Background : Diabetes-induced cardiorenal complications are characterized by chronic inflammation, fibrosis, and metabolic dysfunction, contributing to both renal and cardiac impairments. Although current therapeutic strategies focus on managing hyperglycemia and minimizing organ damage, complementary approaches are still needed. Wiryeongtang (WRT), a traditional herbal formula provided by Hanpung Pharm & Foods Co. Ltd. (Jeonju, Korea), has shown potential in alleviating metabolic disorder-related complications. This study aimed to investigate the protective effects of WRT on cardiorenal complications in db/db diabetic mice. Methods : This study involved four experimental groups to evaluate the therapeutic effects of WRT. The control group consisted of db/m mice (non-diabetic), while the diabetes group included untreated db/db mice. The positive control group was treated with vildagliptin at 50 mg/kg/day, and the WRT group received WRT at 200 mg/kg/day. Mice were randomly assigned to the groups and treated for the designated period. To assess metabolic improvements, plasma blood glucose levels, lipid accumulation, and oral glucose tolerance were measured. Insulin resistance was evaluated using glucose tolerance tests. Renal outcomes were assessed through histological examinations, focusing on glomerulosclerosis, mesangial matrix expansion, and fibrosis biomarkers. Cardiac tissues were examined for structural and functional changes, including hypertrophy, fibrosis, and inflammation. Apoptotic signaling pathways were also analyzed by measuring the expression levels of caspase-3, caspase-9, Bcl-2, and Bax. Results : WRT administration significantly reduced plasma blood glucose levels and attenuated lipid accumulation in db/db mice. The WRT group showed marked improvements in oral glucose tolerance and insulin resistance. In the kidneys, WRT treatment reduced glomerulosclerosis, mesangial matrix expansion, and fibrosis markers, demonstrating renal protective effects. In the heart, WRT mitigated diabetes-induced cardiac dysfunction and histopathological changes, including hypertrophy, fibrosis, and inflammation. Mechanistically, WRT downregulated the expression of apoptotic markers (caspase-3 and caspase-9) while upregulating the Bcl-2/Bax ratio, suggesting anti-apoptotic effects. Conclusions : The findings of this study suggest that WRT may serve as a potential therapeutic agent for managing cardiorenal complications associated with type II diabetes. WRT effectively alleviated hyperglycemia, improved insulin sensitivity, and reduced inflammation and fibrosis in both the heart and kidneys. These results highlight the therapeutic potential of WRT in addressing diabetes-induced cardiorenal dysfunction through its anti-apoptotic and anti-fibrotic mechanisms.

Aging is characterized by progressive physiological decline and increased vulnerability to metabolic and inflammatory disturbances. Palmijihwang-hwan (PM), a traditional East Asian herbal formula, has been used empirically for age-related complaints, but its mechanistic basis remains unclear. Here, we evaluated the effects of early-onset PM administration (starting at 2 months of age) on longevity-related phenotypes and metabolic regulation. PM significantly prolonged lifespan in Caenorhabditis elegans and improved survival in ICR mice without evident toxicity. Preventive PM administration reduced epididymal white adipose tissue (eWAT) mass and circulating insulin/adipokine levels. Lipidomic analysis showed a shift from lysophospholipids toward phospholipids, accompanied by downregulation of PLA2G7, indicating attenuation of adipose inflammation. PM also reshaped the gut microbiota, decreasing inflammation-associated taxa such as Oscillibacter valericigenes, and lowered adipose IL-6 and TNF-α expression. Collectively, these findings indicate that preventive early-onset PM administration modulates the gut microbial composition, counteracting the age-related enrichment of inflammation-related bacteria.

