Quantitative Imaging in Medicine and Surgery
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2025
·Vol. 16
·期 1
·18
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IF 2.3
Xi Weizhe,Liu Fenfang,Zhong Guangen,Chen Fen,Xie Yin,Lai Meilian,He Qiting,Lu Yiqing,Zhang Jiping,Chen Ying,Meng Luo,Yang Lu
Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that leads to cartilage degradation and bone destruction, significantly impacting daily life. Melittin acupoint injection (MAI) is a promising traditional Chinese medicine treatment, but its molecular mechanisms are not fully understood. This study aimed to investigate the therapeutic effects of MAI on RA and elucidate its underlying mechanisms. Methods A collagen-induced arthritis (CIA) mouse model was established using bovine type II collagen, administered every other day for 28 days. The mice were randomly divided into a CIA model group (MO group), melittin acupoint subcutaneous injection group (ST group), melittin acupoint intramuscular injection group (IT group), and methotrexate group (MTX group), with an additional normal control group (NC group) established. Each group contained 8 mice, all of which were treated for 28 days. Therapeutic outcomes were assessed by measuring body weight, swollen joint count (SJC), arthritis index (AI), ankle circumference, and plantar thickness. Radiological and histological changes were analyzed with micro-computed tomography (CT) imaging and pathological staining. Cytokine levels were measured via enzyme-linked immunosorbent assay (ELISA), and autophagy levels were assessed using immunofluorescence staining. The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway and autophagy status were examined through western blot (WB) and immunofluorescence techniques. Results MAI significantly improved clinical symptoms in CIA mice by reducing plantar thickness, AI scores, and swollen joints (P<0.05). Histopathological analysis showed decreased inflammatory cell infiltration, synovial proliferation, and cartilage damage (P<0.01). Micro-CT and immunohistochemistry revealed reduced inflammation, bone destruction, and cartilage erosion, along with decreased tumor necrosis factor-α (TNF-α) expression (P<0.05). MAI also lowered serum levels of interleukin (IL)-1β (P<0.05), IL-17A, and TNF-α (P<0.01), while increasing IL-10 levels (P<0.05). Immunofluorescence indicated increased microtubule-associated protein 1 light chain 3 beta (LC3B) fluorescence intensity (P<0.05). WB analysis showed elevated levels of Unc-51-like autophagy activating kinase 1 (ULK1), beclin-1 (P<0.01), and microtubule-associated protein 1 light chain 3 II (LC3II) (P<0.05), and reduced phosphorylation of PI3K, AKT, and mTOR (P<0.05). Conclusions MAI alleviates RA symptoms by inhibiting the PI3K/AKT/mTOR pathway and promoting autophagy.
研究领域:
风湿病学
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分子医学
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中医中药
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免疫学
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信号转导
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
·
IF 5.895
Xiaofei Zhou,Bowei Zhang,Xiuli Zhao,Yongxi Lin,Yuan Zhuang,Jingting Guo,Shuo Wang
Hyperuricemia is an independent hazard factor of renal injury and can induce renal fibrosis, promoting the development of chronic kidney disease (CKD). This study aimed to explore the probability of chlorogenic acid (CGA) as a potential substance for preventing hyperuricemia nephropathy (HN). Pretreatment with CGA downregulated SUA, BUN, and CR levels, relieved oxidative stress and inflammatory response, alleviated kidney fibrosis, and contributed to the prevention of HN. In the gut microbiota, Blautia, Enterococcus, and Faecalibaculum related to trimethylamine N-oxide (TMAO) synthesis were significantly increased in HN rats. In addition, it showed a significant increase in serum TMAO content in HN rats. However, CGA regulated the cascade response of the microbiota-TMAO signaling to reverse the increase of serum TMAO. CGA also decreased the protein expression of protein kinase B (AKT) phosphorylation, phosphatidylinositide 3-kinase (PI3K), and mammalian target of rapamycin (mTOR) by reducing the production of TMAO. CGA delayed kidney fibrosis in HN rats as evidenced by regulating the cascade response of the microbiota-TMAO-PI3K/AKT/mTOR signaling pathway. In summary, CGA can be an excellent candidate for HN prevention.
