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Discovery of trans-3,4,4'-trihydroxystilbene as new lead vasorelaxant agent for antihypertensive drug development

Loh YC, Chan SY, Oo CW, Yam MF

Life Sci, 2021 Aug 01;278:119560.
PMID: 33915131 DOI: 10.1016/j.lfs.2021.119560

AIMS: The structure-vasorelaxant activity relationships (SARs) assessment in previous study has found that trans-3,4,4'-trihydroxystilbene (344OH) could potentially act as a vasorelaxing agent with demonstration of over 2-fold maximal relaxation (Rmax) compared to its analogue, resveratrol. The present study focuses on the mechanism of actions and pathways employed by 344OH and compared to its analogue to further speculate the SAR of stilbenoids towards vasorelaxation.
MATERIALS AND METHODS: The 344OH employed in present study was synthesized based on the protocol in previous study. The vascular responses towards the cumulative addition of 344OH were evaluated using in vitro rat aortic rings assays.
KEY FINDINGS: The pEC50 and Rmax values were found to be 4.33 ± 0.05 and 106 ± 3.99%, respectively. Results showed that the vasorelaxation of 344OH were predominated by G-protein-coupled muscarinic- (M3) and β2-adrenergic receptors, followed by PGI2/AC/cAMP- and NO/sGC/cGMP-dependent pathways. It was also identified that 344OH employed voltage-activated- (Kv), calcium-activated- (Kca) and inwardly-rectifying (Kir) potassium channels and act as an antagonist for both VOCC and IP3R while regulating the action potential in the vasculature.
SIGNIFICANCE: The different position of hydroxyl substituent located in A-ring of the stilbenoid backbone in 344OH compared to resveratrol resulted in a significant difference in mechanistic actions that lead to 344OH's fast-acting and less time-dependent vasorelaxation behaviour. This has substantially increased the potential of 344OH to be developed as an effective antihypertensive drug in future. Present findings further strengthen our inferences where the SARs study approach should be carried out as the mainstream methodology in future drug development research.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext In vivo Toxicity Assessment of Refined Red Palm-pressed Mesocarp Olein in Sprague-Dawley Rats

Jin Y, Teh SS, Lau HLN, Mah SH

J Oleo Sci, 2021 Dec 03;70(12):1749-1759.
PMID: 34759114 DOI: 10.5650/jos.ess21215

Refined red palm-pressed mesocarp olein (PPMO) is recovered from palm-pressed mesocarp fiber, which is a by-product from palm oil mill. Its utilization in food industry is extremely limited even though it contains various phytonutrients. Thus, this study aimed to evaluate its toxicity effects by using the male Sprague-Dawley rat model. The rats were administered with a single dose of 2 g/kg PPMO in an acute toxicity study while administered with 2, 1, or 0.5 g/kg PPMO daily for 28 days in a sub-chronic toxicity study. The mortality, oral LD50 value, clinical observation, body and organ weight, hematological and biochemical analyses, pathological and histopathological examinations were assessed. The overall outcomes indicated that PPMO is non-toxic up to 2 g/kg and considered safe to be used in food application, especially as functional food ingredient and supplement attributed to its phytonutrients. Besides, this study provides an insight in alternative utilization of the wastes from palm oil mill.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Bee bread mitigates downregulation of steroidogenic genes, decreased spermatogenesis, and epididymal oxidative stress in male rats fed with high-fat diet

Suleiman JB, Abu Bakar AB, Noor MM, Nna VU, Othman ZA, Zakaria Z, et al.