Background: Diabetes causes cardiorenal complications characterized by inflammation, fibrosis, and metabolic dysfunction. Wiryeongtang (WRT), a traditional herbal formula, has shown potential in alleviating metabolic disorder-related complications. This study aimed to investigate the protective effects of WRT on cardiorenal complications in diabetic mice. Methods: Four groups were studied: a non-diabetic control (db/m), an untreated diabetic group (db/db), a vildagliptin-treated group (50 mg/kg/day) as a positive control, and a WRT-treated group (200 mg/kg/day). Metabolic parameters, including plasma blood glucose, lipid accumulation, and oral glucose tolerance, were measured. Renal histology was assessed for glomerulosclerosis, mesangial matrix expansion, and fibrosis. Cardiac tissues were examined for hypertrophy, fibrosis, and inflammation. Apoptotic markers (caspase-3, caspase-9, Bcl2, and Bax) were also measured. Results: WRT significantly reduced plasma blood glucose levels and lipid accumulation in db/db mice and improved oral glucose tolerance and insulin resistance. WRT reduced glomerulosclerosis, mesangial matrix expansion, and fibrosis markers in the kidneys. WRT also mitigated diabetes-induced cardiac dysfunction and histopathological changes, including hypertrophy, fibrosis, and inflammation. Additionally, WRT downregulated apoptotic markers (caspase-3 and caspase-9) while increasing the Bcl-2/Bax ratio. Conclusions: The findings suggest that WRT may serve as a potential therapeutic agent for managing cardiorenal complications associated with type 2 diabetes. It alleviated hyperglycemia, improved insulin sensitivity, and reduced inflammation and fibrosis in both cardiac and renal tissues through anti-apoptotic and anti-fibrotic mechanisms.

Cardio-Renal Metabolic Syndrome (CRS) encompasses metabolic disorders such as type 2 diabetes, hypertension, hyperlipidemia, chronic kidney disease, and heart failure. It is associated with obesity, systemic inflammation, and insulin resistance. Atractylodes lancea (AL), a traditional herbal remedy, has been previously reported to exhibit diuretic, sedative, antibacterial, and anticancer effects. However, the impact of AL on cardiovascular and renal functions within a metabolic syndrome (MS) model remains to be explored. Metabolic syndrome was induced in rats through an 8-week high-fat, high-fructose diet. After induction, experimental groups were orally administered olmesartan (10 mg/kg/day) or Aqueous extract of Atractylodes lancea (AAL) at 100 or 200 mg/kg/day for an additional 8 weeks. Body weight, fasting blood glucose, triglycerides, abdominal circumference, systolic blood pressure, and HDL-cholesterol levels were measured. Insulin levels and oral glucose tolerance tests (OGTT) were conducted to evaluate insulin resistance. Cardiac function was assessed using echocardiography, and ejection fraction and fractional shortening were analyzed. Masson’s trichrome and Picrosirius red staining were performed to evaluate fibrosis in the heart and aorta. Renal function was measured through creatinine clearance, blood urea nitrogen (BUN), and electrolyte levels. Periodic acid-Schiff (PAS) staining was additionally performed to evaluate histological changes in the kidney. Administration of AAL resulted in significant reductions in body weight, fasting blood glucose, triglycerides, abdominal circumference, and systolic blood pressure, while HDL-cholesterol levels increased. AAL improved insulin resistance, as indicated by enhanced insulin levels and OGTT results. Echocardiography revealed improvements in ejection fraction and fractional shortening in AAL-treated groups compared to the MS group. Histological analysis showed that AAL reduced heart and aorta fibrosis, as well as attenuated kidney injury. Additionally, AAL improved renal function by enhancing creatinine clearance, reducing BUN levels, and stabilizing electrolyte balance. The aqueous extract of Atractylodes lancea (AAL) effectively ameliorated cardiovascular and renal dysfunction in a rat model of metabolic syndrome model. These results suggest that AAL may have preventive and therapeutic potential for cardio-renal complications associated with MS. However, further investigation is needed to evaluate its suitability for diet-based interventions and evaluate its safety and pharmacological profile.

