Review on the Anti-Hyperglycemic Potential of Psidium guajava and Seriphium plumosum L.

The treatment and management of diabetes mellitus (DM) with conventional therapies, such as insulin injections and oral hypoglycemic agents, present significant challenges due to their side effects and burdensome administration. Therapies often manage symptoms rather than addressing insulin regulation, akin to medications like thiazolidinediones and glinides, which resemble many medicinal plants. Medicinal plants offer potential alternative treatments due to bioactive compounds targeting diabetes causes. We aimed to explore the antidiabetic potential of two medicinal plants, Psidium guajava and Seriphium plumosum L., by investigating their phytochemical constituents, medicinal uses, pharmacological actions, and mechanisms. This review followed specific guidelines and searched databases including PubMed, Scopus, ScienceDirect, and Web of Science for studies on medicinal plants and DM. Eligible studies underwent quality assessment and were categorized based on their design and interventions for data synthesis. This review identified the phytochemical constituents in Psidium guajava and Seriphium plumosum L., including tannins, flavonoids, phenols, and steroids, exerting antidiabetic effects through various mechanisms like antioxidant activity, anti-inflammatory effects, stimulation of insulin secretion, glucose regulation, and inhibition of carbohydrate-digesting enzymes. Psidium guajava and Seriphium plumosum L. exhibit promising antidiabetic potential, offering alternative approaches to diabetes management. Polyherbalism, combining multiple plant extracts, may enhance therapeutic efficacy in diabetes treatment. Comprehensive research is needed to explore the combined therapeutic effects of these plants and develop more effective antidiabetic treatments. This review highlights the importance of harnessing natural resources to combat the global burden of DM. Further research is warranted to fully explore the combined therapeutic effects of these plants and develop novel treatments.

Corrigendum: An in vitro study to elucidate the effects of Product Nkabinde on immune response in peripheral blood mononuclear cells of healthy donors.

[This corrects the article DOI: 10.3389/fphar.2024.1308913.].

An in vitro study to elucidate the effects of product Nkabinde on immune response in peripheral blood mononuclear cells of healthy donors.

Introduction: A significant number of the South African population still rely on traditional medicines (TM) as their primary healthcare due to their belief in their holistic healing and immune-boosting properties. However, little to no scientific data is available on the effects of most TM products on cytokine and cellular biomarkers of the immune response. Here, we evaluated the impact of traditional medicine [Product Nkabinde (PN)] in inducing cellular and cytokine biomarkers of inflammation in peripheral blood mononuclear cells (PBMCs) from eight healthy volunteers. Methods: PN was supplied by a local Traditional Health Practitioner (THP). The IC50 (half maximum concentration) of the standardized extract on isolated PBMCs was established using the cell viability assay over 24 h of incubation. Luminex and flow cytometry assays were used to measure cytokine and cellular levels in PBMCs stimulated with PN and/or PHA over 24, 48, and 72 h, respectively. Results: The IC50 concentration of PN in treated PBMCs was established at 325.3 µg/mL. In the cellular activation assay, the percentages of CD38-HLA-DR + on total CD4+ T cells were significantly increased in PBMCs stimulated with PN compared to unstimulated controls after 24 h (p = 0.008). PN significantly induced the production of anti-inflammatory IL-10 (p = 0.041); proinflammatory cytokines IL-1α (p = 0.003), TNF-α (p < 0.0001); and chemokine MIP-1ß (p = 0.046) compared to the unstimulated control after 24 h. At 48 h incubation, the production of proinflammatory cytokines IL-1α (p = 0.034) and TNF-α (p = 0.011) were significantly induced following treatment with PN. Conclusion: We conclude that the PN possesses in vitro immunomodulatory properties that may influence immune and inflammatory responses. More studies using PN are needed to further understand key parameters mediating induction, expression, and regulation of the immune response in the context of pathogen-associated infections.

Attitudes and perceptions of traditional health practitioners towards documentation of patient health information in their practice in eThekwini Municipality, KwaZulu-Natal, Natal Province, South Africa.

