Biomed Research International
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2015
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IF 1.579
Wen-Hao Yu,Na Zhang,Jin-Feng Qi,Chen Sun,Yong-Hui Wang,Mei Lin
Toxic heavy metals, including mercury (Hg) and arsenic (As), accumulate preferentially in kidneys and always cause acute renal failure. The aim of this study was to investigate whether these samples affect organic anion transporters, Oat1 and Oat3, in vivo in mice kidney. Mice () were orally treated with investigational samples. After last administration, all mice were i.v. p-aminohippuric acid (PAH), and the blood and kidneys samples were collected. The concentrations of PAH were quantified by spectrophotometry. mRNA expressions of Oat1 and Oat3 were assayed by real-time PCR. In comparison with corresponding control, major pharmacokinetic parameters of PAH in sera were significantly changed by investigational samples (), PAH accumulations in the kidney tissues were significantly higher (), PAH uptake by renal slices was greatly reduced, Oat1 and Oat3 mRNA expression were significantly inhibited in investigational sample groups. Arsenic and mercury containing traditional Chinese medicine (Realgar and Cinnabar) probably induce kidney damage through inhibiting several members of the organic anion transporters (such as OAT1 and OAT3).
研究领域:
药理学
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毒理学
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肾脏病学
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PubMed
高影响因子
ACS Applied Nano Materials
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2022
·
IF 6.14
Dongsheng Shi,Shengyan Pu,Haitao Yin,Yingying Song,Hongmei Liu,Xiaolian Yu,Yang Zhao,Chengkun Ye,Shuangyu Liu,Xingqi Wang,Jinjin Huang,Yu Zhang,Jun Xie
Realgar as a traditional Chinese medicine for curing cancer has unique advantages, such as great antitumor effect, low genotoxicity, and good organism tolerability. Unfortunately, its poor solubility and body absorptive capacity may cause an extremely low bioavailability. To overcome the therapeutic hurdle, we have successfully synthesized high-performance fluorescent realgar nanoclusters (RNCs), which encapsulate “ethanolamine-modified nano-realgar (NR) assemblies” into functional a poly(ethylene glycol) (PEG)–phospholipid hydrophobic layer, simultaneously coupling with a targeting ligand of hyaluronic acid (HA). As a chemotherapeutic agent, the designed HA-modified RNCs (RNCs@HA) possess excellent water dispersbility, pH-sensitive NR quantum dots (QDs) release capacity, low toxicity, and enhanced anticancer efficacy. As a fluorescent probe, RNCs@HA can be used as an in vivo fluorescence trace system to measure and image biological activity. Herein, we have established a BALB/c mice model bearing a subcutaneous transplanted breast tumor and designed the intravenous RNCs@HA-mediated tumor theranostics in vivo. Under the guidance of targeting HA ligands, RNCs@HA concentrates in the tumor tissue from fenestrated neovascularization, gradually degrades into hydrophobic NR QDs, gathers around nucleopores, and moves into the nucleus regions of cancer cells in an acidic environment, conclusively facilitating nuclear targeting-associated chemotherapy. Our work aims to improve the chemotherapeutic efficacy of realgar and facilitate its more widespread use for clinical application.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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高影响因子
Frontiers in Endocrinology
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2025
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IF 4.6
Yifan Zhang,Qingsong Qu,Ertong Dai,Ruiyan Liu,Bilin Jin,Zixuan Lu,Hui Kong,Yue Zhang,Huihua Qu,Yan Zhao
Background Glucose metabolism plays a central role in maintaining systemic energy homeostasis, and its dysregulation is closely linked to the pathogenesis of metabolic diseases such as diabetes mellitus. While traditional mineral medicines such as realgar and cinnabar have a long history of use, their roles in glycometabolism remain poorly defined. Methods Male C57BL/6J mice were used to establish both normoglycemic and streptozotocin (STZ)-induced diabetic models. Oral glucose, starch, protein, fat, and cellulose load tests were performed to evaluate the effects of realgar and cinnabar on postprandial glycemia and thermoregulation. Random blood glucose, body temperature, and insulin levels were monitored. α-Glucosidase and α-amylase inhibition assays were conducted in vitro to explore potential digestive enzyme-targeted mechanisms. Results Realgar and cinnabar significantly reduced blood glucose levels in diabetic mice and attenuated postprandial glycemic excursions in normal mice following oral glucose and starch loading. Further analysis revealed elevated insulin levels and dose-dependent inhibition of α-glucosidase and α-amylase activities. However, these hypoglycemic effects were abolished when glucose was administered intraperitoneally, and no significant changes in blood glucose were observed under non-carbohydrate nutrient loads (fat, protein, or fiber). Conclusion This study provides the first systematic evidence that realgar and cinnabar exert hypoglycemic effects, which involving enhanced insulin secretion and inhibition of key digestive enzymes. Their substrate-specific actions and partial influence on thermoregulation suggest broader roles in metabolic regulation and warrant further investigation in chronic models and energy homeostasis pathways.
