect of Aloe gel against L-T4-induced hyperthyroidism via suppression of thyrotropin receptors, inflammation and oxidative stress.

Untreated hyperthyroidism may develop serious complications. This attempt was made to investigate the potential of Aloe vera gel in regulating experimentally induced hyperthyroidism in rats. Female Wistar rats were made hyperthyroid with L-thyroxine (L-T4) at 0.5 mg/kg/day, i.p. for 14 days and the effects of Aloe vera methanolic fraction (AVMF) (50 or 500 mg/kg/day, p.o.,) and a conventional antithyroid drug propylthiouracil (PTU) (10 mg/kg, i.p.) for 30 days were studied in those hyperthyroid rats. At the end, alterations in serum thyroid hormones and thyroid stimulating hormone (TSH); hepatic 5'mono-deiodinase-1(5'D1) activity, oxidative stress markers and antioxidants; serum inflammatory cytokines and the expression of thyrotropin receptor in thyroid gland were evaluated in all experimental animals. Hyperthyroid condition was confirmed by an increase in thyroid hormone levels and hepatic 5'D-1 activity with a decrease in TSH. However, either AVMF or PTU treatment in hyperthyroid rats decreased the levels of thyroid hormones and 5'D1 activity. AVMF administration in T4-induced rats also decreased the oxidative stress markers such as thiobarbituric acid reactive substances and lipid hydroperoxides and increased the antioxidant levels in liver tissues. Levels of liver marker enzymes, cytokines and different lipids were decreased in T4-induced AVMF treated rats. Further, a down regulation in the TSHR expression in thyroid was observed in AVMF or PTU treated groups. All these thyroid inhibiting effects were supported by an improvement in thyroid histology in hyperthyroid rats. It appears, about 15 compounds, as evidenced by LC-MS/MS study, mostly phenolics are involved in this anti-thyroid effects of the test compound.

Towards further Understanding the Structural Requirements of Combretastatin- like Chalcones as Inhibitors of Microtubule Polymerization.

BACKGROUND: Microtubules are dynamic filamentous cytoskeletal structures which play several key roles in cell proliferation and trafficking. They are supposed to contribute in the development of important therapeutic targeting tumor cells. Chalcones are important group of natural compounds abundantly found in fruits & vegetables that are known to possess anticancer activity. We have used QSAR and docking studies to understand the structural requirement of chalcones for understanding the mechanism of microtubule polymerization inhibition. METHODS: Three dimensional (3D) QSAR (CoMFA and CoMSIA), pharmacophore mapping and molecular docking studies were performed for the generation of structure activity relationship of combretastatin-like chalcones through statistical models and contour maps. RESULTS: Structure activity relationship revealed that substitution of electrostatic, steric and donor groups may enhance the biological activity of compounds as inhibitors of microtubule polymerization. From the docking study, it was clear that compounds bind at the active site of tubulin protein. CONCLUSION: The given strategies of modelling could be an encouraging way for designing more potent compounds as well as for the elucidation of protein-ligand interaction.

Allylpyrocatechol, isolated from betel leaf ameliorates thyrotoxicosis in rats by altering thyroid peroxidase and thyrotropin receptors.

Allylpyrocatechol (APC) was isolated from betel leaf and its possible role in L-thyroxin (L-T4)-induced thyrotoxic rats was evaluated. The disease condition, thyrotoxicosis was confirmed by higher levels of thyroid hormones and low thyrotropin (TSH) in serum. Increased hepatic activities of 5'-mono-deiodinase(5'D1), glucose-6-phospatase (G-6-Pase); serum concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase(LDH) and tumour necrosis factor-alpha(TNF-α) were observed in thyrotoxic rats. Hepatic lipid peroxidation(LPO) was also increased and the endogenous antioxidants were depleted in these rats. In western blot analysis thyroid peroxidase expression was found to be reduced, whereas thyrotropin receptor(TSHR) expression was enhanced in thyroid gland of these animals. On the other hand, APC treatment in thyrotoxic rats decreased the levels of serum thyroid hormones, ALT, AST, TNF-α and LDH, as well as hepatic 5' D1 and G-6-Pase activities. However, it increased the serum TSH levels. APC also reduced the hepatic LPO and increased the cellular antioxidants in thyrotoxic rats. However, expression of TSHR was inhibited and TPO was increased by APC. The test compound also improved histological features in both liver and thyroid. Present report appears to be the first one that indicates the positive role of APC in ameliorating T4-induced thyrotoxicosis.

