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

BACKGROUND: 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. OBJECTIVES: This study investigated the effect of aloperine on testicular torsion/detorsion injury in rats. MATERIALS AND METHODS: 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 3 h of right spermatic cord torsion (720°, clockwise), followed by 3 h of detorsion. Aloperine (10 mg/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. RESULTS: 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. DISCUSSION AND CONCLUSION: 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.

Aloperine Attenuates Hepatic Ischemia/Reperfusion-Induced Liver Injury via STAT-3 Signaling in a Murine Model.

Hepatic ischemia/reperfusion (I/R) damage is one of the most common side effects of liver surgery. This pathophysiological process may lead to excessive hepatic damage. Aloperine is an active ingredient isolated from Sophora alopecuroides Linn and has a variety of therapeutic effects, including organ protection. However, the hepatoprotective effect of aloperine against hepatic I/R damage has not yet been determined. C57BL/6 mice were allocated to the sham-operated (sham), hepatic ischemia/reperfusion (I/R), and aloperine groups. The mice were exposed to 30 min of hepatic hilum occlusion. Then a 3-h reperfusion was performed. Mice in the sham group underwent sham surgery. Hepatic injury was evaluated by plasma aspartate aminotransferase (AST) and transaminase alanine aminotransferase (ALT) levels, histological evaluation, cell apoptosis, the number of activated inflammatory cells, and the expression levels of inflammatory cytokines, including tumor necrosis factor-α and interleukin-6. The protein phosphorylation status of the reperfusion-associated survival pathways was evaluated. Mice with hepatic I/R injury presented increased plasma ALT and AST levels, increased hepatic apoptosis, abnormal histological structure, and elevated inflammatory responses. However, aloperine ameliorated hepatic I/R-induced injury. Moreover, aloperine enhanced the level of signal transducer and activator of transcription (STAT)-3 phosphorylation after I/R. Ag490, an agent that inhibits STAT-3 activity, abolished aloperine-induced STAT-3 phosphorylation and liver protection. Aloperine ameliorates hepatic I/R-induced liver injury via a STAT-3-mediated protective mechanism. Patients with hepatic I/R injury may benefit from aloperine treatment. SIGNIFICANCE STATEMENT: Hepatic I/R can cause excessive liver damage. This study revealed that aloperine, an active component isolated from Sophora alopecuroides Linn, ameliorates hepatic I/R injury and related liver damage in vivo. The underlying protective mechanism may involve the STAT-3 signaling pathway. These findings may lead to the development of a novel approach for treating hepatic I/R damage in clinical practice.

Remote liver ischemic preconditioning protects against renal ischemia/reperfusion injury via phosphorylation of extracellular signal-regulated kinases 1 and 2 in mice.

Perioperative acute kidney injury (AKI), which is mainly mediated by renal ischemia‒reperfusion (I/R) injury, is commonly observed in clinical practice. However, effective measures for preventing and treating this perioperative complication are still lacking in the clinic. Thus, we designed this study to examine whether remote liver ischemic preconditioning (RLIPC) has a protective effect on damage caused by renal I/R injury. In a rodent model, 30 mice were divided into five groups to assess the effects of RLIPC and ERK1/2 inhibition on AKI. The groups included the sham-operated (sham), kidney ischemia and reperfusion (CON), remote liver ischemic preconditioning (RLIPC), CON with the ERK1/2 inhibitor U0126 (CON+U0126), and RLIPC with U0126 (RLIPC+U0126). RLIPC consisted of 4 liver ischemia cycles before renal ischemia. Renal function and injury were assessed through biochemical assays, histology, cell apoptosis and protein phosphorylation analysis. RLIPC significantly mitigated renal dysfunction, tissue damage, inflammation, and apoptosis caused by I/R, which was associated with ERK1/2 phosphorylation. Furthermore, ERK1/2 inhibition with U0126 negated the protective effects of RLIPC and exacerbated renal injury. To summarize, we demonstrated that RLIPC has a strong renoprotective effect on kidneys post I/R injury and that this effect may be mediated by phosphorylation of ERK1/2.

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.

Aloperine Alleviates Myocardial Injury Induced by Myocardial Ischemia and Reperfusion by Activating the ERK1/2/ß-catenin Signaling Pathway.

OBJECTIVE: Myocardial ischemia/reperfusion (I/R) injury can cause severe cardiac damage. Aloperine is a quinolizidine alkaloid found in the leaves and seeds of Sophora alopecuroides L. It has been recognized that aloperine has organ-protective properties; however, its role in cardioprotection is poorly characterized. This study aimed to evaluate the cardioprotective effects of aloperine against myocardial I/R injury in vivo. METHODS: Adult male Sprague‒Dawley rats were randomly divided into sham-operated, control, and aloperine groups. All rats except for the sham-operated rats were subjected to 45 min of myocardial ischemia (by left anterior descending ligation) followed by 3 h of reperfusion. Aloperine (10 mg/kg) was given intravenously at the onset of reperfusion. The cardioprotective effects of aloperine were evaluated by determining infarct size, hemodynamics, histological changes, cardiac biomarkers, and cardiac apoptosis. RESULTS: Aloperine limited infarct size; improved hemodynamics; attenuated myocardial I/R-induced histological deterioration; decreased serum LDH, CK-MB, and α-HBDH levels; and inhibited apoptosis after myocardial I/R injury. Moreover, aloperine stimulated the phosphorylation of ventricular ERK1/2, which is a major module of MAPK signaling pathways. Furthermore, aloperine increased the ventricular expression levels of ß-catenin. Pharmacological inhibition of ERK1/2 diminished aloperine-induced cardioprotection and blocked ERK1/2/ß-catenin signaling. CONCLUSIONS: These data support the cardioprotective effect of aloperine against myocardial I/R injury, which is mediated, at least in part, by the ERK1/2/ß-catenin signaling pathway.