The Three-Herb Formula Shuang-Huang-Lian stabilizes mast cells through activation of mitochondrial calcium uniporter

Gao, Yuan; Hou, Rui; Fei, Qiaoling; Fang, Liwei; Han, Yanxi; Cai, Rong; Peng, Cheng; Qi, Yun

doi:10.1038/srep38736

Cited by 20 publications

(20 citation statements)

References 72 publications

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“…However, the mouse ear (Evans blue) and local toe swelling tests are the most common evaluation methods because enhanced vascular permeability is a major pathological characteristic of anaphylactoid reactions 15 , 16 . The release of anaphylactic mediators, including histamine and β-hexosaminidase, is commonly assessed by ELISA 17 , 18 , although there are difficulties associated with the detection of histamine and β-hexosaminidase, including but not limited to low sensitivity, poor reproducibility, and a complicated protocol.…”

Section: Introductionmentioning

confidence: 99%

Use of the relative release index for histamine in LAD2 cells to evaluate the potential anaphylactoid effects of drugs

Han

Kong

et al. 2017

Sci Rep

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Anaphylactoid reactions are common clinical acute adverse drug reactions that can exacerbate a patient’s condition and produce effects that may become life-threatening. Therefore, it is important to establish a novel method to evaluate drugs for anaphylactoid reactions. In this study, we developed a sensitive and rapid method to detect histamine release from LAD2 cells using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and constructed a relative release index based on various release curve parameters, including allergen release time and sudden change rate, to evaluate the potential and strength of allergen-induced anaphylactoid reactions. This LAD2 release model was used to evaluate anaphylactoid reactions induced by ciprofloxacin, norfloxacin, lomefloxacin, moxifloxacin, and baicalin. The results positively correlated with those obtained with an Evans blue ear test and negatively correlated with the Ca2+ influx EC50. In summary, the current study established a novel in vitro method to analyze the properties of histamine release from LAD2 cells and characterize the sensitization and strength of sensitization of drugs or components that may induce anaphylactoid reactions.

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Section: Introductionmentioning

confidence: 99%

Use of the relative release index for histamine in LAD2 cells to evaluate the potential anaphylactoid effects of drugs

Han

Kong

et al. 2017

Sci Rep

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“…Human C3a ELISA kit was from BD Biosciences (San Diego, CA, USA). Shrimp tropomyosin (ST) from Metapenaeus ensis was prepared as we previously described (Gao et al, 2017). Normal human serum was obtained from Solarbio life sciences Co. (Beijing, China).…”

Section: Materials and Reagentsmentioning

confidence: 99%

“…The reaction proceeded at 37°C for 1.5 h and was stopped by adding stop buffer (50 mM glycine and 5 mM EDTA-Na2, pH 10.5; 200 ml/well). Fluorescence was determined with a fluorescence microplate reader at lex 355 nm and lem 460 nm (Gao et al, 2017).…”

Section: B-hexosaminidase Release Assaymentioning

confidence: 99%

Qing-Kai-Ling Injection Induces Immediate Hypersensitivity Reaction via the Activation of Anaphylatoxin C3

Gao

Zhang

et al. 2020

Front. Pharmacol.

