HEPATOCYTE APOPTOSIS INDUCTION BY ACETAMINOPHEN THROUGH MODULATION OF CASPASE/BAX PATHWAY IN MICE

Objective: Acetaminophen (APAP) overdose contributes to liver damage through modulation of pro-apoptotic processing. This study evaluated the involvement of caspase/Bax factors in APAP hepatotoxicity in vivo and in vitro. Methods: The involvement of caspase/Bax factors in APAP hepatotoxicity was evaluated in BALB/c mice and on isolated primary mouse hepatocytes. In vitro MTT assay was carried out on primary cultured mouse hepatocytes treated with APAP (2.5, 5, 10 mmol) and Annexin V/PI staining was employed to cell suspension for imaging under fluorescence microscopy. In addition, caspase-3 concentrations were determined in cell lysates. In vivo, mice were treated with a toxic dose of APAP (700 mg/kg) and immunodetection of Bax was made by Western Blot. Vitamin C (Vit C) was used as a hepato-protectant due to its known antioxidant activities. Results: In vitro dose-dependent increase in mitochondrial electron transport capacity was evident in isolated mouse primary hepatocytes incubated with the high dose of APAP (10 mmol) compared to both nontreated cells and cells pre-treated with Vitamin C (Vit C) (0.5 mmol) (p<0.05). Apoptosis was confirmed in hepatocytes through Annexin V staining after APAP treatment and the signal was reduced when hepatocytes were pre-treated with Vit C. In addition, caspase-3 concentration was decreased in cells pretreated with Vit C prior to APAP exposure. In vivo, Bax immunodetection utilizing western blotting was increased in mice treated with the toxic dose of APAP (700 mg/kg) and attenuated through pre-treatment with Vit C. Conclusion: Modulation of apoptotic caspase/Bax pathway is present in hepatocytes undergoing APAP-induced toxicity

SOD1 and DJ-1 Converge at Nrf2 Pathway: A Clue for Antioxidant Therapeutic Potential in Neurodegeneration

Neurodegenerative diseases share diverse pathological features and among these oxidative stress (OS) plays a leading role. Impaired activity and reduced expression of antioxidant proteins have been reported as common events in several aging-associated disorders. In this review paper, we first provide an overview of the involvement of reactive oxygen species- (ROS-) induced oxidative damage in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Subsequently, we focus on DJ-1 and SOD1 proteins, which are involved in PD and ALS and also exert a prominent role in the interaction between redox homeostasis and neurodegeneration. Interestingly, recent studies demonstrated that DJ-1 and SOD1 are both tightly connected with Nrf2 protein, a transcriptional factor and master regulator of the expression of many antioxidant/detoxification genes. Nrf2 is emerging as a key neuroprotective protein in neurodegenerative diseases, since it helps neuronal cells to cope with toxic insults and OS. We herein summarize the recent literature providing a detailed picture of the promising therapeutic efficacy of Nrf2 natural and synthetic inducers as disease-modifying molecules for the treatment of neurodegenerative diseases

2ʹ,3,3,5ʹ-Tetramethyl-4ʹ-nitro-2ʹH-1,3ʹ-bipyrazole exerts antinociceptive effect using various nociception models

Background: 2ʹ,3,3,5ʹ-Tetramethyl-4ʹ-nitro-2ʹH-1,3ʹ-bipyrazole (TMNB) is a novel bipyrazole compound that exhibited antidiabetic and anti-inflammatory properties. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of TMNB using different nociception mouse models. Methods: TMNB doses (50, 100, 150, and 200 µg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone. Capsaicin- and glutamate-induced paw-licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Results: TMNB produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 66% inhibition at a dose of 200 µg/kg. TMNB also caused a significant increase in the latency period in response to the hot plate test (68.2% at 200 µg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw-licking test. Naloxone significantly reverses the effect of TMNB in both the hot plate test and formalin-induced paw-licking test. Moreover, TMNB significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (53% and 77.1%, respectively at a dose of 200 µg/kg). Conclusion: TMNB possesses antinociceptive activity in mice that is mediated through both central and peripheral pathways

Formononetin suppresses hyperglycaemia through activation of GLUT4-AMPK pathway

Background: Formononetin (FMN) is a flavonoid that has different pharmacological effects. Thus, the anti-diabetic effects of FMN has been investigated in a high-fat diet/Streptozotocin-(HFD/STZ)-induced diabetes mice model. Methods: Mice were fed with HFD followed by STZ. Diabetic mice were treated orally with FMN or metformin for 28 days before collecting plasma and soleus muscle for further analysis. Results: FMN reduced serum glucose (p>0.001) and increased serum insulin in diabetic group compared to the vehicle control. Additionally, FMN decreased homeostasis model assessment of insulin resistance (HOMA-IR). Fasting glucose level was also reduced with FMN during the intraperitoneal glucose tolerance test (IPGTT). GLUT4 and p-AMPK-α1 were upregulated following treatment with FMN. LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with FMN. FMN reduced MDA, increased GSH levels , and reduced GSSG levels in diabetic mice. Conclusion: FMN could represent a promising therapeutic agent to treat T2D

