Anemoside A₃-induced Relaxation in Rat Renal Arteries: Role of Endothelium and Ca²⁺Channel Inhibition

Abstract

Anemoside A(3), a lupane-type triterpenoid saponin, exists in the roots of Pulsatilla chinensis, but its pharmacological properties are largely unknown. The present study aimed to investigate the mechanisms underlying anemoside A(3)-induced relaxation in rat renal arteries. Changes of isometric force were determined on arteries with a myograph. Anemoside A(3) caused concentration-dependent relaxation in precontracted aortas, mesenteric, left coronary, and renal arteries. Removal of endothelium or treatment with charybdotoxin plus apamin slightly but significantly attenuated the relaxation in renal arteries. TEA(+) inhibited the relaxation caused by anemoside A(3) in renal arteries with and without endothelium while glibenclamide, BaCl(2), or capsaicin had no effect on it. Anemoside A(3) produced less relaxation in rings contracted by 60 mM KCl compared with rings contracted by receptor-dependent constrictors. It further inhibited contractions induced by Ca(2+) influx through nifedipine-sensitive voltage-gated Ca(2+) channels, nifedipine-insensitive receptor-operated Ca(2+) channels, and by intracellular Ca(2+) release. Pretreatment with nifedipine attenuated anemoside A(3)-induced relaxation. Taken together, the present results indicate that anemoside A(3) produces relaxation in rat renal arteries through multiple mechanisms. The release of CTX/apamin-sensitive endothelium-derived hyperpolarizing factor, stimulation of TEA(+)-sensitive K(+) channel, and inhibition of Ca(2+) influx jointly contribute to the relaxation.

Pharmacological activities and molecular mechanisms of Pulsatilla saponins

“…2 ), while endothelium-derived hyperpolarizing factor and K + channel activation in vascular smooth muscle cells play a minor role. AA3 could be applied to the treatment of renovascular hypertension by reducing vascular tension [ 63 ]. As a first-line chemotherapy agent, cisplatin also has toxic side effects on the kidney, and AB4 showed detoxicating effect against cisplatin-caused body weight loss and kidney injury without reducing anticancer activity of cisplatin [ 61 ].…”

Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

“…Among them, anemoside A 3 (AA3), a natural triterpenoid glycoside isolated from the root of P . chinensis [ 14 , 17 , 18 ], induces relaxation in rat renal arteries through the stimulated release of endothelium-derived hyperpolarizing factor, activation of K + channel, and inhibition of Ca 2+ influx [ 19 ]. AA3 protects PC12 cells from cell death induced by sodium cyanide or glucose deprivation [ 20 ].…”

A sensitive HPLC–MS/MS method for the simultaneous determination of anemoside B4, anemoside A3 and 23‐hydroxybetulinic acid: Application to the pharmacokinetics and liver distribution of Pulsatilla chinensis saponins

“…Among the saponins, anemoside B4, a marker for the quality control of the herb as documented by the Chinese Pharmacopoeia Commission (), showed the highest content in the herb with antitumor, anti‐inflammatory, antiviral and immunomodulatory activities (He et al, ; Hu et al, ; Hu, He, & Wang, ; Liu et al, ). Anemoside A3 also showed substantial content in the herb and exerted cognitive enhancing, neuroprotective and vasorelaxing effects (Gao et al, ; Ip et al, ; Zhang et al, ). Moreover, 23‐hydroxybetulinic acid, the aglycone of anemoside B4 and anemoside A3, exhibited anti‐inflammatory and strong cytotoxicity in several cancer cell lines, such as human leukemia HL‐60 cells, hepatocellular carcinoma, cervical adenocarcinoma and melanoma cells (Liu et al, ; Suh et al, ; Zhang et al, ).…”