BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2020
·
IF 1.863
Yuanguo Xiong,Hao Lu,Hanlin Xu
Hepatic fibrosis (HF) is a common disease, with currently no available treatment. Galangin, a natural flavonoid extracted from Alpinia officinaruim Hance, has multiple effects demonstrated in previous studies. The aim of the present study was to explore the anti-fibrogenic effect of galangin in vitro, and research its potential molecular mechanisms. LX-2 cells were chosen as an in vitro HF model, and were treated with galangin in different concentrations. Cell viability was analyzed using Cell Counting Kit-8 (CCK-8) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis was measured using flow cytometry, and the anti-fibrogenic effect of galangin was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunofluorescence, and western blotting. The results show that the proliferation of LX-2 cells was efficiently inhibited by galangin, and apoptosis was induced in a dose-dependent manner. Both the mRNA and protein expression of α-SMA and collagen I were markedly downregulated. Galangin also inhibited the PI3K/Akt and Wnt/β-catenin signaling pathways and increased the Bax/Bcl-2 ratio. The results of this study suggest that galangin has an anti-fibrogenic effect and may represent a promising agent in the treatment of hepatic fibrosis.
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高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Tian-tian Wang,Meng-yuan Zhou,Xue-na Gong,Yan Huang,Fei-long Li,Sheng-long Gu,Man-yu Zhang,Ling-ling Li,Ze-shan Xu,Rong Li,Li Cai
Eupalinolide B (EB), a primary bioactive compound isolated from Eupatorium lindleyanum DC ., has exhibited various pharmacological properties, such as antitumor, anti-inflammatory, and notably, neuroprotective effects in neurodegenerative diseases. However, the in-depth studies on the antidepressant potential of EB and its underlying mechanisms are still lacking. Herein, we investigated the therapeutic effects of EB on corticosterone (CORT)-induced neurotoxicity in PC12 cells and its antidepressant-like effects in rats subjected to chronic unpredictable mild stress (CUMS). In particular, we focused on the molecular mechanisms related to modulating the GSK-3β/β-catenin pathway. Our findings revealed that EB promoted cell proliferation while decreasing apoptosis and oxidative stress in CORT-induced PC12 cells. In vivo, EB alleviated the depressive-like behaviors in CUMS rats, as assayed by the sucrose preference test, open field test, and forced swim test. Additionally, EB attenuated the hippocampal pathological damage and increased Ki67- and doublecortin-positive cell numbers in hippocampal dentate gyrus, thus restoring hippocampal neurogenesis in CUMS rats. The binding of EB to GSK-3β was confirmed using molecular docking and cellular thermal shift assays. Overexpression of GSK-3β diminished the therapeutic effects of EB on CORT-induced PC12 cells, further indicating that GSK-3β is the target of EB. Mechanistically, EB hindered GSK-3β activity and thus activated β-catenin signaling in both CORT-induced PC12 cells and CUMS rat hippocampus, as demonstrated by increased p-GSK-3β (Ser9), reduced p-β-catenin, and elevated β-catenin expression. Collectively, this study offers new insights into the antidepressant mechanisms of EB, highlighting its potential as a candidate for depression treatment.
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Animal Nutrition
·
2025
·
IF 7.5
Li Dong,Yangshu Zhou,Mengxuan Wang,Qingqing Yuan,Guangzhi Qiu,Jun Liu,Hongrong Wang,Aimin Wu,Lihuai Yu,Daiwen Chen
This study aims to elucidate intestinal injury from the perspective of intestinal epithelial cell homeostasis and to explore the modulatory roles of terpine-4-ol (a major bioactive component of tea tree oil). Forty 28-day-old piglets (7.82 ± 0.43 kg) were randomly divided into 5 groups with 8 pigs per group. Piglets in the control (CON) and lipopolysaccharide (LPS) groups were fed a basal diet, while those in the remaining 3 groups were fed the basal diet supplemented with 30 (LTP), 60 (MTP), or 90 mg/kg terpine-4-ol (HTP), respectively. Piglets in the LPS and terpine-4-ol supplementation groups were intraperitoneally injected with 100 μg/kg BW of LPS at the end of the 21-day growth period. Six hours after injection, 6 piglets from each group were randomly selected and slaughtered to detect