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Sutherlandia frutescens may exacerbate HIV-associated neuroinflammation

Significance Statement

Society is increasingly turning to natural medicines for especially alleviation of chronic conditions, commonly stress- and/or inflammation-related. The benefits of many of these products are clearly evident. Sutherlandia frutescens (cancer bush) has been used in the context of stress-relief by indigenous practitioners for decades and has been shown by modern research to effectively inhibit synthesis of stress hormones such as cortisol and corticosterone, as well as to prevent muscle breakdown in chronic disease, such as cancer and other stress-related illnesses. Recently, Sutherlandia was in the news for suspected ARV drug-interactions and its use by HIV+ individuals has been discouraged in the scientific literature.

However, especially in developing countries, the use of Sutherlandia is still officially endorsed and promoted at primary health care level, particularly in HIV+ patients prior to ARV roll-out, with the intention to inhibit the stress response and associated muscle wasting to improve prognosis. However, HIV-associated neuroinflammation was recently shown to be initiated very soon after infection. Neuroinflammaton promotes the development of neurodegeneration and dementia – and this process is thus already in progress before roll-out of ARV therapy.  Our data, obtained in a validated cell co-culture simulation of the human blood-brain barrier, support earlier work of beneficial action of Sutherlandia: in non-HIV conditions, it had no effect on inflammatory cytokine production. However, in the HIV+ condition, the HIV-induced secretion of inflammatory cytokines and pro-inflammatory immune cell (monocytes) infiltration across the blood-brain barrier was exacerbated.

Despite this seemingly negative report, our purpose was by no means to argue against the use of Sutherlandia as originally prescribed by indigenous knowledge practitioners. Our research on plant medicines are aimed at distinguishing between populations (and conditions) who would most benefit by any specific plant and those would do better to avoid taking it at all. In our experience, side-effects reported for medicinal plants recognized by indigenous knowledge systems, usually follow the use of these plants outside of the context originally intended. This paper thus discourages the use of Sutherlandia in HIV+ populations at all stages of the disease, for two reasons: firstly, to prevent further detriment to patients already severely challenged by HIV/AIDS and secondly, to prevent inappropriate application of indigenous knowledge from unfairly damaging the reputation of medicinal plants in general.

Sutherlandia frutescens may exacerbate HIV-associated neuroinflammation. Global Medical Discovery

Journal Reference

J Negat Results Biomed. 2015 Jul 18;14:14.

Africa LD1, Smith C2.

Show Affiliations
  1. Department of Physiological Sciences, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa. [email protected]
  2. Department of Physiological Sciences, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa. [email protected]

Abstract

BACKGROUND:

Neuroinflammation is central to the aetiology of HIV-associated neurocognitive disorders (HAND) that are prevalent in late stage AIDS. Anti-retroviral (ARV) treatments are rolled out relatively late in the context of neuroinflammatory changes, so that their usefulness in directly preventing HAND is probably limited. It is common practice for HIV+ individuals in developing countries to make use of traditional medicines. One such medicine is Sutherlandia frutescens – commonly consumed as a water infusion. Here its efficacy as an anti-inflammatory modality in this context was investigated in an in vitro co-culture model of the blood-brain barrier (BBB).

METHODS:

Single cultures of human astrocytes (HA), HUVECs and primary human monocytes, as well as co-cultures (BBB), were stimulated with HIV-1 subtype B & C Tat protein and/or HL2/3 cell secretory proteins after pre-treatment with S.frutescens extract. Effects of this pre-treatment on pro-inflammatory cytokine secretion and monocyte migration across the BBB were assessed.

RESULTS:

In accordance with others, B Tat was more pro-inflammatory than C Tat, validating our model. Sutherlandia frutescens  decreased IL-1β secretion significantly (P < 0.0001), but exacerbated both monocyte chemoattractant protein-1 (P < 0001) – a major role player in HIV-associated neuroinflammation – and CD14+ monocyte infiltration across the BBB (P < 0.01).

CONCLUSIONS:

Current data illustrates that the combined use of HL2/3 cells and the simulated BBB presents an accurate, physiologically relevant in vitro model with which to study neuroinflammation in the context of HIV/AIDS. In addition, our results caution against the use of Sutherlandia frutescens as anti-inflammatory modality at any stage post-HIV infection.

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