Research Articles (Pharmacology)

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Antiproliferative effects of cannabinoids and cisplatin in cervical cancer cells
Mathibela, Sanele Priscilla; Lebelo, Maphuthi Tebogo; Steenkamp, Vanessa (Wiley, 2026-04-29)
INTRODUCTION: Cervical cancer remains a leading cause of cancer-related mortality among women globally, particularly in low-and middle-income countries. Cisplatin, a standard chemotherapeutic agent, is limited by severe toxicities and chemoresistance. This study aimed to assess the effects of cisplatin in combination with phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on cell proliferation, morphology, cell cycle progression, cell death, and DNA damage. METHODS: Synergistic interactions between THC, CBD, and cisplatin were assessed in HeLa, SiHa, and MCF-12A cells using the checkerboard assay and SRB assay. Cell morphology, cell cycle progression, apoptosis induction, autophagic activity, and DNA repair gene expression were evaluated using various techniques. RESULTS: The THC–CBD–cisplatin combination exhibited the strongest apoptotic response in cancer cells (HeLa 53%, SiHa 58%),while minimally affecting MCF-12A cells (32%). Cannabinoid co-treatment amplified the antiproliferative and pro-apoptotic effects of cisplatin in HeLa and SiHa cells. The triple combination induced a G2/M arrest in HeLa cells and sub- G1 accumulation inSiHa cells. Autophagic activity, indicated by LC3B puncta formation, increased in HeLa and SiHa cells following THC and CBD exposure. DNA repair genes XRCC1 and RAD51 were downregulated by the cannabinoid–cisplatin combination. CONCLUSION: These findings demonstrate that combining THC and CBD with cisplatin results in enhanced and mechanistically diverse anticancer effects, with a higher degree of selectivity for cervical cancer cells compared to non-cancerous MCF-12A cells by inducing apoptosis and autophagy while inhibiting DNA repair capacity. This study highlights the potential of cannabinoid-based combination therapies as a promising approach for cervical cancer treatment.
Cytotoxicity potency of cannabinoids is by serum supplementation : implications for In Vitro cancer studies
Mathibela, Sanele Priscilla; Lebelo, Maphuti Tebogo; Steenkamp, Vanessa (Wiley, 2026-03-11)
BACKGROUND: Fetal calf serum (FCS) is a key supplement in cell culture, providing nutrients, and growth factors that support cancer cell proliferation. Studies suggest that compound cytotoxicity profiles in vitro vary depending on FCS concentration in culture medium. The study aimed to examine how extracellular conditions influence the in vitro response of cancer cells to phytocannabinoids, with particular emphasis on serum supplementation. METHODS AND RESULTS: Cells were exposed to CBD and THC in media containing 0.5% or 10% FCS for 24–72 h. Cell viability was assessed using the sulforhodamine B assay and live-cell imaging. Significantly enhanced cytotoxic effects of CBD and THC were noted under low-serum conditions (0.5% FCS) compared to standard conditions (10% FCS), particularly after 72 h incubation. THC demonstrated greater cytotoxicity than CBD in SiHa cells, while both compounds showed similar effects in HeLa cells. CONCLUSION: The study demonstrates that serum concentration critically modulates the cytotoxic potency of cannabinoids. Reduced FCS enhances cannabinoid efficacy by limiting protein binding, emphasizing the need to optimize serum conditions for accurate in vitro cytotoxicity assessments
Mapping current use of artificial intelligence in pharmacology education via a scoping review
Cordier, Werner; Ijeoma, Princess (Wiley, 2026-08)
Pharmacology education, often reputed as complex, overtly didactic and decontextualised, may benefit from artificial intelligence-supported strategies. However, current guidance is fragmented across disciplines and contexts, thus weakening evidence-based curricular implementation. This scoping review mapped existing research to identify applications, strengths, limitations, and areas for future development. A double-blinded screening process facilitated by Covidence yielded 17 eligible studies from four databases. Studies mostly comprised cross-sectional studies from high-income countries in the medical context, with generative artificial intelligence being predominant (ChatGPT-3.5 and ChatGPT-4.0). Research comprised assessment (n = 12), paedagogy (n = 4), curriculum design (n = 1), and programme evaluation (n = 1). Most studies assessed tools' ability to answer examinations, with mixed success depending on the version, question type, and inclusion of context in prompt engineering. Few studies incorporated students, limiting insights into learning impact. Zero-shot prompting was mostly used, limited further by unclear design frameworks, which may bias outcomes considering downstream inefficiencies. Current research prioritises the performance of artificial intelligence, rather than its integration or impact in learning, which reduces its applicability for curriculum design and competency development. Although promising, the impact is limited, requiring clearer instructional design and rationalisation within the education ecosystem. Although there is considerable potential for pharmacology education, research requires greater structure, longitudinal design, and incorporation of students to inform clear impact. Purposeful, context-aligned implementation and continuous evaluation are needed to ensure ethical, valid, and meaningful use in pharmacology education. To support future research, recommendations are provided for practical reporting, scientific design, and impact measurement.