Background: In the realm of cardiovascular and renal health, the modulation of oxidative stress and inflammation within the cardio-renal axis plays a pivotal role. This study investigates the therapeutic potential of Gunryeong-tang (GRT), a traditional Korean herbal formula combining Oryeongsan (Wulingsan) and Sagunza-tang (Sijunzi-tang), specifically in addressing cardio-renal axis dysfunction induced by pulmonary arterial hypertension (PAH-r). Methods: PAH-r models were induced through intraperitoneal injection of monocrotaline (MCT) at a daily dose of 50 mg/kg for 5 days to simulate pulmonary hypertension, a common cause of cardio-renal syndrome. The primary focus is on evaluating its anti-fibroinflammatory effects and its ability to modulate oxidative stress and inflammation. The treatment group received oral administration of GRT (100 mg/kg/day). Results: Various parameters were assessed, including right ventricular (RV) enlargement and fibrosis, lung weight, pulmonary fibrosis, expression of cardiac hypertrophy markers, and involvement of specific pathways (TGF-β/p-Smad2 and HMGB-1/TLR4/MyD88/NF-κB). Renal dysfunction markers, such as blood urea nitrogen (BUN), creatinine clearance rate (Ccr), glomerular dilatation, tubular fibrosis, and protein expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), were evaluated to highlight the formula's anti-fibroinflammatory effects. Treatment resulted in significant improvements in the PAH-r group. It alleviated RV enlargement and fibrosis, suppressed lung weight increase, and mitigated pulmonary fibrosis. The administration downregulated cardiac hypertrophy markers (CTGF, TGF-β, and α-SMA mRNA levels) and inhibited the TGF-β/p-Smad2 and HMGB-1/TLR4/MyD88/NF-κB pathways, showcasing GRT's anti-fibroinflammatory properties. Additionally, the treatment ameliorated renal dysfunction, as evidenced by reduced BUN and Ccr levels, improved glomerular dilatation, and reduced protein expression of KIM-1 and NGAL. GRT demonstrates significant therapeutic potential in managing cardio-renal axis dysfunction induced by PAH-r, emphasizing its multifaceted benefits in modulating oxidative stress and inflammation within this axis. Conclusions: This study provides valuable insights into the underlying mechanisms, highlighting the modulation of cardiac hypertrophy markers and specific pathways. These findings underscore the promising role of GRT as a viable treatment option for cardio-renal axis dysfunction associated with PAH-r.

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.

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.

Heart failure, a major public health issue, often stems from prolonged stress or damage to the heart muscle, leading to cardiac hypertrophy. This can progress to heart failure and other cardiovascular problems. Doxorubicin (DOX), a common chemotherapy drug, and isoproterenol (ISO), a β-adrenergic agonist, both induce cardiac hypertrophy through different mechanisms. This study investigates TongGuanWan (TGW,), a traditional herbal remedy, for its effects on cardiac hypertrophy and fibrosis in DOX-induced H9c2 cells and ISO-induced mouse models. TGW was found to counteract DOX-induced increases in H9c2 cell surface area (n = 8, p < 0.01) and improve biomarkers like ANP (n = 3, p < 0.01)) and BNP (n = 3, p < 0.01). It inhibited the MAPK pathway (n = 4, p < 0.01) and GATA-4/calcineurin/NFAT-3 signaling, reduced inflammation by decreasing NF-κB p65 translocation, and enhanced apoptosis-related factors such as caspase-3 (n = 3, p < 0.01), caspase-9 (n = 3, p < 0.01), Bax (n = 3, p < 0.01), and Bcl-2 (n = 3, p < 0.01). Flow cytometry showed TGW reduced apoptotic cell populations. In vivo, TGW reduced heart (n = 8~10, p < 0.01), and left ventricle weights (n = 6~7), cardiac hypertrophy markers (n = 3, p < 0.01), and perivascular fibrosis in ISO-induced mice, with Western blot analysis confirming decreased levels of fibrosis-related factors like fibronectin, α-SMA (n = 3, p < 0.05), and collagen type I (n = 3, p < 0.05). These findings suggest TGW has potential as a therapeutic option for cardiac hypertrophy and fibrosis.

