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Fulltext The Ameliorative Effects of a Tocotrienol-Rich Fraction on the AGE-RAGE Axis and Hypertension in High-Fat-Diet-Fed Rats with Metabolic Syndrome

Cheng HS, Ton SH, Tan JBL, Abdul Kadir K

Nutrients, 2017 Sep 07;9(9).
PMID: 28880217 DOI: 10.3390/nu9090984

The clinical value of tocotrienols is increasingly appreciated because of the unique therapeutic effects that are not shared by tocopherols. However, their effect on metabolic syndrome is not well-established. This study aimed to investigate the effects of a tocotrienol-rich fraction (TRF) from palm oil in high-fat-diet-treated rats. Male, post-weaning Sprague Dawley rats were provided high-fat (60% kcal) diet for eight weeks followed by a TRF (60 mg/kg) treatment for another four weeks. Physical, metabolic, and histological changes were compared to those on control and high-fat diets respectively. High-fat feeding for eight weeks induced all hallmarks of metabolic syndrome. The TRF reversed systolic and diastolic hypertension, hypercholesterolemia, hepatic steatosis, impaired antioxidant defense, and myeloperoxidase hyperactivity triggered by the high-fat diet. It also conferred an inhibitory effect on protein glycation to reduce glycated hemoglobin A1c and advanced glycation end products (AGE). This was accompanied by the suppression of the receptor for advanced glycation end product (RAGE) expression in the liver. The treatment effects on visceral adiposity, glycemic control, triglyceride level, as well as peroxisome proliferator-activated receptor α and γ expression were negligible. To conclude, treatment with a TRF exhibited protective effects on the cardiovascular and liver health in addition to the amelioration of plasma redox imbalance and AGE-RAGE activation. Further investigation as a therapy for metabolic syndrome is therefore worthwhile.

Matched MeSH terms: Rats, Sprague-Dawley
Effects of age on the glucoregulatory response following acute glucoprivation induced by 2-deoxyglucose (2DG) in the adrenal medulla of Sprague Dawley rats

Muda NA, Ramlan H, Damanhuri HA

Neuro Endocrinol. Lett., 2017 Jul;38(3):224-235.
PMID: 28759191

OBJECTIVES: Impairment in glucose homeostasis is one of the factors that may alter the feeding drive, hunger and satiety signals, which essential to maintain a sufficient level of energy for daily activities especially among the elderly. Adrenal medulla is one of the important organs that involves in glucose homeostasis through secretion of catecholamines. The catecholamines biosynthesis pathway utilizes various enzymes and protein kinases. The aims of this study are to investigate the effects of age on the biosynthetic pathway of catecholamines in adrenal medulla by determining the level of blood glucose and blood catecholamines, the gene and protein expression of biosynthetic catecholamine enzymes (TH, DBH and PNMT) as well as protein kinase substrates that involved in the phosphorylation of TH in 2DG-induced rats.
METHODS: Adrenal medulla from male Sprague Dawley rats at the age of 3-months (n=12) and 24-months (n=12) were further divided into two groups: 1) treatment group with 2DG to create glucoprivation condition and 2) the vehicle group which received normal saline as control.
RESULTS: The results showed that the level of glucose, adrenaline and noradrenaline were increased in response to acute glucoprivation conditions in both young and old rats. No age-related differences were found in the basal gene expression of the enzymes that involved in the catecholamines biosynthesis pathway. Interestingly the expressions of TH and DBH protein as well as the level of TH phosphorylation at Ser40, PKA, PKC and ERK1/2 substrates were higher in basal condition of the aged rats. However, contradicted findings were obtained in glucoprivic condition, which the protein expressions of DBH, pERK1/2 and substrates for pPKC were increased in young rats. Only substrate for pCDK was highly expressed in the old rats in the glucoprivic condition, while pPKC and pERK1/2 were decreased significantly. The results demonstrate that adrenal medulla of young and old rats are responsive to glucose deficit and capable to restore the blood glucose level by increasing the levels of blood catecholamines.
CONCLUSION: The present findings also suggest that, at least in rats, aging alters the protein expression of the biosynthetic catecholamine enzymes as well as protein kinase substrates that may attenuate the response to glucoprivation.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Anticarcinogenic activity of Muntingia calabura leaves methanol extract against the azoxymethane-induced colon cancer in rats involved modulation of the colonic antioxidant system partly by flavonoids

