Normal Control Rats Research Articles

Tempol a superoxide dismutase mimic reduces cardiac muscle cell death through the control of oxidative stress in streptozotocin-induced diabetes

ABSTRACT Diabetes mellitus (DM) a metabolic disorder resulting in myocardial injury and diabetic cardiomyopathy (DCM) in association with oxidative stress induction. This study was therefore, investigated the potential protective effect of Tempol (TPL) on oxidative cardiac damage in experimental diabetic rats. Rats were assigned to three equal groups: group (NC); normal control rats received citrate buffer injections. Group (DC): diabetic control rats received a single i.p. STZ injection (60 mg/kg body weight), and Group (D/TPL) diabetic rats treated with TPL (10 mg/kg b.w; by i.p. injection) for four weeks. Our results showed a significant increment in plasma creatine phosphokinase (CPK), lactate dehydrogenase (LDH) activities, cholesterol, triglycerides, Nitric oxide (NO), and lipid peroxidation (LPO), In addition, GSH content and antioxidant enzyme activity were significantly deceased in DC group compared to normal control. While TPL treatment significantly ameliorated the observed biochemical abnormalities. Further, TPL reduced number of dead myocardial cells in diabetic-treated rats and, remarkably improved the histopathological alterations of the aorta. The results proved the protective effect of tempol on STZ-induced diabetic cardiomyopathy by reducing myocardial cell death through reducing oxidative stress and inhibition of lipid peroxidation.

Evaluation of Phytochemical and Antidiabetic Potentials of Aqueous, Ethanol, and Acetone Crude Extracts of Plectranthus Neochilus Leaves on Alloxan Induced Diabetic Wistar Rats.

Diabetes mellitus is a metabolic disorder which leads to abnormally high blood glucose level (hyperglycemia). This research work is aimed at evaluating the antidiabetic potentials of aqueous, ethanol and acetone extracts of plectranthus neochilus leaves on alloxan induced diabetic wistar rats. Materials and Methods: The experimental rats were induced and made diabetic by single intra-peritoneal administration of Alloxan monohydrate at a dose rate of 150 mg/kg dissolved in 0.9% freshly prepared normal saline at pH 5.5. Sixty-five adult (male) albino rats weighing 160-200g were used for this study. The Animals were divided into 12 groups of 5 rats each namely: A: Normal control, B: Diabetic control 150kg/body weight of alloxan, C: Diabetic + 1000mg/kg body weight of Standard drug (Metformin), D: Diabetic + 250mg/kg body weight of aqueous extract, E: Diabetic + 500mg/kg body weight of aqueous extract, F: Diabetic + 1000mg/kg body weight of aqueous extract, G: Diabetic + 250mg/kg body weight ethanol extract, H: Diabetic + 500mg/kg body weight of ethanol extract, I: Diabetic + 1000mg/kg body weight of ethanol extract, J: Diabetic + 250mg/kg body weight of acetone extract, K: Diabetic + 500mg/kg body weight of acetone extract, L: Diabetic + 1000mg/kg body weight of acetone extract. The extracts were administered orally for a duration of 28days at doses of (250, 500, and 1000 mg/kg body weight). Results: Treatment with extracts significantly reduced (p<0.05) elevated blood glucose level associated with alloxan induced diabetic (27.85±0.95) rats in the aqueous extract (5.90±0.10), ethanol extract (10.15±4.35) but no significant ameliorative effect with the acetone extract (23.35±2.82) at dosage of 1000mg/kg body weight. The aqueous extract significantly reduced (p<0.05) elevated blood glucose level more when compared to the normal control (5.85±0.05) rats as when compared to the ethanol and acetone extracts at dose 1000mg/kg body weight. Conclusion: The blood glucose data obtained using Alloxan hyperglycaemic rats clearly shows that the crude aqueous extract has better anti-diabetic effect at dose of 1000mg/kg, followed by the ethanol extract and then the acetone extract in the 28 days of treatment, the ameliorative effect is also dose dependent. Thus, the leaves caused significant and consistent reductions in diabetic drug-induced hyperglycaemia in albino rats.

Antidiabetic and hepato-renal protective effects of medicinal plants in STZ induced diabetic rats.