Ethnopharmacological relevance: Dohongsammul-tang (DH) is a Korean traditional herbal medicine used to alleviate symptoms caused by extravasated blood. It is known to protect against cardiovascular diseases and promote blood circulation by activating blood circulation to dispel blood stasis. The DH based on the characteristics of its medicinal properties has discovered the potential of alleviating cardiac hypertrophy. Therefore, this study was performed to verify the pharmacological effect of DH on improving cardiovascular disorders and to demonstrate its mutual improvement effect on renal function. Furthermore, aim of this study is founding the new potential beyond the traditional medicinal efficacy of DH, a traditional medicine. Aim of the study: In cardiovascular disease, cardiac hypertrophy refers to a change in the shape of the heart's structure due to pressure overload. It is known that an increase in myofibrils causes thickening of the heart, resulting in high blood pressure. Therefore, suppressing cardiac hypertrophy may be a major factor in lowering the morbidity, mortality, and heart failure associated with cardiovascular disease. Therefore, the study was performed to investigate whether DH, traditionally used, has effects on improving and alleviating cardiac injury and fibrosis caused by cardiac hypertrophy. Materials and methods: Dohongsamul-tang was composed of 6 herbal medicine and each material were boiled with 4 L distilled water for 2 h. The mixture for dohongsamul-tang centrifuged at 3000 rpm for 10 min and concentrated. The concentrated dohongsamul-tang extraction freeze-dried and sotred at 70 degrees C. The powder of dohongsamul-tang was diluted with distilled water and administered orally. In this study, pressure overload was induced by tying the transverse aortic arch, which is connected to the left ventricle, to the thickness of a 27G needle by performing a surgical operation. The resulting cardiac hypertrophy and heart remodeling was induced and maintained for 8 weeks. Results: The study administered propranolol and dohongsamul-tang orally for 10 weeks to investigate their effects on cardiac hypertrophy induced by transverse aortic contraction (TAC) surgery. Results showed that TAC group increased the left ventricle weight and decreased cardiac function, but dohongsamul-tang treatment attenuated these effects. The pressure-volume curve experiment revealed that dohongsamul-tang improved cardiovascular function, which was worsened by TAC group. Dohongsamul-tang treatment also downregulated collagen I and III through the TGF-& beta;/Smad2 signaling pathway and improved hematological biomarkers of cardiac hypertrophy. In addition, dohongsamul-tang treatment improved renal function-related biomarkers, such as blood creatinine, blood urea nitrogen, and neutrophil gelatinase-associated lipocalin, which were increased by TAC-induced cardiac hypertrophy. Conclusions: Taken together, dohongsamul-tang treatment inhibited cardiac remodeling due to pressure overload in the TAC-induced cardiac hypertrophy model, and this effect is thought to be manifested by improving the functional and morphological changes through the calcineurin/NFATc4 and reducing the cardiac fibrosis by suppressing TGF-& beta;/Smad2 signaling pathways.

Myocardial infarction (MI) is a leading cause of heart failure, characterized by adverse cardiac remodeling. This study evaluated the cardioprotective potential of Dohongsamul-tang (DHT), a traditional Korean herbal formula, in a rat model of MI-induced heart failure. Rats underwent left anterior descending (LAD) artery ligation and were treated with either 100 mg/kg or 200 mg/kg of DHT daily for 8 weeks. DHT treatment significantly improved cardiac function, as evidenced by increased ejection fraction (EF) from 62.1% to 70.1% (100 mg/kg) and fractional shortening (FS) from 32.3% to 39.4% (200 mg/kg) compared to the MI control group. Additionally, DHT reduced infarct size by approximately 63.3% (from 60.0% to 22.0%) and heart weight by approximately 16.7% (from 3.6 mg/g to 3.0 mg/g), and significantly decreased levels of heart failure biomarkers: LDH was reduced by 37.6% (from 1409.1 U/L to 879.1 U/L) and CK-MB by 47.6% (from 367.3 U/L to 192.5 U/L). Histological analysis revealed a reduction in left ventricle (LV) fibrosis by approximately 50% (from 24.0% to 12.0%). At the molecular level, DHT inhibited the expression of phospho-JAK by 75% (from 2-fold to 0.5-fold), phospho-STAT3 by 30.8% (from 1.3-fold to 0.9-fold), Bax/Bcl-2 by 56.3% (from 3.2-fold to 1.4-fold), and caspase-3 by 46.3% (from 1.23-fold to 0.66-fold). These results suggest that DHT exerts cardioprotective effects by modulating the JAK/STAT3 signaling pathway, highlighting its potential as a therapeutic option for heart failure.

