JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Teng Wang,Weilin Liu,Chunyi Lyu,Yunxiao Luo,Xinyu Tang,Chen Han,Ruirong Xu
Ethnopharmacological relevance Realgar is an arsenic-containing mineral medicine and a key component of Realgar-Indigo naturalis formula, an oral traditional Chinese medicine preparation clinically used in China for acute promyelocytic leukemia (APL), a biologically distinct subtype of acute myeloid leukemia (AML). Realgar Transforming Solution (RTS) is a microbially processed realgar preparation. Its activity in AML stem cell-like contexts outside APL remains insufficiently defined, particularly in cell-line-derived CD34 + CD38 − LSC-like models. Aim of the study: To evaluate whether RTS suppresses stemness-associated phenotypic features in KG-1a-derived CD34 + CD38 − LSC-like cells and to explore its association with endoplasmic reticulum stress (ERS), mitochondrial injury, and mitophagy-related alterations. Materials and methods CD34 + CD38 − LSC-like cells were enriched from KG-1a cells and used as a cell-line-derived in vitro model. Cell viability, apoptosis, cell cycle, CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression were assessed after RTS treatment. RNA sequencing, Ca 2+ measurement, ROS detection, mitochondrial membrane potential assay, MDC staining, western blotting, RT-qPCR, immunofluorescence, and transmission electron microscopy were performed. 4-phenylbutyric acid and Mdivi-1 were used as pharmacological rescue agents. Results RTS reduced the CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression, while inducing apoptosis in KG-1a-derived LSC-like cells. Transcriptomics implicated ER protein processing, unfolded protein response, apoptosis, autophagy, and mitophagy-related pathways. RTS increased Ca 2+ levels, ROS accumulation, mitochondrial depolarization, PERK-eIF2α-ATF4-CHOP signaling, and PINK1/Parkin-associated mitophagy-like marker changes. 4-phenylbutyric acid and Mdivi-1 partially rescued RTS-impaired LSC-like phenotypic features, supporting pathway involvement. Conclusions RTS suppressed stemness-associated phenotypic features in a KG-1a-derived CD34 + CD38 − LSC-like model. These effects were associated with ERS, mitochondrial injury, and PINK1/Parkin-related mitophagy-like alterations.
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DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2021
·
IF 2.63
Songsong Wang,Xiao Xiao,Ao Li,Peng Li
An-Gong-Niu-Huang Wan (AGNH) has been a well-known cinnabar- and realgar-containing compound recipe for cerebral diseases. Unfortunately, its clinical practice is often restrained by the specific hepatorenal toxicity of cinnabar and realgar (C + R). In previous research studies, we have found that the antioxidative and anti-inflammatory effects of its herbal constituents could mitigate the risks from the toxicity. The underlying detoxification mechanisms are still unsolved. The present study investigated the protective effects of AGNH’s herbal constituents on hepatorenal injury induced by C + R. For the mice treated with C + R, the increased expression levels of sensitive biomarkers of metal exposure and hepatorenal toxicity, including metallothionein (MT) in both hepatorenal tissues and kidney induced molecule-1 (KIM-1) in the kidney, were simultaneously reduced when C + R coadministered with other herbal medicines. In addition, the contents of trivalent As (AsIII), pentavalent As (Asv), and mercury (Hg) in hepatorenal tissues of mice were also significantly reduced benefiting from the herbal constituents in AGNH. Further mechanism studies showed that the herbal constituents in AGNH could downregulate the expressions of uptake transporters (AQP9 and OAT1) and upregulate the expressions of efflux transporters (P-gp, MRP2, and MRP4) in mice intoxicated by C + R. Our results suggested that AGNH’s herbal constituents protect the body against C + R-induced hepatorenal toxicity and accumulations of Hg and As, which could be associated with the reestablishment of heavy metal homeostasis and the detoxification system.
研究领域:
药理学
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毒理学
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2022
·Vol. 18
·期 2
·193-198
·
IF 0.743
Xu Bo-Yang,Zhu Si-Qi,Cheng Xian-Xin,Xu Yu,Liu Ji-Wu
Background: Compound Niuhuang Xiaoyan capsule is a realgar and cinnabar-containing traditional Chinese medicine, the contents of total arsenic and total mercury are found over regulation defined limits. However, only small amounts of arsenic in realgar and mercury in cinnabar are dissolved
in the gastric juice, so the determination of soluble arsenic and soluble mercury is more significant than that of total arsenic and total mercury in Compound Niuhuang Xiaoyan capsule. Objective: To study the contents of total arsenic, total mercury, soluble arsenic and soluble mercury
in Compound Niuhuang Xiaoyan capsule. Methods: Microwave digestion and semi-bionic extraction were used to pretreat the samples of Compound Niuhuang Xiaoyan capsule, and the inductively coupled plasma mass spectrometry method was established to determine the contents of total arsenic,
total mercury, soluble arsenic and soluble mercury in Compound Niuhuang Xiaoyan capsule. The accuracy of the established method was further evaluated by using a certified standard reference material prepared from dried citrus leaves (GBW10020(GSB-11)). Results: The spiked recoveries were
within 95-105 %. The R.S.D% of repeatability (N=6) and precision (N = 6) were below 5.0 %. The correlation coefficients of linear (R) for arsenic and mercury were both above 0.998. The limits of quantification (LOQ) were below 0.1 μg/L. The contents of As and Hg were defined in the dried
citrus leaves and very near to the standard values provided by the manufacturer. The established method was applied for the analysis of three batches of Compound Niuhuang Xiaoyan capsule produced by three different manufacturers successfully. Insufficient realgar or cinnabar was formulated
in some Compound Niuhuang Xiaoyan capsule samples. Conclusion: The analysis showed that the contents of soluble arsenic and soluble mercury in artificial gastric juice were significantly less than that of total arsenic and total mercury in Compound Niuhuang Xiaoyan capsule. The results
provided a reference for further study on the toxicology and pharmacokinetics of Compound Niuhuang Xiaoyan capsule.
研究领域:
中药学
·
分析化学
·
毒理学
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DOI
高影响因子
危险品化学品经营许可证（带存储）