Introduction: Non-alcoholic fatty liver disease (NAFLD) is intimately linked to hepatic steatosis, inflammation, insulin resistance (IR), oxidative stress (OS), and ballooning. A high fat diet (HFD) is considered a major etiological factor that primarily covers the numerous features of NAFLD. Methods: The present study aimed to evaluate the protective effect of safranal on hepatic steatosis, OS, liver index, IR index, liver function enzymes, plasma lipids, TNF-α, malondialdehyde (MDA), advanced oxidation protein products (AOPPs) and nitrite (NO₂^–) levels in a NAFLD rat model fed with a HFD for 12 weeks. The ELISA kits were used to measure TNF-α and insulin in serum and plasma, respectively. Results: HFD significantly induced hepatic steatosis, OS, IR, liver, and oxidative enzyme elevation and inflammation in experimental animals. Rats treated with safranal in ascending order of doses 250 and 500 mg/kg orally for 4-weeks showed a reduction in hepatic lipid’s accumulation, liver index, hepatic enzymes, collagen, hepatic oxidonitrative stress markers (like AOPP, MDA and NO₂^–), and raised the levels of catalase (CAT) and superoxide dismutase (SOD) enzymes. Glutathione system components, namely glutathione (GSH), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were also restored in the safranal-treated groups. The reduction in serum TNF-α and IR provided further support to the anti-NAFLD effect of safranal. Moreover, the histopathological images indicated reverse of NAFLD activity score (NAS) through mild fatty degeneration, ballooning and inflammation in hepatocytes of treated groups. Conclusion: Findings of blood and tissue analysis concluded that safranal can be a good choice in the management and cure of NAFLD. Graphical Abstract:

Western diet style (fast food), which includes fatty frozen junk food, lard, processed meats, whole-fat dairy foods, cream, mayonnaise, butter, snacks, and fructose, is a primary etiological determinant for developing nonalcoholic steatohepatitis (NASH) worldwide. Here the primary focus is to see the impact of naturally identified essential oil on disease mechanisms developed in an animal model using the same ingredients. Currently, symptomatic therapies are recommended for the management of NASH due to non-availability of specific treatments. Therefore, the present study was designed to evaluate the potential anti-NASH effect of nerolidol in a rat model fed with a purpose-built diet. The diet substantially induced insulin resistance, hepatic steatosis, dyslipidemia, and elevation of liver enzymes in the experimental animals. The levels of liver oxidative stress markers, nitrites (NO₂^-), serum pro-inflammatory cytokine (TNF-α) and hepatic collagen were increased in disease control rats. Nerolidol oral treatment in ascending dose order of 250 and 500 mg/kg substantially reduced the steatosis (macrovesicular and microvesicular), degeneration of hepatocytes, and inflammatory cells infiltration. The amounts of circulatory TNF-α and tissue collagen were also reduced at 500 mg/kg dose of nerolidol, expressing its anti-fibrotic effect. The current study described the multiple-hit pathophysiology of NASH as enhanced steatosis, pro-inflammatory markers, and oxidative stress in rats, which resulted in the development of vicious insulin resistance. Nerolidol treatment significantly reduced hepatic lipid accumulation and halted disease progression induced by a hypercaloric diet.

Objective: Diosmetin is a flavonoid that is found in many important medicinal plants that have antihypertensive therapeutic potential. Diosmetin has been shown to have antiplatelet, anti-inflammatory and antioxidant properties, which suggests that it could be a potential candidate for use in antihypertensive therapy. Methods: In vivo and in vitro methods were used for our investigation into the antihypertensive effects of diosmetin. Results: Diosmetin significantly decreased the mean arterial pressure (MAP). The effects of diosmetin on the MAP and heart rate were more pronounced in hypertensive rats. To explore the involvement of the muscarinic receptors-linked NO pathway, Nω-nitro-L-arginine methyl ester (L-NAME) and atropine were pre-administered in vivo. The pretreatment with L-NAME did not significantly change the effects of diosmetin on the MAP by excluding the involvement of NO. Unlike L-NAME, the atropine pretreatment reduced the effects of diosmetin on the MAP, which demonstrated the role of the muscarinic receptors. In the in vitro study, diosmetin at lower concentrations produced endothelium-dependent and -independent (at higher concentrations) vasorelaxation, which was attenuated significantly by the presence of atropine and indomethacin but not L-NAME. Diosmetin was also tested for high K+-induced contractions. Diosmetin induced significant relaxation (similar to verapamil), which indicated its Ca2+ antagonistic effects. This was further confirmed by diosmetin shifting the CaCl₂ CRCs toward the right due to its suppression of the maximum response. Diosmetin also suppressed phenylephrine peak formation, which indicated its antagonist effects on the release of Ca2+. Moreover, BaCl₂ significantly inhibited the effects of diosmetin, followed by 4-AP and TEA, which suggested that the K+ channels had a role as well. Conclusions: The obtained data showed the Ca2+ channel antagonism, potassium channel activation and antimuscarinic receptor-linked vasodilatory effects of diosmetin, which demonstrated its antihypertensive potential.