The antidiabetic and hepato-renal protective effects of Citrullus colocynthis and Momordica charantia ethanol extracts were investigated in streptozotocin (STZ) induced diabetic male albino rats. Diabetic rats were treated with C. colocynthis, M. charantia or C. colocynthis + M. charantia mixed extract at a dose of 250 mg /kg body weight per oral per day for 21 days. The mean body weight of all the diabetic rat groups on day 1 of treatment (day 10 of diabetes) was significantly lower than the normal control rat group (P<0.05). The blood glucose level of all the diabetic rat groups on day 1 of treatment (day 10 of diabetes) was significantly (P<0.05) higher (> 200 mg/dl) than the normal control rat group (95.5 ± 2.7). At the end of treatment (day 21), the diabetic rats treated with plant extracts showed significant increase (P<0.05) in body weight and significant (P<0.05) reduction in blood glucose level when compared to diabetic control animals. Significant increase (< 0.05) was observed in the serum bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea and creatinine levels of diabetic control rat group. The serum levels of these liver and kidney-related parameters of diabetic rats treated with plant extract were significantly lower when compared to diabetic control rat group (p < 0.05). Photomicrographs of liver and kidney microsections from diabetic rats treated with these plant extracts showed amelioration in the hepato-renal histoarchitectures. It was concluded that the C. colocynthis and M. charantia methanol extracts are antidiabetic and hepato-renal protective in STZ induced diabetic male rats. Treatment of the diabetic rats with C. colocynthis + M. charantia mixed extract is more effective in the amelioration of diabetes and hepato-renal injuries in STZ induced diabetic male rats.

Duodenal-Jejunal Bypass Restores Sweet Taste Receptor-Mediated Glucose Sensing and Absorption in Diabetic Rats.

Aim: The aim of the study is to identify the regulatory role of intestinal sweet taste receptors (STRs) and glucose transporters (SGLT1, GLUT2) and gut peptide secretion in duodenal-jejunal bypass (DJB)-ameliorated glycemic control in Type 2 diabetes. Materials and Methods: DJB and sham surgeries were performed in streptozotocin-induced diabetic male rats. The blood GLP-1 and GLP-2 levels were evaluated under feeding and fasting conditions. The expression of STRs (T1R2, T1R3), sweet taste signaling effector (Gα-gustducin), SGLT1, and GLUT2 was detected in the intestinal alimentary limb (A limb), biliopancreatic limb (BP limb), and common limb (C limb). The effects of STR inhibition on glucose control were measured with lactisole. Results: Glucose tolerance was improved in DJB-operated rats compared with the sham group, similar to that of normal control rats, without significant differences in food intake and body weight. The plasma GLP-1 levels of DJB rats were increased under diet-fed condition, and GLP-2 levels were increased after fasting. The villus height and crypt depth were significantly increased in the A limb of DJB-operated rats. In addition, GLP-1 expression was restored in enterocytes. The expression of T1R2, Gα-gustducin, and SGLT1 was elevated in the A limb after DJB, while GLUT2 was downregulated in the A, BP, and C limbs. The localization of GLUT2 was normalized in the three intestinal limbs after DJB. However, the beneficial effects of DJB on glucose control were abolished in the presence of lactisole in vivo. Conclusion: DJB ameliorates glycemic control probably by restoring STR-mediated glucose sensing and absorption with the responses of GLP-1 and GLP-2 to carbohydrate.

Propolis attenuates diabetes-induced testicular injury by protecting against DNA damage and suppressing cellular stress.

Introduction: Propolis has a wide range of biological and pharmacological actions, including antioxidant properties-particularly its phenolic and flavonoid constituents-that could potentially protect the reproductive system from oxidative damage. Method: Four groups were allocated 40 male Wistar rats each. The vehicle was given to the first group's normal control rats negative control. The second, third, and fourth groups of diabetic rats were given vehicle (diabetic control) and propolis orally at 50 and 100mg/kg, respectively, for 8weeks. Diabetes was induced in rats via injection of nicotinamide and streptozotocin (STZ). Fasting blood glucose (FBG) and insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and semen analysis were assessed. In addition, assessments of serum reproductive hormones, including total testosterone (TTST), estradiol (E2), follicle-stimulating hormone luteinizing hormone (LH), and prolactin (PRL), were measured at the end of the study. Tissue total testosterone, E2, and dihydrotestosterone were also evaluated. Serum and tissue oxidative enzymes, including catalase (CAT), superoxide dismutase, and glutathione peroxidase activities, were examined, and malondialdehyde content was determined. The pancreatic and testicular tissues were histopathologically examined, and proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (Bcl-2) in testicular tissue were immunohistochemically analyzed. Testicular tissue was examined for DNA integrity using a comet assay. Results: Compared to the STZ-control group, propolis greatly decreased FBG levels and improved the glycemic status of diabetic rats. In comparison to the STZ-DC group, propolis increased the number of sperm cells and the percent of morphologically normal and viable sperm in male rats, improving their fertility. Propolis also restored the pancreatic islets, protected the testis from oxidative stress, and increased levels of reproductive hormones in the blood, especially testosterone. Moreover, propolis at high doses demonstrated a strong positive response for Bcl-2 and a negative expression of proliferating cell nuclear antigen in spermatogenic cells. Conclusion: The data obtained strongly indicate that STZ causes severe impairments to the testis whereas propolis, acting as an antioxidant, protects against the adverse effects of STZ on the testis.

