Arabic gum acacia improves diabetic peripheral neuropathy in rats: a biochemical and histopathological evidence

Background: Diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes mellitus and unfortunately, its present therapeutic alternatives are exceptionally poor. Objectives of this study was to assess the antidiabetic, antioxidant and hypolipidemic action of Gum Arabic (GA) and its role in promoting the functional recovery from diabetic neuropathy developed in in an experimental model of diabetic neuropathy.Methods: Sixty adult male Sprague-Dawley rats were utilized and randomly assigned into six groups (n= 10); control, Arabic gum-treated, untreated diabetic, diabetic received metformin, diabetic received metformin and B12 vitamin and diabetic received metformin, B12 vitamin and AG. Locomotor activity and hyperalgesia were assed at the end of the study. Fasting and two hours post-prandial blood glucose, serum insulin levels, lipid Profile, oxidants/antioxidants parameters were assessed in the blood. Sciatic nerve was assessed histopathologically.Results: The locomotor activity of the untreated diabetic rats was significantly (p<0.001) reduced compared to the control group while it was significantly increased in all treated groups. The lipid profile and Malondialdehyde were significantly improved in all treated groups. Levels of CAT, GSH, SOD, GPx were significantly decreased in untreated diabetic group compared to the control while they were significantly increased in all treated groups compared to the untreated diabetic group. Sciatic nerve fibers of untreated diabetic rats showed degenerated axons with dilated myelin sheaths and degenerated Schwann cells. The nerve had significantly fewer fiber compared to the control. These changes were alleviated in all the treated groups specifically that received metformin, vitamin B12 and GA.Conclusions: It could be concluded that Arabic gum had hypoglycemic, antioxidant and hypolipidemic activity and had a protective effect on diabetic neuropathy. Based on this it is recommended that human clinical trials are necessary to prove this therapeutic effect

Brain-derived Neurotropic factor (BDNF) mediates the protective effect of Cucurbita pepo L. on salivary glands of rats exposed to chronic stress evident by structural, biochemical and molecular study

Acute and chronic stresses affect the salivary glands, representing the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects.&nbsp;Objective: To assess the structural and biochemical effects induced by exposure to chronic unpredictable mild stress (CUMS) on salivary glands of albino rats, and to evaluate the role of pumpkin extract (Pump) in ameliorating this effect.&nbsp;Methodology: Four groups (n=10 each) of male albino rats were included in this study: the control, CUMS, Fluoxetine-treated and Pump-treated. The corticosterone, the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the oxidant/antioxidant profile were all assessed in the serum. The level of BDNF mRNA was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed.&nbsp;Results: The depressive-like status was confirmed behaviorally and biochemically. Exposure to CUMS significantly up-regulated (p&lt;0.001) the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal elements of the salivary glands evident by increased apoptosis. Both Fluoxetine and Pumpkin significantly up-regulated (p&lt;0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological and biochemical alterations in the salivary glands. Pumpkin significantly (p&lt;0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT, and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6.&nbsp;Conclusion: Pumpkin ameliorates the depressive-like status induced in rats following exposure to chronic stress through exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects. The pumpkin, subsequently, improved stress-induced structural changes in the salivary glands that might be due to up-regulation of BDNF expression in the glands

Cinnamon and ginger extracts attenuate diabetes-induced inflammatory testicular injury in rats and modulating SIRT1 expression

The current study aimed to evaluate the efficacy of simultaneous administration of Zingiber officinale (ginger) and Cinnamomum cassia (cinnamon) extracts in mitigating testicular changes associated with diabetes mellitus in rats and to investigate its molecular mode of action. After induction of diabetes using streptozotocin, 36 male rats were divided to six groups namely control, diabetic, metformin-treated, cinnamon-treated, ginger-treated and combined, each group having 6 rats. Fasting blood glucose, serum insulin, testosterone was measured. Expression of inflammatory mediators; tumor necrosis factor-alpha (TNF-α), Nuclear factor kappa B (NF-κB) and Sirtuin 1 (SIRT1) was assessed in the testicular tissue. Histopathological changes in the testis were observed and spermatogenesis and apoptosis were assessed immunohistochemically. The histological and biochemical studies of the untreated group confirmed structural changes in testes induced by diabetes. Oral administration of ginger and cinnamon increased insulin level significantly increased while the blood glucose level significantly decreased in diabetic rats, improving structural testicular changes considerably. Joint intake of ginger and cinnamon increased antihyperglycemic, antioxidant and anti-inflammatory effects markedly improving the testicular injury compared to the administration of either of them. SIRT1 expression in the testis significantly increased in ginger plus cinnamon-treated rats. These results indicate that when administrated together, ginger and cinnamon synergistically enhanced antioxidant, antiapoptotic and anti-inflammatory effects and induced antihyperglycemic effect comparable to metformin. The combination of ginger and cinnamon also upregulated SIRT1 in the testis

