Outlining the keyword co-occurrence trends in Shuanghuanglian injection research: A bibliometric study using CiteSpace Ⅲ

Objective:To explore the evolvement and new trends in the use of Shuanghuanglian injection(SHLI).Methods:China National Knowledge Infrastructure(CNKI),PubMed,and Embase were extensively searched using the search terms“Shuanghuanglian injection”and“Shuanghuanglian fenzhen”to retrieve articles relevant to SHLI(1992e2020).Retrieved articles were further investigated by two authors to exclude those unrelated to SHLI.The bibliographical references of the included articles were exported as raw data and then treated using the CiteSpace tool to visualize the mapping of the SHLI research domain.Essential clusters and highly frequent keywords were quantified for further analysis.The clusters were automatically labeled by the algorithm of tf*idf for objective analysis.Basic bibliometric features,including article types and yearly trend in article numbers were also determined and discussed.Results:The modules of the keywords of interest presented clear boundaries with a high modularity score(Q=0.73).High-confidence clusters were identified,including bioactivity fingerprint(S=0.99),equal pupils(S=0.91),drug preparation department(S=0.87),difficulty in respiration(S=0.85),peristalsis(0.88),and Danshen powder injection(S=0.94).The characteristic keywords in terms of frequency and burstiness were Shuanghuanglian powder for injection(F=235,B=5.22),SHLI(F=112,B=11.39),and adverse drug reactions(ADRs;F=104,B=7.35).Conclusion:In the field of SHLI study,there are five major topic categories:bioactivity fingerprint;ADR mechanism and cause detection;proper preparation;clinical evidence accumulation;and efficacy in diseases with no effective treatment and combination usage.The trend for using modern methodologies from a science-based perspective to study SHLI will continue to exist.The causes of multi-factorial ADRs may be an important topic for future studies.

Shuanghuanglian injection downregulates nuclear factor-kappa B expression in mice with viral encephalitis

A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and protein expression of intelectin-2 and nuclear factor-kappa B in the viral encephalitis and control groups. Nuclear factor-kappa B and intelectin-2 mRNA and protein expression were significantly increased in mice with viral encephalitis. After intraperitoneal injection of Shuanghuanglian at a dose of 1.5 mg/kg for 5 successive days, intelectin-2 and nuclear factor-kappa B protein and mRNA expression were significantly decreased. To elucidate the relationship between intelectin-2 and nuclear factor-kappa B, mice with viral encephalitis were administered an intracerebral injection of 107 pfu recombinant lentivirus expressing intelectin shRNA. Both protein and mRNA levels of intelectin and nuclear factor-kappa B in brain tissue of mice were significantly decreased. Experimental findings suggest that Shuanghuanglian injection may downregulate nuclear factor-kappa B production via suppression of intelectin production, thus inhibiting inflammation associated with viral encephalitis.

Inhibitory effects of Shuanghuanglian injection on nuclear factor-kappa B expression in mice with viral encephalitis in a time-and dose-dependent manner

Previous studies have confirmed that the anti-virus effects of Shuanghuanglian injection may be associated with nuclear factor-kappa B activity. This study observed nuclear factor-kappa B expression in mice with viral encephalitis, and showed significant decreases in nuclear factor-kappa B protein and mRNA levels following Shuanghuanglian injection. The inhibitory effect was more significant with prolonged intervention duration and increased treatment dose. These findings verify that Shuanghuanglian injection plays a therapeutic role in viral encephalitis by reducing expression of nuclear factor-kappa B in a time- and dose-dependent manner.

Baicalin and rutin are major constituents in Shuanghuanglian injection involving anaphylactoid reaction

OBJECTIVE: To identify the constituents in Shuanghuanglian injection(SHLI) that correlate with anaphylactoid reaction.METHODS: Chemical fingerprints of 10 batches SHLI samples were determined by High Performance Liquid Chromatography(HPLC), and further investigated by similarity analysis. Combined with optical microscopy, both anaphylactoid experiments and confirmatory assay were displayed in Rat basophil leukemia cells(RBL-2H3) to obtain the histamine release inducing by SHLI. The content of histamine was tested by Enzyme-Linked Immuno Sorbent As-say method. Partial least squares regression(PLSR)method and HPLC-DAD-ESI-MSntechnology were conducted to analyze constituents in SHLI involving anaphylactoid reaction.RESULTS: The results of spectrum and effect relationships showed that the eight constituents were positively correlated with anaphylactoid reaction.Among which, nearly 90% of them were identified as baicalin and rutin with PLSR and HPLC-DAD-ESI-MSn. This result was in accordance with confirmatory assay on RBL-2H3 cells.CONCLUSION: Baicalin and rutin from SHLI were the main constituents involving anaphylactoid reaction.