ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription （BSZY） on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group （Control）， a model group （Model）， low-dose BSZY （BSZY-L）， medium-dose BSZY （BSZY-M）， and high-dose BSZY （BSZY-H） groups （2.57， 5.14， 10.28 g·kg^-¹）， and a Zishen Yutai Pill （ZSYT） group （1.575 g·kg^-¹）. Hematoxylin-eosin （HE） staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of estrogen （E₂）， progesterone （P）， luteinizing hormone （LH）， prolactin （PRL）， and follicle-stimulating hormone （FSH） in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0 databases， while disease targets for recurrent spontaneous abortion （RSA） were retrieved from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM）， and Therapeutic Target Database （TTD）. The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor （ERα）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） and explore its protective mechanism on RSA rats. ResultsCompared with the control group， the model group exhibited significantly decreased uterine， ovarian， and embryonic wet weights （P<0.05， P<0.01）， with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles， primary follicles， mature follicles， and corpora lutea， along with a large number of atretic follicles. The endometrium was thinner， and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast， compared with the model group， the BSZY groups at all doses and the ZSYT group demonstrated increased uterine， ovarian， and embryonic wet weights， along with a reduced abortion rate. The number of primordial follicles， primary follicles， mature follicles， and corpora lutea increased， while atretic follicles decreased. The endometrium thickened， and decidual tissue displayed normal cellular structure with tight arrangement. Additionally， the model group showed significantly decreased levels of E₂， P， PRL， and FSH in serum （P<0.05， P<0.01）， along with a decreasing trend in LH level. In contrast， the BSZY groups at all doses exhibited significantly elevated levels of E₂， P， LH， PRL， and FSH in serum （P<0.05， P<0.01）. Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα， PI3K， and p-Akt proteins （P<0.05， P<0.01）. ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome， possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function， thereby lowering the abortion rate.

Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

ObjectiveTo investigate the effect of total glucosides of paeony （TGP） on neurotoxicity induced by aqueous extract of Strychni Semen （SA） in mice and to explore its mechanism. MethodThirty-two male KM mice were randomly divided into normal group，SA group （19.5 mg·kg^-1），TGP group （225 mg·kg^-1），and SA+TGP group （SA 19.5 mg·kg^-1+TGP 225 mg·kg^-1）. The open field test and beam walking test were used to observe the behavioral changes in mice. Pathological changes in the Nissl bodies of the cerebral cortex were assessed through Nissl staining. The levels of malondialdehyde （MDA），glutamate （Glu） in the mouse brain tissue，and serum levels of 5-hydroxytryptamine （5-HT） were detected using enzyme-linked immunosorbent assay （ELISA）. Transcriptome sequencing was employed to analyze gene expression profiles in the brain tissue. Common differentially expressed genes （DEGs） underwent gene ontology （GO） and kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses. The mRNA expression levels of key targets were determined using quantitative real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group，the SA group exhibited significant increases in side-to-side distance and average speed in the open field test，as well as increased walking time on the balance beam. The axons of cortical neurons were absent，and the levels of Glu and MDA in the brain tissue were significantly elevated （P<0.05，P<0.01），along with a notable increase in serum 5-HT levels （P<0.05）. In contrast to the SA group，the SA+TGP group significantly reduced the side-to-side distance，average speed，and balance beam walking time （P<0.05 or P<0.01）. The neuronal axons were clearly visible，and levels of 5-HT，Glu，and MDA were decreased （P<0.05，P<0.01）. Transcriptome analysis indicated that TGP could regulate the glutamate receptor，ionotropic，N-methyl-D-aspartate 2a （GRIN2A）/phospholipase C β₁ （PLCB1）/protein kinase C，gamma （PRKCG） signaling pathway. Compared with the normal group，SA significantly decreased the expression of GRIN2A，PLCB1，and PRKCG genes in the mouse brain （P<0.01），while the mRNA levels of GRIN2A and PRKCG significantly increased after TGP administration （P<0.05，P<0.01）. ConclusionSA induces significant neurotoxicity in the mouse brain，and TGP significantly alleviates SA-induced neurological damage，potentially through the GRIN2A/PLCB1/PRKCG signaling pathway.

Objective: To investigate the expression of circular RNA hsa_circ_0128298 in hepatocellular harcinoma (HCC) and evaluate its function in the growth process of HCC. Methods: qPCR was used to detect the expressions of hsa_circ_0128298 in 50 HCC tissues, corresponding paracancerous tissues and HCC cells. The effects of hsa_circ_0128298 on HCC growth was analyzed by CCK-8 kit, flow cytometry and western blot assays. The values of hsa_circ_0128298 for the diagnosis and prognosis of HCC were assessed by ROC curve and survival curve analyses. Results: Compared with the paracancerous tissues, the expression of hsa_circ_0128298 was significantly increased in HCC tissues ( U =846.0， P =0.005). The area under ROC curve (AUCROC) was 0.661, 95% confidence interval ( CI ) was 0.560 to 0.753, sensitivity was 80.0% and specificity was 50.0%. HCC patients with high expression of hsa_circ_0128298 displayed less overall survival time than those with low expression of hsa_circ_0128298 ( χ 2=6.294, P =0.012). RNA interference of hsa_circ_0128298 (si-hsa_circ_0128298) significantly inhibited HCC cell proliferation and induced cell cycle arrest at G0/G1, and also induced mRNA upregulation and protein expression of cyclin p21. Meanwhile，si-p21 partially reversed the proliferation inhibition and cell cycle arrest of HCC cells induced by si-hsa_circ_0128298, and restore its growth and proliferation potential. Conclusion The highly expressed hsa_circ_0128298 in HCC could promote the growth of HCC by regulating the expression of p21 and promise to be a new target for diagnosis and treatment of HCC.