Summoning the sandman : mitigating the rebound effects of hypnotic therapy
Lurie, Brittany Lisa; Cordier, Werner (Medpharm Publications, 2025)
Insomnia significantly impairs quality of life, productivity, and mental health. Pharmacotherapy, such as benzodiazepines and Z-drugs, are often used, though notable risks include tolerance, dependence, withdrawal, and rebound insomnia, especially when used beyond shortterm recommendations. This review summarises the pharmacological mechanisms and potential adverse effects, and further discusses the deprescribing strategies to reduce the occurrence of rebound and withdrawal effects. These include gradual dose tapering, substitution with longer-acting agents, adjunct use of melatonin, and integration of cognitive behavioural therapy for insomnia to support withdrawal and relapse prevention. Non-pharmacological approaches should be prioritised wherever feasible, and pharmacotherapy should be used judiciously, with patient education and interprofessional support. Ultimately, a balanced, individualised management plan that emphasises resolving the underlying reasons for insomnia, and incorporating judiscious use of non-pharmacological and pharmacotherapeutic options, should be aimed for.
The pharmacovigilance of complementary medicines : unpacking the complexities
De Beer, A.D.; Padayachee, N.; Booth, Z.; Leuschner, Machel (Medpharm Publications, 2025)
Complementary medicines in South Africa are defined as substances originating from natural sources such as plants, fungi, and minerals, intended to support physical or mental well-being. Unlike allopathic medicines, which are pure chemical compounds requiring registration through rigorous safety and efficacy dossiers, complementary medicines can be registered without such evidence. While allopathic medicines are backed by clinical trials, complementary medicines, especially herbal products, often lack robust clinical data. This disparity highlights the importance of pharmacovigilance (PV) to monitor adverse reactions (ADRs) and potential interactions in complementary medicines. Complementary herbal medicines (Category D) fall within the regulatory ambit of the South African Health Products Regulatory Authority (SAHPRA), under the Medicines and Related Substances Act 101 of 1965. These products, however, are challenging to regulate due to variability in constituency, batch-to-batch inconsistencies, and a lack of clinical trial evidence. Herbal medicines, composed of multiple active compounds, are particularly complex, with potential synergistic or antagonistic interactions with conventional medicines complicating their safety profiles. Despite their widespread use, adverse drug reactions (ADRs) from herbal products remain undetected and underreported, often due to a lack of standardisation, insufficient clinical studies, and health illiteracy among consumers. This paper proposes a methodology for investigating ADRs from complementary medicines, including understanding the formulation, clinical presentation, and phytochemical composition. By improving pharmacovigilance practices and fostering greater collaboration among experts, a more comprehensive safety profile for herbal-based medicines can be developed, ultimately benefiting public health.
Can increasing the number and role of community pharmacists in South Africa help address rising antimicrobial resistance rates, and what are the implications?
Maluleke , T.M.; Schellack, Natalie; Kalungia, A.C.; Rehman, I.U.; Moodley, R.; Sefah, I.A.; Jelić, A.G.; Kurdi, A.; Godman, B.; Meyer, J.C. (Medpharm Publications, 2025)
Antimicrobial resistance (AMR) is a critical issue globally as well as in South Africa, exacerbated by concerns with inappropriate antibiotic use in primary care. This includes prescribers in South Africa with variable dispensing of antibiotics without a prescription. Where this does occur, this is principally for patients with urinary tract infections (UTIs), including those associated with sexually transmitted infections (STIs), and STIs. There is little dispensing of antibiotics without a prescription for self-limiting conditions including upper respiratory tract infections (URTIs). Community pharmacists in South Africa typically offer symptomatic relief first for patients presenting with URTIs unlike prescribers. In view of this, coupled with the key role that community pharmacists played during the COVID-19 pandemic, and the fact that in a number of countries trained community pharmacists can diagnose and dispensed antibiotics for certain infections including UTIs, we believe it is time for the South African Government and Health Authority to review current legislation and expand the services of community pharmacists. An increased number of community pharmacists can also work with prescribers to improve their antibiotic use, building on examples in South Africa and across developing countries. This paper summarises published evidence to promote an increasing role for community pharmacists in the country to reduce AMR, and the suggested next steps to take this debate forward. We believe this is essential if South Africa is to effectively tackle rising AMR rates.
