Evaluation of the Impact of the Traditional Medicine Formulation Goreisan and Its Components on Mesenteric Lymphatic Vessel Contraction and Lymphatic Endothelial Barrier Function

Abstract

Kampo medicines are traditional herbal formulas used to treat and prevent various diseases. The Kampo medicine Goreisan is a known diuretic and is currently being tested in the clinic to reduce symptoms of surgically induced lymphedema in OB/GYN patients in Japan. The present study was aimed to clarify how Goreisan and its five different components affect lymphatic pump function. Mesenteric collecting lymphatics were isolated from anesthetized male Sprague Dawley rats, and mounted on resistance‐matched glass micropipettes in a 37 °C physiological salt solution bath for studies. The luminal pressure was set at 2 cm H2O and vessels that established intrinsic phasic contractions were studied. Contraction frequency (CF), end diastolic diameter (EDD), and end systolic diameter (ESD) were measured. From these, amplitude (AMP), ejection fraction (EF), and fractional pump flow (FPF) were calculated. Goreisan was applied at concentrations of 1–30 μg/ml. Its components, Cinnamomi Cortex, Atractilodys Rhizoma, Alismatis Rhizoma, Polyporus, and Poria were also studied at concentrations of 1–30 μg/ml. To measure barrier function, human dermal lymphatic endothelial cells (LEC) were treated with 1–100 μg/ml of each compound and transendothelial electrical resistance (TER) was determined by electric cell‐substrate impedance sensing (ECIS). The results show that treatment with Goreisan causes no significant changes in all parameters compared to baseline. However, 30ug/ml Alismatis Rhizoma caused a significant reduction in CF and FPF. The other components did not affect pumping. Goreisan also does not significant affect TER. Polyporus significantly increased TER compared to baseline, while the other components elicited no change. Collectively, the results suggest that Goreisan does not directly affect lymphatic pumping or barrier function, although at its component Alismatis Rhizoma can influence pump activity and Polyporus can enhance barrier function. By extension, in the lymphedema patients treated with Goreisan, its pharmacological action is more likely to be on renal mechanism to reduce excess body fluids. Additional work is needed to determine whether Goreisan may have direct effect to rescue impaired lymphatic vessel functions under inflammatory conditions.Support or Funding InformationThis work was supported by Rotary International Global Grants Scholarship Grant Number GG1746618.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.