The effect of an anti-malarial herbal remedy, Maytenus senegalensis, on electrocardiograms of healthy Tanzanian volunteers.

BACKGROUND: The emergence of resistance to artemisinin-based combination therapy necessitates the search for new, more potent antiplasmodial compounds, including herbal remedies. The whole extract of Maytenus senegalensis has been scientifically investigated for potential biological activities both in vitro and in vivo, demonstrating strong antimalarial activity. However, there is a lack of data on the electrocardiographic effects of M. senegalensis in humans, which is a crucial aspect in the investigation of malaria treatment. Assessing the electrocardiographic effects of M. senegalensis is essential, as many anti-malarial drugs can inadvertently prolong the QT interval on electrocardiograms. Therefore, the study's objective was to evaluate the electrocardiographic effects of M. senegalensis in healthy adult volunteers. METHODS: This study is a secondary analysis of an open-label single-arm dose escalation. Twelve healthy eligible Tanzanian males, aged 18 to 45, were enrolled in four study dose groups. A single 12-lead electrocardiogram (ECG) was performed at baseline and on days 3, 7, 14, 28, and 56. RESULTS: No QTcF adverse events occurred with any drug dose. Only one volunteer who received the highest dose (800 mg) of M. senegalensis experienced a moderate transient change (△QTcF > 30 ms; specifically, the value was 37 ms) from baseline on day 28. There was no difference in maximum QTcF and maximum △QTcF between volunteers in all four study dose groups. CONCLUSIONS: A four-day regimen of 800 mg every 8 h of M. senegalensis did not impact the electrocardiographic parameters in healthy volunteers. This study suggests that M. senegalensis could be a valuable addition to malaria treatment, providing a safer alternative and potentially aiding in the battle against artemisinin-resistant malaria. The results of this study support both the traditional use and the modern therapeutic potential of M. senegalensis. They also set the stage for future research involving larger and more diverse populations to explore the safety profile of M. senegalensis in different demographic groups. This is especially important considering the potential use of M. senegalensis as a therapeutic agent and its widespread utilization as traditional medicine. Trial registration ClinicalTrials.gov, NCT04944966. Registered 30 June 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04944966?term=kamaka&draw=2&rank=1.

Motivations and barriers for healthy participants to participate in herbal remedy clinical trial in Tanzania: A qualitative study based on the theory of planned behaviour.

BACKGROUND: The success of any randomized clinical trial relies on the willingness of people to be recruited in the trial. However, 90% of all clinical trials worldwide have been reported to have failed to recruit the required number of trial participants within the scheduled time. This study aimed to qualitatively explore the motivations and barriers for healthy participants to participate in herbal remedy clinical trials in Tanzania. MATERIALS AND METHODS: This study used a qualitative descriptive research design based on the theory of planned behaviour. A total of five Focus Group Discussions (FGD) were conducted at Bagamoyo Clinical Trial Facility from 29 to 30 May 2021. Each group consisted of 5 to 10 participants. The participants of the study were 30 healthy males aged 18 to 45 male who participated in the clinical trial that evaluated the safety, tolerability, and efficacy of Maytenus Senegalensis. The focus group discussions were recorded audio-recorded. Verbatim transcription and thematic analysis were performed on the data. RESULTS: The prominent motivations mentioned were the opportunity for self-development, altruism, flexible study visit schedule, and financial compensation. Furthermore, the Participants' mothers and friends were reported as those most likely to approve of participation in an herbal remedy. The most mentioned barriers were inconvenience related to time commitment requirements, possible side effects, inflexible study visit schedule, and having other commitments. Moreover, the participants' father was reported to be more likely to disapprove of participation in a clinical trial of herbal remedy clinical trial. CONCLUSIONS: The results of this study showed that the motivations and barriers of healthy participants to participate in clinical trials of herbal remedies are varied and that participants are motivated by more than financial gains. The identified motivations and barriers can be used as a guideline to improve the design of recruitment and retention strategies for herbal remedy clinical trials.

Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy.

Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs) of infected patients on combination antiretroviral therapy (cART). The mechanism of viral reactivation was determined through the compound's effect on cytokine production, histone deacetylase (HDAC) inhibition, and protein kinase C (PKC) activation. Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers, 3-hydroxy-4,6a,6b,11,12,14b-hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene-4,8a-dicarboxylic acid (HHODC), significantly (p < 0.05) induced HIV-1 expression in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated the production of interleukin (IL)-2, IL-6, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ but had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of HHODC for the first time here.

Antioxidant and anti-inflammatory activity of Ocimum labiatum extract and isolated labdane diterpenoid.

BACKGROUND: Plants from the genus Ocimum are used as folk medicine for treating various diseases including inflammatory and immune-related diseases. Numerous reports have suggested plant extracts and their constituents as possible anti-inflammatory agents. Here, in vitro evidence of Ocimum labiatum's immune-enhancing and antioxidant properties is presented for the first time. METHODS: The anti-inflammatory effect of O. labiatum ethanolic extract and an isolated diterpenoid was determined using a cytometric bead array (CBA) technique. The effect on phytohemagglutinin (PHA)-induced nitric oxide (NO) production in peripheral blood mononuclear cells (PBMCs) was also assessed. A battery of antioxidant assays were used for detecting antioxidant activity while the anti-inflammatory mechanism was evaluated using an ELISA-based activator protein (AP-1) (c-Jun) assay. Cytotoxicity was determined on TZM-bl and PBMCs using a tetrazolium dye and confirmed by a novel label-free real-time assay. RESULTS: A 25 µg/mL non-cytotoxic concentration of O. labiatum extract significantly (p < 0.05) inhibited the production of pro-inflammatory cytokines; IL-2, IL-4, IL-6 and IL-17A. Except for the dual acting pro- or anti-inflammatory cytokine, IL-6, which was upregulated, a non-cytotoxic 50 µM concentration of the isolated labdane diterpenoid compound significantly (p < 0.05) decreased the production of all the pro-inflammatory cytokines. In the anti-inflammatory pathway studies, the compound also inhibited AP-1 significantly (p < 0.05) at 50 µM. The extract demonstrated strong, dose dependent antioxidant activity with IC50 values ranging from 13 ± 0.8 to 54.86 ± 1.28 µg/mL while the terpene had no antioxidant property. The extract and diterpenoid decreased the production of the inflammatory mediator NO, at non-cytotoxic concentrations. The CC50 of the extract in TZM-bl and PBMCs was 62.6 ± 0.6 and 30.1 ± 0.4 µg/mL while that of the compound was 112.6 ± 0.2 and 70 ± 0.4 µM respectively. The real time studies confirmed tetrazolium dye assessed viability and also detected a unique growth pattern for the plant materials compared to untreated cells. CONCLUSIONS: O. labiatum extract demonstrated promising anti-inflammatory and antioxidant properties while the terpenoid showed anti-inflammatory but no antioxidant activity. The anti-inflammatory mechanism of the terpene was a result of inhibition of AP-1. These data represents promising first steps towards the development of naturally derived anti-inflammation drugs.