The pill and the profession : the evolving role of pharmacists in oral contraceptive access for women in South Africa
Edward, Kim Cherise; Ndinisa, Yogi Chelsea; Maboa, R.M.; Parkar, Hafiza (Medpharm Publications, 2025)
Oral contraceptives (OCs) play a key role in reproductive health and family planning, yet their use and accessibility in South Africa remain shaped by sectoral dynamics, socioeconomic factors, and persistent systemic barriers. Nationally, the prevalence rate of contraceptive use is estimated at around 60% among women of reproductive age. Injectables dominate public-sector provision while OCs are more frequently accessed in the private sector. Within the public sector, free combined oral contraceptive (COCs) and progestin-only pill (POPs) are available, although counselling and patient support are often limited. In contrast, the private sector provides a wider range of formulations, including extended-cycle regimens, but affordability and medical aid coverage remain decisive factors. Certain (emergency contraception) ECs are legally available for non-prescription access in community pharmacies, yet studies indicate poor awareness and low utilisation among adolescents and socioeconomically disadvantaged groups. Pharmacists are strategically positioned as accessible healthcare providers, offering both dispensing and counselling services. However, their role is undermined by limited training recognition, regulatory restrictions, and stigma surrounding EC provision, often reinforced by overly restrictive Good Pharmacy Practice (GPP) requirements. Contraceptive use often comes with complications such as adherence difficulties and side-effects like nausea and breakthrough bleeding, as well as risks such as venous thromboembolism (VTE). Despite these challenges, pharmacists express readiness to expand their role within primary health care, aligning with South Africa’s broader shift toward universal health coverage. This review highlights the importance of strengthening pharmacist-led contraceptive management through policy reform, structured training, and multidisciplinary collaboration to improve reproductive health outcomes for women. African women; contraceptive challenges
Calming the acid : pharmacotherapeutic approaches to gastro-oesophageal reflux disorder
Cordier, Werner (Medpharm Publications, 2025)
Gastro-oesophageal reflux disease (GORD) is a chronic disorder where gastric contents, inclusive of gastric acid, pepsin and foodstuff, enter the oesophagus which leads to irritation and potential erosion. While refluxate regurgitation is a physiological process, pathophysiological levels of reflux may manifest as heartburn, regurgitation, and non-cardiac chest pain. Management should be approached from a non-pharmacotherapeutic vantage, where pharmacotherapy is included where justified to support treatment outcomes. In this review, the broad medication classes used for GORD treatment in South Africa are discussed, including the first-line proton pump inhibitors, histamine-2-receptor antagonists, antacids, and alginate-based treatments.
Acute complications of diabetes mellitus : current insights into pathophysiology and clinical management
Nyane, Ntsoaki Annah; Balmith, Marissa; Ravhengani, Muano Lucy; Flepisi, B.T. (Medpharm Publications, 2025)
Diabetes mellitus is a chronic metabolic disorder with rising global prevalence and significant morbidity and mortality due to its complications. Among these, acute complications such as diabetic ketoacidosis (DKA), hyperosmolar hyperglycaemic state (HHS), hypoglycaemia, and lactic acidosis represent urgent and life-threatening conditions requiring immediate medical intervention. DKA and HHS share common pathophysiological pathways involving insulin deficiency and counter-regulatory hormone excess, leading to profound metabolic disturbances. Although DKA is more common in type 1 diabetes (T1D) and HHS in type 2 diabetes (T2D), both demand prompt diagnosis and structured therapeutic strategies to restore fluid and electrolyte balance and normalise blood glucose levels. Hypoglycaemia is often due to drug-induced insulin overdosing, and is associated with neuroglycopenic symptoms, while lactic acidosis involves derangements in lactate metabolism and may be triggered by conditions such as sepsis or metformin use. This review explores the pathophysiology, clinical presentation, diagnostic features, and management protocols for these acute complications. It further highlights the importance of preventive strategies, patient education, and the potential role of digital health and personalised medicine in reducing the risk of complications and improving diabetes outcomes.