Am J Physiol Endocrinol Metab, 2021 Sep 01;321(3):E351-E366.
PMID: 34229480 DOI: 10.1152/ajpendo.00093.2021

The pituitary-gonadal axis plays an important role in steroidogenesis and spermatogenesis, and by extension, fertility. The aim of this study was to investigate the protective role of bee bread, a natural bee product, against obesity-induced decreases in steroidogenesis and spermatogenesis. Thirty-two adult male Sprague-Dawley rats weighing between 200 and 300 g were divided into four groups (n = 8/group), namely: normal control (NC), high-fat diet (HFD), HFD plus bee bread administered concurrently for 12 wk (HFD + B), HFD plus orlistat administered concurrently for 12 wk (HFD + O) groups. Bee bread (0.5 g/kg) or orlistat (10 mg/kg/day) was suspended in distilled water and given by oral gavage daily for 12 wk. Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and adiponectin, as well as sperm count, motility, viability, normal morphology, and epididymal antioxidants decreased, whereas levels of leptin, malondialdehyde, and sperm nDNA fragmentation increased significantly in the HFD group relative to the NC group. There were significant decreases in the testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme, 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD in the testes of the HFD group. Furthermore, mount, intromission and ejaculatory latencies increased, and penile cGMP level decreased significantly in the HFD group. Supplementation with bee bread significantly reduced leptin level and increased adiponectin level, enhanced sperm parameters and reduced sperm nDNA fragmentation, upregulated the levels of steroidogenic genes and proteins in HFD-induced obese male rats. Bee bread improved steroidogenesis and spermatogenesis by upregulating steroidogenic genes. Therefore, bee bread may be considered as a potential supplementation to protect against infertility in overweight men or men with obesity.NEW & NOTEWORTHY The high-fat diet utilized in the present study induced obesity in the male rats. Bee bread supplementation mitigated impaired steroidogenesis, spermatogenesis, mating behavior, and fertility potential by counteracting the downregulation of steroidogenic genes, thus increasing testosterone levels and suppressing epididymal oxidative stress. These benefits may be due to the abundance of phenolic and flavonoid compounds in bee bread.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Evaluation of antinociceptive effect of methanolic leaf and root extracts of Clitoria ternatea Linn. in rats

Kamilla L, Ramanathan S, Sasidharan S, Mansor SM

Indian J Pharmacol, 2014 Sep-Oct;46(5):515-20.
PMID: 25298581 DOI: 10.4103/0253-7613.140583

Clitoria ternatea Linn. (C. ternatea) is an Ayurvedic herb traditionally used as medicine to relieve inflammatory, rheumatism, ear diseases, fever, arthritis, eye ailments, sore throat and body ache. This study aims to evaluate and elucidate the possible mechanism underlying the antinociceptive action of methanolic extracts of C. ternatea leaf and root using several antinociception models.

Matched MeSH terms: Rats, Sprague-Dawley
Comparison of relaxin receptors in rat isolated atria and uterus by use of synthetic and native relaxin analogues

Tan YY, Wade JD, Tregear GW, Summers RJ

Br J Pharmacol, 1998 Feb;123(4):762-70.
PMID: 9517397

1. The receptors for relaxin in the rat atria and uterus were investigated and compared by use of a series of synthetic and native relaxin analogues. The assays used were the positive chronotropic and inotropic effects in rat spontaneously beating, isolated right atrium and electrically driven left atrium and the relaxation of K+ precontracted uterine smooth muscle. 2. Relaxin analogues with an intact A- and B-chain were active in producing powerful chronotropic and inotropic effects in the rat isolated atria at nanomolar concentrations. Single-chain analogues and structural homologues of relaxin such as human insulin and sheep insulin-like growth factor I had no agonist action and did not antagonize the effect of the B29 form of human gene 2 relaxin. 3. Shortening the B-chain carboxyl terminal of human gene 1 (B2-29) relaxin to B2-26 reduced the activity of the peptide and removal of another 2 amino acid residues (B2-24) abolished the activity. This suggests that the B-chain length may be important for determination of the activity of relaxin. More detailed studies are needed to determine the effect of progressive amino acid removal on the structure and the bioactivity of relaxin. 4. Porcine prorelaxin was as active as porcine relaxin on a molar basis, suggesting that the presence of the intact C-peptide did not affect the binding of the prorelaxin to the receptor to produce functional responses. 5. Relaxin caused relaxation of uterine longitudinal and circular smooth muscle precontracted with 40 mM K+. The pEC50 values for human gene 2 and porcine relaxins were lower than those in the atrial assay, but rat relaxin had similar pEC50 values in both atrial and uterine assays. Rat relaxin was significantly less potent than either human gene 2 or porcine relaxin in the atrial assay, but in the uterine assay they were equipotent. The results suggest that the relaxin receptor or the signalling pathway in rat atria may differ from that in the uterus.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Cardiovascular activity of labdane diterpenes from Andrographis paniculata in isolated rat hearts

