Gastroprotective potential of <i>Bixa orellana</i>: A critical review of extract-specific phytochemistry and preclinical evidence

<jats:p>Peptic ulcer disease remains clinically important despite effective Helicobacter pylori (H. pylori) eradication and acid-suppressive therapy. Gastric injury reflects an imbalance between aggressive factors, including acid-pepsin activity, H. pylori, non-steroidal anti-inflammatory drugs (NSAIDs), ethanol, oxidative stress, inflammation, apoptosis, and microvascular disturbance and protective mechanisms such as mucus-bicarbonate secretion, prostaglandin signaling, nitric oxide-regulated blood flow, epithelial restitution, and endogenous antioxidant defenses. Bixa orellana L. (annatto or achiote) is a tropical medicinal plant whose seed arils are rich in the apocarotenoids bixin and norbixin, whereas its leaves contain variable phenolics, flavonoids, tannins, terpenoids, alkaloids, and other constituents depending on geography, maturity, and extraction method. This critical narrative review uses a structured search and qualitative evidence-appraisal framework to evaluate extract-specific phytochemistry, direct gastric evidence, indirectly relevant gastrointestinal and vascular evidence, mechanistic plausibility, safety, quality control, and translational readiness. The available literature supports B. orellana as a biologically plausible preclinical mucosal-protective candidate, particularly for prevention of acute chemical injury; however, it does not establish clinical efficacy or chronic ulcer-healing activity. Confidence is limited by the small number of direct gastric studies, incomplete chemical characterization, inconsistent separation of leaf and seed evidence, limited dose-response testing, narrow model selection, and insufficient mechanistic and histological endpoints. Future studies should use authenticated plant material, voucher specimens, chromatographic fingerprints, quantitative markers, complementary prevention and healing models, acute and repeated-dose toxicology, mucus and prostaglandin measurements, oxidative and inflammatory biomarkers, and blinded histological scoring before human investigation is justified.</jats:p>