Oryeongsan (Wulingsan in China and Goreisan in Japan), a formula composed of five herbal medicines, has long been used for the treatment of imbalance of the body fluid homeostasis in Asian countries. However, the mechanism by which Oryeongsan (ORS) improves the impaired body fluid and salt metabolism is not clearly defined. The present study was performed to define the role of the cardiorenal humoral system in the ORS-induced changes in blood pressure and renal function in hypertension. Experiments were performed in normotensive and two-kidney, one-clip hypertensive rats. Changes in the fluid and salt balance were measured in rats individually housed in metabolic cages. Changes in the systemic and local renin-angiotensin system (RAS) and cardiac natriuretic peptide hormone system (NPS) were evaluated. ORS water extract was administered by oral gavage (100mg/kg daily) for 3 weeks. ORS induced diuresis and natriuresis along with an increase in glomerular filtration rate and downregulation of the Na⁺/H⁺ exchanger 3 (NHE3) and aquaporin 2 expression in the renal cortex and medulla, respectively. Furthermore, treatment with ORS significantly decreased systolic blood pressure with contraction of body sodium and water accumulation in hypertensive rats. ORS-induced changes were accompanied by modulation of the RAS and NPS, downregulation of the systemic RAS and cardiorenal expression of angiotensin-converting enzyme (ACE) and angiotensin II subtype 1 (AT₁) receptor, and upregulation of the plasma ANP concentration and cardiorenal expression of ANP, ACE2, Mas receptor, and AT₂ receptor. These findings indicate that ORS induces beneficial effects on the high blood pressure through modulation of the RAS and NPS of the cardiorenal system, suppression of the prohypertensive ACE-AT₁ receptor pathway and NHE3, accentuation of the antihypertensive ACE2-Mas axis/AT₂ receptor pathway in the kidney, suppression of the systemic RAS, and elevation of the plasma ANP levels and its synthesis in the heart. The present study provides a biological basis for the use of ORS in the treatment of impaired volume and pressure homeostasis.

Background: Oryeongsan (Wulingsan, Goreisan) has long been used for the treatment of impaired body fluid metabolism. However, the action mechanisms have not been clearly defined. Recently, effects of Oryeongsan on the body fluid and Na⁺ metabolism and the action mechanisms have been shown more clearly. The present review focuses on the recent findings on the effects of Oryeongsan in the cardio-renal system in relation with body fluid metabolism and action mechanisms leading to a decrease in blood pressure in animal models of hypertension. Methods: The new and recent findings were searched by using searching systems including PubMed-NCBI and Google-Scholar. Results: Oryeongsan induced an increase in glomerular filtration rate, and natriuresis and diuresis with a decreased osmolality and resulted in a contraction of the body fluid and Na⁺ balance. These findings were associated with a suppression of abundance of Na⁺-H⁺-exchanger isoform 3 expression and V₂ receptor/aquaporin2 water channel signaling pathway in the kidney. Further, treatment with Oryeongsan accentuated atrial natriuretic peptide secretion in the atria from spontaneously hypertensive rats in which the secretion was suppressed. In addition, Oryeongsan ameliorated impaired vasodilation in spontaneously hypertensive rats. Conclusion: The effects of Oryeongsan in the kidney, atria, and vessel were accompanied by a suppression of AT₁ receptor and concurrent accentuation of abundance of AT₂/Mas receptors expression and modulation of the natriuretic peptide system in these organs from hypertensive rats. The review shows multiple sites of action of Oryeongsan and mechanisms involved in the regulation of volume and pressure homeostasis in the body.