Awang K, Abdullah NH, Hadi AH, Fong YS

J Biomed Biotechnol, 2012;2012:876458.
PMID: 22536026 DOI: 10.1155/2012/876458

The dichloromethane (DCM) extract of Andrographis paniculata Nees was tested for cardiovascular activity. The extract significantly reduced coronary perfusion pressure by up to 24.5 ± 3.0 mm Hg at a 3 mg dose and also reduced heart rate by up to 49.5 ± 11.4 beats/minute at this dose. Five labdane diterpenes, 14-deoxy-12-hydroxyandrographolide (1), 14-deoxy-11,12-didehydroandrographolide (2), 14-deoxyandrographolide (3), andrographolide (4), and neoandrographolide (5), were isolated from the aerial parts of this medicinal plant. Bioassay-guided studies using animal model showed that compounds, (2) and (3) were responsible for the coronary vasodilatation. This study also showed that andrographolide (4), the major labdane diterpene in this plant, has minimal effects on the heart.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Antinociceptive activity of Melicope ptelefolia ethanolic extract in experimental animals

Sulaiman MR, Mohd Padzil A, Shaari K, Khalid S, Shaik Mossadeq WM, Mohamad AS, et al.

J Biomed Biotechnol, 2010;2010:937642.
PMID: 21274262 DOI: 10.1155/2010/937642

Melicope ptelefolia is a medicinal herb commonly used in Malaysia to treat fever, pain, wounds, and itches. The present study was conducted to evaluate the antinociceptive activity of the Melicope ptelefolia ethanolic extract (MPEE) using animal models of nociception. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin-induced paw licking tests. Oral administration of MPEE produced significant dose-dependent antinociceptive effects when tested in mice and rats using acetic acid-induced abdominal constriction test and on the second phase of the formalin-induced paw licking test, respectively. It was also demonstrated that MPEE had no effect on the response latency time to the heat stimulus in the thermal model of the hot-plate test. In addition, the antinociception produced by MPEE was not blocked by naloxone. Furthermore, oral administration of MPEE did not produce any effect in motor performance of the rota-rod test and in acute toxicity study no abnormal behaviors as well as mortality were observed up to a dose level of the extract of 5 g/kg. These results indicated that MPEE at all doses investigated which did not produce any sedative and toxic effects exerted pronounce antinociceptive activity that acts peripherally in experimental animals.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Protective Effects of Tamarillo (Cyphomandra betacea) Extract against High Fat Diet Induced Obesity in Sprague-Dawley Rats

Abdul Kadir NA, Rahmat A, Jaafar HZ

J Obes, 2015;2015:846041.
PMID: 26171246 DOI: 10.1155/2015/846041

This study aims to investigate the protective effect of Cyphomandra betacea in adult male Sprague-Dawley rats fed with high fat diet. Rats were fed on either normal chow or high fat diet for 10 weeks for obesity induction phase and subsequently received C. betacea extract at low dose (150 mg kg(-1)), medium dose (200 mg kg(-1)), or high dose (300 mg kg(-1)) or placebo via oral gavages for another 7 weeks for treatment phase. Treatment of obese rats with C. betacea extracts led to a significant decrease in total cholesterol and significant increase in HDL-C (p < 0.05). Also there was a trend of positive reduction in blood glucose, triglyceride, and LDL-C with positive reduction of body weight detected in medium and high dosage of C. betacea extract. Interestingly, C. betacea treated rats showed positive improvement of superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity along with a significant increase of total antioxidant status (TAS) (p < 0.05). Further, rats treated with C. betacea show significantly lower in TNF-α and IL-6 activities (p < 0.05). This study demonstrates the potential use of Cyphomandra betacea extract for weight maintenance and complimentary therapy to suppress some obesity complication signs.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae)

Wong KH, Naidu M, David P, Abdulla MA, Abdullah N, Kuppusamy UR, et al.

