Verification of the folkloric and anecdotal antidiabetic effects of Hypoxis hemerocallidea (Fisch., C.A. Mey. & Avé-Lall) and isolated, ß-sitosterol using early-stage type II spontaneous diabetic mutant BKS-Leprdb mice.

BACKGROUND: Previous studies in our laboratory in ex vivo assays have demonstrated H. hemerocallidea extract as potential antidiabetic agent through increased insulin release from pancreatic beta cells. Thus, for this study the early stage type II spontaneous diabetic mutant mice model was used to evaluate and determine the degree of the antidiabetic efficacy of H. hemerocallidea. METHODS: Eight-weeks-old type II spontaneous pre-diabetic mutant BKS-Leprdb mice were fed with feed supplemented with either H. hemerocallidea extract, isolated compound (ß-sitosterol) or chlorpropamide (positive control) for 4 weeks. The haematological parameters, clinical chemistry, glucose tolerance, feed intake, faecal output and body weights were measured. RESULTS: The blood glucose concentrations of all the animals treated with plant extract, ß-sitosterol compound and non-treated pre-diabetic animals did not return to baseline levels. Only the ß-sitosterol treatment and positive control groups resulted in a respective small decrease of 5.8 and 5.2% in the mouse weights over the study period, with no significant changes (p > 0.05) in food intake. However, there was a general trend for decrease in faecal output for all the groups. Albumin, triglycerides, and total cholesterol levels in ß-sitosterol and chlorpropamide-treated animals were lower, relative to untreated-animals. Animals fed with plant extract showed large amounts of internal fat. There were no significant changes (p > 0.05) in total serum protein, globulin, alanine aminotransferase, alkaline phosphatase, urea nitrogen and creatinine attributed to administration of treatments. In all groups, some animals showed lesions associated with cardiac puncture. Few animals except animals treated with plant extract, showed presence of a left-ventricular hypertrophic cardiomyopathy. The liver and kidneys for all groups appeared macroscopically normal and the thymuses were small (±2 mg). There were pathological signs in some of the animals particularly in myocardial fibres, renal tubular, glomerular, hepatocyte granularity and pancreas islets. However, there was no significance trend between the groups. CONCLUSION: Based on the results, none of the treatments could be considered highly effective for the management of type II pre-diabetes as sole therapeutic intervention.

Benzoylcyclopropane Derivatives from Hypoxis hemerocallidea Corms.

Two monobenzoylcyclopropane (hypoxhemerol A (1: ) and hypoxhemeroloside G (2: )) and three dibenzoylcyclopropane (hypoxhemerol B (3: ), hypoxhemeroloside H (4: ), and hypoxhemeroloside I (5: )) derivatives were isolated from the hydro-alcoholic extract of Hypoxis hemerocallidea corms. This is the first instance where benzoylcyclopropane analogs were isolated from any natural source. Structure elucidation was mainly based on 1D- and 2D-NMR and HRESIMS data. The absolute configuration (2R, 4R) of 1: was determined via NOESY NMR and experimental and calculated ECD data analyses. Compounds 1: -5: and 11 recently reported metabolites (hypoxoside, obtuside A, interjectin, acuminoside, curcapicycloside, and hypoxhemerolosides A - F) were screened for in vitro antimicrobial activity against various bacterial and fungal strains. Curcapicycloside and acuminoside exhibited antibacterial activity against Escherichia coli with 78 and 79% inhibition at 20 µg/mL, respectively. Hypoxhemeroloside A showed mild antifungal activity against Cryptococcus neoformans with 63% inhibition at 20 µg/mL.

Synergistic broad-spectrum antibacterial activity of Hypoxis hemerocallidea-derived silver nanoparticles and streptomycin against respiratory pathobionts.

