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Fulltext Insulin-Loaded Barium Salt Particles Facilitate Oral Delivery of Insulin in Diabetic Rats

Zaman R, Karim ME, Othman I, Zaini A, Chowdhury EH

Pharmaceutics, 2020 Jul 29;12(8).
PMID: 32751231 DOI: 10.3390/pharmaceutics12080710

Oral delivery is considered as the most preferred and yet most challenging mode of drug administration; especially a fragile and sensitive peptide like insulin that shows extremely low bioavailability through the gastro-intestinal (GIT) route. To address this problem, we have designed a novel drug delivery system (DDS) using precipitation-induced Barium (Ba) salt particles. The DDS can load insulin molecules and transport them through the GIT route. There were several in vitro simulation tests carried out to prove the efficiency of Ba salt particles as oral delivery candidates. All three Ba salt particles (BaSO4, BaSO3, and BaCO3) showed very good loading of insulin (>70% in all formulations) and a degree of resistance throughout a wide range of pHs from basic to acidic conditions when assessed by spectrophotometry. Particles and insulin-associated particles were morphologically assessed and characterized using FE-SEM and FT-IR. A set of tests were designed and carried out with mucin to predict whether the particles are potentially capable of overcoming one of the barriers for crossing intestinal epithelium. The mucin binding experiment demonstrated 60-100% of mucin adhesion to the three different particles. FT-IR identifies the characteristic peaks for mucin protein, particles, and particle-mucin complex re-confirming mucin adhesion to the particles. Finally, the effectiveness of nano-insulin was tested on streptozotocin (STZ) induced diabetic rats. A short acting human insulin analog, insulin aspart, was loaded into Ba salt particles at a dose of 100 IU/Kg prior to oral administration. Among the three formulations, insulin aspart-loaded BaSO4 and BaCO3 particles dramatically reduced the existing hyperglycemia. BaSO4 with loaded Insulin showed an onset of glucose-lowering action within 1 hr, with blood glucose level measured significantly lower compared to the 2nd and 3rd h (p < 0.05). Insulin-loaded BaCO3 particles showed a significant decrease in blood glucose level at 1-2 h, although the glucose level started to show a slight rise at 3rd h and by 4th h, it was back to baseline level. However, although BaSO3 particles with loaded insulin showed a trend of reduction in blood glucose level, the reduction was not found to be significant (p < 0.05) at any point in time. Therefore, oral formulations of insulin/BaSO4 and insulin/BaCO3 particles were observed as effective as native insulin aspart subcutaneous formulation in terms of onset and duration of action. Further investigation will be needed to reveal bioavailability and mechanism of action of this novel Nano-Insulin formulations.

Matched MeSH terms: Diabetes Mellitus, Experimental
Evaluation of wound healing activity of plumbagin in diabetic rats

Shao Y, Dang M, Lin Y, Xue F

Life Sci, 2019 Aug 15;231:116422.
PMID: 31059689 DOI: 10.1016/j.lfs.2019.04.048

This study was performed to evaluate the antidiabetic and wound healing activity of plumbagin in diabetic rats by macroscopical, biochemical, histological, immunohistochemical and molecular methods. Percentage of wound closure and contraction was delayed in diabetic rats when compared to non-diabetic group. There was significant reduction in period of epithelialization, collagen and protein content. Serum insulin level was significantly lowered together with increase in glucose level in diabetic rats. Lipid levels were increased significantly with concomitant decrease in HDL level. The mRNA levels of Nrf2, collagen-1, TGF-β and α-SMA were significantly lowered whereas Keap-1 levels were increased in diabetic rats. The level of lipid peroxides was increased while the levels of antioxidants were lowered significantly. ELISA results reveal upregulated levels of inflammatory markers. Western blot result shows upregulated levels of CD68 and CD163 proteins in wound area of diabetic rats. Histopathological observation revealed increased inflammatory cells infiltration in diabetic control. Immunofluorescent staining and immunohistochemical analysis also displayed delayed wound healing in diabetic groups. Diabetic rats treated with 10% and 20% plumbagin showed increased epithelialization, collagen deposition, increased serum insulin level and increased antioxidant status. Lipid peroxides and lipid levels were lowered significantly with increase in HDL level. Inflammatory markers were lowered, and growth factors expressions were increased markedly. Thus, the results of the study indicated that plumbagin administration could improve wound healing activity and could serve as a potent antidiabetic and anti-inflammatory agent.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Glutathione (GSH) improves sperm quality and testicular morphology in streptozotocin-induced diabetic mice

