Arooj Mohsin Alvi’s research while affiliated with International Islamic University, Islamabad and other places

Periodic epileptic episodes are the hallmark of epilepsy, a prevalent neurological disorder. Research suggests a significant correlation between neuroinflammation and oxidative stress in a variety of neurological diseases, such as epilepsy. A substantial amount of evidence supports the role of N-methyl-d-aspartate receptors (NMDARs) in the progression of epilepsy. Although several lines of research have disclosed numerous biochemical effects of early seizures, its connection with disturbed NMDAR/NR2B subunit expression remains unclear. 2-Mercaptobenzothiazole (MBT) is a vital scaffold with several biological activities, and its various substitutes show promising anti-inflammatory potential. The current study aimed to investigate the newly synthesized 1,3-(benzothiazole-2-sulfanyl)-1-(morpholine-4-yl)ethan-1-one (1 M), a substituted MBT, for its neuroprotective potential in a mice model of pentylenetetrazole-induced epilepsy (PTZ), by modulating NMDA/NR2B pathway. The compound was tested for docking and simulation analysis, demonstrating a solid and stable bond with the NR2B subunit of NMDA. To ascertain the effects of 1 M, as well as to further illustrate its mechanism of neuroprotection via NMDA/NR2B in PTZ-induced kindling model, mice of either sex were given two doses of test compound, 1 M (10 mg/kg and 20 mg/kg). The behavioral assessments were evaluated using open-field, Y-maze, and elevated-plus maze tests, which indicated improved behavioral alterations caused by PTZ after 1 M treatment. The antioxidant profiling was done by estimating glutathione-S-transferase (GST), catalase (CAT), reduced glutathione (GSH), and LPO (lipid peroxidation) in hippocampal tissues, where the test compound 1 M significantly restored the depleted antioxidants, showcasing its antioxidant potential. Moreover, the cellular morphological damages induced by PTZ were detected by H&E staining, which was rescued after 1 M administration. Furthermore, the activation of the inflammatory pathway was confirmed by quantitative analysis of inflammatory mediators tumor necrotic factor (TNF-α), nuclear factor kappa B (NF-κB), and cylooxegenase2 (COX-2) by enzyme-linked immunosorbent assay (ELISA), where 1 M administration significantly ameliorated their expression. Furthermore, to demonstrate the involvement of the NR2B pathway, NR2B-antagonist ifenprodil was employed, and results were further confirmed through RT-PCR analysis. Our results, when considered collectively, indicate that 1 M may act by inhibiting the NR2B subunit of the NMDA receptor, subsequently mitigating downstream oxidative stress and inflammatory mediators through various pathways.

Background: Pain and inflammation are complex biological mechanisms often associated with sensory, emotional, and cognitive discomfort resulting from tissue damage. Traditional medicine frequently employs medicinal plants for managing these conditions due to the adverse effects associated with conventional drugs. Ducrosia anethifolia, a medicinal plant native to Balochistan, Pakistan, is traditionally used for its analgesic and anti-inflammatory properties.Objective: This study aimed to evaluate the acute toxicity, analgesic, and anti-inflammatory effects of the methanolic extract of D. anethifolia seeds in mice.Methods: The seeds of D. anethifolia were collected, authenticated, and extracted using methanol. Acute toxicity was assessed by administering oral doses of 100, 500, 1000, 2000, and 3000 mg/kg to groups of mice and observing mortality rates over 24 hours. The analgesic effects were evaluated using the acetic acid-induced writhing test and the formalin-induced pain test. For the writhing test, mice were divided into groups and treated with 0.5 ml of normal saline (control), 250 mg/kg or 500 mg/kg of the extract, or 50 mg/kg of diclofenac sodium. Writhing responses were recorded for 30 minutes post-injection of acetic acid. In the formalin test, mice received treatments as in the writhing test, and licking and biting behaviors were recorded during acute (0-5 minutes) and chronic (15-30 minutes) phases. The anti-inflammatory effect was assessed using the carrageenan-induced paw edema method, where paw volumes were measured at 0, 1, 2, 3, 4, and 5 hours post-carrageenan injection.Results: In the acute toxicity test, the LD50 of the extract was determined to be 2000 mg/kg. In the acetic acid-induced writhing test, the 250 mg/kg and 500 mg/kg doses of the extract showed significant analgesic effects with percentage inhibitions of 41.16% (p<0.05) and 62.07% (p<0.01), respectively. In the formalin test, the 250 mg/kg and 500 mg/kg doses significantly reduced licking and biting behaviors in the chronic phase to 39.66 ± 0.60 (p<0.05) and 30.16 ± 1.24 (p<0.05) respectively, compared to the control. In the anti-inflammatory test, the 500 mg/kg dose significantly reduced paw edema with a percentage inhibition of 48.40% (p<0.05).Conclusion: The methanolic seed extract of D. anethifolia demonstrated significant analgesic and anti-inflammatory effects, supporting its traditional use for pain relief and inflammation management. These findings suggest that D. anethifolia could be a potential source for developing new analgesic and anti-inflammatory agents with fewer side effects than conventional drugs

