The review was designed to map how the 71 RENISUS species have been validated for potential use in SUS, with the researchers also comparing the evidence with traditional uses. Two reviewers independently screened titles, abstracts and full texts, removing duplicates before eligibility assessment and resolving differences by discussion. Searches covered Scopus and Web of Science for studies published through May 2026 without language restrictions, and botanical names were checked against World Flora Online and Flora e Funga do Brasil. The work followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, but its protocol was not prospectively registered. It also used a qualitative assessment of sample size, controls, blinding, randomization and tested concentrations rather than a formal instrument such as Cochrane RoB 2 or ROBINS-I, because the included designs ranged from laboratory assays to clinical trials and case reports.

Based on the predominant evidence available for each species, the authors assigned plants to three descriptive categories: clinical evidence available, moderate evidence based mainly on preclinical pharmacology and toxicology, and low or emerging evidence based on limited experimental or ethnobotanical reports. These labels describe the type of research available, not a formal ranking of evidence quality or a conclusion that a plant is safe and ready for routine clinical use. Only five plants had published human clinical data: cashew, Anacardium occidentale L.; pineapple, Ananas comosus (L.) Merr.; Bidens pilosa L.; Copaifera langsdorffii Desf.; and pau d’arco, Handroanthus impetiginosus (Mart. ex DC.) Mattos. Even among these five, many interventions involved mixed formulations, small samples or preparations whose chemical standardization markers and doses were not reported.

Pineapple research produced some of the more concrete human findings, although results varied by preparation and condition. In a randomized, double-blind, placebo-controlled trial involving 60 women recovering from episiotomy, participants received 500 mg of oral bromelain every eight hours for six days. Compared with placebo, the treatment was associated with reduced perineal pain and faster wound closure. In a cohort of 100 mothers, daily consumption of 200 mL of fresh pineapple juice was reported to accelerate uterine involution, while a separate study of 30 participants found concentration-dependent effects of aqueous and hydroalcoholic fruit and stem extracts on uterine contractility. A clinical pharmacokinetic study in 40 patients with chronic rhinosinusitis detected bromelain in the bloodstream and sinonasal mucosa after oral dosing. By contrast, a honey-and-bromelain syrup produced no measurable benefit over controls for acute irritative cough in 50 children. A trial involving 80 overweight or obese women also reported improved lipid and glucose measures, but pineapple was only one of six ingredients in the beverage, preventing attribution of the effects to the plant alone.

The evidence for B. pilosa centered on oral mucositis in patients receiving radiochemotherapy and involved FITOPROT, a mucoadhesive gel or rinse combining hydroethanolic B. pilosa extract with curcuminoids from Curcuma longa. In a triple-blind, randomized, placebo-controlled trial of 120 patients, the formulation reduced mucositis severity from day 15 onward and produced fewer ulcerative lesions by the end of radiotherapy. A separate phase I dose-escalation trial in 20 patients found temporary, low-intensity mucosal pigmentation in seven participants and tooth sensitivity in four; both resolved after discontinuation, and no significant genotoxic effects were detected. But a randomized trial of 52 patients found no statistically significant between-group difference in the primary mucositis assessment, while quality of life declined in both groups during radiotherapy. A small pilot involving 14 men reported improved glucose regulation and insulin secretion after a whole-plant oral formulation, yet the preparation and dose were not fully characterized. Because the mucositis studies tested a multi-ingredient product, their effects cannot be attributed to B. pilosa alone.

Copaifera evidence was still thinner and included a direct safety warning. A six-patient case series reported faster healing of chronic wounds after topical copaiba oleoresin, but neither the oleoresin concentration nor the amount applied per dressing was recorded. A separate case report described hepatotoxicity following oral use of C. langsdorffii oil-resin together with Hypericum perforatum, or St. John’s wort. The authors described this as a possible herb–drug interaction and a signal for pharmacovigilance, while emphasizing that a single case cannot establish causation or incidence. For pau d’arco, an open-label, single-arm trial involving 12 adults with primary dysmenorrhea reported that an oral bark-extract capsule was safe and well tolerated and was associated with reduced symptoms. The naphthoquinone content of the capsules was not quantified. Three additional reports involving oesophageal cancer, diffuse large B-cell lymphoma and metastatic thyroid cancer described positive responses while the extract was used as complementary therapy. These were individual case reports, not controlled demonstrations of anticancer efficacy.

