Concept: Sutherlandia frutescens
- Drug metabolism and disposition: the biological fate of chemicals
- Published almost 8 years ago
Sutherlandia frutescens (ST) is a popular medicinal herb widely consumed in Africa by people living with HIV/AIDS. Concomitant use with antiretroviral drugs has generated concerns of herb-drug interaction. This study investigated the inhibitory effects of the crude extracts of ST on the major cytochrome P450 isozymes employing pooled human liver microsomes. Its effect on the metabolic clearance of midazolam using cryopreserved hepatocytes was also monitored. The potential of ST to inhibit human ATP-binding cassette (ABC) transporters (P-gp and BCRP) and the human organic anion transporting polypeptide (OATP1B1 and OATP1B3) activity was assessed using cell lines overexpressing the transporter proteins. ST showed inhibitory potency for CYP1A2 (IC(50) = 41.0 μg/mL), CYP2A6 (IC(50) = 160 μg/mL), CYP2B6 (IC(50) = 20.0 μg/mL), CYP2C8 (IC(50) = 22.4 μg/mL), CYP2C9 (IC(50) = 23.0 μg/mL), CYP2C19 (IC(50) = 35.9 μg/mL) and CYP3A4/5 (IC(50,) = 17.5 μg/mL [with midazolam1'-hydroxylation]; IC(50) = 28.3 μg/mL [with testosterone 6β-hydroxylation]). Time-dependent (irreversible) inhibition by ST was observed for CYP3A4/5 (KI = 296 μg/mL, kinact = 0.063 min(-1)) under the conditions of this study. ST also delays the production of midazolam metabolites in the hepatocytes, decreasing its clearance by 40%. Further, ST inhibited P-gp (IC(50) = 324.8 μg/mL); OATP1B1 (IC(50) = 10.4 μg/mL, and of OATP1B3 (IC(50) = 6.6 μg/mL). The result indicates the potential for HDI between ST and the substrates of the affected enzymes, if sufficient in vivo concentration of ST is attained.
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).
Sutherlandia frutescens (L.) R. Br. is widely used as an over the counter complementary medicine and in traditional medications by HIV seropositive adults living in South Africa; however the plant’s safety has not been objectively studied. An adaptive two-stage randomized double-blind placebo controlled study was used to evaluate the safety of consuming dried S. frutescens by HIV seropositive adults with CD4 T-lymphocyte count of >350 cells/μL.
Sutherlandia frutescens (L) R.Br. is one of traditional herbal medicines that formed the basis of primary health care systems since the earliest days and is still widely used. Sutherlandia is prescribed for people with tuberculosis (TB), but is still not known which compound(s) acts against M. tuberculosis and its mode of action. The aim of this study was to identify and isolate antimycobacterial compounds from S. frutescens extracts against shikimate kinase, a drug target for M. tuberculosis.
Sutherlandia frutescens (L.) R. Br is endemic to Southern Africa where it has been traditionally used for cancer and diabetes. In recent times it has been marketed for its reputed (but not proven) anticancer, antidiabetic and anti-HIV properties. Little is known about the mutagenic and antimutagenic potential of extracts and common marker compounds of Sutherlandia frutescens. Therefore this study aimed to investigate the putative efficacy and possible long-term adverse effects of using this herb.
Sutherlandia frutescens is widely used in indigenous medicine for the treatment of stress- and anxiety-related disorders, and although anecdotal evidence has been scientifically confirmed, relatively little data are available on its potential mechanisms of action. We manipulated a rodent model of acute psychological stress by acutely administering a low dose (4 mg/kg body mass) of S. frutescens extract 30 min prior to stress exposure (1 h restraint), to elucidate both its central and peripheral mechanisms of action in the context of acute stress. After 1 h of exposure to stress, acute restraint resulted in a significant increase in plasma corticosterone levels (56 ± 33 versus 499 ± 50 ng/ml; P < 0.0001) and anterior pituitary adrenocorticotropic hormone (ACTH) levels (0.066 ± 0.017 versus 0.202 ± 0.033% fluorescent area; P = 0.07), while decreasing hippocampal glucocorticoid receptor (GR) and gamma-aminobutyric acid (GABA)(A)α1 receptor levels (both P < 0.05). While the low dose of S. frutescens administered did not seem to have an effect on the down-stream stress response, it abolished the stress-induced down-regulation of GR, in a manner independent of GABA(A)α1 receptor. Results suggest a non-sedative effect of low-dose S. frutescens and points to central mechanisms of action that is in support of the anecdotal claims for its effectiveness as complimentary treatment in chronic stress-associated diseases.
Sutherlandia frutescens (L.) R. Br. is an indigenous plant of southern Africa that has been traditionally used for various cancers, infections, and inflammatory conditions.
Spiral countercurrent-chromatography has great potential for improving the capacity and efficiency of purification of secondary metabolites, and here we describe applications useful for the isolation of flavonoids from the widely used South African medicinal plant, Sutherlandia frutescens (L.) R. Br. In the spiral tubing support rotor, STS-4 for high-speed counter-current chromatography, several polar butanol aqueous solvent systems were selected using a logK plot, and the novel flavonol glycosides (sutherlandins A-D) were well separated by the optimized solvent system (ethyl acetate:n-butanol:acetic acid:water; 5:1:0.3:6 by vol.). The yield of purified flavonoids from 0.9g extract varied from 8.6mg to 54mg of the sutherlandins for a total of 85.3mg. The same extract was fractionated in the new STS-12 rotor of the same outside dimensions but with more radial channels forming 12 loops of the tubing instead of 4. The rotor holds more layers and increased length of tubing. From 0.9g extract the STS-12 rotor yielded more recovery of 110.4mg total with amounts varying from 11.2mg to 64mg of the sutherlandins and apparent increased separation efficiency as noted by less volume of each fraction peak. Thus from 1-g amounts of extract, good recovery of the flavonoids was achieved in the butanol aqueous solvent system.
Sutherlandia frutescens is a traditional African medicinal plant used in the treatment of stress and anxiety, while also exhibiting anti-inflammatory properties.
Unlike the case of conventional drug formulations, dissolution tests have hitherto not been required for herbal medicinal products commercially available in South Africa. This study investigated dissolution of the South African Sutherlandia frutescens using selected flavonoid glycosides as marker compounds. Dissolution of markers was assessed in three dissolution media at pH 1.2, 4.5 and 6.8, and samples were analysed using a validated HPLC method. The dissolution profile of each marker varied for the different materials investigated. All three media utilised showed differences in flavonoid glycoside dissolution between the S. frutescens products evaluated, with f2 values < 50 for comparison of flavonoid dissolution from any two of the materials. Dissolution of S. frutescens materials could thus be characterised using the markers in all the media tested. This tool may be employed in the future for comparison of orally administered S. frutescens products, provided between- batch variability is evaluated and found less than between-sample variability.