Evid Based Complement Alternat Med, 2011;2011:580752.
PMID: 21941586 DOI: 10.1093/ecam/neq062

Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Brain Cortical and Hippocampal Dopamine: A New Mechanistic Approach for Eurycoma longifolia Well-Known Aphrodisiac Activity and Its Chemical Characterization

Ezzat SM, Ezzat MI, Okba MM, Hassan SM, Alkorashy AI, Karar MM, et al.

Evid Based Complement Alternat Med, 2019;2019:7543460.
PMID: 31275418 DOI: 10.1155/2019/7543460

Eurycoma longifolia Jack (Fam.: Simaroubaceae), known as Tongkat Ali (TA), has been known as a symbol of virility and sexual power for men. Metabolic profiling of the aqueous extract of E. longifolia (AEEL) using UPLC-MS/MS in both positive and negative modes allowed the identification of seventeen metabolites. The identified compounds were classified into four groups: quassinoids, alkaloids, triterpenes, and biphenylneolignans. AEEL is considered safe with oral LD50 cut-off >5000 mg/kg. Oral administration of 50, 100, 200, 400, or 800 mg/kg of AEEL for 10 consecutive days to Sprague-Dawley male rats caused significant reductions in mounting, intromission, and ejaculation latencies and increased penile erection index. AEEL increased total body weight and relative weights of seminal vesicles and prostate. Total and free serum testosterone and brain cortical and hippocampal dopamine content was significantly elevated in treated groups with no significant effects on serotonin or noradrenaline content.

Matched MeSH terms: Rats, Sprague-Dawley
Ameliorative Effect of Curcumin on Olanzapine-induced Obesity in Sprague-Dawley Rats

Parasuraman S, Zhen KM, Banik U, Christapher PV

Pharmacognosy Res, 2017 Jul-Sep;9(3):247-252.
PMID: 28827965 DOI: 10.4103/pr.pr_8_17

OBJECTIVE: To evaluate the effect of curcumin on olanzapine-induced obesity in rats.

MATERIALS AND METHODS: Sprague-Dawley (SD) rats were used for experiments. The animals were divided into six groups, namely, normal control, olanzapine control, betahistine (10 mg/kg), and curcumin 50, 100, and 200 mg/kg treated groups. Except the normal control group, all other animals were administered with olanzapine 4 mg/kg intraperitoneally to induce obesity. The drugs were administered once daily, per oral for 28 days. During the experiment, body weight changes and behavior alterations were monitored at regular intervals. At the end of the experiment, blood sample was collected from all the experimental animals for biochemical analysis. Part of the liver and kidney tissues was harvested from the sacrificed animals and preserved in neutral formalin for histopathological studies.

RESULTS: Curcumin showed a significant reduction in olanzapine-induced body weight gain on the rats and improved the locomotor effects. The effect of curcumin on olanzapine-induced body weight gain is not comparable with that of betahistine.

CONCLUSION: This study has shown metabolic alteration effect of curcumin on olanzapine, an antipsychotic drug, treated SD rats.

