Organ-protective Effects Research Articles

Pharmacological Attributes of Hesperidin

: Hesperidin is a major flavonoid in sweet oranges and lemons. Aglycone form of hesperidin i.e., hesperetin, and their various derivatives possess significant potential as therapeutic agents for a wide range of diseases and disorders. No signs of toxicity have been observed with the normal intake of hesperidin or related compounds. Hesperidin has been reported to possess a wide range of pharmacological properties, which includes antioxidant, anti-viral, anticancer, antidiabetic, analgesic, organ protective, neuroprotective, antihypertensive, and cardioprotective effects. This needs to be effectively studied at the clinical level so as to firmly establish the usefulness of these compounds in the treatment or prevention of disease in humans. This paper reviews various aspects of hesperidin, including their chemistry, biosynthesis, and bioactivity.

Cardioprotective effects of S-equol, a soybean metabolite with estrogen activity, and role of the PI3K/Akt pathway in a male rat model of ischemic reperfusion

PurposeS-equol, an isoflavone metabolite with high estrogenic activity, exhibits organ-protective effects via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. While estrogen has cardioprotective effects against ischemia–reperfusion injury, whether S-equol shares this capability remains uncertain. This study aimed to assess the cardioprotective effects of S-equol on stunned myocardium using an isolated rat heart model and investigate the involvement of PI3K/Akt signaling pathway. MethodsMale rat hearts were perfused using the Langendorff system and divided into four groups: 1) modified Krebs–Henseleit (KH) buffer containing 1 μmol/L S-equol (EQ); 2) KH buffer (Cont); 3) KH buffer supplemented with 1 μmol/L S-equol and 100 nmol/L wortmannin (a specific PI3K inhibitor) (EQW); or 4) KH buffer containing wortmannin (ContW). After stabilization, each group was perfused for 20 min before undergoing 7.5 min of no-flow ischemia, followed by 20 min reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (left ventricle [LV] dP/dt max)after 20 min of reperfusion. Myocardial Akt and glycogen synthase kinase-3 beta (GSK-3β) were assayed using western blotting. ResultsLV dP/dt max was greater in the EQ group than that in the Cont group after 15 and 20 min of reperfusion; however, this effect was attenuated in the presence of PI3K inhibitors. S-equol treatment increased Akt and suppressed GSK-3β expression in the EQ group compared to that in the Cont group. However, these effects were not observed in the presence of wortmannin. ConclusionS-equol exerts a protective effect against myocardial ischemia–reperfusion injury, possibly by activating PI3K/Akt signaling.

The Potential Therapeutic Use of Agarwood for Diabetes: A Scoping Review.

In 2019, 9.3% (463 million) of adults worldwide had diabetes, according to the International Diabetes Federation (IDF). By 2030, the number will rise to 10.2% (578 million) and 10.9% (700 million) by 2045 if effective prevention methods are not implemented. Agarwood is a pathological product and valuable plant due to its numerous medicinal properties, and it is used as an essential ingredient in medicine. Therefore, we conducted this review to determine agarwood's potential health benefit effect on type 2 diabetes. Although no clinical trials were found, the evidence from in vitro and in vivo studies is promising. Agarwood has shown the ability to reduce the activity of α-glucosidase, α-amylase, and lipase, promote adiponectin secretion during adipogenesis, and reduce oxidative stress. Animal studies elucidated hypoglycaemic, antidyslipidemia, anti-obesity, and organ protective effects from agarwood. Original articles were searched in three databases (PubMed, Scopus, and Cochrane Library) using the medical subject heading (MeSH) term "diabetes" crossed with the term "agarwood" from 2008 to 2024. Synonyms and relevant search terms were also searched. This effect underscores the need for further research and the potential for groundbreaking discoveries in the field of diabetes treatment.

Metal-Free CO Prodrugs Activated by Molecular Oxygen Protect against Doxorubicin-Induced Cardiomyopathy in Mice.

Carbon monoxide has been extensively studied for its various therapeutic activities in cell cultures and animal models. Great efforts have been made to develop noninhalational approaches for easy and controlled CO delivery. Herein, we introduce a novel metal-free CO prodrug approach that releases CO under near-physiological conditions. CO from the quinone-derived CO prodrugs is initiated by general acid/base-catalyzed tautomerization followed by oxidation by molecular oxygen to form the key norbornadienone intermediate, leading to cheletropic CO release only in an aerobic environment. Representative CO prodrug analog QCO-105 showed marked anti-inflammatory effects and HO-1 induction activity in RAW264.7 macrophages. In a mouse model of doxorubicin-induced cardiomyopathy, we show for the first time that the CO prodrug QCO-105 prevented cardiomyocyte injury, consistent with the known organ-protective effects of HO-1 and CO. Overall, such a new CO prodrug design serves as the starting point for developing CO-based therapy in attenuating the cardiotoxicity of doxorubicin.