BACKGROUND: Documentation of patient health information in the form of patient medical records (PMRs) is an essential, ethical and regulatory requirement in any healthcare system. African traditional medicine (ATM) exists parallel to biomedicine and continues to play a significant role in primary healthcare of the majority of South Africans. The World Health Organization (WHO) has promoted the integration of ATM into the national health system of South Africa. Patient health information documentation can facilitate this integration, and PMRs promote communication between the two health systems through referrals. Documentation in biomedicine is a clear, compulsory, routine activity, but does not occur regularly or routinely in ATM. OBJECTIVE: To examine the attitudes and perceptions of traditional health practitioners (THPs) towards documentation of patient health information in their practice. METHODS: This quantitative cross-sectional survey involved snowball sampling to recruit THPs in Umlazi Township and rural parts surrounding the township, in Durban, South Africa. A semi-structured questionnaire was used. Quantitative data were analysed using SPSS 25 and the Relative Importance Index (RII) and qualitative data were analysed using Excel for themes. RESULTS: Sampling resulted in 248 THPs of whom 178 (72%) were females. The RII ranked the factors that negatively influenced the participants' attitudes towards documentation of patient health information. Of the 178 females who participated in the study, 129 (72.5%) showed their willingness to introduce documentation in their practice. Of the 127 participants with less than 10 years of practice experience, 126 (99.2%) agreed to the importance of introducing PMRs in their practice. The majority of participants perceived documentation of patient health information as vital to improve their practice. A prominent theme was that the THPs regarded documenting patient health information as important and effective in their practice. CONCLUSION: More than half of participants showed positive attitudes and perceptions towards documenting of patient health information in ATM. The majority of the participants in this study acknowledged the importance of introducing documentation of patient health information in their practice even though they lacked experience and more knowledge. This reflects a need for essential intervention in developing specialised tools to begin promoting documentation of patient health information in ATM.

Anticancer effects of herbal medicine Emelia-M, Mshikazi and Delosma H against human leukaemia cells.

Background: Leukaemia is one of the three major types of blood cancers that lead to the overproduction of abnormal white blood cells. Emelia M (EMB), Mshikazi and Delosma H are herbal medicines that are being used by traditional healers in KwaZulu-Natal, South Africa to treat leukaemia and other diseases. Objectives: To gain insight into the safety (non-toxic effect), anti-cancer activity, mechanisms of action and phytochemical profiles of traditional herbal medicines (Emelia M (EMB), Mshikazi and Delosma H) in South Africa. Methods: The viability of human peripheral blood mononuclear cells (PBMCs), monocytic (THP-1) and T-lymphocyte (Jurkat) cell lines exposed to varying concentrations of aqueous extracts of the three herbal medicines were assessed using adenosine triphosphate (ATP) assay. Results: All three extracts showed a dose-dependent effect on the viability of PBMCs. Cell viability decreased with increasing concentrations of extracts when compared with the untreated cells at 24 and 48 hours. The inhibitory activities (IC50) of the extract were found in the order of Mshikazi > EMB, > Delosma H. All the extracts induced apoptosis with minimal necrosis. Many bioactive compounds that have been previously reported to have anticancer effects were identified in the extracts. Conclusion: Mshikazi extract significantly inhibited the growth of THP-1 and Jurkat cells and induced cell death through apoptosis than the other two extracts.

Unravelling the drugability of MSI2 RNA recognition motif (RRM) protein and the prediction of their effective antileukemia inhibitors from traditional herb concoctions.

