Supplements

Combined tetrahydroberberine and protopanaxadiol synergistically improves sleep in PCPA-induced insomnia in rats via microbiota-gut-brain axis and PI3K/AKT/AGE-RAGE pathways.

In a rat model of PCPA-induced insomnia, the combination of tetrahydroberberine (THB) and protopanaxadiol (PPD) showed synergistic effects, shortening sleep latency by 56.2% and prolonging sleep duration by 112.8% compared to the model group. The combination outperformed monotherapies and restored gut microbiota balance, neurotransmitter levels, and blood-brain barrier integrity.

1 min read•Updated Jul 7, 2026•0 RCTs•View structured evidence →
Evidence Score26/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism☆☆☆☆☆
Safety☆☆☆☆☆
Confidencelow

This article is automatically generated from the structured evidence profile behind the claim above. Scores reflect the quality and quantity of available research, not clinical advice.

Combined tetrahydroberberine and protopanaxadiol synergistically improves sleep in PCPA-induced insomnia in rats via microbiota-gut-brain axis and PI3K/AKT/AGE-RAGE pathways. The current body of evidence comprises 1 study. EvidenceHub rates the overall confidence at 26/100 (low).

The Claim

Combined tetrahydroberberine and protopanaxadiol synergistically improves sleep in PCPA-induced insomnia in rats via microbiota-gut-brain axis and PI3K/AKT/AGE-RAGE pathways.

This conclusion is most relevant to: Sprague-Dawley rats with PCPA-induced insomnia.

What the Research Shows

The conclusion draws on 1 linked study. Highlights from the cited literature:

  • ▸Synergistic Therapeutic Effects of Tetrahydroberberine Combined with Protopanaxadiol on PCPA-Induced Insomnia in Rats: Involvement of the Microbiota-Gut-Brain Axis and Regulation of PI3K/AKT/AGE-RAGE Pathways. (Pharmaceuticals (Basel, Switzerland), 2026) —

How It Works

The proposed biological pathway:

  • ▸Combined THB+PPD activates PI3K/AKT neurotrophic pathway (upregulates p-PI3K and p-AKT).
  • ▸Combined THB+PPD inhibits AGE/RAGE pro-inflammatory axis (downregulates RAGE).
  • ▸Combined THB+PPD restores gut microbial homeostasis (increases beneficial bacteria like Lactobacillus) and modulates glycine-serine-threonine metabolism.
  • ▸Result: Reduced sleep latency, prolonged sleep duration, restored neurotransmitter balance, suppressed HPA axis overactivation, decreased inflammation, and improved blood-brain barrier integrity.

Who Might Benefit

Evidence fit by population:

  • ▸Sprague-Dawley rats with PCPA-induced insomnia

Limitations & Caveats

Important context when interpreting this evidence:

  • ▸Animal model (rats) may not directly translate to human insomnia.
  • ▸Exact doses and treatment duration for THB and PPD are not reported in the abstract, limiting replicability.

References

  1. 1.Li M, Wang Y, Liang Z, Li H, Zhao Y, Kong L, Guo N, Dai G, Zhang G, Lu X, Yao J. “Synergistic Therapeutic Effects of Tetrahydroberberine Combined with Protopanaxadiol on PCPA-Induced Insomnia in Rats: Involvement of the Microbiota-Gut-Brain Axis and Regulation of PI3K/AKT/AGE-RAGE Pathways..” Pharmaceuticals (Basel, Switzerland), 2026. PMID: 41901236 DOI: 10.3390/ph19030390
Disclaimer: This article is auto-generated from structured research data for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.