Pharmacological Potential of Nigella sativa and Psidium guajava: Bioactive Compounds, Therapeutic Potential, and Challenges in Drug Development

Antimicrobial resistance (AMR) is a growing global health crisis exacerbated by the slow pace of new drug development. This study systematically evaluated the pharmacological and antimicrobial properties of Nigella sativa and Psidium guajava, focusing on their bioactive constituents, clinical relevance, and therapeutic potential. A comprehensive search of eight databases covering the period 2015–2024 yielded 1,057 records, of which 111 full-text articles met the inclusion criteria. Ultimately, 24 studies were included in the qualitative synthesis, and 12 provided quantitative MIC data suitable for meta-analysis. Using a random-effects model, the pooled MIC estimate for thymoquinone was 6.83 μg/mL (95% CI: 4.85–8.82), indicating consistent broad-spectrum antimicrobial activity. Heatmaps and Venn diagrams highlighted compound-pathogen interactions and revealed overlapping and unique antibacterial spectra among thymoquinone, carvacrol, and quercetin-glycosides. The ROBINS-I tool revealed a low to moderate risk of bias in most domains, although the confounding and outcome measurement domains showed a serious risk in a few studies. Notably, publication bias was evident due to selective reporting of favorable MIC values. N. sativa and P. guajava exhibited significant antimicrobial, anti-inflammatory, and antitumor activities, mediated by compounds such as thymoquinone, carvacrol, tannins, and quercetin. These findings emphasize the potential of these plants as adjuncts or alternatives in antimicrobial therapy. However, challenges including standardization, bioavailability, and regulatory frameworks must be addressed through multidisciplinary research and sustainable bioproduction approaches.