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Sutherlandia and AIDS Patients - Summary of a field trip in South Africa... more...

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Thesis: The influence of Sutherlandia frutescens on adrenalcytochrome P450 11ß-hydroxylase by Catherine Anne Sergeant

 

Sutherlandia and HIV/AIDS


Improvements in appetite, weight-gain, sleep, exercise tolerance, anxiety and overall sense of well-being can be expected. Researchers anticipate that there will be a delayed progression of HIV into Aids, and actual remission of the disease is hoped for. This will require compliance of appropriate does of the correct selection of Sutherlandia take on an ongoing basis, in addition to meticulous attention to diet. Alcohol, recreational drugs and other drugs that damage the immune system should be avoided.

Most wasted patients show an increase in weight within six weeks of starting treatment. Weight gains of 10-15 kg have been documented in wasted cancer and AIDS patients. Interestingly weight-gain is typically not seen in people without underlying wasting conditions.

Improvements in CD4 counts and decreases in the viral load in AIDS patients taking Sutherlandia have been reported by clinicians in South Africa and Australia. Anecdotal reports that Sutherlandia can improve the immune status of some people living with HIV still need to be verified by a controlled clinical trial. People using Sutherlandia for improving quality of life in HIV should do so under the supervision of a doctor or healthcare professional


Publications:
A number of recent published scientific studies on Sutherlandia have shown interesting results, including anti-HIV activity, anti-oxidant activity, anti-inflammatory activity, anti-cancer activity, and also potential drug interaction between Sutherlandia and anti-retroviral drugs. Summaries of the published studies are included. People living with HIV should discuss the potential use of Sutherlandia with their doctor or healthcare professional.

J Ethnopharmacol. 2005 Jan 4;96(1-2):113-9.

Anti-HIV activities of organic and aqueous extracts of Sutherlandia frutescens and Lobostemon trigonus.
Harnett SM, Oosthuizen V, van de Venter M.


Department of Biochemistry and Microbiology, University of Port Elizabeth, PO Box 1600, Port Elizabeth, 6000 South Africa.

A screening process was applied to extracts made from Sutherlandia frutescens (L.) R. Br (Fabaceae) and Lobostemon trigonus (Boraginaceae) as identified by the Botany Department, University of Port Elizabeth to detect if any of the extracts inhibited the human immunodeficiency virus (HIV). For purposes of dereplication, sulphated polysaccharides were removed and bovine serum albumin (BSA) was included in the assays to adsorb non-specific tannins potentially present. In the reverse transcriptase (RT) assay, an aqueous extract of the Lobostemon leaves inhibited HIV-1 RT with an IC50 value of 49 microg/ml, while in the protease assay no inhibition was seen. In the alpha- and beta-glucosidase assays, no significant inhibition was seen with the inclusion of BSA, indicating tannin-based inhibitory effects on these two enzymes. The beta-glucuronidase inhibitory activity, however, was retained in the presence of BSA. The study shows that Sutherlandia extracts contain inhibitory compounds active against HIV target enzymes, while aqueous Lobostemon leaf extracts contain a potent HIV-1 RT inhibitor, thus showing a potential mechanistic action of these plants in aiding HIV-positive patients.


J Ethnopharmacol. 2004 Nov;95(1):1-5.

The antioxidant potential of Sutherlandia frutescens.
Fernandes AC, Cromarty AD, Albrecht C, van Rensburg CE.

Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa.

One of the best-known multi-purpose medicinal plants in Southern Africa, Sutherlandia frutescens subsp. microphylla (family: Fabaceae/Leguminosa), is used for a wide range of conditions, including cancer, viral diseases and inflammatory conditions. Little scientific data has been documented on the mechanism by which Sutherlandia frutescens acts on the immune system. Phagocyte derived reactive oxygen species, such as hydrogen peroxide and superoxide radicals, are responsible for the pathogenesis of various inflammatory conditions. Anti-inflammatory properties of various medicinal-plant extracts have been explained, at least in part, by their antioxidant activities. We investigated the effects of a hot water extract of Sutherlandia frutescens on both luminol and lucigenin enhanced chemiluminescence of neutrophils stimulated with L-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) as well as its superoxide and hydrogen peroxide scavenging properties in a cell free system. The results indicate that Sutherlandia frutescens extract possesses superoxide as well as hydrogen peroxide scavenging activities at concentrations as low as 10 microg/ml, which could account for some of the anti-inflammatory properties that have been described.


Methods Find Exp Clin Pharmacol. 2004 Jul-Aug;26(6):409-16.

Analgesic, antiinflammatory and hypoglycemic effects of Sutherlandia frutescens R. BR. (variety Incana E. MEY.) [Fabaceae] shoot aqueous extract.
Ojewole JA.

Department of Pharmacology, Faculty of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.