Chavibetol corrects thyrotoxicosis through alterations in thyroid peroxidase.

Thyrotoxicosis is a clinical syndrome that commonly results from excess secretion and/or release of thyroid hormones in the circulation. It affects most of the body systems and if not treated properly may lead to serious health problems. In this investigation, we isolated a phenolic compound, chavibetol (CHV) from Piper betel leaf and evaluated its possible ameliorative effects in thyrotoxicosis of rats. Adult female rats were rendered thyrotoxic by the administration of L-thyroxine (L-T4) at 500 µg/kg/day, i.p., for 12 days, and then chavibetol (20.0 mg/kg, p.o.) was administered for 2 weeks. L-T4 administration elevated the concentration of serum thyroxine and triiodothyronine, activities of alanineaminotransferase and aspartate aminotransferase, and decreased the thyrotropin level as well as the expression of thyroid peroxidase (TPO). Further, it increased the activities of hepatic 5'mono-deiodinase-I, glucose-6--phosphatase, sodium-potasium-ATPase, and lipid peroxidation, and depleted the cellular antioxidants. However, chavibetol treatment to thyrotoxic rats normalized almost all these indices including TPO and also preserved the integrity of thyroid tissues suggesting its potential to correct thyrotoxicosis. Effects of CHV were more or less similar to a conventional antithyroid drug, propylthiouracil (PTU).

Administration of Fenugreek Seed Extract Produces Better Effects in Glibenclamide-Induced Inhibition in Hepatic Lipid Peroxidation: An in vitro Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the comparative effects of fenugreek (Trigonella foenum graecum) seed extract (FSE) alone and in combination with an antidiabetic conventional medicine, glibenclamide (GLB), on the inhibition of in vitro lipid peroxidation (LPO) in liver, the major target organ of a drug.@*METHODS@#LPO was induced by ferrous sulphate (FeSo), hydrogen peroxide (HO) and carbon tetrachloride (CCl) and the effects of test seed extract and/or GLB were evaluated.@*RESULTS@#While FeSo, HO and CCl markedly enhanced the hepatic LPO, simultaneous administration of FSE reduced it in a concentration dependent manner. However, when both FSE and GLB were added to the incubation mixture, chemically induced hepatic LPO was further inhibited. The test extract also exhibited high antioxidative activity in 1,1-diphenyl-2-picrylhydrazyl radical and in 2,2'-azinobis, 3-ethylbenzothiazoline-6-sulphonic acid radical scavenging assays.@*CONCLUSION@#FSE therapy in moderate concentration along with a hypoglycemic drug may prove to be advantageous in ameliorating diabetes mellitus and other diseases that are LPO mediated.

Preventive effect of Agnucastoside C against Isoproterenol-induced myocardial injury.

An iridoid glycoside, agnucastoside C (ACC) was isolated from the leaves of Moringa oliefera and its cardio protective potential was investigated in adult rats by examining the effects of this test compound, ACC at 30 mg/kg for 14 days in isoproterenol (100 mg/kg)-induced myocardial injury. Isoproterenol (ISO) administration induced the myocardial injury as evidenced by the altered ECG pattern with ST-segment elevation and an increase in the levels of cardiac injury markers including troponin-I, creatine kinase-MB, alanine transaminase, aspartate transaminase, lactate dehydrogenase; inflammatory markers, interleukine-6 and tumor necrosis factor. In this group, there was also an increase in cardiac lipid peroxidation and a decrease in cellular antioxidants. However, pretreatment with ACC maintained the normal ECG pattern and nearly normal levels of all the cardiac markers in ISO-induced animals. Electron microscopic and histological studies also showed marked reduction in ISO-induced cardiac damages including infarct size by ACC. Analysis by 2-DE revealed the involvement of 19 different cardiac proteins, associated with energy metabolism, oxidative stress and maintenance of cytoskeleton. The expression of those proteins were altered by ISO, but maintained in ACC pretreated rats. Our findings reveal the potential of isolated ACC in the prevention of myocardial damage.