Abdullah F, Khan Nor-Ashikin MN, Agarwal R, Kamsani YS, Abd Malek M, Bakar NS, et al.

Asian J Androl, 2021 1 22;23(3):281-287.
PMID: 33473013 DOI: 10.4103/aja.aja_81_20

Diabetes mellitus (DM) is known to cause reproductive impairment. In men, it has been linked to altered sperm quality and testicular damage. Oxidative stress (OS) plays a pivotal role in the development of DM complications. Glutathione (GSH) is a part of a nonenzymatic antioxidant defense system that protects lipid, protein, and nucleic acids from oxidative damage. However, the protective effects of exogenous GSH on the male reproductive system have not been comprehensively examined. This study determined the impact of GSH supplementation in ameliorating the adverse effect of type 1 DM on sperm quality and the seminiferous tubules of diabetic C57BL/6NTac mice. GSH at the doses of 15 mg kg-1 and 30 mg kg-1 was given intraperitoneally to mice weekly for 6 consecutive weeks. The mice were then weighed, euthanized, and had their reproductive organs excised. The diabetic (D Group) showed significant impairment of sperm quality and testicular histology compared with the nondiabetic (ND Group). Diameters of the seminiferous lumen in diabetic mice treated with 15 mg kg-1 GSH (DGSH15) were decreased compared with the D Group. Sperm motility was also significantly increased in the DGSH15 Group. Improvement in testicular morphology might be an early indication of the protective roles played by the exogenous GSH in protecting sperm quality from effects of untreated type 1 DM or diabetic complications. Further investigation using different doses and different routes of GSH is necessary to confirm this suggestion.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Protective effect of aqueous extracts from Canarium odontophyllum Miq. leaf on liver in streptozotocin-induced diabetic rats

Siti Balkis Budin, Kumar, Shashi, Nor Malia Abd Warif, Shafikha Mohd Saari, Dayang Fredalina Basri

Life Sciences, Medicine and Biomedicine, 2018;2(1):1-5.
MyJurnal

The fruit of Canarium odontophyllum Miq. is a traditional delicacy in Borneo for its anti-aging benefit. This study evaluated the protective effect of C. odontophyllum leaf aqueous extract on damaged liver in streptozotocin-induced diabetic rats. A total of 30 male Spraque-Dawley rats (150-250g) were randomly divided into three groups: control group, diabetic without treatment and diabetic treated with 300 mg/kg aqueous extract of C. odontophyllum for 28 consecutive days. The diabetic condition was induced by intraperitoneal injection of streptozotocin at 65 mg/kg body weight. At the end of study period, blood was collected to assess the biochemical changes and the oxidative stress markers whereas the liver section was examined for morphological changes. Result showed that the level of aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in diabetic rats treated with C. odontophyllum were significantly reduced (p

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Metabolic and immunologic alterations of ginger rhizome among streptozotocin-nicotinamide induced diabetic rats

Mansooreh, Sadat Mojani, Asmah Rahmat, Rajesh, Ramasamy, Vahid, Hosseinpour Sarmadi, Pratheep, Sandrasaigaran, Shalini, Vellasamy, et al.

