Phytomedicine as a source of SGLT2 inhibitors, GLP-1 secretagogues and DPP-IV inhibitors for mitigation of Diabetic Nephropathy

Diabetic nephropathy (DN) has been the major contributor to chronic kidney disease (CKD), end stage renal disease (ESRD), and cardiovascular risks. Incretin pathway modulators (GLP-1 analogs, GLP-1R agonist, GLP-1 secretagogues and DPP-IV inhibitors) and SGLT2 inhibitors are presently the favourable outlooks among the numerous therapeutic approaches and efforts considered for DN beyond RAAS modulation. The current state of art is an attempt to mine and demonstrate extant knowledge of plausible plant source of SGLT2 inhibitors, GLP-1 secretagogues and DPP-IV inhibitors towards mitigation of DN. Scientific search engines PubMed, Google Scholar, Scopus, and SciFinder are accessed towards collecting literatures on pathophysiology of DN, treatment regimens, herbs for DN, and available literatures regarding plant sources of SGLT2 inhibitors and incretin modulators. This literature review has comprehensively collated, critically analyzed, and documented the state of art phyto-preparations and phytocompounds based strategies for management of DN. GLP-1 secretagogues activity, DPP-IV and SGLT2 inhibitory activity elicited from plant -based compounds have been extensively reviewed. The literature on mechanism of action, dose and principles of the treatments, and the degree of evidence for plant derived formulations have been rigorously examined and critiqued. Consequently, the review has brought into focus that the bioactive principle of many of the effective investigated phyto-preparations with potential against DN are yet to be discovered. It is also revealed the need of toxicological safety assessment and effectiveness in vivo investigation for many of the plant preparations and plant compound demonstrating in vitro potential against DN towards availing effective, safer and economically sound alternatives to synthetic incretin modulators and SGLT2 inhibitors. The extant literature reviewed in the present article provides a good scope to further investigate in-depth mechanistic aspects of phytomedicine reported for DN management. The reviewed literatures suggest that in vivo investigations can be made with toxicologically safe phytomedicine and plant derived incretin modulators, and SGLT2 inhibitors having excellent therapeutic potential against DN. Further, this review endeavors to bolster research into plant based alternatives that are comparatively safe and less costly, to augment extant state of art incretin modulators and SGLT2 inhibitors.