MSI2 is a homolog 2 of the Musashi RNA binding proteins (MSI) and is known to contribute to acute myeloid leukaemia (AML) and expressed up to 70% in AML patients. High expression of MSI2 has been found to lead to the lower overall survival of patients with AML. This study proposed the potential antagonists of MSI2 RNA-recognition motifs (MSI2 RRM1) derived from the LC-MS analysis of three traditional herbal samples. The LC-MS analysis of the three traditional herbs concoctions yields a total of 271 unique molecules of which 262 were screened against MSI2 RRM1 protein. After the dynamic study of the selected 8 top molecules from the virtual screening, the five most promising ligands emerged as potential MSI2 antagonists compare to the reference experimental molecule. The results show that the dynamic of MSI2 RRM1 protein is accompanied by a rare even of protein chain dissociation and re-association as evident in both the bound and unbound state of the protein. The unbound protein experience earlier chain dissociation compare to ligand-bound protein indicating that ligand binding to the protein slows down the dissociation time but thereafter increases the frequency of alternation between the protein chain association and dissociation after the first experience. Interestingly, the re-association of the protein chain is also accompanied by full restoration of the ligands to the binding site. The drug candidate Methotrexate (M3) and rescinnamine (M9) are listed among the promising antagonist of MSI2 with unique properties compared to a less promising molecule Ergotamine (M6).Communicated by Ramaswamy H. Sarma.

Knowledge and documentation of patient health information among traditional health practitioners in urban and peri-urban areas of eThekwini Municipality, KwaZulu-Natal Province, South Africa.

BACKGROUND: Documentation of patient health information (PHI) is a regulatory requirement and hence a standard procedure in allopathic healthcare practice. The opposite is true for African traditional medicine (ATM) in most African countries, including South Africa, despite legal and policy frameworks that recognise and mandate the institutionalisation of ATM. Developing good practice standards for PHI documentation is an essential step in the institutionalisation of ATM. OBJECTIVE: This study examined the knowledge and practices of documentation of PHI by traditional health practitioners (THPs) in Durban, eThekwini Municipality, KwaZulu-Natal Province, South Africa. METHODS: In this quantitative cross-sectional study, snowball sampling was used to identify and recruit THPs. An interviewer-administered questionnaire was used to gather data. Chi-square tests and logistic regression were used to assess associations of knowledge and practice of documentation of PHI with potential predictors; age, gender, education, type of practitioner, experience, number of patients seen per day and location of the practice. RESULTS: Of the 248 THPs who participated, 71.8% were female. Mean (SD) age was 47.4 (14.2), ranging 18-81 years. The majority (65.7%) were Izangoma (diviners). Overall, 42.9% of the THPs reported knowledge of patient medical records (PMRs). In logistic regression, only number of patients seen per day remained a significant predictor of knowledge about PMR. THPs who reported seeing 6-10 patients were five times more likely (Odds Ratio (OR): 5.164, 95% Confidence Interval (CI): 1.270-20.996; p = 0.022) to report knowledge of PMR than those seeing <6 patients per day. Overall, 25.0% of THPs reported that they were documenting some PHI. Documentation was associated with having knowledge of PMR (OR: 29.323, 95% CI: 10.455-82.241; p < 0.0001) and being an Isangoma (OR: 3.251, 95% CI: 1.092-9.679; p = 0.02). Not knowing what (56.5%) and how (50.5%) to record were the most commonly cited reasons for not documenting. CONCLUSION: Knowledge of PMR is low, and the practice of documenting PHI is even lower among THPs in eThekwini. That knowledge of PMR was a strong predictor of documentation practice, and the most common reason for not documenting was lack of knowledge about what and how to document suggests that training could improve PHI documentation in traditional medicine practice.

Phytochemical profile and in vitro antioxidant activity of Emelia M (EMB), Mshikazi and Delosma H herbal medicines as demonstrated in THP-1 and Jurkat leukaemia cell lines.

Background: Three decoctions, namely Emelia M (EMB), Mshikazi and Delosma H are used by traditional health practitioners in KwaZulu-Natal, South Africa to treat and manage leukaemia and related conditions. Objectives: This study evaluated the in vitro antioxidant activity and phytochemical profile of the aqueous extracts of Emelia M (EMB), Mshikazi and Delosma H decoctions. Methods: Antioxidant activity of the extracts was evaluated using1-diphenyl-2-picrylhydrazyl (DPPH), glutathione (GSH), phosphomolybdate and thiobarbituric acid reactive substance (TBARS) assays. Phytochemical screening was used to determine the presence of compounds. Results: The DPPH radical scavenging activity was similar to ascorbic acid for EMB and Delosma H, but not for Mshikazi. At 24 h, EMB increased GSH in both THP-1 and Jurkat cells similar to Delosma H while Mshikazi demonstrated the lowest activity. At 48 h, EMB and Delosma H revealed increased GSH in THP-1 cells with no significant decrease in GSH levels in Jurkat cells. However, EMB showed the lowest lipid peroxidation activity compared to Delosma H and Mshikazi after 24 h treatment of both cells. Phenols, flavonoids, terpenoids, saponins were present in all extracts. Conclusion: Extracts of the three decoctions possess both antioxidant and prooxidant properties through high scavenging activity and increased in lipid peroxidation.