Insulin-sensitizing and antioxidant effects of &lt;i&gt;Ethulia&lt;/i&gt; &lt;i&gt;conyzoïdes&lt;/i&gt; aqueous extract in dexamethasone-induced insulin resistant rats

Rising the prevalence of type 2 diabetes mellitus in sub-saharian Africa has necessitated surveys of antidiabetic medicinal plants. Ethulia conyzoïdes is a plant widely used in traditional medicine to treat diabetes. However, the different mechanisms by which it exerts its antidiabetic effects remain unknown. Thus, this study aimed to investigate the effect of Ethulia conyzoïdes aqueoux extract on dexamethasone-induced insulin resistance in Wistar rats. Insulin resistance was induced by intraperitoneal injection of dexamethasone (1mg/kg) for 8 days and the animals received simultaneously, orally, distilled water (insulin resistant control group) and, metformin (100 mg/kg) or Ethulia conyzoïdes aqueoux extract at doses of 133 and 266 mg/kg. Normal control rats received NaCl 0.9% (intraperitoneal by injection) and distilled water orally. Insulin sensitivity, total cholesterol, triglycerides, transaminases activity and redox status were evaluated. Results showed a significant reduction of insulin tolerance (p&lt;0.001), a drastic increased of transaminase activity (p&lt;0.05), hyperlipidemia, and a great potentiation of liver antioxidant enzymes (GSH, SOD and catalase) in insulin resistant control group. Ethulia conyzoïdes aqueoux extract markedly improved insulin sensitivity and reversed all the modified parameters. This study demonstrated the efficacy of Ethulia conyzoïdes aqueoux extract to improve insulin sensitivity and manage biochemical disorders induced by insulin resistance. Short term administration of dexamethasone appears to stimulate the first line antioxidant defense in order to counteract oxidative stress, meaning that Ethulia conyzoïdes aqueoux extract inhibited free radicals production.

Sesamin mitigates lead-induced behavioral deficits in male rats: The role of oxidative stress

Lead (Pb) is a well-known toxic pollutant that has negative effects on behavioral functions. Sesamin, a phytonutrient of the lignan class, has shown neuroprotective effects in various neurological disorder models. The present study was undertaken to evaluate the putative protective effects of sesamin against Pb-induced behavioral deficits and to identify the role of oxidative stress in male rats. The rats were exposed to 500 ppm of Pb acetate in their drinking water and simultaneously treated orally with sesamin at a dose of 30 mg/kg/day for eight consecutive weeks. Standard behavioral paradigms were used to assess the behavioral functions of the animals during the eighth week of the study. Subsequently, oxidative stress factors were evaluated in both the cerebral cortex and hippocampal regions of the rats. The results of this study showed that Pb exposure triggered anxiety-/depression-like behaviors and impaired object recognition memory, but locomotor activity was indistinguishable from the normal control rats. These behavioral deficiencies were associated with suppressed enzymatic and non-enzymatic antioxidant levels, and enhanced lipid peroxidation in the investigated brain regions. Notably, correlations were detected between behavioral deficits and oxidative stress generation in the Pb-exposed rats. Interestingly, sesamin treatment mitigated anxio-depressive-like behaviors, ameliorated object recognition memory impairment, and modulated oxidative-antioxidative status in the rats exposed to Pb. The results suggest that the anti-oxidative properties of sesamin may be one of the underlying mechanisms behind its beneficial effect in ameliorating behavioral deficits associated with Pb exposure.

Malva parviflora seed oil; Isolation, gas chromatographic profiling and its cardioprotective activity against myocardial infraction in animal model

