Biol. Pharm. Bull. 30(11) 2079—2083 (2007)

tion in Kampo medicine and consists of Stephania tetrandra Radix (Stephania), Astragalus membranaceus BUNGE Radix (Astragali), Atractylodes Lancea Rhizoma, Glycyrrhizae Radix, Zingiberis Rhizoma and Zizyphi Fructus. Boi-ogi-to has long been used clinically in the treatment of arthritis and edema in China and Japan. It also improves abnormal glucose and lipid metabolism in obese diabetic patients. We have reported that Boi-ogi-to increases blood insulin and decreases blood glucose levels in streptozotocin (STZ)-diabetic mice. The anti-hyperglycemic and anti-hypoinsulinemic actions of Boi-ogi-to depend on the combination of Stephania and Astragali. Astragali does not have a direct anti-hyperglycemic effect, but potentiates the actions of Stephania on blood levels of both glucose and insulin in STZ-induced diabetes. In addition, Stephania suppresses abnormal choroidal and retinal neovascularization in STZ-induced diabetes in vitro and in vivo. Stephania contains many bis-benzylisoquinoline-type constituents, such as tetrandrine and fangchinoline. Fangchinoline significantly improves hyperglycemia of STZ-diabetic mice. Tetrandrine inhibits precapillary formation of vascular endothelial cells and neovascularization of cultured choroidal explants in STZ-diabetic rats, but does not affect hyperglycemia in diabetic mice. Fangchinoline and tetrandrine show different anti-inflammatory actions via inhibition of cyclooxygenase and interleukin-5 activities. In other studies, fangchinoline and tetrandrine were found to have similar inhibitory activities on both angiotensin I converting enzyme, and induction of proinflammatory cytokines, interleukin-1 and tumor necrosis factor-alpha by Staphylococcus aureus Cowan 1-stimulated human peripheral blood mononuclear cells. Astragali contains many isoflavones and isoflavonoids, such as formononetin, calycosin and ononin, and many saponins, such as astragaloside IV, astragaloside II, astragaloside I, and acetylastragaloside I. Formononetin significantly reduces arachidonic acid release and production of nitric oxide in lipopolysaccharide activated RAW 264.7 macrophages. It also shows estrogen receptor agonistic activity in human breast cell line MCF-7. Formononetin and calycosin activate the peroxisome proliferator-activated receptors (PPAR) alpha and gamma. The action of formononetin is more potent than that of calycosin. Calycosin is a vasorelaxant and is a noncompetitive Ca channel blocker, whose action is endothelium-independent and unrelated to intracellular Ca release. The effect of calycosin on Ca channel blockade may be different from that of dihydropyridines. In addition, formononetin, calycosin and ononin all inhibit glutamate-induced cell damage by increasing endogenous antioxidant and stabilizing cell membrane structures. In the present study, the combined effects of fangchinoline with formononetin, calycosin and ononin on the blood levels of glucose and insulin in STZ-diabetic mice were investigated to throw light on the combined effect of Stephania and Astragali in Boi-ogi-to.