Clinical effects of dexmedetomidine on patients with sepsis and myocardial injury.

This study aimed to explore the organ-protective effects of dexmedetomidine in patients with sepsis combined with myocardial injury. From December 2021 to December 2023, 263 sepsis patients with myocardial injury were included based on inclusion and exclusion criteria. They were divided into an experimental group (n = 122), who had previously received dexmedetomidine, and a control group (n = 141), who had received midazolam. After matching baseline characteristics, the treatment outcomes between the 2 groups were compared. In a propensity score-matched cohort of 263 patients, each group had 62 individuals with balanced baseline characteristics. The experimental group showed significantly lower heart rates on days 1, 3, and 7 compared to the control (P < .05). Biomarkers high-sensitivity troponin I and creatine kinase-MB decreased significantly by days 3 and 7, with lower levels in the experimental group. B-type natriuretic peptide levels were also lower in the experimental group on days 3 and 7. Heart function improved in both groups, with the experimental group showing better outcomes. Inflammatory markers decreased significantly after 7 days, with the experimental group having lower levels. Hospitalization duration was similar between groups. Dexmedetomidine reduces heart rate and inflammatory markers, protects myocardial cells, and improves cardiac function in patients with sepsis and myocardial injury. It shows potential as a treatment option, with future research needed to assess its long-term efficacy and safety.

Therapeutic Applications of Xenon (Literature Review).

Introduction: Xenon is a noble gas with unique properties that make it an attractive anesthetic agent. In addition to its anesthetic and analgesic effects, xenon has demonstrated organ-protective properties in preclinical studies, suggesting potential therapeutic applications beyond anesthesia. This review aims to systematically evaluate the available clinical evidence on the therapeutic use of xenon, focusing on its effects on various organ systems. Methods: A comprehensive literature search was conducted in medical databases including PubMed, Google Scholar, Cochrane Library, and eLIBRARY.RU. Original clinical studies evaluating the therapeutic use of xenon were included and analyzed. Results: The review identified several areas of potential therapeutic application for xenon: 1. Neuroprotection: Xenon has shown promise in reducing neurological injury and improving outcomes in patients with conditions such as cardiac arrest, traumatic brain injury, and neonatal hypoxic-ischemic encephalopathy. However, the clinical evidence remains limited, and larger randomized controlled trials are ongoing to further evaluate its efficacy. 2. Cardioprotection: Xenon has been found to attenuate myocardial injury and improve cardiac function in patients undergoing cardiac surgery or experiencing cardiac arrest, potentially through its anti-inflammatory and anti-apoptotic effects. 3. Addiction treatment: Inhalation of xenon has been investigated for its potential to alleviate withdrawal symptoms and cravings in patients with opioid and alcohol dependence, with some studies suggesting beneficial effects on cognitive function and mood. 4. Psychiatric applications: Preliminary evidence suggests that xenon may have anxiolytic and antidepressant properties, with potential applications in the treatment of panic disorder and other mood disorders. Conclusion: The available clinical data indicate that xenon may have therapeutic potential beyond its use as an anesthetic agent. However, further well-designed, large-scale studies are needed to establish the efficacy and safety of xenon in various clinical settings and to elucidate the underlying mechanisms of its organ-protective and psychoactive effects.

Organ-protective effects of the alternative renin-angiotensin system and prospects for therapeutic treatment. Review

