**Abbreviations**

*Malaria*

Na<sup>+</sup>

by AA administration.

**6. Conclusion**

mal drug delivery of AA studies above.

Electrolyte loss in malaria results from inhibition of Na<sup>+</sup>

These enzymes catalyze the interconversion of cortisone and cortisol in humans [185]. The isoform 11β-HSD 1 is located in the liver, adipose and brain where it converts the inactive cortisone to the active cortisol and 11β-HSD 2 is primarily expressed in kidney catalyzing the reverse conversion. The two enzymes provide a balance in glucocorticoid metabolism. AA was shown to selectively inhibit 11β-HSD 1 and not the other isoform. When 11β-HSD 1 is inhibited there is a resultant reduction in liver gluconeogenesis, lipophilia and there is improved insulin sensitivity [186], which may explain the positive influence of AA administration on glucose homeostasis in malaria [30]. Therefore, 11β-HSD inhibition by AA works in tandem with AA glycogen phosphorylase (GP) inhibition (see above) that preserve glycogen stores. Indeed, the kidney glycogen stores tend to be significantly higher in AA administered SD rats than untreated controls. Nevertheless, inhibition of 11β-HSD 2 leads to sodium retention, hypokalemia and hypertension [187] parameters which were not observed with AA administration as compared to controls in the transder-

Further, selective inhibition of 11β-HSD 1 has been suggested to induce antiinflammatory effect via the stimulation of haeme oxygenase-1 in LPS-activated mice and J774.1 in murine macrophages [188], which may explain the preservation of renal electrolyte handling that was observed when AA was administered.

other electrolyte channels by OS (ROS) in the proximal convoluted tubules which results in an increased sodium load reaching the distal convoluted tubes. Excess

 is as a result lost in the urine in a what is referred to as pseudohypoaldosteronism. Therefore, a dual role of AA may be observed in malarial AKI in that the anti-inflammatory and antioxidant effect through the selective inhibition of 11β-HSD 1 with ultimate reduction in gluconeogenesis which reduce glycolysis and in lipid synthesis which reduces lipid peroxidation. Antioxidant capacity is seen through AA inhibition of glycogen phosphorylase and glycolysis modulation. Increased insulin insensitivity, that is usually seen in end-stage malaria fronted by increasing glucose concentrations and OS, is abolished by AA inhibition of 11β-HSD 1. Furthermore, glycogen synthase upregulation when glycogen phosphorylase is inhibited increases glycogen storage in the kidneys and this way restoring optimum renal function and electrolyte handling deranged by OS driven AKI. Also, inhibition of 11β-HSD1 promotes autophagy and correlates with reduced OS, inflammation [189] which are key pundits in malarial AKI eradicable

Oxidative stress drives malaria pathophysiology by ROS and NS insults upon pRBC's and npRBC's from parasitic infection, immunological host response. The inflammatory milieu has a cross cutting foot print in malarial syndromes intricately intertwining complex disease events, processes and systems to bring about malaria disease. Here we have shown how artemisinin, a commonly used antimalarial phytotherapeutic and asiatic acid, an experimental antimalarial phytochemical, to

Asiatic acid, armed with constitutive antioxidant and oxidative properties inhibit parasitic growth, host inflammasome and ameliorates systemic abnormalities in malaria. With selective enzymatic inhibition propensities, apoptotic influences and amelioration of malaria-induced systemic metabolic derangements, AA shows potential as an anti-parasitic, anti-disease, anti-inflammatory, antioxidant,

explain their various interactions in the combat of malarial disease.

immunomodulatory, renoprotective and malarial disease elixir.

/K<sup>+</sup>

ATPase, ENac and

**32**

