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An Investigation into the Immunomodulatory Activities of Sutherlandia frutescens in Healthy Mice.

ABSTRACT: Sutherlandia frutescens is a medicinal plant that has been traditionally used in southern Africa for cancers, infections, and inflammatory conditions. We recently published experiments demonstrating that an aqueous extract of S. frutescens possessed potent immune-stimulatory activity. This work was carried out with murine macrophages, an immune cell type that plays a pivotal role in host defense from infection and in shaping host inflammatory and immune responses. Here, we conducted a series of follow-up experiments to explore the impact of consuming S. frutescens on host response to bacterial challenge using healthy mice. We found that feeding mice a diet containing S. frutescens failed to significantly alter host response to systemic infection by either a gram-positive or gram-negative bacterium (i.e., L. monocytogenes and E. coli, respectively). In contrast to the in vitro observations, we found no evidence that S. frutescens consumption stimulated in vivo inflammatory responses; instead, consumption of S. frutescens tended to diminish in vivo inflammatory responses. Several possible reasons for this are discussed.

SUBMITTER: Lei W

PROVIDER: S-EPMC5004858 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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An Investigation into the Immunomodulatory Activities of Sutherlandia frutescens in Healthy Mice.

Lei Wei W Browning Jimmy D JD Eichen Peggy A PA Folk William R WR Sun Grace Y GY Lubahn Dennis B DB Fritsche Kevin L KL

PloS one 20160830 8

Sutherlandia frutescens is a medicinal plant that has been traditionally used in southern Africa for cancers, infections, and inflammatory conditions. We recently published experiments demonstrating that an aqueous extract of S. frutescens possessed potent immune-stimulatory activity. This work was carried out with murine macrophages, an immune cell type that plays a pivotal role in host defense from infection and in shaping host inflammatory and immune responses. Here, we conducted a series of ...[more]

PMID: 27575007

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Project description:BackgroundSutherlandia frutescens is one of the most promising commercialized, indigenous and medicinal plants of South Africa that is used as an immune-booster, and a traditional treatment for cancer. However, few studies report on its toxicology and dosage in vivo. There is still room to better understand its cytotoxicity effects in animal systems.MethodsWe prepared two extracts, one with 80% (v/v) ethanol, and the other, with water. Both were studied to determine the maximum tolerable concentration when extracts were applied at 0 to 200 μg/ml to a Tuebingen zebrafish embryo line. The development of zebrafish embryos after 24 h post fertilization (hpf) was studied. A concentration range of 5 μg/ml to 50 μg/ml was then chosen to monitor the ontological development of cultured embryos. A liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method was used to study the differences of the two experimental extracts. Chemical variation between the extracts was illustrated using chemometrics.ResultsBoth extracts led to bleeding and pericardial cyst formation when applied at high concentrations to the zebrafish embryo culture. Chronic teratogenic toxicities, leading to pericardial edema, yolk sac swelling, and other abnormal developmental characteristics, were detected. The aqueous extracts of S. frutescens were less toxic to the larvae than the ethanol extracts, validating preference for aqueous preparations when used in traditional medicine. Chemical differences between the water extracts and alcoholic extracts were analysed using LC-MS/MS. A supervised metabolomics approach, targeting the sutherlandiosides and sutherlandins using orthogonal partial least squares-discriminant analysis (OPLS-DA), illustrated that sutherlandiosides were the main chemical features that can be used to distinguish between the two extracts, despite the extracts being highly similar in their chemical constituents.ConclusionThe water extract caused less cytotoxic and abnormal developmental effects compared to the ethanolic extract, and, this is likely due to differences in concentrations of extracted chemicals rather than the chemical profile per se. This study provides more evidence of cytotoxicity effects linked to S. frutescens using the zebrafish embryo bioassay as a study tool.

Project description:ObjectivesIndigenous medicines are widely used throughout Africa, despite a lack of scientific evidence for their safety or efficacy. The aims of this study were: (a) to conduct a pilot study of the safety of a common indigenous South African phytotherapy, Lessertia frutescens (Sutherlandia), in healthy adults; and (b) to contribute to establishing procedures for ethical and scientifically rigorous clinical trials of African indigenous medicines.DesignA randomized, double-blind, placebo-controlled trial of Sutherlandia leaf powder in healthy adults.SettingTiervlei Trial Centre, Karl Bremer Hospital, Bellville, South Africa.Participants25 adults who provided informed consent and had no known significant diseases or allergic conditions nor clinically abnormal laboratory blood profiles during screening.Intervention12 participants randomized to a treatment arm consumed 400 mg capsules of Sutherlandia leaf powder twice daily (800 mg/d). 13 individuals randomized to the control arm consumed a placebo capsule. Each participant received 180 capsules for the trial duration of 3 mo.Outcome measuresThe primary endpoint was frequency of adverse events; secondary endpoints were changes in physical, vital, blood, and biomarker indices.ResultsThere were no significant differences in general adverse events or physical, vital, blood, and biomarker indices between the treatment and placebo groups (p > 0.05). However, participants consuming Sutherlandia reported improved appetite compared to those in the placebo group (p = 0.01). Although the treatment group exhibited a lower respiration rate (p < 0.04) and higher platelet count (p = 0.03), MCH (p = 0.01), MCHC (p = 0.02), total protein (p = 0.03), and albumin (p = 0.03), than the placebo group, these differences remained within the normal physiological range, and were not clinically relevant. The Sutherlandia biomarker canavanine was undetectable in participant plasma.ConclusionConsumption of 800 mg/d Sutherlandia leaf powder capsules for 3 mo was tolerated by healthy adults.

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An Investigation into the Immunomodulatory Activities of Sutherlandia frutescens in Healthy Mice.

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An Investigation into the Immunomodulatory Activities of Sutherlandia frutescens in Healthy Mice.

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