Respiratory tract infections arise due to the introduction of microbes into the airway, disrupting the normal, healthy, complex interdependent microbiome. The selective disruption of this community can be either beneficial or dangerous. Nanoparticles are a potential tool for modifying this population. Coated silver nanoparticles (AgNPs) were synthesized using ethanolic extracts of Hypoxis hemerocallidea (EEHH), a Southern African plant used extensively in traditional medicine and the source of many bioactive secondary metabolites. The room temperature reaction between silver nitrate and EEHH forms largely spherical AgNPs with an average diameter of 6-20 nm. These nanoparticles show similar levels of antibacterial activity as the broad-spectrum antibiotic streptomycin against Bacillus cereus, Streptococcus pneumonia, Escherichia coli, Pseudomonas aeuroginosa, and Moraxella catarrhalis. However, the AgNPs synergistically increase the antibacterial activity of streptomycin when they are applied in combination (30-52%). AgNPs are reiterated to be promising dual-function antibiotics, synergistically enhancing activity while also acting as delivery agents for small molecules.

African potato (Hypoxis hemerocallidea): a systematic review of its chemistry, pharmacology and ethno medicinal properties.

BACKGROUND: African Potato (hypoxis hemerocallidea), is used for enhancing immune system in Southern Africa. It is among the plants of intense commercial and scientific interest; hence, the aim of this study was to describe its chemistry and pharmacology. METHODS: PubMed, Cochrane Controlled Trials Register (CENTRAL) and Google Scholar were searched independently for relevant literature. The last search occurred in October 2018. Other research material was obtained from Google. The following search terms were used, but not limited to: "African Potato", "hypoxis", "hemerocallidea", "rooperol." Articles that were explaining the chemistry and pharmacology of hypoxis hemerocallidea were included. RESULTS: Thirty articles from PubMed, Cochrane and Google Scholar were eligible. Three webpages were included from Google. Results showed that the tuberous rootstock (corm) of African Potato is used traditionally to treat wasting diseases, testicular tumours, insanity, barrenness, impotency, bad dreams, intestinal parasites, urinary infection, cardiac disease and enhancing immunity. The plant contains hypoxoside, which is converted rapidly to a potent antioxidant, rooperol in the gut. The corm contains sterols, sterol glycosides, stanols, terpenoids, saponins, cardiac glycosides, tannins and reducing sugars. A dose of 15 mg/kg/day of hypoxoside is reportedly therapeutic. Preclinical studies of African Potato have shown immunomodulation, antioxidant, antinociceptive, hypoglycaemic, anti-inflammatory, anticonvulsant, antibacterial, uterolytic, antimotility, spasmolytic and anticholinergic effects. The common side effects of African Potato are nausea and vomiting, which subside over time. In vitro, African Potato demonstrated inhibitory effects on CYP1A2, 2C9, 2D6, 3A4, 3A5, CYP19-metabolism and induction of P-glycoprotein. In vivo, it did not alter the pharmacokinetics of efavirenz or lopinavir/ritonavir. CONCLUSION: African Potato is mainly used as an immunostimulant. The exact mechanisms of action for all the pharmacological actions are unknown. More research is required to substantiate claims regarding beneficial effects. There are many research gaps that require investigation including pharmacokinetic interactions with conventional drugs, especially those used in HIV/AIDS.

The In Vitro Immunomodulatory Effects Of Gold Nanoparticles Synthesized From Hypoxis hemerocallidea Aqueous Extract And Hypoxoside On Macrophage And Natural Killer Cells.

