BRAIN RESEARCH BULLETIN
·
2018
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IF 3.44
Tianhang Wang,Jiling Cheng,Shuyu Wang,Xudong Wang,Hongquan Jiang,Yueqing Yang,Ying Wang,Chunting Zhang,Weiwei Liang,Honglin Feng
Amyotrophic lateral sclerosis (ALS) is a degenerative disease with a progressive loss of motor neurons in the central nervous system (CNS). However, there are unsolved problems with the therapies for this disease. α-Lipoic acid (LA) is a natural, universal antioxidant capable of scavenging hydroxyl radicals as well as regenerating a series of antioxidant enzymes that has been widely used in clinical settings. This study aimed to evaluate the antioxidant and neuroprotective effects of LA in ALS cell and Drosophila models with mutant G85R and G93A hSOD1 genes. The biological effects of LA and the protein levels of several antioxidant factors were examined, as were those of phospho-Akt and phospho-ERK. Furthermore, specific inhibitors of the PI3K/Akt and MEK/ERK signaling pathways were used to analyze their effects on LA-induced antioxidant expression in vivo and in vitro . Evidences showed that the mutant hSOD1 resulted in the increased oxidative stress, abnormal antioxidant signaling and pathological behaviors in motor performance and survival compared with non-mutant hSOD1 models, treatment with LA improved motor activity and survival in transgenic flies, prevented NSC34 cells from mutant hSOD1 or H 2 O 2 induced decreased antioxidant enzymes as well as increased ROS levels. In addition, LA regulated the expression levels of antioxidant proteins in a dose- and periodical time-dependent manner, which might be mediated by ERK/Akt pathway activation and independent from the mutant hSOD1 gene. Our observations suggest that LA exerts strong and positive antioxidant and neuroprotective effects through the activation of the ERK-Akt pathway in hSOD1 ALS models.
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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2024
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IF 3.1
Sun Hui,Wang ZiTong,Tu BingHua,Shao ZiChen,Li YiDan,Han Di,Jiang YinJie,Zhang Peng,Zhang WeiChang,Wu YunYan,Wu XiaoMing,Liu Chi-Ming
Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.
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Asian Journal of Pharmaceutical Sciences
·
2024
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IF 10.7
Hechen Wang,Xudan Shen,Xinlan Zhu,Su Zeng,Sheng Cai
Hepatocellular carcinoma (HCC) shows the highest morbidity among liver cancers and accounts for a major factor inducing cancer-associated mortality globally. It is characterized by genetic mutations in hepatocytes, leading to uncontrolled cell growth and proliferation. Treatment options for HCC include surgery, chemotherapy, and immunotherapy. But chemotherapeutics, which focus on single-targeted drug therapy, are still associated with certain limitations and may affect the treatment outcomes. Compared with chemotherapy drugs, natural products also show the anticancer effect of HCC and hypotoxicity, but overall low activity of natural products limits their further application. MiRNAs can modulate post-transcriptional functions of target genes. An increasing body of evidence has demonstrated that miRNAs are the key regulators in HCC by targeting different molecules in different signaling pathways. However, miRNAs are fragile and liable to catabolism by RNases in serum and other body fluids and small molecules separated from natural products may have limited bio-availability. According to this background, a chitosan based, targeted sustained-release nanoparticle delivery miR-128-3p agomir (NA-miR-128-3p) was developed in this work. This nanoparticle was prepared by pentasodium tripolyphosphate (TPP), chitosan hydrochloride, and miR-128-3p agomir with target aptamer which was loaded into the chitosan nanoparticle by self-assembly. It can intervene in HCC progress by affecting AKT1 expression. Based on this, a novel, efficient, long-acting, multi-mechanism, low-dosage combination drug delivery strategy was proposed in this work and showed a prominent anti-tumor effect. NA-miR-128-3p combined with natural product Oroxin B significantly affected HCC progression by the interference with VEGF and PI3K-AKT pathways, better than using NA-miR-128-3p and Oroxin B alone. Taken together, this nanoparticle and combinative administration compensate for the shortcomings of the fragile RNA drugs and the low activity of natural products, with high prospects in HCC treatment.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Lianghui Zhan,Qian Liu,Changjun Zhang,Jinbao Pu,Ligang Ren