Malays J Nutr, 2016;22(3):421-432.
MyJurnal

Introduction: This study was conducted to determine immunological and metabolic effects of different concentrations of ginger rhizome (Zingiber officinale Roscoe) in streptozotocin (STZ)-nicotinamide (NA) induced diabetic rats.

Methods: Forty-eight fasted male Sprague-Dawley rats were induced diabetes using a single intraperitoneal injection of NA(110 mg/kg b.w.) and STZ (65 mg/kg b.w, 15 min after NA). Diabetic rats orally received either different concentrations (250, 500 and 750 mg/kg body weight) of ginger rhizome suspension or glibenclamide (10 mg/kg body weight) for 6 weeks. Two control diabetic and normal groups were gavaged with only distilled water as a vehicle.

Results: The results indicated that the lower concentrations of ginger modulated body weight, fasting blood glucose, level of triglyceride and tumor necrosis factor-a (TNF-a) (p

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Antihyperglycaemic and Toxicological Evaluations of Extract and Fractions of Gynura procumbens Leaves

Algariri K, Atangwho IJ, Meng KY, Asmawi MZ, Sadikun A, Murugaiyah V

Trop Life Sci Res, 2014 Aug;25(1):75-93.
PMID: 25210589 MyJurnal

The acute and sub-chronic antihyperglycaemic activity, safety margin evaluations and chemical composition of ethanol extract (EE) and fractions of Gynura procumbens (GP) were studied. Streptozotocin (STZ)-induced diabetic rats (SDRs) and the Organisation for Economic Cooperation and Development (OECD) guidelines 425 and 407 were used in the antidiabetic and toxicity studies, respectively. Biochemical and haematological data obtained from both acute and sub-chronic procedures suggest that the extract is safe at the limit test dose (2000 mg/kg); thus, the oral lethal dose (LD50) exceeds 2000 mg/kg. The acceptable daily intake (ADI) was determined to be 700 mg/kg/day. In the acute antihyperglycaemic study, the n-butanol fraction (n-BF) was found to consistently lower glucose levels the most effectively, which was also demonstrated in the 14-day study. Not only did the n-BF show the highest dose-dependent glucose-lowering action (51.2% and 62.0% at 500 mg/kg and 1000 mg/kg, respectively), its effect was the closest to that of metformin (63.6%, p<0.05). The estimated amount of flavonoids in n-BF were 62.90% and 79.68% higher than the ethyl acetate fraction (EAF) and aqueous fraction (AF), respectively (p<0.05), with a corresponding value of 61.22% and 49.33% for phenolics (p<0.05). GP leaves have a no-observed-adverse-effect-level (NOAEL) and antihyperglycaemic activity corresponding to the high content of phenols and flavonoids. Therefore, GP leaves are a promising source of new antidiabetic natural products.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Antidiabetic and In Vitro Enzyme Inhibition Studies of Methanol Extract of Ocimum tenuiflorum Linn Leaves and Its Fractions

Mousavi L, Salleh RM, Murugaiyah V

Trop Life Sci Res, 2020 Apr;31(1):141-158.
PMID: 32963716 DOI: 10.21315/tlsr2020.31.1.9

The current study aimed to determine the best dose of methanol extract of Ocimum tenuiflorum L. leaves extract, and it is a fraction to blood-glucose-lowering in diabetic rats, and evaluated the α-amylase, α-glucosidase inhibitors and insulin level of diabetic rats used to achieve greater control over hyperglycemia. The result of the antihyperglycaemic of oral administration of a different dose of methanol extract in streptozotocin-induced rats showed that the highest dose of methanol extract significantly reduced the blood glucose level compared to another dose. Also, the result of repeated administration of methanol fractions indicates that ethyl acetate-butanol fraction exhibited a stronger antihyperglycemic effect than chloroform and ethanol-water fractions. Moreover, the result showed that effect of methanol extract and its fraction on α-glucosidase and α-amylase enzymes activities and its insulin level by in vitro study, ethyl acetate-butanol fraction could control with low concentration compared to other fractions and acarbose that used as a positive control. From the result of insulin level, methanol extract and fraction did not show any significant. These findings indicated that the active crude extract (methanol) and its active fractions (ethyl acetate/butanol) could exert significant glucose-lowering effect due to the presence of polyphenolics active constituents. In conclusion, isolation of the active components of Ocimum tenuiflorum L. may pave the way to the development of new agents for the treatment of diabetes and its complications.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Effects of Canarium odontophyllum leaves on plasma glucose and T lymphocyte population in streptozotocin-induced diabetic rats

