Byakkokaninjinto prevents body water loss by increasing the expression of kidney aquaporin‐2 and skin aquaporin‐3 in KKAy mice

Abstract

Byakkokaninjinto (BKN) is an herbal medicine used for the relief of diuresis, thirst and dermal pruritis that are associated with diabetes. The effects of BKN on the expression of aquaporins (AQPs) in the kidney, salivary gland and skin were investigated in order to clarify the mechanism of drug action. Seven-week-old KKAy mice were given feed containing 4.5% BKN for 4 weeks. Compared with the control group, BKN administration did not affect the blood glucose and insulin concentration. However, water intake and urine volume were significantly reduced. AQP2 protein expression in the kidney inner medullary was significantly increased after BKN administration. AQP3 mRNA and protein expression in skin tissue was significantly increased after BKN administration. However, BKN administration did not affect AQP5 mRNA expression in the salivary gland. These results suggest that BKN treatment relieves diuresis, thirst, and dermal pruritis by increasing kidney AQP2 expression and skin AQP3 expression.

Elucidating the Mechanism by Which <i>Gypsum fibrosum</i>, a Traditional Chinese Medicine, Maintains Cutaneous Water Content

“…5) It has also been shown that an increase in the expression of cutaneous AQP3 is involved in the improvement of cutaneous pruritus that is observed following administration of Byakkokaninjinto. 5) In addition, it has been reported that the CaSO 4 in Gypsum fibrosum can lead to an increase in cutaneous AQP3 expression levels by triggering an increase in the concentration of cutaneous Ca. 6) In this study, we elucidated the mechanism by which Gypsum fibrosum leads to an increase in cutaneous AQP3, focusing on the increase in the intracellular concentration of cutaneous Ca.…”

“…The results of these studies demonstrated that oral administration of Byakkokaninjinto to KKAy mice, a model of type 2 diabetes mellitus, 3,4) relieved thirst and polyuria caused by diabetes mellitus. 5) Additionally, the improvement in these symptoms were attributable to an increase in the expression level of aquaporin-2 (AQP2), a membrane water channel, that is expressed in large quantities in kidneys. 5) It has also been shown that an increase in the expression of cutaneous AQP3 is involved in the improvement of cutaneous pruritus that is observed following administration of Byakkokaninjinto.…”

“…5) Additionally, the improvement in these symptoms were attributable to an increase in the expression level of aquaporin-2 (AQP2), a membrane water channel, that is expressed in large quantities in kidneys. 5) It has also been shown that an increase in the expression of cutaneous AQP3 is involved in the improvement of cutaneous pruritus that is observed following administration of Byakkokaninjinto. 5) In addition, it has been reported that the CaSO 4 in Gypsum fibrosum can lead to an increase in cutaneous AQP3 expression levels by triggering an increase in the concentration of cutaneous Ca.…”

Gypsum fibrosum and its major component CaSO4 increase cutaneous aquaporin-3 expression levels

“…Preparation of the membrane fraction of skin for immunoblotting (Aburada et al, 2011) The skin tissue was homogenised in dissecting buffer (0.3 M sucrose, 25 mM imidazole, 1 mM EDTA, 8.5 M leupeptin, 1 M phenylmethylsulfonyl fluoride; pH 7.2) using a physcotron homogeniser (Microtec Co., Ltd., Chiba, Japan) on ice. The homogenate was centrifuged (800 × g at 4 • C for 15 min).…”

“…We have indicated the possibility that Byakkokaninjinto improves this itchy sensation in the skin by increasing cutaneous water content. Moreover, we have revealed that Byakkokaninjinto exerts this effect by increasing cutaneous AQP3 levels (Aburada et al, 2011). Byakkokaninjinto is composed of Gypsum fibrosum (gypsum), Anemarrhenae rhizoma (rhizome of Liliaceae Anemarrhena asphodeloides Bunge), Glycyrrhizae radix (radix of Leguminosae Glycyrrhizae uralensis Fisch), Ginseng radix (radix of Araliaceae Panax ginseng C.A.…”