# Neuroprotective Pathway Modulation by a Novel Coriandrum sativum, N-Acetylcysteine and Glutathione-Based Formulation: Insights from In Vitro 3D Models

## TL;DR

A new supplement formulation using coriander extract, NAC, and glutathione shows better neuroprotection and anti-inflammatory effects than existing products in lab models.

## Contribution

Replacing alpha-lipoic acid and vitamin D3 with coriander extract, NAC, and glutathione improves neuroprotective and anti-inflammatory properties in a novel supplement formulation.

## Key findings

- IperALA® Forte improved cell viability, barrier integrity, and permeability compared to IperALA®.
- The formulation reduced ROS and pro-inflammatory cytokines while increasing analgesic markers in CNS models.
- C. sativum, NAC, and GSH combination enhanced antioxidant and anti-inflammatory effects over individual agents.

## Abstract

Pain remains a major clinical challenge due to its complex physiopathology and limited treatment options. In this context, several supplements based on palmitoylethanolamide (PEA) and alpha-lipoic acid (ALA) are known for their neuroprotective properties. ALA-based supplements have shown potential, but concerns about adverse effects persist. This study examines the formulations of two commercial products based on ALA and PEA, IperALA® and IperALA® Forte, in which ALA and vitamin D3 are replaced with Coriandrum sativum extract (C. sativum e.s.), N-acetylcysteine (NAC) and glutathione (GSH), assessing improvement of neuroprotective, anti-inflammatory and analgesic properties of the new formulation. Intestinal, blood–brain barrier (BBB), and central nervous system (CNS) models were sequentially stimulated with the test compounds. Both formulations were assessed for cytotoxicity, barrier integrity, permeability, oxidative stress, inflammation, and neuroprotection-related biomarkers. IperALA® Forte demonstrated superior performance compared to IperALA® and individual agents. It enhanced cell viability, preserved intestinal and BBB integrity, and improved compound permeability. Notably, it reduced ROS and pro-inflammatory cytokines (TNFα, IL-1), while increasing analgesic markers (CB2R, GABA) in the central system. The replacement of ALA and vitamin D3 with C. sativum, NAC, and GSH in IperALA® Forte significantly improved the neuroprotective, antioxidant, and anti-inflammatory profile of the supplement. These results indicate a possible connection between the observed neuroprotective properties and the pathways involved in nociception and pain regulation, stating the hypothetical potential relevance of this approach for the treatment of pain-related conditions.