Saari SM, Basri DF, Budin SB, Warif NM

Saudi J Biol Sci, 2017 Feb;24(2):320-323.
PMID: 28149168 DOI: 10.1016/j.sjbs.2015.09.032

Type 1 diabetes mellitus is a chronic disease characterized by lack of insulin production. Immune mechanisms are implicated in the pathogenesis of Type 1 diabetes. Canarium odontophyllum (CO) fruits and leaves have been shown to possess high antioxidant activity. This study was conducted to evaluate the effects of CO leaves aqueous extract on the blood glucose and T lymphocyte population in the spleen of streptozotocin (STZ)-induced diabetic rats. Nineteen male Sprague-Dawley rats were randomly divided into three groups: normal, diabetic control and CO treated diabetic groups. Diabetes was induced by a single intraperitoneal injection of 65 mg STZ/kg body weight. The extract of CO leaves was administered orally by force feeding daily at the dose of 300 mg/kg for 28 days. The rats were sacrificed at the end of the study and the spleen was harvested for flow cytometry analysis. The results showed a significant decrease in body weight of diabetic and CO treated diabetic groups compared with the normal group (p

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Hypertension influences the exponential progression of inflammation and oxidative stress in streptozotocin-induced diabetic kidney

Muthaian R, Pakirisamy RM, Parasuraman S, Raveendran R

J Pharmacol Pharmacother, 2017 2 7;7(4):159-164.
PMID: 28163536 DOI: 10.4103/0976-500X.195898

OBJECTIVE: To investigate the association of hypertension coexisting with diabetes mellitus with oxidative stress and inflammation in the kidneys of streptozotocin (STZ)-induced diabetic rats.
MATERIALS AND METHODS: Male Wistar rats were used for the experiments. Blood glucose (BG), urea, blood pressure (BP), and heart rate (HR) were analyzed before and 48 h after STZ injection. Further, these parameters were monitored up to 3 months of diabetes induction. Subsequently, the inflammatory markers (C-reactive protein, tumor necrosis factor-alpha, and nitrate) and oxidative stress markers were estimated after 3 months of diabetes induction in the kidney homogenate. Histological analysis of renal tissue was also carried out.
RESULTS: Linear elevation of BG, urea, mean arterial pressure (MAP), and HR was observed up to 3 months of diabetes induction. In the same manner, inflammatory and oxidative stress markers were also found to be significantly increased. Notably, the histological analysis revealed the signs of nephropathy such as increased mesangial cell number, thickness of basement membrane, and renal artery. Inflammatory and oxidative stress markers positively correlated with elevated BP and BG, but the correlation was better with BP rather than BG.
CONCLUSION: Hypertension has a strong implication in the increased oxidative stress and inflammation of diabetic kidney at the very early stage of diabetes mellitus.