BACKGROUND: Macrophages and Natural Killer (NK) cells are an integral part of the innate immune system. These cells produce pro-inflammatory cytokines in response to bacterial infections. However, prolonged inflammation can be a contributing factor in the etiology of several diseases such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, psoriasis and eczema. Reducing the secretion of pro-inflammatory cytokines is an effective treatment strategy for these conditions. Gold nanoparticles (AuNPs) have been shown to have immunosuppressive effects. Extracts of the Hypoxis hemerocallidea plant have also been shown to have immunomodulatory effects. It has been demonstrated previously that extracts of the H. hemerocallidea can be used to synthesize AuNPs. PURPOSE: This study aimed to investigate whether AuNPs synthesized using H. hemerocallidea extract and its major secondary metabolite, hypoxoside, have any immunomodulatory effects in macrophages and NK cells. METHODOLOGY: AuNPs derived from the H. hemerocallidea extract were synthesized as previously described. Using similar methodologies, this study shows for the first time the synthesis of AuNPs from hypoxoside. The AuNPs were characterized using several optical and spectroscopic techniques. The immunomodulatory effects of the aqueous extract of H. hemerocallidea, hypoxoside, as well as the AuNPs produced from the extract and hypoxoside, were investigated by measuring the cytokine levels in macrophages (IL-1ß, IL-6 and TNF-α) and NK cells (IFN-γ) using solid phase sandwich ELISA technique. RESULTS: The results show that spherical AuNPs (average size 26 ± 2 nm) were synthesized from hypoxoside. The results also show that the four treatments (H. hemerocallidea extract, hypoxoside and their respective AuNPs can lower the pro-inflammatory cytokine levels in the macrophages cells, while only AuNPs produced from hypoxoside can reduce cytokine responses in NK cells. CONCLUSION: This study shows that all four treatments investigated here could be further explored for the development of anti-inflammatory therapies.

Proximate and elemental composition of leaf, corm, root and peel of Hypoxis hemerocallidea: A Southern African multipurpose medicinal plant.

Hypoxis hemerocallidea also known as African potato is a medicinal plant widely distributed in Southern Africa, which has enjoyed long usage as a traditional multipurpose herbal medicine. This study evaluated the leaf, corm, peel and root of H. hemerocallidea for their nutritional attributes. Crude protein was highest in leaf (5.56%), followed by peel (2.79%), root (2.30%) and corm (1.79%) respectively. Crude fat ranged from 0.40% in root to 1.88% in leaf, while ash and acid detergent fibre (ADF) were highest in corm (16.77% and 49.75%) and lowest in root (3.20% and 5.46%) respectively. Neutral detergent fibre (NDF) was highest in leaf (55.47%), followed by corm (52.38%), peel (35.23%) and root (10.51%); while total carbohydrate calculated as non-fibre carbohydrate was highest in the root. The corm had the highest content (P<0.05) of calcium, zinc, copper and manganese, the root exhibited the highest content of magnesium, potassium and iron, while sodium and phosphorus content was highest in the leaf. The study revealed that H. hemerocallidea leaf, corm, peel and root are good sources of nutrients and minerals for humans and animals. This implies that the plant as a whole could be more effective therapeuticaly than the corm alone.

The In Vitro and In Vivo Effects of Hypoxis hemerocallidea on Indinavir Pharmacokinetics: Modulation of Efflux.

Hypoxis hemerocallidea (African potato) is a popular medicinal plant that has been used traditionally for the treatment of various disorders. Some HIV/AIDS patients use this traditional medicine together with their antiretroviral therapy. This study aimed to determine the impact of selected H. hemerocallidea materials (i.e., a commercial product, an aqueous extract, and biomass reference plant material) on the bidirectional permeability of indinavir across Caco-2 cell monolayers as well as the bioavailability of indinavir during an acute, single administration study in Sprague-Dawley rats. All of the selected H. hemerocallidea test materials demonstrated inhibition effects on indinavir efflux across Caco-2 cell monolayers, albeit to different extents. An increase in the bioavailability of indinavir was obtained in vivo when administered concomitantly with the H. hemerocallidea materials, albeit not statistically significantly. The change in bioavailability directly correlated with the in vitro permeability results. It can therefore be concluded that the change in permeability and bioavailability of indinavir was caused by efflux inhibition and this effect was dependent on the type of H. hemerocallidea material investigated, which was found to be in the following order: commercial product > aqueous extract > reference plant material. The clinical significance of the combined effect of efflux and metabolism inhibition by H. hemerocallidea should be determined in another in vivo model that expresses the cytochrome P450 3A4 enzyme.

In Vitro Investigation of Potential Anti-Diabetic Activity of the Corm Extract of Hypoxis Argentea Harv. Ex Baker.