Core competencies acquired in indigenous training of traditional health practitioners in Kwazulu-Natal.

INTRODUCTION: Despite the recognition of Traditional Medicine systems as a critical component of health care by the WHO and the African Union, its integration into the health care mainstream remains very subdued in South Africa. This is partly due to the lack of empirical data pertinent to traditional healer training that could inform the accreditation process. OBJECTIVE: To determine core competencies acquired by Traditional Health Practitioners (THP) of KwaZulu-Natal Province, South Africa during their apprenticeship. MATERIALS AND METHODS: Purposeful, convenient and snowballing sampling and the sequential data collection methods of questionnaires, journaling and focus groups was used to collect data from the THP tutors and their trainees in rural, peri-urban and urban areas of eThekwini and uThungulu Districts of Kwa Zulu Natal (KZN). RESULTS: Eleven core competencies were identified: consultation, diagnoses, holistic patient care and treatment, integrative and holistic healing, application of healing procedures and cultural rituals, spiritual development, ethical competencies, problem solving, herbalism, ancestral knowledge and end of life care. CONCLUSION: The apprenticeship of THPs in KZN is based on eleven core competencies. These competencies are fundamental pillars for critical health care provided by THPs and are crucial for setting standards for the accreditation of traditional training in South Africa if the THP Act 22 of 2007 is to achieve its purpose of providing for the management of and control over the registration, training and conduct of the practitioners. Hence, the appointed interim THP Council should include the identified competencies when articulating bases for accreditation of the training and assessments.

The Immune Effects of an African Traditional Energy Tonic in In Vitro and In Vivo Models.

Most of the African traditional medicines (ATM) are formulated as energy tonics to boost and maintain immune defences. In this study, we aimed to evaluate the immune effects of a traditional energy tonic using peripheral blood mononuclear cells (PBMCs), THP-1 monocytes, and bacteria infected rats. When tested in mitogen and peptidoglycan stimulated PBMCs, this energy tonic showed minimal cytotoxicity, while in acute toxicity studies in rats it did not exhibit any significant toxicity at doses up to 2000 mg/mL/kg. The energy tonic doses between 100 and 10 µg/mL were shown to stimulate secretion of cytokines and increase sIL-2R levels in PHA-treated PBMCs. Similar doses in PG-S. aureus-stimulated PBMCs significantly (p < 0.05) increased IL-1α, IL-2, and GM-CSF while causing a significant (p < 0.05) decrease in sIL-2R levels. NF-κß transcriptional activity was increased in LPS stimulated THP-1 cells. In Sprague Dawley rats pretreated with the energy tonic and then infected with S. aureus, there were insignificant increases in cytokines and sIL-2R when compared to bacteria infected only and 5% Enrofloxacin treated rats. Posttreatment with energy tonic doses after infection with S. aureus did not enhance inflammatory cytokines significantly but changed the immune response profile and decreased corticosterone levels. This ATM showed promising immunomodulatory effects on isolated immune cells and modulated the immune response of rat models infected with S. aureus.

Evaluation of the immunomodulatory effects of a South African commercial traditional immune booster in human peripheral blood mononuclear cells.