Matched MeSH terms: Diabetes Mellitus, Experimental
Protective role of Hibiscus sabdariffa calyx extract against streptozotocin induced sperm damage in diabetic rats

Idris MH, Budin SB, Osman M, Mohamed J

EXCLI J, 2012;11:659-669.
PMID: 27847454

Diabetes mellitus contributes to male sexual dysfunction and infertility by modulating oxidative damage. To date, a number of studies have demonstrated antioxidant properties of Hibiscus sabdariffa Linn. This study was designed to investigate the effects of H. sabdariffa UKMR-2 variety on sperm functioning of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were allotted into four groups, namely control group (C), H. sabdariffa extract (HSE) group, diabetes group (D) and diabetes plus HSE group (D+HSE). HSE (100 mg/ kg/body weight) was administered orally for 28 consecutive days. After 28-days of supplementation, the rats were sacrificed to obtain epididymal sperm. Administration of HSE significantly lowered the level of fasting blood glucose and increased plasma insulin level in D+HSE group as compared to D group (p<0.05). Sperm quality in the D+HSE group was improved with significantly higher sperm concentrations (p<0.05) and sperm motility (p<0.001) as well as lower percentage of sperm abnormality (p<0.05) as compared to the diabetic group. Plasma follicle-stimulating hormone (FSH) level was significantly elevated (p<0.05) in D+HSE group than in D group while no significant alteration in plasma testosterone and luteinizing hormone (LH) level were seen between groups. In conclusion, this study suggested that H. sabdariffa UKMR-2 variety has a potential protective role against diabetes-induced sperm damage.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Edible Bird's Nest Protects Against Hyperglycemia-Induced Oxidative Stress and Endothelial Dysfunction

Murugan DD, Md Zain Z, Choy KW, Zamakshshari NH, Choong MJ, Lim YM, et al.

Front Pharmacol, 2019;10:1624.
PMID: 32116666 DOI: 10.3389/fphar.2019.01624

Increased oxidative stress by hyperglycemia is a major cause of vascular complications in diabetes. Bird's nest, which is made from the saliva of swiftlets has both medicinal and nutritional values dated back to ancient China. However, its role in improving endothelial dysfunction due to diabetes is yet to be elucidated. The present study examined the protective effect and mechanism of action of the aqueous extract of hydrolyzed edible bird nest (HBN) on endothelium in models of diabetes, in vitro and in vivo. Male db/m+ and db/db mice were orally administered with or without HBN and glibenclamide for 28 days, followed by vascular reactivity studies in mouse aortas. Human umbilical vein endothelial cells (HUVECs) and isolated mouse aorta from C57BL/6J were treated with high glucose (HG), HBN, sialic acid (SA), glibenclamide, and apocynin, respectively. The effects of HBN on reactive oxygen species (ROS) production and nitric oxide (NO) bioavailability were assessed by Western blot, 2',7'-dichlorofluorescin-diacetate (DCF-DA), and 4-amino-5-methylamino-2',7' difluorofluorescein (DAF-FM DA) in HUVECs, isolated mouse aorta, and db/db diabetic mice. HBN significantly reversed the endothelial dysfunction in diabetic mice and isolated mouse aorta. HBN normalized ROS over-production of NOX2 and nitrotyrosine, reversed the reduction of anti-oxidant marker, SOD-1 as well as restored NO bioavailability in both HUVECs challenged with HG and in db/db diabetic mice. Similarly, HG-induced elevation of oxidative stress in HUVECs were reversed by SA, glibenclamide, and apocynin. This attests that HBN restores endothelial function and protects endothelial cells against oxidative damage induced by HG in HUVECs, isolated mouse aorta, and db/db diabetic mice via modulating ROS mechanism, which subsequently increases NO bioavailability. This result demonstrates the potential role of HBN in preserving endothelial function and management of micro- or macrovascular complications in diabetes.

Matched MeSH terms: Diabetes Mellitus, Experimental
Evaluation of antihyperglycemic and antihyperlipidemic potential of Nelumbo Nucifera seeds in diabetic rats

Khan SH, Ali F, Shah A, Kamran F, Jahan S

Sains Malaysiana, 2016;45:1517-1523.