Md Nasir NL, Kamsani NE, Mohtarrudin N, Othman F, Md Tohid SF, Zakaria ZA

Pharm Biol, 2017 Dec;55(1):2102-2109.
PMID: 28872373 DOI: 10.1080/13880209.2017.1371769

CONTEXT: Leaves of Muntingia calabura (Elaeocarpaceae) are widely used in traditional medical practice; scientific findings show various pharmacological activities. However, its anticancer effect has not been investigated thoroughly yet.
OBJECTIVE: The objective of this study is to study the chemoprevention effects of MEMCL against azoxymethane (AOM)-induced colon cancer and to examine the involvement of endogenous antioxidants Materials and methods: Male Sprague-Dawley rats, divided into five groups (n = 7), were injected intraperitoneally once weekly for 2 weeks with 15 mg/kg AOM, except for the normal group (received saline). The animals were then administered orally for 8 weeks with 8% Tween-80 (vehicle; normal group), 8% Tween-80 (vehicle; cancer group) or, 50, 250 or 500 mg/kg MEMC. After treatments, colon samples were collected from each rat for the histopathological analysis, quantification of aberrant crypt foci formed and determination of colon antioxidant levels. MEMC was also subjected to HPLC analysis.
RESULTS: The extract exerted significant (p

Matched MeSH terms: Rats, Sprague-Dawley
Anti-hypertensive and vasodilatory effects of amended Banxia Baizhu Tianma Tang

Tan CS, Loh YC, Ng CH, Ch'ng YS, Asmawi MZ, Ahmad M, et al.

Biomed Pharmacother, 2018 Jan;97:985-994.
PMID: 29136777 DOI: 10.1016/j.biopha.2017.11.021

Although Banxia Baizhu Tianma Tang (BBT) has been long administered for hypertensive treatment in Traditional Chinese Medicine (TCM), the ratio of the herbal components that makes up the formulation has not been optimized with respect to the anti-hypertensive effect that it inherently possesses. A newly amended BBT (ABBT) formulation was developed using the evidence-based approach of orthogonal stimulus-response compatibility model. The ABBT showed enhanced therapeutic effect while maintaining its traditional theoretical approach rooted in TCM. This study was designed to investigate the possible mechanism of actions involved in the vasodilatory activity of ABBT-50 by evaluating its vasodilative effect on isolated Sprague Dawley rats in the presence of absence of various antagonists. When pre-contracted with phenylephrine, relaxation was observed in endothelium intact (EC50=0.027±0.003mg/ml, Rmax=109.8±2.12%) and denuded aortic rings (EC50=0.409±0.073mg/ml, Rmax=63.15±1.78%), as well as in endothelium intact aortic rings pre-contracted with potassium chloride (EC50=32.7±12.16mg/ml, Rmax=34.02±3.82%). Significant decrease in the vasodilative effect of ABBT-50 was observed in the presence of Nω-nitro-l-arginine methyl ester (EC50=0.12±0.021mg/ml, Rmax=75.33±3.28%), 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (EC50=0.463±0.18mg/ml, Rmax=54.48±2.02%), methylene blue (EC50=0.19±0.037mg/ml, Rmax=83.69±3.19%), indomethacin (EC50=0.313±0.046mg/ml, Rmax=71.33±4.12%), atropine (EC50=0.146±0.013mg/ml, Rmax=77.2±3.41%), and 4-aminopyridine (EC50=0.045±0.008mg/ml, Rmax=95.55±2.36%). ABBT-50 was also suppressing Ca2+ release from sarcoplasmic reticulum and inhibiting calcium channels. Vasodilatory effects of ABBT-50 are mediated through NO/sGC/cGMP cascade and PGI2, followed by muscarinic pathways and calcium channels.

Matched MeSH terms: Rats, Sprague-Dawley
Effect of Ipomoea aquatica ethanolic extract in streptozotocin (STZ) induced diabetic rats via1H NMR-based metabolomics approach

Abu Bakar Sajak A, Mediani A, Maulidiani, Mohd Dom NS, Machap C, Hamid M, et al.