Myocardial infarction (MI), one of the most perilous types of cardiac illness, carries a significant burden of mortality and morbidity. This study aims to shed light on the impact of Malva parviflora seed oil (MPSO) on plasma cardiac function tests, levels of cardiac inflammatory mediators, and the expression of cardiac miRNA140-5p and miRNA208b genes in a rat model of MI induced by isoproterenol (ISO). The methods involved the extraction of MPSO using hexane, with the determination of fatty acid contents accomplished through GC spectrometry. Adult albino rats, weighing 185 ± 7 g, were divided into five groups (n = 6): normal control rats, ISO-treated rats, ISO-treated rats with MPSO (157 and/or 314 mg/kg, respectively), and ISO-treated rats with omega (100 mg/kg, respectively) for a duration of four weeks. The results revealed that Malva parviflora seeds yielded 3.3 gm/100 dry seeds. Among the nine fatty acid components identified, coriolic acid was the most abundant (31.60 %), followed by pentadecanoic acid (30.05 %). The cardioprotective potential of MPSO was assessed in rats subjected to ISO-induced cardiac injury. Following 24 h of ISO treatment, rats displayed elevated levels of plasma cardiac troponin I (cTnI), troponin T (cTnT), lactate dehydrogenase (LDH), and B-Type Natriuretic Peptide (BNP), as well as cardiac BcL-2, P53, toll-like receptor 4 (TLR4), NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells), thiobarbituric acid reactive substances (TBARs), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), miRNA-140-5p, and miRNA-208b gene expression. Histopathological examination confirmed cardiac injury in ISO-treated rats. Furthermore, MPSO mitigated the elevation of cardiac enzymes and TBARS, as well as cardiac inflammatory mediators, while concurrently downregulating the expression levels of miRNA-140-5p and miRNA-208b genes. Conversely, the enhancement of cardiac GSH, SOD, and CAT activity demonstrated the antioxidant capabilities of MPSO against ISO-induced cardiac injury. Histopathological findings underscored MPSO's protective effect on cardiac tissue against oxidative damage in ISO-treated rats. In nutshel, the findings of this study unveil the cardioprotective and free radical scavenging attributes of MPSO in rats with ISO-induced cardiac damage. MPSO appears to provide cardiac protection against free radicals and inflammation induced by xenobiotics, potentially owing to its rich content of polyphenols, flavonoids, polyunsaturated fatty acids (PUFAs), and cyclopropenoid fatty acids.

α-Tocopherol Ameliorates Redox Equilibrium Disorders and Reduces Inflammatory Response Caused by Diclofenac-Induced Nephrotoxicity in Male Wistar Rats.

Background Diclofenac (DCF), a nonsteroidal anti-inflammatory drug (NSAID), is widely used for its analgesic and anti-inflammatory properties, but it can also be nephrotoxic. Vitamin E (α-tocopherol) has been shown to protect against renal toxicity caused by various agents, including NSAIDs. This study aims to evaluate the pathophysiology of renal damage and the nephroprotective effect of vitamin E against DCF-induced renal damage in male Wistar rats. Animal and methods Twenty-four male Wistar rats, divided into six equal groups, were used for the study. Group 1 (control group) was treated with distilled water only, while the other groups received either high or low doses of DCF with or without a fixed dose of vitamin E. Renal function was assessed by measuring serum urea, creatinine, and kidney injury molecule-1 (KIM-1). Oxidative damage and renal antioxidant levels were also assessed. Additionally, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), renal cytokine tumor necrosis factor-α (TNF-α), and histopathological changes were evaluated. Results DCF caused a significant increase in serum urea, creatinine, KIM-1, TNF-α, NF-κB, and malondialdehyde levels compared to the control group. However, in the groups treated with DCF plus vitamin E, a significant reduction (P<0.05) in the levels of pro-inflammatory cytokines and malondialdehyde was observed, along with improvement in renal function indices, superoxide dismutase, catalase, and glutathione peroxidase levels comparable to the control group. The observed renal histopathological changes were consistent with the results of the biochemical parameters between the treated groups and the normal control rats. Conclusion Findings from this investigation suggested that DCF can be nephrotoxic at a certain dose when used for a prolonged duration. Co-administration of vitamin E suppressed the elevated inflammatory cytokines and led to changes in the cell redox-sensitive signaling pathways induced by DCF, with eventual amelioration of the nephrotoxicity.

Combination Therapy with Enalapril and Paricalcitol Ameliorates Streptozotocin Diabetes-Induced Testicular Dysfunction in Rats via Mitigation of Inflammation, Apoptosis, and Oxidative Stress.

