Therapeutic Effects and Analgesic Mechanisms of Iridoid Glycosides from Corni Fructus in Chronic Nonbacterial...

Cornus officinalis Sieb. et Zucc. is a medicinal and edible plant whose dried ripe fruit, Corni Fructus, has long been used in traditional Chinese medicine to treat seminal emission, enuresis, frequent urination, and erectile dysfunction. In modern clinical practice, Corni Fructus is used either alone or in combination with other herbal medicines to manage chronic nonbacterial prostatitis (CNP). However, its therapeutic efficacy and underlying molecular mechanisms in CNP remain insufficiently understood.

This study systematically examined the anti-inflammatory and analgesic effects of an iridoid glycoside-enriched fraction (SID) obtained from Corni Fructus by using a carrageenan-induced rat model of CNP and a lipopolysaccharide- (LPS-) stimulated WPMY-1 human prostate stromal cell model and elucidated the underlying analgesic signaling pathways.

Carrageenan was injected into the prostate to establish an in vivo rat model of CNP, whereas LPS was used to induce inflammatory responses in immortalized human prostate stromal WPMY-1 cells. High-performance liquid chromatography (HPLC) was employed to qualitatively and quantitatively characterize the major bioactive constituents of SID. Mechanistic analyses were conducted through pelvic pain threshold detection, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, Western blotting, and intracellular calcium flux measurement.

Chemical profiling revealed that SID comprised morroniside (21.6%), loganin (9.2%), sweroside (1.7%), and cornuside (0.7%), yielding a total iridoid glycoside content of 33.2%. SID markedly increased pelvic pain thresholds and alleviated prostatic inflammatory infiltration and histological lesions in CNP rats. SID also significantly modulated the expression of proinflammatory and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) and pain-sensing ion channels (TRPV1 and TRPM8). In addition, it suppressed the production of prostaglandin E2 and cyclooxygenase-2. Cellular experiments confirmed that SID blocked the PGE2/TRPV1/CaMKII signaling cascade, upregulated TRPM8 protein expression, and attenuated LPS-evoked intracellular Ca²⁺ influx in WPMY-1 cells.

SID ameliorates CNP through multitargeted mechanisms integrating anti-inflammatory and analgesic effects and the regulation of pain-associated transient receptor potential ion channels. These findings support the ethnomedicinal use of Corni Fructus for the management of inflammatory prostate disorders.