Zuogui(左归丸)and Yougui pills(右归丸)improve perimenopausal syndrome via regulation of apoptosis in mice

OBJECTIVE:To examine,dissect,and understand the molecular mechanisms and combinatorial effects of Zuogui(左归丸,ZGP)and Yougui pills(右归丸,YGP)in 4-vinyl cyclohexene diepoxide(4-VCD)-induced Perimenopausal syndrome(PMS).METHODS:Using the 4-VCD-induced PMS mouse model,uterine and ovary index were measured,and serum sex steroidal hormone levels were evaluated after treatment with ZGP,YGP,ZGP+YGP,estradiol valerate(EV),and Gengnian An(更年安,GNA).Histopathological examinations,ingredient-target network predictions,western blotting,and real-time quantitative polymerase chain reaction(RT-q PCR)analyses were performed to ascertain the possible pharmacological effects and molecular mechanisms of ZYP and YGP.RESULTS:Treatment with ZGP and YGP remarkably improves estrous cyclicity and prevents pathological damage to the uterus.Also,altered sex hormones,including AMH,E2,FSH,LH,P,and T,were restored to normal levels after ZGP and YGP administration.Ingredient-target network analysis showed that the 5 ingredients common to the ZGP and YGP formula modulate 53 targets shared with PMS.Pathwayenrichment analysis further predicted that ZGY and YGP likely regulate of apoptosis and other essential pathways during PMS.In-vivo studies showed that ZGP and YGP suppress PMS via modulating apoptosis through decreasing Caspase-3 and Bcl-2-associated X(Bax)levels and increasing B-cell lymphoma-2(Bcl-2)/Bax and Bcl-2 levels.Importantly,ZGP+YGP treatment modulation effects were somewhat or significantly better compared to ZGP or YGP alone treatment.CONCLUSION:ZGP and YGP represent novel anti-PMS agents whose effects involve restoring altered hormonal levels,protecting the uterus,and regulating apoptosis.

The status of fertility control for rodents—recent achievements and future directions

Management of overabundant rodents at a landscape scale is complex but often required to sustainably reduce rodent abundance below damage thresholds.Current conventional techniques such as poisoning are not species specific,with some approaches becoming increasingly unacceptable to the general public.Fertility control,first proposed for vertebrate pest management over 5 decades ago,has gained public acceptance because it is perceived as a potentially more species-specific and humane approach compared with many lethal methods.An ideal fertility control agent needs to induce infertility across one or more breeding seasons,be easily delivered to an appro-priate proportion of the population,be species specific with minimal side-effects(behavioral or social structure changes),and be environmentally benign and cost effective.To date,effective fertility control of rodents has not been demonstrated at landscape scales and very few products have achieved registration.Reproductive targets for fertility control include disrupting the hormonal feedback associated with the hypothalamic-pituitary-gonadal axis,gonad function,fertilization,and/or early implantation.We review progress on the oral delivery of various agents for which laboratory studies have demonstrated efficacy in females and/or males and synthesize progress with the development and/or use of synthetic steroids,plant extracts,ovarian specific peptides,and immunocontracep-tive vaccines.There are promising results forfield application of synthetic steroids(levonorgestrel,quinestrol),chemosterilants(4-vinylcyclohexene diepoxide),and some plant extracts(triptolide).For most fertility control agents,more research is essential to enable their efficient and cost-effective delivery such that rodent impacts at a population level are mitigated and food security is improved.