Impact of Goreisan components on rat mesenteric collecting lymphatic vessel pumping

Abstract

Background Goreisan is a traditional herbal formulation with diuretic properties tested as a clinical therapeutic to alleviate lymphedema in Japan. The present study aimed to determine how Goreisan and its five different components affect lymphatic pump function. Methods Mesenteric collecting lymphatics were isolated from anesthetized Sprague–Dawley rats and mounted on resistance‐matched glass micropipettes in a 37°C physiological salt solution bath for studies. Diameter was continuously measured to obtain the following lymphatic pump parameters: contraction frequency (CF), end diastolic diameter (EDD), and end systolic diameter (ESD), contraction amplitude (AMP), ejection fraction (EF), and fractional pump flow (FPF). Goreisan and each of its components (Cinnamomi Cortex, Atractylodis Rhizoma, Alismatis Rhizoma, Polyporus, and Poria) were applied to the bath at concentrations of 1–30 μg/mL. Results The results show that while Goreisan causes no significant changes to lymphatic pumping, Alismatis Rhizoma and Polyporus each significantly reduce CF and FPF. In addition, rats that received oral administration of Goreisan and Alismatis Rhizoma for 1 week had elevated expression of VEGFR‐3 in their mesenteric collecting lymphatics. Conclusions Collectively, the results suggest that some components of Goreisan have a direct, rapid impact on lymphatic pumping. These findings provide new insights but also raise new questions about the therapeutic potential of Goreisan in patients with secondary lymphedema.

Effect of Goreisan, a Traditional Japanese Medicine, on Rat Hindlimb Lymphedema

“…Rats were orally administered the test drugs (goreisan, 1 g/kg; FRS, 5 mg/kg; and PDN, 10 mg/kg) or distilled water (10 mL/kg) once a day starting 6 d after PLN dissection. The doses of goreisan, 15,16) FRS, 17,18) and PDN 19,20) were estimated according to previous animal studies, respectively.…”

“…13) In patients with lymphedema of the lower extremities, the ratio of extracellular water to total body water was significantly decreased by combined treatment with goreisan compared to CDT alone. 14) While an animal study has demonstrated that goreisan could augment the pumping function of lymphatic vessels through the elevated expression of vascular endothelial growth factor receptor-3 in rat mesenteric lymphatic vessels, 15) the effect of goreisan on lymphedema remains unknown.…”

Lymphatic Pathophysiology

“…In the work by Jo et al, 7 the effects of five different components which comprise Goreisan, a traditional herbal formulation (used as a therapeutic in Japan to alleviate lymphedema symptoms), were investigated for their effects on mesenteric lymphatic pumping in rats. They showed that that acute exposure of two components of Goreisan decreased lymphatic pumping in isolated rat mesenteric collecting lymphatics while oral administration of Goreisan induced vascular endothelial growth factor receptor 3 (VEGFR3), in these lymphatic vessels.…”

“…Their findings revealed a differential response in AML‐cell infiltrated spleen and liver, indicating that interstitial fluid and efferent lymph can provide unique information about the specific microenvironment responses that are variable in target organs during AML progression. In the work by Jo et al, 7 the effects of five different components which comprise Goreisan, a traditional herbal formulation (used as a therapeutic in Japan to alleviate lymphedema symptoms), were investigated for their effects on mesenteric lymphatic pumping in rats. They showed that that acute exposure of two components of Goreisan decreased lymphatic pumping in isolated rat mesenteric collecting lymphatics while oral administration of Goreisan induced vascular endothelial growth factor receptor 3 (VEGFR3), in these lymphatic vessels.…”