SUMMARY: Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia and bipolar disorder. Obesity is an adverse effect of olanzapine, and the present study was made an attempt to study the effect of curcumin on olanzapine-induced obesity in rats. In this present study, curcumin significantly reduced olanzapine-induced body weight gain in rats. Abbreviations Used: 5HT: 5-hydroxytryptamine, ALP: Alkaline phosphatase, ALT: Alanine transaminase, ANOVA: Analysis of variance, AST: Aspartate transaminase, CMC: Carboxymethyl cellulose, D: Dopamine, H and E: Hematoxylin and Eosin stain, H: Histamine, HDL-C: Highdensity lipoprotein cholesterol, IP: Intraperitoneal, MAO: Monoamine oxidase, NaOH: Sodium hydroxide, SD rats: Sprague Dawley rats, TCs: Total cholesterols, TG: Triglyceride.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Lipid peroxidation and decline in antioxidant status as one of the toxicity measures of diazinon in the testis

Leong CT, D'Souza UJ, Iqbal M, Mustapha ZA

Redox Rep, 2013;18(4):155-64.
PMID: 23849340 DOI: 10.1179/1351000213Y.0000000054

The rapid emergence of various pesticides in the market is inevitable due to the demands from agriculture industries and domestic needs to control nuisance pests and to sustain green resources worldwide. However, long-term exposure to pesticide has led to adverse effects on male fertility. Organophosphate diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphorothiote) is an often abusively used pesticide, as it is effective and economical. This study is to determine the adverse effects of low-dose diazinon exposure on the male reproductive system. In this study, 72 Sprague-Dawley rats were segregated into 1, 2, and 8 weeks of exposure groups and further sub-grouped (n = 6) to receive 0, 10, 15, and 30 mg/kg body weight diazinon treatment. Rats were gavaged orally with diazinon and sacrificed under anaesthesia the day after the last exposure. Our results showed that consistent diazinon exposure decreased glutathione and catalase, and increased lipid peroxidation which together lead to diazinon-mediated oxidative stress. Additionally, diazinon increased serum lactate dehydrogenase and decreased serum testosterone, which may have caused sperm and histopathological anomalies. In conclusion, exposure to diazinon caused changes in lipid peroxidation and sperm, and these two effects might be causally linked.

Matched MeSH terms: Rats, Sprague-Dawley
Lipopolysaccharide reduces gonadotrophin-releasing hormone (GnRH) gene expression: role of RFamide-related peptide-3 and kisspeptin

Lee CY, Li S, Li XF, Stalker DAE, Cooke C, Shao B, et al.

Reprod Fertil Dev, 2019 May;31(6):1134-1143.
PMID: 30922440 DOI: 10.1071/RD18277

RFamide-related peptide (RFRP)-3 reduces luteinising hormone (LH) secretion in rodents. Stress has been shown to upregulate the expression of the RFRP gene (Rfrp) with a concomitant reduction in LH secretion, but an effect on expression of the gonadotrophin-releasing hormone (GnRH) gene (Gnrh1) has not been shown. We hypothesised that lipopolysaccharide (LPS)-induced stress affects expression of Rfrp, the gene for kisspeptin (Kiss1) and/or Gnrh1, leading to suppression of LH levels in rats. Intracerebroventricular injections of RFRP-3 (0.1, 1, 5 nmol) or i.v. LPS (15μgkg-1) reduced LH levels. Doses of 1 and 5 nmol RFRP-3 were then administered to analyse gene expression by in situ hybridisation. RFRP-3 (5 nmol) had no effect on Gnrh1 or Kiss1 expression. LPS stress reduced GnRH and Kiss1 expression, without affecting Rfrp1 expression. These data indicate that LPS stress directly or indirectly reduces Gnrh1 expression, but this is unlikely to be due to a change in Rfrp1 expression.

Matched MeSH terms: Rats, Sprague-Dawley
Vitamin D ameliorates memory function in association with reducing senescence and upregulating neurotrophin mRNA expression in transient global cerebral ischemic injury model in rats

Melindah T, Sari DCR, Setiawan J, Alex, Thamrin MM, Zahra F, et al.