Role of a gitogenin-type steroidal saponin (3-O-ß-d-glucopyranosyl (1→2)-ß-d-glucopyranosyl (1→4)-ß-d-galactopyranoside-25R,5α-spirostane-2α,3ß-diol), isolated from the leaves of Malvastrum coromandelianum in regulating thyrotoxicosis in rats.

The hitherto unknown role of saponin in the regulation of thyrotoxicosis has been revealed in chemically-induced thyrotoxic rats. l-T4 (l-thyroxine) administration at pre-standardized dose of 500-µg/kg body weight for 12days increased the levels of thyroid hormones, enhanced the activity of hepatic 5'-monodeiodinase I (5'DI) and glucose-6-phosphatase (G-6Pase) as well as lipid peroxidation (LPO) with a parallel decrease in the levels of antioxidative enzymes. However, administration of the isolated saponin for 15days ameliorated the T4-induced alterations in serum thyroid hormones, hepatic LPO, G-6-Pase and 5'DI activity, and improved the cellular antioxidant status, indicating its antithyroidal and antioxidative potential. These effects of the test compound were comparable to a reference antithyroid drug, Propylthiouracil (PTU), suggesting that the test saponin may act as a potent anti-thyroid agent.

In vitro evaluation of bioremediation capacity of a commercial probiotic, Bacillus coagulans, for chromium (VI) and lead (II) toxicity.

INTRODUCTION: The bioaccumulation of heavy metals including chromium (VI) (Cr (VI)) and lead (II) (Pb (II)) causes fatal toxicity in humans. Some naturally occurring bacterial genera such as Bacillus and Pseudomonas help in bioremediation of these heavy metals and some of the species of Bacillus are proven probiotics. However, no study has been conducted on Bacillus coagulans, which is a proven probiotic species of genus Bacillus. OBJECTIVES: The primary objective of the present study was to assess the potential of a proven probiotic, B. coagulans, marketed as "Sporlac-DS," to survive in the presence of Cr (VI) and Pb (II) and its ability to reduce its concentration in vitro. MATERIALS AND METHODS: The Minimum inhibitory concentration (MIC) of the organism for Cr (VI) and Pb (II) was determined followed by its biochemical and morphological characterization. Its antibiotic sensitivity and probiotic efficacy were assessed. Further, its bioremediation capacity was observed in vitro by determining the residual Cr (VI) and Pb (II) concentration after 72 h. RESULTS: B. coagulans could tolerate up to 512 ppm concentration of Cr (VI) and had an MIC of 128 ppm for Pb (II). After 72 h, the organism reduced 32 ppm Cr (VI) and 64 ppm Pb (II) by 93% and 89%, respectively. When B. coagulans was studied before and after growing on Cr (VI) and Pb (II) for 24 h, an increase was seen in sensitivity toward the tested antibiotics whereas no change was observed in morphological and biochemical characters. It also showed no change in their bile and acid tolerance, indicating that it retains its probiotic efficacy. CONCLUSION: The tested probiotic B. coagulans may have a potential role in bioremediation of Cr (VI) and Pb (II), in vivo.

Protective effects of 5,7,4'-trihydroxy-6,3'dimethoxy-flavone 5-O-α-l-rhamnopyranoside, isolated from Annona squamosa leaves in thyrotoxicosis and in hepatic lipid peroxidation in rats.

