Reproductive toxicity of ZishenYutai pill in rats: Perinatal and postnatal development study

Zhou, Li; Zhou, Jie; Jiang, Juan; Yang, Yang; Huang, Qiuling; Yan, Dawei; Xu, Li; Chai, Yu-Shuang; Chong, Liming; Sun, Zheng

doi:10.1016/j.yrtph.2016.07.015

Cited by 9 publications

(6 citation statements)

References 14 publications

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“…As a new deuterated drug, JJH201501 should be assessed for potential effects on reproductive and developmental health in humans at all stages of development (Iew Group, 2011;Sjberg & Jones, 2013;Zhou et al, 2016). Several factors can be taken into consideration when assessing a substance's systemic toxicity in an animal lab, such as its body weight, water intake, feed consumption, and organ weight (Paula et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Reproductive toxicity of JJH201501 in rats: Perinatal study

Sun,

Yue,

Qiao

2024

Birth Defects Research

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IntroductionIn this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5‐HT) antidepressant. Pregnant Sprague–Dawley rats (F0, n = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21.MethodsDuring this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH‐treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance.ResultsAutopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high‐dose group throughout the experiment. Due to the lack of dose‐dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results.ConclusionIn conclusion, the no‐observed‐adverse‐effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.

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Section: Discussionmentioning

confidence: 99%

Reproductive toxicity of JJH201501 in rats: Perinatal study

Sun,

Yue,

Qiao

2024

Birth Defects Research

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“…Topological feature analysis was subsequently performed by intersecting both PPI networks based on "betweenness (BC)," "closeness (CC)," and "eigenvector (EC)," deriving a total of 8511 nodes and 190,297 edges (Figure 3(a)). Based on a previous study by Zhou et al [16], targets were selected with parameters above twice the median value. e first selection criteria were set as degree >48, and 2352 nodes and 96,928 edges were derived (Figure 3(b)).…”

Section: Constructed Zsytp Compound-potential Target Network (C-t Network)mentioning

confidence: 99%

“…Compared with HRT treatment, ZSYTP can induce follicle development and stimulate ovulation [12]. Toxicological experiments have been conducted to prove no perinatal toxicity and observed adverse effects on livers, suggesting the pharmaceutical safety of ZSYTP [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology Approach for Predicting Targets of Zishen Yutai Pills on Premature Ovarian Insufficiency

Feng

Chai

Chen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background and Purpose. Premature ovarian insufficiency (POI) is a serious reproductive disease in females that is characterized by menstrual and ovulation disorders and infertility. The clinical efficacy of complementary and alternative medicine (CAM) has been reported in POI, including compound Chinese medicine. Zishen Yutai Pills (ZSYTP), a well-known patented Chinese medicine, has been widely used for treating POI; however, the pharmacological mechanism and molecular targets of ZSYTP remain unknown. Here, we systematically elucidated the pharmacological mechanism of ZSYTP on POI using a network pharmacology approach and further validated our findings with molecular docking. Methods. A comprehensive strategy based on several Chinese herb databases and chemical compound databases was established to screen active compounds of ZSYTP and predict target genes. For network pharmacological analysis, network construction and gene enrichment analysis were conducted and further verified by molecular docking. Results. A total of 476 target genes of ZSYTP were obtained from 205 active compounds. 13 herbs of ZSYTP overlapped on 8 active compounds based on the compound-target-disease network (C-T network). 20 biological processes and 9 pathways were strongly connected to the targets of ZSYTP in treating POI, including negative regulation of gene expression, mRNA metabolic process, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and gluconeogenesis. Finally, molecular docking was visualized. Conclusion. Intriguingly, the signal pathways and biological processes uncovered in this study implicate inflamm-aging and glucose metabolism as potential pathological mechanisms of POI. The therapeutic effect of ZSYTP could be mediated by regulating glucose metabolism and HIF-1 signal pathway. Collectively, this study sheds light on the therapeutic potential of ZSYTP on POI.

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“…In practice, TCM practitioners generally utilize CHM formulas in the treatment of threatened miscarriage, not single crude CHM extracts like those used in the animal experiments. For example, Zishen Yutai Pill, which is a common CHM to treat threatened miscarriage, shows no toxicity in the perinatal period in pregnant rats [87]. CHM synergies based on TCM theory might reduce the toxic effects, and there is a close correlation between the safety and efficacy of CHMs and the quality of the source materials used in their production.…”

Section: Safety and Adverse Events Of Chm Formentioning

confidence: 99%

Complementary and Alternative Medicine for Threatened Miscarriage: Advantages and Risks

Zhou

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Threatened miscarriage is one of the most common complications causing pregnancy loss, and it affects approximately 20% of confirmed pregnancies. More and more women are seeking treatment with complementary and alternative medicine (CAM) for this common complication, and it has been reported that women have had successful pregnancies after threatened miscarriage when being treated with CAM, which mainly includes Chinese herbal medicines, acupuncture, and nutritional supplements as well as psychological interventions and other approaches. However, many experts are concerned about the safety and adverse events of certain CAM approaches in women with threatened miscarriage. Therefore, this review focuses on the status of CAM for threatened miscarriage and presents the potential therapeutic efficacy and safety of CAM based on some clinical and experimental studies. We thus hope to provide some instructive suggestions for the application of CAM for treating threatened miscarriage in the future.

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Reproductive toxicity of ZishenYutai pill in rats: Perinatal and postnatal development study

Cited by 9 publications

References 14 publications

Reproductive toxicity of JJH201501 in rats: Perinatal study

Reproductive toxicity of JJH201501 in rats: Perinatal study

Network Pharmacology Approach for Predicting Targets of Zishen Yutai Pills on Premature Ovarian Insufficiency

Complementary and Alternative Medicine for Threatened Miscarriage: Advantages and Risks

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