The present study was aimed at evaluating antihyperglycemic and antihyperlipidemic activity of nuciferin and
norcoclaurine constituents of N. nucifera seeds, a well-known medicinal plant. The alloxan (100 mg/kg b.w) induced
diabetic rats (200-250 g) were divided into seven groups (n = 6). Group I; normal control, Group II; diabetic control,
Group III; standard, Group lV-VII were fed with methanolic crude extracts (100, 200 mg/kg), nuciferin and norcoclaurine
(10 mg/kg b.w.), received for 15 days in dose dependent manner. The study included different parameters; examination of
oral glucose, fasting blood glucose, serum lipid profile and checking for body weight changes. In oral glucose examination,
within 60 and 80 min of treatment, extracts, nuciferin and norcoclaurine significantly reduced blood glucose (p<0.05)
and restored body weight in diabetic rats. Alloxan- induced diabetic rats showed 30-50% reduction of blood glucose
level (p<0.05) and recovered 5-20% body weight at day 15 after ingestion of crude extracts (100-200 mg/kg b.w.); and
nuciferin and norcoclaurine (each at 10 mg/kg b.w.). It also recovered significantly elevated biochemical parameters such
as triglycerides (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC), serum urea and
creatinine. Our findings indicated that N. nucifera seeds possess significant antihyperglycemic and antihyperlipidemic
activity in diabetic rats.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Psidium guajava fruit peel extract reduces oxidative stress of pancreas in streptozotocin-induced diabetic rats

Siti Balkis Budin, Hawa Ismail, Pek LC

Sains Malaysiana, 2013;42:707-713.

Abundant natural products with medicinal properties have been used as food and traditional medicine for diabetes mellitus all over the world. Psidium guajava fruit from the family of Myrtaceae has gained attention for its antioxidant potential. This study was conducted to determine the effects of P. guajava fruit peel aqueous extract on oxidative stress of pancreas in streptozotocin-induced (45 mg/kg) diabetic rats. Diabetic rats were administered with 400 mg/kg of aqueous extract of P. guajava fruit peel daily for 28 days duration. The results showed that diabetic rats supplemented with P. guajava extract did not cause significant difference in blood glucose level (p>0.05) as compared with diabetic rats alone. For oxidative stress evaluation, malondialdehyde (MDA) and protein carbonyl level were significantly lower and the activity of superoxide dismutase (SOD) and glutathione (GSH) level were significantly higher (p<0.05) in P. guajava supplemented rats compared with non-supplemented diabetic rats. However, histological observation showed that supplementation of P. guajava extract did not give protective effects towards alterations in pancreas histology in diabetic rats. The findings suggested that aqueous extract of P. guajava fruit peel supplementation has the ability to reduce oxidative stress in pancreas of diabetic rats and may play a role in reducing the development of diabetic complications.

Matched MeSH terms: Diabetes Mellitus, Experimental
Safety assessment of standardized aqueous Brucea javanica extract in rats

Man F, Choo CY

J Ethnopharmacol, 2018 Apr 06;215:21-26.
PMID: 29288829 DOI: 10.1016/j.jep.2017.12.040

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Brucea javanica and its aqueous decoction is a traditional medicine consumed by diabetic patients in Malaysia. The daily consumption of B. javanica seeds and it's aqueous decoction causes much concern as the quassinoids and its glycosides from the seeds exhibited various pharmacological activity at low doses.
AIMS OF STUDY: The aim of the present study is to evaluate the repeated dose toxicity of the standardized aqueous extract administered daily for 30 days through oral administration at its effective hypoglycemia doses.
MATERIALS AND METHODS: The seeds were dried, ground and extracted in deionized water. A HPLC-photodiode array method was developed and validated for the standardization of both the hypoglycemia agents, namely bruceine D and E in aqueous extract. Both normoglycemia and streptozotocin (STZ)-induced diabetic rats were fed orally with 15, 30 and 60mg/kg body weight of standardized aqueous extract. The blood glucose was measured at 0-8h. In repeated dose toxicity, similar doses were administered orally to rats for 30 days. At the end of 30 days, the blood was withdrawn and subjected to biochemical and haematology analysis while organs were harvested for histology analysis.
RESULTS: Oral administration of standardized aqueous extract exhibited a dose-response relationship in both the normoglycemia and STZ-induced diabetic rats. Daily oral administration of 15, 30 and 60mg/kg standardized aqueous extract for 30 days to rats did not show signs to toxicity in its biochemical, haematology and histology analysis.
CONCLUSION: In conclusion, although the seeds were reported to contain compounds with various pharmacological activity, the daily oral administration to rats for 30 days do not showed signs of toxicity at its effective hypoglycemia doses.