The article is devoted to review the data regarding the identification of biochemical and functional features of the components of the renin‑angiotensin system using the tools of bibliometric analysis of scientific literature. A modern interpretation by the dividing of the multifunctional complex into two systems, namely the classical renin‑angiotensin system and alternative renin‑angiotensin system, in accordance with the definition of biological effects, is given. The enzymatic cascade involved in the production and metabolism of peptides in both classical and non‑classical pathways of renin‑angiotensin systems is shown from the point of view of the evolution of scientific concepts. The triggering role of components of the classical renin‑angiotensin system in pathophysiological processes with transformation into cardiovascular diseases and metabolic dysfunction has been proven. The history of the creation of pharmacological drugs for the correction of the classic renin‑angiotensin system is presented. In view of the achievement of recent years, the revision of the alternative renin‑angiotensin system is emphasized due to the discovery of the counter‑regulatory action of the angiotensin‑converting enzyme 2, angiotensin‑(1—7), the Mas receptor in relation to their correction of metabolic processes, regulation of blood pressure, and the presence of anti‑fibrotic, anti‑inflammatory and antioxidant properties. The positive effect of the components of the non‑classical renin‑angiotensin system on the protection of the cardiovascular system and kidney is presented based on the results of experimental studies on animals. Pharmacokinetic and pharmacodynamics characteristics of recombinant angiotensin‑converting enzyme 2 in experiments on healthy volunteers are highlighted. The potential protective effects of angiotensin‑converting enzyme 2 and angiotensin‑(1—7) concerning cardiometabolic risk are presented. The available data indicate the need for further comprehensive scientific investigations of the components of alternative renin‑angiotensin system to create a new class of pharmacological agents with their implementation in medical practice.

Research progress in the clinical application of inhaled anesthetic sevoflurane.

Sevoflurane has been widely used in clinical anesthesia as an inhalation anesthetic. With the development of medicine, there have been several new applications in recent years, such as daytime surgery, labor analgesia, and combined nerve block for some surgeries. Moreover, as research progresses, it has been found that it not only has potential organ protection effects but can also be used to treat severe asthma and relieve the tracheal spasm state. In addition, local administration can effectively treat vascular ulcers. We briefly review the organ protective effect of sevoflurane, its application in dental treatment, asthma treatment, vascular ulcer treatment and some new progress in clinical application.

Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39

We previously reported that normothermic ex vivo kidney perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS). Mitochondrial respiration and ATP levels were further enhanced when AP39, a mitochondria-targeted hydrogen sulfide donor, was administered during warm perfusion. Correspondingly, the combination of NEVKP and AP39 was associated with decreased oxidative stress and inflammation, and with improved graft function after transplantation. In conclusion, our findings suggest that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by AP39 administration. Activation of mitochondrial function through the combination of AP39 and normothermic perfusion could represent a new therapeutic strategy for long-term renal preservation.

Anti-inflammatory effect of colchicine on organ damage during the perioperative period of cardiac surgery: a study protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial

IntroductionThe systemic inflammatory response syndrome during the perioperative period of cardiac surgery can lead to serious postoperative complications and significantly increase the hospital mortality rate. Colchicine, a widely used traditional...

Aloperine protects the testis against testicular ischemia/reperfusion injury in rats.

Testicular torsion/detorsion can cause testis loss and infertility. Aloperine is a major active alkaloid extracted from Sophora alopecuroides Linn. It has been shown to have organ-protective effects. However, the effects of aloperine on the testis and its underlying mechanisms remain unclear. This study investigated the effect of aloperine on testicular torsion/detorsion injury in rats. Male Sprague-Dawley rats were randomized to the sham-operated (sham), testicular I/R (TI/R), or aloperine preconditioning (ALOPre) or postconditioning (ALOPost) groups. All rats except for the sham-operated rats were subjected to 3h of right spermatic cord torsion (720°, clockwise), followed by 3h of detorsion. Aloperine (10mg/kg) was intravenously administered before testicular torsion (ALOPre) or at the onset of testicular detorsion (ALOPost). The therapeutic efficacy of aloperine was evaluated by histological analysis, oxidative stress evaluation, inflammatory response examination, apoptosis analysis, protein analysis, and immunohistological assessment. Compared with TI/R, aloperine protected both the ipsilateral and contralateral testes against unilateral testicular I/R, as evidenced by a reduced testicular weight to body weight (TW/BW) ratio (ALOPre: p=0.0037; ALOPost: p=0.0021) and volume (ALOPre: p=0.0020; ALOPost: p=0.0009), less structural damage with better Johnsen (ALOPre: p=0.0013; ALOPost: p=0.0021), and Cosentino scores (ALOPre: p<0.0001; ALOPost: p<0.0001), increased mean seminiferous tubule diameter and mean seminiferous tubule epithelial height, decreased testicular apoptosis, and less oxidative stress and inflammatory response. In addition, aloperine significantly stimulated the phosphorylation of signal transducer and activator of transcription (STAT)-3 in the ipsilateral testes following detorsion. Administration of Ag490 suppressed STAT-3 phosphorylation, thereby abrogating the protective effects exerted by aloperine on the ipsilateral testis. Aloperine has a strong testicular protective effect on the ipsilateral and contralateral testes after testicular torsion/detorsion. This aloperine-induced ipsilateral testicular protection is mediated via the STAT-3 signaling pathway.