The corms of Hypoxis argentea are widely used as a traditional remedy for diabetes mellitus in South Africa. In this study, we investigated the effects of non-toxic concentrations (12.5-100 µg mL-1) of the aqueous extract of H. argentea (HAA) corms on glucose uptake, pancreatic beta cell proliferation, and adipocyte differentiation. HAA stimulated glucose uptake in HepG2 cells up to 19.6 % and 17.0 % in L6 myotubes. Live-cell imaging microscopy revealed significant increases (p < 0.001) in total INS-1 cell numbers exposed to HAA, although no effect was observed on adipogenesis in 3T3-L1 pre-adipocytes. HAA produced weak to moderate inhibition of porcine pancreatic α-amylase, α-glucosidase, porcine pancreatic lipase, dipeptidyl peptidase IV (DPP IV) activities, as well as protein glycation. Our results suggest that the acclaimed anti-diabetic effects of H. argentea could be mediated by its promotion of glucose utilization and preservation of pancreatic beta cell populations while preventing fat accumulation in adipocytes.

Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea.

INTRODUCTION: Wide spectrum of alterations associated with highly active antiretroviral therapy (HAART) has been reported. The current study aimed at evaluating the role of Hypoxis hemerocallidea (HH) aqueous extract on the testosterone levels, expression of androgen receptors and collagen fibers in the testes of streptozoto-cin-nicotinamide-induced diabetic rats under HAART regimen. MATERIAL AND METHODS: Sixty two adult male Sprague-Dawley rats (189.0 ± 4.5 g) were divided into eight groups (8 animals in each treatment groups and 6 rats in the control group). Diabetes was induced by a single intraperi-toneal injection of nicotinamide (110 mg/kg bw) followed by streptozotocin (45 mg/kg bw) and the animals were then subjected to various treatments with HAART, HH extract or melatonin. At the end of the experiment, blood samples were collected to measure serum testosterone levels. Testes were fixed in buffered formaldehyde and paraffin processed. The expression of androgen receptor (AR) was assessed by immunohistochemistry and collagen fibers were visualized by Masson trichrome staining. RESULTS: Serum testosterone level was drastically (p < 0.0001) reduced in all rats with induced diabetes. In the testis of diabetic rats increased collagen fibers deposition with varying derangements in germinal epithelium of spermatogenic layers were observed. Intertubular hemorrhages and absence of spermatozoa were also noted in the testes of diabetic rats subjected to HAART. Reduced immunoexpression of ARs was found in the nuclei of Sertoli cells and the cytoplasm of spermatogonia and spermatocytes in III-IV stages of the seminiferous epithelium cycle of diabetic animals treated with different dosages of HH alone and those treated with HAART concomitantly with melatonin and HH. The expression of ARs was almost negative in the testes of rats treated with HAART alone. CONCLUSIONS: Concomitant treatment of rats with aqueous HH extract during the HAART did not change se-rum testosterone level nor mitigate the altered expression of collagen fibers and androgen receptor resulting from STZ-nicotinamide-induced diabetes. Therefore, anti-diabetic properties of Hypoxis extract require further investigation.

Effect of co-administration of Hypoxis hemerocallidea extract and antiretroviral therapy (HAART) on the histomorphology and seminal parameters in Sprague Dawley rats.

Although the successful introduction and rollout of antiretroviral therapy has impacted positively on morbidity and mortality of HIV-positive patients, its interaction with plant-based adjuvants remain sparsely investigated. We report the interaction and effects of adjuvant treatment with highly active antiretroviral therapy (HAART) and Hypoxis hemeocallidea (HH) extracts on testicular structure of rats. A total of 63 pathogen-free adult male Sprague Dawley rats were divided into nine groups and treated according to protocols. HAART cocktail predisposed to significant negative testicular parameters of sperm count, motility and seminiferous tubular epithelial height (quantitatively) (p < .03) and also altered the histomorphology of tubules with diffuse hypoplasia in seminiferous tubules. The higher dose of HH showed a better ability to mitigate the altered parameters and compares favourably with vitamin C in this protocol. While HH did not show any deleterious impact on morphometric data, its role as adjuvant did not significantly reduce the negative impact of HAART on morphometric indices especially with the lower dosage. Further investigations are warranted on the interactions between HAART and Hypoxis.

