Bioactive compound emodin from clinical formula Zhi-Lou-Xun-Xi decoction exerts rapid analgesic effects by targeting...

Effective postoperative pain management after hemorrhoidectomy remains a significant clinical challenge, largely due to the scarcity of safe and effective non-opioid analgesics. Zhi-Lou-Xun-Xi decoction (J5) is a traditional Chinese formula that has been used clinically for decades, yet its active components and mechanism of action remain unclear.

This study aimed to systematically identify the active analgesic components in J5 and elucidate their molecular mechanism of action.

We employed an integrated pharmacological approach, beginning with a retrospective clinical analysis to confirm the analgesic and wound-healing effects of J5. Pharmacodynamic assays were conducted to evaluate its interaction with TRPV1. High-resolution mass spectrometry and structure-based virtual screening were used to identify candidate compounds. The mechanism of emodin, the primary active constituent, was further investigated through SPR assays, patch-clamp recording, molecular dynamics simulations, and extensive in vivo pain models using TRPV1 knockout (KO) mice.

Emodin was identified as the key TRPV1-antagonizing component in J5. In multiple pain models, emodin produced dose-dependent analgesia without inducing common TRPV1 antagonist-related side effects, particularly altered thermal sensitivity or hyperthermia. These findings not only clarify the mechanistic basis of J5's clinical efficacy but also position emodin as a promising topical analgesic candidate that acts via local TRPV1 inhibition.