Putative thiazide-like diuretic medicinal plants: an electrolyte fingerprint-based review of preclinical evidence.

OBJECTIVES: Thiazide and thiazide-like diuretics remain first-line antihypertensive agents, exerting their primary renal effect through inhibition of the Na+-Cl- cotransporter (NCC) in the distal convoluted tubule, producing natriuresis and saluresis with relative K+ and Ca2+ sparing. Although numerous medicinal plants possess diuretic properties, most preclinical studies assess only urine volume, preventing mechanistic classification and obscuring whether observed diuresis reflects NCC-mediated tubular activity. METHODS: This focused review applied an electrolyte-based pharmacological framework to critically appraise medicinal plants with putative thiazide-like diuretic activity. KEY FINDINGS: Of nine studies assessed across seven plant species, Tagetes erecta most closely approximated the thiazide-like fingerprint-natriuresis with relative K+ sparing and a partial Ca2+-sparing effect under HCTZ-referenced conditions, with additive interaction with HCTZ. Remaining candidates showed broader saluretic profiles, HCTZ-comparable natriuresis through mechanistically distinct pathways, or mixed/loop-like electrolyte patterns, illustrating the pharmacological heterogeneity of herbal diuretics. Isoquercitrin and related flavonol scaffolds were identified as plausible candidates for NCC-targeted investigation. CONCLUSIONS: Genuinely thiazide-like electrolyte profiles are uncommon in the herbal diuretic literature, largely due to reliance on urine volume, inconsistent electrolyte profiling, and infrequent HCTZ comparison. Electrolyte-based classification frameworks would improve mechanistic interpretation and facilitate identification of pharmacologically selective candidates. T. erecta represents the priority candidate for future NCC-focused mechanistic investigation.