BACKGROUND: With the burden of HIV and AIDS still very high, South Africa has seen an increase in commercial traditional medicines claiming to have immune-enhancing effects. Because of lack of regulation of the traditional medicine sector, these products have proliferated. This study aimed to evaluate the immunomodulatory effects of uMakhonya®, a commercial traditional immune booster, using various models of normal human peripheral blood mononuclear cells (PBMCs). METHODS: Immunosuppressed, mitogen-, and peptidoglycan (PG)-stimulated PBMCs were treated with various doses of uMakhonya® and incubated for 24 h. The treated and control samples were analyzed for cytotoxicity, secretion of 12 different inflammatory cytokines, soluble interleukin-2 receptor (sIL-2R) levels, and nitric oxide (NO) secretion. RESULTS: In cytotoxicity assays, uMakhonya® induced dose-dependent cytotoxic effects in all three models, with IC50 values of 512.08, 500, and 487.91 µg/mL for immunosuppressed, phytohaemagglutinin (PHA)-, and PG from Staphylococcus. aureus (PG-S. aureus)-stimulated PBMCs, respectively. UMakhonya® at 100 and 10 µg/mL induced a significant (p < 0.05) increase in the secretion of IL-1α, IL-1ß, IL-6, IL-10, tumor necrosis factor alpha (TNF)-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in cyclosporine-, immunosuppressed, and PHA-stimulated PBMCs. In the same samples, there was a significant increase (p < 0.05) in sIL-2R concentration, which correlated with an increase in the secretion of inflammatory cytokines. In PBMCs stimulated with PG-S. aureus, uMakhonya® at doses of 100 and 10 µg/mL significantly (p < 0.05) suppressed the secretion of inflammatory cytokines, especially IL-1ß and TNF-α. PG-S. aureus-stimulated PBMCs also showed a significant decrease (p < 0.05) in sIL-2R concentration when compared to control samples. UMakhonya® insignificantly (p > 0.05) decreased NO levels in PBMCs after PG-S. aureus stimulation. CONCLUSIONS: These results showed that uMakhonya® can induce both pro-inflammatory and anti-inflammatory effects depending on the initial stimuli applied to immune cells.

Sick certificates issued by South African traditional health practitioners: current legislation, challenges and the way forward.

Traditional health practitioners (THPs) play a significant role in South African healthcare. However, the Basic Conditions of Employment Act (BCEA) does not consider sick notes issued by THPs to be valid. This creates a dilemma for employees, whose right to consult a practitioner of their choice is protected by the Constitution. We assessed the current legislation and highlight the challenges that employees face in selecting a healthcare system of their choice. The services of THPs represent an untapped capacity that can complement and strengthen healthcare services, especially in the workforce. The BCEA legislative technicality, coupled with the delayed establishment of the Interim THP Council, does not relieve the employer's burden of 'illegitimate' medical certificates issued by THPs. While seen as a dilemma for some employers, others have accommodated African cultural beliefs and accept THP-issued sick notes. Finalising the Interim THP Council will allow THP registration and oblige employers to honour sick notes issued by THPs. The empowerment of THPs to play a meaningful role in healthcare delivery is of national importance.

Effects of Sutherlandia frutescens extracts on normal T-lymphocytes in vitro.

Sutherlandia frutescens (SF), a popular traditional medicinal plant found in various parts of southern Africa, is used for treatment or management of HIV/AIDS and other diseases including cancer. However, its toxicity profile has not been fully established. The aims of this study were to examine the effects of 70% ethanol (SFE) and deionised water (SFW) extracts on normal isolated human T cells. An experimental study on normal human lymphocytes treated with doses SF extract doses ranging from 0.25 to 2.5 mg/ml. Untreated, vehicle-treated (Ethanol) and camptothecin (CPT) treated normal T cells were used as controls. Induction of cell death, changes in intracellular ATP, caspase-3/-7 activity and nuclear changes were analysed using flow cytometry, luminometry and nuclear staining (Hoechst) respectively. The highest concentration (2.5 mg/ml) of SFE extract induced significant necrosis (95%), depletion of ATP (76%), and inhibition of caspase-3/-7 activity (11%) following a 24 hour incubation period (p< 0.001). The 2.5 mg/ml concentration of SFW showed the same trend but were less effective (necrosis- 26%, ATP- 91%, & caspase-3/-7- 15%). These effects showed a time-dependence over 48 hours of incubation, with high doses of SFE extracts eliminating viable cells by necrosis, depleting ATP levels and decreasing caspase-3/-7 activity (p< 0.001). The activity of SFE extract was independent of ethanol. The SFW extract dilutions were less toxic than the SFE extracts. Significant DNA fragmentation as demonstrated by Hoechst staining was also seen over 48-hour incubation for high doses of both types of SF extracts. These results showed that although high concentrations of SF extracts can be toxic to normal T cells in vitro, SFW fractions were relatively safe for use.

