Table 1 Animal studies investigating the physiological role of Apelin-13

Male Wistar rats

Cardiac muscle tissue

10 nmol/kg/d

5 days

I: Blood sampling was conducted at specified intervals post-myocardial infarction to assess serum levels of LDH, CK-MB, MDA, and NO. II: Myocardial infarct size and hemodynamic function were measured on day 14.

I: Reduces infarct size and serum biomarkers.

II: Elevates heart rate and NO levels. III: No notable blood pressure differences were observed.

Apelin has long-term cardioprotective effects against myocardial infarction by attenuating cardiac tissue damage and lipid peroxidation and increasing NO production.

[125]

Male SD rats

Pulmonary artery

10 nmol/kg/d

3 weeks

mPAP, RVHI, lung tissue morphology, and LC3 protein detection, as well as mRNA levels of P62 and Beclin-1, and expressions of LC3, LC3-II/I, and P62 were measured.

I: Decreased mPAP

II: Reduction of RVHI

Apelin may prevent pulmonary arterial hypertension by inhibiting autophagy.

[126]

ApoE-male/- rat

Carotid vascular endothelial cells

2 mg/kg/d

3 weeks

Atherosclerotic plaque formation was induced in the carotid artery, and Mice were treated with apelin-13 (2 mg/Kg/day) or vehicle for the last 3 weeks

I: Decreased inflammatory response. II: Reduction of total cholesterol. III: Decreased low-density lipoprotein. IV: Reduction of free fatty acid

Apelin-13 did not alter the lesion size but stabilized atherosclerotic plaques and improved lipid profiles. Activating the Aplin system reduces plaque vulnerability.

[127]

Albino rats

System evaluation

2 × 6 × 10 –8 mol/Kg/d

from 6th to 20th day of pregnancy

I: Measurement of mean arterial blood pressure, total urine protein, serum urea, creatinine, NO, ET-1, IL-6, and MDA

II: istopathological investigation of kidney tissue

Maintain uterine perfusion pressure

Apelin treatment notably enhanced blood pressure, urine proteins, serum urea, creatinine, ET-1, IL-6, NO levels, and MDA while improving kidney histoarchitecture in the treated group.

[128]

Healthy albino rats

Renal vessel

(6 × 10 –8 mol/kg body-weight/twice d)

day 6 to 20 of gestation

I: blood pressure and urine protein at GD 0, 10, and 18 were determined

II: serum apelin, PLGF, VEGF, sFlt-1, sEng, IFN-γ, and IL-10 levels and serum SOD enzyme and CAT activities estimated

III: Placental histopathological examination performed.

I: reduction of blood pressure

II: Increase in ejection fraction

III: Decreased proteinuria

the protective role of apelin in preeclampsia pathogenesis is examined. Apelin may confer benefits through angiogenic balance restoration, antioxidant enhancement, and inflammation inhibition.

[129]

Male Wistar rats

Cerebral

Three treatment groups (MCAO + apelin-13 at 10, 20, 40 µg/kg)/ injected 5 min before reperfusion.

I: Neural loss and infarct volume were assessed using Nissl and TTC staining. II: Neurological deficits were scored by modified criteria. III: Serum NO was measured colorimetrically

Apelin-13 (20, 40 µg/kg) reduced neural death, infarct volume, and sensory-motor issues (p < 0.05) and normalized serum NO levels at 20 µg/kg (p < 0.05) in MCAO groups.

Apelin-13 IV injection improves sensory-motor balance by reducing neural degeneration and restoring serum NO levels, effectively treating ischemic stroke.

[130]

Male Wistar rats

Cerebral

50 ng/kg, 10 µl per rat/ 2 h MCAO followed by 24 h reperfusion.

Neurological deficits and infarct volume were assessed with TTC staining. MPO activity and cytokines were measured by PCR, while APJ, Iba1, GFAP, and HMGB1 were evaluated using immunohistochemistry and western blot.

Apelin-13 in I/R rats improved neurological function, reduced infarct size, and lowered MPO, IL-1, TNF-, and ICAM-1 levels. APJ expression increased, while apelin-13 decreased Iba1, GFAP, and HMGB1, indicating less microglial and astrocytic activation.

apelin-13 exhibits neuroprotective properties for neurons in the context of ischemia/reperfusion by mitigating neuroinflammatory responses.

[131]

Male SD rats

lung

1 mg/kg of Apelin-13 was added

in 5 ml saline/pumping time of 10 min

The effects of apelin-13 on LIRI were assessed histologically via H&E staining, and lung edema was measured by the wet/dry weight ratio. UCP2 protein expression and mitochondrial changes were evaluated using western blotting and electron microscopy.

Group IR showed lung damage with increased IL-1b, IL-6, and TNFa levels, indicating oxidative stress. In contrast, apelin-13 in group APL reduced these effects, with lower ROS and higher UCP2 expression.

Apelin-13 protects against lung ischemia-reperfusion injury by reducing edema, inflammation, oxidative stress, and mitochondrial dysfunction.

[132]