Does Hypoxis hemerocallidea mitigate renal histopathological injuries following highly active antiretroviral therapy? An experimental animal study.

BACKGROUND: Nephrotoxicity has become an important public health problem following the success recorded with highly active antiretroviral therapy, and there is paucity of literature reporting the attenuating influence of plant-based adjuvants that can mitigate the effects. METHODS: Sixty three adult male Sprague-Dawley rats were divided into 9 groups (A-I) and treated as follows: group A received HAART cocktail (lamivudine, stavudine and nevirapine), group B received HAART and Hypoxis hemerocallidea (HH) extract (200 mg/kg), group C received HAART and HH (100 mg/kg), group D received HAART and vitamin C, group E received HAART and vitamin E, group F received HAART, vitamin C and vitamin E, group G received HH extract (100 mg/kg), group H received HH extract (200 mg/kg), and group I received saline as placebo. After 56 days, animals were euthanized, kidneys harvested and prepared for H&E staining and blood samples were collected for BUN and serum creatinine analyses. RESULTS: The results from histological slides showed distorted glomerular and epithelial components with extensive loss of Bowman's capillary integrity in HAART-treated group. Adjuvant treatment with HH both high and low doses did not show any remarkable attenuating influence. However, HH100mg/kg-alone treated group showed improved histological layout as compared to the higher dose. Co-administration of HAART and vitamins C and E did not improve the parameters examined. The serum creatinine and BUN levels were significantly increased (P<0.05) following HAART with observable increase in kidney body weight ratio. SCR levels in group D was significantly reduced (P<0.05) but elevated in groups B, C, G and H (P<0.001). Groups B and C, as well as groups F and H recorded higher BUN values (P<0.05). CONCLUSIONS: Adjuvant treatment with HH extract did not attenuate the nephrotoxicity of HAART in this model.

Ultrastructure and elemental analysis of Hypoxis hemerocallidea: a multipurpose medicinal plant.

BACKGROUND: Herbal medicine is a popular means of medical management in some parts of the world especially in Africa. Hypoxis hemerocallidea Fisch.C.A.Mey. & Avé-Lall, also known as African potato of the Hypoxidaecae family, is one of the medicinal plants that have enjoyed long usage as an herbal medicine in South Africa. In this study, the morphology and elemental constituents of H. hemerocallidea leaf was investigated to correlate the functional role of the ultrastructure in the production of therapeutic compounds. MATERIALS AND METHODS: Fresh leaves of H. hemerocallidea were prepared for analysis using standard methods. The ultrastructure and crystal deposits of the plant were assessed using scanning electron microscopy (SEM), and energy dispersive x-ray (EDX). RESULTS: It was observed that the leaves were characterised by multicelullar glandular and non glandular trichomes which are sparsely distributed over the entire surfaces. The glandular trichomes (GTs) in H. hemerocallidea leaf have boulbous heads which are probably filled with secretions, while the non glandular trichomes were long, fibrous and sparse. EDX-SEM of Hypoxis hemerocallidea leaf revealed that carbon, oxygen, nitrogen and silicon are the major components of the deposits, while other elements such as iron, sulphur, sodium, calcium, magnesium, potassium, manganese, iodine, chromium and iodine were present in small but variable amounts. CONCLUSION: The presence of these elements which are crucial to maintaining good health, in addition to other bioactive constituents might be accountable for the multipurpose therapeutic uses of Hypoxis hemerocallidea in the treatment of cancers, HIV/AIDS related diseases, urinary tract infections, cardiovascular disorders, diabetes and other chronic ailments of humans.

The design of dextran-based hypoxia-inducible hydrogels via in situ oxygen-consuming reaction.

