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Oxygen-free radicals have been implicated in the initiation of diabetic complications. Thiazolidinediones (TZDs), known for their antidiabetic properties, also demonstrate notable antioxidant and anti-inflammatory effects. Although a recently developed imidazolyl analogue of pioglitazone (PA9) has exhibited superior glucose-lowering efficacy compared to pioglitazone, its antioxidant effects remain unexplored. Thus, the objective of this study is to evaluate the antioxidant properties of PA9 in animal models with diabetes. Rats were randomly separated into the following four groups: control, diabetic, and two groups treated orally with pioglitazone as a standard drug and PA9 for ten days. Upon completion of the experiment, tissues from the liver, heart, brain, pancreas, spleen, and kidneys were collected to assess oxidant/antioxidant markers and histological alterations. The administration of PA9 resulted in a noteworthy reduction in malondialdehyde (MDA) levels compared to the diabetic group (p < 0.05). The group receiving PA9 displayed elevated levels of three antioxidant markers, catalase (CAT), superoxide dismutase (SOD), and total thiol, in pancreatic tissue compared to diabetic rats (p < 0.05). Furthermore, increased content of CAT was evident in the heart (p < 0.05), spleen (p < 0.001), brain, and kidney tissues in the PA9-treated group, along with augmented thiol content in the spleen compared to the diabetic group. Remarkably, no significant histological changes were observed in the liver, pancreas, heart, brain, spleen, and kidneys of the PA9-treated groups relative to diabetic rats. PA9 effectively mitigates oxidative stress, modulates redox homeostasis, and shows promise in preventing diabetic complications. The proven safety profile of this analogue underscores its potential, warranting comprehensive clinical evaluation to thoroughly understand its therapeutic scope and efficacy in the management of diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus represents a prominent global health concern, characterized by a rising prevalence rate. Type 2 Diabetes Mellitus (T2DM) is purported to be associated with an intricate interplay of genetic, environmental, and lifestyle factors. While some progress have been made in T2DM management, controlling associated complications remains a great challenge in medicine., Objectives: This study investigated a synthesized Imidazolyl Thiazolidinedione antidiabetic agent (PA9), focusing on serum parameters., Methods: Streptozotocin-induced diabetic rats (n = 6) were subjected to orally treatment with PA9 (synthesized by Shakour et al. in an equal dose of a standard drug, 0.011 mmol/kg). The study conducted to measure some specific serum factors, including lipid profiles, liver and kidney enzymes, cardiac enzymes, and oxidative stress markers, both before and after treatment., Results: The study findings indicated that PA9 effectively ameliorates hyperlipidemia by significantly reducing total cholesterol and triglyceride levels in serum. Additionally, PA9 demonstrated hepatoprotective effects against TZD-induced injuries, as evidenced by decreased levels of alanine transaminase and, alkaline phosphatase. In addition, PA9 also exhibited a modulatory effect on a cardiac injury marker, creatine kinase MB. Moreover, PA9 demonstrated antioxidant properties by reducing oxidative stress markers and enhancing the activities of catalase, thiol, and superoxide dismutase., Conclusions: The synthesized TZD compound (PA9) stands out as a highly promising agent for the management of diabetes. Its significant antihyperlipidemic effects, preventive influences on organ injuries, and demonstrated efficacy in reducing oxidative stress marker (SOD) make it therapeutic agent in diabetes management. This study lays the groundwork for innovative strategies in diabetes management., Competing Interests: Declaration Conflict of interests The authors declare that they have no conflicts of interest. Ethical approval The ethical clearance for the animal experimentation was obtained from the Ethics Committee at Mashhad University of Medical Sciences, with approval referenced as IR.MUMS.SP.1396.196., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Type-one diabetes (T1D), a chronic autoimmune disease with marked inflammatory responses, is associated with infertility complications and implications. Based on the anti-diabetic, antioxidant, and anti-hyperlipidemic potential of Portulaca oleracea (PO), this study aimed to evaluate the protective effect of this plant extract on streptozotocin-induced type-I-diabetes-associated reproductive system dysfunction and inflammation., Methods: Male rats were randomly divided into four experimental groups: control, diabetic, and treatment/s (PO extract at 100 or 300 mg/kg/daily). Then food and water consumption, body, testis and epididymis weights, histopathological evaluation, seminiferous tubules diameter, sperm count and motility, glucose levels, sex hormones, and inflammatory and oxidative stress markers were evaluated., Results: Our results showed that streptozotocin-induced diabetes significantly increased food and water consumption; increased glucose, MDA, TGF-β1, and TNF-α levels; and decreased the seminiferous tubules diameter, sperm count and motility, levels of LH, testosterone, total thiol, VEGF, and SOD activity. Interestingly, PO extract (phytochemically characterized by using liquid chromatography-mass spectrometry to detect bioactive molecules) significantly ameliorated these parameters and histopathological indexes' damage in rats., Conclusion: Even if more preclinical assessments are needed to better characterize the mechanism/s of action, the results of this study will pave the way for the rational use of PO on diabetic-associated clinical complications and implications.

