Chemical Markers for Quality Control of Medicinal Plants Used in Sickle Cell Disease Management: Application of the Herbal Marker Ranking System (Herb MaRS)

Sickle cell disease (SCD) remains a major public health burden, especially in sub-Saharan Africa, where access to conventional therapies is limited. Consequently, herbal medicines/medicinal plants are increasingly utilised for SCD management. However, standardisation and quality control of these medicinal plants are hindered by variability in phytochemical composition, underscoring the relevance of marker compounds. This systematic review applies the Herbal Marker Ranking System (Herb MaRS) to identify and prioritise appropriate marker compounds for quality control of the most frequently reported anti-sickling medicinal plants. Selected plants include Carica papaya , Terminalia catappa, Annona muricata, Ceiba pentandra, Ocimum gratissimum, Garcinia kola , and Rauvolfia vomitoria . Data on phytochemical composition, anti-sickling bioactivity, toxicity, compound concentration, and availability of analytical methods and standards were obtained through a systematic literature review. Marker compounds were ranked based on adapted Herb MaRS criteria prioritising anti-sickling activity, safety, and analytical feasibility. Overall, 35 compounds were identified, with rutin and ellagic acid achieving the highest scores (8/8), indicating their suitability as marker compounds. Quercetin (7/8), carpaine (6/8), gallic acid (6/8), campesterol (6/8), and stigmasterol (6/8) also ranked highly. Several compounds demonstrated toxicity concerns requiring monitoring, while others lacked sufficient data for full evaluation. This study demonstrates the utility of the Herb MaRS framework for systematic marker selection to support the quality control of herbal formulations for SCD management. It highlights promising chemical markers that can facilitate standardisation, advancing the safe and effective use of plant-based therapies for SCD.