Abstract
Typhonii rhizoma, a widely used herb in traditional Chinese medicine, has acute irritating toxicity related to Typhonium giganteum lectin (TGL). TGL exhibits acute inflammatory effects, but the underlying molecular mechanisms are largely unknown. This paper is designed to assess the pro-inflammatory response of TGL on RAW 264.7 cells. RAW 264.7 treated with 6.25, 12.5, 25, and 50 µg/mL TGL showed elevated levels of inflammatory factors (TNF-α, IL-1β) and of p-IκB and p-p65, all dose-dependent, indicating that TGL had a substantial inflammatory effect and mobilized the nuclear factor-κB (NF-κB) pathway. All four TGL treatments also induced the up-regulation of reactive oxygen species (ROS) and cytosolic free Ca2+ and down-regulation of mitochondrial membrane potential (MMP). The production of cytokines and p-IκB, p-p65 were reduced by N-acetylcysteine (NAC), an ROS scavenger, which somewhat abrogated ROS production. The results showed the TGL-activated inflammatory signaling pathway NF-κB to be associated with the overproduction of ROS. Moreover, 50 μg/mL treatment with TGL led to cell apoptosis after 1 h and increased necrosis over time. These results provided potential molecular mechanisms for the observed inflammatory response to TGL including up-regulation of ROS and cytosolic free Ca2+, down-regulation of MMP, the mobilization of the NF-κB pathway, and the subsequent overproduction of pro-inflammatory factors resulting in apoptosis. Long-term stimulation with TGL resulted in strong toxic effects related to inflammation that induced necrosis in macrophages.
Highlights
Typhonii rhizoma is the dry tuber of Typhonium giganteum Engl. (Araceae)
We reported previously that the pro-inflammatory activity of Typhonium giganteum lectin (TGL) was related to mobilization of the nuclear factor-κB (NF-κB) pathway accompanied by overproduction of inflammatory factors [1]; the specific mechanisms are still unknown
Were associated with less of p-p65 p-IκB.involving. These results revealed that pathway accompanied by overproduction of reactive oxygen species (ROS) was of considerable importance to inflammation caused by TGL, involving mobilization of the NF-κB pathway accompanied by overproduction of TNF-α and IL-1β
Summary
Typhonii rhizoma is the dry tuber of Typhonium giganteum Engl. (Araceae). It is widely used in traditional Chinese medicine to dispel gas and relieve convulsions. Toxins 2017, 9, 275 tastes spicy and can irritate the tongue and throat, leading to soreness, excessive salivation, or even suffocation. We found its toxicity to be related to Typhonium giganteum lectin (TGL), a type of monocot lectin from the tuber of T. giganteum. This lectin demonstrated pro-inflammatory activity, including stimulation of macrophages to generate excessive inflammatory factors (TNF-α, IL-1β), and induction of neutrophil migration [1]. Pinellia ternata lectin (PTL), another monocot lectin from the tuber of Pinellia ternata (Thunb.) Breit. (Araceae) has similar pro-inflammatory activities involving the overproduction of reactive oxygen species (ROS), mobilization of the NF-κB pathway, and the subsequent release of large quantities of inflammatory factors [2]
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