研究领域:
药理学
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肾病学
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微生物学
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分子生物学
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病理生理学
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Virulence
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2026
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IF 6.8
Xinxian Wang,Shurui Yang,Lichun Xie,Shanshan Qi,Libo Gao,Yongmei Li,Qian Li,Junlong Bi,Jianping Liu,Yongneng Li,Gefen Yin
Classical swine fever virus (CSFV) remains a major threat to the global swine industry, yet the involvement of host miRNAs in its pathogenic mechanisms is not fully understood. In this study, we demonstrate for the first time that miR-17-5p inhibits CSFV replication through an autophagy-dependent mechanism by targeting polycystin-2 (PKD2), a key calcium channel protein that regulates the AMPK/mTOR signaling pathway. Using the PK-15 cell model, we found that CSFV infection significantly upregulates miR-17-5p expression. Functional assays revealed that miR-17-5p exerts antiviral effects by directly binding to the 3’-UTR of PKD2, as confirmed by bioinformatics prediction and dual-luciferase reporter assays. Silencing of PKD2 recapitulated the antiviral effect of miR-17-5p overexpression, while PKD2 reconstitution restored viral replication by activating AMPK signaling and suppressing mTOR activity, thereby significantly enhancing autophagic flux – as evidenced by increased LC3-II/I ratio and decreased p62 levels. Mechanistically, PKD2 regulates intracellular calcium dynamics, modulating the AMPK/mTOR-autophagy axis to promote CSFV proliferation. This work uncovers a novel host antiviral mechanism in which a miRNA controls virus-induced autophagy via calcium signaling. To our knowledge, this is the first report to establish the pivotal role of miRNA-mediated calcium signaling modulation in flavivirus-host interactions. These findings provide a mechanistic framework and potential therapeutic targets for anti-CSFV interventions focused on PKD2 or autophagy regulation.
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International Journal of Nanomedicine
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2026
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IF 6.5
Aiqiu Wei,Ziyi Zhong,Yiming Zhang,Jincheng He,Haihe Pang,Xinhua Xia,Xiaoqing Zhang
Purpose: Cantharidin (CTD) is a natural anticancer compound whose clinical application is limited by poor water solubility, low bioavailability, and significant toxicity. To develop a more effective and safer therapeutic strategy, we proposed a synergistic combination therapy by integrating CTD with staurosporine (STS), a protein kinase inhibitor that shares complementary mechanisms of action targeting the mTOR/HIF-1α/VEGF pathway. We further developed an aptamer-guided liposomal nanosystem for the co-delivery of CTD and STS (Apt/CTD-STS/NL), aiming to enhance tumor targeting, improve bioavailability, and reduce the systemic toxicity of both drugs.Methods: We constructed aptamer-guided co-delivery nanoliposomes encapsulating CTD and STS (Apt/CTD-STS/NL). The targeted delivery efficiency, synergistic antitumor efficacy, and biocompatibility of this nanosystem were comprehensively evaluated through both in vitro and in vivo experiments.Results: Apt/CTD-STS/NL achieved approximately 1.3-fold higher cellular uptake in HCC cells compared to non-targeted liposomes in vitro. In vivo, it demonstrated superior tumor accumulation. In a murine HCC model, Apt/CTD-STS/NL exhibited the strongest tumor growth inhibition (79.50 ± 4.39%), significantly outperforming free CTD, STS, or single-drug loaded liposomes. Mechanistic studies revealed that the core synergy between CTD and STS enabled simultaneous inhibition of the key oncoproteins mTOR, HIF-1α, and VEGF, thereby disrupting tumor proliferation, survival, and angiogenesis.Conclusion: This study demonstrates a novel targeted nanoplatform that combines an active ingredient from traditional Chinese medicine with a modern kinase inhibitor. This strategy achieves a synergistic anti-HCC effect through multi-pathway inhibition and offers a promising approach for cancer therapy with enhanced efficacy and reduced toxicity.