Partnerships for building leadership capacity for nurse educators in sub-saharan Africa
Manning, Dianne; Kelly, Frances; Cordier, Werner; Dreyer, Abigail; Keiller, Lianne; Nyoni, Champion; Van Wyk, Jacky; Wolvaardt, Jacqueline Elizabeth (Liz) (REGENT Business School Press, 2026-07)
Capacity development for educators of health profession students in low-income countries is an essential contributor to improving health outcomes. A multi-stakeholder partnership was created to offer a leadership programme for nurse educators in Sub-Saharan Africa. Partners were the Johnson and Johnson Foundation (grant funder), the Foundation for Professional Development, a private higher education institution, (coordinator and monitoring and evaluation provider), and the Association for Health Professions Education and Leadership (AHPEL), an NGO and community of practice with education providers affiliated to public universities in South Africa. AIM : The aim of the study was to evaluate the success of the programme. LITERATURE REVIEW : Partnerships between stakeholders from different sectors, public and private, are acknowledged as important contributors to leveraging resources for capacity development in health professions education. (World Health Organisation, 2013) Examples of successful partnerships in Sub-Saharan Africa include the FAIMER/SAFRI fellowships (Frantz et al, 2015; 2019; Keiller et al, 2023), MEPI and AFREHEALTH programmes (Omaswa et al, 2017; 2018). RESEARCH DESIGN METHODOLOGY : Sixteen fellows were recruited, representing seven Sub-Saharan countries. The 18-month fellowship covered key aspects of educational methodology with a strong focus on leadership. Hybrid delivery included contact sessions, synchronous online engagements and a quality improvement project (QIP). Evaluation included pre-and post-fellowship surveys and participant reflections. PRELIMINARY FINDINGS AND DISCUSSION : The results of the surveys showed that fellows’ self-perceptions of competence and confidence improved in all domains of Education, Research, Leadership and Academic Citizenship. They developed a stronger sense of self and community through engaging with their peers, mentors, and leaders in the nursing profession. Tangible impact was noted in their institutions after completion of their QIP, which created new opportunities for growth. The fellowship helped to develop a community of practice of future nurse educator leaders that can be added to the network in the region. The most significant challenges were access to passports, visas and travel funding, resulting in more than half of the fellows being unable to complete. CONCLUSIONS : Fellows bolstered their leadership qualities over the 18-month period and developed new skills which supported the value of the partnership approach. The shortcomings will be addressed in future collaborative endeavours.
Stakeholders' perspectives on pharmacy-based point-of-care diagnostic services in South Africa : a nominal group technique
Mjuza, Lonwabo; Maimela, Charles; De Beer, Niel; Chetty, Darren; Leuschner, Machel; Ncube, Keith Ntokozo; Salvides, Isabella; Ijeoma, Princess; Chibi, Buyisile; Naidoo, Kiolan; Duah, Evans; Mashamba-Thompson, Tivani Phosa (Wiley, 2026-07)
BACKGROUND AND AIM : Community pharmacies are gaining recognition as key access points for primary healthcare. Incorporating point-of-care (POC) diagnostic services in these environments has the potential to enhance early disease detection. However, regulatory and operational obstacles might impede their implementation. This study aimed at identifying and ranking the factors that facilitate and hinder the introduction of POC diagnostic services in South African community pharmacies. METHODS : A nominal group technique (NGT) workshop was conducted with eight stakeholders, including pharmacists, academics, and diagnostic specialists. The stakeholders generated, discussed, and ranked ideas on a seven-point Likert scale. Quantitative rankings were analyzed descriptively, and qualitative data underwent thematic analysis. Theme scores are reported as a percentage of the maximum possible score (number of scorers × 7), not as a proportion of participants endorsing a theme. RESULTS : The key facilitators included accessibility and convenience (94%), professional training and competence (88%), cost and time savings (82%), patient demand and public health initiatives (80%), and stakeholder engagement (78%). The corresponding barriers included infrastructure and space constraints (88%), training gaps (94%), affordability and reimbursement challenges (80%), patient mistrust (71%), regulatory ambiguities (78%), and system-level challenges (78%). CONCLUSION : Pharmacies seem ideally situated to offer POC diagnostic services; however, structural and regulatory challenges need resolution for effective integration. Establishing clear policy frameworks, investing in pharmacist education, and fostering stakeholder collaboration have been identified as key priorities for sustainable implementation. Due to the exploratory nature of the study and the limited stakeholder sample, these findings should guide further research and policy discussions rather than serve as conclusive implementation advice.
