Natural Extract Combination Modulates Intestinal Barrier and Hepatic Cholesterol via the Gut-Liver Axis In Vitro

Area of Science:

• Integrative medicine
• Nutraceuticals
• Gastroenterology and Hepatology

Background:

• The gut-liver axis is crucial for cholesterol homeostasis, with dysregulation contributing to hypercholesterolemia and cardiometabolic risk.
• Novel interventions targeting both intestinal and hepatic cholesterol mechanisms are needed.

Purpose of the Study:

• To evaluate a multi-botanical formulation (MIX) comprising Gastrodia elata, Black Garlic, Primula veris, and Emblica officinalis (AMLA) for its effects on cholesterol metabolism.
• To investigate the synergistic effects of MIX on intestinal barrier integrity and hepatic lipid regulation.

Main Methods:

• Chemical characterization of individual botanical extracts.
• In vitro assessment using Caco-2 cells for intestinal barrier function and HepG2 cells for hepatic lipid metabolism under high-glucose conditions.
• Analysis of cholesterol synthesis (HMGR), LDL receptor (LDLR) expression, PCSK9, bile acid production, and associated signaling pathways (SRC/ERK-MAPK).

Main Results:

• MIX significantly enhanced intestinal barrier integrity and cell viability compared to individual extracts.
• In HepG2 cells, MIX synergistically reduced HMGR expression, increased LDLR expression, suppressed PCSK9, and improved cholesterol and LDL uptake.
• MIX promoted bile acid production and free cholesterol excretion, favorably modulating SRC/ERK-MAPK signaling.

Conclusions:

• The multi-botanical MIX formulation demonstrates complementary and synergistic actions on intestinal and hepatic cholesterol regulation.
• MIX effectively suppresses cholesterol synthesis, enhances LDL clearance, and stimulates elimination via bile acids.
• This formulation holds promise for modulating metabolic cholesterol dysregulation, warranting further in vivo and clinical studies.