Phytomedicine, 2017 Dec 01;36:201-209.
PMID: 29157816 DOI: 10.1016/j.phymed.2017.10.011

BACKGROUND: Ipomoea aquatica (locally known as "kangkung") has previously been reported to have hypoglycemic activities on glucose level in diabetes patients. However, the effect of I. aquatica ethanolic extract on the metabolites in the body has remained unknown.
PURPOSE: This study provides new insights on the changes of endogenous metabolites caused by I. aquatica ethanolic extract and improves the understanding on the therapeutic efficacy and mechanism of I. aquatica ethanolic extract.
METHODS: By using a combination of 1H nuclear magnetic resonance (NMR) with multivariate analysis (MVDA), the changes of metabolites due to I. aquatica ethanolic extract administration in obese diabetic-induced Sprague Dawley rats (OB+STZ+IA) were identified.
RESULTS: The results suggested 19 potential biomarkers with variable importance projections (VIP) above 0.5, which include creatine/creatinine, glucose, creatinine, citrate, carnitine, 2-oxoglutarate, succinate, hippurate, leucine, 1-methylnicotinamice (MNA), taurine, 3-hydroxybutyrate (3-HB), tryptophan, lysine, trigonelline, allantoin, formiate, acetoacetate (AcAc) and dimethylamine. From the changes in the metabolites, the affected pathways and aspects of metabolism were identified.
CONCLUSION: I. aquatica ethanolic extract increases metabolite levels such as creatinine/creatine, carnitine, MNA, trigonelline, leucine, lysine, 3-HB and decreases metabolite levels, including glucose and tricarboxylic acid (TCA) intermediates. This implies capabilities of I. aquatica ethanolic extract promoting glycolysis, gut microbiota and nicotinate/nicotinamide metabolism, improving the glomerular filtration rate (GFR) and reducing the β-oxidation rate. However, the administration of I. aquatica ethanolic extract has several drawbacks, such as unimproved changes in amino acid metabolism, especially in reducing branched chain amino acid (BCAA) synthesis pathways and lipid metabolism.

Matched MeSH terms: Rats, Sprague-Dawley
Urinary metabolic profiling of cisplatin nephrotoxicity and nephroprotective effects of Orthosiphon stamineus leaves elucidated by 1H NMR spectroscopy

Pariyani R, Ismail IS, Azam A, Khatib A, Abas F, Shaari K, et al.

J Pharm Biomed Anal, 2017 Feb 20;135:20-30.
PMID: 27987392 DOI: 10.1016/j.jpba.2016.12.010

Orthosiphon stamineus (OS) is a popular medicinal herb used in traditional Chinese medicine as a diuretic agent and for renal system disorders. This study employed 1H NMR based metabolomics approach to investigate the possible protective activity of OS in cisplatin induced nephrotoxicity owing to its diuretic and antioxidant activities. Aqueous (OSAE) and 50% aqueous ethanolic (OSFE) extracts of OS leaves were orally administered at 400mg/kg BW doses to rats which were then intraperitoneally injected with cisplatin at 5mg/kg BW dose. The 1H NMR profile of the urine samples collected on day 5 after cisplatin administration were analyzed by multivariate pattern recognition techniques, whereby 19 marker metabolites suggestive in the involvement of TCA cycle, disturbed energy metabolism, altered gut microflora and BCAA metabolism pathways were identified. It was observed that OSFE caused significant changes (p<0.05) in the levels of 8 markers namely leucine, acetate, hippurate, lysine, valine, 2-oxoglutarate, 3-HBT and acetoacetate resulting in a moderate ameliorative effect, however, it did not completely protect from nephrotoxicity. OSAE did not demonstrate significant down regulatory effects on any markers, albeit, it potentiated the cisplatin nephrotoxicity by inducing significant increase in glucose, glycine, creatinine, citrate, TMAO, acetate and creatine levels. A Principal Component Analysis (PCA) of the 1H NMR spectra of OS extracts identified that OSFE had higher concentrations of the secondary metabolites such as caffeic acid, chlorogenic acid, protocatechuic acid and orthosiphol, among others. Whereas, OSAE was characterized by higher concentrations of acetate, lactate, succinic acid, valine and phosphatidylcholine. This research denotes the first comprehensive analysis to identify the effects of OS extracts on cisplatin nephrotoxicity.

Matched MeSH terms: Rats, Sprague-Dawley
Vasorelaxant activities and the underlying pharmacological mechanisms of Gynura procumbens Merr. leaf extracts on rat thoracic aorta

Iqbal Z, Bello I, Asmawi MZ, Al-Mansoub MA, Ahmad A, Jabeen Q, et al.