研究领域:
药理学
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内分泌学
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代谢性疾病
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传统医学
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营养代谢
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DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
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2025
·
IF 3.6
Li Jianchao,Deng Nuo,Wang Fei,Zhu Huilin,Li Yongming,Wu Xiao
As a traditional Chinese medicine (TCM) composed of As 2 S 2 , realgar has been widely used for treating various diseases. However, its safety has raised significant concerns due to the well-documented toxicity of arsenic. The Chinese Pharmacopoeia has imposed strict controls on the dosage of realgar, but the bioaccessibility and health risks associated with arsenic in realgar-containing TCMs remain poorly understood. This study developed a hydride generation–atomic fluorescence spectrometry (HG-AFS) method to determine the total arsenic and bioaccessible arsenic contents in 20 realgar-containing TCMs through wet digestion and simulated gastrointestinal fluid extraction. Health risk assessments were evaluated from the bioaccessible arsenic content using single pollution index (Pi), maximum daily intake (MDI), estimated daily intake (EDI), hazard quotient (HQ), and carcinogenic risk (CR). Additionally, the particle size of realgar in representative preparations was analyzed using a light microscope. The tested realgar-containing TCMs exhibited significant variations in the contents of total arsenic and bioaccessible arsenic. Bioaccessible arsenic is a more reasonable indicator for the safety evaluation of realgar-containing TCMs. The daily dosage of realgar in its-containing TCMs exceeded the limit standard prescribed in the Chinese Pharmacopoeia. The evaluation of the health risk index suggested that arsenic in realgar-containing TCMs exceeded the corresponding regulatory thresholds. Furthermore, realgar crystals in preparations were not uniform and exhibited noticeable differences under the microscope. The current quality standards in the Chinese Pharmacopoeia are insufficient to ensure the safety of realgar-containing TCMs, which urgently need to be revised. The study provided scientific evidence for the quality control and clinical safety application of realgar-containing TCMs. Graphical
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JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Shengmei Wang,Xuanjun Liu,Shengfeng Wang,Linqi Ouyang,Hui Li,Jinsong Ding,Guiming Deng,Wenhu Zhou
Discovery of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has revolutionized the therapy of chronic myeloid leukemia (CML), a malignant myeloproliferative disease characterized by abnormal activation of BCR-ABL fusion oncoprotein with protein tyrosine kinase (PTK) activity. However, the long-term treatment outcomes with TKIs are strongly limited by multiple drug resistances, resulting in relapse albeit with initial high response rate. Here, we reported a realgar (As 4 S 4 ) nanocrystal-based delivery system to reverse drug resistance for synergistic CML therapy. While As 4 S 4 is extremely insoluble in water, bovine serum albumin (BSA) was rationally screened to effectively stabilize As 4 S 4 nanocrystal with uniformed size of ~40 nm. Imatinib (IMA), a representative TKIs, can be readily loaded into the hydrophobic domain of BSA to develop As 4 S 4 /IMA co-delivery system. Mechanistically, IMA inhibits PTK activity, while As 4 S 4 degrades BCR-ABL1, which co-contribute to tumor suppression via complementary pathways for synergistic effect. Moreover, the nanosystem was modified with folic acid (FA) to enable tumor targetability, which has been demonstrated both in vitro and in vivo, resulting in robust tumor growth inhibition and significantly prolonged mice survival without any noticeable adverse effects. This work designed a synergistic nanoplatform for targeted CML therapy, provided a strategy to address the key limitation of As 4 S 4 for biomedical applications, and highlighted the advantages of the combination between traditional Chinese and western medicine for diseases treatment.