Ethnopharmacological relevance Hedysarum polybotrys Hand.-Mazz. (Hongqi, HQ) is a prized Qi-tonifying herb in Traditional Chinese Medicine (TCM), historically employed to enhance the body's resistance and modulate immune function. While its anti-tumor properties are recognized, the specific immunomodulatory mechanisms by which HQ empowers Natural Killer (NK) cells to combat prostate cancer (PCa) remain under-explored. Aim of the study To systematically elucidate the material basis and molecular mechanisms through which the aqueous extract of HQ enhances NK cell-mediated cytotoxicity against PCa cells, utilizing an integrated approach of multi-omics and experimental validation. Methods The chemical profile of HQ aqueous extract was characterized using UHPLC-MS/MS untargeted metabolomics. Network pharmacology and transcriptomic analyses (RNA-seq) were integrated to predict core targets and signaling pathways. Specific interactions were simulated via molecular docking. Validations were performed using an in vitro co-culture model of NK-92 and PC-3 cells. Assays included CCK-8, LDH release, flow cytometry (apoptosis, surface markers), ELISA (cytokines), and Western blot. Results A total of 69 compounds were identified in HQ, with Genistein and Isoliquiritigenin highlighted as key active constituents. HQ treatment significantly enhanced NK-92 cell cytotoxicity against PC-3 cells, evidenced by increased LDH release and PC-3 apoptosis. Mechanistically, HQ upregulated the expression of cytolytic effectors (Perforin, Granzyme B) and pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17A). Crucially, HQ treatment achieved a "dual-effect": it reactivated the PI3K/AKT signaling pathway in NK cells (confirmed by increased p-PI3K and p-AKT levels) while concurrently downregulating the immunosuppressive PD-1/PD-L1 checkpoint axis. Conclusion This study demonstrates that HQ potentiates NK cell anti-tumor immunity against prostate cancer through a dual mechanism involving PI3K/AKT pathway activation and PD-1/PD-L1 axis inhibition. These findings provide modern pharmacological evidence supporting the traditional use of HQ for enhancing immune surveillance in cancer therapy.
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Foods
·
2026
·Vol. 15
·期 9
·1535
·
IF 6
Fangling Feng,Shuo Zhang,Chencen Lai,Zhiyu Chen,Jian Zhang,Jiuming He,Min Zhang,Pengjiao Wang,Xiuli Gao
Depression is a common mental disorder that substantially impairs patients’ daily life and work. To identify natural and safe preventive options, we investigated the preventive effect and underlying mechanism of theGanoderma lucidumandRosa roxburghiiTratt formula (GLRRTF) on depression. A total of 72 chemical components in GLRRTF were identified by UHPLC-ESI-Q-Exactive Plus Orbitrap-MS Analysis. GLRRTF (containing 400 mg/kg ofG. lucidumextract and 800 mg/kg ofR. roxburghiiextract per day), administered as a 1-week preventive intervention followed by 4 weeks of co-administration with chronic unpredictable mild stress, prevented the development of depression-like behaviors in male C57BL/6J mice and reduced neuronal damage in the hippocampus. Airflow-assisted desorption electrospray ionization mass spectrometry imaging and enzyme-linked immunosorbent assays showed that GLRRTF corrected abnormalities in neurotransmitter levels. The 16S rRNA sequencing indicated that GLRRTF restored dysbiosis of the gut microbiota. Metabolomic profiling revealed that GLRRTF increased the level of tryptophan and promoted tryptophan metabolism towards the 5-HT and indole pathways in feces and the brain. Western blot demonstrated that GLRRTF increased 5-HT production from tryptophan in the brain by regulating tryptophan hydroxylase 2 and DOPA decarboxylase. GLRRTF activated the PI3K/AKT pathway by regulating brain-derived neurotrophic factor and its receptor tropomyosin receptor kinase B. This research provides a comprehensive mechanistic understanding of GLRRTF’s preventive effect against depression, highlighting its potential as a novel, safe, and preventive functional food formulation.
