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Fulltext Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats

Shaikh SA, Muthuraman A

Pharmaceuticals (Basel), 2023 Jun 01;16(6).
PMID: 37375775 DOI: 10.3390/ph16060828

Neurovascular dysfunction leads to the second most common type of dementia, i.e., vascular dementia (VaD). Toxic metals, such as aluminium, increase the risk of neurovascular dysfunction-associated VaD. Hence, we hypothesized that a natural antioxidant derived from palm oil, i.e., tocotrienol-rich fraction (TRF), can attenuate the aluminium chloride (AlCl3)-induced VaD in rats. Rats were induced with AlCl3 (150 mg/kg) intraperitoneally for seven days followed by TRF treatment for twenty-one days. The elevated plus maze test was performed for memory assessment. Serum nitrite and plasma myeloperoxidase (MPO) levels were measured as biomarkers for endothelial dysfunction and small vessel disease determination. Thiobarbituric acid reactive substance (TBARS) was determined as brain oxidative stress marker. Platelet-derived growth factor-C (PDGF-C) expression in the hippocampus was identified using immunohistochemistry for detecting the neovascularisation process. AlCl3 showed a significant decrease in memory and serum nitrite levels, while MPO and TBARS levels were increased; moreover, PDGF-C was not expressed in the hippocampus. However, TRF treatment significantly improved memory, increased serum nitrite, decreased MPO and TBARS, and expressed PDGF-C in hippocampus. Thus, the results imply that TRF reduces brain oxidative stress, improves endothelial function, facilitates hippocampus PDGF-C expression for neovascularisation process, protects neurons, and improves memory in neurovascular dysfunction-associated VaD rats.
Fulltext Palm Oil Derived Tocotrienol-Rich Fraction Attenuates Vascular Dementia in Type 2 Diabetic Rats

Shaikh SA, Varatharajan R, Muthuraman A

Int J Mol Sci, 2022 Nov 04;23(21).
PMID: 36362316 DOI: 10.3390/ijms232113531

Vascular dementia (VaD) is a serious global health issue and type 2 diabetes mellitus (T2DM) patients are at higher risk. Palm oil tocotrienol-rich fraction (TRF) exhibits neuroprotective properties; however, its effect on VaD is not reported. Hence, we evaluated TRF effectiveness in T2DM-induced VaD rats. Rats were given a single dose of streptozotocin (STZ) and nicotinamide (NA) to develop T2DM. Seven days later, diabetic rats were given TRF doses of 30, 60, and 120 mg/kg orally for 21 days. The Morris water maze (MWM) test was performed for memory assessment. Biochemical parameters such as blood glucose, plasma homocysteine (HCY) level, acetylcholinesterase (AChE) activity, reduced glutathione (GSH), superoxide dismutase (SOD) level, and histopathological changes in brain hippocampus and immunohistochemistry for platelet-derived growth factor-C (PDGF-C) expression were evaluated. VaD rats had significantly reduced memory, higher plasma HCY, increased AChE activity, and decreased GSH and SOD levels. However, treatment with TRF significantly attenuated the biochemical parameters and prevented memory loss. Moreover, histopathological changes were attenuated and there was increased PDGF-C expression in the hippocampus of VaD rats treated with TRF, indicating neuroprotective action. In conclusion, this research paves the way for future studies and benefits in understanding the potential effects of TRF in VaD rats.
Physiological and Pathophysiological Role of Cysteine Metabolism in Human Metabolic Syndrome

Muthuraman A, Ramesh M, Shaikh SA, Aswinprakash S, Jagadeesh D

Drug Metab Lett, 2021;14(3):177-192.
PMID: 34895129 DOI: 10.2174/1872312814666211210111820

Cysteine is one of the major intermediate products of cellular amino-acid metabolism. It is a semi-essential amino acid for protein synthesis. Besides, it is also employed in the regulation of major endogenous anti-oxidant molecule i.e., reduced glutathione (GSH). Further, it is a precursor of multiple sulfur-containing molecules like hydrogen sulfide, lanthionine, taurine, coenzyme A and biotin. It is also one of the key molecules for post-translational modifications of various cellular proteins. In physiological conditions, it is employed in the sulfhydration process and plays a key role in the physiology modification of the inflammatory process in various organs, including the neurological system. The catabolism of cysteine is regulated by cysteine dioxygenase enzyme activity. The dysregulated conditions of cysteine and cysteine-associated hydrogen sulfide metabolism are widely employed in the acceleration of the neurodegenerative process. Moreover, the upregulation of cysteine and hydrogen sulfide synthesis occurs via the reverse trans-sulfuration process. This process helps to manage the worsening of a pathological condition of a cellular system. Moreover, it is also employed in the accumulation of homocysteine contents. Further, both cysteine and homocysteine molecules are widely accepted as biomarkers for various types of diseases. Therefore, the targets involved in the regulation of cysteine have been considered as valid targets to treat various disorders like cardiac disease, ischemic stroke, diabetes, cancer, and renal dysfunction.
Chemosensitivity assessments of curdlan-doped smart nanocomposites containing erlotinib HCl

Bera H, Abbasi YF, Gajbhiye V, Ping LL, Salve R, Kumar P, et al.

