Centella asiatica

Diabetes mellitus has been reported to affect functions of the hippocampus. We hypothesized that Centella asiatica, a herb traditionally being used to improve memory, prevents diabetes-related hippocampal dysfunction. Therefore, the aim of this study was to investigate the protective role of C. asiatica on the hippocampus in diabetes. Methods. Streptozotocin- (STZ-) induced adult male diabetic rats received 100 and 200 mg/kg/day body weight (b.w) C. asiatica leaf aqueous extract for four consecutive weeks. Following sacrifice, hippocampus was removed and hippocampal tissue homogenates were analyzed for Na+/K+-, Ca2+- and Mg2+-ATPases activity levels. Levels of the markers of inflammation (tumor necrosis factor, TNF-α; interleukin, IL-6; and interleukin, IL-1β) and oxidative stress (lipid peroxidation product: LPO, superoxide dismutase: SOD, catalase: CAT, and glutathione peroxidase: GPx) were determined. The hippocampal sections were visualized for histopathological changes. Results. Administration of C. asiatica leaf aqueous extract to diabetic rats maintained near normal ATPases activity levels and prevents the increase in the levels of inflammatory and oxidative stress markers in the hippocampus. Lesser signs of histopathological changes were observed in the hippocampus of C. asiatica leaf aqueous extract treated diabetic rats. Conclusions. C. asiatica leaf protects the hippocampus against diabetes-induced dysfunction which could help to preserve memory in this condition

Testosterone down-regulates expression of αvβ3-integrin, E-cadherin and mucin-1 during uterine receptivity period in rats

Adequate development of uterine receptivity is crucial for establishment of pregnancy. Expression of uterine receptivity molecules i.e. αvβ3 integrin, E-cadherin and mucin-1 could be affected by testosterone. The objective of this study was to investigate effect of testosterone on expression of these molecules during early pregnancy. 30 ovariectomised female Sprague-Dawley rats were divided into 5 groups that consisted of vehicle control, rats received eight days sex-steroid replacement regime (intended to mimic the hormonal changes in early pregnancy) and three groups of rats given testosterone (1 mg/kg/day) subcutaneously with or without flutamide or finasteride between day 6 and 8 representing the period of uterine receptivity. At the end of the treatment, rats were sacrificed and uteri were removed. Expression and distribution of αvβ3 integrin, E-cadherin and mucin-1 were examined by immunoflourescence and levels of messenger RNA (mRNAs) were evaluated by real-time PCR. Expression of αvβ3 integrin, E-cadherin and mucin-1 in the uteri of rats receiving sex-steroid replacement regime increased significantly as compared to control (p<0.05). In these rats, concomitant administration of testosterone between day 6 and 8 resulted in expression of αvβ3 integrin, E-cadherin and mucin-1 to decrease significantly (p<0.05) as compared to rats receiving sex-steroid replacement regime without testosterone treatment. Moreover, the testosterone effects were not antagonized by either flutamide or finasteride. As a result, reduced expression of uterine receptivity molecules by testosterone might interfere with early pregnancy establishment, therefore could adversely affect the female fertility

Marantodes pumilum (Blume) Kuntze (Kacip Fatimah) stimulates uterine contraction in rats in post-partum period

thnopharmacological relevance: Marantodes pumilum (Blume) Kuntze has traditionally been used to firm the uterus after delivery, however scientific evidences behind this claim is still lacking. Aims of study: To demonstrate Marantodes pumilum leaves aqueous extract (MPE) has an effect on uterine contraction after delivery and to elucidate the molecular mechanisms involved. Methods: Day-1 post-delivery female rats were given MPE (100, 250 and 500 mg/kg/day) orally for seven consecutive days. A day after the last treatment (day-8), rats were sacrificed and uteri were harvested and subjected for ex-vivo contraction study using organ bath followed by protein expression and distribution study by Western blotting and immunohistochemistry techniques, respectively. The proteins of interest include calmo- dulin-CaM, myosin light chain kinase-MLCK, sarcoplasmic reticulum Ca2+-ATPase (SERCA), G-protein α and β (Gα and Gβ), inositol-triphosphate 3-kinase (IP3K), oxytocin receptor-OTR, prostaglandin (PGF)2α receptor- PGFR, muscarinic receptor-MAChR and estrogen receptor (ER) isoforms α and β. Levels of estradiol and pro- gesterone in serum were determined by enzyme-linked immunoassay (ELISA). Results: Ex-vivo contraction study revealed the force of uterine contraction increased with increasing doses of MPE. In addition, expression of CaM, MLCK, SERCA, Gα, Gβ, IP3K, OTR, PGF2α, MAChR, Erα and ERβ in the uterus increased with increasing doses of MPE. Serum analysis indicate that estradiol levels decreased while progesterone levels remained low at day-8 post-partum in rats receiving 250 and 500 mg/kg/day MPE. Conclusions: These findings support the claims that MPE help to firm the uterus and pave the way for its use as a uterotonic agent after delivery