In vitro testing of African traditional medicines for cytotoxic, immune modulatory and anti-HIV activities.

African Traditional Medicines (ATMs) serve as a major source of primary healthcare for African people. The reasons for their use range from easy access, affordability, beliefs in traditional systems and long term safety. ATMs have been used to treat individuals infected with HIV and therefore need scientific validation; a view supported by Traditional Health Practitioners (THPs). This study aimed to evaluate the in vitro cytotoxicity, immune modulatory and anti-HIV activities of traditional multiple herbal preparations from local THPs. Ugambu, Ihashi, Product Nene, Product Blue, SPNa and SDKc ATM were supplied by local THPs. Changes in adenosine triphosphate (ATP) & glutathione (GSH) over 24 hours were measured using luminometry. Changes in 12 cytokines were assayed using an ELISA-based absorbance assay. Protective effects against HIV killing of MT-4 cells were tested using the XTT assay and antiviral activity was measured using an HIV-1 viral load assay. Cyclosporine and AZT were used as positive controls. Ugambu, Ihashi, Product Nene and SDKc induced a dose dependent toxicity on treated PBMCs by reducing ATP and GSH at high doses (p< 0.001). These medicinal preparations, along with SPNa, showed immunomodulatory activity by significantly (p< 0.001) changing the secretion of pro-inflammatory cytokines. Product Blue stimulated the levels of ATP and GSH in treated PBMCs at all doses however this product did not show any immunomodulatory activity on cytokine secretion when compared to control cells. Ugambu, Ihashi, Product Nene showed promising anti-HIV activity relative to AZT (p< 0.01). This study has shown that some of these traditional medicinal preparations have at least one or all the properties of immunostimulation, immunomodulation or antiretroviral effects. The mechanism of action of the shown activities should further be investigated.

The immunomodulatory effects of Sutherlandia frutescens extracts in human normal peripheral blood mononuclear cells.

Sutherlandia frutescens (SF) is one of the medicinal plants used as an immune booster in the treatment of chronic ailments such as HIV/AIDS and cancer. Limited data suggest that its efficacy is based on its regulatory effect on cytokines, the critical components of the immune response. In this study, we investigated the in vitro immunomodulatory effects of SF extracts on normal human peripheral blood mononuclear cells (PBMCs). An ELISA-based assay was used to assess the levels of expression of 12 cytokines in treated cells. An adenosine triphosphate (ATP) assay was used to assess cell viability in relation to cytokine secretion. SF ethanol extracts induced changes in cytokine secretion relative to the dose of the extract. Generally cytokine expression and secretion was low in concentration because were not stimulated with any endotoxin. The high SFE dose (2.5 mg/ml) significantly (p<0.001) decreased some cytokines including TNF-α and IL 1ß. Low doses of this extract (0.5 mg/ml) did not change TNF-α and IL 1ß secretion from the baseline (untreated cells). Changes in cytokine secretion of SFE treated cells tracked changes in ATP levels (cell viability). The SFW extract-induced changes in cytokine secretion were independent of cell viability. TNF-α was decreased (p<0.001) by the high dose of SFW extract while IL 1ß and IFNγ were increased (p<0.01) by the same dose. High doses decreased cell viability which was reflected in cytokine secretion. It is evident, from these results, that SF extracts can modulate cytokine secretion in unstimulated normal PBMCs in vitro. Further studies in animal models are recommended to advance understanding of this immunomodulatory activity.