Int J Biol Macromol, 2021 Jun 30;181:169-179.
PMID: 33775757 DOI: 10.1016/j.ijbiomac.2021.03.152

Curdlan (CN)-doped montmorillonite/poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide) [CN/MT/P(NIPA-co-MBA)] smart nanocomposites (NCs) were developed for efficient erlotinib HCl (ERL) delivery to lung cancer cells. The placebo NCs demonstrated excellent biodegradability, pH/thermo-responsive swelling profiles and declined molar mass (M¯c) between the crosslinks with increasing temperature. The XRD, FTIR, DSC, TGA, and SEM analyses revealed the architectural chemistry of these NC scaffolds. The NCs loaded with ERL (F-1-F-3) displayed acceptable diameter (734-1120 nm) and zeta potential (+1.16 to -11.17 mV), outstanding drug entrapping capability (DEE, 78-99%) and sustained biphasic ERL elution patterns (Q8h, 53-91%). The ERL release kinetics of the optimal matrices (F-3) obeyed Higuchi model and their transport occurred through anomalous diffusion. The mucin adsorption behaviour of these matrices followed Freudlich isotherms. As compared to pure ERL, the formulation (F-3) displayed an improved anti-proliferative potential and induced apoptosis more effectively on A549 cells. Thus, the CN-doped smart NCs could be utilized as promising drug-cargoes for lung cancer therapy.
Fulltext Influence of information source regarding COVID-19 knowledge among the undergraduate dental students during the early lockdown: a multi-national study

Mallineni SK, Nuvvula S, Ismail AF, Aldhuwayhi S, Shaikh SA, Deeban Y, et al.

Eur Rev Med Pharmacol Sci, 2022 Dec;26(23):9030-9039.
PMID: 36524522 DOI: 10.26355/eurrev_202212_30578

OBJECTIVE: To assess the influence of information sources on the knowledge regarding COVID-19 among undergraduate dental students in India, Saudi Arabia, Malaysia, and Turkey.
SUBJECTS AND METHODS: An online questionnaire in a Google form link was circulated among the target population via various online platforms. It consisted of 14 close-ended questions assessing these students' knowledge and source of COVID-19-related information. SPSS software version 21.0 (IBM Corp., Armonk, NY, USA) was used to compute descriptive statistics, Chi-square test, independent t-test, and ANOVA tests for comparing various variables, and a p-value<0.05 was considered statistically significant.
RESULTS: The study yielded 809 responses from dental undergraduate students from India, Saudi Arabia, Malaysia, and Turkey. Dental students from Turkey reported a higher mean knowledge score of 7.91±1.34 and 7.88±0.58 for Malaysian dental students. In contrast, the lower scores were achieved by Saudi Arabia (7.36±1.22) and India (7.37±1.21) dental students, and the findings were statistically significant (p<0.05). The study population used various sources to attain information regarding COVID-19. Most respondents (63.1%) utilized information regarding COVID-19 from multiple sources rather than single sources (36.9%).
CONCLUSIONS: Reliable and validated information sources resulted in higher knowledge scores. Turkey and Malaysia dental students reported a higher mean knowledge score and the lowest for Saudi Arabia and India dental students. There is increased popularity of social media platforms as information sources.
Fulltext In vitro antioxidant and in vivo antidepressant activity of green synthesized azomethine derivatives of cinnamaldehyde

Chigurupati S, Shaikh SA, Mohammad JI, Selvarajan KK, Nemala AR, Khaw CH, et al.

Indian J Pharmacol, 2017 10 17;49(3):229-235.
PMID: 29033482 DOI: 10.4103/ijp.IJP_293_16

OBJECTIVES: In this study, three (CS-1 to CS-3) azomethine derivatives of cinnamaldehyde were green synthesized, characterized, and their antioxidant and antidepressant activities were explored.
MATERIALS AND METHODS: The antioxidant effect of these compounds was initially performed in vitro using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay methods before subjecting them to in vivo experiments. Compounds showing potent antioxidant activity (CS-1 and CS-2) were investigated further for their antidepressant activity using the forced swim test (FST) and tail suspension test (TST). Ascorbic acid (AA) and fluoxetine (20 mg/kg, p.o) were used as reference drugs for comparison in the antioxidant and antidepressant experiments, respectively.
RESULTS: It was observed that CS-2 and CS-3 exhibited highest DPPH (half maximal inhibitory concentration [IC50]: 16.22 and 25.18 μg/mL) and ABTS (IC50: 17.2 and 28.86 μg/mL) radical scavenging activity, respectively, compared to AA (IC50: 15.73 and 16.79 μg/mL) and therefore, both CS-2 and CS-3 were tested for their antidepressant effect using FST and TST as experimental models. Pretreatment of CS-2 and CS-3 (20 mg/kg) for 10 days considerably decreased the immobility time in both the FST and TST models.
CONCLUSION: The antioxidant and antidepressant effect of CS-2 and CS-3 may be attributed to the presence of azomethine linkage in the molecule.