研究领域:
肿瘤学
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药学
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纳米技术
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生物医学工程
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PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2022
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IF 2.65
Mingyi Sun,Yaolei Li,Ying Wang,Huimin Wu,Jing Liu,Longtai You,HuLinyue Peng,Huating Huang,Hongyu Jin,Xiaoxu Dong,Changhai Qu,Xingbin Yin,Jian Ni
At present, several experiments have been carried out to study the changes in total arsenic content of realgar and its prescription, but few researches on its form and valence. We evaluated the change in arsenic species concentration in realgar from the perspective of absorption by using an in vitro dissolution study, an in vivo unidirectional intestinal perfusion study, transmembrane transport in Caco-2 cells, and a pharmacokinetic study in rats. In the gastrointestinal tract, arsenic species are mainly present inorganic forms of AsIII and AsV. The cumulative dissolution rates of soluble arsenic in 4 h artificial gastric fluid and 8 h artificial intestinal fluid were 21.99% and 59.20%, respectively. The values of soluble arsenic in realgar in the duodenum, jejunum, and ileum of rats were 5.4 × 10−3, 6.1 × 10−3 and 5.8 × 10−3 cm/min, respectively. In the process of small intestine perfusion, the AsIII of realgar was partially converted into AsV in the duodenum and jejunum. As the transport time increased, the transmembrane transport rate and value of soluble arsenic in realgar were increased in Caco-2 cells, and it also suggested that arsenic species may be passively transported across the Caco-2 cell monolayer. The Cmax and AUC (0-24) of AsIII, AsV, and DMA in plasma of realgar were 41.26 ng L−1/343.977 ng h mL−1, 21.626 ng L−1/47.310 ng h mL−1, and 2.372 ng L−1/30.429 ng h mL−1, respectively. Tmax and MRT (0-∞) of AsIII, AsV, and DMA were 2.571 h/9.649 h, 0.393 h/2.790 h, and 3.143 h/23.145 h, respectively. It is hoped to provide a basis for clarifying the arsenic species in realgar.
研究领域:
药学
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毒理学
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药理学
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PubMed
高影响因子
Frontiers in Pharmacology
·
2026
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IF 5.4
Liping Dong,Wenzhuo Ran,Yanqiong Li,Lixia Yang,Xi Zhou
Realgar (As 4 S 4 ) has shown antitumor activity, but its pharmaceutical application is limited by poor aqueous solubility, low bioavailability, and systemic toxicity. In this study, we developed AS1411-functionalized albumin nanoparticles (As 4 S 4 @ BSA-AS1411 NPs) for targeted delivery of realgar to triple-negative breast cancer (TNBC). Bulk As 4 S 4 was converted into nanosized clusters and encapsulated in a bovine serum albumin (BSA) matrix, followed by surface conjugation with the nucleolin-targeting aptamer AS1411. The resulting nanoparticles showed suitable physicochemical properties and good colloidal stability in physiologically relevant media, together with enhanced cellular internalization in 4T1 cells. Compared with non-targeted nanoparticles, AS1411 modification significantly increased cytotoxicity and reduced the migratory ability of 4T1 cells. Mechanistic studies showed that treatment with As 4 S 4 @BSA-AS1411 NPs was associated with upregulation of GADD45G and downregulation of mTOR, suggesting a stress-related antiproliferative effect. In vivo fluorescence imaging demonstrated increased tumor accumulation of AS1411-functionalized NPs. In 4T1 tumor-bearing mice, systemic administration of As 4 S 4 @BSA-AS1411 NPs produced greater tumor growth inhibition than non-targeted controls, accompanied by increased apoptosis and reduced proliferative activity in tumor tissues. In addition, the formulation showed good in vivo tolerability, with no evident systemic toxicity or hemolytic activity. These findings indicate that AS1411-functionalized albumin NPs are a promising delivery system for improving the antitumor efficacy and safety profile of realgar in TNBC.
