Clinical Response to Traditional Chinese Herbs Containing Realgar (As2S2) is Related to DNA Methylation Patterns in Bone Marrow DNA from Patients with Myelodysplastic Syndrome with Multilineage Dysplasia

Zhou, Qi; Du, Yu; Zhang, Shanshan; Liu, Zheng‐Tang; Ma, Rong; Xu, Yang

doi:10.2147/cmar.s280886

Cited by 4 publications

(5 citation statements)

References 26 publications

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“…Arsenic methylation observed in human urine of this study was highly in consistence with these previously reports. Because of the lower toxicity of the organic arsenics than inorganic arsenics (Zhang et al, 2013;Zhou et al, 2021), the methylated metabolites detected in human urine poses a lower risk in human body.…”

Section: Arsenic Speciation In Plasma and Urinementioning

confidence: 99%

“…Traditional Chinese medicines (TCMs) are effective for many different indications and have been widely used for hundreds of years. Realgar (As 2 S 2 ) is prescribed as a mineral medical material since ancient China has shown beneficial effects on carbuncles, psoriasis, malaria, convulsive epilepsy, and parasitic infections (Zhou et al, 2021). Nowadays, realgar-containing TCMs are used more frequently than realgar alone due to the synergistic effects combined with other herbal ingredients (Wu et al, 2018;Liu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Arsenic-Related Health Risk Assessment of Realgar-Containing NiuHuangJieDu Tablets in Healthy Volunteers Po Administration

Yan

Guan

et al. 2022

Front. Pharmacol.

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Realgar, an arsenic-containing traditional Chinese medicine of As2S2, has significant therapeutic effects for hundreds of years. NiuHuangJieDu tablets (NHJDT) is one of the most commonly prescribed realgar-containing preparations for the treatment of sore throat, swelling, and aching of gums. However, realgar-containing TCMs raise great safety concerns due to the adverse effects reported by arsenic poisoning. In this study, the arsenic-related health risk assessment of NHJDT was conducted in healthy volunteers after single and multiple doses oral administration. Blood, plasma, and urine samples were collected after dosing at predetermined time points or periods. Simple, rapid, and sensitive methods were established for the quantification of total arsenic and arsenic speciation in biological samples. The total arsenic and arsenic speciation were determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) and high-performance liquid chromatography–hydride generation–atomic fluorescence spectrometry (HPLC-HG-AFS), respectively. No significant fluctuation of total arsenic was observed in human blood, and no traces of arsenic speciation were found in human plasma. Dimethylarsenic acid was detected as the predominated arsenic species in human urine after dosing. Therapeutic dose administration of NHJDT was relatively safe in single dose for the limited blood arsenic exposure, but long-term medication may still pose health risks due to the accumulation of arsenics in blood and its extremely slow excretion rate. Therefore, arsenic exposure should be carefully monitored during realgar-containing TCM medication, especially for long-term regimen. The results obtained in this study will provide scientific references for the clinical application of realgar and its-containing TCMs.

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Section: Arsenic Speciation In Plasma and Urinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Arsenic-Related Health Risk Assessment of Realgar-Containing NiuHuangJieDu Tablets in Healthy Volunteers Po Administration

Yan

Guan

et al. 2022

Front. Pharmacol.

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“…Different DNA methylation subtypes may be present in MDS-metachromatic leukodystrophy (MLD) patients. A clinical study found that Chinese herbal medicine containing realgar has good effects in the treatment of MDS-MLD patients with the hypomethylation subtype [ 7 ]. The therapeutic mechanism may involve an increase in DNA methyltransferase expression in MDS [ 6 ].…”

Section: Realgarmentioning

confidence: 99%

“…Realgar is described by the 2020ChP [1] as a sulfide mineral of the realgar family that mainly contains arsenic disulfide (As₂S₂) and has the functions of "detoxifying and killing insects, drying dampness and removing phlegm, and treating malaria." Modern research has further revealed that realgar can be combined with other drugs to treat a variety of blood system diseases [4], including acute promyelocytic leukemia (APL) [5], myelodysplastic syndrome (MDS) [6][7][8][9], and lymphoma. Realgar has also shown significant pharmacological effects against primary or metastatic cancers, such as breast cancer (cells) [4,10,11], cervical cancer [12], lung cancer [13], osteosarcoma [14], gastric cancer [15], oral cancer (cells) [16], and liver cancer [17], in nonclinical studies.…”

Section: Introductionmentioning

confidence: 99%

Pharmacology, Toxicology, and Rational Application of Cinnabar, Realgar, and Their Formulations