Med J Malaysia, 2024 Aug;79(Suppl 4):51-57.
PMID: 39215415

INTRODUCTION: Ischaemic stroke induces oxidative stress, mitochondrial damage, inflammation and senescence and the decrease of cognitive function. Vitamin D is a fat-soluble vitamin that has a neuroprotective effect to repair the function of the nervous system. The aim of this study is to investigate the effect of vitamin D on memory function, p16, p21 (senescence), and nerve growth factor (NGF) mRNA expression on the hippocampus after transient global cerebral ischemic.
MATERIALS AND METHODS: The study was designed as quasiexperimental with a control group that only received posttests. We performed in vivo study with an induction bilateral common carotid artery occlusion (BCCAO) model and vitamin D injection for 10 days. A total of 24 rats were divided into four groups (n = 6): Sham operation (SO [control]), BCCAO (transient global cerebral ischemic model not given vitamin D), VD1 (BCCAO + vitamin D 0.125 μg/kgBW), and VD2 (BCCAO + vitamin D 0.5 μg/kgBW). The spatial memory function was tested with the Morris water maze. We performed immunohistochemistry to localise p16 expression. p16, p21 and NGF mRNA expression were assessed by reverse transcriptase (RT-PCR) method.
RESULTS: The vitamin D treatment group required shorter mileage to find the platform and probe test. The total time spent was longer in the target quadrant than in non-target. The Vitamin D-treated group had lower p16 and p21 mRNA expression and higher NGF mRNA expression than the BCCAO group. Immunostaining showed p16 signal in the pyramidal cell of CA1 area in the BCCAO group.
CONCLUSION: Vitamin D repairs memory function, senescence expression was lower and NGF was higher in the BCCAO model.

Matched MeSH terms: Rats, Sprague-Dawley
Consumption of repeatedly heated soy oil increases the serum parameters related to atherosclerosis in ovariectomized rats

Adam SK, Das S, Soelaiman IN, Umar NA, Jaarin K

Tohoku J Exp Med, 2008 Jul;215(3):219-26.
PMID: 18648182

Repeated heating of soy oil may promote lipid peroxidation. Oxidized unsaturated fatty acids may contribute to the pathogenesis of atherosclerosis, especially in estrogen-deficient states. This study was performed to explore the deleterious effects of repeatedly heated soy oil on the development of atherosclerosis using ovariectomized rats, which represent an estrogen-deficient state. Twenty-four female Sprague-Dawley rats were ovariectomized and were divided equally into four groups. The control group was fed with 2% cholesterol diet without any oil. The three treatment groups each received 2% cholesterol diet fortified with fresh, once-heated or five-times-heated (repeatedly heated) soy oil, respectively. Serum thiobarbituric acid reactive substances (TBARS), lipid profile and homocysteine levels were measured prior to ovariectomy and at the end of four months. Ovariectomized rats treated with repeatedly heated soy oil showed significant increases in lipid peroxidation and low-density lipoprotein (LDL) levels. Treatment with once-heated or repeatedly heated soy oil caused a significant increase in total cholesterol, while fresh soy oil caused significant reduction in homocysteine level as compared to other groups. Repeatedly heated soy oil caused significant increases in TBARS and LDL as compared to fresh oil. The higher level of homocysteine in the ovariectomized rats fed with repeatedly heated oil, as compared to those fed with fresh oil, also suggests the repeatedly heated oil contributes to the development of atherosclerosis. Importantly, the protective effect of the soy oil may be lost once it was being repeatedly heated. In conclusion, the consumption of repeatedly heated oil may predispose to atherosclerosis in estrogen-deficient states.

Matched MeSH terms: Rats, Sprague-Dawley
Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract

Mediani A, Abas F, Maulidiani M, Khatib A, Tan CP, Ismail IS, et al.

J Pharm Biomed Anal, 2016 Sep 05;128:302-312.
PMID: 27318080 DOI: 10.1016/j.jpba.2016.06.003

Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2

Hanafi NI, Mohamed AS, Md Noor J, Abdu N, Hasani H, Siran R, et al.

