Background: Diabetes mellitus-induced hyperglycemia triggers oxidative stress, characterized by elevated malondialdehyde (MDA) and impaired catalase (CAT) activity. Stevia rebaudiana, rich in steviol glycosides and polyphenols, demonstrates promising antioxidant properties, yet systematic dose-response data on oxidative stress biomarkers remain limited. Objectives: To evaluate the dose-dependent effects of stevia leaf extract on serum MDA levels and CAT activity in alloxan-induced hyperglycemic rats. Methods: Twenty-five male Wistar rats were allocated into normal control, diabetic control (alloxan 120 mg/kg), and three treatment groups receiving alloxan plus stevia extract at 100, 200, or 400 mg/kg body weight orally for 14 days (n=5/group). Serum MDA and CAT were measured spectrophotometrically. Results: Diabetic control showed significantly elevated MDA (2.68±0.62 mg/dL) versus normal control (1.78±0.30 mg/dL). Stevia extract dose-dependently reduced MDA: 1.70±0.19, 1.54±0.20, and 1.38±0.09 mg/dL at 100, 200, and 400 mg/kg, respectively, representing 36.6%, 42.5%, and 48.5% reduction. The 400 mg/kg dose achieved MDA levels comparable to normal control. CAT activity showed dose-dependent restoration trend (7.92±0.76 to 8.58±0.52 mg/dL). Conclusion: Stevia leaf extract (400 mg/kg BW) effectively reduces oxidative stress in hyperglycemic rats through significant dose-dependent MDA reduction, with potential catalase benefits requiring further investigation.

Background: Protein malnutrition during early development can alter the hormonal pathways essential for female reproductive maturation. It remains a significant concern in regions where inadequate protein intake contributes to stunting and long-term reproductive risks. However, evidence remains limited regarding how maternal and early-life protein deficiency affects reproductive hormone formation in offspring, and whether locally available nutrient sources can reverse these disruptions. Objective: This study evaluated the effects of supplementation of Rasbora borneensis and Vigna unguiculata spp. cylindrica on reproductive hormones in female rat offspring subjected to protein deficiency. Methods: A protein-deficient model was generated by feeding rats a low-protein AIN-76A diet from birth to weaning, followed by continuation of the same diet in female offspring for four weeks. The offspring were then assigned to a normal control group receiving a standard diet, a negative control group maintained on the low-protein diet, and three treatment groups receiving Seluang fish feed, cowpea cowpea feed, or a combination of both for four weeks. FSH and estrogen levels were assessed to evaluate reproductive endocrine function. Results: All treatment diets increased FSH and estrogen levels compared with the negative control. FSH concentrations were significantly higher in all treatment groups (p = 0.012), with the combination diet yielding the greatest increase. Estrogen levels also rose substantially in the treatment groups with statistical analyses confirming significant differences (p < 0.001). Conclusion: Seluang fish and Nagara cowpea effectively improved reproductive hormone profiles in protein-deficient female rats, highlighting their potential as relevant nutritional strategies to counter early-life protein malnutrition.

Background: Obesity is associated with hyperlipidemia and enhanced adipogenesis mediated by HMGR and GPDH enzymes. Eurycoma longifolia represents a potential natural therapeutic alternative to statins for obesity management. Objective: To investigate the anti-obesity potential of E. longifolia compounds through HMGR and GPDH inhibition using integrated in silico and in vivo approaches. Methods: Molecular docking was performed using AutoDock Vina to evaluate interactions between seven bioactive compounds and HMGR/GPDH proteins. Validation was confirmed by RMSD values below 2 Å. Binding affinities and dissociation constants were analyzed. In vivo study employed Wistar rats fed high-calorie, high-fat diet for 12 weeks, followed by four weeks of E. longifolia extract treatment at varying doses. Body weight and intra-abdominal fat were measured. Results: Three compounds exhibited binding affinities equivalent to atorvastatin against HMGR (-8.4 kcal/mol). Four compounds demonstrated stronger affinity than metformin against GPDH. Extract administration significantly reduced intra-abdominal fat in a dose-dependent manner (p = 0.000). Conclusion: E. longifolia compounds demonstrate dual inhibitory potential against HMGR and GPDH through computational modeling, with experimental validation confirming significant reduction in visceral adiposity in obese rats.

