Postprandial hyperglycemia represents a critical therapeutic target in type 2 diabetes mellitus (T2DM), requiring interventions that simultaneously address glycemic dysregulation and oxidative stress. This study evaluated the anti-hyperglycemic and antioxidant properties of Sclerocarya birrea leaf crude extract (CE) and biosynthesized silver nanoparticles (AgNPs). Phytochemical screening, nanoparticle characterization (UV–Vis, XRD, TEM, SEM, DLS, FTIR), enzyme inhibition assays (α-amylase, α-glucosidase, DPP-IV), glucose dynamics in Caco-2 cells, and antioxidant assays (DPPH, total antioxidant capacity, H₂O₂ cytoprotection) were performed. Phytochemical analysis identified flavonoids, tannins, alkaloids, and terpenoids as major constituents of Sclerocarya birrea leaf extract. AgNPs exhibited spherical morphology (36.8 ± 8.6 nm, n = 100 particles analyzed), face-centered cubic crystallinity (crystallite size: 32.1 nm), and characteristic surface plasmon resonance at 451 nm. Both formulations inhibited α-amylase (CE IC₅₀: 14 µg/mL; AgNPs IC₅₀: 14.07 µg/mL, n = 3) and α-glucosidase (CE IC₅₀: 15.96 µg/mL; AgNPs IC₅₀: 15.82 µg/mL, n = 3), showing substantial inhibition, though less potent than acarbose. Uniquely, AgNPs demonstrated selective DPP-IV inhibition (IC₅₀: 220.5 µg/mL, n = 3, p < 0.001 vs. CE), completely absent in CE. In antioxidant assays, DPPH scavenging potency was comparable between formulations (CE IC₅₀: 23.45 µg/mL; AgNPs IC₅₀: 22.26 µg/mL, n = 3), while CE achieved higher maximal scavenging at the tested concentrations. Conversely, AgNPs provided superior intracellular cytoprotection against H₂O₂-induced oxidative stress in kidney cells (80.2 ± 2.1% viability at 76 µg/mL vs. CE 69.8 ± 3.4% at 190 µg/mL, n = 3, p < 0.001), representing a 2.5-fold dose advantage. Neither formulation significantly altered glucose uptake or SGLT1 expression in intestinal epithelial cells (p > 0.05, two-way ANOVA, n = 3). These findings establish S. birrea-based formulations, particularly AgNPs, as promising multifunctional candidates for managing postprandial hyperglycemia and oxidative complications in T2DM. They also highlight nanotechnology-enhanced phytomedicine as an innovative therapeutic strategy.

Type 2 diabetes (T2D) remains a major public health challenge in Africa, where limited healthcare access and the high cost of conventional therapies sustain reliance on African traditional medicine (ATM). This systematic review and meta-analysis evaluated the efficacy, mechanisms of action, and safety of African polyherbal formulations for T2D management. This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines, following a protocol registered with PROSPERO (CRD420251168831). We searched PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar for studies published between 1 January 2011 and 31 December 2024. Seventeen studies met the inclusion criteria. Polyherbal formulations consistently improved glycaemic control, insulin sensitivity, antioxidant status, and lipid profiles. Meta-analysis of 10 preclinical studies demonstrated a significant reduction in fasting blood glucose compared with that of diabetic controls (SMD = −5.22, 95% CI: −5.55 to −4.89; p < 0.001; I² = 93.88%). Proposed mechanisms included β-cell protection, stimulation of insulin secretion, inhibition of α-amylase and α-glucosidase, and attenuation of oxidative stress. Safety data were limited and inconsistently reported. Human evidence was limited to one quasi-experimental clinical study and one acute human OGTT study. African polyherbal formulations demonstrate promising antidiabetic potential; however, methodological heterogeneity, limited phytochemical characterisation, inadequate safety assessment, and scarce clinical evidence highlight the need for standardised preclinical studies and well-designed clinical trials to support evidence-based integration into healthcare.

This systematic review protocol outlines the planned approach to evaluate the efficacy and safety of polyherbal plant combinations in managing Type 2 Diabetes Mellitus (T2DM) within African populations. Given the rising burden of T2DM in Africa and limited access to conventional treatments, polyherbal formulations are widely used as alternative or complementary therapies. This review will include quantitative studies such as randomized controlled trials, cohort studies, and in vivo/in vitro research, as well as qualitative ethnopharmacological studies. Primary outcomes focus on glycemic control markers, fasting serum glucose, HbA1c, and postprandial glucose, while secondary outcomes include lipid profiles, safety, and phytochemical characteristics. Comprehensive literature searches will be conducted across multiple databases from 2011 to 2024. Risk of bias will be assessed, and where appropriate, meta-analyses will be performed. Findings aim to provide evidence-based insights to guide clinical practice, research, and policy on the use of polyherbal therapies for T2DM management in Africa.