Vitis vinifera

The effect of V. vinifera seeds on carbohydrate metabolizing enzymes and other enzymes of the liver in diabetes is currently unknown. We therefore investigated changes in the activity levels of these enzymes following V. vinifera seed extract administration to diabetic rats. Methods. V. vinifera seed ethanolic extract (250 and 500 mg/kg/day) or glibenclamide (600 μg/kg/day) was administered to streptozotocin-induced male diabetic rats for 28 consecutive days. At the end of treatment, liver was harvested and activity levels of various liver enzymes were determined. Levels of thiobarbituric acid reactive substances (TBARS) were measured in liver homogenates and liver histopathological changes were observed. Results. V. vinifera seed ethanolic extract was able to prevent the decrease in ICDH, SDH, MDH, and G-6-PDH and the increase in LDH activity levels in liver homogenates. The seed extract also caused serum levels of ALT, AST, ALP, ACP, GGT, and total bilirubin to decrease while causing total proteins to increase. Additionally, the levels of ALT, AST, and TBARS in liver homogenates were decreased. Histopathological changes in the liver were reduced. Conclusion. Near normal activity levels of various enzymes and histology of the liver following V. vinifera seed ethanolic extract administration may be due to decrease in liver oxidative stress in diabetes

Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

P. niruri has been reported to possess antidiabetic and kidney protective effects. In the present study, the phytochemical constituents and in vitro antioxidant activity of P. niruri leaf aqueous extract were investigated together with its effect on oxidative stress and antioxidant enzymes levels in diabetic rat kidney. Results. Treatment of diabetic male rats with P. niruri leaf aqueous extract (200 and 400 mg/kg) for 28 consecutive days prevents the increase in the amount of lipid peroxidation (LPO) product, malondialdehyde (MDA), and the diminution of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity levels in the kidney of diabetic rats. The amount of LPO showed strong negative correlation with SOD, CAT, and GPx activity levels. P. niruri leaf aqueous extract exhibits in vitro antioxidant activity with IC 50 slightly lower than ascorbic acid. Phytochemical screening of plant extract indicates the presence of polyphenols. Conclusion. P. niruri leaf extract protects the kidney from oxidative stress induced by diabetes

Gallocatechin-silver nanoparticles embedded in cotton gauze patches accelerated wound healing in diabetic rats by promoting proliferation and inhibiting apoptosis through the Wnt/β-catenin signaling pathway

Background: Diabetes mellitus is a chronic metabolic disorder characterized by elevated plasma glucose levels. It is often defined as a lifestyle disease having severe economic and physiological repercussions on the individual. One of the most prevalent clinical consequences of diabetes is the lagging pace of injury healing leading to chronic wounds, which still to date have limited treatment options. The objective of this research is to look into the wound healing capabilities of gallocatechin (GC) and silver nanoparticles (AgNPs) impregnated patches in diabetic rats. Experimental rats were dressed patches and the wound healing skin region was dissected at the end of the experiment for molecular analysis. The wound healing rate in diabetic rats dressed with CGP2 and CGP3 & silver sulfadiazine (AgS) patches were found to be high. While mRNA and immunofluorescence or immunohistochemistry assays reveal that Wnt3a and β-catenin levels were higher with Gsk-3β and c-fos levels were lower in diabetic rats dressed with in CGP2 and CGP3 as compared with diabetic rats dressed with DC+CGP1. Furthermore, apoptosis markers such as caspase-3, caspase-9, and Bax levels were reduced, whereas anti-apoptosis maker (Bcl-2) and proliferation marker (PCNA) levels were increased in diabetic rats dressed with CGP2 and CGP3 as compared with diabetic rats dressed with DC+CGP1. In conclusion, the results demonstrated that GC-AgNPs-CGP (CGP2 & CGP3) dressing on diabetes wound rats decreased changes in Wnt3a/β-catenin pathways, resulting in lower apoptosis and greater proliferation, so drastically improving diabetic wound healing

Bitter gourd honey ameliorates hepatic and renal diabetic complications on type 2 diabetes rat models by antioxidant, anti-Inflammatory, and anti-apoptotic mechanisms