Hitherto unknown protective effects of 5,7,4'-trihydroxy-6,3'dimethoxy-flavone 5-O-α-l-rhamnopyranoside (THDMF-Rha); isolated from Annona squamosa leaves were evaluated in l-thyroxine (l-T4)-induced thyrotoxicosis in rats. Administration of l-T4 at 500µg/kg body weight for 12days increased the levels of serum thyroid hormones, the activity of 5'-monodeiodinase-I (5'DI) and hepatic glucose-6-phosphatase (G-6Pase) as well as lipid peroxidation (LPO); with a parallel decrease in the levels of cellular antioxidants and serum lipids. However, administration of the isolated THDMF-Rha at a pre-standardized dose for 15days ameliorated the l-T4-induced alterations in the levels of thyroid hormones, hepatic LPO, G-6-Pase, 5'DI activity, and cellular levels of antioxidants and improved the status of different serum lipids, suggesting its antithyroidal and antioxidative potential. As compared to standard antithyroid drug, propylthiouracil, THDMF-Rha appeared to be more promising.

Pyrroloquinoline quinone (PQQ) has potential to ameliorate streptozotocin-induced diabetes mellitus and oxidative stress in mice: A histopathological and biochemical study.

Enhanced oxidative stress and hyperglycemia are associated with diabetes mellitus (DM). As pyrroloquinoline quinone (PQQ) is known to protect cells from oxidative stress, the present study was undertaken to reveal the hitherto unknown effects of PQQ in DM and associated problems in different tissues. Forty two mice were randomly divided into six groups. Group I receiving only citrate buffer served as the normal control, while group II animals were injected with citrate buffer and PQQ at 20 mg/kg for 15 days and served as test drug control. Animals of groups III-VI were rendered diabetic by single dose of streptozotocin (STZ, 150 mg/kg body weight), following which PQQ at a dose of 5, 10 and 20 mg/kg, was injected to the animals of group IV, V and VI respectively for 15 days. At the end, alterations in serum indices such as glucose, different lipids, insulin, amylase, urea, uric acid, serum glutamate pyruvate transaminase and serum glutamate oxaloacetate transaminase; tissue antioxidants and histopathological alterations in liver, kidney and pancreas were evaluated. STZ-treated animals developed oxidative stress as indicated by a significant increase in tissue lipid peroxidation (LPO) and lipid hydroperoxide, serum glucose, total cholesterol, triglyceride and urea, with a parallel decrease in the levels of serum insulin and tissue antioxidants. When diabetic animals received different doses of PQQ, these adverse effects were ameliorated. However, 20 mg/kg of PQQ appeared to be most effective. Findings revealed for the first time that PQQ has the potential to mitigate STZ-induced DM and oxidative damage in different organs of mice, suggesting that it may ameliorate diabetes mellitus and associated problems.

Pyrroloquinoline quinone ameliorates oxidative stress and lipid peroxidation in the brain of streptozotocin-induced diabetic mice.

Diabetes, characterized by hyperglycemia, leads to several complications through the generation of reactive oxygen species and initiates tissue damage. Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant, as it protects cells from oxidative damage. In this study, we elucidated the hitherto unknown potential of PQQ to ameliorate the brain damage caused by diabetes mellitus and the associated hyperglycemia-induced oxidative damage. Administration of a single dose of streptozotocin (STZ), i.e., 150 mg·(kg body mass)(-1) significantly enhanced the brain tissue levels of lipid peroxidation and hydroperoxidation and decreased the levels of antioxidants. It also increased the serum levels of glucose, cholesterol, and triglycerides. However, when STZ-treated animals received PQQ (20 mg·(kg body mass)(-1)·d(-1), for 15 days), this significantly decreased the serum levels of glucose and lipid peroxidation products, and increased the activities of antioxidants in the diabetic mouse brain. These findings suggest that PQQ has the potential to ameliorate STZ-induced oxidative damage in the brain, as well as the STZ-induced diabetes.

Combined Effects of Vincristine and Quercetin in Reducing Isoproterenol-Induced Cardiac Necrosis in Rats.

