Novel Antihypertension Mechanism of β-Glucan by Corin and ANP-Mediated Natriuresis in Mice

Figures & data

Table 1. Expression of proteolysis-associated genes in mice liver by single (SOA) or multiple oral (MOA) BGF administrations.

Gene symbol	Biological activity	NOA	Expression in liver (log2)		Average fold change
			Control	BGF
PLTP	Transportation of lipid and cholesterol Vitamin E biosynthetic process Sperm motility	SOA	9.7	10.8	2.2
SLC3A1	Amino acid transport in membrane Proteolysis Reabsorption of cystine in the kidney	SOA	10.1	9.1	0.5
Corin	Regulation of systemic arterial blood pressure by atrial natriuretic peptide Proteolysis Peptide hormone processing Neuron differentiation Protein maturation by peptide bond cleavage	SOA	8.2	6.8	0.4
		MOA	6.6	9.2	5.8
CST3	Biomarker of kidney or cardiovascular diseases Regulation of Alzheimer’s disease Inhibition of lysosomal proteinases	SOA	12.5	11.5	0.5
Serpin A7	Transportation of thyroid hormones in the serum High affinity for T4 and T3 hormones	MOA	10.6	9.4	0.4

BGF was orally administered at 100 mg/kg/day to ICR mice (n = 5) for one or seven days. NOA: number of oral administration; BGF: β-glucan fraction of Phellinus baumii; SOA: single oral administration; MOA: multiple oral administration for seven days. PLTP: phospholipid transfer protein; SLC3A1: solute carrier family 3 member 1; CST3: cystatin 3; Serpin A7: serpin family A member 7.

Figure 1. Real-time PCR of corin mRNA expression in mice tissues. (A) ICR mice (n = 4) were orally administered zymosan, barley β-glucan, and BGF at 100 mg/kg for seven consecutive days. RT-PCR analysis of corin was performed on the mRNAs of mice liver and kidney tissues. (B) RT-PCR analysis of corin was performed on the kidney tissue of ICR mice treated with β-glucans from Phellinus baumii, Phellinus linteus, and Ganoderma lucidum at 100 mg/kg for seven consecutive days. CON: control; ZYM: β-glucan of yeast zymosan A from Saccharomyces cerevisiae; BAR: β-glucan of barley; BGF: β-glucan fraction of carpophores of Phellinus baumii. The values are expressed as the average ± SD. *p < 0.01, **p < 0.005.

Figure 2. Effects of β-glucans on the production of ANP in various mice tissues. ICR mice (n = 6) were orally administered zymosan, barley β-glucan, and BGF at 100 mg/kg/day for seven consecutive days. ANP peptides were extracted from the heart, kidney, and liver of mice with protein extraction kit solution by lysing with a bead-beater homogenizer. The ANP concentrations were determined by an ELISA kit for mouse ANP by measuring the OD₄₅₀ with a spectrophotometer. CON: control; ZYM: β-glucan of yeast zymosan A from Saccharomyces cerevisiae; BAR: β-glucan of barley; BGF: β-glucan fraction of carpophores of Phellinus baumii. The values are expressed as the average ± SD. *p < 0.01.

Figure 3. Effects of orally administered β-glucans on changes in body weight and food and water intakes in high-salt diet-fed mice. ICR mice (n = 4) kept in metabolic cages and were orally administered zymosan, barley β-glucan, and BGF at 100 mg/kg/day for seven consecutive days. Mouse body weight (A), food (B) and water (C) intakes were measured daily. CON: control; ZYM: β-glucan of yeast zymosan A from Saccharomyces cerevisiae; BAR: β-glucan of barley; BGF: β-glucan fraction of carpophores of Phellinus baumii. The values are expressed as the average ± SD.

Figure 4. Effect of orally administered β-glucan on sodium excretion in normal-salt-fed mice. β-Glucans of zymosan, barley, and BGF were orally administered at 100 mg/kg/day to ICR mouse (n = 4) for eight days by feeding with normal-salt diet. (A) Urinary sodium excretion in mice fed a normal-salt diet for eight days. (B) Average urinary sodium excretion in mice fed a normal-salt diet for eight days. The values are expressed as the average ± SE. *p < 0.01, **p < 0.005.

Figure 5. Effect of orally administered β-glucan on sodium excretion in high-salt-fed mice. β-Glucans of zymosan, barley, and BGF were orally administered at a concentration of 100 mg/kg/day to ICR mouse (n = 4) for 21 days by feeding with high-salt diet. (A) Sodium excretion in urine of high-salt fed mice for 21 days; (B) Average sodium excretion in urine of high-salt fed mice for 21 days. Values are average ± SE. *p < 0.01, **p < 0.005.

Figure 6. Proposed corin enzyme induced antihypertension mechanism of β-glucan. Oral administration of β-glucan induced corin in the liver or kidney, which cleaves pro-ANP into biologically active atrial natriuretic peptide (ANP) and N-terminal peptide (NTP). Upon the binding of ANP to its receptor, signals of the receptor promote natriuresis, diuresis, and vasodilation, which lower blood volume and pressure. Corin, a trypsin-like serine protease, induced by β-glucan, acts at the beginning of the ANP pathway to regulate the salt-water balance and blood pressure. The finding of ANP-initiated cGMP vasodilation was reported elsewhere [32]. AAs: amino acids; ANP: atrial natriuretic peptide; NTP: N-terminal peptide.

Chen H, Levine YC, Golan DE, et al. Atrial natriuretic peptide-initiated cGMP pathways regulate vasodilator-stimulated phosphoprotein phosphorylation and angiogenesis in vascular endothelium. J Biol Chem. 2008;283:4439–4447.

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