Hypoxia plays a critical role in the development and wound healing process, as well as a number of pathological conditions. Here, dextran-based hypoxia-inducible (Dex-HI) hydrogels formed with in situ oxygen consumption via a laccase-medicated reaction are reported. Oxygen levels and gradients were accurately predicted by mathematical simulation. It is demonstrated that Dex-HI hydrogels provide prolonged hypoxic conditions up to 12 h. The Dex-HI hydrogel offers an innovative approach to delineate not only the mechanism by which hypoxia regulates cellular responses, but may facilitate the discovery of new pathways involved in the generation of hypoxic and oxygen gradient environments.

The potential of Hypoxis hemerocallidea for herb-drug interaction.

CONTEXT: Aqueous decoction of Hypoxis hemerocallidea Fisch. & C.A. Mey. (Hypoxidaceae) (Hypoxis) is widely consumed in Southern Africa by people living with HIV/AIDS, some of whom are on ARV and other medications. OBJECTIVE: The aim of this study was to investigate the potential of the crude aqueous extracts of Hypoxis to inhibit major forms of CYP450 and transport proteins. MATERIALS AND METHODS: Corms of Hypoxis were water-extracted and incubated (in graded concentrations: 1-100 µg/mL) with human liver microsomes (20 min) to monitor the effects on phenacetin O-deethylation, coumarin 7-hydroxylation, bupropion hydroxylation, paclitaxel 6α-hydroxylation, diclofenac 4'-hydroxylation, S-mephenytoin 4'-hydroxylation, bufuralol 1'-hydroxylation, chlorzoxazone 6-hydroxylation, midazolam 1'-hydroxylation and testosterone 6ß-hydroxylation as markers for the metabolic activities of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4/5, respectively. The generation of metabolites were monitored and quantified with the aid of LC-MS/MS. The potential of the extracts to inhibit human ATP-binding cassette transporter activity was assessed using recombinant MDCKII and LLC-PK1 cells over-expressing human breast cancer resistant protein and human P-glycoprotein , respectively (with Ko143 and cyclosporin A as positive controls). Similar assessment was performed with human organic anion transporting polypeptide (OATP1B1 and OATP1B3) using recombinant HEK293 cells over-expressing OATP1B1 and OATP1B3, respectively (with rifamycin and 10 µM atorvastatin as positive controls). RESULTS: Extracts of Hypoxis inhibited the production of the metabolites of the substrates of the following enzymes (as compared to controls) with the indicated IC50 values (µg/mL): CYP1A2 (120.6), CYP2A6 (210.8), CYP2B6 (98.5), CYP2C8 (195.2), CYP2C9 (156) and CYP3A4/5 (185.4). The inhibition of the uptake activity of OATP1B1 and OATP1B3 were also observed with IC50 values of 93.4 and 244.8 µg/mL, respectively. DISCUSSION: Extract concentrations higher than the estimated IC50 values are achievable in the gastrointestinal tract when traditional doses of Hypoxis are considered. This may have profound effects on presystemic metabolism of the drug substrates. If absorbed, systemic inhibition of metabolic enzymes/transporters by Hypoxis may be expected. CONCLUSION: The result suggests that there is the potential for HDI between Hypoxis and the substrates of the affected enzymes/transporters, if sufficient in vivo concentration of Hypoxis extracts is attained.

Potential efficacy of some african plants in benign prostatic hyperplasia and prostate cancer.

Traditional medicine is very popular in Africa and it is considered as an alternative form of health care. Plants and vegetables used in folk and traditional medicine have gained wide acceptance as one of the main sources of prophylactic and chemopreventive drug discovery and this is due to the evidence of particular biological and biochemical characteristics of each plants extracts. The role of these compounds in urological field may be explained by the antiinflammatory effect through interference with prostaglandin metabolism, alteration of lipid peroxidation, direct inhibition of prostate growth and moreover through an antiandrogenic or antiestrogenic effect and a decrease of the availability of sex hormone-binding globulin. Since Benign Prostatic Hyperplasia and Prostate Cancer are two of the most diffuse diseases of aging male and considering that standard medical therapy is accompanied with different side effects, the emerging use of African plants may be justified. This review takes a look at some African plants extracts properties and their relative urological application. Different biomolecular mechanisms of action are promising, suggesting a real application in reducing prostate cells proliferation.