Previous studies on the pharmacology of South African medicinal plants in our laboratories and elsewhere have shown that some plants possess therapeutic attributes. One such ethnomedically useful plant is Sutherlandia frutescens R. BR. (family: Fabaceae). S. frutescens is widely used in South African traditional medicine for the management and/or control of a plethora of human ailments. In order to scientifically appraise some of the ethnomedical uses of S. frutescens, the present study was undertaken to investigate the analgesic, antiinflammatory and antidiabetic properties of the plant's shoot aqueous extract in experimental animal models. The analgesic effect of the herb's shoot extract was evaluated using the hot-plate and acetic acid test models of pain in mice, while the antiinflammatory and hypoglycemic effects of the plant's shoot aqueous extract were investigated in rats, using fresh egg albumin-induced pedal (paw) edema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (100 mg/kg) and chlorpropamide (250 mg/kg) were used, respectively, as reference drugs for comparison. S. frutescens shoot aqueous extract (50-800 mg/kg i.p.) produced significant (p < 0.05-0.001) analgesic effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (50-800 mg/kg p.o. or i.p.) also significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced acute inflammation and caused significant (p < 0.05-0.001) hypoglycemia in rats. The various chemical constituents and secondary metabolites of the herb are speculated to account for the observed analgesic, antiinflammatory and hypoglycemic effects of the plant. The results of this experimental animal study suggest that S. frutescens shoot aqueous extract possesses analgesic, antiinflammatory, and hypoglycemic properties, and thus lend pharmacological credence to the suggested folkloric uses of the herb in the management and/or control of painful, arthritic and other inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in some communities of South Africa.


Biofactors. 2004;21(1-4):149-53.

Inhibition of phorbol ester-induced COX-2 expression by some edible African plants.
Na HK, Mossanda KS, Lee JY, Surh YJ.

Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul National University, South Korea.

Cancer bush (CB, Sutherlandia frutescens), Devil's claw (DEV, Harpagophytum procumbens), Rooibos tea (RT, Aspalathus linearis), and Bambara groundnut (BB, Vignea subterranean) have been used to treat some malignancies and inflammatory disorders in Africa. However, biochemical basis for chemopreventive effects of these medicinal plants remains unclear. An abnormally elevated expression of cyclooxygenase-2 (COX-2) has been implicated in pathogenesis and progression of carcinogenesis. In the present study, we found that the methanol extracts of CB, DEV, RT, and BB inhibited, to a different extent, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression in human breast epithelial (MCF10A) cells and in mouse skin in vivo. To determine the molecular mechanism of COX-2 inhibition by the above medicinal plants, we examined their effects on activation of NF-kappaB which is one of the major transcription factors responsible for regulating COX-2 expression. Methanol extracts of both CB and BB inhibited the DNA binding of NF-kappaB activated by TPA in MCF10A cells in a dose-dependent manner. Based on above findings, CB and BB are likely to inhibit TPA-induced COX-2 expression through suppression of DNA binding of NF-kappaB, which may contribute to the chemopreventive or chemoprotective activity of these African plants


J Ethnopharmacol. 2005 Apr 8;98(1-2):163-70.

Sutherlandia frutescens extracts can induce apoptosis in cultured carcinoma cells.
Chinkwo KA.

Laboratory of Biochemistry, Department of Biotechnology, University of the Western Cape, Private Bag X17, Bellville 7535, Cape Town, South Africa.

Sutherlandia frutescens popularly known as cancer bush is endemic to Southern Africa. Whole plant parts have been used and traditional healers claim that it can treat cancer. In this study it is shown that a crude aqueous Sutherlandia frutescens whole plant extract induced cytotoxicity in neoplastic cells (cervical carcinoma) and CHO (Chinese Hamster Ovary cells) cell lines. Morphological observation and monitoring with other biological assays involving chromatin condensation as well as phosphotidyl serine externalisation point to apoptotic responses. Further biochemical assays showed similar DNA fragmentation patterns induced by Sutherlandia frutescens extracts compared to other inducers of apoptosis such as staurosporine and ceramide. Furthermore, Sutherlandia frutescens extracts induced apoptosis was confirmed by flow cytometric analysis. These findings warrant further research with a view to develop Sutherlandia frutescens extracts for use in anti-cancer therapy.


Endocr Res. 2004 Nov;30(4):745-51.

The effect of Sutherlandia frutescens on steroidogenesis: confirming indigenous wisdom.
Prevoo D, Smith C, Swart P, Swart AC.

Department of Biochemistry, University of Stellenbosch, Stellenbosch, South Africa.

Sutherlandia frutescens (Cancer bush), a Southern African indigenous plant, is traditionally used to treat stress related maladies linked to the endocrine system. Extracts of the shrub were used to investigate the claimed stress-relieving properties of the shrub. Dysregulation of the stress response is associated with elevated glucocorticoid levels. A model of chronic intermittent immobilization stress was investigated in 40 adult male Wistar rats to determine the effect of Sutherlandia. Immobilization stress resulted in increased corticosterone levels in the control group while rats receiving Sutherlandia extract showed significantly decreased corticosterone levels (P < 0.005). Since the biosynthesis of glucocorticoids in the adrenals is catalyzed by the cytochrome P450-dependent enzymes, the influence of Sutherlandia extracts on adrenal steroidogenesis was determined in ovine adrenocortical microsomes and mitochondria, using spectral binding and enzyme conversion assays. Water extracts showed inhibition of substrate binding to cytochrome P450 21-hydroxylase (CYP21) by 38% and cytochrome P450 11beta-hydroxylase (CYP11B1) by 60%. The conversion of progesterone and pregnenolone was inhibited by 34% and 30%, respectively. Subsequent extractions with chloroform and methanol showed inhibition of substrate binding and conversion with hydrophobic compounds exhibiting a greater inhibitory effect on deoxycorticosterone binding to CYP11B1 (30%) and on progesterone binding to CYP21 (50%). The inhibition of binding of pregnenolone to CYP17 by the chloroform extract was 62%, with negligible inhibition by the methanol extract. The chloroform extract showed a greater inhibitory effect than the methanol extract on progesterone and pregnenolone metabolism (20%-50%).