Natural compounds derived from plants have been extensively employed in conventional treatments and are a key component of medicinal products. Perovskia abrotanoides, a plant native to Pakistan, is historically used to cure several ailments, while little is known regarding its pharmacological properties. This study aimed to investigate the pharmacological characteristics of the crude methanolic extract of Perovskia abrotanoides. Phytochemical analysis indicated many phytoconstituents capable of profound antioxidant activity, which may play an important role as anti-asthmatic and hepato-protectant. Its anti-asthmatic and hepatoprotective properties were evaluated using models of histamine-induced asthma and liver damage brought on by carbon tetrachloride, respectively. Research was also conducted on the extract's phytotoxic, antibacterial, and anticancer effects. The results demonstrated strong hepatoprotective and anti-asthmatic effects; while no harm other than a drop in platelet count was noted. Also, the extract showed significant antimicrobial activities against Staphylococcus aureus. However, no apoptotic or anticancer potential was found.

Neuropathic pain has been characterized as chronic pain resulting from pathological damage to the sensorimotor system. Because of its complex nature, it remains refractory to most of the therapeutic interventions, and surgical intervention and physiotherapy alongside steroidal treatments remain the only treatment protocols with limited success, hence solidifying the need to find efficacious therapeutic alternatives. Emodin was used as a post-treatment for its potential to be neuroprotective in the treatment of chronic constriction injury-induced NP. The first day following surgery, Emodin treatment began, and it lasted until the 21st day. On days 3, 7, 14 and 21, all behavioral investigations were conducted. The sciatic nerve and spinal cord were extracted for further molecular examination. Emodin elevated response latency, was able to delay the onset of mechanical hyperalgesia in rats on days 7, 14, and 21 and reduced the CCI-induced paw deformation. Emodin treatment significantly reduced lipid peroxidation and NO levels while restoring the GST, GSH and catalase. It significantly improved the disorientation of the sciatic nerve and spinal cord confirmed by H & E staining and reduced inflammatory markers as observed by the quantification of COX-2, TNF-α, p-NFκb and up-regulated PPAR-γ levels by ELISA and PCR. According to the findings, Emodin has antinociceptive and anti-hyperalgesic properties, which reduced pain perception and inflammation. We also suggested the involvement of PPAR-γ pathway in the therapeutic potential of emodin in chronic nerve injury.