Bronchorelaxant property of 'African potato' (Hypoxis hemerocallidea corm) aqueous extract in vitro.

This study was undertaken to investigate the bronchorelaxant effect of Hypoxis hemerocallidea corm ('African potato') aqueous extract (APE) on spasmogen-provoked contractions of guinea-pig isolated tracheal smooth muscle preparations. APE (25-400 mg/ml) relaxed spasmogen (histamine-, carbachol- and potassium-)-induced contractions of the isolated tracheal muscle preparations in a concentration-dependent manner. The relaxant effects of APE on spasmogen-evoked contractions of the tracheal muscle preparations were not altered by bath-applied propranolol (0.1-5.0 microg/ml), which markedly inhibited or completely abolished the relaxant effects of isoprenaline (0.1-5.0 microg/ml). Although the precise mechanism of the bronchorelaxant effect of APE could not be established in the present study, it is unlikely that the herb's aqueous extract stimulates the beta(2)-adrenoceptors present on the bronchial smooth muscles to produce its bronchodilatation. The finding that APE significantly relaxed (P<0.05) histamine-, carbachol- and high potassium ion concentration (K(+), 80 mM)-induced contractions of guinea-pig isolated bronchial muscle preparations appears to suggest that the bronchospasmolytic effect of the plant's extract is probably not mediated through a specific receptor, but rather, probably mediated via a non-specific bronchospasmolytic mechanism.

Antidiarrhoeal activity of Hypoxis hemerocallidea Fisch. & C. A. Mey. (Hypoxidaceae) Corm ('African potato') aqueous extract in rodents.

This study investigated the antidiarrhoeal activity of Hypoxis hemerocallidea corm aqueous extract (APE) on experimentally-induced diarrhoea, gastrointestinal motility, intestinal transit and enteropooling in rodents. H. hemerocallidea corm aqueous extract (APE, 50-400 mg/kg, p.o.) produced dose-dependent and significant (p < 0.05-0.01) protection of rats and mice against castor oil-induced diarrhoea, inhibited intestinal transit and delayed gastric emptying. Like atropine (1 mg/kg, p.o.), APE (50-400 mg/kg, p.o.) produced dose-dependent and significant (p < 0.05-0.01) antimotility effect, and caused dose-related inhibition of castor oil-induced enteropooling in the animals. Like loperamide (10 mg/kg, p.o.), APE (50-400 mg/kg, p.o.) dose-dependently and significantly (p < 0.05-0.01) delayed the onset of castor oil-induced diarrhoea, decreased the frequency of defaecation and reduced the severity of diarrhoea in the rodents. Compared with control animals, APE (50-400 mg/kg, p.o.) dose-dependently and significantly (p < 0.05-0.01) decreased the volume of castor oil-induced intestinal fluid secretion, and reduced the number, weight and wetness of faecal droppings. APE (50-400 mg/mL) also produced concentration-related and significant (p < 0.05-0.01) inhibitions of the spontaneous, pendular contractions of the rabbit isolated duodenum, and attenuated acetylcholine (ACh, 0.1-5.0 microg/mL)-induced contractions of the guinea-pig isolated ileum. Although the precise mechanism of the antidiarrhoeal activity of APE could not be established, the results of this study indicate that APE possesses antidiarrhoeal activity. This finding supports the use of 'African potato' as a natural supplementary remedy for the treatment, management and/or control of diarrhoea in some rural communities of southern Africa.

'African potato' (Hypoxis hemerocallidea corm): a plant-medicine for modern and 21st century diseases of mankind? - a review.