Matched MeSH terms: Diabetes Mellitus, Experimental
Gynura procumbens Improved Fertility of Diabetic Rats: Preliminary Study of Sperm Proteomic

Kamaruzaman KA, Aizat WM, Mat Noor M

Evid Based Complement Alternat Med, 2018;2018:9201539.
PMID: 30363997 DOI: 10.1155/2018/9201539

Gynura procumbens (GP) is a medicinal herb that has long been known as anti-inflammatory and antihyperglycaemic. Recently, this herbal extract has been associated with a profertility effect, suggesting its applicability in treating both diabetes and male infertility. In this study, the effects of GP aqueous extract (GPAE) on diabetic rats were investigated through evaluating testes histology and androgen hormone levels as well as the implantation sites of female rats on copulation with the treated male rats. Three dosages of GPAE were used (150, 300, and 450 mg/kg), and there were three control groups [normal, diabetic, and metformin-treated diabetic]. Testes histology, androgen hormone levels, and number of implantation sites of the GPAE-treated groups matched those of the normal group in contrast to the diabetic and metformin-treated diabetic controls. Sperm proteomics analysis identified 666 proteins, but only 88 were consistently found in all the control and 450-mg/kg GPAE-treated groups. Four proteins, including cysteine-rich secretory protein 1, carboxylesterase 5A, zona pellucida binding protein, and phosphatidylethanolamine-binding protein 1, were significantly upregulated with GPAE treatment compared with the diabetic control, matching the protein levels of the normal group. These proteins were mainly involved in sperm maturation, sperm capacitation, and sperm-egg interaction, suggesting that GP treatment was able to restore the fertility of male diabetic rats at molecular protein level. In conclusion, GP treatment effectively treats infertility of male diabetic rats, possibly through the upregulation of proteins related to sperm maturation and sperm-egg interaction.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Antihyperglycemic, Antidiabetic, and Antioxidant Effects of Garcinia pedunculata in Rats

Ali MY, Paul S, Tanvir EM, Hossen MS, Rumpa NN, Saha M, et al.

Evid Based Complement Alternat Med, 2017;2017:2979760.
PMID: 29234381 DOI: 10.1155/2017/2979760

The antihyperglycemic, antidiabetic, and antioxidant potentials of the methanolic extract of Garcinia pedunculata (GP) fruit in rats were investigated. The acute antihyperglycemic effect of different doses of GP was studied in normal male Wistar rats. Diabetes was induced by streptozotocin (STZ) injection in another cohort of male Wistar rats and they showed significantly higher blood glucose and glycated hemoglobin (HbA1c) levels, altered lipid profiles, and lower insulin levels compared to nondiabetic control animals. There were increased lipid peroxidation and reduced levels of cellular antioxidant enzymes in different tissues of diabetic rats. However, oral administration of GP extracts, especially the highest dose (1000 mg/kg), significantly ameliorated hyperglycemia (42%); elevated insulin levels (165%); decreased HbA1c (29.4%); restored lipid levels (reduction in TG by 25%, TC by 15%, and LDL-C by 75% and increase in HDL-C by 4%), liver and renal function markers, and lipid peroxidation (reduction by 52% in the liver, 39% in the kidney, 44% in the heart, and 46% in the pancreas); and stimulated tissue antioxidant enzymes to near normalcy. Overall, the findings suggest that GP fruit is effective against hyperglycemia and could be used in the treatment of diabetes and its complications and other oxidative stress-mediated pathological conditions.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Effects of Brown Seaweed (Sargassum polycystum) Extracts on Kidney, Liver, and Pancreas of Type 2 Diabetic Rat Model