Autoimmune hepatitis : a review of molecular mechanisms and research gaps in African populations
Wheeler, Caitlin; Scholefield, Janine; Hurrell, Tracey; Naidoo, Jerolen (MDPI, 2026-02-28)
Autoimmune hepatitis (AIH) is an inflammatory liver disease characterised by immune-mediated hepatic injury, often leading to liver failure. The underlying molecular mechanisms of AIH remain poorly elucidated, hindering diagnostic and therapeutic advances. This review overviews the current understanding of AIH pathogenesis, which arises from a complex interplay of genetic predisposition, environmental triggers, and immune mechanisms (loss of tolerance, regulatory T cell dysfunction). Furthermore, current technologies and models which are being used to deconvolve the molecular profiles and pathophysiology of AIH are also discussed. Although AIH has a low reported global burden, AIH research is critically skewed towards European ancestry populations. This leaves a significant knowledge gap in diverse ancestry groups, such as those of African ancestry, where emerging research suggests that these patients may experience a more aggressive disease. Collectively, this highlights the need for research in underrepresented global populations to develop tailored diagnostics and effective targeted treatments.
Proteomic profiling of extracellular vesicle-enriched plasma using Mag-Net for biomarker discovery in pancreatic ductal adenocarcinoma
Buthelezi, Sindisiwe; Elebo, Nnenna; Naicker, Previn; Mokoena, Rethabile; Dubazana, Sinegugu; Govender, Ireshyn; Mamputha, Sipho; Ellero, Andrea Antonio; Stoychev, Stoyan; Mazibuko, Jeanet; Ojo, Dupe; Candy, Geoffrey; Devar, John; Cacciatore, Stefano; Omoshoro-Jones, Jones; Nweke, Ekene Emmanuel (American Chemical Society, 2026-06-30)
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer and was ranked among the top seven leading causes of cancer-related deaths in South Africa in 2020. Highlighting the urgent need for ongoing research to identify reliable biomarkers to improve clinical outcomes. This study compared the plasma proteomes of patients with PDAC, those with benign biliary pathologies (BBP), and healthy controls (HC). We used Mag-Net, a magnetic-bead-based method that enriches membrane-bound vesicles. Comparative analyses identified distinct and overlapping dysregulated proteins between PDAC, BBP, and HC. PDAC showed enrichment for epithelial-mesenchymal transition, complement activation, hypoxia, glycolysis, and extracellular matrix remodeling pathways, consistent with aggressive tumor biology. Proteins including SPP1, THBS2, PTX3, FBLN2, SDC1, CTSS, and VCAN were significantly increased in PDAC, with LRG1 showing the strongest association with disease severity. Proteins, namely GPNMB, H4C1, SAA1, and CCDC47, demonstrated progressive upregulation across disease comparisons, suggesting potential relevance to disease progression. These findings demonstrate that plasma proteomics provides discriminatory molecular insights and supports the development of population-relevant biomarker panels. While several candidate proteins show promise for inclusion in multianalyte panels, further validation in larger cohorts is necessary to establish their diagnostic and translational utility for early detection, risk stratification, and improved differential diagnosis of PDAC.
Exploring the therapeutic potential of cannabidiol in cutaneous squamous cell carcinoma : an integrated computational and experimental study
Josiah, Andrea Jess; Govender, Krishna Kuben; Govender, Penny Poomani; Cordier, Werner; Nell, Margo Judith; Ray, Suprakas Sinha (Wiley, 2026-03-05)
Cutaneous squamous cell carcinoma (cSCC) poses a significant therapeutic challenge due to its aggressive nature and recurrence rates. The current treatment 5-fluorouracil (5-FU) is associated with adverse skin reactions. This study investigates cannabidiol (CBD) as a potential alternative therapy for cSCC through an integrated computational and experimental approach. Density functional theory (DFT) using the M06-2X/6-31+G(d,p) basis set revealed that CBD's smaller HOMO–LUMO gap (0.282 eV) compared to 5-FU (0.288 eV) indicates a higher reactivity and potential biological interactions. Cannabidiol exhibits a higher binding affinity toward the CB1 receptor (−9.986 kcal/mol) than 5-FU (−3.760 kcal/mol). Molecular dynamics simulations demonstrate that the CBD–CB1 complex remains stable through hydrogen bonding and hydrophobic interactions. Binding free energy calculations (MM-GBSA) further confirmed CBD's enhanced affinity (−69.696 kcal/mol) over 5-FU (−28.241 kcal/mol). Experimentally, CBD exhibited greater cytotoxicity against A431 cSCC cells with an IC50 of 2.76 μM compared to 5-FU's IC50 of 5.61 μM. These integrated findings suggest that CBD is a promising alternative therapeutic candidate for cSCC, offering superior cytotoxicity and stable molecular interactions compared to 5-FU.
