This study investigated the adverse effects of high salt intake as well as the plausible therapeutic effects of the stem bark of Parkia biglobosa (PB) aqueous extract or Spironolactone (Sp), and both on markers of cardiometabolic functions. Previous experimental studies have shown that the hydroalcoholic extract of PB stem bark caused vasorelaxation and the aqueous extract of the bark decreased the blood pressure [2, 23]. However, the present study showed that the aqueous extract of PB stem bark ameliorates cardiometabolic dysfunctions in high-salt diet. High-salt diet (HSD) has been reported to cause some cardiometabolic changes such as electrolytes imbalance (especially sodium and potassium imbalance), dyslipidaemia, cardiac dysfunctions and inflammatory responses [4, 5].
In this study, HSD caused a significant increase in plasma sodium and a slight but insignificant decrease in potassium concentration. Increased plasma sodium concentration has been known to elicit deleterious cardiometabolic changes which may involve activation of mineralocorticoid receptors. Spironolactone (Sp) is a mineralocorticoid blocking agent that competes with the cytoplasmic aldosterone receptor . Its mechanism of action is to competitively block the epithelial and non-epithelial actions of aldosterone in the distal tubule of the nephron, thus, preventing sodium and water retention, and causing potassium retention. It is not surprising that the administration of Sp ameliorated plasma concentrations of sodium and caused potassium retention in HSD-fed animals. This observation is consistent with other studies [1, 14]. The potassium-retention effect of Sp in this study was significantly increased in HSD-fed animals and this showed that Sp acted as a potassium sparing diuretic. Therefore, Sp can cause deleterious elevation of circulating potassium as an adverse effect if used for therapy in salt-induced cardiometabolic disease. On the other hand, administrations of either only PB extract or both PB extract and Sp normalized the sodium and potassium plasma concentrations in HSD-fed animals. Therefore, it is reasonable to suggest that PB extract has a mineralocorticoid blocking action since administration of only PB extract normalized plasma sodium and does not spare potassium as inSp administration. We therefore infer that the combination of PB extract and Sp prevented the deleterious increase in potassium level when Sp was administered alone. Thus, PB may be appropriate for co-administration with Sp (as a diuretic) to prevent the potassium-retention effect of Sp.
Moreover, HSD caused a significant decrease in plasma concentration of high-density lipoprotein and a significant increase in plasma concentrations of triglycerides, low density lipoprotein and total cholesterol, thus, showing an overt dyslipidaemia. Dyslipidaemia has been reported in different studies in association with metabolic syndrome, cardiometabolic dysfunction and salt-induced hypertension [9, 24]. In addition, the mechanism by which HSD increases triglycerides is still controversial but it is well known that high salt intake impairs lipid metabolism . Interestingly, administration of Sp to HSD-fed animals did not normalize dyslipidaemia.
However, administration of only PB extract or both PB extract and Sp ameliorated lipid profile in HSD-fed animals. Evidence in previous studies has shown that the aqueous extract of PB stem bark has anti-lipidaemic effects due to its component called tannin which reduces hypertriglyceridaemia and hypercholesterolaemia [25–27]. The anti-lipidaemic effects of PB have also been attributed to its hypolipidaemic component called saponins . Therefore, the observed anti-lipidaemic effects of PB in this study agreed with other previous studies [25–28].
Furthermore, CRP is a general marker of inflammation and a risk marker for cardiovascular diseases.CRP plasma concentration increases whenever there is tissue damage in the body due to inflammation (29). Therefore, the significant increase in the plasma and cardiac CRP in both the untreated HSD-fed rats and HSD-fed rats that received Sp indicated that there was occurrence of systemic and cardiac inflammation in both groups. On the other hand, the PB extract caused a significant decrease in the plasma and cardiac CRP in the HSD-fed animals. Hence, this suggests that PB stem bark has anti-inflammatory properties as reported in the findings of Kouadio et al and Nwaehujor et al [30, 31].
In this study, HSD disrupts the endothelial function by a decrease in the plasma and cardiac concentrations of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS). In previous studies, reduction in NO has been shown to be strongly associated with increased levels of reactive oxygen species (ROS) which are generated by NADPH oxidase, xanthine oxidase (XO) or uncoupled eNOS within the vascular wall [32, 33]. These previous studies were corroborated with the observed increase in the cardiac XO and profound reduction of NO and eNOS in the plasma and cardiac tissues of the untreated HSD-fed rats. However, administration of PB extract ameliorated the endothelial function by a significant increase in NO and eNOS. Therefore, we suggest that since PB stem bark has been reported to have antioxidant and anti-inflammatory properties, the production of ROS that disrupts NO and eNOS functions was reduced in HSD-fed rat that received either PB extract or both PB extract and Sp. Similarly, the enhancement of endothelial function via NO production because of the antioxidant property of PB is supported by other study .
Furthermore, uric acid is known to cause endothelial dysfunction, vascular smooth muscle cell proliferation, increased IL-6 synthesis, and impairment of nitric oxide production, all of which contribute to the progression of cardiometabolic diseases [34–36]. The administration of PB extract or its combination with Sp showed a significant decrease in plasma uric acid level with a concurrent decrease in ADA and XO. It is expected that a decrease in uric acid levels should be accompanied by a decrease in both ADA and XO. This probably suggests that the observed uric acid lowering properties of the PB extract is mediated through the ADA/XO/UA pathway.