Zulfiqar Z, Shah FA, Shafique S, et al. J Inflamm Res. 2020;13:1185–1205. The Editor and Publisher of Journal of Inflammation Research wish to retract the published article. Concerns were raised regarding the duplication of several images from Figures 9–11. Specifically, Figure 9E, HO-1, Striatum, Vehicle + Sham appears to have been duplicated with the same image for Figure 10B, p-JNK, Striatum, Vehicle + Sham. Figure 9E, HO-1, Striatum, Estazolam + MCAO appears to have been duplicated with the same image for Figure 11A, p-NFκB, Striatum, Vehicle + MCAO. Figure 9E, HO-1, Striatum, Vehicle + Sham appears to have been duplicated with the same image for Figure 11A, p-NFκB, Striatum, Vehicle + Sham. Figure 9E, HO-1, Striatum, Vehicle + Sham appears to have been duplicated with the same image for Figure 11B, TNF-α, Striatum, Vehicle + Sham. Figure 10B, p-JNK, Cortex, Vehicle + Sham appears to have been duplicated with the same image for Figure 11B, TNF-α, Cortex, Vehicle + Sham. Figure 10B, p-JNK, Cortex, Vehicle + MCAO appears to have been duplicated with the same image for Figure 11B, TNF-α, Cortex, Vehicle + MCAO. Figure 10B, p-JNK, Striatum, Leucovorin + MCAO appears to have been duplicated with the same image for Figure 11B, TNF-α, Striatum, Vehicle + MCAO. Figure 11A, p-NFκB, Striatum, Vehicle + Sham appears to have been duplicated with the same image for Figure 11B, TNF-α, Striatum, Vehicle + Sham. Figure 11A, p-NFκB, Cortex, Estazolam + MCAO appears to have been duplicated with the same image for Figure 11B, TNF-α, Cortex, Estazolam + MCAO. The authors responded to our queries but were unable to provide a satisfactory explanation for the duplicated images. The Editor requested for the article to be retracted and the authors were notified of this. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Alvi AM, Shah FA, Muhammad AJ, Feng J, Li S. J Inflamm Res. 2021;14:7393–7409. The Editor and Publisher of Journal of Inflammation Research wish to retract the published article. Concerns were raised regarding the alleged duplication of images within the article with those from another article published in Oxidative Medicine and Cellular Longevity, Carveol Attenuates Seizure Severity and Neuroinflammation in Pentylenetetrazole-Kindled Epileptic Rats by Regulating the Nrf2 Signaling Pathway, Alvi et al, 2021 (https://doi.org/10.1155/2021/9966663). Both articles have authors in common. Specifically, Figure 6, panel Cortex, Saline appears to have been duplicated with Figure 5, panel Cortex, Diaz from Alvi et al, 2021. Figure 6, panel Cortex, Diaz+PTZ appears to have been duplicated with Figure 5, panel Cortex, Car-20 from Alvi et al, 2021. Figure 7C, panel Cortex, Diaz+PTZ appears to have been duplicated with Figure 7 (TNF-alpha), panel Cortex, CA1, ATRA+PTZ from Alvi et al, 2021. Figure 7C, panel Cortex, PTZ appears to have been duplicated with Figure 7 (p-NF-κB), panel Cortex, Saline from Alvi et al, 2021. Figure 7C, panel Hippocampus, Diaz+PTZ appears to have been duplicated with Figure 7 (p-NF-κB), panel Cortex, CA1, PTZ from Alvi et al, 2021. Figure 7D, panel Cortex, A3-30+PTZ appears to have been duplicated with Figure 6, panel Cortex, ATRA+PTZ+Car from Alvi et al, 2021. Figure 8D, Cortex, PTZ appears to have been duplicated with Figure 8, panel Cortex, ATRA+PTZ+Car from Alvi et al, 2021. Figure 8D, Hippocampus, ATRA+PTZ+A3 appears to have been duplicated with Figure 8, Hippocampus, CA1, PTZ from Alvi et al, 2021. Figure 8D, Hippocampus, ATRA+PTZ appears to have been duplicated with Figure 8, Hippocampus, CA1, ATRA+PTZ from Alvi et al, 2021. Figure 8E, Cortex, ATRA+PTZ+A3 appears to have been duplicated with Figure 7 (p-NF-κB), Cortex, ATRA+PTZ from Alvi et al, 2021. The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged image duplication. The Editor requested for the article to be retracted and the authors agreed with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Background Mercury compounds are the world's third most hazardous substance. Mercury (II) chloride, also known as mercuric chloride (HgCl2), has been shown to have neurotoxic properties in a variety of forms. In numerous investigations, oxidative stress has been established as a key contributor to HgCl2-induced neurotoxicity. Carveol has been researched as an antioxidant and Nrf2-activator in several studies. This study was conducted to investigate if the carveol could protect mice against HgCl2-induced neuronal damage. Methods Mice were exposed to a dose of 0.4 mg/kg of HgCl2 and 20 mg/kg of carveol for 21 days. Animals were then subjected to behavioral evaluation through various methods such as open field test (OFT), elevated plus maze test (EPM), morris-water maze test (MWM), and Y-maze test. Results Results indicated hippocampal-related behavior anomalies which were improved significantly after carveol treatment. Oxidative stress was accompanied by excessive neuroinflammation, which was demonstrated by elevated levels of inflammatory markers such as TNF-α, p-NFkB, and COX-2, and were measured by Western blot, ELISA, and immunohistochemistry. These elevated levels of inflammatory markers were significantly mitigated upon treatment with carveol. To further investigate the participation of the JNK pathway, we used SP-600125 to inhibit JNK, which enhanced the neuroprotective effects of carveol. Moreover, molecular docking and modeling studies were used to validate these effects. Conclusion Our findings indicate that carveol can inhibit the p-JNK pathway, thereby inhibiting HgCl2-induced apoptosis and downregulating the expression of inflammatory mediators.

Major depressive disorder (MDD) is a progressive deteriorating mental state with a feeling of worthlessness and frequent mood swings. Several studies reported the favorable effects of natural drug substances on MMD associated oxidative stress and neuroinflammation. The present study is attempted to examine whether carveol could affect lipopolysaccharide- (LPS-) induced depression, and if so, how nuclear factor E2-related factor (Nrf2) contributed to the neuroprotective effects of carveol mechanistically. Two experimental cohorts were used using the SD rats: first to evaluate the promising dose of carveol (whether 20 mg/kg or 50 mg/kg) and secondly to determine the effect of carveol on Nrf2-mediated antidepression. Significant neuronal alterations were noticed in the cortex and hippocampus regions in the LPS-treated group, accompanied by elevated inflammatory cytokine levels such as tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), and c-Jun N-terminal kinase (p-JNK). Moreover, amassing of free radicals exacerbated lipid peroxidase (LPO) and oxidative stress with a limited antioxidant capacity. Carveol (20 mg/kg) significantly ameliorated these detrimental effects by promoting the antioxidant Nrf2 gene and protein, which critically regulate the downstream antioxidant and anti-inflammatory pathway. To further elaborate our hypothesis, we employed all-trans retinoic acid (ATRA), an Nrf2 inhibitor, and we found that ATRA exaggerated LPS-induced depressive-like effects associated with elevated neuroinflammatory markers. Our results demonstrated that carveol (20 mg/kg) could activate the endogenous antioxidant Nrf2, which regulates the downstream antioxidant signaling pathway, eventually leading to amelioration of LPS-induced neuroinflammation and neurodegeneration.