Genet. Mol. Res., 2016 Jun 17;15(2).
PMID: 27323195 DOI: 10.4238/gmr.15028150

Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing ceramide, and inhibition of SMases activity can promote cell survival. We hypothesized that UDCA regulates activation of ERK and Akt survival signaling pathways and SMases in protecting cardiac cells against hypoxia. Neonatal cardiomyocytes were isolated from 0- to 2-day-old Sprague Dawley rats, and given 100 μM CoCl2, 150 μM H2O2, or placed in a hypoxia chamber for 24 h. The ameliorative effects of 100-μM UDCA treatment for 12 h were then assessed using MTS, QuantiGene Plex (for Smpd1 and Smpd2), and SMase assays, beating rate assessment, and western blotting (for ERK and Akt). Data were analyzed by the paired Student t-tests and one-way analyses of variance. Cell viability decreased significantly after H2O2 (85%), CoCl2 (50%), and hypoxia chamber (52%) treatments compared to the untreated control (100%). UDCA significantly counteracted the effects of chamber- and CoCl2- induced hypoxia on viability and beating rate. However, no significant differences were observed in acid SMase gene and protein expression between the untreated, CoCl2, and UDCA-CoCl2 groups. In contrast, neutral SMase gene and protein expression did significantly differ between the latter two groups. ERK and Akt phosphorylation was higher in hypoxic cardiomyocytes treated with UDCA than those given CoCl2 alone. In conclusion, UDCA regulates the activation of survival signaling proteins and SMases in neonatal rat cardiomyocytes during hypoxia.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Evaluation of chemopreventive potential of Strobilanthes crispus against colon cancer formation in vitro and in vivo

Al-Henhena N, Khalifa SA, Ying RP, Ismail S, Hamadi R, Shawter AN, et al.

BMC Complement Altern Med, 2015;15(1):419.
PMID: 26608653 DOI: 10.1186/s12906-015-0926-7

With cancer being one of the major causes of death around the world, studies are ongoing to find new chemotherapeutic leads. There are common mechanisms for colorectal cancer (CRC) formation. Several are connected with oxidative stress-induced cell apoptosis and others are related to imbalanced homeostasis or intake of drugs/toxins. Plants that have been used for decades in folk and traditional medicine have been accepted as one of the commonest sources of discovered natural agents of cancer chemotherapy and chemoprevention. The aim was to study the antioxidant and chemopreventive effects of Strobilanthes crispus on colorectal cancer formation.

Matched MeSH terms: Rats, Sprague-Dawley
Flavonoids and phenylethanoid glycosides from Lippia nodiflora as promising antihyperuricemic agents and elucidation of their mechanism of action

Cheng LC, Murugaiyah V, Chan KL

J Ethnopharmacol, 2015 Dec 24;176:485-93.
PMID: 26593216 DOI: 10.1016/j.jep.2015.11.025