As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

Dyslipidemia Protective Effect of Resistant Starch-Based Dough Meals on Diabetes-Induced Rats

Aim: The adoption of functional foods as healthy diet therapy for the management of metabolic disorders such as diabetes is in vogue in the present world where many are no longer consuming carbohydrate or starchy foods. This study investigated the effect of resistant starch-based dough meals on dyslipidemia in rats with streptozotocin (STZ)-induced diabetes.&#x0D; Place and Duration: Functional Foods Laboratory and Animal House of Department of Biochemistry, Federal University of Technology, Akure, from July 2022 to February 2023.&#x0D; Methodology: Flour samples were prepared by dispersing the flour into boiling water and turning and being allowed to cook for 15 min to obtain dough meals: PLD – (100% Plantain flour), used as a control sample; PLPRD – plantain flour: pigeon pea flour: rice bran flour (73.08:15.15:11.76); PSPRD – native plantain starch: pigeon pea flour: rice bran flour (73.08:15.15:11.76); AP1SPRD – acetylated plantain starch: pigeon pea flour: rice bran flour (73.08:15.15:11.76); AP2SPRD – acetylated plantain starch: pigeon pea flour: rice bran flour (70.67:18.15:11.18). The weight gained, food intake, haematological parameters, fasting blood glucose and lipid profile of the resistant starch-based dough meal were compared with the commercial flour product, CRD (100% Cerolina flour: wheat and soybean) and the DM (untreated high-fat diet–STZ-induced diabetic rats) and NC (Normal control rats).&#x0D; Results: The weight gained and food intake ranged from 50.98±0.53 g to 180.12±1.07 g in NC and 33.98±1.64 g to 140.87±1.80 g in DM. The feed conversion ratio to the feed efficiency ratio was 0.28:0.25 and 4.15:3.53 in NC and DM respectively, which attributed to the food product to weight loss. The values of the haematological parameters (PCV, RBC, HB, MCV, MCH and MCHC) confirmed that the experimental rats had no trace of infection due to the generation of antibodies by WBC and differential counts (neutrophils, eosinophils, basophils, monocytes and lymphocytes). Rats fed with DM+AP1SPRD showed a decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglyceride, and an increase in high-density lipoprotein cholesterol (HLDL-C).&#x0D; Conclusion: A resistant starch-based dough meal was significant for the production of short-chain fatty acids with lots of benefits on health. The intervention of resistant starch-based dough meals, AP1SPRD and AP2SPRD used in this study, almost normalized metabolic profiles in the experimental rats, similar to the control group by reducing the total cholesterol, total triglycerides and LDL-C while increasing HDL-C.

Autonomic and cytokine mechanisms of acute electroacupuncture in a rodent model of functional dyspepsia.

Cytokines have been presumed to play an important role in the pathophysiology of functional dyspepsia (FD). Electroacupuncture (EA) has been used for FD treatment; however, its mechanisms remain largely unknown. This study aimed to (1) compare the plasma levels of cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10, in "FD" rats with normal control rats; (2) investigate whether EA, using chronically implanted electrodes, could inhibit the release of these cytokines; and (3) explore the correlation of cytokine levels with plasma norepinephrine (NE) levels and gastric emptying (GE). A rodent model of FD was established via neonatal treatment with intragastric iodoacetamide. After 8 weeks, the rats were implanted with electrodes at acupoint ST36 for EA. The plasma levels of cytokines and NE were measured using enzyme-linked immunosorbent assay. We explored the correlations of cytokine levels with NE levels and GE. (i) "FD" rats demonstrated increased levels of TNF-α, IL-1β, and IL-6 (p < 0.05 each) compared with the control rats. (ii) EA significantly decreased the plasma levels of TNF-α, IL-1β, and IL-6 in "FD" rats (p < 0.05 each) compared with sham EA. (iii) The plasma levels of NE were positively correlated with those of IL-6 (r = 0.86, p < 0.05) and IL-1β (r = 0.81, p < 0.05), whereas NE levels and GE were negatively correlated with IL-10 levels (r = -0.870, p < 0.05 and r = -0.791, p < 0.05, respectively). EA inhibits the release of proinflammatory cytokines probably via the suppression of sympathetic activity in "FD" rats.

Mechanisms of anti-ulcer actions of Prangos pabularia (L.) in ethanol-induced gastric ulcer in rats

