Nootropic effect of Indian Royal Jelly against okadaic acid induced rat model of Alzheimer's disease: Inhibition of neuroinflammation and acetylcholineesterase

Rahul Dubey; L Sathiyanarayanan; Sandeep Sankaran; S Arulmozhi

doi:10.1016/j.jtcme.2023.11.005

Nootropic effect of Indian Royal Jelly against okadaic acid induced rat model of Alzheimer's disease: Inhibition of neuroinflammation and acetylcholineesterase

J Tradit Complement Med. 2023 Nov 15;14(3):300-311. doi: 10.1016/j.jtcme.2023.11.005. eCollection 2024 May.

Authors

Rahul Dubey^{1

2}, L Sathiyanarayanan¹, Sandeep Sankaran³, S Arulmozhi⁴

Affiliations

¹ Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India.
² Department of Pharmacy, Government Polytechnic, Ratnagiri, Maharashtra, India.
³ Department of Quality Assurance Techniques, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India.
⁴ Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India.

Abstract

Background: Royal jelly is an anti-inflammatory, antioxidant, and neuroprotective bee product. There are several sources for royal jelly and one of them is Indian Royal Jelly (IRJ). However, the neuroprotective actions of IRJ and the underlying molecular mechanisms involved are not well known.

Objective: To evaluate the neuroprotective effect of IRJ in the okadaic acid (OKA)-induced Alzheimer's disease (AD) model in rats.

Methods: In male Wistar rats, OKA was intracerebroventricularly (ICV) administered, and from day 7, they were treated orally with IRJ or memantine for 21 days. Spatial and recognition learning and memory were evaluated from days 27-34; employing the Morris water maze (MWM) and the novel object recognition tests (NORT), respectively. In vitro biochemical measurements were taken of the cholinergic system and oxidative stress markers. In silico docking was used to find the role of tau protein kinase and phosphatase in the pharmacological action.

Results: In OKA-induced rats, IRJ decreased the escape latency and path length in MWM and increased the exploration time for novel objects and the discrimination index in NORT. ICV-OKA rats had higher free radicals and cytokines that caused inflammation and their level of free radical scavengers was back to normal with IRJ treatment. IRJ increased the level of acetylcholine and inhibited acetylcholinesterase. Moreover, the in silico docking study revealed the strong binding affinity of 10-hydroxy-2-decenoic acid (10-HDA), a bioactive constituent of IR, to the tau protein kinases and phosphatases.

Conclusion: IRJ may serve as a nootropic agent in the treatment of dementia, and owing to its capacity to prevent oxidative stress and neuroinflammation, and increase cholinergic tone; it has the potential to be explored as a novel strategy for the treatment of dementia and AD. More studies may be needed to develop 10-HDA as a novel drug entity for AD.

Keywords: 10-Hydroxy-2-decenoic acid; Alzheimer's disease; Indian royal jelly; Neuroinflammation; Okadaic acid; Tau protein kinases.