Examination of the nitric oxide production-suppressing activity inSanguisorbae Radix > Volume 02 - 2002

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Oriental Pharmacy and Experimental Medicine
Volume 02 - 2002
Date: 2002

Journal: Pages 69-79

August 2002 | Examination of the nitric oxide production-suppressing activity inSanguisorbae Radix…

Takako Yokozawa



​Nitric oxide (NO) is an interesting and importantmolecule with diverse functions, exerting a varietyof both beneficial and detrimental effects indifferent tissues, including the kidney. It has beendemonstrated that NO plays an important role inrenal function by participating in the regulation ofrenal hemodynamics, sodium excretion and reninrelease, tubuloglomerular feedback, pressure natriuresis,and tubule function (Galle and Wanner, 1996;Lahera et al., 1997). However, excessive NOproduced under certain pathological conditionsmay also produce cytotoxic effects and aggravaterenal dysfunction. It still remains debatablewhether NO is beneficial or harmful in acute andchronic renal failure or other renal diseases, andwhether NO or NO synthase inhibitors should beused to regulate these conditions. Conflictingresults have been reported in studies on humans,and also in animal experimental models (Fujihara etal., 1995; Noiri et al., 1996; Thorup and Persson, 1996). Lipopolysaccharide (LPS) releases many mediatorsand produces the condition known as endotoxemia.These mediators include interleukins, tumor necrosisfactor, oxygen free radicals, toxic eicosanoids,platelet activating factor and NO (Wolkow, 1998).Endotoxemia gives rise to a multiple organdysfunction syndrome involving failure of thecirculatory system, liver, lungs and kidney. Anincrease in the production of NO due to theinduction of inducible NO synthase (iNOS) hasbeen proposed to be responsible for this multipleorgan dysfunction (Thiemermann et al., 1995), andselective iNOS inhibition has been shown to attenuateor prevent the syndrome (Liaudet et al., 1998).On the other hand, NO, which has an enormousrange of beneficial functions in organisms, includingregulation of vascular tone, ventilation, hormonesecretion, inflammation, immunity and neurotransmission,is also suspected to be cytotoxic or cytostatic tohost cells, and to act as a toxic radical (Moncada etal., 1991; Nathan, 1992; Gross and Wolin, 1995;Harrison, 1997). In addition, recent experimentshave revealed that the toxicity and damage causedby NO in tissues and cells is multiplied enormously ifit reacts with the superoxide radical (O2-) to yieldperoxynitrite (ONOO-), an extremely reactiveradical (Radi et al., 1991; Akaike et al., 1998).Sanguisorbae Radix is an oriental medicine thatis rarely used in Japan, and is not used in any of theoriental medical prescriptions that are in currentclinical use. In China, however, it is used ininternal medications for hemostasis and for thetreatment of hematemesis, hemoptysis, melenaand hypermenorrhea, and in external medicationsfor the treatment of dermatitis, eczema and incisedwounds. On the other hand, experimental pharmacologicaldata related to this medicine are insufficient; thereare only a few reports on its anti-burn, hemostaticand antiemetic effects in rabbits and pigeons, andon its antibacterial effects on Staphylococcus aureusand Pseudomonas aeruginosa (Jiangsu New MedicalCollege, 1987). In a previous study, to investigatethe effects of some oriental medicines on diseases that are attributable to excessive NO, we carriedout a screening test using the NO donor sodiumnitroprusside in an in vitro evaluation system, andreported the newly found NO-suppressive activityof Sanguisorbae Radix (Chen et al., 1999a ; Yokozawaet al., 1999).In this study, we investigated whether SanguisorbaeRadix has a protective effect against pathologicalconditions involving NO and ONOO-. The presentstudy was also designed to determine whichcomponent of Sanguisorbae Radix is responsiblefor NO-suppressive activity, using LPS-stimulatedmacrophages, and then investigated the mechanism bywhich sanguiin H-6 acts, with special reference toiNOS.

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