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PubMed
高影响因子
Minerals
·
2025
·Vol. 15
·期 3
·200
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IF 2.2
Zhiqiang Zhao,Zehui Gao,Chuanyao Sun,Yingheng Zhang,Chongjun Liu,Tong Lu,Yangge Zhu,Guiye Wu,Ruidong Li,Jun Hu
In lead concentrate cleaning, achieving efficient separation of galena from realgar—both significant naturally floatable minerals-relies critically on selective galena depression. This study introduces dimercaptosuccinic acid (DMSA) as a novel organic depressant by leveraging its distinct carbon-sulfur hybridization compared to diethyldithiocarbamate (DDTC). Quantum chemical analyses reveal that the sp3-hybridized sulfur in DMSA exhibits enhanced p-orbital reactivity, enabling stronger chemical adsorption on galena via Pb-S bonding. At pH 6.5, DMSA (4 mg/L) achieved optimal separation with a separation index of 11.88, outperforming DDTC (10 mg/L). FTIR/XPS confirmed DMSA’s chemisorption on galena, while theoretical calculations highlighted its superior Pb-S bond strength compared to DDTC. Notably, DMSA’s lower dosage and reduced environmental impact position it as a sustainable alternative to inorganic depressants. This work provides fundamental insights into sulfur orbital-driven adsorption mechanisms, advancing the rational design of eco-friendly flotation reagents.
研究领域:
矿物加工工程
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量子化学
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环境科学
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高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Yihan Wang,Yizhen Wei,Yichun Wu,Yue Zong,Yingying Song,Shengyan Pu,Wenwen Wu,Yun Zhou,Jun Xie,Haitao Yin
Purpose Realgar, as a kind of traditional mineral Chinese medicine, can inhibit multiple solid tumor growth and serve as an adjuvant drug in cancer therapy. However, the extremely low solubility and poor body absorptive capacity limit its application in clinical medicine. To overcome this therapeutic hurdle, realgar can here be fabricated into a nano-realgar hydrogel with enhanced chemotherapy and radiotherapy (RT) ability. Our objective is to evaluate the superior biocompatibility and anti-tumor activity of nano-realgar hydrogel.Methods We have successfully synthesized nano-realgar quantum dots (QDs) coupling with 6-AN molecules (NRA QDs) and further encapsulated with a pH-sensitive dextran hydrogel carrier with hyaluronic acid coating (DEX-HA gel) to promote bioavailability, eventually forming a multifunctional nano-realgar hydrogel (NRA@DH Gel). To better investigate the tumor therapy efficiency of the NRA@DH Gel, we have established the mice in situ bearing GL261 brain glioblastoma as animal models assigned to receive intratumor injection of NRA@DH Gel.Results The designed NRA@DH Gel as an antitumor drug can not only exert the prominent chemotherapy effect but also as a “sustainable reactive oxygen species (ROS) generator” can inhibit in the pentose phosphate pathway (PPP) metabolism and reduce the production of nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting the conversion of glutathione disulfide (GSSG) to glutathione (GSH), reducing GSH concentrations in tumor cells, triggering the accumulation of ROS, and finally enhancing the effectiveness of RT.Conclusion Through the synergistic effect of chemotherapy and RT, NRA@DH Gel effectively inhibited the proliferation and migration of tumor cells, suppressed tumor growth, improved motor coordination, and prolonged survival in tumor-bearing mice. Our work aims to improve the NRA@DH Gel-mediated synergistic chemotherapy and RT will endow a “promising future” for the old drug in clinically comprehensive applications.