Cassia plants have a considerable position in conventional systems of medicine. The possible anti-nociceptive, anti-inflammatory, and anti-neuropathic properties of Cassia artemisiodes (CAD) extract were tested using the standard animal models. In this study, in vitro antioxidant, cyclooxygenase (COX-1 and 2), and 5-lipoxygenase (5-LOX) inhibitory assays were performed. The anti-inflammatory activity was evaluated using carrageenan, histamine, and serotonin-induced paw edema models. Antipyretic activity, thermally and chemically-induced nociception, and naloxone antagonistic activities were carried out. The CAD extract was tested for anti-neuropathic activity in the streptozotocin-induced diabetic neuropathy model. Suppressing the effect of CAD extract on the mRNA level of inducible nitric oxide synthase (iNOS), COX-2, and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) was determined by performing RT-PCR. The CAD extract inhibited COX-2 and 5-LOX enzymes, paw inflammation, and reduced nociceptive behaviors. The mRNA gene expression of iNOS, COX-2, and inflammatory cytokines was reduced significantly with increased DPPH scavenging activity. The extract significantly reduced the diabetes-induced neuropathic pain. In a nutshell, these results recommended that the CAD extract has anti-nociceptive and anti-neuropathic activities due to inhibition of inflammatory and oxidative signaling.

Objective: The study investigated the effect 5-[(naphthalen-2-yloxy) methyl]-1,3,4-oxadiaszole2-thiol (B3) in animal model of acute epileptic shock. Methods: The pharmacokinetics profile of B3 was checked through SwissADME software. The binding affinities of B3, diazepam, and flumazenil (FLZ) were obtained through Auto Dock and PyRx. Post docking analysis and interpretation of hydrogen bonds were performed through Discovery Studio Visualizer 2016. Molecular dynamics simulations of three complexes were carried out through Desmond software package. B3 was then proceeded in PTZ-induced acute seizures models. Flumazenil was used in animal studies for elucidation of possible mechanism of B3. After behavioral studies, the animals were sacrificed, and the brain samples were isolated and stored in 4% formalin for molecular investigations including H and E staining, IHC staining and Elisa etc. Results: The results demonstrate that B3 at 20 and 40 mg/kg prolonged the onset time of generalized seizures. B3 considerably increased the expression of protective glutathione S-transferase and glutathione reductase and reduced lipid peroxidation and inducible nitric oxide synthase (P < 0.001) in the cortex. B3 significantly suppressed (P < 0.01) the over expression of the inflammatory mediator tumor necrosis factor–α, whose up-regulation is reported in acute epileptic shocks. Conclusion: Hence, it is concluded from the aforementioned results that B3 provides neuroprotective effects PTZ-induced acute epileptic model. FLZ pretreatment resulted in inhibition of the anticonvulsant effect of B3. B3 possesses anticonvulsant effect which may be mediated through GABA_A mediated antiepileptic pathway.

Neurodegenerative complications, like Alzheimer's disease (AD) exert adverse effects i.e. psychological and physiological in the central nervous system. The synthetic drugs used for these complications have negative effects on body health and therefore natural remedies are a good and targeted approach to counter such complications. Alternatively, fruits and a variety of biochemicals which are an important source of diet, can be used for remedial purposes. Due to the antioxidant properties of polyphenolic compounds, several companies utilize this property to advertise polyphenol-rich beverages. Pomegranate (Punica granatum L.), is one such fruit that is well known for its medical usage due to its antioxidant properties. In the cuurent study a literature search survey was performed on traditional uses, phytochemicals on pomegranate and their medical applications especaily in neurodegenerative deasese using electronic data bases like PubMed, Google Scholar, Scopus, Science Direct Wikipedia and Springer Nature. Based on previous preclinical and clinical studies, pomegranate juice, extracts, and its bioactive constituents have shown many mitigating properties, including suppression of inflammatory cell signaling, reduction in expression of genes associated with oxidative stress as well as pro-inflammatory cytokines in neurons, decreased production of inflammatory and oxidative stress biomarkers and increased expression of endothelial nitric oxide synthase. It also decreases the expression of soluble amyloid protein procurer β (sAPPβ), β-secretase and carboxyl terminal fragment β (CTFβ). Similarly, during an in-vivo study on APP/PS1 mice, pomegranate supplementation has been shown to impart cognitive aid by the protection of neurons and triggering neurogenesis through anti-inflammatory signaling pathway. In conclusion, pomegranate supplementation can be a promising source of protection against Alzheimer's disease.