Annexin-A1 short peptide alleviates septic myocardial injury by upregulating SIRT3 and inhibiting myocardial cell apoptosis.

Septic myocardial injury is a common complication of severe sepsis, which occurs in about 50% of cases. Patients with this disease may experience varying degrees of myocardial damage. Annexin-A1 short peptide (ANXA1sp), with a molecular structure of Ac-Gln-Ala-Tyr, has been reported to exert an organ protective effect in the perioperative period by modulating sirtuin-3 (SIRT3). Whether it possesses protective activity against sepsis-induced cardiomyopathy is worthy of study. This study aimed to investigate whether ANXA1sp exerts its anti-apoptotic effect in septic myocardial injury in vitro and in vivo via regulating SIRT3. In this study, we established in vivo and in vivo models of septic myocardial injury based on C57BL/6 mice and primary cardiomyocytes by lipopolysaccharide (LPS) induction. Results showed that ANXA1sp pretreatment enhanced the seven-day survival rate, improved left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and cardiac output (CO), and reduced the levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). Western blotting results revealed that ANXA1sp significantly increased the expression of SIRT3, Bcl-2, and downregulated Bax expression. TUNEL staining and flow cytometry results showed that ANXA1sp could attenuate the apoptosis rate of cardiomyocytes, whereas this anti-apoptotic effect was significantly attenuated after SIRT3 knockout. To sum up, ANXA1sp can alleviate LPS-induced myocardial injury by reducing myocardial apoptosis via SIRT3 upregulation.

Sílybum Mariánum’s Impact on Physiological Alterations and Oxidative Stress in Diabetic Rats

This study delves into the crucial role of oxidative stress in non-infectious diseases and emphasizes the necessity of precise control over cellular oxidative processes using both natural and external antioxidant systems. Dysfunctions in these systems often result in various pathologies, underscoring the therapeutic promise of antioxidants in restoring cellular balance. Sílybum mariánum, known for its multifaceted biological properties such as antioxidative, hepatoprotector, anti - toxic, and organ-protective effects, emerges as a compelling subject for investigating its mechanisms, particularly in diabetes mellitus. Our research examines the impact of Sílybum mariánum's ethanolic extract on oxidative stress levels in alloxan-induced diabetic conditions. Our results demonstrate significant antioxidant effects of the extract on the heart and aorta preparations in diabetic rats. This study adds to the expanding body of research on the potential therapeutic utility of Sílybum mariánum in addressing oxidative stress-related complications linked with diabetes mellitus.

Platelet membrane coated Cu9S8-SNAP for NIR-II photoacoustic imaging guided NO repairing acute kidney injury

Acute kidney injury (AKI) is a prevalent critical condition in hospitalized patients with an elevated risk of death. Challenges in AKI management persist due to the absence of efficient early diagnostic modalities and the lack of effective therapeutic interventions, imposing significant burdens on medical resources for prolonged treatment. Here, we proposed a second near-infrared (NIR-II) photoacoustic imaging (PAI) guided triggered on-demand release of (nitric oxide) NO from the injury zone to monitor and treat AKI through the anti-inflammatory, anti-apoptotic, and oxidative stress-damage-reducing cell- or organ-protective effects of NO. We engineered hollow copper sulfide nanoparticles (Cu9S8 NPs) loaded with platelet membrane-encapsulated NO-releasing precursors (S-Nitroso-N-acetylpenicillamine, SNAP), as a nanoplatform for early AKI diagnosis and precise spatiotemporal NO release Besides acting as a drug carrier, the inherent PAI compatible Cu9S8 also enables targeted renal injury localization, exploiting the natural propensity of platelets to accumulate at vascular injury sites, facilitating real-time AKI monitoring in murine models. Experiments demonstrated that nitric oxide delivery nanoparticles can specifically target and accumulate in the kidney, reduce inflammation, and promote damage repair. Overall, this gas therapy strategy represents a new therapeutic pathway for the clinical AKI management.