Peptic ulcer disease is the greatest digestive disorder that has increased incidence and recurrence rates across all nations. Prangos pabularia (L.) has been well documented as a folkloric medicinal herb utilized for multiple disease conditions including gastric ulcers. Hence, the target study was investigation the gastro-protection effects of root extracts of Prangos pabularia (REPP) on ethanol-mediated stomach injury in rats. Sprague Dawley rats were clustered in 5 cages: A and B, normal and ulcer control rats pre-ingested with 1 % carboxymethyl cellulose (CMC)); C, reference rats had 20 mg/kg omeprazole; D and E, rats pre-supplemented with 250 and 500 mg/kg of REPP, respectively. After one hour, group A was given orally 1 % CMC, and groups B-E were given 100 % ethanol. The ulcer area, gastric acidity, and gastric wall mucus of all stomachs were determined. The gastric tissue homogenates were examined for antioxidant and MDA contents. Moreover, the gastric tissues were analyzed by histopathological and immunohistochemically assays. Acute toxicity results showed lack of any toxic effects or histological changes in rats exposed to 2 and 5 g/kg of REPP ingestion. The ulcer controls had extensive gastric mucosal damage with lower gastric juice and a reduced gastric pH. REPP treatment caused a significant reduction of the ethanol-induced gastric lacerations represented by an upsurge in gastric mucus and gastric wall glycoproteins (increased PAS), a decrease in the gastric acidity, leukocyte infiltration, positively modulated Bax and HSP 70 proteins, consequently lowered ulcer areas. REPP supplementation positively modulated oxidative stress (increased SOD, CAT, PGE2, and reduced MDA) and inflammatory cytokines (decreased serum TNF-α, IL-6, and increased IL-10) levels. The outcomes could be scientific evidence to back-up the folkloric use of A. Judaica as a medicinal remedy for oxidative stress-related disorders (gastric ulcer).

Emodin alleviates joint inflammation and bone erosion in rats with collagen-induced arthritis by inhibiting ferroptosis and degrading matrix metalloproteinases

To investigate the osteoprotective mechanism of emodin in light of the ferroptosis signaling pathway in a rat model of rheumatoid arthritis. SD rat models of collagen-induced arthritis (CIA) were treated with methotrexate or low or high doses of emodin, and the changes in arthritis scores and toe volume were recorded. model of CIA rats. Malondialdehyde (MDA) content in the joint cartilage was determined, and ankle joint tissue pathologies were observed using caffein solid green staining and hematoxylin-spermine red staining. MMP3 and MMP13 expressions in the ankle joint tissues were detected using immunohistochemistry, and Western blotting was used to detect the protein expressions of ACSL4, SLC7A11, GPX4, and FTH1. Compared with the normal control rats, the CIA rats showed significantly increased arthritis score index with obvious toe swelling (P<0.05), rough cartilage surface, and loss and irregular aligment of chondrocytes. The rat models also showed significantly increased MDA and ACSL4 contents, lowered SLC7A11, GPX4, and FTH1 contents (P<0.05), and decreased expressions of MMP3 and MMP13 in the ankle joint (P<0.05). The rat models treated with either methotrexate or emodin (40 and 80 mg/kg) had significantly reduced arthritis score index and toe swelling with smooth cartilage surface and neat arrangement of the chondrocytes. The treatments with methotrexate and emodin both decreased the contents of MDA and ACSL4 and increased the contents of SLC7A11, GPX4, and FTH1 in the joint tissues (P<0.05). Emodin can effectively control joint inflammation and improve joint bone erosion in CIA rats possibly by inhibiting the ferroptosis signaling pathways and reducing the expressions of MMP3 and MMP13.

Butin prevent liver damage triggered by D-galactosamine via regulating lipid peroxidation and proinflammatory cytokines in rodents

ObjectivesLiver damage is becoming a more severe problem around the world. Unfortunately, there is still a great need for clinically effective pharmacological therapy for liver injury. The investigation aimed to assess the favorable outcome of butin hepatoprotective efficacy against D-galactosamine (D-GalN)-produced liver damage in experimental rats. MethodsA single dose of D-GalN 400 mg/kg b. wt. was injected intraperitoneally, 24 hr prior to scarification of rats to cause liver damage. The liver injury was assessed biochemically, investigating parameters like aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), total-bilirubin, -albumin and -protein. Butin (25 and 50 mg/kg b. wt.) was managed for 21st days and at the end of the experimental period, normal control, D-GalN control, and butin treatment group rats for further biochemical as well as histopathological consideration. ResultsButin pretreatment significantly attenuated D-GalN-induced hepatocytes damage by reducing hepatic markers and its ability in attenuating oxidative damage (MDA, GSH, SOD, CAT) and pro-inflammatory cytokine (TNF-α, IL-6, IL-1β) and MPO. Histopathological assessment of the liver and biochemical estimation confirmed the hepatoprotective effects of butin. Conclusions: These results demonstrated that butin protects experimental rats against D-GalN-induced liver injury by modulating lipid peroxidation and pro-inflammatory cytokine. Current research will give preliminary experimental evidence for butin, and possible therapeutic effects in liver disorders.