Sunbanghwalmyung-eum (SBH) is a traditional herbal medicine that exhibits various pharmacological properties, such as antioxidant, anti-inflammatory, and anticancer activities. In this study, we investigated the systemic anti-obesity effects of an aqueous extract of SBH in the liver, adipose, and muscle tissue from high-fat and high-cholesterol diet (HFHCD)-induced obese C57BL/6J mice. After 6 weeks of an HFHCD, the mice were continuously fed HFHC with oral administration of SBH (100 mg/kg/day), Sim (simvastatin, 5 mg/kg/day, positive control), or water (HFHC only) for another 6 weeks. Our results showed that SBH attenuated the HFHCD-induced body weight gain and fat accumulation in the liver, and improved plasma lipid levels, such as those of triglycerides (TGs), blood total cholesterol (TC), and low-density lipoprotein (LDL-c). SBH and Sim inhibited the inflammation accompanied by obesity via decreasing inflammatory cytokine interleukin (IL)-1β, tumor necrosis factor α (TNFα), and monocyte chemoattractant protein 1 (MCP1). Moreover, SBH downregulated the expression of protein levels of adipogenic-related factors, including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), in the liver, adipose, and muscle tissue. The SBH and Sim treatment also significantly upregulated the phosphorylation of AMP-activated protein kinase α (AMPKα) in the liver and hormone-sensitive lipase (HSL) in the adipose tissue. Overall, the effects of SBH on HFHCD-induced obesity were similar to or more potent than those of simvastatin. These results indicated that SBH has great potential as a therapeutic herbal medicine for obesity.

Herbal medicine Oryeongsan (ORS), also known as Wulingsan in Chinesehas been used for the treatment of impaired body fluid balance. However, the mechanisms involved are not clearly defined. The purpose of the present study was to identify the actions of ORS on the renal excretory function and blood pressure (BP) and to define the mechanisms involved in association with renin-angiotensin system (RAS) and natriuretic peptide system (NPS) in spontaneously hypertensive rats (SHR), an animal model of human essential hypertension. Changes in urine volume (UV), excretion of electrolytes including Na⁺ (urinary excretion of Na⁺ (U_NaV)) were measured. RT-PCR was performed to trace the changes in expression of RAS, NPS and sodium (Na⁺)-hydrogen (H⁺) exchanger 3 (NHE3) in the renal cortex. In the SHR treated with vehicle (SHR-V) group, UV and U_NaV were suppressed and the Na⁺ balance was maintained at the higher levels leading to an increase in BP compared to WKY-V group. These were accompanied by an increase in NHE3 expression with an accentuation of angiotensin I converting enzyme-angiotensin II type 1 (ACE-AT₁) receptor and concurrent suppression of angiotensin II type 2 (AT₂) receptor/ACE2-Mas receptor expression in the renal cortex. Chronic treatment with ORS increased UV and U_NaV, and decreased the Na⁺ and water balance with a decrease in BP in the ORS-treated SHR-ORS group compared to SHR-V. These were accompanied by a decrease in NHE3 expression with a suppression of ACE-AT₁ receptor and concurrent accentuation of AT₂/ACE2-Mas receptor. The present study shows that ORS reduced BP with a decrease in Na⁺ and water retention by a suppression of NHE3 expression via modulation of RAS and NPS in SHR. The present study provides pharmacological rationale for the treatment of hypertension with ORS in SHR.

Atopic dermatitis (AD), a chronic inflammatory skin disease, is exacerbated by obesity, yet the precise linking mechanism remains elusive. This study aimed to elucidate how obesity amplifies AD symptoms. We studied skin samples from three mouse groups: sham control, AD, and high-fat (HF) + AD. The HF + AD mice exhibited more severe AD symptoms than the AD or sham control mice. Skin lipidome analysis revealed noteworthy changes in arachidonic acid (AA) metabolism, including increased expression of pla2g4, a key enzyme in AA generation. Genes for phospholipid transport (Scarb1) and acyltransferase utilizing AA as the acyl donor (Agpat3) were upregulated in HF + AD skin. Associations were observed between AA-containing phospholipids and skin lipids containing AA and its metabolites. Furthermore, imbalanced phospholipid metabolism was identified in the HF + AD mice, marked by excessive activation of the AA and phosphatidic acid (PA)-mediated pathway. This imbalance featured increased expression of Plcb1, Plcg1, and Dgk involved in PA generation, along with a decrease in genes converting PA into diglycerol (DG) and CDP-DG (Lpin1 and cds1). This investigation revealed imbalanced phospholipid metabolism in the skin of HF + AD mice, contributing to the heightened inflammatory response observed in HF + AD, shedding light on potential mechanisms linking obesity to the exacerbation of AD symptoms.

Background: Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension. Methods: Consecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined. Results: The study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT. Conclusions: The findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.