Cirsimaritin alleviates dextran sodium sulfate-induced acute colitis in experimental animals: a therapeutic approach for inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease that affects the entire digestive tract. IBD can be classified as ulcerative colitis or Crohn’s disease. The key symptoms of IBD include the emergence of abscesses or pustules, pronounced abdominal discomfort, diarrhea, fistulas, and intestinal narrowing, all of which can greatly affect a patient’s daily well-being. Several factors, including bacterial infections, immune response irregularities, and changes in the intestinal milieu, can contribute to the onset of IBD. The aim of this study was investigating the role of cirsimaritin in reducing the severity of colitis in animal model. To induce colitis in laboratory Swiss albino mice, a 4% dextran sulfate sodium (DSS) concoction was provided in their hydration source for a duration of six days. Before the onset of colitis, mice were treated with cirsimaritin (10 mg/kg) once daily to evaluate its potential treatment effects against DSS-induced inflammation. The results showed that 10 mg/kg of cirsimaritin decreased colitis severity (P<0.05). Moreover, cirsimaritin successfully reversed the detrimental effects induced by DSS, including weight reduction, colon truncation, tissue-related damage, increased levels of inflammatory cells in the affected region, and secretion of proinflammatory cytokines. Our findings suggest that cirsimaritin can effectively alleviate acute colitis triggered by DSS

Potential anti-inflammatory activity of the Tamarix aphylla essential oil

Aim: This study aimed to assess the anti-inflammatory activity and potential mechanisms of essential oil of Tamarix aphylla (EOTA). Methods: The essential oils were extracted from the plant’s aerial parts using hydrodistillation and analyzed through gas chromatography and mass spectrometry (GC/MS). The essential oils were assessed for their anti-inflammatory effects using well-established inflammation models, namely carrageenan-induced paw edema and peritonitis. To evaluate the antioxidant activity of the essential oil, measurements were taken for nitric oxide radical-scavenging activity and lipid peroxidation. Results: The predominant components of the EOTA were 6,10,14-Trimethyl-2-pentadecanone (20.2%), β-Ionone (20.1%), Dodecanoic acid (12.2%), and trans-β-Caryophyllene (10%.1). The study found that EOTA significantly reduced edema, peritonitis, myeloperoxidase activity, and NOx-peritoneal lavage concentration induced by carrageenan. Additionally, the essential oil exhibited significant inhibition of nitric oxide radical production triggered by sodium nitroprusside. Furthermore, EOTA demonstrated the ability to prevent lipid peroxidation induced by Fe+2- or Fe+2 plus H2O2. Conclusion: The findings suggest that EOTA possesses anti-inflammatory activity, potentially linked to its antioxidant capacity

Vitamins C and D Exhibit Similar Antidepressant Effects to Escitalopram Mediated by NOx and FKBPL in a Stress-Induced Mice Model

The aim of this study was to investigate the potential antidepressant and anxiolytic effects of vitamin C and vitamin D in a stress-induced mouse model of depression, while also exploring the association between these effects and the levels of circulating NOx, periostin, and FKBPL. Our findings revealed that both vitamin C and vitamin D exhibited comparable antidepressant effects to escitalopram, a commonly used antidepressant, without demonstrating any anxiolytic effects. The antidepressant properties of vitamin C and vitamin D were linked to the normalization of Nox and FKBPL levels, while the levels of periostin showed no significant correlation. These results are consistent with previous research, indicating that the antidepressant effects of vitamin C and vitamin D may be attributed to their antioxidant and anti-inflammatory properties, as well as their modulation of neurotransmission and norepinephrine release. Additionally, our study uncovered elevated levels of periostin in stress-induced depression, which were only restored to normal levels by escitalopram, suggesting a potential role for periostin in mood disorders. Furthermore, FKBPL and NOx levels were increased in stress-induced depression and normalized by treatment with vitamin C, vitamin D, and escitalopram, indicating their involvement in the stress response and gene expression regulation. However, it is important to acknowledge certain limitations of our research, such as the use of a single depression induction model and limited dosing regimens. Future investigations should focus on examining these markers in specific brain regions, such as the hippocampus and prefrontal cortex, to gain a more comprehensive understanding of their potential implications for depression. Overall, our findings suggest that vitamin C, vitamin D, and escitalopram may possess antidepressant properties mediated by NOx and FKBPL levels, while emphasizing the potential significance of periostin in the context of depression

The effect of and psycho-education on stress, anxiety and fatigue among refugees

Background: Refugees and war survivors are at higher risk of developing mental health disorders. Anxiety and stress are caused by many factors, including a stressful environment that could cause fatigue and low quality of life. Despite the existence of many synthetic anxiolytic and antidepressant drugs, symptom management has still not been successful. Ginkgo biloba extract has been used as one of the potential herbal remedies to enhance cognitive functions. Psycho-education plays a significant role in alleviating psychological distress. However, the role of G. biloba in alleviating anxiety, stress and fatigue among refugees was not well studied previously. Objectives: In this study, we aimed to compare the effect of G. biloba and psycho-education with only psycho-education on refugees’ anxiety, stress and fatigue. Methods: A randomized controlled, pre-test–post-test design was used. Data were measured at baseline and 6 weeks later. Results: Providing psycho-education for the control group showed a non-significant improvement in outcome variables. However, adding G. biloba to psycho-education for the experimental group showed a significant reduction in mental, physical, activity fatigue and anxiety. Conclusion: The addition of G. biloba to the psycho-education proved superior to psycho-education alone. Therefore, combining the two approaches is beneficial in alleviating anxiety and fatigue