Mitigative Potential of Novel Lactobacillus plantarum TISTR 2076 against the Aflatoxins-Associated Oxidative Stress and Histopathological Alterations in Liver and Kidney of Broiler Chicks during the Entire Growth Period

Aflatoxins are the secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus and have severe pathological effects on the health of human and animals. The present study was designed to investigate the toxicopathological changes induced by aflatoxins and mitigative potential of Lactobacillus plantarum in broiler birds. One hundred and eighty broiler chicks at one day of age was procured from the local market, and chicks were equally divided into six groups with thirty birds in each group. These birds were treated with aflatoxins (300 and 600 &micro;g/kg) and Lactobacillus plantarum (1 &times; 108 cfu/kg of feed) in different combinations. The first group was kept as the control, and only a basal diet was provided to birds (BD). In the second group (AF1), the first level of aflatoxins (300 &micro;g/kg) was fed to the birds. In the third group (AF2), the second level of aflatoxins (600 &micro;g/kg) was fed to birds. In the fourth group (AF1LP), Lactobacillus plantarum was given with first level of aflatoxins. In the fifth group (AF2LP), Lactobacillus plantarum was given with the second level of aflatoxins, and in the 6th group (BDLP), Lactobacillus plantarum alone was fed to the chicks. This experimental study was continued for 42 days. Birds were slaughtered after 42 days, and different parameters were assessed. Parameters studied were gain in body weight, organ weight along with some histopathological, hematological, biochemical parameters and residues of aflatoxins in liver and kidney. Lactobacillus plantarum improved the body weight gain and restored the relative organ weight. Hepatic and renal biomarkers returned to normal concentrations, serum proteins were restored in combination group AF1LP, and partial amelioration was observed in the AF2LP group. Red blood cells, white blood cells, hemoglobin centration and packed cell volume became normalized in the AF1LP group, while partial amelioration was observed in the AF2LP group. LP also reduced the concentration of aflatoxin residues in liver kidney and improved the TAC concentrations. The results of this study elucidated the mitigative potential of Lactobacillus plantarum against serum biochemical, histopathological, hematological and toxicopathological changes induced by aflatoxins in the chicks

Exploring bi-carbazole-linked triazoles as inhibitors of prolyl endo peptidase via integrated in vitro and in silico study

Abstract A serine protease called prolyl endopeptidase (PEP) hydrolyses the peptide bonds on the carboxy side of the proline ring. The excessive PEP expression in brain results in neurodegenerative illnesses like dementia, Alzheimer’s disease, and Parkinson's disease. Results of the prior studies on antioxidant activity, and the non-cytotoxic effect of bi-carbazole-linked triazoles, encouraged us to extend our studies towards its anti-diabetic potential. Hence, for this purpose all compounds 1–9 were evaluated to reveal their anti-prolyl endo peptidase activity. Fortunately, seven compounds resulted into significant inhibitory capability ranging from 26 to 63 µM. Among them six compounds 4–9 exhibited more potent inhibitory activity with IC50 values 46.10 ± 1.16, 42.30 ± 1.18, 37.14 ± 1.21, 26.29 ± 0.76, 28.31 ± 0.64 and 31.11 ± 0.84 µM respectively, while compound 3 was the least active compound in the series with IC50 value 63.10 ± 1.58 µM comparing with standard PEP inhibitor bacitracin (IC50 = 125 ± 1.50 µM). Moreover, mechanistic study was performed for the most active compounds 7 and 8 with K i values 24.10 ± 0.0076 and 23.67 ± 0.0084 µM respectively. Further, the in silico studies suggested that the compounds exhibited potential interactions and significant molecular conformations, thereby elucidating the structural basis for their inhibitory effects

Origanum majorana L. Extract Attenuated Benign Prostatic Hyperplasia in Rat Model: Effect on Oxidative Stress, Apoptosis, and Proliferation