intestinal cell homeostasis. The results showed that the average daily weight gain (ADG) and average daily feed intake (ADFI) of piglets in MTP and HTP groups were higher than those in the CON group ( P < 0.05), whereas the feed conversion ratio (FCR) of piglets in LTP group were lower as compared to the CON group ( P < 0.05). Terpine-4-ol supplementation also decreased the diarrhea rate of piglets. Lipopolysaccharide challenge decreased the villus length and the ratio of villus length to crypt depth (V/C) in the jejunum ( P < 0.05), decreased the V/C ratio and increased the crypt depth in the ileum ( P < 0.05). In contrast, terpine-4-ol supplementation led to increased villus length and V/C ratio in the jejunum, raised the V/C ratio in the HTP group, and decreased crypt depth in the LTP and MTP groups in the ileum ( P < 0.05). Lipopolysaccharide reduced the number of Ki67 + cells and increased the number of caspase 3 + cells ( P < 0.05) in both the jejunum and ileum, whereas terpine-4-ol increased the number of Ki67 + cells in the crypts of the jejunum and ileum, while decreasing the number of caspase 3 + cells of the the ileum and in the jejunum of MTP and HTP groups ( P < 0.05). Lipopolysaccharide down-regulated the expression of the intestinal stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) ( P < 0.05, execpt for Lgr5 gene in the jejunum), while terpine-4-ol supplementation alleviated the effect. Lipopolysaccharide decreased the number of goblet cells and mucin 2 (Muc2) secretion ( P < 0.05), whereas the number of goblet cells and Muc2 secretion in the small intestine of MTP group was increased ( P < 0.05). In addition, LPS injection led to a reduction in the expression of endocrine cell marker chromogranin A and absorption cell marker villin ( P < 0.05). Conversely, terpine-4-ol increased the abundance of endocrine cells and absorption cells in the small intestine ( P <0.05). Moreover, LPS inhibited the expression of genes and proteins of wingless-type MMTV integration site family (Wnt)/β-catenin signaling pathway ( P < 0.05), whereas terpine-4-ol reversed this effect. In conclusion, terpine-4-ol supplementation improved growth performance, decreased diarrhea in piglets and alleviated the damage to the intestinal epithelial cell homeostasis under LPS challenge, probably via Wnt/β-catenin signaling activation. A dose of 60 mg terpine-4-ol per kilogram diet was recommended based on the present study.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Liting Zhu,Linjie Mu,Xiaoqiu Ni,Feng Wang,Xinyi Peng,Yujiu Gao,Tingting Wei,Congcong Zeng,Yongheng Bai,Fangyan Wang,Zhengzhong Yuan,Jinguo Cheng
Ethnopharmacological relevance Xin-Zi-Sheng-Wan Decoction (XZSWD), a formulation rooted in the classic Zi-Sheng Pill first recorded in the Qing-dynasty compendium “ Golden Mirror of Medicine ,” is traditionally employed to resolve turbid pathogenic stagnation and restore metabolic equilibrium. Modern ethnopharmacological studies reveal a marked uric acid–lowering effect, although its precise molecular mechanisms have yet to be fully clarified. Aim of the study This study aimed to evaluate the therapeutic efficacy of XZSWD in hyperuricemia (HUA)-induced kidney injury and to elucidate its molecular mechanisms. Methods UPLC-QTOF/MS was used to identify compounds in XZSWD medicated serum. A HUA mouse model was induced by potassium oxonate and hypoxanthine to evaluate the therapeutic effects of XZSWD on renal injury. RNA-Seq, qRT-PCR, Western blot, immunofluorescence, and flow cytometry were applied to investigate immune infiltration and key signaling pathways. A THP-1/HK-2 co-culture system combined with SPP1 overexpression and knockdown was used to explore the molecular mechanisms. Results 99 compounds were identified in XZSWDS. XZSWD improved renal function, reduced serum uric acid levels, and downregulated macrophage-related inflammatory genes while modulating mixed M1/M2 polarization. XZSWD also inhibited the SPP1-CD44 axis and downstream SRC/FAK/β-Catenin signaling to reduce renal extracellular matrix (ECM) deposition. In vitro, SPP1 was identified as a critical target mediating these effects. Conclusions XZSWD alleviates HUA-induced renal injury by suppressing macrophage-mediated inflammation via regulation of the SPP1–CD44 axis and SRC/FAK/β-Catenin signaling, highlighting its therapeutic potential for HUA-related renal dysfunction.