Background: Type 2 diabetes mellitus (T2DM) remains a major global health challenge, prompting interest in plant-based interventions with multi-target metabolic effects. This study evaluated the individual and combined effects of Psidium guajava (PG) and Seriphium plumosum (SP) on hepatic and skeletal muscle glucose metabolism. Methods: HepG2 hepatocytes and differentiated C2C12 myotubes were treated with PG, SP, and a 1:1 PG+SP combination. Cell viability, glucose uptake, GLUT2 expression, glycogen content, and AMP levels were assessed. Interactions were evaluated using Bliss Independence, Combination Index (CI), Loewe Additivity, and Zero Interaction Potency (ZIP) models. Results: SP exhibited minimal cytotoxicity, whereas PG induced concentration-dependent reductions in HepG2 viability. The PG+SP combination maintained higher viability than PG alone and demonstrated additive-to-synergistic interactions (CI = 0.51–0.89). In HepG2 cells, all treatments significantly enhanced glucose uptake relative to controls (p < 0.05), with the combination achieving approximately 94% of the metformin response. The combination also significantly reduced GLUT2 expression, with the greatest effect observed at 125 + 125 µg/mL (0.77 ± 0.14-fold, p < 0.0001). In C2C12 myotubes, PG, SP, and PG+SP significantly increased glucose uptake and glycogen accumulation (p < 0.05). SP increased AMP levels at lower concentrations, whereas the PG+SP combination reduced AMP levels below control values. Synergy analyses consistently indicated concentration- and endpoint-dependent interactions ranging from additivity to synergy. Conclusions: The PG+SP combination co-ordinately modulated glucose uptake, glycogen storage, GLUT2 expression, and AMP-related energy status across hepatic and skeletal muscle models. These findings provide mechanistic support for further investigation of this botanical combination as a potential multi-target strategy for T2DM and metabolic dysfunction.

African Traditional Medicine (ATM) remains an important component of primary healthcare in South Africa; however, evidence for plants used in cutaneous wound care is dispersed across ethnobotanical, pharmacological, toxicological, and conservation literature. This narrative review integrates these evidence streams and proposes a conservation- and safety-aware translational prioritization framework for wound-healing botanicals used in South African ethnomedical practice. A structured search of PubMed, ScienceDirect, Web of Science, Google Scholar, and SciFinder identified eligible peer-reviewed ethnobotanical and preclinical studies published between January 1999 and June 2026. After taxonomic harmonization, 173 accepted taxa were documented from South African ethnobotanical reports as being traditionally used for wound care. Only seven taxa had direct wound closure evidence in relevant in vitro or in vivo models, while twenty-eight taxa had wound-relevant anti-inflammatory evidence. Reported mechanisms included keratinocyte and fibroblast migration, collagen-associated responses, angiogenesis, wound contraction, and inflammatory modulation. The evidence base remains uneven: many taxa are supported primarily by traditional use, while dose, formulation, treatment frequency, duration of use, dermal safety, and sustainable sourcing are poorly reported. Safety concerns were identified for selected toxic or irritant taxa, and destructive harvesting of roots, bulbs, corms, rhizomes, and bark may increase conservation risk. Overall, the review highlights a substantial gap between ethnomedical documentation and pharmacological validation, and it provides a prioritization strategy to guide future phytochemical, mechanistic, formulation, dermal-safety, and preclinical wound-healing research in South Africa.

Product Shezi (PS) is a polyherbal African traditional medicine (ATM) formulated from six known South African medicinal plants and is used for treating cutaneous wounds. However, its ethnopharmacological properties have not been scientifically validated. This study aimed to evaluate the antioxidant, anti-inflammatory, and antimicrobial activities of PS in vitro. Aqueous and methanolic extracts were prepared and qualitatively screened for phytochemical constituents. Cytotoxicity in fibroblasts and macrophages was assessed using an ATP-based viability assay. Antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and a hydrogen peroxide (H₂O₂)-induced oxidative stress model. Anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophages were measured using the Griess reagent system, a human prostaglandin E₂ (PGE₂) ELISA, and a bovine serum albumin (BSA) anti-denaturation assay. Antimicrobial activity was assessed by twofold serial broth microdilution, agar well diffusion, and a crystal violet biofilm assay. Phytochemical screening confirmed the presence of saponins, alkaloids, tannins, glycosides, terpenoids, flavonoids, and steroids. PS exhibited IC₁₀ values of 3 and 10 μg/mL in fibroblasts and macrophages, respectively. PS (1–5 μg/mL) showed 70% DPPH scavenging potential and potent H₂O₂ cytoprotection (p < 0.001). Nitric oxide inhibition was non-significant (p > 0.05) whilst PGE₂ decreased significantly (p < 0.05) compared to LPS-stimulated cells. BSA denaturation was inhibited in a dose-dependent manner (p < 0.05). Staphylococcus aureus and S. epidermidis were the only microorganisms susceptible to PS (MIC 650–5000 μg/mL) with low SI (SI ≈ 0.05–0.06), while others were resistant. PS showed no antibiofilm activity (crystal-violet assay). Overall, PS demonstrated antioxidant and anti-inflammatory activities and selective antibacterial effects against planktonic bacteria in vitro. However, further optimization of extraction methods, detailed mechanistic studies, and in vivo investigations are warranted to substantiate therapeutic relevance.