Oxalic acid in ginger specifically denatures the acrid raphides in the unprocessed dried tuber of Pinellia ternata

Abstract Objective: Pinellia Tuber, the dried tuber of Pinellia ternata, is widely used in Japanese Kampo medicines and traditional Chinese medicines. The unprocessed Pinellia Tuber is known to cause very strong acrid irritation at oral and laryngopharynx mucosa. Recent studies have shown that the sharp needle-like crystals called raphides, that are composed of calcium oxalate and proteins, are the main causative substances of the irritation. Ginger, the rhizome of Zingiber officinale, has been used in the processing to reduce the acridity of Pinellia Tuber since before the sixth century, however, the mechanisms of reducing acridity have not been scientifically proved yet. Methods: We developed the raphides denaturation assay (RDA) to quantify the degree of denaturation in the raphides to cause irritation. By their lipophilic characters, the raphides could be extracted in petroleum ether (PE) layer from powdered Pinellia Tuber suspended in water, and the contents of the raphides in PE layer were measured by the absorbance. By this assay, we conducted the activity-guided fractionation from the boiling water extract of ginger to find the ingredients to denature the raphides. We also conducted the gustatory tests to detect the change of the irritation of the denatured raphides. Results: The treatment of powdered Pinellia Tuber suspension with ginger extract reduced the distribution of raphides in PE layer in RDA in a concentration-dependent manner. The activity-guided fractionation using RDA revealed that oxalic acid was the main active ingredient in ginger extract to denature the raphides of Pinellia Tuber. Oxalic acid reduced the lipophilicity of the raphides in the thermo-, time-, and concentration-dependent manners, and its activity was affected by pH. The treatment of powdered Pinellia Tuber suspension with oxalic acid significantly reduced its acrid irritation in gustatory test in human. Conclusions: We found that oxalic acid is the main active ingredient in ginger to reduce the acrid irritation of Pinellia Tuber. Graphical abstract: http://links.lww.com/AHM/A10