| This project was supported by national natural science foundation (No.30772785, NO. 30973939), "Eleven-Five" national projects of technological supporting (No.2006BAI09B06-10).Pinellia ternata (Thunb.) Breit. whose tuberous stems are important Chinese medicines, is taxonomically belonged to Araceae family, and are well known for their irritant properties. If chewed and touched raw, the corms of the plants could result in swelling and burning pain in the mucous membranes, and an unbearable itching in skin. The needle-like raphides of calcium oxalate were proved to be their common poisonous components, named as toxic raphides. The raphides caused severe conjunctival edema in rabbit, increased capillary permeability and content of PGE2 in the exudates in mice. Toxic raphide were a complex compsed by mainly calcium oxalate crystals and protein. The content of protein was 6.084%. The study found that the agglutinin on the toxic raphide can significantly induce rat peritoneal neutrophil migration to peritoneal and rat paw edema. These results indicated that the reason of the toxic effects of raphides were the dual role of mechanical damage by calcium oxalate and chemical inflammation induced by agglutinin.Ginger was used to detoxificate to P. ternate in clinic. Traditional Chinese medicine theory held that "P. ternata feared ginger, and cooked with ginger for detoxification". Tao Hongjing held that "P. ternata was toxic and was detoxificated by ginger juice and dry ginger" However, the mechanism of ginger detoxification to P. ternata was unknown. Modern research showed that ginger had anti-inflammatory, analgesic, immune and other pharmacological activity. This paper was put forward the hypothesis "the irritating toxic of P. ternata in the body can be expressed as an inflammation. Ginger detoxification of P. ternata was related to the antagonistic effect of inflammation caused by P. ternata". This paper was designed according to this line of the research hypothesis.Inflammation models were used to reseach the raphides. The result found that raphides can cause irritant toxicity, and ginger juice can really antagonize to inflammation induced by the raphides. Gingerols were an effective part of ginger which did not depend on the anti-inflammatory mechanisms of the release of adrenal cortex hormone by activating adrenocorticotropic hormone, and its anti-inflammatory mechanism may be an inhibition of inflammatory mediators induced by the raphides in P. ternate. The result also found that gingerols can inhibit the inflammatory effects caused by P. ternate agglutinin. Main contents and findings were the following:1. The inflammatory effect induced by raphides in P. ternateThe mouse capillary permeability test, mouse peritonitis and toe swelling of rat induced by the raphides were applied to investigate the inflammatory effects of different concentrations of raphides. The result showed that raphides can increase the capillary permeability, caused the release of inflammatory mediator (PGE2) and toe swelling of rat.2 Anti-inflammatory effect of ginger juice on inflammation induced by raphides in P. ternateThe mouse peritonitis model induced by the raphides was applied to investigate the anti-inflammatory effects of ginger juice by detecting the capillary permeability, quantity of leukocytes, and the protein content in the exudates. Toe swelling of rat induced by the raphides was used to determine the swelling extent. The result showed that ginger juice exhibited comparable anti-inflammatory effects in terms of the inhibitions on the exudation and leukocytes efflux, and the production of protein. Ginger juice inhibited penetration of capillary vessel in mouse and toe swelling of rat induced by the raphides.3 Three extracts of ginger and component analysisGinger volatile oils, extracted by steam distillation, were analyzed by GC/MS. Gingerols were obtained from ginger which was extracted by ethyl acetate and was removed of volatile oils. The content of total gingerols was determined by UV spectrophotometry. The content of 6-gingeroland 6-shogaol was determined by HPLC. After extracted by the ethyl acetate, ginger dregs were extracted again by water, called as aqueous extract. The result showed that ginger volatile oil, gingerols, and aqueous extract of ginger were obtained. GC/MS analysis showed that there were 64 compounds in volatile oil which were identified mainly terpenoids. The content of total gingerols,6-gingerol, and 6-shogaol were 88.15%,19.40%and 8.11%, respectively. The results were ready to screen the active part from three extracts further.4 Anti-inflammatory effect of three parts of ginger extract on inflammation induced by raphides in P. ternate The mouse peritonitis model induced by the raphides induced was applied to investigate the anti-inflammatory effects of three ginger extracts by detecting the capillary permeability, quantity of leukocytes, and the protein content in the exudates. Toe swelling of rat induced by the raphides was used to determine the swelling extent. The result showed that gingerols exhibited comparable anti-inflammatory effects in terms of the inhibitions on the exudation and leukocytes efflux, and the production of protein. Gingerols inhibited penetration of capillary vessel in mouse and toe swelling of rat induced by the raphides. The volatile oils and aqueous extract did not have the anti-inflammatory effects.5 Anti-inflammatory mechanisms of gingerols related to inhibiting inflammatory by raphides in P. ternateAccording to the results of previous studies, toe swelling induced by the raphides of normal rat and toe swelling induced by the raphides of bilaterally adrenalectomized rats were used to determine the swelling extent. The contents of VitC and cholesterol were measured in normal adrenal glands. The result showed that gingerols had a significantly suppressive effect on paw edema of normal rat and adrenalectomized rat induced by raphides and had no effect on the contents of VitC and cholesterol in normal adrenal glands. The result showed gingerols had an anti-inflammatory effect, which were independent on pituitary-adrenal axis.The content of PGE2, NO and MDA in the mouse exudate were respectively measured in rats with acute peritonitis induced by raphides. The activity of COX-2 and the content such as PGE2, TNF-a were examined in the toe of rats induced by raphides. The result showed that gingerols significantly inhibited the production of NO, PGE2, and MDA in exudate of peritonitis rats. Furthermore, gingerols inhibited the activity of COX-2, and reduced the production of PGE2 and TNF-a in the toe. The anti-inflammatory mechanisms of gingerols may be related to inhibiting the production of inflammatory mediators and free radicals.6 Anti-inflammatory effect of gingerols on inflammation induced by P. ternate agglutininThe mouse peritonitis model induced by the agglutinin was applied to investigate the anti-inflammatory effects of gingerols by detecting the releases of inflammatory mediators PGE2 in the exudates. Toe swelling of rat induced by the agglutinin was used to determine the swelling extent. The result showed that gingerols exhibited comparable anti-inflammatory effects in terms of the inhibitions on the releases of inflammatory mediator(PGE2) and the swelling extent of rat The research showed that raphides of P. ternate can cause intense inflammatory toxicity. Ginger juice and gingerols effectively antagonized to inflammatory induced by raphides of P. ternate. The anti-inflammatory mechanism of gingerols is not related to the release of adrenal cortex hormone by activating adrenocorticotropic hormone, and it may be an inhibition of COX-2, PGE2, TNF-a, NO, and MDA. The result also found that gingerols can inhibit the inflammatory effects induced by agglutinin. This paper clarified the scientific content on the theory of Chinese medicine "P. ternate can be detoxification by Ginger". It provided a basis to the clinical application of ginger detoxification to P. ternate. |
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