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JOURNAL OF MOLECULAR HISTOLOGY
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2026
·Vol. 57
·期 1
·30
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IF 2.2
Xiang Shouyu,Liu Wei,Tang Cheng,Xie Chuhai,Hu Hailan,Zhou Jianhui,Cao Yanming,Ling Long
Bone marrow mesenchymal stem cells (BMSCs) play a significant role in bone defect repair. Currently, the limited survival and function of transplanted BMSCs pose major obstacles to tissue repair mediated by these cells. Therefore, the exploration of BMSCs transplantation activity has become an urgent clinical problem. In this experiment, we constructed lentiviral vectors with overexpression and silencing of miR-19b-3p and utilized a rat fracture model. The effects of BMSCs proliferation were examined using CCK-8, the Annexin V-FITC apoptosis kit and TUNEL assay, the effects of BMSCs osteogenic differentiation were detected using ALP and Alizarin red staining. Furthermore, Western blotting and qRT-PCR were employed to examine the expression of key proteins in the PTEN/Akt/mTOR signaling pathway and autophagy-related proteins. Moreover, the impact of miR-19b-3p on bone microstructure was assessed using Micro CT, HE, Safranin O/Fast Green, as well as Masson staining, and Immunohistochemistry analysis examined PTEN, p62 and Runx2 expression levels on fracture site. By constructing lentiviral vectors with overexpression and silencing of miR-19b-3p, we found that silencing miR-19b-3p significantly promoted the proliferation as well as the osteogenic differentiation of BMSCs under hypoxia. Western blotting and qRT-PCR results showed that silencing miR-19b-3p significantly increased PTEN, LC3, and Beclin1 expression while decreasing p-Akt, p-mTOR, and p62 expression. Furthermore, by constructing the fracture rats and administering hypoxia-treated BMSCs transfected with miR-19b-3p via tail vein injection, we found that silencing miR-19b-3p obviously increased the formation of trabecular and promoted the healing of the fractures. Immunohistochemistry analysis showed that silencing miR-19b-3p upregulated PTEN and Runx2 expression levels and suppressed p62 expression with statistical significance. In summary, these findings suggest that miR-19b-3p may regulate BMSCs’ autophagy and osteogenic differentiation under hypoxia via the PTEN/Akt/mTOR signaling pathway, thereby promoting fracture healing and providing a potential target for the treatment of fractures.
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JOURNAL OF PHARMACEUTICAL SCIENCES
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2026
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IF 3.9
Xinyi He,Xu Jiang,Huazhong Lin,Kexin Zhang,Xuewen Yu,Jiaxin Bi,Lu Zhang,Yingying Liang,Lijuan Chen,Mumin Shao
Breast malignant phyllodes tumor (MPT) is a fibroepithelial neoplasm characterized by high recurrence rates. Currently, no effective therapeutic agents are available, and surgery remains the mainstay of treatment for MPT. Niclosamide ethanolamine (NEN), an antiparasitic agent, has recently demonstrated broad-spectrum antitumor activity against various solid malignancies. This study aimed to evaluate the antitumor efficacy of NEN against MPT and elucidate the underlying molecular mechanisms. The effects of NEN on MPT cell proliferation and migration were assessed using CCK-8, wound healing, and Transwell migration assays. Ultrastructural alterations following NEN treatment were examined by transmission electron microscopy. Bioinformatics analyses, quantitative real-time PCR (qPCR), Western blotting, and immunofluorescence staining were employed to investigate the molecular mechanisms underlying NEN-mediated modulation of autophagy and lysosomal function. NEN significantly inhibited MPT cell proliferation and migration. Transmission electron microscopy revealed the accumulation of numerous autolysosomal structures in NEN-treated cells. Mechanistically, NEN suppressed mTOR phosphorylation, promoted nuclear translocation of transcription factor EB (TFEB), and induced lysosomal biogenesis. However, lysosomal function was compromised, as evidenced by elevated luminal pH, impaired cathepsin D maturation, and lysosomal membrane permeabilization, ultimately resulting in autophagic flux blockade at the degradation stage. Furthermore, lysosomal cathepsin leakage activated the mitochondrial apoptotic pathway, culminating in caspase-3-dependent apoptosis. NEN effectively kills MPT cells by inducing "lysosomal biogenesis–function uncoupling." This study is the first to reveal a novel anti-MPT mechanism that targets the mTOR-TFEB-lysosome axis and disrupts lysosomal homeostasis, providing a potential drug candidate for the treatment of MPT.