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia nodiflora has been traditionally used in the Ayurvedic, Unani, and Sidha systems, as well as Traditional Chinese Medicine (TCM) for the treatment of knee joint pain, lithiasis, diuresis, urinary disorder and swelling.
AIM OF THE STUDY: The present study aims to investigate the antihyperuricemic effect of the L. nodiflora methanol extract, fractions, and chemical constituents and their mechanism of action in the rat model.
MATERIALS AND METHODS: The mechanisms were investigated by performing xanthine oxidase inhibitory, uricosuric, and liver xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitory studies in potassium oxonate- and hypoxanthine-induced hyperuricemic rats. The plant safety profile was determined using acute toxicity study. The molecular docking of the active compound to the xanthine oxidase was simulated using computer aided molecular modeling analysis.
RESULTS: Oral administration of methanol extract showed a dose-dependent reduction effect on the serum uric acid level of hyperuricemic rats. F3 was the most potent fraction in lowering the serum uric acid level of hyperuricemic rats. Bioactivity-guided purification of F3 afforded two phenylethanoid glycosides, arenarioside (1) and verbascoside (2) and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4), and nodifloretin (5). The highest serum uric acid reduction effect was exhibited by 3 (66.94%) in hyperuricemic rats, followed by 5 (55.97%), 4 (49.16%), 2 (29.03%), and 1 (22.08%) at 0.2 mmol/kg. Dose-response investigation on 3 at doses of 0.05, 0.1, and 0.3 mmol/kg produced a significant dose-dependent reduction on the serum uric acid level of hyperuricemic rats. Repeated administration of F3 or 3 to the hyperuricemic rats for 10 continuous days resulted in a significant and progressive serum uric acid lowering effect in hyperuricemic rats. In contrast, methanol extract and F3 did not reduce serum uric acid level of normoruricemic rats. In addition, F4 significantly increased the uric acid excretion of hyperuricemic rats at 200mg/kg. No toxic effect was observed in rats administered with 5000 mg/kg of methanol extract or F3.
CONCLUSION: The potential application of L. nodiflora against hyperuricemia in the animal in accordance with its traditional uses has been demonstrated in the present study for the first time. The antihyperuricemic effect possessed by L. nodiflora was contributed mainly by liver XOD/XDH inhibitory activities and partially by uricosuric effect. Flavonoids mainly accountable for the uric acid lowering effect of L. nodiflora through the inhibition of XOD/XDH activities.
KEYWORDS: Antihyperuricemic; Hypoxanthine-induced hyperuricemic rat; Lippia nodiflora; Liver xanthine oxidase and xanthine dehydrogenase; Serum uric acid; Uric acid excretion

Matched MeSH terms: Rats, Sprague-Dawley
Rhinacanthin C ameliorates hyperglycaemia, hyperlipidemia and pancreatic destruction in streptozotocin-nicotinamide induced adult male diabetic rats

Adam SH, Giribabu N, Rao PV, Sayem AS, Arya A, Panichayupakaranant P, et al.

Eur J Pharmacol, 2016 Jan 15;771:173-90.
PMID: 26703866 DOI: 10.1016/j.ejphar.2015.12.028

Effect of Rhinacanthin C on hyperglycaemia, hyperlipidemia and pancreatic dysfunction in diabetes was investigated. In-vitro effect of Rhinacanthin C on glucose uptake was studied in 3T3-L1 cell line. Meanwhile, in-vivo effect of 28-days treatment with 5mg/kg/day or 20mg/kg/day Rhinacanthin C was studied in streptozotocin-nicotinamide induced male diabetic rats. Following completion of treatment, fasting blood glucose (FBG), HbA1c, insulin and lipid profile levels were measured by biochemical assays. Histopathological changes in pancreas were observed by light microscopy while levels of pancreatic oxidative stress were determined by enzymatic assays. Expression of insulin, TNFα, Ikkβ and caspase-3 in pancreas were quantified by immunohistochemistry. Molecular docking was used to identify interactions between Rhinacathin C with SOD or GPx enzymes. Dose-dependent increase in glucose uptake was observed with increasing doses of Rhinacathin C. Plasma FBG, HbA1c and lipid profile except LDL levels and pancreatic malonaldehyde level were reduced but serum insulin and pancreatic anti-oxidative enzymes (SOD, CAT and GPx) levels were increased in diabetic rats receiving Rhinacanthin C treatment. Decreased pancreatic histopathological changes with higher pancreatic insulin and Glut-2 levels but lower TNFα, Ikkβ and caspase-3 levels were observed in diabetic rats receiving Rhinacanthin C (P<0.05 compared to non-treated diabetic rats). In diabetic rats which received Rhinacathin C, changes in the above parameters did not achieve the value in non-diabetic rats. Docking shows Rhinacathin C possesses high degree interactions with SOD and GPx. By possessing these effects, Rhinacanthin C could be used as agent to alleviate pancreatic and other complications in diabetes.

Matched MeSH terms: Rats, Sprague-Dawley

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