Neuroprotective and antioxidant properties of Polygala virgata fractions in a 6-hydroxydopamine-induced neurotoxicity model
De Beer, Andries Daniël; Rudolph, Wiehan; Maharaj, Vinesh J.; Steenkamp, Vanessa; Balmith, Marissa; Cordier, Werner (Elsevier, 2026-05)
INTRODUCTION : Ferroptosis contributes to Parkinson's disease progression given dysregulation of iron homeostasis and redox status. Polygala virgata is used ethnomedicinally for memory enhancement. This study assessed the cytoprotective and antioxidant properties of crude extracts and fractions of P. virgata using a 6-hydroxydopamine-induced (6-OHDA) SH-SY5Y neuroblastoma cytotoxicity model. METHOD : Dried roots of P. virgata (14% w/v) were sequentially extracted using dichloromethane/methanol (1:1) and methanol, which was combined to give a crude extract. The crude extract was separated into seven fractions using different ratios of water, acetonitrile and methanol on solid phase extraction (SPE). Inherent cytotoxicity of the samples (10 μg/mL), as well as their ability to reduce 6-OHDA-induced cytotoxicity (35 μM), was determined using the sulforhodamine B (SRB) assay after 48-h (h) exposure. The active fractions' cytoprotective effect in relation to reactive oxygen species (ROS), glutathione levels (GSH), lipid peroxidation, and mitochondrial integrity was determined fluorometrically. Cytoprotective fractions’ phytochemical constituency was elucidated using liquid chromatography high resolution mass-spectrometry (UPLC-HRMS). RESULTS : Fractions 3 to 7 increased cell density after exposure to 6-OHDA by 31.14%, 28.08%, 30.72%, 40.58% (p < 0.01) and 28.86%, respectively, with no inherent cytotoxicity observed. Fraction 4 reduced 6-OHDA-induced ROS generation (2.09-fold) and lipid peroxidation (0.28-fold). Non-significant increases in GSH were noted (1.34 to 19.25%), while all fractions hyperpolarised the mitochondrial membrane. Multi-hydroxylated xanthones, flavones and flavans were tentatively identified using UPLC-HRMS. CONCLUSION : P. virgata fractions reduced 6-OHDA-induced cytotoxicity via decreased oxidative stress and hyperpolarisation of the mitochondrial membrane, most likely ascribed to the identified xanthones, flavones and flavans. Isolation and purification of these compounds are warranted as potential antioxidant scaffolds. HIGHLIGHTS • First in vitro neuroprotective activity of Polygala virgata identified. • Little to no cytotoxicity present in fractions. • Neuroprotection linked to reactive oxygen species reduction (F4) and glutathione modulation (F6). • Possible synergism with identified compounds due to ratiometric differences.
An overview of HIV-associated neurocognitive disorder in South Africa
Flepisi, Brian Thabile; Balmith, Marissa (Springer, 2025-01-29)
PURPOSE OF REVIEW : It is well established that South Africa has the highest prevalence of human immunodeficiency virus (HIV) worldwide. The increasing widespread availability of combination antiretroviral therapy (cART) has improved the life-expectancy of people living with HIV. cART has dramatically reduced morbidity, however many people living with HIV continue to experience central nervous system (CNS) complications including neuropsychiatric conditions such as depression, anxiety, and neurocognitive disorders. RECENT FINDINGS: The pathological effects of HIV on the CNS have not been well elucidated. There are limited studies focusing on the prevalence, screening, and treatment strategies of HIV-associated neurocognitive disorder (HAND) in South Africa. The few studies included in this review indicate that the prevalence of HAND may be higher than estimated. In addition, only a limited number of cases have been reported. This may be due to a lack of registry, screening tools, expertise, and awareness. SUMMARY : This review aimed to provide an overview of HAND in South Africa including prevalence, screening, and current treatment strategies. Whether South Africa has the necessary and effective screening tools remains to be determined; however, HAND screening should be mandated for all HIV-infected individuals. cART remains the mainstay treatment of HAND, currently there are no alternative treatment strategies other than adjuvant therapies. In addition, it is yet to be established whether cART plays a role in the development of HAND.