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Yu Dun,Jinxi Xie,Jian Zhou,Hanbing Hu,Fuli Liu,Yiru Shao,Jie Shen
CD34/CD45-DSCs alleviate phosgene-induced acute lung injury (P-ALI) in rats. • CD34 + CD45 + cells reside in bone marrow, peripheral blood, and BALF with dynamic changes post-injury. • CD34/CD45-DSCs exhibit MSC-like properties with osteogenic, adipogenic, and chondrogenic potential in vitro. • CD34/CD45-DSCs showed prolonged lung retention perivascular engraftment, and PVSC-like phenotype acquisition without exacerbating fibrosis. • CD34/CD45-DSCs restore pulmonary vascular barrier via VEGF-PI3K/AKT/eNOS signaling pathway. Phosgene inhalation causes acute lung injury (ALI) with high mortality and no effective antidote, and stem cell therapy is limited by poor cell survival and low engraftment efficiency. Here, we identified a rare endogenous CD34 + CD45 + cell fraction that reside in bone marrow, peripheral blood, and bronchoalveolar lavage fluid (∼1% baseline), exhibits a “decrease-then-recovery” dynamic after phosgene injury, and displays MSC-like properties with trilineage (osteogenic, adipogenic, and chondrogenic) potential in vitro. Intravenous administration of expanded CD34 + CD45 + -derived stromal cells (CD34/CD45-DSCs) significantly alleviated pulmonary vascular leakage and inflammatory in a rat model of phosgene-induced ALI (P-ALI). In vivo bioluminescence imaging further revealed that CD34/CD45-DSCs exhibited prolonged pulmonary retention compared with BMSCs (11.3 days vs. 48 h), proliferated, engrafted around the pulmonary vasculature, and acquired a perivascular stromal cell (PVSC)-like phenotype expressing late-stage mesenchymal progenitor, pericyte, and fibroblast markers. In a bleomycin-induced pulmonary fibrosis model, CD34/CD45-DSCs did not exacerbate fibrotic changes at day 28. Mechanistically, VEGF knockdown or neutralization abolished the barrier-protective effect, which was rescued by an AKT agonist and blocked by an inhibitor. Moreover, CD34/CD45-DSCs upregulated tight junction proteins ZO-1 and Occludin in injured endothelial cells via VEGF-PI3K/AKT/eNOS signaling. Collectively, our study defines the origin, spatiotemporal dynamics, perivasucular engraftment, PVSC-like fate acquisition, and VEGF-PI3K/AKT/eNOS-dependent mechanism of CD34/CD45-DSCs, supporting their potential as a relatively safe, long-engrafting, and mechanistically transparent cell-based strategy for ALI.
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Food & Function
·
2019
·Vol. 10
·期 9
·6009-6019
·
IF 3.241
Yun Yu,Xiu-Yuan Lang,Xi-Xi Li,Run-Ze Gu,Qing-Shan Liu,Rongfeng Lan,Xiao-Yan Qin
The major bioactive ingredient THSG of Polygonum multiflorum is well established for its anti-oxidation, anti-aging and anti-inflammation properties. Increasing evidence supports the capacity of THSG to ameliorate the biochemistry of neurotrophins and their downstream signaling axis in mouse models to attenuate neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this study, the neuroprotective effects of THSG were studied in vitro and in vivo. In cultured mesencephalic dopamine neurons and SH-SY5Y cell line, it was found that THSG protected the integrity of the cell body and neurite branching from MPP+-induced toxicity by restoring the expression of FGF2 and BDNF and their downstream signaling pathways to inhibit apoptosis and promote cell survival. The inhibition of Akt signaling by LY294002 or TrkB activity by K252a eliminated the neuroprotective effects of THSG. In the MPTP-induced mouse models of Parkinson's disease, THSG ameliorated the animal behaviors against MPTP-induced neurotoxicity, which was demonstrated by the pole test and the tail suspension test. Biochemical and immunohistochemical analysis verified the THSG-mediated restoration of the FGF2-Akt and BDNF-TrkB signaling axis in the substantia nigra and corpus striatum and the recovery of dopaminergic neurons. These results establish the neuroprotective effects of THSG in vitro and in vivo and unravel the underlying mechanism against toxin-induced neural atrophy, providing a new avenue for the use and pharmacological research of edible medicine for anti-neurodegenerative diseases.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Wenjie Jiang,Yanna Cheng,Na Zhao,Lian Li,Yikang Shi,Aizhen Zong,Fengshan Wang
Previous studies demonstrated that SIP-SII, a sulfated derivative of SIP that is isolated from the ink of Sepiella maindroni , showed significant inhibition of tumor growth and metastasis. In this study, the effects of SIP-SII on the migration, invasion and molecular mechanism in ovarian cancer cell line, SKOV-3 cells, were investigated. The flow cytometry, confocal microscope observation, western blot and RT-PCR results indicated that SIP-SII located on cell membrane and inhibited the expression and activation of epidermal growth factor receptor (EGFR). Moreover, the binding capacity of SIP-SII with EGFR was confirmed by surface plasmon resonance (SPR) analysis and co-localization of EGFR and SIP-SII. Accordingly, SIP-SII was proved to attenuate the EGF-induced EGFR phosphorylation and migration by western blot and wound healing assay, respectively. Additionally, SIP-SII inhibited p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells significantly. What is more, SIP-SII showed amplified inhibitory activity on migration, invasion, and MMP-2 expression in combination with p38-specific inhibitor, PI3K-specific inhibitor or mTOR-specific inhibitor in SKOV-3 cells. Therefore, the mechanism that SIP-SII suppressed EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways to inhibit migration and invasion of SKOV-3 cells was demonstrated. These findings suggested that SIP-SII might be used as a potential inhibitor against tumor metastasis.