Objective: The beneficial effect of carvacrol on neuroinflammation, oxidative damage of brain tissue, and depressive- and anxiety-like behaviors after lipopolysaccharide (LPS) administration were evaluated in rats., Materials and Methods: Vehicle (1% Tween 80), 1 mg/kg of LPS, and carvacrol (25, 50, or 100 mg/kg administered prior to LPS) were injected and behavioral and biochemical tests were done., Results: The results of forced swim test revealed that carvacrol attenuated immobility time and increased activity and climbing times (p<0.05 to p<0.001). The results of elevated plus maze also revealed that treatment by carvacrol prolonged the open arms time and entries and decreased the time and entries in the closed arms (p<0.05 to p<0.01). Carvacrol enhanced crossing, time, and traveled distance in the central segment of the open field and increased total crossing and distance while attenuating the peripheral zone time (p<0.05 to p<0.001). All doses of carvacrol attenuated TNF- α (tumor necrosis factor α) and NO (nitric oxide) in the brain (p<0.01 to p<0.001). The 50 and the 100 mg/kg doses of carvacrol decreased malondialdehyde (p<0.001 for both), and the 100 mg/kg dose of carvacrol increased the content of the thiol (p<0.001)., Conclusion: In conclusion, carvacrol improved the behavioral consequences of LPS challenge and attenuated neuroinflammation and brain tissue oxidative stress in rats., Competing Interests: The authors have declared that there is no conflict of interest.

Although Sanguisorba minor has been used as herbal medicine, no study has ever examined its potential toxicity. This study investigated acute and subacute toxicities of S. minor hydroalcoholic extract (SE). In the acute toxicity test, a single oral dose (300, 2,000, and 3,000 mg/kg) of SE was given to mice. The oral administration of SE (100, 200, and 400 mg/kg for 4 weeks) was performed to evaluate subacute toxicity. After the treatments, neurobehavioral, histopathology, hematological, and biochemical parameters were monitored. In vitro cytotoxicity was also assessed. Moreover, high-performance liquid chromatography fingerprint was done for the standardization of SE. The no-observed-adverse-effect level of SE was up to 2,000 mg/kg, and the LD 50 of the prepared extract was over 3,000 mg/kg. The rats exposed to the extract did not show any marked change in their body weight. The extract at used doses did not affect neuromuscular coordination. According to the hematological, biochemical, and histological examinations, no significant treatment-related adverse effect of the extract was observed, even at 400 mg/kg. Only 48 h exposure to 400 μg/mL of SE reduced the viability of PC12 cells. The findings revealed that this plant could be well-tolerated, regarded safe, and used as herbal medicine., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Morus nigra is a rich source of anthocyanins, phytochemicals that have anticancer effects. This study aimed to investigate the effects of M. nigra extract (MNE) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Male Sprague-Dawley rats were assigned into four groups (n = 10): control, DEN, and DEN +100 or 400 mg/kg of MNE. After 4 months, the DEN group showed a significant mortality rate, hepatic lipid peroxidation, dysplastic nodules in the cirrhotic liver, and an increase of blood bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Also, the body weight gain, blood albumin and glucose, liver antioxidant capacity (thiol groups), and some hematological parameters (RBC, hematocrit, hemoglobin, and platelet) were significantly decreased in the DEN group. MNE significantly increased survival, reduced the size of HCC nodules, improved liver oxidant/antioxidant status, and prevented the above-mentioned changes in the blood (except ALP, glucose, and platelet). Quantitative real-time PCR showed that MNE decreased the expression of Wnt4 and β-catenin, while had no significant effect on PI3K, Akt, and PTEN expression. The MNE did not exhibit antiproliferative activity against HepG2 liver cancer cells. In conclusion, MNE exhibits a hepatoprotective effect through inhibiting oxidative stress and Wnt4/β-catenin pathway and therefore prolongs the survival of rats with HCC., (© 2021 John Wiley & Sons, Ltd.)

Background and Purpose: Previous studies have shown the antioxidant, anti-inflammatory, immunomodulatory, and hypolipidemic activities of Iris germanica . The aim of the present study was to evaluate the protective effects of hydroalcoholic extract of Iris germanica rhizomes on streptozotocin-induced diabetic rats., Experimental Approach: Twenty-four male Wistar rats were randomly assigned into four groups including a normal control group, diabetic control group, diabetic groups treated for 4 weeks with 100 and 200 mg/kg/day of the Iris germanica extract (IGE)., Findings/results: Induction of diabetes significantly decreased the body weight gain and considerably increased the serum levels of glucose, triglyceride, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Diabetes also diminished the antioxidant capacity of the liver (decrease of thiol groups) and significantly degenerated pancreatic islands. The IGE at both doses of 100 and 200 mg/kg significantly reduced the levels of glucose, triglyceride, AST, ALT, and ALP. Moreover, IGE increased the total antioxidant capacity of the liver and ameliorated pancreatic island morphology. The extract had no significant effect on body weight and BUN level., Conclusion and Implication: These findings suggest that Iris germanica rhizomes inhibits the progression of hyperglycemia and hypertriglyceridemia and has protective effects against diabetes-induced injury of the liver and pancreas. Therefore, this plant has the potential to be used as a natural product for controlling diabetes., Competing Interests: The authors declared no conflict of interest in this study., (Copyright: © 2021 Research in Pharmaceutical Sciences.)