Ganoderic acid A attenuated hepatic impairment by down-regulating the intracellular JAK2-STAT3 signaling pathway in induced mushroom poisoning

Abstract

Background: Mushroom poisoning is one of the most prominent public health problems. However, there is no special antidote so far. In the present study, we verified that Ganoderma lucidum may be an effective approach for treatment of acute mushroom poisoning.

Methods: A retrospective study was performed within the past 20 years, we compiled information on the treatment of α-Amatoxin mushroom poisoning with Ganoderma lucidum by evaluating the mortality rate and liver function before and after treatment. Moreover, we explore the potential underlying mechanism of Ganoderma lucidum in the treatment of α-amanita poisoning in both in vivo animal experiments and in vitro cell experiments.

Results: In our study, a total of 556 cases of mushroom poisoning were integrated over the past 20 years, the primary outcome was in-hospital mortality. Specificity, descriptive data of ALT, AST, BA and STB were evaluated for the effectiveness of protection to acute liver damage. From 1994 to 2002, there were 55 cases of mushroom poisoning in which 372 individuals were poisoned, 129 individuals died, with a mortality of 35%. Since 2002, after being treated with Ganoderma lucidum, surprisingly, the mortality decreased to 0%, and all the 184 patients were cured, the hepatic impairment improved significantly within 10 days. Based on a multivariate logistic regression analyses, after adjusting for age, gender and baseline clinical indicators, it was found that Ganoderma lucidum treatment was effective in reducing the morbidity (OR = 0.58), and Ganoderma lucidum treatment also showed an improvement in liver enzymes and in shortening the length of hospitalization significantly. Meanwhile, the main components of Ganoderma lucidum, Ganoderic acid A could significantly improve the survival rate and liver function in α-Amatoxin poisoned mice and may effectively inhibit the JAK2-STAT3 pathway, which could contribute to the detoxification in poisoned patients.

Conclusion: Ganoderma lucidum is very effective in treating mushroom poisoning by α-amanita and is worth promoting.

Keywords: Ganoderma lucidum; Ganoderma lucidum A; liver toxicity; mushroom poisoning; α-amatoxin.

Figure 1

Pictures of Amanita (A) and Ganoderma lucidum (B).

Figure 2

The change trend of the mortality and curves of liver function after treatment with Ganoderma lucidum.

Figure 3

(A) a survival analysis of NC, α-Amanitin and or Ganoderic acid A mice indicated subjected to α-Amanitin (n = 10). (B) plasma concentrations of ALT, AST and SCr in mice 24 hours after α-Amanitin or Ganoderic acid A injection (n = 8), (C) representative images of liver tissue hematoxylin and eosin (H&E) staining of liver from three group mice. Data were pooled from at least two independent experiments. Circles represent individual mice. Error bars indicate ±SDs. ns, not significant, **P<0.01, ***P<0.001. Statistics are by one-way analysis of variance (ANOVA) or survival curve comparison [log-rank (Mantel-Cox) test].

Figure 4

Ganoderic acid A return to RNA polymerase II activity via JAK2/STAT3 pathway. A. JAK2 and STAT3 were determined by chromatin immunoprecipitation-RT-PCR in melanoma cell lines (AML12). P values were calculated using one-way ANOVA and Dunnett’s multiple comparison test. Results are presented as mean ± SD, n = 3, **P<0.01, ***P<0.001; B. Western-blot analysis of the quantity of phosphorylated (p) JAK2 and STAT3, total JAK2, total STAT3 in the livers of mice of indicated genotypes at the indicated time points after α-Amanitin and or Ganoderic acid A. n = 3 independent biological repeats.