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FREE RADICAL BIOLOGY AND MEDICINE
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2026
·
IF 8
Pingping Zhao,Binjing Pan,Xiaoyu Lv,Lihua Ma,Jingfang Liu
Non-enzymatic glycation is an important post-translational modification of proteins, ultimately forming advanced glycation end products (AGEs). In a high-glucose environment, the glycation degree of transferrin (Tf) increases, leading to elevated levels of AGE-modified transferrin (AGE-Tf), which reduces the binding capacity of Tf for iron. However, the role of AGE-Tf-associated iron dysregulation in diabetic nephropathy remains unclear. In this study, human podocytes were treated in vitro with AGE-Tf prepared by incubating Tf with 5.6 or 33.3 mM glucose (hereafter termed 5.6-Glc-AGE-Tf and 33.3-Glc-AGE-Tf, respectively) in combination with iron. Additionally, plasmids encoding Tf with mutations at three glycation sites (K206 A/K296 A/K534A; MT-Tf) or wild-type Tf (WT-Tf) were packaged into adeno-associated viral vectors and administered to diabetic rats. Compared with podocytes treated with 5.6-Glc-AGE-Tf, podocytes treated with 33.3-Glc-AGE-Tf exhibited reduced viability and greater oxidative stress. After ferric-citrate addition, intracellular Fe 2+ was also higher in the 33.3-Glc-AGE-Tf group than in the 5.6-Glc-AGE-Tf group. The 33.3-Glc-AGE-Tf group showed decreased GPX4, Nrf-2, and SLC7A11 expression and increased ACSL4 expression. In vivo, diabetic rats receiving an empty vector (DM-empty-vector) or a wild-type Tf vector (DM-WT-Tf-vector) exhibited higher renal AGE-Tf, Fe 2+ , and oxidative stress levels; lower nephrin and podocin expression; ferroptosis-related alterations; mesangial cell proliferation and matrix expansion; increased interstitial collagen deposition; and focal nodular sclerosis. These alterations were attenuated in diabetic rats receiving the glycation-resistant mutant Tf vector (DM-MT-Tf-vector). Deferoxamine (DFO) or TBHQ (an Nrf-2 activator) ameliorated oxidative stress, iron dysregulation, and ferroptosis in AGE-Tf-treated podocytes and in the kidneys of diabetic rats receiving the WT-Tf vector, whereas LY294002 (a PI3K/AKT pathway inhibitor) primarily alleviated oxidative stress. These findings identify AGE-Tf-associated iron dysregulation as a potential therapeutic target in diabetic kidney disease.
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TISSUE & CELL
·
2022
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IF 2.586
Jie Pan,Xiaoping Cai,Xiao Zheng,Xiaoyu Zhu,Jihong Feng,Xiaoqiu Wang
Luteolin inhibits tumorigenesis of non-small cell lung cancer (NSCLC), but its mechanism still needs to be clarified. We hereby explored the effects of luteolin in vascular endothelial cells of NSCLC (NSCLC-VECs). After extraction and identification of NSCLC-VECs, cells were treated with luteolin and transfected. The viability, migration, angiogenesis and invasion of the cells were measured. The levels of miR-133a-3p, purine rich element binding protein B (PURB), vascular endothelial growth factor (VEGF), phosphatidylinositol 3-kinase (PI3K), Akt, mitogen-activated protein kinases (MAPK), matrix metalloproteinase (MMP)-2/-9 were determined. The interaction relationship of miR-133a-3p and PURB was identified. Luteolin inhibited the viability, migration, angiogenesis and invasion of NSCLC-VECs yet up-regulated miR-133a-3p level, while miR-133a-3p inhibitor counteracted the repressive effect of luteolin on the viability, migration, angiogenesis, and invasion in NSCLC-VECs. Luteolin inhibited the expressions of migration- and invasion-associated proteins (VEGF, MMP-2 and MMP-9), PI3K/Akt and MAPK signaling pathways-related factors, while miR-133a-3p inhibitor reversed the inhibitory effect of Luteolin on NSCLC-VECs. Luteolin decreased the level of PURB, which was targeted by miR-133a-3p. ShPURB promoted miR-133a-3p level in NSCLC-VECs, while reversing the promoting effects of miR-133a-3p inhibitor on the migration, invasion, and levels of migration- and invasion-associated proteins, PI3K/Akt and MAPK pathways-associated factors in NSCLC-VECs. Collectively speaking, luteolin inhibits the migration and invasion of NSCLC-VECs via miR-133a-3p/PURB- mediated MAPK and PI3K/Akt pathways.