Background: Arenga pinnata leaves have been traditionally used for medicinal purposes; however, their phytochemical composition and toxicity profile remain poorly characterized. Objective: This study aimed to identify bioactive compounds in A. pinnata leaf aqueous extract and evaluate its acute oral toxicity in Wistar rats. Methods: Qualitative phytochemical screening was performed using standard colorimetric and precipitation methods. Twenty-five male Wistar rats were randomly assigned to five groups (n=5): one control (distilled water) and four treatment groups receiving single oral doses of 200, 400, 800, and 1600 mg/kg body weight of aqueous extract. Animals were monitored for 14 days for mortality, behavioral changes, and clinical toxicity signs. Results: Phytochemical analysis confirmed the presence of alkaloids, flavonoids, tannins, and triterpenoids. No mortality, adverse clinical signs, or pathological organ changes were observed throughout the study period. All animals exhibited normal behavior and progressive weight gain. The median lethal dose (LD₅₀) exceeded 1600 mg/kg body weight, indicating low acute oral toxicity. Conclusion: A. pinnata leaf aqueous extract contains pharmacologically relevant bioactive compounds and demonstrates a favorable acute safety profile. These findings support traditional use while highlighting the need for sub-chronic and chronic toxicity studies.

Background: Arenga pinnata leaves have been traditionally used for medicinal purposes; however, their phytochemical composition and toxicity profile remain poorly characterized. Objective: This study aimed to identify bioactive compounds in A. pinnata leaf aqueous extract and evaluate its acute oral toxicity in Wistar rats. Methods: Qualitative phytochemical screening was performed using standard colorimetric and precipitation methods. Twenty-five male Wistar rats were randomly assigned to five groups (n=5): one control (distilled water) and four treatment groups receiving single oral doses of 200, 400, 800, and 1600 mg/kg body weight of aqueous extract. Animals were monitored for 14 days for mortality, behavioral changes, and clinical toxicity signs. Results: Phytochemical analysis confirmed the presence of alkaloids, flavonoids, tannins, and triterpenoids. No mortality, adverse clinical signs, or pathological organ changes were observed throughout the study period. All animals exhibited normal behavior and progressive weight gain. The median lethal dose (LD₅₀) exceeded 1600 mg/kg body weight, indicating low acute oral toxicity. Conclusion: A. pinnata leaf aqueous extract contains pharmacologically relevant bioactive compounds and demonstrates a favorable acute safety profile. These findings support traditional use while highlighting the need for sub-chronic and chronic toxicity studies.

Background: Chronic administration of non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac sodium generates excessive reactive oxygen species (ROS), causing lipid peroxidation and elevated malondialdehyde (MDA) levels, a biomarker of oxidative tissue damage. Turmeric extract (Curcuma longa L.) contains curcuminoids with antioxidant properties that may reduce MDA formation and mitigate NSAID-induced injury. Objectives: To determine the effect of turmeric extract on malondialdehyde (MDA) levels in white rats (Rattus norvegicus) induced with sodium diclofenac. Methods: This laboratory experimental study employed a posttest-only control group design. Twenty-eight white rats were divided into four groups: normal control, negative control (diclofenac 10 mg/kg), treatment 1 (diclofenac + extract 100 mg/kg), and treatment 2 (diclofenac + extract 200 mg/kg). MDA levels were measured spectrophotometrically. Data were analyzed using One-Way ANOVA and post hoc Dunnett T3 test. Results: Turmeric extract significantly reduced MDA levels (p<0.001). The 200 mg/kg dose demonstrated superior protective effects compared to 100 mg/kg, effectively preventing diclofenac-induced oxidative stress. Conclusion: Turmeric extract demonstrates dose-dependent protective effects against diclofenac-induced oxidative stress, with 200 mg/kg achieving 18.3% MDA reduction and restoring oxidative balance. These findings support its potential as adjunct therapy for chronic NSAID users.

