Journal of ethnopharmacology · 2026
Multi-component, multi-target actions of Wuzi Yanzong Pill in male infertility: An evidence map linking clinical signals to mechanistic networks.
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Ren Xiaoli, Chen Ken, Li Shu, Wang Tongsheng, Li Jingya
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Wuzi Yanzong Pill (WZYZP) is a classical Traditional Chinese Medicine (TCM) formula long used for male reproductive disorders, particularly oligoasthenozoospermia (OAT). However, current research is fragmented across formula-level trials, monomer pharmacology, and computational studies, accompanied by inconsistent clinical outcomes and limited translational frameworks.
AIM OF THE STUDY: To construct an evidence map linking clinical signals of WZYZP in male infertility to convergent mechanistic networks and actionable research gaps.
MATERIALS AND METHODS: ACS Publications, Web of Science, PubMed, Elsevier ScienceDirect, SpringerLink, and CNKI were searched from inception to December 2025. A PRISMA-informed screening workflow was applied for evidence mapping (no meta-analysis). Of 1140 records screened, 135 publications were retained: 64 WZYZP intervention studies (56 preclinical; 8 clinical) and 71 mechanistic publications, comprising published in silico analyses (e.g., network pharmacology and molecular docking/molecular dynamics simulations) and single-constituent studies relevant to WZYZP.
RESULTS: Clinical studies frequently reported improvements in semen concentration, motility, morphology, and reproductive hormones, but were heterogeneous in formulation sources, diagnostic criteria, comparators, and endpoints. Preclinical interventions consistently indicated enhanced spermatogenesis and testicular function, with pathway convergence on redox and lipid-peroxidation control, mitochondrial bioenergetics, apoptosis modulation (Bcl-2/Bax-caspase axis), inflammatory signaling, blood-testis barrier (BTB) integrity, and hypothalamic-pituitary-gonadal (HPG)-axis/steroidogenesis support. In silico and monomer studies provided hypothesis-generating links between constituent classes and target engagement.
CONCLUSIONS: The mapped evidence suggests that WZYZP may exert multi-component, multi-target effects for OAT, but translation requires formula standardization and quality control, exposure/PK-informed dosing, biomarker-guided target validation, and adequately powered registered trials with pregnancy/live-birth outcomes. Due to the limited number and variable quality of the included clinical trials, our findings should be interpreted with caution.
AIM OF THE STUDY: To construct an evidence map linking clinical signals of WZYZP in male infertility to convergent mechanistic networks and actionable research gaps.
MATERIALS AND METHODS: ACS Publications, Web of Science, PubMed, Elsevier ScienceDirect, SpringerLink, and CNKI were searched from inception to December 2025. A PRISMA-informed screening workflow was applied for evidence mapping (no meta-analysis). Of 1140 records screened, 135 publications were retained: 64 WZYZP intervention studies (56 preclinical; 8 clinical) and 71 mechanistic publications, comprising published in silico analyses (e.g., network pharmacology and molecular docking/molecular dynamics simulations) and single-constituent studies relevant to WZYZP.
RESULTS: Clinical studies frequently reported improvements in semen concentration, motility, morphology, and reproductive hormones, but were heterogeneous in formulation sources, diagnostic criteria, comparators, and endpoints. Preclinical interventions consistently indicated enhanced spermatogenesis and testicular function, with pathway convergence on redox and lipid-peroxidation control, mitochondrial bioenergetics, apoptosis modulation (Bcl-2/Bax-caspase axis), inflammatory signaling, blood-testis barrier (BTB) integrity, and hypothalamic-pituitary-gonadal (HPG)-axis/steroidogenesis support. In silico and monomer studies provided hypothesis-generating links between constituent classes and target engagement.
CONCLUSIONS: The mapped evidence suggests that WZYZP may exert multi-component, multi-target effects for OAT, but translation requires formula standardization and quality control, exposure/PK-informed dosing, biomarker-guided target validation, and adequately powered registered trials with pregnancy/live-birth outcomes. Due to the limited number and variable quality of the included clinical trials, our findings should be interpreted with caution.