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Antioxidants
·
2025
·Vol. 14
·期 10
·1206
·
IF 6.6
Haoyu Liu,Zhen Yang,Qian Chen,Hongjuan Zhang,Yu Liu,Di Wu,Dan Shao,Shengyi Wang,Baocheng Hao
Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus , Romboutsia , and Enterobacter . Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Jiabao Lu,Jianchao Li,Peiyi Yin,Nana Huang,Rong Sun
BAP improved glycolipid metabolism, insulin resistance, and hepatic steatosis in MAFLD mice. • Human iPSC-derived liver organoids were used to model MAFLD and evaluate BAP. • Network pharmacology and multi-model validation revealed the mechanism of BAP. Ethnopharmacological relevance Bupleuri Radix (Chaihu) and Aurantii Fructus Immaturus (Zhishi) is a classic herb pair from Si-Ni-San. In traditional Chinese medicine theory, they regulate liver-spleen qi movement through a “one ascending, one descending” dynamic, and are used for syndromes of liver depression and spleen deficiency with phlegm-stasis intermingling. This syndrome pattern closely mirrors the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the mechanisms underlying the anti-MAFLD effect of this herb pair remain unclear. Aim of the study To determine the effects and molecular mechanisms of the Bupleuri Radix- Aurantii Fructus Immaturus pair (BAP) in alleviating MAFLD. Materials and methods The quality of the BAP preparation used in this study was partially assessed by high-performance liquid chromatography (HPLC). Potential mechanisms were predicted via network pharmacology and functional enrichment analysis, and experimentally explored using high-fat high-sucrose diet mice, FFA-induced AML12 hepatocytes and human induced pluripotent stem cell (iPSC)-derived liver organoids. The PI3K/Akt-GSK3β/FoxO1 signaling pathway was further examined by LY294002 rescue assay. Results BAP ameliorated MAFLD-related hepatic phenotypes both in vivo and in vitro. Four representative quality control markers, namely synephrine, naringin, saikosaponin A, and saikosaponin D, were identified using validated reference standard methods. Network pharmacological analysis predicted that AKT1, GSK3B, and FOXO1 might be central targets, and the PI3K-Akt signalling pathway was identified as a potential pathway associated with the anti-MAFLD effects of BAP. GO and KEGG enrichment analyses revealed that the overlapping targets were significantly enriched in insulin signalling, lipid metabolism, and FoxO signalling pathways. In vivo, BAP treatment significantly reduced body weight gain, improved serum lipid profiles and liver function, alleviated insulin resistance, and attenuated hepatic steatosis and inflammation in HFSW-fed mice. Energy metabolism monitoring indicated that BAP markedly enhanced oxygen consumption and carbon dioxide production throughout the 24-hour light-dark cycle. In human iPSC-derived liver organoids, BAP reduced FFA-induced hepatocyte injury, lipid accumulation, and oxidative stress, and partially normalized the aberrant expression of genes involved in lipogenesis (SREBF1, FASN, SCD1), fatty acid oxidation (PPARA, CPT1A), and gluconeogenesis (G6PC). Western blot analysis demonstrated that BAP significantly upregulated PI3K expression and the phosphorylation levels of Akt (Ser473), GSK-3β (Ser9), and FoxO1 (Ser256), while downregulating p-GS (Ser641) in mouse livers, liver organoids, and AML12 cells. Moreover, co-treatment with the PI3K inhibitor LY294002 partially counteracted the beneficial effects of BAP on these proteins and counteracted the improvements in glycolipid metabolism, suggesting that the anti-MAFLD effects of BAP are associated with modulation of the PI3K/Akt pathway. Conclusions With BAP as the research subject, this study conducts cross-validation across a multi-model system including whole-animal models, hepatocytes and human liver organoids, and suggests that BAP ameliorates glucolipid metabolic disorders and slows MAFLD progression, effects that are closely associated with modulation of the PI3K/Akt-GSK3β/FoxO1 signaling pathway. These findings provide novel compatibility insights and experimental evidence for traditional Chinese medicine-based intervention of MAFLD. Download: Download high-res image (291KB) Download: Download full-size image
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危险品化学品经营许可证（带存储）