Research Progress on the Pharmacological Effects and Network Regulatory Mechanisms of Pedunculoside

Pedunculoside (PE), a primary bioactive constituent of the traditional Chinese medicines (TCM) Ilex chinensis (Sijiqing) and Ilex rotunda (Jiubiying), has garnered growing interest for its broad pharmacological profile. This review synthesizes literature from 1999 to 2026, highlighting anti-inflammatory, cardioprotective, lipid-regulating, neuroprotective, and antitumor activities of PE. By modulating key signaling cascades, including NF-κB, MAPK, NLRP3, and Nrf2/HO-1, PE disrupts the interconnected “inflammation–oxidative stress–cell death” network, conferring multi-organ protection. These findings position PE as a key material basis underlying the Qing Re Jie Du properties of its parent herbs, while rationalizing their distinct clinical applications: Sijiqing for resolving swelling and blood stasis, and Jiubiying for promoting diuresis and alleviating pain. PE exhibits multi-target potential, directly or indirectly engaging proteins such as GATA6, TRAF6, and ACSL4, thereby contributing to formulation synergy. Despite its promise as a TCM-derived lead compound, PE research remains transitional, constrained by undefined direct molecular targets, limited pharmacokinetic data, and insufficient long-term safety profiling. Future efforts should integrate chemical biology and multi-omics to validate target engagement, systematically characterize pharmacokinetics and toxicology, and decode formulation synergy to accelerate clinical translation.