Benign prostatic hyperplasia (BPH) is a widespread androgenic illness influencing elderly men. It is distinguished by prostatic epithelial and stromal muscle cell proliferation. Inflammation, oxidative stress, and apoptosis have all been interrelated to the development of BPH. Marjoram (Origanum majorana L.) is a herb with reported antiproliferative, proapoptotic, and antioxidative properties, which have not yet been studied in relation to BPH. Consequently, in this work, an ethanolic extract of O. majorana was prepared in two doses (250 and 500 mg/kg/day) to be injected into castrated rats after induction of a testosterone-BPH model. Testosterone propionate (TP) was subcutaneously injected (0.5 mg/kg/day) for one week after castration to induce BPH. Forty adult Wistar male rats were randomly allocated into five groups: control, BPH model, high and low O. majorana doses (250, 500 mg/kg/day), and finasteride (FN) (0.8 mg/kg/day) as a positive control. Treatment was continued with drugs/normal saline for 28 days. Rat&rsquo;s body and prostate were weighed, prostate index (PI) and % of prostate growth inhibition were calculated, serum dihydrotestosterone (DHT), prostatic content of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA), DN damage, histopathological changes, immune expression of proliferating cell nuclear antigen (PCNA), caspase-3, &alpha;-SMA, and TGF-&beta;1 were assessed. In addition, molecular quantitative PCR and ELISA analyses were performed to identify the expression of mRNAs and related proteins of both caspase-3 and TGF-&beta;1 in prostate tissue from O. majorana-treated and untreated groups. Rats with BPH had significantly higher prostate weights and PI, higher DHT, DNA damage (8-hydroxyguanine, 8-OH-dG), and MDA levels with prominent PCNA, &alpha;-SMA, and TGF-&beta; expression, but lower SOD, CAT, and TAC activity and caspase-3 expression. O. majorana (250 and 500 mg/kg/day)-treated groups revealed a decrease in prostate weights and PI, lower levels of DHT, suppressed oxidative stress, reduced tissue proliferation and fibrosis, and restored antioxidant and proapoptotic activity. Additionally, quantitative PCR and ELISA analysis showed that treatment with O. majorana significantly upregulated the expression of caspase-3 and downregulated the expression of TGF-&beta; in prostate tissues of BPH rats. The data were confirmed by the immunohistological reactivity of these targeted markers in the prostate tissues. These effects were more significant with O. majorana 500 mg/mL/rat. In conclusion, the current study indicates the efficient use of O. majorana in the treatment of testosterone-induced BPH through its antiproliferative, proapoptotic, and antioxidative mechanisms

Measurement and Modeling of Zolpidem Solubility in Supercritical Carbon Dioxide: Effect of Two Cosolvents

Obtaining data on the solubility of zolpidem, a sedative–hypnotic drug, in supercritical CO2 (scCO2) is a crucial step in the development of an efficient supercritical process designed to formulate an effective drug delivery system for this medication. The current investigation entailed determining the solubility of this substance in scCO2 across a range of temperatures (308.0, 318.0, 328.0, 338.0, and 348.0 K) and pressure values between 17 and 41 MPa. Furthermore, the research delved into assessing the impact of two cosolvents, DMSO and ethanol, on the supercritical solubility of this drug under the given conditions. The solubility of zolpidem in scCO2 was within the mole fraction range of 1.19 × 10–4–3.23 × 10–4. However, when ethanol and DMSO were introduced, the solubilities were enhanced to the ranges of 3.09 × 10–4–22.13 × 10–4 and 1.31 × 10–4–12.44 × 10–4, respectively. It was noted that the impact of ethanol is more substantial, leading to an approximately 4–5 times improvement in the supercritical solubility of zolpidem. Utilizing validated empirical models to correlate supercritical solubility data for both the scCO2–zolpidem and scCO2–ethanol–zolpidem systems, it was observed that the empirical models developed by Nejad and Keshmiri for the zolpidem–scCO2 system (AARD% ≈ 1.50 and Radj = 0.996) and by MST–Sauceau for the zolpidem–scCO2–ethanol system (AARD% = 3.51 and Radj = 0.995) exhibited the highest levels of consistency between the predicted solubility values and the actual experimental data. Also, the supercritical solubility data of the scCO2–zolpidem binary system were evaluated by using the SRK and UNIQUAC models. It was observed that the SRK model demonstrated exceptional accuracy (AARD% = 1.53 and Radj = 0.999) in modeling zolpidem solubility in scCO2

Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain

Manganese neurotoxicity has been reported to cause a neurodegenerative disease known as parkinsonism. Previous reports have shown that the expression of the KH-type splicing regulatory protein (KHSRP), a nucleic acid-binding protein, and NLRP3 is increased upon Mn exposure. However, the relation between these two during Mn toxicity has not been fully deduced. The mouse neuroblastoma (N2a) and SD rats are treated with LPS and MnCl2 to evaluate the expression of KHSRP and NLRP3. Further, the effect of the NLRP3 inhibitor MCC950 is checked on the expression of NLRP3, KHSRP and pro-inflammatory markers (TNFα, IL-18 and IL-1β) as well as the caspase-1 enzyme. Our results demonstrated an increment in NLRP3 and KHSRP expression post-MnCl2 exposure in N2a cells and rat brain, while on the other hand with LPS exposure only NLRP3 expression levels were elevated and KHSRP was found to be unaffected. An increased expression of KHSRP, NLRP3, pro-inflammatory markers and the caspase-1 enzyme was observed to be inhibited with MCC950 treatment in MnCl2-exposed cells and rats. Manganese exposure induces NLRP3 and KHSRP expression to induce neuroinflammation, suggesting a correlation between both which functions in toxicity-related pathways. Furthermore, MCC950 treatment reversed the role of KHSRP from anti-inflammatory to pro-inflammatory