A549 alveolar carcinoma spheroids as a cytotoxicity platform for carboxyl- and amine-polyethylene glycol gold nanoparticles
Petzer, Melissa; Fobian, Seth-Frerich; Gulumian, Mary; Steenkamp, Vanessa; Cordier, Werner (Wiley, 2025-02)
Gold nanoparticles (AuNPs) present with unique physicochemical features and potential for functionalization as anticancer agents. Three‐dimensional spheroid models can be used to afford greater tissue representation due to their heterogeneous phenotype and complex molecular architecture. This study developed an A549 alveolar carcinoma spheroid model for cytotoxicity assessment and mechanistic evaluation of functionalized AuNPs. A549 spheroids were generated using an agarose micro‐mold and were characterized (morphology, acid phosphatase activity, protein content) over 21 culturing days. The 72‐h cytotoxicity of carboxyl‐polyethylene glycol‐ (PCOOH‐) and amine‐polyethylene glycol‐ (PNH2‐) functionalized AuNPs against Day 7 spheroids was assessed by determining spheroid morphology, acid phosphatase activity, protein content, caspase‐3/7 activity, and cell cycle kinetics. Spheroids remained stable over the experimental period. Although the A549 spheroids' volume increased while remaining viable over the culturing period, structural integrity decreased from Day 14 onwards. The PCOOH‐AuNPs lacked cytotoxicity at a maximum concentration of 1.2 × 1012 nanoparticles/mL with no prominent alteration to the cellular processes investigated, while the PNH2‐AuNPs (at a maximum of 4.5 × 1012 nanoparticles/mL) displayed dose‐ and time‐dependent cytotoxicity with associated loss of spheroid compactness, debris formation, DNA fragmentation, and a 75% reduction in acid phosphatase activity. Differentiation between cytotoxic and non‐cytotoxic AuNPs was achieved, with preliminary elucidation of cytotoxicity endpoints. The PNH2‐AuNPs promote cytotoxicity by modulating cellular kinetics while destabilizing the spheroid ultrastructure. The model serves as a proficient platform for more in‐depth elucidation of NP cytotoxicity at the preclinical investigation phase.
Herbal remedies in global health care : classification, toxicology, and clinical management
Steenkamp, Vanessa; Parkar, Hafiza; Raphiri, Boitumelo Metse; Neuman, Manuela G.; Dasgupta, Amitava (Lippincott, Williams and Wilkins, 2026-04)
PURPOSE : Traditional herbal medicines are crucial in the health care system worldwide, particularly for individuals with chronic illnesses. These remedies are commonly classified by purpose, composition, mechanism of action, and origin, with the World Health Organization outlining 4 main categories: indigenous herbal medicines, those used in traditional systems, modified herbal medicines, and imported herbal products. The authors explored the toxicology of commonly used herbal remedies, including their mechanisms, signs and symptoms of toxicity, and treatment strategies. METHODS : Literature was searched using different published resources and databases, PubMed and ScienceDirect. The searched terms included “herbal medicine,” “herbal remedies,” “traditional medicine systems,” “herbal toxicity,” “herbal toxicity mechanism of action/toxicity,” among others. The searches were limited to the English language, with no restrictions on publication date. RESULTS : The perception that herbal medicines are inherently safe is misleading. Herbal remedies can be toxic due to the plant's intrinsic properties or through contamination and adulteration. Moreover, 15%–20% of individuals on prescription drugs concurrently use herbal supplements, increasing the risk of harmful interactions. Incidence of herb-induced toxicities, particularly hepatotoxicity, is related to the use of Kava, Chaparral, Comfrey, Germander, and green tea extract. Moreover, cardiovascular toxicity due to Chan Su and oleander-containing herbal remedy use is detected by assessing serum digoxin concentration and is treated with Digibind. Although advances in modern formulations and increased regulatory oversight have improved safety, shortcomings remain, particularly in public awareness and standardized regulations. CONCLUSIONS : Comprehensive clinical management, patient education, and integration of traditional medicine into mainstream health care ensures safe, effective, and responsible use of herbal products.
