Metabolomics and network pharmacology reveal the mechanism of the Jiawei Yangshen pill in treatment of cyclophosphamide-induced dyszoospermia in mice

Background:The Jiawei Yangshen pill enhances sperm abundance.However,the pharmacological mechanism of action of the Jiawei Yangshen pill remains unclear.This study aimed to explore the therapeutic effect of the Jiawei Yangshen pill in the treatment of dyszoospermia and study the underlying mechanism.Methods:A dyszoospermia model was established by injecting mice with cyclophosphamide(50 mg/kg)consecutively for 7 days.Physiological and pathological indicators of the testis and hormone levels were examined after 4 weeks of treatment.Untargeted metabolomics using high-performance liquid chromatograph-mass spectrometry was performed on testis specimens.Network pharmacology analysis was used to construct an“ingredient-target-disease”interactive network,followed by metabolic pathway enrichment analysis.Western blotting was performed to examine the levels of the related proteins.Results:The Jiawei Yangshen pill significantly increased the testis index,epididymal index,sperm count,and testosterone level,while concurrently decreasing sperm mortality and luteinizing hormone levels.The spermatogenic cells in the Jiawei Yangshen pill-treated mice were well arranged with an increased number.Significantly different metabolites were identified.Western blotting showed that the expression levels of p-anti-adenosine monophosphate-activated protein kinase/anti-adenosine monophosphate-activated protein kinase and p-protein kinase B/protein kinase B were significantly increased after the Jiawei Yangshen pill treatment,whereas the expression levels of transforming growth factor-β1 and nuclear factor kappa B(p65)were remarkably decreased.Conclusion:The Jiawei Yangshen pill significantly improved testicular microcirculatory injury and overall metabolic levels in mice with dyszoospermia.

Molecular mechanisms underlying the toxicity and detoxification of trace metals and metalloids in plants

Plants take up a wide range of trace metals/metalloids(hereinafter referred to as trace metals)from the soil,some of which are essential but become toxic at high concentrations(e.g.,Cu,Zn,Ni,Co),while others are non-essential and toxic even at relatively low concentrations(e.g.,As,Cd,Cr,Pb,and Hg).Soil contamination of trace metals is an increasing problem worldwide due to intensifying human activities.Trace metal contamination can cause toxicity and growth inhibition in plants,as well as accumulation in the edible parts to levels that threatens food safety and human health.Understanding the mechanisms of trace metal toxicity and how plants respond to trace metal stress is important for improving plant growth and food safety in contaminated soils.The accumulation of excess trace metals in plants can cause oxidative stress,genotoxicity,programmed cell death,and disturbance in multiple physiological processes.Plants have evolved various strategies to detoxify trace metals through cell-wall binding,complexation,vacuolar sequestration,efflux,and translocation.Multiple signal transduction pathways and regulatory responses are involved in plants challenged with trace metal stresses.In this review,we discuss the recent progress in understanding the molecular mechanisms involved in trace metal toxicity,detoxification,and regulation,as well as strategies to enhance plant resistance to trace metal stresses and reduce toxic metal accumulation in food crops.