A therapeutic approach to identify leading molecules from natural products and therapeutic targets in CKD by network pharmacology

Chronic kidney disease (CKD), a condition characterized by diminished kidney function, affects approximately 10 % of the population worldwide. With its high mortality rate of ∼1.2 million, CKD poses a high global burden. The complexity increases severalfold due to its vast variety of aetiologies and relatively limited treatment options that, too, are associated with adverse effects. The continuous deterioration of the kidneys makes them reliant on external purification systems i.e., dialysis or whole kidney transplantation, both having certain limitations, making CKD one of the highly prevalent diseases across the globe. The multi-faceted disease requires multi-targeted therapies that can potentially improve CKD care. Natural products have long been considered the “holy grail” for many diseases, including CKD; their multi-targeting nature, fewer side effects, and ability to target multiple pathways have caught attention. The complexity increases when a single phytopharmaceutical cures a disease by acting on various targets and affecting diverse mechanisms. Identifying therapeutic targets and lead molecules thus becomes difficult and, at times, a big task! The network pharmacology (NP) tool has shifted this drug discovery paradigm towards a “multi-drug, multi-target” approach to underscore responsible molecular interconnections that unwind the therapeutic potential of natural products against CKD by predicting potential therapeutic targets and underlined molecular mechanisms. Applying NP for natural products in CKD can be a time-saving and cost-effective strategy. The present review emphasizes prominent classes of natural products and lead molecules obtained from herbal preparations, their explored multi-targeted effects against CKD, and novel targets predicted and validated using the NP approach.