Background: Non-steroidal anti-inflammatory drugs, particularly diclofenac sodium, are widely prescribed but can cause nephrotoxicity through oxidative stress mechanisms. Turmeric (Curcuma longa L.) contains curcumin and other bioactive compounds with potent antioxidant properties that may protect against drug-induced kidney damage. Objective: To evaluate the dose-dependent effects of turmeric ethanol extract on kidney histopathology in rats with established diclofenac sodium-induced nephrotoxicity. Methods: Twenty-eight male Sprague Dawley rats were randomly divided into four groups: normal control, diclofenac (10 mg/kg for 7 days), and two treatment groups receiving diclofenac followed by turmeric extract at 100 mg/kg or 200 mg/kg for 14 days. Kidney histopathology was assessed using the Arsad scoring system by a blinded pathologist. Results: Significant differences existed between groups (p < 0.001). The negative control exhibited severe kidney damage with hydropic degeneration, granular casts, and cellular casts (mean score: 2.78 ± 0.24). Treatment with 100 mg/kg showed partial improvement (1.65 ± 0.31), while 200 mg/kg demonstrated substantial improvement approaching normal histology (0.52 ± 0.18) with only minimal residual damage. Conclusion: Turmeric extract demonstrates significant dose-dependent nephroprotective effects against diclofenac-induced kidney damage, with 200 mg/kg providing superior protection, suggesting potential therapeutic applications in mitigating NSAID-induced nephrotoxicity.

Proteostasis, the integrated network regulating protein synthesis, folding, trafficking, and degradation, is essential for cellular function and organismal health. Reduced oxygen availability disrupts proteostasis through increased reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, impaired ATP-dependent protein folding, and altered chaperone expression. In cancer, tumor cells exploit chronic unfolded protein response (UPR) signaling to enhance survival, angiogenesis, and therapeutic resistance. Inhibition of IRE1α and PERK pathways has shown efficacy in preclinical models, though clinical translation faces challenges including off-target toxicity. In neurodegenerative diseases—Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis—chronic hypoxia accelerates protein aggregate accumulation through oxidative modifications and impaired autophagy-lysosome function. Therapeutic strategies targeting γ-secretase, BACE1, and protein clearance pathways have demonstrated limited clinical success despite mechanistic rationale. Understanding hypoxia-induced proteostasis failure may inform therapeutic development, though significant obstacles remain in translating preclinical findings to effective treatments for cancer and neurodegenerative diseases.

Background: Glutathione (GSH), the primary endogenous antioxidant, protects cells against oxidative stress. Diclofenac sodium, a commonly prescribed nonsteroidal anti-inflammatory drug (NSAID), depletes GSH through hepatic metabolic byproducts, causing oxidative damage. Objective: To evaluate the protective effect of turmeric extract (Curcuma longa L.) on glutathione levels in rats subjected to diclofenac-induced oxidative stress. Methods: Twenty-eight male Wistar rats were randomly divided into four groups (n=7): normal control, negative control (diclofenac sodium 10 mg/kg body weight [BW]), and two treatment groups receiving turmeric extract (100 mg/kg BW or 200 mg/kg BW) following diclofenac induction. Diclofenac was administered for 7 days; turmeric extract was given orally for 14 days. Cardiac blood glutathione levels were measured spectrophotometrically. Results: Turmeric extract significantly increased glutathione levels in diclofenac-induced rats compared to negative controls (p<0.05). The 200 mg/kg BW dose produced superior protection, elevating GSH levels significantly above all groups (p<0.001), demonstrating a dose-dependent antioxidant effect. Conclusion: Turmeric extract demonstrates significant dose-dependent antioxidant activity against diclofenac-induced oxidative stress, with the 200 mg/kg BW dose achieving superior GSH elevation (p < 0.001), suggesting potential as a protective agent against NSAID-induced oxidative damage.

Background: Diclofenac sodium, a widely used nonsteroidal anti-inflammatory drug (NSAID), causes significant hepatotoxicity through oxidative stress mechanisms. Turmeric (Curcuma longa L.), rich in curcuminoid antioxidants, may offer hepatoprotection. Objective: To evaluate the hepatoprotective effects of turmeric extract against diclofenac sodium-induced liver injury in rats. Methods: Twenty-eight male Sprague Dawley rats were randomly divided into four groups (n=7): normal control, negative control (diclofenac sodium 10 mg/kg BW for 7 days), and two treatment groups receiving diclofenac sodium followed by turmeric extract at 100 or 200 mg/kg BW for 14 days. Liver histopathology was assessed using hematoxylin-eosin staining. Data were analyzed descriptively. Results: Turmeric extract attenuated hepatocellular damage in a dose-dependent manner. The 200 mg/kg BW dose completely prevented necrosis, demonstrating superior hepatoprotection compared to 100 mg/kg BW. Conclusion: Turmeric extract exerts hepatoprotective effects against diclofenac-induced liver injury through attenuation of histopathological damage.