Inflammopharmacology, 2019 Apr;27(2):421-431.
PMID: 29185178 DOI: 10.1007/s10787-017-0422-4

Previous studies have investigated the cardiovascular activity of Gynura procumbens Merr. single-solvent extracts. The objective of this study was to evaluate the in vitro vasorelaxant properties and the underlying pharmacological mechanisms of serial extracts and fractions of Gynura procumbens (GP). The leaves of GP were serially extracted with petroleum ether, chloroform, methanol and water using the maceration method. Suspended aortic ring preparations were pre-contracted with phenylephrine (PE 1 µM), followed by cumulative addition of GP extracts (0.25-3 mg/mL). The petroleum ether extract (GPPE) was the most potent among the four extracts. Pre-incubation of endothelium-intact aorta with atropine (1 µM), indomethacin (10 µM), methylene blue (10 µM), propranolol (1 µM) and potassium channel blockers such as TEA (1 µM), glibenclamide (10 µM), 4-aminopyridine (1 µM) and barium chloride (10 mM) had no effect on GPPE-induced vasorelaxation. The vasorelaxant effect of GPPE was partly diminished by pretreatment of aortic rings preparations with L-NAME (10 µM) and even more so in endothelium-denuded aortic rings, indicating a minimal involvement of endothelium-dependent pathway in GPPE-induced vasorelaxation. The calcium-induced vasocontractions were antagonized significantly and concentration-dependently by GPPE in calcium free and high potassium medium. These results illustrate that Ca2+ antagonizing actions of GPPE in rat isolated aorta are comparable to that of verapamil and may be mainly responsible for its vasodilation effect. The antioxidant activity of GPPE supports its vasorelaxant effect by attenuating the production of deleterious free radicals and reactive oxygen species in the vasculature.

Matched MeSH terms: Rats, Sprague-Dawley
Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats

Yusoff NHM, Mansor SM, Müller CP, Hassan Z

Behav Brain Res, 2018 06 01;345:65-71.
PMID: 29499286 DOI: 10.1016/j.bbr.2018.02.039

Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABAB receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABAB receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABAB receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABAB receptor.

Matched MeSH terms: Rats, Sprague-Dawley
Hypocholesterolemic Effects of Kenaf Seed Oil, Macroemulsion, and Nanoemulsion in High-Cholesterol Diet Induced Rats

Cheong AM, Jessica Koh JX, Patrick NO, Tan CP, Nyam KL

J Food Sci, 2018 Mar;83(3):854-863.
PMID: 29412455 DOI: 10.1111/1750-3841.14038

This study aimed to evaluate the effect of kenaf seed oil (KSO), kenaf seed oil-in-water macroemulsion (KSOM), kenaf seed oil-in-water nanoemulsions (KSON), and emulsifier mixtures (EM) on serum lipid profile, liver oxidative status, and histopathological changes in high-cholesterol fed rats. Stability and characteristic of KSOM and KSON were carried out prior to in vivo study. Forty-two Sprague-Dawley rats were divided into 7 groups (6 rats each) and induced hypercholesterolemia by feeding high cholesterol diet (HCD) for 14 days prior to treatments. Different treatments were introduced on day 15 to 29 while supplemented with HCD and removal of HCD during treatment on day 30 to 43, except for HCD group. Body weight and serum lipid profiles were measured at 3 different points: after hypercholesterolemia was induced, on day 29, and at the end of the experiment. Relative liver weight, atherogenic index, coronary risk index, and fecal total bile acids were also determined at the end of experiment. KSON showed significantly higher stability than KSOM and FTIR exhibited good encapsulation of KSO after 1.5 years of storage. Serum total cholesterol, low density lipoprotein cholesterol, lipid peroxidation levels in HCD group without treatment were significantly higher compared to normal control group and all treatment groups. All samples demonstrated hypocholesterolemic effect, but KSON exhibited higher efficiency in cholesterol-lowering properties, weight control and decreased liver fat as confirmed by histopathological evaluation. The overall results revealed that the efficacy of different treatments was in descending order of KSON, KSO, KSOM, and EM.
PRACTICAL APPLICATION: Kenaf seed oil-in-water nanoemulsion (KSON) has the potential to be used as a natural alternative to the synthetic hypocholesterolemic drug in the future. However, larger sample size and clinical trial are needed to confirm on this potential application. In addition, treatment with KSON was suggested to prevent cardiovascular disease and fatty liver.