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Journal of Inflammation Research
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2026
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IF 4.6
Jianglong Chen,Yunfei Cui,Rujie Zhou,Yu Zhu,Meijia Chen,Jinhua Su,Jinhui Wang,Guang Li
Objective To explore the therapeutic effect and molecular mechanism of Arundina graminifolia (D.Don) Hochr (BYJ) on renal fibrosis in chronic kidney disease (CKD) mice.Methods Phytochemical profiles of the methanol extract BYJ were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS), while network pharmacology and molecular docking were employed to predict the core active components and therapeutic targets. For experimental validation, a CKD mouse model was established via adenine induction. Mice were randomly assigned to normal control, model, and three BYJ treatment groups (low-dose: 2 g/kg·d, middle-dose: 4 g/kg·d, and high-dose: 8 g/kg·d, crude drug equivalent). Assessments included renal function parameters, histopathological changes, inflammatory markers, and oxidative stress indicators. The associated molecular mechanisms were analyzed using immunohistochemistry staining and Western blot.Results In silico analysis identified five core targets—PIK3R1, AKT1, SRC, MTOR, and EGFR—and suggested esculetin as a key active component with strong binding affinity to these targets. Experimentally, BYJ administration significantly reduced in serum creatinine (SCr), blood urea nitrogen (BUN), and the kidney index, and ameliorated glomerular atrophy and tubular dilation. Furthermore, BYJ treatment downregulated pro-inflammatory factors (eg, IL-1β), elevated superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) content. The intervention suppressed the epithelial-mesenchymal transition (EMT) process, as evidenced by the upregulation of E-cadherin and downregulation of α-SMA expression. Mechanistic verification indicated that BYJ treatment was associated with attenuated the overactivated of TGF-β/PI3K-AKT/mTOR pathway in renal tissues.Conclusion The methanolic extract of BYJ effectively attenuates CKD progression in mice, which is associated with by modulated the overactivation of the TGF-β/PI3K-AKT/mTOR pathway, inhibited the EMT process, and ameliorated inflammatory response and oxidative stress. These findings provide a preliminary theoretical basis for the development of BYJ as a potential candidate agent for CKD treatment.
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MATERIALS & DESIGN
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2026
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IF 8.2
Yue Peng,Cuiman Tang,Mingcong Niu,Tianyi Xu,QingYu Meng,Xinran Li,Rongheng Ma,Huimin Yu
A traditional medicine-inspired strategy provides a logical framework for constructing carrier-free hybrids. • Precise structural modifications successfully circumvent the inherent bioaccessibility limitations of natural products. • The covalent integration of diverse functional modules enables synergistic therapeutic efficacy against arthritis. • The therapeutic action is closely associated with the modulation of protein kinase B and hypoxia-inducible factor signaling. Curcumin (Cur) possesses potent anti-inflammatory activity but faces clinical challenges due to poor aqueous dispersibility, insufficient membrane affinity, and low bioavailability. Borneol (Bor), a classic “envoy” component in Traditional Chinese Medicine (TCM), exhibits prominent membrane-penetrating properties. Inspired by the “monarch-envoy” compatibility theory, we rationally designed carrier-free hybrids by covalently conjugating Cur (“monarch”) with Bor (“envoy”). Systematic characterization confirmed the successful synthesis and controllable optimization of key properties, including enhanced dispersibility, improved cellular uptake, and favorable biocompatibility. Using rheumatoid arthritis (RA) as a disease model, we identified SCBMS as the optimal formulation owing to its superior dispersibility and uptake, which directly translated into the most potent anti-RA efficacy. The hybrids exerted synergistic multifunctional effects—including robust anti-inflammatory and antioxidant activities—effectively reducing the arthritis index and ameliorating synovial hyperplasia and joint destruction in vivo . Mechanistically, our results indicate a close correlation between the therapeutic effects and the downregulation of the AKT/mTOR/HIF-1α signaling pathway, supporting the involvement of this pathway in the observed anti-RA activity. This study provides a generalizable framework for developing functional hybrids guided by TCM principles and validates their translational potential. Download: Download high-res image (152KB) Download: Download full-size image