Guan

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Ethnopharmacological Relevance. Mineral medicines are widely used traditional Chinese medicines with curative effects. These medicines are used for many refractory diseases. Aim of the Review. In this review, cinnabar (HgS) and realgar (As₂S₂) serve as examples of mineral medicines, and their pharmacology, therapeutic toxicity, use in traditional medicine mixtures, and research perspectives are discussed. Materials and Methods. A search was performed for the literature on cinnabar and realgar in PubMed, the Chinese Pharmacopeia, Google, and other sources. The search included studies using single herbs, traditional formulations, or novel dosage forms. Results. Cinnabar and cinnabar formulas exhibit good efficacy for sedation, sleep improvement, anxiety alleviation, and brain protection. However, previous studies on neurotransmitters have reached different conclusions, and detailed pharmacological mechanisms are lacking. Realgar and its formulas exert promising antitumor activity through regulation of cell cycle arrest, intrinsic and extrinsic apoptosis, induction of differentiation, autophagy, metabolic reprogramming, matrix metalloproteinase-9 (MMP-9) signaling, and reactive oxygen species (ROS) generation. In addition, realgar can be used to treat a variety of refractory diseases by regulating immunity and exerting antibacterial, antiviral, and other effects. However, the existing pharmacological research on the use of realgar for epidemic prevention is insufficient, and animal experiments and research at the cellular level are lacking. Inappropriate applications of cinnabar and realgar can cause toxicity, including neurotoxicity, liver toxicity, kidney toxicity, and genotoxicity. The toxicological mechanism is complex, and molecular-level research is limited. For clinical applications, theory and clinical experience must be combined to guide scientific and rational drug use and to achieve reduced toxicity and increased efficacy through the use of modern preparation methods or combined drugs. Notably, when cinnabar and realgar are used to treat targeted diseases, these agents have a bidirectional effect of “treatment” and “toxicity” on the central nervous system in pathological and normal states. The pharmacological and toxicological mechanisms need to be elucidated in greater detail in the future. Overall, systematic research is needed to provide a basis for better promotion of the rational use of cinnabar and realgar in the clinic. Conclusion. Mineral medicines are multicomponent, multiactivity, and multitargeted substances. The pharmacology and mechanisms of the toxicity and action of realgar and cinnabar are extremely complex. A number of Chinese medicinal preparations of realgar and cinnabar have demonstrated unique efficacy in the treatment of refractory diseases.

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“…Realgar (R), a traditional Chinese medicine containing mainly tetrasulfide of arsenic (As 4 S 4 ), has been used clinically in China for thousands of years to treat inflammation, poisoning, cancer, convulsion, and parasites (Liu et al, 2018; Wu et al, 2011). Since the 1950s, the compound preparation or single prescription of Realgar has been used in treating hematological system diseases, malignant lymphatic system diseases, and even solid tumors (Lou et al, 2021; Zhou et al, 2021). Especially, Realgar has achieved remarkable clinical efficacy in chronic granulocytic leukemia (Zhu et al, 2019) and is expected to be an alternative option to arsenic for the leukemia treatment.…”

Section: Introductionmentioning

confidence: 99%

Realgar‐induced nephrotoxicity via ferroptosis in mice

Zhang

Cao

Zhou

et al. 2022

J of Applied Toxicology

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Ferroptosis is a novel form of iron-dependent cell death that is involved in arsenicinduced toxicity. Realgar is an arsenic-containing Chinese medicine, which can result in nephrotoxicity because of long-term exposure. However, it remains scientifically unknown whether Realgar is an inducer of ferroptosis in the kidney. This study investigated the role of ferroptosis in Realgar-induced kidney toxicity in mice. ICR mice were exposed to Realgar for 28 days, and HK2 cells were exposed to Realgar in the presence or absence of treatment with ferrostatin-1, a ferroptosis inhibitor. The ferroptosis-related indicators were further evaluated. Realgar can cause nephrotoxicity in mice by continuous gavage for 28 days, accompanied by an increase in iron accumulation and reactive oxygen species (ROS). The reduced expression of Slc7A11 and Gpx4 further confirmed the ferroptosis mediated by Realgar. Meanwhile, Realgar disrupted the antioxidant system as evidenced by the formation of ROS leading to the inactivation of antioxidant enzymes. Realgar caused ferroptosis in a dosedependent manner, which was significantly reduced by ferrostatin-1 in HK2 cells.This study revealed that Realgar-induced ferroptosis triggered nephrotoxicity in mice and provided new clues to elucidate the mechanism of Realgar-induced nephrotoxicity.

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Clinical Response to Traditional Chinese Herbs Containing Realgar (As2S2) is Related to DNA Methylation Patterns in Bone Marrow DNA from Patients with Myelodysplastic Syndrome with Multilineage Dysplasia

Cited by 4 publications

References 26 publications

Arsenic-Related Health Risk Assessment of Realgar-Containing NiuHuangJieDu Tablets in Healthy Volunteers Po Administration

Arsenic-Related Health Risk Assessment of Realgar-Containing NiuHuangJieDu Tablets in Healthy Volunteers Po Administration

Pharmacology, Toxicology, and Rational Application of Cinnabar, Realgar, and Their Formulations

Realgar‐induced nephrotoxicity via ferroptosis in mice

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