Honokiol and Magnolol Selectively Interact with GABA_A Receptor Subtypes in vitro

Abstract

Honokiol and magnolol have been identified as modulators of the GABA_A receptors in vitro. Our previous study suggested a possible selectivity of honokiol and magnolol on GABA_Areceptor subtypes. This possibility was examined in the current study by ³H-muscimol and ³H-flunitrazepam binding assays on various rat brain membrane preparations and human recombinant GABA_A receptor subunit combinations expressed by the Sf-9/baculovirus system. Generally, honokiol and magnolol have a similar enhancing effect on ³H-muscimol binding to various membrane preparations in nonsaturation binding assays. Honokiol and magnolol preferentially increased ³H-muscimol binding to hippocampus compared to cortex and cerebellum (with a maximum enhancement of 400% of control). As for subunit combinations, honokiol and magnolol have a more potent enhancing effect on α₂ subunit containing combinations (with a maximum enhancement of 400–450% of control). This action was independent of the γ subunit. In saturation binding assays, magnolol affected either the number of binding sites (ca. 4-fold on α₂ containing combinations) or the binding affinity (on α₁ containing combinations) of ³H-muscimol binding to various GABA_A receptor subunit combinations. In contrast, honokiol increased only binding sites on α₂β₃γ_2s and α₂β₃ combinations, but both the number of binding sites and the binding affinity on α₁β₂γ_2S and α₁β₂ combinations. These results indicate that honokiol and magnolol have some selectivity on different GABA_A receptor subtypes. The property of interacting with GABA_A receptors and their selectivity could be responsible for the reported in vivo effects of these two compounds.

Interactions of Magnolia and Ziziphus extracts with selected central nervous system receptors

“…The selected receptor/receptor subtypes for testing were adenosine A 1 , dopamine (transporter, D 1 , D 2S , D 3 , D 4.4 and D 5 ), serotonin (transporter, 5-HT 1A , 5-HT 1B , 5-HT 4e , 5-HT 6 and 5-HT 7 ) and the GABA benzodiazepine receptor. This work expands on previous receptor binding studies on extracts of Magnolia officinalis (Squires et al, 1999;Ai et al, 2001;Li and Bi, 2006) and Ziziphus spinosa (Liao et al, 1995). Rhamnaceae] (ZE).…”

Honokiol, a Natural Plant Product, Inhibits Inflammatory Signals and Alleviates Inflammatory Arthritis

“…NO and reactive oxygen species have both been shown to contribute to the chronic inflammation of arthritis (56) and the direct alteration in joint cartilage homeostasis (57). One possible common mechanism to explain the effect of HNK on these varied mediators of inflammation is its binding with peripheral ␥-aminobutyric acid GABA(A) receptors (58). Peripheral GABA(A) receptors are present on immune cells and have been shown to inhibit lymphocyte activation and lymphocyte-mediated inflammatory disease (59).…”

Neurorestorative Role of Hypericum Hookerianum Ethanolic Extract on Brain Total Antioxidant Status and Lipid Peroxidation in Haloperidol Induced Schizophrenia in Swiss Albino Mice

“…The effect can be related to reduction in specific antioxidant mechanisms 29 . Umadevi P, 2001 studied on Occumum sanctum 30 and Ali et al; 2000 studied on Rhazye stricta 31 ascertain that the herbal preparation that have anti-depressant potential also possess antioxidant effect. Sagara using rat primary cortical neurons and mouse hippocampal cell line HT-22 showed that Haloperidol caused a sequence of cellular alteration that lead to cell death and production of reactive oxygen species 32 .…”