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
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IF 5.7
Jia Liu,Yangxian Chen,Mengyu Li,Guobao Chen,Junhui Yang,Ying Jiang,Xiao Zhang,Fang Li,Haibing Hua
Chronic atrophic gastritis (CAG) is a critical precancerous condition with limited therapeutic options to halt its progression toward gastric cancer. Targeting dysregulated metabolism and inflammation-driven transformation represents a promising yet underexplored strategy. Herein, through systematic screening of Jianwei Xiaoyan Granule (JWXYG)-derived compounds via molecular docking and surface plasmon resonance (SPR), we identified hederagenin as a potent and novel mechanistic target of rapamycin (mTOR) binder (Kd = 1.30 μM). In a rat CAG model, hederagenin administration resulted in marked histological and biochemical improvements. Histopathological evaluation revealed that hederagenin effectively restored gastric mucosal architecture, significantly attenuated characteristic glandular atrophy, and reduced the extent of intestinal metaplasia, a key precancerous lesion. Concurrently, serum analysis demonstrated that hederagenin treatment normalized critical biomarker levels, including a significant reduction in gastrin-17 (G-17) and the pro-inflammatory cytokine interleukin-6 (IL-6), alongside a notable increase in the levels of pepsinogen I (PG I) and pepsinogen II (PG II). Functionally, hederagenin exhibited potent anti-tumor properties in vitro by significantly suppressing the proliferation, migration, and invasion capabilities of premalignant gastric epithelial cells. Mechanistically, transcriptomic analyses revealed that hederagenin targeted cancer-associated metabolic reprogramming through the mTOR/hypoxia-inducible factor-1α (mTOR/HIF-1α) signaling axis. Experimental validation further confirmed that hederagenin significantly suppressed the mTOR/HIF-1α pathway. Additionally, it downregulated the expression of key rate-limiting glycolytic enzymes, including hexokinase II (HK II), pyruvate kinase M2 (PKM2), enolase 1 (ENO1), and lactate dehydrogenase A (LDHA), thereby attenuating glycolytic flux, a hallmark metabolic adaptation in precancerous lesions. Importantly, mTOR knockdown abolished hederagenin-mediated LDHA suppression and compromised its therapeutic efficacy, validating mTOR as an essential target. Our findings demonstrated that hederagenin could inhibit inflammation-cancer transformation in CAG via regulation of glycolysis through the mTOR/HIF-1α pathway, which provided new candidate compounds for regulating the transformation of CAG into cancer.
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Journal of Stroke & Cerebrovascular Diseases
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2026
·Vol. 35
·期 5
·108628
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IF 2.1
Zhihong Zhong,Shuhong Wang,Canxin Xu,Qingyun Liu,Xiao Chen,Dong Lin,Liuguan Bian
Background and purpose Intracerebral hemorrhage (ICH) is a devastating acute neurological condition with high mortality and disability. Induced pluripotent stem cell-derived neural progenitor cells (iPSC NPCs) have been shown to promote behavioral recovery by enhancing neural connectivity and providing trophic support. As the adenosine monophosphate-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) signaling pathway is a key regulator of autophagy in stroke, we investigated its role in the context of iPSC NPC transplantation for ICH. Materials and methods The therapeutic effects of iPSC NPC transplantation were evaluated in both in vivo and in vitro ICH models. We analyzed changes in the protein and mRNA expression, along with immunofluorescence, of key markers including glial fibrillary acidic protein (GFAP), AMPK, mTOR, sequestosome 1 (SQSTM1/ P62), and microtubule-associated protein 1 light chain 3 (LC3). Results Our findings demonstrate that iPSC NPCs secrete cytokines that mitigate brain injury and protect astrocytes from autophagy. Specifically, iPSC NPCs promoted astrocyte activation by inhibiting AMPK phosphorylation and promoting mTOR activation in both model systems. The anti-autophagic effect of iPSC NPCs on astrocytes was abolished by an mTOR inhibitor. Conversely, AMPK knockdown with siRNA promoted mTOR phosphorylation and suppressed autophagy in astrocytes. Conclusion This study identifies the interaction between AMPK and mTOR in astrocytes as a critical mechanism underlying the therapeutic benefits of iPSC-NPC transplantation, highlighting it as a promising target for ICH treatment.
