<p>Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis</p>

Abstract

Background: Honokiol has been reported to possess anti-inflammatory and neuroprotective activities. However, the poor aqueous solubility of honokiol limits its clinical application for systemic administration. Purpose: This study aims to develop a novel formulation of nanosome-encapsulated honokiol (NHNK) for intravenous therapy against mouse experimental autoimmune encephalomyelitis (EAE) that mimics human multiple sclerosis. Methods: Nanosomes and NHNK were prepared by using an ultra-high pressure homogenization (UHPH) method. Mice were treated with NHNK or empty nanosomes during the peak phase of EAE symptoms. Symptoms of EAE were monitored and samples of the spinal cord were obtained for histopathological examinations. Results: The stock of NHNK containing honokiol in the nanosome formulation, which showed the structure of single phospholipid bilayer membranes, was well formulated with the particle size of 48.0 ± 0.1 nm and the encapsulation efficiency 58.1 ± 4.2%. Intravenous administration of NHNK ameliorated the severity of EAE accompanied by a significant reduction of demyelination and inflammation in the spinal cord. Furthermore, NHNK decreased the number of IL-6 + , Iba-1 + TNF + , Iba-1 + IL-12 p40 + , and CD3 + IFN-γ + cells infiltrating the spinal cord. Conclusion: The UHPH method simplified the preparation of NHNK with uniformly distributed nanosize and high encapsulation efficiency. Intravenous administration of NHNK ameliorated the severity of EAE by suppressing the infiltration of activated microglia and Th1 cells into the spinal cord. Collectively, these results suggest that the formulation of NHNK is a prospective therapeutic approach for inflammatory CNS diseases, such as multiple sclerosis.

Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol

“…Animals were given water and standard mice lab chow (Oriental yeast, Tokyo, JP) ad libitum. Preparation of nanosized liposome-encapsulated honokiol (nHNK) were described earlier, qualitative and quantitative characterization of nNNK was carried out at the department of chemistry at National Taiwan University (NTU Mass Spectrometry Platform) and described earlier [ 17 , 22 ]. Animals were randomly allocated into 4 experimental groups (n = 10–12 for each group) and cisplatin-induced testicular injury mouse model was established as summarized in Figure S2A and described as follow.…”

“…nHNK (blue closed circle, 100 μL volume) as indicated in the G2. Determination of nanosome honokiol tissue distribution in reproductive organs was carried out as described earlier [ 17 , 22 ].…”

“…Although HNK might be effective on reducing cisplatin-induced OS, its lipophilic property restrains its bioavailability to tissue. To overcome this natural chemical solubility barrier of HNK, we encapsulated HNK into nanosized liposome (nanosome honokiol, nHNK) as described earlier to increase its bio-distribution and bio-availability [ 17 , 22 ]. This liposome-encapsulation approach has been shown to exhibit synergic and beneficial effects on anti-cancer ability when used in combination with cisplatin [ 23 , 24 , 25 ], which allows for the slow release of HNK into the body that prolongs its anti-oxidation effects in vivo.…”

Progress in the Application of Drugs for the Treatment of Multiple Sclerosis

“…An et al ( An et al, 2020 ) showed that this compound could reduce demyelination, inflammation, microglial activation, and the expression of IL-2, IFN-γ, IL-1 β, IL-6, and TNF-α in EAE mice. It is expected to become a new drug for the treatment of MS. Honokiol, a nano-liposome developed by Hsiao et al ( Hsiao et al, 2020 ), is a drug that could reduce the number of IL-6 + , Iba-1 + TNF + , Iba-1 + IL-12 p40 + , and CD3 + IFN-γ+cells infiltrating the spinal cord and clearing the inhibitory effect of nanosome-encapsulated honokiol on the infiltration of activated microglia and Th1 cells into the spinal cord. Studies on microglia have shown that resveratrol-treated microglia can significantly inhibit the production of nitric oxide and TNF-α ( Pallares et al, 2012 ).…”

Effectiveness in the Block by Honokiol, a Dimerized Allylphenol from Magnolia Officinalis, of Hyperpolarization-Activated Cation Current and Delayed-Rectifier K+ Current

“…M. officinalis was demonstrated to reduce the long-term effects of status epilepticus induced by kainic acid [13]. Nanosomes used for the encapsulation of HNK were also recently reported to improve the feasibility of HNK for its intravenous administration tailored against autoimmune encelphalomyelitis [14,15]. Additionally, at the cellular level, HNK or magnolol has been shown to induce Ca 2+ mobilization in cortical neurons and in neuroblastoma cells [16], as well as to suppress glutamate-evoked Ca 2+ influx in rat cerebellar granule cells [17].…”