Animal models have been utilized to understand the pathogenesis of Zellweger spectrum disorders (ZSDs); however, the link between clinical manifestations and molecular pathways has not yet been clearly established. We generated peroxin 5 homozygous mutant zebrafish (pex5−/−) to gain insight into the molecular pathogenesis of peroxisome dysfunction. pex5−/− display hallmarks of ZSD in humans and die within one month after birth. Fasting rapidly depletes lipids and glycogen in pex5−/− livers and expedites their mortality. Mechanistically, deregulated mitochondria and mechanistic target of rapamycin (mTOR) signaling act together to induce metabolic alterations that deplete hepatic nutrients and accumulate damaged mitochondria. Accordingly, chemical interventions blocking either the mitochondrial function or mTOR complex 1 (mTORC1) or a combination of both improve the metabolic imbalance shown in the fasted pex5−/− livers and extend the survival of animals. In addition, the suppression of oxidative stress by N-acetyl L-cysteine (NAC) treatment rescued the apoptotic cell death and early mortality observed in pex5−/−. Furthermore, an autophagy activator effectively ameliorated the early mortality of fasted pex5−/−. These results suggest that fasting may be detrimental to patients with peroxisome dysfunction, and that modulating the mitochondria, mTORC1, autophagy activities, or oxidative stress may provide a therapeutic option to alleviate the symptoms of peroxisomal diseases associated with metabolic dysfunction.

Respiratory exposure to Particulate matter (PM), including Diesel exhaust particulate (DEP), causes oxidative stress-induced lung inflammation. Especially, fine particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) is a serious air pollutant associated with various health problems including cardiovascular diseases. The present study aimed to examine the inhibitory effect of Securiniga suffruticosa (S. suffruiticosa) on DEP and PM-induced lung and cardiovascular diseases. Mice inhaled DEP by using nebulizer chamber for two weeks. Treatment with S. suffruiticosa reduced the expression of C-X-C motif ligand 1/2 in bronchoalveolar lavage fluid and Muc5ac, ICAM-1, TNF-⍺, IL-6 mRNA in lung were also attenuated by S. suffruiticosa. In thoracic aorta, DEP increased CAMs, TNF-⍺ and inflammasome markers such as NLRP3, Caspase-1, and ASC. However, S. suffruiticosa suppressed these levels. S. suffruiticosa inhibited PM2.5 induced production of intracellular reactive oxygen species (ROS); and inhibited the translocation of NF-κB p65 to the nucleus in human umbilical vein endothelial cells. Taken together, this study proved that exposure to PM2.5 induced both lung and vascular inflammation, however, S. suffruiticosa attenuated this injury via the downregulation of the NLRP3 signaling pathway. These findings suggest that S. suffruiticosa may have potential therapeutic benefit against air pollution-mediated lung and cardiovascular diseases.

