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From Formulation to Function: γ‑Oryzanol Solid Dispersion Development and Its Neuroprotective Effects on the

Pichaya Jumnongprakhon1, Andaman Nitjapol2, Khwankaew Lonlab1

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A novel solid dispersion of gamma-oryzanol (GO) enhances its solubility and oral bioavailability, offering a potent, natural treatment for major depressive disorder (MDD) by protecting neurons and restoring synaptic plasticity.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Major depressive disorder (MDD) presents significant public health challenges, with current treatments often limited by side effects and delayed efficacy.
  • Natural compounds with antioxidant properties, like gamma-oryzanol (GO), are being explored as alternatives.
  • GO's poor water solubility and low oral bioavailability hinder its clinical use.

Purpose of the Study:

  • To develop a gamma-oryzanol solid dispersion (GOSD) to enhance GO's water solubility and oral bioavailability.
  • To evaluate the neuroprotective effects of GOSD against dexamethasone-induced toxicity in neuronal cells.
  • To establish a link between the GOSD formulation and its functional therapeutic potential for depressive disorders.

Main Methods:

  • GOSD was prepared using a solvent melting method.
  • Enhanced water solubility and drug release under simulated intestinal conditions were assessed.
  • Neuroprotection was evaluated in SK-N-SH cells exposed to dexamethasone, measuring cell viability, reactive oxygen species (ROS), superoxide dismutase (SOD) activity, monoamine oxidase (MAO) activity, glucocorticoid receptor (GR) expression, and synaptophysin expression.

Main Results:

  • The developed GOSD significantly increased GO water solubility to 1.37 ± 0.05 mg/mL and demonstrated improved release profiles.
  • GOSD exhibited excellent physical and chemical stability over a 6-month storage period.
  • GOSD pretreatment showed superior neuroprotective effects compared to free GO, reducing dexamethasone-induced cytotoxicity by lowering ROS, increasing SOD activity, normalizing MAO and GR levels, and upregulating synaptophysin.

Conclusions:

  • The GOSD formulation effectively enhances GO's solubility and oral bioavailability.
  • GOSD demonstrates significant neuroprotective properties against cytotoxic insults relevant to depression.
  • The findings support GOSD as a promising, safe, and effective therapeutic strategy for managing depressive disorders.