NATURAL PRODUCT–DRUG COMBINATIONS IN THE MANAGEMENT OF DIABETIC NEPHROPATHY: FROM BENCH TO BEDSIDE

Abstract

Diabetic nephropathy (DN) is the most common form of end-stage renal disease worldwide, where it is estimated that 30 per cent of all people with diabetes mellitus have nephropathy. Although there have been some important progresses in knowledge about the pathophysiology of diabetic nephropathy, the existing treatment options are mainly confined to renin-angiotensin-aldosterone system (RAAS) blockage using angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which have incomplete nephroprotective effects. The multifactorial and complex structure of the DN pathogenesis. It has been observed that the potential adjunctive therapy of natural products has distinct modes of action, including TLR4/NF-KB, Nrf2/Keap1 antioxidant response, and TGF-B/Smad-inhibitions, complementing the conventional pharmaceutical interventions. Recent findings indicate that bioactive compounds like quercetin, curcumin, resveratrol, and multi-component traditional medicine formulations have synergistic nephroprotective effects when used with conventional therapies and produce better effects in reducing proteinuria, preserving eGFR, and preventing renal fibrosis than monotherapy strategies do. Clinical trials show superior therapeutic potential and safer side effects, and new technologies, such as nanotechnology-based targeted delivery systems and artificial intelligence-based combination optimization, provide unprecedented possibilities of application in precision medicine. This syntactic survey looks at the mechanistic rationale behind natural product-drug combinations, the existing clinical evidence, and the future directions of translating such promising synergies into evidence-based clinical practice to achieve better DN management results.