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Pharmaceutics
·
2026
·Vol. 18
·期 7
·869
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IF 6.9
Jiangtao Zhou,Yuhui Ge,Ran Li,Zhuoyang Cheng,Jianping Gao,Bin Zheng
Background: Skin photoaging, primarily induced by chronic ultraviolet (UV) radiation exposure, is characterized by dryness, wrinkle formation, pigmentation abnormalities, and reduced skin elasticity, resulting from oxidative stress, inflammation, and degradation of the extracellular matrix. Codonopsis pilosula , a traditional food–medicine homologous plant, is recognized for its anti-aging properties. However, its lipophilic components (designated as CP-L) remain insufficiently explored. Methods: Herein, we developed a thermosensitive nanogel encapsulating CP-L-loaded transferosomes (CP-L nanogel) to enhance topical delivery and evaluated its effects in both a UV-induced photoaging mouse model and UVB-irradiated HaCaT keratinocytes. Results: In UV-induced mice, topical application of the nanogel markedly reduced skin wrinkling and epidermal hyperplasia, with epidermal thickness decreased by 83.2% compared to the model group ( p < 0.01), and restored skin elasticity and collagen deposition, as evidenced by a 35.5% increase in collagen area fraction ( p < 0.01). Correspondingly, in UVB-irradiated HaCaT cells, it significantly increased cell viability from 53.0 ± 9.6% to 89.4 ± 1.0% ( p < 0.01) and suppressed apoptosis from 30.1 ± 0.48% to 12.4 ± 0.66% ( p < 0.01). Furthermore, the CP-L nanogel consistently attenuated oxidative stress, with SOD, CAT, and GSH-Px activities increased by 73.1%, 188.1%, and 18.2%, respectively ( p < 0.01), and MDA levels reduced by 71.0% ( p < 0.01), while inflammatory responses were suppressed, as TNF-α, IL-1α, IL-1β, and IL-6 levels decreased by 28.3%, 22.6%, 12.8% and 31.9%, respectively ( p < 0.01). Mechanistically, transcriptomic and molecular analyses revealed that the nanogel potently inhibited the UV-induced activation of the FGFR/PI3K/AKT/mTOR/p70S6K signaling cascade at both transcriptional and protein levels, with the phosphorylation levels of FGFR, PI3K, AKT, mTOR, and p70S6K significantly reduced by 43.9%, 30.9%, 38.8%, 34.9%, and 57.3%, respectively ( p < 0.01). Molecular docking and dynamics simulations identified isofuranodienone and aromadendrene oxide-(2) as key constituents with high-affinity, stable binding to FGFR1 and AKT1. The cytoprotective effect of the nanogel was completely abolished by co-treatment with the FGFR inhibitor PD173074 , confirming functional reliance on this pathway. Enhanced cellular delivery of the formulation was directly demonstrated by flow cytometry, showing an approximately 1.8-fold increase in cellular uptake compared to the free drug ( p < 0.01). Conclusions: Collectively, these results demonstrated that the CP-L nanogel alleviated skin photoaging through a multi-faceted mechanism involving enhanced cellular delivery, potent antioxidant and anti-inflammatory activities, and specific inhibition of the FGFR/PI3K/AKT/mTOR signaling cascade, highlighting its potential as a multitargeted topical agent derived from an edible plant.
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Journal of Radiation Research and Applied Sciences
·
2026
·Vol. 19
·期 2
·102372
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IF 3.5
Qiuying Lin,Guanlun Zhou,Yingyu Yao,Hongxiu Jiang,Qiuhui Hong,Qingmin Wang,Wenzeng Chen,Guorong Han
Background Intrahepatic cholestasis of pregnancy (ICP) is linked to negative outcomes in pregnancy, potentially due to placental autophagy dysfunction. Yinchenhao decoction (YCHD) may improve ICP outcomes, the object of this study was to examine the impact of YCHD on autophagy in the placenta of ICP rats and elucidate the underlying mechanisms. Methods The ICP rat model was induced with 17α-ethinyl estradiol and treated with intragastric YCHD. An ICP HTR-8/SVneo cell model was created using taurocholic acid and treated with YCHD drug-containing serum. The decoction's impact on ICP was evaluated using hematoxylin-eosin staining and serum biochemical markers. Assessment of cell viability was conducted by employing the CCK-8 assay. Immunohistochemistry and Western blotting analyzed autophagy markers LC3I and LC3II in placental tissues. Key proteins and genes related to the mTOR pathway were studied via Western blotting and quantitative real-time PCR. An electron microscope was used to observe an autolysosome. Results The damage induced by TCA in HTR-8/SVneo cells was notably alleviated by YCHD, which resulted in an upregulation of mTOR mRNA expression, a counteraction of rapamycin's mTOR pathway inhibition, and a decrease in LC3 expression. It improved survival and birth weight in ICP rats, restored liver function, and reduced bile acid. Additionally, YCHD lessened liver and placenta damage and decreased placental thrombosis. It activated p-mTOR/mTOR and p-PI3K/PI3K in the ICP rat placenta while inhibiting LC3II/LC3I, indicating mTOR pathway activation and autophagy inhibition. Conclusion YCHD alleviated symptoms and pathological damage in ICP rats and counteracted the damage induced by TCA. Its therapeutic mechanism involved activating the mTOR signaling pathway, thereby inhibiting aberrant placental autophagy. These findings hold significant importance in enhancing the clinical utility of YCHD.
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