The traditional uses, therapeutic attributes, phytochemical and pharmacological profiles of 'African potato' (Hypoxis hemerocallidea corm) extracts have been reviewed. Available biomedical evidence suggests that 'African potato' is a potential plant-medicine for some modern and 21st century diseases of mankind. Thus far, biomedical evidence has revealed that 'African potato' extracts possess antiinflammatory, antineoplastic, antioxidant, antidiabetic and antiinfective properties in vivo and in vitro. However, more laboratory and clinical studies are required to clarify these observations, and to isolate, purify and characterize the active chemical constituents responsible for the herb's pharmaco-therapeutic effects.

Development of dissolution tests for the quality control of complementary/alternate and traditional medicines: application to African potato products.

PURPOSE: Unlike orthodox medicines, specific guidelines for dissolution testing of complementary/alternate (CAMs) and traditional medicines (TMs) have not been developed nor is dissolution testing a requirement for the quality control of such products. In this report, the dissolution of African Potato (AP) products, an African traditional medicine (ATM) which has been ingested by man for a diversity of ailments, has been investigated. A norlignan glycoside namely hypoxoside and a sterol, beta-sitosterol (BSS) are purported to be the most important phytochemicals in marketed products of AP. Dissolution testing of AP products containing labelled content of sterols and those containing only hypoxoside is proposed whereby BSS and hypoxoside are monitored as markers for the release of the contents of the abovementioned products, respectively. METHODS: The FDA dissolution guidance for industry was used to study the best dissolution condition for several formulations of AP. Buffers in the range of pH 1.2 to 7.5 were used to investigate the dissolution of AP products containing hypoxoside as a marker compound. Similarly, biorelevant dissolution media such as fasted state simulation fluid (FaSSIF) and fed state simulation fluid (FeSSIF) at different pH were used to investigate the release of BSS in AP formulations labelled to contain sterols which exhibited poor water solubility. RESULTS: Dissolution testing of AP products containing hypoxoside, conducted at pH 1.2 using USP Apparatus 1 indicated that more than 75% of hypoxoside was released within 1 hr. Dissolution testing of products containing sterols, conducted in FeSSIF at a pH of 5.0 resulted in a release of at least 75% of BSS after 1 hr for all but one of the products tested. CONCLUSIONS: Dissolution testing conditions have been developed for AP products containing two different marker compounds where one of the components, hypoxoside, is water soluble, whereas another component, BSS is poorly water soluble. This necessitated the use of different dissolution media and pHs in order to monitor the respective release of hypoxoside and BSS from AP products. The results of this study indicate the necessity and possibility of developing appropriate dissolution testing procedures for use in the quality control of CAMs/TMs.

Impact of traditional medicinal plant extracts on antiretroviral drug absorption.

ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Traditional herbal medicines are often used for the treatment of different diseases in developing countries, especially in the rural areas where a lack of an efficient primary health care system is usually experienced. Many patients infected with the human immunodeficiency virus are taking traditional herbal medicines in conjunction with their modern antiretroviral medication and drug-herb interactions can occur in these cases. AIM OF THE STUDY: To investigate the effect of water extracts of two traditional medicinal plants, Hypoxis hemerocallidea and Sutherlandia frutescens as well as l-canavanine (a constituent of Sutherlandia frutescens) on the transport of nevirapine across human intestinal epithelial cells. MATERIALS AND METHODS: Nevirapine transport in the apical to basolateral and basolateral to apical directions across Caco-2 cell monolayers was determined alone (normal control) and in the presence of verapamil (positive control), water extracts of Hypoxis hemerocallidea and Sutherlandia frutescens and an aqueous solution of l-canavanine. The cumulative transport and apparent permeability coefficient (P(app)) values were calculated and compared. RESULTS: Nevirapine alone was substantially effluxed in the basolateral to apical direction across the intestinal epithelial cell monolayers, which was statistically significantly (p < or = 0.05) decreased by addition of verapamil, Hypoxis hemerocallidea extract and the l-canavinine solution. The effect of Sutherlandia frutescens on nevirapine transport was not statistically significantly different from the control. CONCLUSIONS: Hypoxis hemerocallidea and l-canavanine interact with the efflux of nevirapine across intestinal epithelial cells and therefore can potentially increase the bioavailability of this antiretroviral drug when taken concomitantly.