Matched MeSH terms: Rats, Sprague-Dawley
Antiulcer activity of methanol-chloroform extract of Channa striatus fillet

Azemi AK, Abd Rahim MH, Mamat SS, Mat Jais AM, Zakaria ZA

Pak J Pharm Sci, 2018 Jan;31(1):143-151.
PMID: 29348096

Channa striatus (Haruan) is Malaysian freshwater fish that is traditionally used to treat ailments related to wound and also ulcers. The aimed of the present study was to determine the mechanisms of anti-ulcer activity of chloroform: methanol extract of C. striatus fillet (CMCS) in rats. The antiulcer profile of CMCS, given orally in the doses of 50, 250 and 500mg/kg, was assessed using the ethanol- and indomethacin-induced gastric ulcer models. The mechanisms of antiulcer of CMCS were determined as follows; i) the antisecretory activity of CMCS was measured using the pyloric ligation rat model, and; ii) the role of nitric oxide (NO) and sulfhydryl compounds in the modulation of CMCS antiulcer activity were determined by pre-treating the rats with L-NAME or NEM, respectively, followed by the pre-treatment of rats with CMCS before subjecting the animals to the ethanol-induced gastric ulcer model. From the results obtained, CMCS exerted significant (P<0.05) antiulcer activity in both models of gastric ulcer wherein the macroscopic and microscopic analysis of the stomach supported the antiulcer claim. With regard to its antisecretory effect, CMCS did not change the volume and pH, but reduce the total acidity only at the lower doses of the gastric juice. Moreover, CMCS demonstrated antiulcer activity was reversed by NEM, but not affected by L-NAME. In conclusion, CMCS shows antiulcer activity that is modulated via its cytoprotective, but not antisecretory effect, and in the presence of sulfhysryl compounds, but not NO.

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext Modulation of Immune Function in Rats Using Oligosaccharides Extracted from Palm Kernel Cake

Faseleh Jahromi M, Shokryazdan P, Idrus Z, Ebrahimi R, Bashokouh F, Liang JB

Biomed Res Int, 2017;2017:2576921.
PMID: 29349067 DOI: 10.1155/2017/2576921

To investigate the prebiotic and immunomodulatory effects of PKC extract (OligoPKC) a total of 24 male rats were randomly assigned to three treatment groups receiving basal diet (control), basal diet containing 0.5% OligoPKC, or basal diet containing 1% OligoPKC for four weeks. We found that OligoPKC had no significant effect on the tested growth parameters. However, it increased the size of the total and beneficial bacterial populations while reducing pathogen populations. OligoPKC increased the concentration of immunoglobulins in the serum and cecal contents of rats. It also enhanced the antioxidant capacity of the liver while reducing lipid peroxidation in liver tissue. OligoPKC affected the expression of genes involved in immune system function in the intestine. Therefore, OligoPKC could be considered a potential mannan-based prebiotic for humans and animals due to its beneficial effects on the health and well-being of the model rats.

Matched MeSH terms: Rats, Sprague-Dawley
Java Tea (Orthosiphon stamineus) protected against osteoarthritis by mitigating inflammation and cartilage degradation: a preclinical study

Bokhari RA, Tantowi NACA, Lau SF, Mohamed S

Inflammopharmacology, 2018 Aug;26(4):939-949.
PMID: 29380171 DOI: 10.1007/s10787-017-0432-2

The effect of Orthosiphon stamineus aqueous (OSA) extract against osteoarthritis (OA) was investigated in explant cartilage culture and in postmenopausal OA rat model. Female rats were bilaterally ovariectomized (OVX). Osteoarthritis was induced after surgical recovery, by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Rats were grouped (n = 8) into: healthy sham control; non-treated OA; OA + diclofenac (positive control 5 mg/kg); and two doses OSA (150-300 mg/kg). After 4 weeks' treatment, rats were evaluated for OA-related parameters and biomarkers. The OSA reduced proteoglycan and ROS release from the cartilage explants under inflammatory (IL-1b) conditions. In the OA-induced rats' cartilages, the OSA downregulated the mRNA expressions for IL-1β, IL-6, IL-10, TNF-α, NF-κβ, NOS2, PTGS2, PTGER2, ACAN, COL2A1, MMP1, MMP13, ADAMTS4, ADAMTS5 and TIMP1, mostly dose-dependently. The OSA reduced the OA rats' serum levels for PGE2, CTX-II, TNF-α, MMP1, MMP13, PIINP, OPG, RANKL, OC and BALP, but not dose-dependently. The OSA contained polyphenols and flavonoids (tetramethoxyflavone). The OSA alleviated articular cartilage degradation, inflammation, collagenase/aggrecanase activities, to improve joint and subchondral bone structure. O. stamineus mitigated osteoarthritis by downregulating inflammation, peptidases and aggrecanases, at a dose equivalent to about 30 mg/kg for humans.