Non-alcoholic fatty liver disease (NAFLD) induced by long term high-fat and high-fructose diet has led to serious medical problems such as non-alcoholic steatohepatitis or cirrhosis. NAFLD has related to obesity, insulin resistance or type Ⅱ diabetes induced by western diet. With the increasing the incidence of obesity and NFALD due to western diet consisting of high-fat and high-fructose diets, research of the treatment or prevention of NFALD due to western diets is urgently needed. Atractylodes lancea (AL) is traditional Chinese medicine and has been used for diuretic, sedation or antibacterial effect. To investigate effect of AL on NAFLD rat model induced by high-fat and high fructose diet, present study was performed. To induce NAFLD, wistar rats, which were 9-weeks-old, were fed with 45 kcal% high fat diet and 10% fructose water daily for 16 weeks. The olmesartan and atractylodes lancea were treated by oral administration for 8 weeks every day. The groups were composed of 5 groups; control (CON, n=9) fed with 10 kcal% general diet, non-alcoholic fatty liver disease group (NFD, n=9) induced by 45 kcal% high fat diet and 10% fructose diet, NFD group with 10 mg/kg/day Olmesartan orally (OLM, n=9), NFD group with 100 mg/kg/day AL (ALL, n=9) and NFD group with 200 mg/kg/day AL (ALH, n=9). AL decreased body weight, liver weight and epididymal fat pads weight compared with NFD group induced by high-fat and high fructose diet. In serum biomarkers, glucose level of plasma, triglyceride level and total cholesterol level in plasma were increased in NFD group compared with CON. AL restored the serum biomarkers including glucose, or triglycerides and total cholesterol level in serum. The plasma HDL-Cholesterol level, which was decreased in NFD group, attenuated by AL treatment. The atherogenic coeffient was upregulated by chronic high-fat and high-fructose diet, however, the atherogenic coeffient was significantly restored in AL treatment group. Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) were significantly deteriorated by long term high-fat and high-fructose diet. However, the GOT and GPT level in serum were alleviated in AL treatment groups. Oil red O staining showed that the lipid accumulation in the liver was increased in NFD group compared with CON. However, the lipid accumulation was restored by AL treatment groups. The fibrosis in liver was deteriorated in NFD induced by chronic high-fat and high fructose diet, however, the AL inhibited collagen deposition in liver. Also, AL suppressed the mRNA expressions of TGF-β, collagen Ⅰ and collagen Ⅲ in liver compared with NFD group. In liver tissue, the LXR and SREBP-1c mRNA expressions were downregulated in ALH group. Taken together, these results showed that AL could be potential supplements for NAFLD induced by long term high-fat and high-fructose diet by regulating fibrosis and LXR/SREBP-1c signaling pathway in liver. This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2022R1A6A3A01087272). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Respiratory exposure to Particulate Matter (PM), including Diesel exhaust particulate (DEP), causes oxidative stress-induced lung inflammation. Especially, fine particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) is a serious air pollutant associated with various health problems. DEP and PM2.5 pollutants in the air are enter into pulmonary and even bloodstream, and can be causes of inflammatory disorders that are related with respiratory response. The present study aimed to examine the inhibitory effect of Securiniga suffruticosa (S. suffruiticosa) on DEP-induced lung and cardiovascular diseases. The mice groups are follows; sham group: C57BL6 male mice, DEP group: C57BL6 male mice inhaled DEP, S. suffruiticosa Low group: DEP + 100 mg/kg/day S. suffruiticosa, and S. suffruiticosa High group: DEP + 300 mg/kg/day S. suffruiticosa. Mice inhaled DEP by using nebulizer chamber and were sacrificed 48 hours after final exposure of DEP. Treatment with S. suffruiticosa reduced the expression of inducible CXCL1 and CXCL2 in bronchoalveolar lavage fluid and Muc5ac, ICAM-1, TNF-α, IL-6 mRNA in lung were also attenuated by S. suffruiticosa. In thoracic aorta, DEP increased CAMs, TNF-α and inflammasome markers such as NLRP3, Caspase-1, and ASC. However, S. suffruiticosa suppressed these levels. In HUVECs, S. suffruiticosa inhibited PM2.5 induced production of intracellular reactive oxygen species (ROS); and inhibited the translocation of NF-κB p65 to the nucleus in HUVECs (human umbilical vein endothelial cells). Taken together, this study proved that exposure to PM2.5 induced both lung and vascular inflammation, however, S. suffruiticosa attenuated this injury via the downregulation of the NLRP3 signaling pathway. These findings suggest that S. suffruiticosa may have potential therapeutic benefit against air pollution-mediated lung and cardiovascular diseases. This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2021R1I1A1A01056937). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background: 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. Methods: Changes in urine volume (UV), excretion of electrolytes including Na+ (urinary excretion of Na+ (UNaV)) 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. Results: In the SHR treated with vehicle (SHR-V) group, UV and UNaV 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 UNaV, 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. Conclusion: 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.