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BIOMATERIALS
·
2025
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IF 12.9
Xinrong Zou,Xinyao Fan,Ping Xu,Xiufeng Yu,Chan Luo,Zhuxi Kang,Xin Shen,Jiaoni Zheng,Jisheng Wang,Baicheng He,Zeng Tu,Xiaoming Fu,Yongbo Peng
Diabetes mellitus (DM) aggravates periodontitis due to disordered glucose metabolism, leading to accelerated bone destruction and increasing dental plaque reproduction to induce local inflammation. The hyperglycemic state of DM leads to reactive oxygen species (ROS) overproduction that inhibits osteogenic differentiation in periodontal. These make a great challenge for the treatment of diabetic periodontitis. ROS-scavenging materials with additional anti-inflammation and anti-bacterial properties are highly sought after for the treatment of diabetic periodontitis. Herein, we have prepared the selenium-albumin corona rinse (H@Se NPs) through the albumin/nano-Se assembly strategy. H@Se NPs have better anti-inflammation via promoting the polarization of macrophages from the M1 to M2 phenotype and anti-bacterial effects than the commercially available selenium nanoparticles (Se NPs). Additionally, H@Se NPs can scavenge ROS to modulate the periodontal osteogenic microenvironment, a mechanism that involves regulating thioredoxin reductase 1 (TrxR1) synthesis and activating the TrxR1/ROS/β-catenin cascade. Furthermore, studies conducted in vivo have verified that H@Se NPs can suppress the formation of subgingival microbial colonies while enhancing osteogenic differentiation in diabetic pathological environments and improving periodontal bone regeneration via ROS scavenging. Collectively, these findings unveil new therapeutic paradigms for the clinical management of diabetic periodontitis.
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高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2024
·Vol. 479
·期 7
·1747-1766
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IF 3.5
Wang Qun,Lu Weijun,Lu Li,Wu Ruopu,Wu Dongde
Receptor interacting protein serine/threonine kinase 4 (RIPK4) is widely involved in human cancer development. Nevertheless, its role in colon cancer (COAD) has not been elucidated till now. Our research aimed at exploring the function and underlying molecular mechanism of RIPK4 in COAD progression. Through bioinformatic analyses and RT-qPCR, RIPK4 was discovered to be increased in COAD cells and tissues, and its high level predicted poor prognosis. Loss-of-function assays revealed that RIPK4 silencing suppressed COAD cell growth, induced cell cycle arrest, and enhanced cell apoptosis. In vivo experiments also proved that tumor growth was inhibited by silencing of RIPK4. Luciferase reporter assay validated that RIPK4 was targeted and negatively regulated by miR-575. Western blotting demonstrated that Wnt3a, phosphorylated (p)-GSK-3β, and cytoplasmic and nuclear β-catenin protein levels, β-catenin nuclear translocation, and Cyclin D1, CDK4, Cyclin E, and c-Myc protein levels were reduced by RIPK4 knockdown, which however was reversed by treatment with LiCl, the Wnt/β-catenin pathway activator. LiCl also offset the influence of RIPK4 knockdown on COAD cell growth, cell cycle process, and apoptosis. Finally, RIPK4 downregulation reduced RUNX1 level, which was upregulated in COAD and its high level predicted poor prognosis. RIPK4 is positively associated with RUNX1 in COAD. Overexpressing RUNX1 antagonized the suppression of RIPK4 knockdown on RUNX1, Wnt3a, p-GSK-3β, cytoplasmic β-catenin, nuclear β-catenin, Cyclin D1, CDK4, Cyclin E, and c-Myc levels. Collectively, miR-575/RIPK4 axis repressed COAD progression via inactivating the Wnt/β-catenin pathway through downregulating RUNX1.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-26
·
IF 12.6
Zhao Feng,Gong Liming,Wang Ping,Chen Dong,Cao Shijie,Yang Feifei,Tang Manqing,Meng Yuanyuan,Wang Yuming,Miao Lin,Li Yunfei,Huang Wei
In the absence of tumor antigen specificity, direct chemokine administration carries the risk of significant “on-target, off-tumor” toxicities, highlighting the need for small-molecule approaches with reduced immunogenicity. This study investigates the synergistic potential of norcantharidin (NCTD) and lomitapide (lomi) in selectively restoring CCL4 expression by deactivating the tumor intrinsic β-catenin pathway. Due to its similar lipophilicity to lomi and potential to suppress β-catenin, NCTD prodrug (C12) was selected to be co-encapsulated with lomi in a nanoparticle-mediated co-delivery system (NP“C12 + lomi”). The NP“C12 + lomi” formulation exhibited a high encapsulation rate, uniform particle size, and