Publications by authors named "Khurram Aamir"

6 Publications

  • Page 1 of 1

Lauric acid ameliorates lipopolysaccharide (LPS)-induced liver inflammation by mediating TLR4/MyD88 pathway in Sprague Dawley (SD) rats.

Life Sci 2021 Jan 11;265:118750. Epub 2020 Nov 11.

School of Biosciences, Faculty of Science, The University of Melbourne, Victoria 3010, Australia; Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia; Department of Pharmacology and Therapeutics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address:

Background: Lipopolysaccharide (LPS) is an endotoxin that leads to inflammation in many organs, including liver. It binds to pattern recognition receptors, that generally recognise pathogen expressed molecules to transduce signals that result in a multifaceted network of intracellular responses ending up in inflammation. Aim In this study, we used lauric acid (LA), a constituent abundantly found in coconut oil to determine its anti-inflammatory role in LPS-induced liver inflammation in Sprague Dawley (SD) rats.

Method: Male SD rats were divided into five groups (n = 8), injected with LPS and thereafter treated with LA (50 and 100 mg/kg) or vehicle orally for 14 days. After fourteen days of LA treatment, all the groups were humanely killed to investigate biochemical parameters followed by pro-inflammatory cytokine markers; tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β. Moreover, liver tissues were harvested for histopathological studies and evaluation of targeted protein expression with western blot and localisation through immunohistochemistry (IHC).

Results: The study results showed that treatment of LA 50 and 100 mg/kg for 14 days were able to reduce the elevated level of pro-inflammatory cytokines, liver inflammation, and downregulated the expression of TLR4/NF-κB mediating proteins in liver tissues.

Conclusion: These findings suggest that treatment of LA has a protective role against LPS-induced liver inflammation in rats, thus, warrants further in-depth investigation through mechanistic approaches in different study models.
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http://dx.doi.org/10.1016/j.lfs.2020.118750DOI Listing
January 2021

Food additive "lauric acid" possess non-toxic profile on biochemical, haematological and histopathological studies in female Sprague Dawley (SD) rats.

PeerJ 2020 31;8:e8805. Epub 2020 Mar 31.

Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Selangor, Malaysia.

Background: Lauric acid (LA), a common constituent of coconut oil, is used as food additives and supplements in various formulations. Despite various potential pharmacological properties, no scientific evidence on its dose-related toxicity and safety is available till date.

Objective: The current study was conducted to evaluate acute oral toxicity of LA on normal rats.

Methods: The study was conducted in accordance with the Organization for Economic Co-operation and Development guidelines (OECD 423) with slight modifications. LA was administered orally to female Sprague Dawley (SD) rats ( = 6/group) at a single dose of 300 and 2,000 mg/kg body weight, respectively, while normal control received vehicle only. Animals from all the three groups were monitored for any behavioural and toxicological changes and mortality for two weeks. Food and fluid consumption, body weight was monitored on daily basis. At the end (on day 15th) of the experimental period, blood was collected for haematological and biochemical analysis. Further, all the animals were euthanized, and internal organs were harvested for histopathological investigation using four different stainings; haematoxylin and eosin, Masson trichrome, Periodic Acid Schiff and Picro Sirius Red for gross pathology through microscopical observation.

Results: The study results showed no LA treatment-related mortality and morbidity at two different dosages. Daily food and water consumption, body weight, relative organ weight, haematological, and biochemical analysis were observed to be normal with no severe alterations to the internal tissues.

Conclusion: The current finding suggests that single oral administration of LA, even up to 2,000 mg/kg body weight, did not exhibit any signs of toxicity in SD rats; thus, it was safe to be used on disease models in animals.
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http://dx.doi.org/10.7717/peerj.8805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120040PMC
March 2020

Impact of HMGB1, RAGE, and TLR4 in Alzheimer's Disease (AD): From Risk Factors to Therapeutic Targeting.

Cells 2020 02 7;9(2). Epub 2020 Feb 7.

Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 46150, Malaysia.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder and a leading cause of dementia, with accumulation of amyloid-beta (Aβ) and neurofibrillary tangles (NFTs) as defining pathological features. AD presents a serious global health concern with no cure to date, reflecting the complexity of its pathogenesis. Recent evidence indicates that neuroinflammation serves as the link between amyloid deposition, Tau pathology, and neurodegeneration. The high mobility group box 1 (HMGB1) protein, an initiator and activator of neuroinflammatory responses, has been involved in the pathogenesis of neurodegenerative diseases, including AD. HMGB1 is a typical damage-associated molecular pattern (DAMP) protein that exerts its biological activity mainly through binding to the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). RAGE and TLR4 are key components of the innate immune system that both bind to HMGB1. Targeting of HMGB1, RAGE, and TLR4 in experimental AD models has demonstrated beneficial effects in halting AD progression by suppressing neuroinflammation, reducing Aβ load and production, improving spatial learning, and inhibiting microglial stimulation. Herein, we discuss the contribution of HMGB1 and its receptor signaling in neuroinflammation and AD pathogenesis, providing evidence of its beneficial effects upon therapeutic targeting.
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http://dx.doi.org/10.3390/cells9020383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072620PMC
February 2020

Wnt signaling mediates TLR pathway and promote unrestrained adipogenesis and metaflammation: Therapeutic targets for obesity and type 2 diabetes.

