Neuropharmacological potential of honokiol and its derivatives from Chinese herb Magnolia species: understandings from therapeutic viewpoint

Abstract

Honokiol is a neolignan biphenol found in aerial parts of the Magnolia plant species. The Magnolia plant species traditionally belong to China and have been used for centuries to treat many pathological conditions. Honokiol mitigates the severity of several pathological conditions and has the potential to work as an anti-inflammatory, anti-angiogenic, anticancer, antioxidant, and neurotherapeutic agent. It has a long history of being employed in the healthcare practices of Southeast Asia, but in recent years, a greater scope of research has been conducted on it. Plenty of experimental evidence suggests it could be beneficial as a neuroprotective bioactive molecule. Honokiol has several pharmacological effects, leading to its exploration as a potential therapy for neurological diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), cerebral ischemia, anxiety, depression, spinal cord injury, and so on. So, based on the previous experimentation reports, our goal is to discuss the neuroprotective properties of honokiol. Besides, honokiol derivatives have been highlighted recently as possible therapeutic options for NDs. So, this review focuses on honokiol's neurotherapeutic actions and toxicological profile to determine their safety and potential use in neurotherapeutics.

Keywords: Alzheimer’s disease; Anxiety; Chinese Herb; Depression; Honokiol; Ischemia; Magnolia species; Neurological diseases; Parkinson’s disease.

Fig. 1

Four novel derivatives of honokiol by Zhang et al. [29]

Fig. 2

a 31 neolignan honokiol analogues of 4-o-methylhonokiol by Talarek et al. [30]. b 31 neolignan honokiol analogues of 4-o-methylhonokiol by Talarek et al. [30]

Fig. 2

a 31 neolignan honokiol analogues of 4-o-methylhonokiol by Talarek et al. [30]. b 31 neolignan honokiol analogues of 4-o-methylhonokiol by Talarek et al. [30]

Fig. 3

Structural-activity relationship of Honokiol

Fig. 4

Mechanistic illustration of the therapeutic applications of honokiol in Alzheimer’s disease, and Parkinson’s disease

Fig. 5

Mechanistic illustration of the therapeutic applications of honokiol in neuroinflammation. Honokiol has the potential to bind and activate peroxisome proliferator-activated receptor gamma (PPAR-γ), subsequently leading to the induction of liver X receptor (LXR), scavenger receptor A (SRA), and cluster of differentiation 36 (CD36) expression. These molecular mechanisms are responsible for facilitating the efficient lysosomal clearance of amyloid-beta (Aβ) in microglial cells. Simultaneously, Honokiol demonstrated inhibitory effects on NF-κB activity and mRNA expression of inflammatory cytokines. Furthermore, it has the capability to stimulate the Nrf2-ARE pathway and mitigate the generation of reactive oxygen species (ROS)