Metabolic characteristics of ginsenosides from Panax ginseng in rat feces mediated by gut microbiota

Ginsenosides in Panax ginseng are regarded to be functional ingredients for diverse pharmacological effects and orally administrated with very low absorption in the gastrointestinal tract to be metabolized by gut microbiota. However, in vivo metabolic characteristics of ginsenosides mediated by gut microbiota are not well-known. This study aimed to explore the metabolic profiles of ginsenosides in rat feces mediated by gut microbiota. Ginsenosides and metabolites were identified and relatively quantified by ultra-performance liquid chromatography tandem/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). As a result, eighty-four metabolites were identified in the normal control rat feces, while only thirty intermediates were found with very low yields in the pseudo-germ-free (GF) group. Similarly, the main bioconversion pathways of ginsenosides in vivo were the same deglycosylation reaction mediated by gut microbiota in vitro. The findings demonstrated significant differences in metabolic profiles between the normal control and pseudo-GF rats, which implied gut microbiota played an important role in the metabolism of ginsenosides.

Moxibustion enables protective effects on rheumatoid arthritis-induced myocardial injury transforming growth factor beta1 signaling and metabolic reprogramming.

To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis (RA) based on the transforming growth factor beta1 (TGF-β1)/Smads signaling pathway. One hundred rats were treated with saline [normal control (NC) group] or complete Freund's adjuvant (CFA) by right plantar injection for the RA model group, and the latter were randomly divided into 4 groups. Tripterygium wilfordii polyglycoside tablets (, TPT) have anti-inflammatory and are widely used in the clinical treatment of RA, therefore serving as a positive control group. Three days post injection rats were given TPT tablet (TPT group), acupuncture therapy (APT group), and moxibustion treatment (MOX group) for 15 consecutive days, while NC group and model group were equally grasped and fixed and received normal saline. Rat joint swelling scores and arthritis index (AI) were evaluated in each group before the CFA challenge, therapy and after receiving therapy. Myocardial ultrastructure was observed by electron microscope. Enzyme-linked immunosorbent assay was used to detect cardiac troponin I (cTnI) levels in rat myocardial tissue. Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-β signaling molecules including TGF-β1, Smad2, Smad3, Smad4, and Smad7. Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer. Compared with model group, RA model rats receiving TPT, acupuncture, or moxibustion therapy all showed reduced joint swelling scores and AI (all P < 0.01) and improved myocardial damage, whereas rats treated with moxibustion were found to be more marked. Consistently, the expressions of cTnI, TGF-β1, Smad2, Smad3, and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT, APT and MOX group when compared with model group, while the levels of Smad7 showed the opposite result (all P < 0.01). Moreover, the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate, dihydroxyacetone phosphate, arachidonic acid, etc was defined and implicated in amino acid, glucose, and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis. Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions. The protective effects might be associated with its role in TGF-β1 inactivation and metabolic reprogramming.

Baicalin: A potential therapeutic agent for diabetes and renal protection

Background: Diabetes is a complex metabolic disease manifested by raised glucose levels in the blood and impaired insulin function leading to various organ complications, including diabetic nephropathy. Baicalin, a flavonoid derived from Scutellaria baicalensis Georgi, has garnered substantial attention for its diverse beneficial effects, including anti-inflammatory, anti-allergic, anti- apoptotic properties, etc. Intriguingly, in vivo studies in rats have further unveiled baicalin’s potential to directly modulate pancreatic beta cells, suggesting a promising role as an anti-diabetic agent.Objective: The purpose of this study is to comprehensively explore the anti-diabetic effect of baicalin, focusing on key parameters such as plasma insulin levels, glucose levels, hemoglobin, and glycated hemoglobin levels in streptozotocin-induced diabetic rats. Additionally, we sought to explore Baicalin’s ability to provide renal protection by evaluating serum renal markers. Methodology: This study involved a total of 30 Wistar albino male rats. Diabetes was created in rats by a single intraperitoneal streptozotocin injection (40 mg/kg). After 72 hours, the rats with diabetes were segregated into four treatment groups (Group II to Group V) comprising 6 animals each. Group I consists of six normal control rats (without diabetes). The groups received different treatment protocols, including normal saline, DMSO, Baicalin (50 mg/kg/day), and glibenclamide (6 mg/kg/day) for 45 days. Throughout the study, meticulous observations were made regarding the animals’ general appearance, body weight, behavior, and their fasting glucose levels in venous blood.Results: Oral dosing with Baicalin at the rate of 50 mg/kg body weight revealed notable enhancements in insulin secretion and hemoglobin levels, alongside notable reductions in blood levels of glucose and glycated hemoglobin compared to the glibenclamide-treated type 2 diabetic rats. Additionally, Baicalin displayed a protective action on renal tissue, as shown by reduced serum creatinine, uric acid, and urea levels.Conclusion: Our investigation unveils Baicalin’s potential as a promising anti-diabetic agent with the added benefit of renal tissue protection. The observed improvements in various physiological parameters warrant further exploration of Baicalin’s therapeutic mechanisms and clinical applications, presenting it as a compelling candidate for diabetes management and diabetic nephropathy prevention. IAEC Approval No: AVMC/IAEC/2019/07/25/08 Keywords: Baicalin, Blood glucose, Diabetes, Male wistar rats, Streptozotocin