研究领域:
药学
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肿瘤学
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纳米技术
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生物医学工程
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癌症治疗
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Jianchao Li,Yuanjing Ma,Nuo Deng,Fei Wang,Yi Tao,Huilin Zhu,Weichen Xu,Jinjun Shan,Yongming Li,Xiao Wu
Ethnopharmacological relevance Realgar is a traditional Chinese medicine rich in arsenic, and long-term use may lead to arsenic poisoning. The toxicity of realgar has primarily focused on the liver and kidney, with limited studies on its intestinal toxicity. Niuhuang Jiedu Tablet (NHJDT) is a renowned realgar-containing formula for clearing heat and detoxifying. NHJDT compatibility significantly reduces the toxicity of realgar, but the detoxification effects and underlying mechanisms in reducing realgar-induced intestinal toxicity remain unclear. Aim of the study The study aims to investigate the detoxification mechanism of NHJDT's compatibility in reducing the intestinal toxicity of realgar. Materials and methods To evaluate the intestinal detoxification efficacy of NHJDT, mice were orally administered 0.5 % CMC-Na, realgar (0.5 and 1.0 g/kg) or NHJDT (3.9 and 7.8 g/kg) for 14 days. The intestinal detoxification effects of NHJDT were evaluated by toxic symptoms and intestinal barrier function. Changes of body weight, colon length, histopathological damage, tight junction and MUC2 proteins, and goblet cells were determined. The inflammatory factors and DAO were detected by ELISA. Further investigations including 16S rRNA sequencing, untargeted metabolomics, targeted short-chain fatty acid metabolomics and molecular docking assays were performed to explore the underlying detoxification mechanisms of NHJDT. Additionally, targeted microbiota and its derived metabolite gavage were conducted in mice to verify the detoxification effects. Results NHJDT's compatibility significantly mitigated realgar-induced intestinal toxicity and gut barrier damage. It restored gut microbiota homeostasis by modulating the abundance of Akkermansia and concurrently enhanced the transformation from tryptophan to indole-3- lactate (ILA). The supplementation with Akkermansia muciniphila ( A. muciniphila ) and its derived ILA activated the aryl hydrocarbon receptor (AhR) in mice, thereby ameliorating realgar-induced intestinal damage. Conclusion NHJDT's compatibility alleviated realgar-induced intestinal toxicity by activating the AhR pathway via A. muciniphila and ILA. This study elucidates the detoxification mechanism of NHJDT's compatibility and offers novel insights for the clinical treatment of arsenic poisoning.