Cashew studies likewise combined direct evidence about the plant with results that could not be isolated from broader dietary or cosmetic interventions. A randomized trial in 40 children with moderate malnutrition found that adding cashew seed flour to the diet improved nutritional status, glycated hemoglobin and lipid profiles. In a phase II trial, 30 patients with inflammatory wrist joint lesions received a topical cream containing crude stem-bark extract, and the investigators reported a significant reduction in inflammatory symptoms; the concentration of extract in the cream was not stated. A separate clinical study of 50 participants assessed a topical bark-and-shell formulation for oily skin. In a randomized trial involving 100 women at cardiometabolic risk, a 30 g-per-day mixed-nut diet reduced hunger, but the contribution of A. occidentale could not be separated from the other nuts or the energy restriction. Cashew preparations were generally well tolerated in the reviewed studies, although tree-nut allergy and possible urushiol cross-reactivity remain relevant safety concerns, and long-term evidence in pregnant people and children was limited.

The review also identified recurring barriers to translating plant research into dependable public-health practice. Extracts varied by plant part, solvent, concentration and route of administration, with many clinical studies omitting the dose, chemical profile or quantitative standardization marker. Such reporting gaps make dose–response relationships difficult to determine and products difficult to reproduce. Small samples, incomplete documentation of randomization or blinding, and differences among comparators and outcomes further limited generalizability. The review noted that in vitro findings such as antioxidant activity or enzyme inhibition cannot by themselves predict systemic bioavailability, complex human inflammatory pathways or clinical effectiveness. It also highlighted sustainability and knowledge-governance challenges, including sustainable harvesting, optimization of extraction, intellectual-property protection, benefit sharing and participation by traditional knowledge holders as co-producers of evidence.

Safety signals emerged alongside the therapeutic reports. Copaifera-associated liver injury was the most prominent concern, with the review pointing to the need for interaction studies and systematic adverse-event monitoring. Bromelain was generally well tolerated in short-term use, but mild gastrointestinal symptoms and hypersensitivity reactions have been reported, including possible cross-reactivity in people allergic to latex or pineapple; no long-term toxicity data were available in the reviewed literature. The B. pilosa formulation caused transient pigmentation and tooth sensitivity in the short phase I trial, with no pregnancy, lactation or pediatric contraindication data identified. Variable naphthoquinone content across pau d’arco bark preparations introduced possible dose-related toxicity, and cashew bark contains anacardic acids that may irritate skin. The review’s conclusion was that efficacy and safety must be assessed together, warning that uncritical dissemination could cause preventable harm.

The authors say the baseline inventory could help guide research priorities, regulatory decisions and evidence-guided incorporation of plants into SUS, but they do not treat the review as a formal clinical guideline. Future systematic reviews should register protocols in advance and apply design-appropriate risk-of-bias tools, including RoB 2 for randomized trials and ROBINS-I for observational studies. Priority gaps include standardized preparation and manufacturing controls, adequate toxicology, pharmacovigilance, herb–drug interaction profiling and larger, well-reported clinical trials. The review also argues that public-health policy should do more than measure plants against conventional biomedical endpoints: it should recognize traditional knowledge, support community-engaged research, address biodiversity and benefit-sharing concerns, and strengthen programs such as Farmácia Viva. The central result is therefore less a verdict on individual plants than a measurement of the distance between a large national inventory and a clinically testable body of evidence: 753 studies have now been mapped, but only 34 involved humans, and even those studies reveal substantial gaps in standardization, safety reporting and methodological rigor.

Subject of Research: Systematic review of clinical and preclinical evidence for 71 medicinal plants prioritized by Brazil’s Unified Health System

Article Title: Traditional medicinal plants in the Unified Health System of Brazil: a systematic review

Article References: Rempel, C., Hernández-Guzmán, D., Vargas-Chaves, I., Turatti, L., Herrera-Tapias, B. A., Pelle, A. R., Luchesi, A. L., Cano, H., Gutiérrez-Reyes, A. M., Fiegenbaum, T. R., Pinto, D., & Fröhlich, S. (2026). Traditional medicinal plants in the Unified Health System of Brazil: a systematic review. Frontiers in Pharmacology, 17, Article 1867902. https://doi.org/10.3389/fphar.2026.1867902

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1867902

Keywords: RENISUS, Brazilian health system, medicinal plants, clinical trials, phytotherapy, bromelain, Bidens pilosa, Copaifera, Anacardium occidentale, systematic review, Traditional, medicinal