Embelin mitigates hepatotoxicity induced by isoniazid and rifampicin in rats

Isoniazid and rifampicin are reliable drugs against tuberculosis, but while effective, their use is associated with the risk of drug-induced liver damage. Embelin, a natural parabenzoquinone derived from the Embelia ribes plant, has gained attention for its potential therapeutic properties, antioxidant and organ-protective effects. The study aimed to assess the hepatoprotective properties of embelin against liver dama­ge induced by isoniazid and rifampicin in rats. Wistar rats were used, and liver damage was induced by administration of isoniazid (100 mg/kg) and rifampicin (100 mg/kg). Embelin was given at doses of 50, 75, and 100 mg/kg for 21 days. All the drugs were given orally. Serum levels of the oxidative stress markers, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) activity measured by enzymatic assay kits (Elabscience, China), and the levels of tumour necrosis factor-α (TNF-α), interleukins IL-1β and IL-6 measured by ELISA kits (Randox, UK) were estimated. Embelin administration at varying doses effectively restored AST, ALT, ALP, SOD and catalase activity and notably decreased MDA and nitric oxide concentration as well as expression of inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum of animals with drug-induced liver damage. These findings underscore embelin’s hepatoprotective effects, likely attributed to its radical scavenging properties and ability to suppress cytokine production. Keywords: antioxidant effect, cytokine suppression, embelin, hepatoprotection, isoniazid, rifampicin

Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect. However, blood pressure reduction may lead to sympathetic activation through the baroreflex. The effect of esaxerenone on the sympathetic nervous system remains unclear. We investigated the effect of esaxerenone on organ damage and the sympathetic nervous system in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), a well-established model of essential hypertension with sympathoexcitation and organ damage. Three-week administration of esaxerenone or hydralazine successfully attenuated the blood pressure elevation. Both esaxerenone and hydralazine comparably suppressed left ventricular hypertrophy and urinary albumin excretion. However, renal fibrosis and glomerular sclerosis were suppressed by esaxerenone but not hydralazine. Furthermore, plasma norepinephrine level, a parameter of systemic sympathetic activity, was significantly increased by hydralazine but not by esaxerenone. Consistent with these findings, the activity of the control centers of sympathetic nervous system, the parvocellular region of the paraventricular nucleus in the hypothalamus and the rostral ventrolateral medulla, was enhanced by hydralazine but remained unaffected by esaxerenone. These results suggest that esaxerenone effectively lowers blood pressure without inducing reflex sympathetic nervous system activation. Moreover, the organ-protective effects of esaxerenone appear to be partially independent of its blood pressure-lowering effect. In conclusion, esaxerenone demonstrates a blood pressure-lowering effect without concurrent sympathetic activation and exerts organ-protective effects in salt-loaded SHRSP. Esaxerenone has antihypertensive and cardiorenal protective effects without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Sodium glucose cotransporter-2 inhibitors and heart disease: Current perspectives.

Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are antidiabetic medications with remarkable cardiovascular (CV) benefits proven by multiple randomised controlled trials and real-world data. These drugs are also useful in the prevention of CV disease (CVD) in patients with diabetes mellitus (DM). Although DM as such is a huge risk factor for CVD, the CV benefits of SGLT-2i are not just because of antidiabetic effects. These molecules have proven beneficial roles in prevention and management of nondiabetic CVD and renal disease as well. There are various molecular mechanisms for the organ protective effects of SGLT-2i which are still being elucidated. Proper understanding of the role of SGLT-2i in prevention and management of CVD is important not only for the cardiologists but also for other specialists caring for various illnesses which can directly or indirectly impact care of heart diseases. This clinical review compiles the current evidence on the rational use of SGLT-2i in clinical practice.

Evaluating the Nephroprotective and Hepato-protective Effects of Hypoestes rosea in Acetaminophen-Induced Toxicity in Albino Rats