suitability for therapeutic use. It effectively inhibited the proliferation of 4T1 cells and restored CCL4 expression. In both primary breast tumor and surgically resected tumor mouse models, NP“C12 + lomi” significantly increased the proportion of CD8 + cells in primary tumors, blood, and lung metastases, approximately doubling their presence. This led to a prolongation of median survival in mice to 59 days. Furthermore, when combined with an immune checkpoint inhibitor, NP“C12 + lomi” substantially inhibited tumor growth and lung metastasis without affecting body weight or causing major tissue or organ damage. This was attributed to the controlled dissociation of the nanoparticle and the subsequent modulation of C12 and lomi, which mitigated CCL4-related toxicity. This study provides valuable insights into the safe production of chemokines using a small-molecule pair through a nanosystem and presents a robust chemo-immunological cascade therapy strategy, demonstrating significant efficacy against malignant metastatic tumors. Graphical abstract
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BMC Complementary Medicine and Therapies
·
2021
·Vol. 21
·期 1
·1-12
·
IF 0
Bian Wei,Xiao Shunqiang,Yang Lei,Chen Jun,Deng Shifang
Background Quercetin and H19 can promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, whether quercetin regulates H19 expression to promote osteogenic differentiation of BMSCs is unclear.Methods BMSC proliferation, matrix mineralization, and alkaline phosphatase (ALP) activity were assessed using the Cell Counting Kit-8, ALP assay kit, and alizarin red staining kit, respectively. Expression of H19, miR-625-5p, BMP-2, osteocalcin, and RUNX2 were measured by qRT-PCR; β-catenin protein level was measured by western blotting.Results Quercetin promoted BMSC proliferation, enhanced ALP activity, and upregulated the expression of BMP-2, osteocalcin, and RUNX2 mRNAs, suggesting that it promoted osteogenic differentiation of BMSCs. Moreover, quercetin increased H19 expression, while the effect of quercetin on BMSCs was reversed by silencing H19 expression. Additionally, miR-625-5p, interacted with H19, was downregulated during quercetin-induced BMSC osteogenic differentiation, which negatively correlated with H19 expression. Silencing miR-625-5p expression promoted BMSC proliferation and osteogenic differentiation, whereas miR-625-5p overexpression weakened the effect of quercetin on BMSCs. Finally, quercetin treatment or downregulation of miR-625-5p expression increased β-catenin protein level in BMSCs. Upregulation or downregulation of miR-625-5p or H19 expression, respectively, inhibited β-catenin protein level in quercetin treated-BMSCs.Conclusion H19 promotes, while miR-625-5p inhibits BMSC osteogenic differentiation. Quercetin activates the Wnt/β-catenin pathway and promotes BMSC osteogenic differentiation via the H19/miR-625-5p axis.
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Cancer Cell International
·
2021
·Vol. 21
·期 1
·1-14
·
IF 5.722
Li Chunyang,Yang Shuangqing,Ma Huaqing,Ruan Mengjia,Fang Luyan,Cheng Jing
Background Cervical cancer is a type of the most common gynecology tumor in women of the whole world. Accumulating data have shown that icariin (ICA), a natural compound, has anti-cancer activity in different cancers, including cervical cancer. The study aimed to reveal the antitumor effects and the possible underlying mechanism of ICA in U14 tumor-bearing mice and SiHa cells.Methods The antitumor effects of ICA were investigated in vivo and in vitro. The expression of TLR4/MyD88/NF-κB and Wnt/β-catenin signaling pathways were evaluated.Results We found that ICA significantly suppressed tumor tissue growth and SiHa cells viability in a dose-dependent manner. Also, ICA enhanced the anti-tumor humoral immunity in vivo. Moreover, ICA significantly improved the composition of the microbiota in mice models. Additionally, the results clarified that ICA significantly inhibited the migration, invasion capacity, and expression levels of TGF-β1, TNF-α, IL-6, IL-17A, IL-10 in SiHa cells. Meanwhile, ICA was revealed to promote the apoptosis of cervical cancer cells by down-regulating Ki67, survivin, Bcl-2, c-Myc, and up-regulating P16, P53, Bax levels in vivo and in vitro. For the part of mechanism exploration, we showed that ICA inhibits the inflammation, proliferation, migration, and invasion, as well as promotes apoptosis and immunity in cervical cancer through impairment of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways.Conclusion sTaken together, ICA could be a potential supplementary agent for cervical cancer treatment.