Ameliorative Effect of Aqueous Crude Extract of the Aerial Parts of Leonurus Cardiaca on Doxorubicin-Induced Cardiovascular Damage in Wistar Rats

This study investigated the ameliorative effect of aqueous crude extract of the aerial parts of Leonurus cardiaca on doxorubicin-induced cardiovascular damage in Wistar rats. Aqueous crude extract of Leonurus cardiaca was prepared based on standard Laboratory condition. A total of 55 male and female rats weighing between 170 ± 15 and 180±15g were used for this study. The rats were grouped into 11 groups of five rats per group. Group 1 and 2 served as normal and negative control rats respectively. Rats in group 3-11 were intraperitoneally administered 18mg/kg of doxorubicin once and were treated with the crude extract at 166, 250, and 500mg/kg for 7, 14, and 21 days. All biochemical, hematological, and histological analyses were carried out based on standard methods. The mean plasma troponin T and I, IL-6 and C-reactive protein concentrations of the negative control were 357.93±0.01 pg/mL, 241.51±0.00 pg/mL, 63.94±0.01 pg/dl, and 41.03±0.01 mg/ml respectively. The plasma troponin T and I, IL-6 and C-reactive protein concentrations treated for 21 days were 270.32±0.01 pg/mL, 217.84±0.01 pg/mL, 42.75±0.01 pg/dl, and 18.03±0.01 mg/ml respectively. The mean MDA, GSH concentrations, GPx, CAT and SOD activities in doxorubicin-induced cardiovascular damage rats, treated with the extract at 500mg/kg were 5.01±0.01mmol/l, 68.46±0.02µg/mg.protein, 70.21±0.01mg/pro.min, 141.62±1.80IU/g, and 19.05±0.02mg/g respectively and were significantly different from those of group 2. Aqueous crude extract of Leonurus cardiaca at 500mg/kg ameliorated the damage induced by doxorubicin on the heart tissues, hence could serve as a novel herbal agent for the treatment of cardiovascular damage.

Phytochemical study and Protective Effect of Trigonella foenum-graecum (Fenugreek Seeds) Methanolic Extract Underlying the Mechanism of Action on Diabetic Nephropathy in Experimental Rats

Background: Advanced glycation end products (AGEs) buildup and hyperglycemia both contribute significantly to the onset of diabetic nephropathy. A plant with high flavonoid content, Fenugreek Seeds Extract (FSE), may be able to reduce the activity of oxidative stress in cells and tissues. The purpose of this study was to determine if Fenugreek Seeds Extract (FSE) could prevent kidney damage in diabetic rats caused by the production of AGEs in the renal glomerulus. Objective: The current study aimed to estimate phytochemical screening, in-vitro antioxidant activity, and nephron-protective effect of Trigonella foenum-graecum (Fenugreek Seeds) methanolic extract. Methods: We have demonstrated the phytochemical composition of extract of fenugreek seeds. The antioxidant activity of the extract was determined using DPPH assay. Total of thirty six albino wistar rats were used for diabetic nephropthic activity. Normal control rats and diabetic rats were given low doses of fenugreek seed extract (100 mg/kg), medium doses (200 mg/kg), and high doses (400 mg/kg) by oral gavage for 8 weeks before being put to sacrificed. Adiponectin, renal function markers, pro-inflammatory markers, antioxidative markers, and glucose concentration were all measured. Results: It has been found that FSE treatment significantly prevented in STZ-induced increases in urine production, urinary albumin excretion, and urine albumin-to-creatinine ratio and markedly attenuated STZ-induced renal damages. Levels of aspartate aminotransferase, alanine aminotransferase and serum creatinine, blood urea nitrogen and malondialdehyde of kidney tissue were lower in extract treated groups than in contrast agent treated group, but the decrease in serum MDA was significant in the group given FSE. Serum antioxidant capacity was higher in the FSE contrast agent group than in the contrast agent group. Kidney tissue anti-oxidant capacity was significantly higher in the group given FSE than the contrast agent group. Conclusion: This study demonstrated that an appropriate amount of FSE 200 mg/kg in rats, could prevent diabetic nephropathy by improving antioxidant status and inhibiting inflammation in renal tissue. FSE extract may be effective in treating high-glucose-induced nephropathy.