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Rationale: Stressors play a critical role in the progression of irritable bowel syndrome (IBS). Heterogenous stress causes alterations in our bowel movements which can further cause anxiety and depression-like symptoms, decreasing the ability of individuals worldwide to function in social, academic, and employment settings., Objectives: This study was aimed to investigate the effect of orally administered Nigella sativa (0.2 mL/kg b.wt.) seed oil (NSSO) on stress-induced IBS, anxiety, and depression-like symptoms in Wistar rats., Methods: In the present study, modelling IBS induced anxiety and depression-like symptoms in rodents have been employed to correlate the pathophysiological mechanisms behind this disorder. Moreover, evaluation of ameliorative potential of traditionally used NSSO in IBS was also carried out., Results: Present investigation indicated that acute stress of 1.5 h daily for 20 days induced hyper cortisol, gastrointestinal (GI) hypermotility, diarrhoea, altered levels of short chain fatty acids (SCFAs), and inflammation which are common symptoms of IBS. Furthermore, depression and anxiety-like symptoms were validated in test groups by various behavioral tests and decreased levels of 5-HT-Transporter mRNA gene expression, which are clear indicators of cognitive impairment., Conclusions: It is possible that these IBS-like symptoms may have contributed to the pathogenesis of cognitive deficits and depression. However, the anti-oxidative, anti-inflammatory, anti-spasmodic, and possibly the anti-anxiolytic properties of NSSO helped in the mitigation of altered gut-brain axis. Because the concurrent treatment of NSSO alleviated the symptoms of modified GI function and consequently, the anxious & depressive behavior of the animals. Overall, this research explored the protective efficacy of NSSO against stress-induced IBS and depression-like symptoms, shedding light on the potential of this natural compound as a therapeutic option in the field of gastroenterology and psychiatry., Competing Interests: Declarations Conflict of interest The authors report that there are no financial or non-financial interests to declare. Ethics Approval This study was performed as per the ‘Guide for the Care and Use of Experimental Animals’ approved by the Institutional Animal Ethics Committee (IAEC), Panjab University (PU/45/99/CPCSEA/IAEC/2023/785). Disclosure Statement The authors report that there are no relevant financial or non-financial interests to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tannic acid (TA) is a metal chelating polyphenol that plays a crucial role in metal detoxification, but its modulatory role in co-exposure of these heavy metals' exposure needs to be explored. Cadmium (Cd) and nickel (Ni) are inorganic hazardous chemicals in the environment. Humans are prone to be exposed to the co-exposure of Cd and Ni, but the toxicological interactions of these metals are poorly defined. Present study was undertaken to study the preventive role of TA in Cd-Ni co-exposure-evoked hepato-renal toxicity in BALB/c mice. In the current investigation, increased oxidative stress in metal intoxicated groups was confirmed by elevated peroxidation of the lipids and significant lowering of endogenous antioxidant enzymes. Altered hepato-renal serum markers, DNA fragmentation, and histological alterations were also detected in the metal-treated groups. Present study revealed that Cd is a stronger toxicant than Ni and when co-exposure was administered, additive, sub-additive, and detrimental effects were observed. Prophylactic treatment with TA significantly reinstated the levels of lipid peroxidation (LPO), non-enzymatic, and enzymatic antioxidants. Moreover, it also restored the serum biomarker levels, DNA damage, and histoarchitecture of the given tissues. TA due to its metal chelating and anti-oxidative properties exhibited cyto- and genoprotective potential against Cd-Ni co-exposure-induced hepatic and renal injury., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Embryonic valproic acid (VPA) has been considered a potential risk factor for autism. Majority of studies indicated that targeting autism-associated alterations in VPA-induced autistic model could be promising in defining and designing therapeutics for autism. Numerous investigations in this field investigated the role of canonical Wnt signaling cascade in regulating the pathophysiology of autism. The impaired blood-brain barrier (BBB) permeability and mitochondrial dysfunction are some key implied features of the autistic brain. So, the current study was conducted to target canonical Wnt signaling pathway with a natural polyphenolic modulator cum antioxidant namely fisetin. A single dose of intraperitoneal VPA sodium salt (400 mg/kg) at gestational day 12.5 induced developmental delays, social behaviour impairments (tube dominance test), and anxiety-like behaviour (sucrose preference test) similar to autism. VPA induced mitochondrial damage and over-activated the canonical Wnt signaling which further increased the blood-brain barrier (BBB) disruption, apoptosis, and neuronal damage. Our findings revealed that oral administration of 10 mg/kg gestational fisetin (GD 13-till parturition) improved social and anxiety-like behaviour by modulating the ROS-regulated mitochondrial-canonical Wnt signaling. Moreover, fisetin controls BBB permeability, apoptosis, and neuronal damage in autism model proving its neuroprotective efficacy. Collectively, our findings revealed that fisetin-evoked modulation of the Wnt signaling cascade successfully relieved the associated symptoms of autism along with developmental delays in the model and indicates its potential as a bioceutical against autism., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Autism is a neurodevelopmental condition, and it's associated pathophysiology, viz., oxidative stress and altered cellular homeostasis, has been extensively intertwined with behavioral impairments. Therefore, targeting oxidative stress and redox cellular homeostasis could be beneficial in relieving autistic-like symptoms. For this purpose, we examined a library of nutraceutical compounds that led us to a bioflavonoid fisetin. Autism-like neurobehavior was induced by subjecting the pregnant rodents to valproic acid at the time of neural tube closure (GD12.5). In this novel study, fisetin was evaluated for its neuroprotective potential at gestational (GD13 until delivery) and post-weaning developmental windows (PND 23-32) in VPA-induced rodent model of autism. Developmental VPA exposure increased intracellular ROS production, oxidative stress, altered AChE and ATPases in brain regions, and induced autistic-like behavioral impairments (social, repetitive, stereotyped, and sensorimotor). The present findings suggested that gestational and post-weaning fisetin treatment significantly improved the behavioral impairments by attenuating elevated oxidative stress, ROS, lipid peroxidation, and re-establishing redox homeostasis. Also, it effectively reinstated the reduced levels of endogenous antioxidants, glutathione, AChE, and ATPases by its antioxidant potential. Therefore, fisetin with its properties could be used as a potential therapeutic agent in overcoming the symptoms associated with autism., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)