Cancer Lett. 2005 Jan 31;218(1):21-31.

Inhibitory effects of the extracts of Sutherlandia frutescens (L.) R. Br. and Harpagophytum procumbens DC. on phorbol ester-induced COX-2 expression in mouse skin: AP-1 and CREB as potential upstream targets.
Kundu JK, Mossanda KS, Na HK, Surh YJ.

Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742, South Korea.

Numerous anti-nflammatory agents have been shown to exert chemopreventive activity by targeting cyclooxygenase (COX)-2, a rate-limiting enzyme involved in the inflammatory process. Sutherlandia frutescens (L.) R. Br. and Harpagophytum procumbens DC., which are commonly known as Cancer bush (CB) and Devil's claw (DC), respectively, have long been used in South Africa for the management of pain and inflammation. In the present study, we investigated the effects of methanolic extracts of CB and DC on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression in mouse skin. Topical application of both extracts inhibited TPA-induced COX-2 expression. As an underlying mechanism of COX-2 inhibition, these extracts diminished TPA-stimulated catalytic activity of extracellular signal-regulated protein kinase (ERK), which is known to regulate the activation of eukaryotic transcription factors mediating COX-2 induction. While TPA-induced activation of nuclear factor-kappaB remained unaffected by both extracts, they inhibited TPA-induced activation of activator protein-1 (AP-1) and attenuated the expression of its key component c-Fos. In another study, topical application of TPA induced DNA binding of cyclic AMP response element binding (CREB) protein in mouse skin in vivo, which was abrogated by pretreatment with either CB or DC


AIDS. 2005 Jan 3;19(1):95-97.

Impact of African herbal medicines on antiretroviral metabolism.
Mills E, Foster BC, Heeswijk RV, Phillips E, Wilson K, Leonard B, Kosuge K, Kanfer I.

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
University of British Columbia, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada
Division of Infectious Diseases, Ottawa General Hospital, Ottawa, Ontario, Canada
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Canadian College of Naturapathic Medicine, Toronto, Ontario, Canada
Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.

We examined the effects of two African herbal medicines recommended for HIV/AIDS patients on antiretroviral metabolism. Extracts from Hypoxis and Sutherlandia showed significant effects on cytochrome P450 3A4 metabolism and activated the pregnane X receptor approximately twofold. P-glycoprotein expression was inhibited, with Hypoxis showing 42-51% and Sutherlandia showing 19-31% of activity compared with verapamil. Initiating policies to provide herbal medicines with antiretroviral agents may put patients at risk of treatment failure, viral resistance or drug toxicity.


J Ethnopharmacol. 2004 Jul;93(1):9-19.

In vitro culture studies of Sutherlandia frutescens on human tumor cell lines.
Tai J, Cheung S, Chan E, Hasman D.

Departments of Pathology and Pediatrics, Center for Complementary Medicine Research, BC's Research Institute for Children's and Women's Health, University of British Columbia, 4480 Oak Street, Vancouver, BC, Canada V5Z 4H4.

Sutherlandia frutescens is a South African herb used traditionally by the natives to treat cancer, and more recently to improve the overall health in HIV/AIDS patients. Gas chromatography/mass spectrometer profiling and liquid chromatographic/mass spectral investigation confirmed and quantified the presence of canavanine, GABA and arginine in the herbal preparation used in this study. In vitro study demonstrated a concentration dependent effect of Sutherlandia on several tumor cell lines, with 50% inhibition (IC50) of proliferation of MCF7, MDA-MB-468, Jurkat and HL60 cells at 1/250, 1/200, 1/150 and 1/200 dilutions, respectively. Sutherlandia treatment did not induce HL60 differentiation along the macrophage/monocyte or granulocyte lineage. It demonstrated antioxidant activity in reducing free radical cations with an estimated activity of 0.5 microl of Sutherlandia extract equivalent to that of 10 microM of Trolox. However, it did not significantly suppress lipopolysaccharide stimulated nitric oxide production by murine macrophage/monocyte RAW 264.7 cells, nor did it significantly inhibit IL-1beta and TNF-alpha mRNA expression in RAW 264.7 cells. In conclusion, Sutherlandia ethanolic extract showed a concentration dependent antiproliferative effect on several human tumor cell lines but did not show significant antioxidant effects. Further studies are needed to explore the activities of this multipurpose South African herbal preparation.

Click here for a summary of a field trip - Sutherlandia and AIDS Patients.

   


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