Combined effects of vincristine and quercetin in the regulation of isoproterenol (ISO)-induced cardiac necrosis have been evaluated in rats. ISO administration (100 mg/kg, s.c., for two consecutive days) increased the levels of serum creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), glutamate pyruvate transaminase (SGPT) and cardiac troponin (cTnT) as well as cardiac lipid peroxidation products (malondialdehyde and lipid hydroperoxides). However, it reduced the activities of superoxide dismutase (SOD), catalase and the glutathione peroxidase and the level of reduced glutathione. It also increased the heart rate and ST-segment elevation in ECG. Pretreatment of vincristine (25 µg/kg) or quercetin (10 mg/kg) alone for 2 weeks ameliorated these cardiotoxic effects partially. However, treatment of both vincristine and quercetin for a similar period reduced the serum CK-MB, LDH, SGPT and cTnT levels near to normal levels in ISO-treated rats. Concomitantly, the test drugs improved the status of antioxidants and decreased the cardiac lipid peroxidation products. Combined treatment of both the drugs also restored the pathological electrocardiographic patterns and reduced the area of myocardial necrosis. Histopathology of heart in ISO-administered rats that received both vincristine and quercetin showed nearly normal myocardium with very little inflammatory infiltration. In conclusion, the present finding appears to be the first one, suggesting a better protection of cardiac tissues by combined treatment of vincristine and quercetin in isoproterenol-induced cardiac toxicity.

Antithyroid effects of naringin, hesperidin and rutin in l-T4 induced hyperthyroid rats: possible mediation through 5'DI activity.

BACKGROUND: Investigations are meager on the ameliorative role of plant based active compounds in regulating hyperthyroidism. We have now explored the possible role of three flavonoids in the regulation of L-thyroxine (l-T4)-induced hyperthyroidism in rats. This investigation attempts to reveal whether rutin, naringin and hesperidin supplementation exhibit antithyroid effects in L-T4-induced hyperthyroid rats and to work out the possible involvement of free radicals in their mode of action. METHODS: Either rutin or naringin or hesperidin (50mg/kg each) was administered to L-T4-induced hyperthyroid rats for two weeks and their effects were evaluated on the alterations in levels of thyroid hormones, 5'-deiodinase I (5'DI) activity, hepatic lipid peroxidation as well as in antioxidants. RESULTS: l-T4 administration significantly enhanced the serum concentrations of thyroxine and triiodothyronine; the activities of hepatic 5'DI, serum lactate dehydrogenase and serum glutamate pyruvate transaminase along with an increase in content of malondialdehyde in hepatic tissues, but depleted the cellular antioxidants. However, on administration of the test flavonoids, these effects were more or less normalized. Electro paramagnetic resonance (EPR) spectra also indicated the suppression of the hydroxyl radicals (OH) in the hepatic tissues. CONCLUSION: Rutin, naringin and hesperidin have the potential to inhibit thyroid functions without hepatotoxicity and the effects are possibly mediated through their free radical scavenging action as evidenced by EPR study. From the comparative analyses of the results, rutin appeared to be the most effective one suggesting its better antithyroid and antioxidative potential over other two.

Pyrroloquinoline quinone ameliorates l-thyroxine-induced hyperthyroidism and associated problems in rats.

Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this study, we have evaluated its hitherto unknown role in l-thyroxin (L-T4 )-induced hyperthyroidism considering laboratory rat as a model. Alterations in the serum concentration of thyroxin (T4 ) and triiodothyronine (T3 ); lipid peroxidation (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants such as superoxide dismutase, catalase and glutathione and in serum total cholesterol, high-density lipoprotien, triglycerides, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea were evaluated. Administration of l-T4 (500-µg kg(-1) body weight) enhanced not only the serum T3 and T4 levels but also the tissue LPO, serum SGOT, SGPT and urea with a parallel decrease in the levels of antioxidants and serum lipids. However, on simultaneous administration of PQQ (5 mg kg(-1) for 6 days), all these adverse effects were ameliorated, indicating the potential of PQQ in the amelioration of hyperthyroidism and associated problems. Possibly, the curative effects were mediated through inhibition of oxidative stress. We suggest that PQQ may be considered for therapeutic use for hyperthyroidism after dose standardization.