Matched MeSH terms: Rats, Sprague-Dawley
Cellular and Molecular Changes in MNU-Induced Breast Tumours Injected with PF4 or bFGF

Mohd Nafi SN, Idris F, Jaafar H

Asian Pac J Cancer Prev, 2017 Dec 28;18(12):3231-3238.
PMID: 29281877

Background: Angiogenic activity has been considered to reflect important molecular events during breast tumour
development. The present study concerned cellular and molecular changes of MNU-induced breast tumours subjected
to promotion and suppression of angiogenesis. Methods: Female Sprague Dawley rats at the age of 21 days received
MNU at the dose 70 mg/kg of body weight by intraperitoneal injection. Three months post-carcinogen initiation,
mammary tumours were palpated and their growth was monitored. When the tumour diameter reached 1.0 ± 0.05 cm,
rats were given bFGF or PF4 intratumourally at a dose of 10 μg/tumour. Entire palpable tumour were subsequently
excised and subjected to histology examination, IHC staining, and RT-PCR. Results: No critical morphological changes
were observed between pro-angiogenic factor, bFGF, and control groups. However, increase of tumour size with more
necrotic and diffuse areas was notable in tumours after anti-angiogenic PF4 intervention. ER and PR mRNA expression
was significantly up- and down-regulated in bFGF and PF4 groups, respectively. The trends were significantly associated
with peri- and intratumoural MVD counts. However, irrespective of whether we promoted or inhibited angiogenesis,
the expression of EGFR and ERBB2 continued to be significantly increased but this was not significantly associated
with the MVD score. No significant differences in E-cadherin and LR gene expression were noted between intervention
and control groups. Conclusion: ER and PR receptor expression shows consistent responses when tumour angiogenesis
is manipulated either positively or negatively. Our study adds to current understanding that not only do we need to
target hormonal receptors, as presently practiced, but we also need to target endothelial receptors to successfully treat
breast cancer.

Matched MeSH terms: Rats, Sprague-Dawley
Association of urodynamics and lower urogenital tract nerve growth factor after synthetic vaginal mesh implantation on a rat model

Lo TS, Lin YH, Chu HC, Cortes EF, Pue LB, Tan YL, et al.

J Obstet Gynaecol Res, 2017 Jan;43(1):173-178.
PMID: 27762470 DOI: 10.1111/jog.13158

AIM: By investigating the association of urodynamics and urogenital nerve growth factor (NGF) levels in vaginal mesh surgery, we may be able to associate the likelihood of postoperative lower urinary tract symptoms developing as a result of synthetic mesh implanted for pelvic floor reconstructive surgery.
METHODS: Thirty-eight female Sprague-Dawley rats were divided into three groups: mesh, sham (no mesh), and control. Urodynamic study and NGF analysis of the urogenital tissues were done and results were compared among all groups. The urodynamic studies of the mesh and sham groups were further divided into the 4th and 10th days. A P-value

Matched MeSH terms: Rats, Sprague-Dawley
Fulltext In utero exposure to germinated brown rice and its oryzanol-rich extract attenuated high fat diet-induced insulin resistance in F1 generation of rats

Adamu HA, Imam MU, Ooi DJ, Esa NM, Rosli R, Ismail M

BMC Complement Altern Med, 2017 Jan 21;17(1):67.
PMID: 28109299 DOI: 10.1186/s12906-017-1571-0

The development of insulin resistance is multifactorial, with maternal pre- and postnatal nutrition having significant influences. In this regard, high fat diet (HFD) feeding in pregnancy has been shown to increase risks of metabolic diseases. Thus, we investigated the effects of supplementation of HFD with germinated brown rice (GBR) and GBR-derived gamma oryzanol-rich extract (OE) on insulin resistance and its epigenetic implications in pregnant rats and their offsprings.