Current status and future direction of antimicrobial stewardship programs and antibiotic prescribing in primary care hospitals in Zambia
Makiko, Faustina; Kalungia, Aubrey Chichonyi; Kampamba, Martin; Mudenda, Steward; Schellack, Natalie; Meyer, Johanna Catharina; Bumbangi, Flavien Nsoni; Okorie, Michael; Banda, David; Munkombwe, Derick; Mutwale, Ilunga; Chizimu, Joseph Yamweka; Kasanga, Maisa Anita; Masaninga, Freddie; Muhimba, Zoran; Lukwesa, Chileshe; Chanda, Duncan; Chanda, Raphael; Mpundu, Mirfin; Mwila, Chiluba; St. Claire-Jones, Anja; Newport, Melanie; Chilengi, Roma; Sefah, Israel Abebrese; Godman, Brian (Oxford University Press, 2025-06)
BACKGROUND : Antimicrobial Stewardship Programs (ASPs) intended to optimize antibiotic use will be more effective if informed by the current status and patterns of antibiotic utilisation. In Zambia's primary healthcare (PHC) settings, data on ASPs and antibiotic utilisation were inadequate to guide improvements. As a first step, this study assessed antibiotic prescribing and ASP core elements among PHC first-level hospitals (FLHs) in Zambia. METHODS : A point prevalence survey was conducted at the five FLHs in Lusaka using the Global-PPS® protocol. Hospital ASP core elements evaluated included hospital leadership commitment, accountability, pharmacy expertise, action, tracking, reporting, and education. RESULTS : Antibiotic use prevalence was 79.8% (146/183). A total of 220 antibiotic prescription encounters were recorded among inpatients, with ceftriaxone (J01DD04, Watch) being the most (50.0%) prescribed. Over 90.0% (202) of the antibiotic prescriptions targeted suspected community-acquired infections, but only 36.8% (81) were compliant with national treatment guidelines. ASP core element implementation was 36.0% (16.2/45), with only two hospitals achieving over 50.0%. The most deficient core elements were accountability, action, tracking, and reporting. CONCLUSIONS : ASP implementation in Zambia's FLHs providing PHC was sub-optimal, with high antibiotic prescribing rates, frequent use of broad-spectrum Watch group antibiotics, and low compliance with national treatment guidelines. As key ways forward, ASPs in Zambia's PHC require strengthening by adapting the WHO AWaRe recommendations and improving accountability, actions, tracking, and reporting antibiotic use to improve stewardship practice and reduce AMR.
Catha edulis and Datura stramonium mitigate oxidative stress, mitochondrial dysfunction, and cell death in an SH-SY5Y model of Parkinson's disease
Mogale, Tidimalo; De Beer, Andries Daniël; Rudolph, Willem Johannes; Steenkamp, Vanessa (Elsevier, 2026-04-06)
INTRODUCTION : Parkinson's disease (PD), the second most common neurological disorder, is often managed with medications targeting specific symptoms. Complementing conventional therapies, medicinal plants are frequently used for neurological disorders, including PD. This study evaluated the effects of crude extracts and fractions of Catha edulis (Vahl) Forssk. ex Endl. and Datura stramonium L.—psychoactive plants—on PD-related mechanisms using SH-SY5Y human neuroblastoma cells. METHOD : Crude extracts of C. edulis (leaves) and D. stramonium (leaf/root mixture) were prepared using dichloromethane/methanol (50/50). Fractionation was performed via C8 solid-phase extraction. Cytotoxicity and cytoprotective effects of the crude extracts and fractions against 6-hydroxydopamine-induced cytotoxicity were assessed using the sulforhodamine B assay. Mechanistic studies included reactive oxygen species (ROS) generation, mitochondrial integrity, and apoptosis assays. In silico analysis was used to assess the binding of biomarkers to dopamine receptors. RESULTS : Both plant extracts exhibited minimal cytotoxicity. Crude extracts and fractions (F1–F7) displayed cytoprotective effects (5.8–34.28 %). The highest ROS reduction was observed for F1 of C. edulis (1.72-fold) and F2 of D. stramonium (1.33-fold). Both extracts reduced caspase 3/7 activation and maintained mitochondrial integrity. Atropine and scopolamine showed cytoprotection with IC50 values of 49.48 μM and 48.26 μM, respectively. In silico analysis indicated strong binding affinities of norephedrine and noradrenaline to dopamine D1 and D2 receptors. CONCLUSION : Both plant extracts preserved cell viability, reduced ROS levels, and maintained mitochondrial integrity, highlighting their potential as therapeutic agents for PD.

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