研究领域:
药理学
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微生物学
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毒理学
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代谢组学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Guangyan Li,Tongshu Wang,Yixuan Xie,Lu He,Huan Liu,Hongying Chen,Hong Jiang,Taoguang Huo
Ethnopharmacological relevance Realgar is extensively utilized in both modern medicine and traditional Chinese medicine. Although it has therapeutic uses, realgar exhibits hepatotoxicity, and improper use can result in liver inflammation and injury. The disruption of bile acid (BA) homeostasis, identified as an initiating event in liver injury, has been observed in the livers of realgar-exposed mice. However, the relationship between realgar-induced BA homeostasis imbalance and liver inflammation remains to be elucidated. Aim of the study To investigate the relationship between hepatic BA homeostasis disorder and liver inflammation caused by realgar exposure in mice, as well as the role and potential mechanism of intestinal farnesoid X receptor (FXR) in realgar-induced liver inflammation. Methods A sub-chronic realgar exposure mouse model was established and subjected to interventions with an intestinal-restricted FXR agonist or inhibitor. Plasma hepatic enzyme activities and total bile acid (TBA) levels were quantified using spectrophotometry. Hepatic inflammatory cytokine levels were analyzed by ELISA or RT-qPCR. Histopathological evaluation of liver injury was performed using HE staining. F4/80 expression was assessed via immunohistochemistry (IHC). Western blot (WB) and IHC were employed to examine the expression of proteins involved in the FXR-FGF15 axis, and plasma FGF15 concentrations were determined by ELISA. The expression of proteins related to enterohepatic circulation and the NLRP3 inflammasome pathway were evaluated using WB. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-TOF-MS) was utilized to analyze BA profiles in both ileal and hepatic tissues. Results Our findings demonstrate that realgar exposure induces changes in ileal BA composition and subsequent suppression of the FXR-FGF15 signaling axis in mice. This axis suppression promotes hepatic BA overproduction and disrupts BA homeostasis in the livers of realgar-exposed mice, particularly elevates the levels of taurochenodeoxycholic acid (TCDCA) and taurolithocholic acid (TLCA). In vitro studies revealed that both TCDCA and TLCA can directly activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in AML-12 cells, triggering pro-inflammatory cascades. Pharmacological activation of intestinal FXR effectively ameliorated realgar-induced hepatic inflammatory damage via restoring BA homeostasis and suppressing NLRP3 inflammasome activation. Conclusion Realgar exposure causes liver inflammatory injury by inducing BA-mediated NLRP3 inflammasome activation through down-regulating ileal FXR. Pharmacological activation of intestinal FXR alleviates realgar-induced liver inflammatory injury by restoring BA homeostasis and inhibiting BA-mediated NLRP3 inflammasome activation. These findings suggest that intestinal FXR may serve as a potential target for the prevention and treatment of realgar-induced liver injury.
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高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Donghan Bai,Zihao Zhang,Jingyue Gao,Qiaochu Wang,Remy Macdonald,Ziwen Xu,Shumin Chen,Nanxi Huang,Lu Luo
Background: Leukemia is a malignant hematologic disease that poses a serious threat to human health. Realgar-Indigo Naturalis formula (RIF), a traditional Chinese medicine formula, have demonstrated anti-tumor activity, but its mechanisms of action remain unclear.Objective: This study aimed to establish a zebrafish HL-60 tumor transplantation model to investigate the anti-leukemic effects of RIF and explore its underlying mechanisms.Methods: The zebrafish HL-60 tumor transplantation model was established, with RIF as the intervention drug and all-trans retinoic acid (ATRA) as the control. Anti-tumor efficacy was assessed via pharmacodynamic analysis. Transcriptomic analysis further elucidated gene expression profiles, differentially expressed genes, and relevant biological pathways.Results: RIF significantly reduced tumor cell fluorescence intensity, demonstrating anti-tumor efficacy. Additionally, it improved HL-60-induced liver damage in zebrafish, as evidenced by a reduction in fatty vacuolar degeneration in liver tissue. Transcriptomic analysis revealed that ATRA mainly affected the FoxO signaling pathway, PI3K-Akt signaling pathway, apoptosis, and complement and coagulation cascades in leukemia treatment. RIF primarily influenced the ubiquitin-proteasome system, ferroptosis, and glutathione metabolism. The combination of ATRA and RIF also affected autophagosome and lysosome pathways, in addition to the aforementioned pathways.Conclusion: RIF exhibit significant anti-tumor effects through modulation of multiple pathways. This study provides a theoretical foundation for the potential clinical application of RIF in leukemia treatment.
研究领域:
肿瘤学
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药理学
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中医学
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发育生物学
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毒理学
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基因组学
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高影响因子
危险品化学品经营许可证（带存储）