Matched MeSH terms: Rats, Sprague-Dawley
Anti-allergic activity of 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis

Tan JW, Israf DA, Harith HH, Md Hashim NF, Ng CH, Shaari K, et al.

Toxicol Appl Pharmacol, 2017 03 15;319:47-58.
PMID: 28167223 DOI: 10.1016/j.taap.2017.02.002

tHGA, a geranyl acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent ovalbumin-induced allergic airway inflammation in a murine model of allergic asthma by targeting cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including asthma by releasing cysteinyl leukotrienes. The anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation. As mast cell degranulation is an important event in allergic responses, this study aimed to investigate the anti-allergic effects of tHGA in cellular and animal models of IgE-mediated mast cell degranulation. For in vitro model of IgE-mediated mast cell degranulation, DNP-IgE-sensitized RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA to induce degranulation. For IgE-mediated passive systemic anaphylaxis, Sprague Dawley rats were sensitized by intraperitoneal injection of DNP-IgE before challenged with DNP-BSA. Both in vitro and in vivo models showed that tHGA significantly inhibited the release of preformed mediators (β-hexosaminidase and histamine) as well as de novo mediators (interleukin-4, tumour necrosis factor-α, prostaglandin D2 and leukotriene C4). Pre-treatment of tHGA also prevented IgE-challenged RBL-2H3 cells and peritoneal mast cells from undergoing morphological changes associated with mast cell degranulation. These findings indicate that tHGA possesses potent anti-allergic activity via attenuation of IgE-mediated mast cell degranulation and inhibition of IgE-mediated passive systemic anaphylaxis. Thus, tHGA may have the potential to be developed as a mast cell stabilizer for the treatment of allergic diseases in the future.

Matched MeSH terms: Rats, Sprague-Dawley
Antidiabetic effects of Brucea javanica seeds in type 2 diabetic rats

Ablat A, Halabi MF, Mohamad J, Hasnan MH, Hazni H, Teh SH, et al.

BMC Complement Altern Med, 2017 Feb 06;17(1):94.
PMID: 28166749 DOI: 10.1186/s12906-017-1610-x

Brucea javanica (B. javanica) seeds, also known as "Melada pahit" in Indo-Malay region are traditionally used to treat diabetes. The objective of this study was to determine antidiabetic, antioxidant and anti-inflammatory effects of B. javanica seeds on nicotinamide (NA)-streptozotocin (STZ) induced type 2 diabetic (T2D) rats and to analyze its chemical composition that correlate with their pharmacological activities.

Matched MeSH terms: Rats, Sprague-Dawley
The properties of red seaweed (Kappaphycus alvarezii) and its effect on mammary carcinogenesis

Chang VS, Okechukwu PN, Teo SS

Biomed Pharmacother, 2017 Mar;87:296-301.
PMID: 28063411 DOI: 10.1016/j.biopha.2016.12.092

The edible red seaweed (Kappaphycus alvarezii) is one of the algae species which was found to be rich in nutrients and nutraceutical. Hence, K. alvarezii may have the ability to suppress cancer through its antiproliferative properties. The aim of this study was to investigate the potential compounds of K. alvarezii, cytotoxicity properties of K. alvarezii extract on breast cancer cell line (MCF-7), investigated toxicity effect of high dosage K. alvarezii extract in rats and determined the effect of K. alvarezii on 7, 12-dimethylbenz[a]anthracene (DMBA) mammary carcinogenesis in rats. The method of LCMS/MS and MTT assay were used. For animal study, sub-chronic toxicity method was used, the rats were supplemented with 2000mg/kg body weight daily of K. alvarezii crude extracts by oral gavage. For the anticancer effect of K. alvarezii crude extracts, this study consisted of three groups of the experimental, untreated and normal group of rats. The experimental and untreated groups of rats were induced with mammary tumour with DMBA. The experimental group of rats was given with K. alvarezii crude extracts orally. The results were being used to compare with the untreated group of rats and normal group of rats. All the rats were fed with standard diet and water ad libitum. Mortality, behavior changes and tumour sizes were observed specifically. The differences between the three groups of rats were evaluated by using the ANOVA test. By using LCMS/MS method, six unknown compounds were analysed. K. alvarezii crude extract reduced the cell viability of MCF-7 from 84.91% to 0.81% and the IC50 value is 4.1±0.69mg/mL. For sub-chronic and heavy metal toxicity studies, no significant difference was found in haematological and biochemical values of the control group and experimental group. The growth rate of tumours in the untreated group of rats was found significantly higher than the experimental group of rats. Besides that, the white blood cells level in untreated group was found significantly higher than the experimental group and the normal group. In conclusion, K. alvarezii extract might able to slow down the growth rate of the tumour cells, therefore, identification of an active compound of inhibition growth rate of the tumour cells can be positively carried out in the future.