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Background and Objective: Qing-Kai-Ling (QKL) is derived from a famous ancient Chinese patent medicine Angong Niuhuang pills (ANP) which has been used across Asia, especially in China, for the treatment of "febrile disease," such as stroke, encephalitis and meningitis for hundreds of years. As an extract of ANP without heavy metal, the clinical applicability of QKL is more intensive, of which its injection is commonly used in acute and serious diseases. This study aims to clarify the potential mechanisms of immediate hypersensitivity reaction (IHR) induced by QKL injection (QKLI). Methods: b-hexosaminidase release assay was performed on the human mast cell line LAD2 and mouse peritoneal mast cells. T helper 2 (Th2) immunity-amplified mice were prepared by aluminum adjuvant. Anaphylactic shock was detected by measuring rectal thermometry in propranolol-pretreated mice. For evaluating microvascular permeability, Evans Blue extravasation assay was used. Serum total IgE (tIgE) and the activated complement-derived anaphylatoxin C3 (C3a) levels were measured by ELISA. Results: QKLI was unable to elevate serum tIgE level in the Th2 immunity-amplified mice, but can increase vasopermeability and trigger anaphylaxis after the first injection. By screening seven fractions of QKLI, only the extract of Isatidis Radix (Isatis tinctoria L.) induced hindpaw Evans Blue extravasation, which was disappeared in Isatidis Radix-free QKLI. Mechanism study indicated that QKLI or Isatidis Radix-caused IHR could be blocked by the antagonists for histamine or C3a, rather than PAF or C5a. Consistently, QKLI and Isatidis Radix could also directly activate human serum complement-derived anaphylatoxin 3 (C3) in vitro with the half effective concentration values of 0.69% and 218.6 mg/ml, respectively. Conclusion: QKLI-IHR is complement activation-related pseudoallergy, rather than an IgE-mediated allergy. QKLI activates C3 and might consequently provoke mast cells to release histamine, which is a principal effector of its IHR. The pseudoallergic reaction induced by QKLI was attributed to the extract of Isatidis Radix. This study suggests a potential therapeutic strategy for the prophylaxis and treatment of QKLI-IHR.

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“…Shuang Huang Lian Injection (SHLI) is a modern formulation composed of three alcohol–water extracts of the herbs honeysuckle, Radix Scutellariae and Fructus Forsythia (Gao et al, ). This formulation has been widely used in China for over 30 years to treat acute respiratory infections, but unfortunately, serious anaphylaxis has been observed (Kua & Lee, ; Lin et al, ; Ma et al, ; H. Wang, Zhang et al, ; Zhou et al, ).…”

Section: Introductionmentioning

confidence: 99%

Screening anaphylactoid components of Shuang Huang Lian Injection by analyzing spectrum–effect relationships coupled with UPLC–TOF–MS

Feng

Jing

et al. 2018

Biomedical Chromatography

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Shuang Huang Lian Injection (SHLI) has been used in China for over 30 years as an effective and widely used Chinese herbal prescription to treat acute respiratory infectious. SHLI has, however, caused many severe anaphylactoid reactions. It is important to identify the potential anaphylactoid components of SHLI. Spectrum-effect relationships were used to explore potentially anaphylactoid components. Based on the original herbal formula, honeysuckle, Fructus Forsythiae and Radix Scutellariae extracts were prepared and combined in appropriate proportions. The preparations were then injected into the caudal vein of rats to obtain in vivo serum samples for pharmacological evaluation and fingerprint analysis. The release rate of β-hexosaminidase from RBL-2H cells and plasma histamine level was used as the pharmacological index. Chromatographic fingerprint analysis identified 22 common peaks. Regression analysis and correlation analysis were used to calculate the relationships between the peaks and the pharmacological effects and identified peaks 5, 6, 11, 12 and 17 as likely anaphylactoid agents. The correlated peaks were identified by comparing the fingerprints with in vitro samples and reference standard samples and the structure was identified by UPLC-TOF-MS. This study established a prospective method to clarify the anaphylactoid components in SHLI, which would provide guidances for screening anaphylactoid components in other traditional Chinese medicine injections.

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The Three-Herb Formula Shuang-Huang-Lian stabilizes mast cells through activation of mitochondrial calcium uniporter

Cited by 20 publications

References 72 publications

Use of the relative release index for histamine in LAD2 cells to evaluate the potential anaphylactoid effects of drugs

Use of the relative release index for histamine in LAD2 cells to evaluate the potential anaphylactoid effects of drugs

Qing-Kai-Ling Injection Induces Immediate Hypersensitivity Reaction via the Activation of Anaphylatoxin C3

Screening anaphylactoid components of Shuang Huang Lian Injection by analyzing spectrum–effect relationships coupled with UPLC–TOF–MS

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