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Protective effect of andrographolide against STZ induced Alzheimer’s disease in experimental rats: possible neuromodulation and Aβ(1–42) analysis

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Abstract

STZ is a glucosamine-nitrosourea compound, causes dysfunctioning of insulin receptors in the brain and disrupts glucose metabolism, produces cognitive decline and AD-like symptoms. ICV injection of STZ causes accumulation of Aβ and cognitive dysfunctions. Andrographolide (ANDRO) is a major bioactive constituent of Andrographis paniculata, has various biological activities such as antioxidant, anti-inflammatory, anti-cholinesterase, and neuroprotective properties. The study aimed to evaluate the neuroprotective effect of ANDRO against ICV-STZ induced AD-like symptoms in rats. To conduct the study, the Wistar rat received two injections of STZ (3 mg/kg) through the ICV route. Rats were treated with three different doses of ANDRO (15, 30, and 60 mg/kg, p.o.) and donepezil (5 mg/kg, p.o.) for 14 days. The behavioral impairments were analyzed on weekly basis. Subsequently, rats were sacrificed for the assessment of biochemical (MDA, Nitrite, GSH, SOD, Catalase and AChE), neuroinflammatory markers (IL-1β, IL-16, and TNF-α), neurotransmitters (glutamate and GABA), level of Aβ1–42 and p tau in the hippocampus on day 21st. Our result indicated that ANDRO treatment provided a protective effect against STZ induced behavioral deficits and changes in the biochemical, neuroinflammatory mediators, and neurotransmitters of the hippocampus. Further, ANDRO also reduced the level of Aβ1–42 and p tau in the rat hippocampus. These findings suggested that the antioxidant, anti-inflammatory, anti-cholinesterase potential of ANDRO contributed to its neuroprotective effect as well as promising therapeutic candidate for the treatment of cognitive impairment and AD-like symptoms.

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Abbreviations

AD:

Alzheimer’s disease

STZ:

Streptozotocin

ANDRO:

Andrographolide

ICV:

Intracerebroventricular

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Acknowledgements

The authors are highly thankful to Mr. Parveen Garg, Chairman, ISFCP for providing an excellent research platform.

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Authors and Affiliations

  1. Department of Pharmacology, ISF College of Pharmacy (Affiliated to IKG-Punjab Technical University, Jalandhar, 144603, Punjab, India), Moga, 142001, Punjab, India

    Royal Patel & Karamjeet Kaur

  2. Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India

    Shamsher Singh

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  1. Royal Patel
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Correspondence to Shamsher Singh.

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Patel, R., Kaur, K. & Singh, S. Protective effect of andrographolide against STZ induced Alzheimer’s disease in experimental rats: possible neuromodulation and Aβ(1–42) analysis. Inflammopharmacol 29, 1157–1168 (2021). https://doi.org/10.1007/s10787-021-00843-6

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