Matched MeSH terms: Rats, Sprague-Dawley
Caffeoylquinic Acids Rich versus Poor Fractions of Gynura procumbens: Their Comparative Antihyperlipidemic and Antioxidant Potential

Murugesu K, Murugaiyah V, Saghir SAM, Asmawi MZ, Sadikun A

Curr Pharm Biotechnol, 2017;18(14):1132-1140.
PMID: 29564975 DOI: 10.2174/1389201019666180322111800

BACKGROUND: Ethanolic extract of G. procumbens leaves has been previously shown to possess antihyperlipidemic effects.
OBJECTIVE: This study was designed to prepare caffeoylquinic acids rich and poor fractions of the ethanolic extract using resin column technology and compare their antihyperlipidemic and antioxidant potentials.
RESULTS: Among the treatment groups, caffeoylquinic acids rich fraction (F2) and chlorogenic acid (CA, one of the major caffeoylquinic acids) showed potent antihyperlipidemic effects, with significant reductions in total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), atherogenic index (AI) and coronary risk index (CRI) (p<0.01 or better) compared to the hyperlipidemic control at the 58 h. The effect was better than that of ethanolic extract. In addition, only F2 significantly increased the high-density lipoproteincholesterol (HDL-C) level (p<0.05). F2 showed better effect than CA alone (60 mg) despite the fact that it only contained 9.81 mg CA/1000 mg dose. The findings suggest that the di-caffeoylquinic acids (86.61 mg/g dose) may also in part be responsible for the potent antihyperlipidemic effect shown by the F2. Likewise, F2 showed the highest antioxidant activity. Thus, simple fractionation of ethanolic extract using the Amberlite XAD-2 resin technique had successfully enriched the caffeoylquinic acids into F2 with improved antihyperlipidemic and antioxidant capacities than that of the ethanolic extract.
CONCLUSION: The resin separation technology may find application in caffeoylquinic acids enrichment of plant extracts for pre-clinical studies. The F2 has potential for development into phytopharmaceuticals as adjunct therapy for management of hyperlipidemia.

Matched MeSH terms: Rats, Sprague-Dawley
Bee bread attenuates the progression of atherosclerosis by activating Nrf2/Keap1 and modulating TNF-α/NF-κβ-associated mast cell migration and a mitochondrial-dependent apoptotic pathway in the obese rat model

Othman ZA, Zakaria Z, Suleiman JB, Che Jalil NA, Wan Ghazali WS, Mohamed M

Food Funct, 2022 Aug 01;13(15):8119-8130.
PMID: 35796099 DOI: 10.1039/d2fo00949h

This study explores the anti-atherosclerotic effects of bee bread in the context of oxidative stress, inflammation, and apoptosis phenomena in an obesity animal model, and its vitamin composition. Forty male Sprague-Dawley rats were administered with a normal diet (Normal group) and a high-fat diet (HFD) to induce obesity. After 6 weeks, obese rats that received the HFD were treated either with distilled water (Ob group), bee bread at 0.5 g per kg per day (Ob + Bb group), or orlistat at 10 mg per kg per day (Ob + Or group) concomitant with the HFD for another 6 weeks. Bee bread significantly improved atherosclerotic changes by enhancing the immunoexpressions of Nrf2/Keap1, impeding the immunoexpressions of NF-κβ downstream proteins, and intensifying Bcl-2 upregulation, attributed to the improvement in mast cell adherence and collagen deposition in the aortic wall of the Ob + Bb group. We have demonstrated that the treatment with bee bread attenuates the progression of atherosclerosis through its inhibition of vascular oxidative stress, and retardation of inflammatory reaction and apoptosis in obese rats, indicating its potential therapeutic targets for obesity-related vascular diseases. This could be partly attributed to the components of vitamins such as vitamins A, C and E that are present in bee bread, which need further study for the exact molecular mechanism of action.

Matched MeSH terms: Rats, Sprague-Dawley

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