Abstract: Honey has several pharmacological effects, including anti-diabetic activity. However, the effectiveness of bitter gourd honey (BGH) in the treatment of diabetes mellitus (DM) is unknown. The aim of this study was to determine the antioxidant, anti-inflammatory, and anti-apoptotic properties of BGH on the kidney and liver of a streptozotocin-induced diabetes rat model. Methods: A single dose (nicotinamide 110 mg/kg, streptozotocin (STZ) 55 mg/kg, intraperitoneal (i.p.)) was used to induce DM in male rats. For 28 days, normal or diabetic rats were administered 1 g/kg/day and 2 g/kg/day of BGH orally. After the treatment, blood, liver, and kidney samples were collected and analysed for biochemical, histological, and molecular parameters. In addition, liquid chromatography–mass spectrometry (LC-MS) was used to identify the major bioactive components in BGH. Results: The administration of BGH to diabetic rats resulted in significant reductions in alanine transaminase (ALT),aspartate aminotransferase (AST), creatinine, and urea levels. Diabetic rats treated with BGH showed lesser pathophysiological alterations in the liver and kidney as compared to non-treated control rats. BGH-treated diabetic rats exhibited reduced levels of oxidative stress (MDA levels), inflammatory (MYD88, NFKB, p-NFKB, IKK�), and apoptotic (caspase-3) markers, as well as higher levels of antioxidant enzymes (SOD, CAT, and GPx) in the liver and kidney. BGH contains many bioactive compounds that may have antioxidative stress, anti-inflammatory, and anti-apoptotic effects. Conclusion: BGH protected the liver and kidney in diabetic rats by reducing oxidative stress, inflammation, and apoptosis-induced damage. As a result, BGH can be used as a potential therapy to ameliorate diabetic complications

Leukemia Inhibitory Factor: Roles in Embryo Implantation and in Nonhormonal Contraception

Leukaemia inhibitory factor (LIF) plays an indispensible role in embryo implantation. Aberrant LIF production is linked to implantation failure. LIF regulates multiple processes prior to and during implantation such as uterine transformation into a receptive state, decidualization, blastocyst growth and development, embryo-endometrial interaction, trophoblast invasion, and immune modulation. Due to its critical role, LIF has been a target for a nonhormonal contraception. In this review, we summarize up-to-date information on the role of LIF in implantation and its role in contraception

Sub-chronic testosterone treatment increases the levels of epithelial sodium channel (ENaC)-α, β and γ in the kidney of orchidectomized adult male Sprague–Dawley rats

Testosterone has been reported to cause blood pressure to increase. However mechanisms that underlie the effect of this hormone on this physiological parameter are currently not well understood. The aims of this study were to investigate effects of testosterone on expression of α, β and γ-epithelial sodium channel (ENaC) proteins and messenger RNAs (mRNAs) in kidneys, the channel known to be involved in Na+ reabsorption, which subsequently can affect the blood pressure. Methods. Adult male Sprague–Dawley (SD) rats were orchidectomized fourteen days prior to receiving seven days treatment with testosterone propionate (125 µg/kg/day or 250 µg/kg/day) with or without flutamide (androgen receptor blocker) or finasteride (5α-reductase inhibitor). Following sacrifice, the kidneys were removed and were subjected for α, β and γ-ENaC protein and mRNA expression analyses by Western blotting and Real-time PCR (qPCR) respectively. The distribution of α, β and γ-ENaC proteins in kidneys were observed by immunofluorescence. Results. The α, β and γ-ENaC proteins and mRNA levels in kidneys were enhanced in rats which received testosterone-only treatment. In these rats, α, β and γ-ENaC proteins were distributed in the distal tubules and collecting ducts of the nephrons. Co-treatment with flutamide or finasteride resulted in the levels of α, β and γ-ENaC proteins and mRNAs in kidneys to decrease. In conclusions, increases in α, β and γ-ENaC protein and mRNA levels in kidneys mainly in the distal tubules and collecting ducts under testosterone influence might lead to enhance Na+ reabsorption which subsequently might cause an increase in blood pressure

Testosterone Down-regulates Expression of αVβ3-integrin, E-cadherin and Mucin-1 during Uterine Receptivity Period in Rats

Adequate development of uterine receptivity is crucial for establishment of pregnancy. Expression of uterine receptivity molecules i.e. αvβ3 integrin, E-cadherin and mucin-1 could be affected by testosterone. The objective of this study was to investigate effect of testosterone on expression of these molecules during early pregnancy. 30 ovariectomised female Sprague-Dawley rats were divided into 5 groups that consisted of vehicle control, rats received eight days sex-steroid replacement regime (intended to mimic the hormonal changes in early pregnancy) and three groups of rats given testosterone (1 mg/kg/day) subcutaneously with or without flutamide or finasteride between day 6 and 8 representing the period of uterine receptivity. At the end of the treatment, rats were sacrificed and uteri were removed. Expression and distribution of αvβ3 integrin, E-cadherin and mucin-1 were examined by immunoflourescence and levels of messenger RNA (mRNAs) were evaluated by real-time PCR. Expression of αvβ3 integrin, E-cadherin and mucin-1 in the uteri of rats receiving sex-steroid replacement regime increased significantly as compared to control (p<0.05). In these rats, concomitant administration of testosterone between day 6 and 8 resulted in expression of αvβ3 integrin, E-cadherin and mucin-1 to decrease significantly (p<0.05) as compared to rats receiving sex-steroid replacement regime without testosterone treatment. Moreover, the testosterone effects were not antagonized by either flutamide or finasteride. As a result, reduced expression of uterine receptivity molecules by testosterone might interfere with early pregnancy establishment, therefore could adversely affect the female fertility