Pharmacol Res 2020 02 14;152:104602. Epub 2019 Dec 14.

Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia; Department of Pharmacology and Therapeutics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, 3010, Australia; Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), Bukit Gambir, Gelugor, Pulau Pinang, Malaysia. Electronic address:

Diabesity is the combination of type 2 diabetes and obesity characterized by chronic low-grade inflammation. The Wnt signaling act as an evolutionary pathway playing crucial role in regulating cellular homeostasis and energy balance from hypothalamus to metabolic organs. Aberrant activity of certain appendages in the canonical and non-canonical Wnt system deregulates metabolism and leads to adipose tissue expansion, this key event initiates metabolic stress causing metaflammation and obesity. Metaflammation induced obesity initiates abnormal development of adipocytes mediating through the non-canonical Wnt signaling inhibition of canonical Wnt pathway to fan the flames of adipogenesis. Moreover, activation of toll like receptor (TLR)-4 signaling in metabolic stress invites immune cells to release pro-inflammatory cytokines for recruitment of macrophages in adipose tissues, further causes polarization of macrophages into M1(classically activated) and M2 (alternatively activated) subtypes. These events end with chronic low-grade inflammation which interferes with insulin signaling in metabolic tissues to develop type 2 diabetes. However, there is a dearth in understanding the exact mechanism of Wnt-TLR axis during diabesity. This review dissects the molecular facets of Wnt and TLRs that modulates cellular components during diabesity and provides current progress, challenges and alternative therapeutic strategies at preclinical and clinical level.
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http://dx.doi.org/10.1016/j.phrs.2019.104602DOI Listing
February 2020

Oral toxicity of arjunolic acid on hematological, biochemical and histopathological investigations in female Sprague Dawley rats.

PeerJ 2019 22;7:e8045. Epub 2019 Nov 22.

Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.

Background: Arjunolic acid (AA) is a potent phytochemical with wider pharmacological activities. Despite potential medicinal properties on various in vitro and in vivo studies, there is still a dearth of scientific data related to its safety profile and toxicological parameters. The current study aimed to investigate acute toxicity of AA in normal female Sprague Dawley rats.

Methods: In this study, AA was administered orally at an individual dose of 300 and 2000 mg/kg body weight to group 1 and 2 respectively, while group 3 served as normal control. All the animals were observed for 2 weeks to determine any behavioral and physical changes. On day 15, blood was collected for hematological and biochemical investigation, later animals from all the three groups were euthanized to harvest and store essential organs for histopathological analysis. Four different staining techniques; hematoxylin and eosin, Masson trichrome, Periodic acid Schiff and Oil O Red were used to investigate any alterations in different tissues through microscopical observation.

Results: The results of the study showed no morbidity and mortality at two different dosage of AA treatment. Daily food & water intake, body weight, relative organ weight, hematological and biochemical parameters were detected to be normal with no severe alteration seen through microscopical investigation in the structure of harvested tissues. Our findings support the safety profile of AA, which was well tolerated at higher dose. Thus, an in-detail study on the subacute disease model is warranted.
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http://dx.doi.org/10.7717/peerj.8045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876537PMC
November 2019

Evaluation of developmental toxicity of guaifenesin using pregnant female rats.

Indian J Pharmacol 2016 May-Jun;48(3):264-9

Pharmacology Section, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan.

Objectives: Guaifenesin possesses expectorant, muscle relaxant, and anticonvulsive properties. To the best of our knowledge, the promising data regarding the developmental toxicity of guaifenesin are scarce. The current study investigates the developmental toxic effects of guaifenesin in detail using female rats.

Materials And Methods: Twenty-five dams were divided into five groups. Group 1 served as a control, while Group-2, -3, -4, and -5 were administered with 250, 350, 500, and 600 (mg/kg b.w.) doses of guaifenesin, respectively, starting from gestation day 6 to day 17. Half of the total recovered fetuses was subjected to morphologic and morphometric analysis, while other half was subjected to skeletal examination.

Results: A significant reduction in maternal weight, and food/water intake, was observed, however, no mortality and morbidity were observed. About 14 dead fetuses were found in Group-3 and -4 each, while 26 in Group 5. Morphological analysis revealed 21.2%, 45.4%, 67.2%, and 86.9% of total fetuses having hemorrhagic spots in Group-2, -3, -4, and -5, respectively. Dropping wrist/ankle and kinky tail were found in Group-4 and -5 only. Morphometric analysis showed a significant decline in fetal weight, full body length, skull length, forelimb length, hindlimb length, and tail length in all guaifenesin treated groups. Skeletal examination displayed that only Group 5 fetuses had increased intercostal space between 7(th) and 8(th) rib. We also observed improper development of carpals, metacarpals, tarsals, and metatarsals of the Group 5 fetuses.

Conclusion: Guaifenesin showed a significant developmental toxicity at selected test doses; therefore, a careful use is suggested during pregnancy.
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http://dx.doi.org/10.4103/0253-7613.182891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899998PMC
May 2017
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