Motshakeri M, Ebrahimi M, Goh YM, Othman HH, Hair-Bejo M, Mohamed S

Evid Based Complement Alternat Med, 2014;2014:379407.
PMID: 24516503 DOI: 10.1155/2014/379407

The edible seaweed Sargassum polycystum (SP) is traditionally used against several human diseases. This investigation evaluated the effects of two dietary doses of SP ethanolic and aqueous extracts on the pancreatic, hepatic, and renal morphology of type 2 diabetic rats (T2DM). T2DM was induced by feeding rats on high calorie diet followed by a low dose streptozotocin. Changes in the diabetic rat organs in SP treated groups with different doses of extracts were compared with normal rats, diabetic control rats, and metformin treated rats. After 22 days of treatment, the pathological lesions of the livers and kidneys in the diabetic rats were quantitatively and qualitatively alleviated (P < 0.05) by both the SP extracts at 150 mg/kg body weight and by metformin. All the treated diabetic groups revealed marked improvement in the histopathology of the pancreas compared with the control diabetic group. Oral administration of 300 mg/kg body weight of aqueous and ethanolic extracts of SP and metformin revealed pancreas protective or restorative effects. The seaweed extracts at 150 mg/kg body weight reduced the liver and kidney damages in the diabetic rats and may exert tissue repair or restoration of the pancreatic islets in experimentally induced diabetes to produce the beneficial homeostatic effects.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Centella asiatica Attenuates Diabetes Induced Hippocampal Changes in Experimental Diabetic Rats

Giribabu N, Srinivasarao N, Swapna Rekha S, Muniandy S, Salleh N

Evid Based Complement Alternat Med, 2014;2014:592062.
PMID: 25161691 DOI: 10.1155/2014/592062

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(+)-, Ca(2+)- and Mg(2+)-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.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

Giribabu N, Rao PV, Kumar KP, Muniandy S, Swapna Rekha S, Salleh N

Evid Based Complement Alternat Med, 2014;2014:834815.
PMID: 24991228 DOI: 10.1155/2014/834815

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 IC50 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.

Matched MeSH terms: Diabetes Mellitus, Experimental
Fulltext Rhinacanthus nasutus Ameliorates Cytosolic and Mitochondrial Enzyme Levels in Streptozotocin-Induced Diabetic Rats

Visweswara Rao P, Madhavi K, Dhananjaya Naidu M, Gan SH

Evid Based Complement Alternat Med, 2013;2013:486047.
PMID: 23662138 DOI: 10.1155/2013/486047

The present study was conducted to evaluate the therapeutic efficacy of Rhinacanthus nasutus (R. nasutus) on mitochondrial and cytosolic enzymes in streptozotocin-induced diabetic rats. The rats were divided into five groups with 6 rats in each group. The methanolic extract of R. nasutus was orally administered at a dose of 200 mg/kg/day, and glibenclamide was administered at a dose of 50 mg/kg/day. All animals were treated for 30 days and were sacrificed. The activities of both intra- and extramitochondrial enzymes including glucose-6-phosphate dehydrogenase (G6PDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH) were measured in the livers of the animals. The levels of G6PDH, SDH, and GDH were significantly reduced in the diabetic rats but were significantly increased after 30 days of R. nasutus treatment. The increased LDH level in diabetic rats exhibited a significant reduction after treatment with R. nasutus. These results indicate that the administration of R. nasutus altered the activities of oxidative enzymes in a positive manner, indicating that R. nasutus improves mitochondrial energy production. Our data suggest that R. nasutus should be further explored for its role in the treatment of diabetes mellitus.

Matched MeSH terms: Diabetes Mellitus, Experimental

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