Anti-allergic potential of Typhonium blumei: Inhibition of degranulation via suppression of PI3K/PLCγ2 phosphorylation and calcium influx

Typhonium blumei Nicolson & Sivadasan (Araceae) is a traditional Chinese medicinal herb possessing detumescent, detoxifying, and anti-inflammatory activities. It is used in Taiwan as a folk medicine to treat cancer and inflammatory diseases. Typhonium blumei is usually not distinguished from Typhonium roxburghii Schott and they are commonly used interchangeably. To evaluate and compare the anti-allergic and anti-inflammatory properties of T. blumei and T. roxburghii, their composition profiles and molecular basis of the anti-allergic effect. The methanolic plant extracts were partitioned with different solvents to obtain the nonpolar fractions. The anti-allergic activity of the nonpolar fractions was assessed by A23187- and antigen-induced degranulation assays using RBL-2H3 mast cells. Several molecular targets were investigated: FcεRI receptor expression by flow cytometry, calcium influx by live cells imaging fluorescent microscopy, cytokines mRNA expression by RT-PCR, and protein expression by Western blotting. The anti-inflammatory activity was evaluated using superoxide anion and elastase release assays in human neutrophils. TLC, NMR and GC–MS analyses were conducted to evaluate the chemical composition of the fractions. The nonpolar fractions of both Typhonium species showed potent inhibitory activity in A23187-induced degranulation assay in RBL-2H3 cells. They also inhibited superoxide production and elastase release in human neutrophils. T. blumei nonpolar fractions inhibited antigen-induced β-hexosaminidase and histamine release. The nonpolar fractions of T. blumei significantly inhibited calcium influx upon activation with either A23187 or an antigen. The fractions did not affect FcεRI receptor expression, mRNA level of IL-4 and MCP-1 cytokine production or MAPK proteins expression, but did suppress the calcium signaling pathway via PI3K/PLCγ2. The active fractions were rich in fatty acids with palmitic, linoleic and α-linolenic acids identified as the major fatty acids in both plants. The content of omega-3 unsaturated fatty acids was higher in T. roxburghii nonpolar fractions compared to T. blumei. Both species possess potent anti-allergic and anti-inflammatory activities. The inhibition of degranulation in mast cells was attributed to calcium influx modulation. The obtained results support the traditional use of T. blumei in the treatment of inflammatory diseases as well as its substitution with T. roxburghii.