The leaves of Hypoestes rosea are in use as traditional medicine in the Niger Delta areas in Nigeria and the Western part of Cameroun for the management of different ailments in children, such as anaemia, malaria, fever and other ailments. Regardless of its uses, scanty studies evaluating its organ protective effects exist. Therefore, this research study evaluates the nephroprotective and hepato-protective effects of Hypoestes rosea in acetaminophen-induced toxicity in Albino rats. The objectives of this research study are to evaluate the protective effect of Hypoestes rosea on the kidney and the liver of albino rats. Acetaminophen, which is frequently used as an analgesic and antipyretic drug at high doses, can be harmful to vital organs of the body, affecting the liver and kidneys. In this study, effects of an aqueous extract of Hypoestes rosea (AEHr) on liver function parameters and kidney function parameters of acetaminophen induced-toxicity in albino rats were evaluated using acute (15 days) and sub-chronic (30 days) duration of study and study group comprising of prophylactic (pre-treatment) and therapeutic (post-treatment) phases with six experimental groups in each phase. A total of 112 adult apparently healthy Albino rats weighing (180-220g) were used for this study, divided into six experimental groups of extract control (EC), negative control (NC), positive control (PC), AEHr100mg/kg b w., AEHr 200mg/kg b w., and AEHr 300mg/kg b w. groups each of six rats. At the end of the research study period, blood samples were collected through jugular puncture for liver and kidney function parameters. Results showed that acetaminophen-induced toxicity in albino rats caused toxicity to the kidney and toxicity to the liver, as evidenced by the raised levels of potassium, urea, creatinine and low bicarbonate from the renal function parameters and also as evidenced by significant elevation of bilirubin and liver enzymes with a significantly low total protein and albumin levels from the liver function parameters when compared with other experimental groups. Conversely, AEHr at different concentrations in a dose-dependent pattern at the different treatment phases and different duration periods were able to repair the injury to the kidney and liver caused by acetaminophen induction to normal. Consequently, the findings of this research propose that Hypoestes rosea contains active ingredients accountable for the nephroprotective and hepato-protective abilities in rats and can be recommended for more studies using higher mammals.

SODIUM RESTRICTION CONCOMITANT WITH SUFFICIENT ALDOSTERONE SUPPRESSION MAY BE ASSOCIATED WITH RENOPROTECTIVE EFFECTS IN THE PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism (PA) is an independent risk factor for various cardiovascular diseases and chronic kidney disease, which makes it important to treat this condition at an early phase. Currently, the use of mineralocorticoid receptor antagonists (MRAs) is recommended for the treatment of bilateral type, mainly idiopathic hyperaldosteronism. However, recent reports suggest that the benefit of the treatment with MRAs is only obtained in the patients with enough aldosterone suppression, which is indicated as post-treatment plasma renin activity (PRA) &gt;=1.0 ng/mL/h. Since PRA is affected by the amount of sodium intake, PRA elevation after MRAs treatment might partially reflect an adherence to strict sodium restriction, thereby leads to organ protective effects in PA patients. Design and method: A total of 91 patients who received eplerenone or esaxerenone for PA treatment were included. The patients with PRA&gt;=1.0 ng/mL/h at one year after the initiation of MRAs were determined as responders, and others were determined as non-responders. The differences between responders and non-responders were analyzed. In addition, these patients were followed for another two years (total three years), and the transitions of estimated glomerular filtration (eGFR) among responders and non-responders were also compared. Results: The doses of MRAs were equivalent between responders and non-responders. Estimated sodium intake was significantly lower in responders (responders: non-responders; 156.2±42.3 mmol/day: 124.7±41.8 mmol/day P&lt;0.05). Multivariate logistic regression analysis has shown that estimated sodium intake was an independent predictor for responders. During three years’ period, eGFR was significantly decreased in non-responders (pre-treatment: post-treatment; 73.0±14.7 ml/min: 69.5±14.1 ml/min P&lt;0.05), whereas it was comparatively preserved in responders (pre-treatment: post-treatment; 68.3±17.9 ml/min: 68.0±19.0 ml/min P=0.84). Conclusions: The present study have shown that responders in PA patients may partially benefit from an adherence to sodium restriction. Sodium restriction concomitant with sufficient suppression of aldosterone effect may exert renoprotective effects for PA patients.

A review on the pharmacology, pharmacokinetics and toxicity of sophocarpine.

Sophocarpine is a natural compound that belongs to the quinolizidine alkaloid family, and has a long history of use and widespread distribution in traditional Chinese herbal medicines such as Sophora alopecuroides L., Sophora flavescens Ait., and Sophora subprostrata. This article aims to summarize the pharmacology, pharmacokinetics, and toxicity of sophocarpine, evaluate its potential pharmacological effects in various diseases, and propose the necessity for further research and evaluation to promote its clinical application. A large number of studies have shown that it has anti-inflammatory, analgesic, antiviral, antiparasitic, anticancer, endocrine regulatory, and organ-protective effects as it modulates various signaling pathways, such as the NF-κB, MAPK, PI3K/AKT, and AMPK pathways. The distribution of sophocarpine in the body conforms to a two-compartment model, and sophocarpine can be detected in various tissues with a relatively short half-life. Although the pharmacological effects of sophocarpine have been confirmed, toxicity and safety assessments and reports on molecular mechanisms of its pharmacological actions have been limited. Given its significant pharmacological effects and potential clinical value, further research and evaluation are needed to promote the clinical application of sophocarpine.