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BIOCHEMICAL PHARMACOLOGY
·
2017
·
IF 4.581
Jinhua Hu,Zhao Mao,Shuangcheng He,Yuanran Zhan,Rui Ning,Wei Liu,Bingfang Yan,Jian Yang
Osteoporosis is a serious public health concern worldwide. Herba epimedii has been used for centuries and even thousands of years to treat osteoporotic conditions. Icariin , a flavonol glycoside , is one of the major active ingredients. In this study, we have shown that icariin protected against glucocorticoid-induced osteoporotic changes in SaoS-2 cells and mice. We have also shown that dexamethasone (a glucocorticoid) suppressed and icariin induced DEC1, a structurally distinct helix-loop-helix protein. DEC1 overexpression promoted whereas DEC1 knockdown decreased osteogenic activity. Likewise, DEC1 overexpression and knockdown inversely regulated the expression of β-catenin and PIK3CA, an essential player in the Wnt/β-catenin and PI3K/Akt signaling pathways, respectively. Interestingly, DKK1, an inhibitor of Wnt/β-catenin signaling inhibitor, and LY294002 , an inhibitor of PI3K/Akt signaling, abolished the induction of DEC1 by icariin. It is established that these two pathways are interconnected by the phosphorylation status of GSK3β. Dexamethasone decreased but icariin increased GSK3β phosphorylation. Finally, DEC1 deficient mice developed osteoporotic phenotypes. Taken together, it is concluded that DEC1 likely supports the action of icariin against glucocorticoid induced osteoporosis with an involvement of the PI3K/Akt/GSK3β/β-catenin integrated signaling pathway.
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ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Lihua Feng,Yuanyuan Lang,Leke Sun,Weihong Shi,Xiangxiang Chen,Yanan Xia,Hengyi Xu,Yang Liu
Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in children’s daily necessities and foods, and their health hazards to children have attracted particular attention. Childhood is a critical time for accelerated bone growth and development. Current studies revealed that TiO 2 NPs exposure causes bone damage in juvenile rats; however, the underlying mechanism is unknown. Ghrelin is a polypeptide hormone that is considered to be a candidate factor for regulating bone growth and development. In this research, 3-week-old juvenile male rats were administered 0, 100 or 200 mg/kg TiO 2 NPs and 50 μg/kg ghrelin for 4 weeks to explore the underlying mechanism of TiO 2 NPs-induced bone damage, and the protective effect of ghrelin. Our results revealed that TiO 2 NPs resulted in decreased synthesis of bone growth-related hormones, disturbed bone metabolism, and destruction of bone structure. Further mechanism studies showed that TiO 2 NPs inhibited Wnt/β-catenin pathway, reduced collagen synthesis, inhibited chondrocyte proliferation and differentiation, promoted chondrocyte apoptosis, and inhibited endochondral osteogenesis, ultimately leading to long bone longitudinal growth retardation and osteoporosis. Ghrelin alleviated the negative effects of TiO 2 NPs-induced bone growth in juvenile rats by upregulating the Wnt/β-catenin signaling pathway. This study provided a reference for the clinical treatment of growth retardation and idiopathic short stature in juvenile children caused by environmental pollutants.
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CHEMICO-BIOLOGICAL INTERACTIONS
·
2020
·
IF 3.723
Xiao-Peng Wang,Chun-Min Ma,Xin-Huai Zhao
The caseinate and glycated caseinate generated from the transglutaminase-catalyzed reaction of caseinate and oligochitosan were digested using pepsin and trypsin, and the activity of the resultant digests was measured in rat intestinal epithelial cell line (IEC-6) using several biological responses as indicators. Compared with the caseinate digest, the glycated caseinate digest had similar contents in 17 amino acids but less reactable –NH 2 contents, and 6.57 g glucosamine per kg protein; moreover, it showed higher activity in the cells ( P < 0.05) to promote cell growth, accumulate the cell-cycle progression at the S-phase, and prevent the camptothecin-induced cell apoptosis . The glycated caseinate digest also showed higher differentiation activity in the cells than the caseinate digest, resulting in enhanced activities of the three brush-border membrane enzymes ( P < 0.05) and increased microvilli on the cell surfaces. The real-time reverse transcription-polymerase chain reaction, Western-blot assay, and Dickkopf-1 (a receptor inhibitor of the Wnt/β-catenin signaling pathway) were used to determine both gene and protein expression changes in the cells. A Wnt/β-catenin signaling pathway responsible for these enhanced effects was proposed because the five genes (glycogen synthase kinase 3β, Wnt3a, β-catenin, c-Myc, and cyclin D1) and three proteins (nuclear and cytosolic β-catenin, cyclin D1 , and c-Myc) as part of this signaling pathway were regulated in the treated cells. The oligochitosan glycation of caseinate induced by transglutaminase is thus suggested endowing the peptic-tryptic caseinate digest with higher activity in the cells through its effects on the Wnt/β-catenin signaling pathway.
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高影响因子
危险品化学品经营许可证（带存储）