Diabetes mellitus (DM) is one of the most common metabolic disorders known to result from abnormal secretion of insulin and/or resistance to insulin. DM is characterized by hyperglycemia, decreased function of pancreatic islet cells and reduced insulin secretion. DM causes many types of complications, among which heart complications are a serious cause of death in people with diabetes. Gunryeong-tang (GRT, 君苓湯) is a traditional oriental herbal formula for the treatment of acute and chronic nephritis, which is used to promote water retention and reduce swelling. However, no study has been conducted on the cardioprotective effects of GRT in diabetes, so this study was investigated whether GRT alleviated diabetes and diabetic heart injury in db/db mice. The experiment was conducted for 8 weeks, distributed into four different groups: db/m control, db/db control, db/db treated with vildagliptin (50 mg/kg/day) or db/db treated with GRT (200 mg/kg/day). As a result, GRT has an impact in lowering high blood glucose levels and insulin resistance in db/db mice. GRT significantly improved cardiac function in db/db mice by inhibiting LDH, CK-MB, and CPK. After 8 weeks of GRT-treatment, M-mode echocardiography was performed to confirm whether GRT had effect on cardiac function. GRT significantly up-regulated impaired LV EF and FS in db/db mice. In addition, GRT was also confirmed to improve histopathological changes (hypertrophy, fibrosis and inflammation) and protein expression levels of related factors caused by diabetes. Furthermore, GRT remarkably improved the expression of factors involved in cardiac apoptosis in db/db mice. Taken together, our results suggest that GRT improves cardiac function and diabetic complications through suppression of cardiac fibrosis and inflammation. Therefore, it is believed that GRT can be developed as a new treatment for diabetes, especially heart complications. This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2021R1C1C2009542). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Oryeongsan (ORS) has 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 rat (SHR), an animal model of human essential hypertension. Changes in urine volume (UV), excretion of electrolytes including Na+ {urinary excretion of Na+ (UNaV)} 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 UNaV 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 UNaV, 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.

CRS (Cardio-Renal Metabolic Syndrome) refers to a series of entangled metabolic disorders, including type 2 diabetes, hypertension, hyperlipidemia, chronic kidney disease and heart failure, and is associated with obesity, systemic inflammation, and insulin resistance. Atractylodes lancea (AL) is the rhizome of Atractylodes. AL has been found to have diuretic, sedation, antibacterial, anticancer effects. Therefore, in this study, confirmed the effect of AL on improving cardiovascular and kidney function in the metabolic syndrome model. In this experiment, HFHFr were provided to rats for 8 weeks to induce metabolic syndrome, and the OMT (10 mg/kg/day) or AL (100 or 200 mg/kg/day) were administered orally for 8 weeks with HFHFr for 8 weeks to confirm its efficacy. Therefore, a total of 16 weeks of experiments were conducted. To compare Cont with HFHFr, MS categorys were measured. As a result, AL confirmed that HFHr decreased BW, fasting glucose, TG, and abdominal circumference, systolic blood pressure, and increased HDL-C. As a result of measuring insulin and performing OGTT to confirm insulin resistance, which is a major symptom of MS, AAL ameliorates increased insulin levels, and AAL2 significantly decreased blood glucose levels over time. As a result of confirming echocardiography for cardiac function diagnosis, ejection fraction (EF) and fractional shortening (FS) levels were lower in metabolic syndrome than in the control group and significantly improved in the AAL administration group. Staining to confirm the effect of the heart on fibrosis confirmed that collagen accumulation and fibrosis were increased in HFHFr, and improved by AAL compared to the control group. Therefore, these findings suggest that AL improves obesity, insulin resistance, dyslipidemia, and high blood pressure caused by metabolic syndrome, and has a protective effect on heart function decline and fibrosis of the heart and blood vessels. This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2021R1C1C2095327). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Myocardial infarction (MI) is a frequent and severe manifestation of ischemic heart disease. We investigated the changes of protein in chronic MI which was occurred with long-term ischemia, without reperfusion. Guaruhaebaekbaekju-tang(瓜蔞薤白白酒湯, GHT) is an established traditional Chinese medicine that is widely used for the treatment of cardiac function, although its mechanisms remain unclear. GHT (100 or 200 mg/kg/day) was administered to rats immediately after coronary artery ligation for 8 weeks. After being sacrificed, the effect of GHT on cardiac fibrosis was confirmed by cardiac function and histological studies. As a result, the biomarker for detecting MI, lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB) and Creatine Phosphokinase (CPK) enzymes, were significantly decreased by GHT. Heart function was evaluated by cardiac ultrasound to determine the effect of GHT on left ventricular dysfunction. MI group have decreased EF (Ejection fraction) as well as FS (Fractional shortening), compared to HT group. Additionally, left-ventricular (LV) dysfunction and dilatation were attenuated in the GHT group compared with MI group. In addition, protein expression levels the effect of GRT on cardiac fibrosis was confirmed by reducing the expression of transforming growth factor β (TGF-β) and collagen 1. This is thought to appear through inhibition of the TGF-β/p-Smad 2 pathway. Additionally, GHT reduced the Masson's trichrome and picrosirius red staining intensity in left ventricle of the MI group. Therefore, these findings suggest tha GHT has protective effects via inhibition of TGF-β/p-Smad 2 pathway, which is associated with improvement of myocardial fibrosis in rats with MI. These results suggest that GHT has a protective effect on heart failure by alleviating cardiac hypertrophy, myocardial fibrosis, cardiac dysfunction caused in MI model. This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2021R1A2C1010859). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiac hypertrophy is developed by various diseases such as myocardial infarction, valve diseases, hypertension, and aortic stenosis. Sibjotang (, Shizaotang, SJT), a classic formula in Korean traditional medicine, has been shown to modulate the equilibrium of body fluids and blood pressure. This research study sought to explore the impact and underlying process of Sibjotang on cardiotoxicity induced by DOX in H9c2 cells. In vitro, H9c2 cells were induced by DOX (1 μM) in the presence or absence of SJT (1-5 μg/mL) and incubated for 24 h. In vivo, SJT was administrated to isoproterenol (ISO)-induced cardiac hypertrophy mice (n = 8) at 100 mg/kg/day concentrations. Immunofluorescence staining revealed that SJT mitigated the enlargement of H9c2 cells caused by DOX in a dose-dependent way. Using SJT as a pretreatment notably suppressed the rise in cardiac hypertrophic marker levels induced by DOX. SJT inhibited the DOX-induced ERK1/2 and p38 MAPK signaling pathways. In addition, SJT significantly decreased the expression of the hypertrophy-associated transcription factor GATA binding factor 4 (GATA 4) induced by DOX. SJT also decreased hypertrophy-associated calcineurin and NFAT protein levels. Pretreatment with SJT significantly attenuated DOX-induced apoptosis-associated proteins such as Bax, caspase-3, and caspase-9 without affecting cell viability. In addition, the results of the in vivo study indicated that SJT significantly reduced the left ventricle/body weight ratio level. Administration of SJT reduced the expression of hypertrophy markers, such as ANP and BNP. These results suggest that SJT attenuates cardiac hypertrophy and heart failure induced by DOX or ISO through the inhibition of the calcineurin/NFAT/GATA4 pathway. Therefore, SJT may be a potential treatment for the prevention and treatment of cardiac hypertrophy that leads to heart failure.