Sutherlandia frutescens extracts can induce apoptosis in cultured carcinoma cells

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.     

The antioxidant potential of Sutherlandia frutescens

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.     

普洱茶提取物的抗HIV活性(英文)

目的:研究普洱熟茶(发酵)和普洱绿茶(未发酵)这 2 种常见普洱茶的抗 HIV 作用。方法:采用 MTT 比色法检测普洱茶提取物对 C8166, MT4 和 PBMC 细胞的毒性作用; 细胞病变法检测化合物对 HIV-1 急性感染的抑制活性。采用细胞病变法和 HIV-1 p24 抗原 ELISA 方法检测普洱茶提取物的抗 HIV 活性作用; 结果:所有普洱茶提取物都具有较低的细胞毒性 CC50为 120.63 524.95 μg·mL 1。所有普洱茶提取物均能抑制 HIV 诱导细胞形成合胞体其 EC50为 11.13 67.49 μg·mL 1。普洱茶水提物的抑制作用比醇提物的抑制作用要好, 并且普洱熟茶的抑制作用好于普洱生茶, 尤其是 YYP-31, 其 SI 值为 42.40。YYP-31 对HIV-RF和 HIV-2CBL-20也有很好的抑制作用, 其 EC50分别为 30.82 和 39.79 μg·mL 1。YYP-31 还能很好地抑制 HIV-1IIIB急性感染C8166 细胞和 HIV-1KM018感染PBMC细胞p24抗原的产生, 其EC50分别为14.95和 74.63 μg·mL 1。YYP-31能阻止正常细胞C8166与 HIV-1 慢性感染细胞 H9/HIV-1IIIB之间的融合, EC50为 234.27 μg·mL 1。提取物 YYP-31 与 AZT 联合用药具有显著的协同抗HIV 作用,但是对 HIV 逆转录没有抑制作用。结论:普洱茶提取物具有很好的抗 HIV 的活性作用, 可以作为一种 HIV 辅助治疗的产品或保健品用于 HIV 患者的治疗过程中。     

Influence of Sutherlandia frutescens extracts on cell numbers, morphology and gene expression in MCF-7 cells

Sutherlandia frutescens is a well-known South African herbal remedy traditionally used for stomach problems, internal cancers, diabetes, various inflammatory conditions and recently to improve the overall health in cancer and HIV/AIDS patients. The influence of crude Sutherlandia frutescens extracts (prepared with 70% ethanol) was investigated on cell numbers, morphology, and gene expression profiles in a MCF-7 human breast adenocarcinoma cell line. Time-dependent (24, 34, 48 and 72 h) and dose-dependent (0.5-2.5 mg/ml) studies were conducted utilizing spectrophotometrical analysis with crystal violet as DNA stain. A statistically significant decrease to 50% of malignant cell numbers was observed after 24 h of exposure to 1.5 mg/ml Sutherlandia frutescens extract when compared to vehicle-treated controls. Morphological characteristics of apoptosis including cytoplasmic shrinking, membrane blebbing and apoptotic bodies were observed after 24h of exposure. A preliminary global gene expression profile was obtained by means of microarray analysis and revealed valuable information about the molecular mechanisms and signal transduction associated with 70% ethanolic Sutherlandia frutescens extracts.     

The influence of Sutherlandia frutescens on adrenal steroidogenic cytochrome P450 enzymes

AIM OF THE STUDY: The aim of this study was to investigate whether Sutherlandia frutescens, subsp. microphylla (family: Fabaceae/Leguminosa), which is traditionally used to treat symptoms of chronic stress generally associated with increased circulating glucocorticoids, influences the biosynthesis of these glucocorticoids. METHODS: We investigated the interaction of Sutherlandia frutescens with cytochrome P450 enzymes, CYP17 and CYP21, which catalyse key reactions in glucocorticoid biosynthesis. The binding of progesterone and pregnenolone to these enzymes and their metabolism were assayed in the presence of extracts and the bioactive compounds, l-canavanine, pinitol, GABA, flavonoids and triterpenoid glucosides present in the shrub. RESULTS: While the aqueous and methanol extracts inhibited the type I progesterone-induced difference spectrum (p<0.05), inhibition of pregnenolone binding (p=0.25) was negligible, with the aqueous extract exhibiting greater inhibition. The triterpenoid fraction inhibited both the type I pregnenolone- and progesterone-induced difference spectra and elicited a type II difference spectrum in the absence of substrate. Both pregnenolone and progesterone metabolism were inhibited by the aqueous extract, the inhibition of CYP21 being greater than that of CYP17, influencing the flux through glucocorticoid precursor pathways. CONCLUSION: This attenuation of adrenal P450 enzymes may thus demonstrate a possible mechanism by which Sutherlandia frutescens reduces glucocorticoid levels and alleviates symptoms associated with stress.     

Anti-diabetic effects of Sutherlandia frutescens in Wistar rats fed a diabetogenic diet

Sutherlandia frutescens has been marked as a potential hypoglycaemic agent for the treatment of type 2 diabetes. We investigated the effects of Sutherlandia frutescens in bringing about hypoglycaemia and promoting glucose uptake in pre-diabetic rats. Crushed Sutherlandia frutescens leaves in drinking water were administered to rats fed a high fat diet. Positive control rats received only metformin. Glucose uptake experiments were undertaken using [(3)H] deoxy-glucose. Various physiological parameters were also measured. Rats receiving Sutherlandia frutescens displayed normoinsulinaemic levels, after 8 weeks medicational compliance, compared to the fatty controls. There was a significant increase in glucose uptake into muscle and adipose tissue, and a significant decrease in intestinal glucose uptake (p<0.001 at 60min) in rats receiving the plant extract. The Sutherlandia frutescens plant extract shows promise as a type 2 anti-diabetes medication because of its ability to normalize insulin levels and glucose uptake in peripheral tissues and suppress intestinal glucose uptake, with no weight gain noted. The exact mechanism of action and the extract's efficacy in humans need further confirmation.     

In vitro culture studies of Sutherlandia frutescens on human tumor cell lines

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.     

Immunomodulatory activities of Cedrela tubiflora leaf aqueous extracts

Human peripheral blood monocytes and polymorphonuclear leukocytes treated with leaf aqueous extracts of the Meliaceae tree Cedrela tubiflora showed a diminution in both their phagocytic and respiratory burst activities. Besides, the extract inhibited the proliferation of Concanavalin A stimulated lymphocytes. A decrease in the hemolytic capacity of the human complement was also observed. The significance of the inhibitory effect observed over some components of the human immune system closely related with the inflammatory process is discussed.     

Immunomodulatory activities of Trichilia glabra leaf aqueous extracts

Human peripheral blood monocytes and polymorphonuclear leukocytes treated with leaf aqueous extracts of the Meliaceae tree Trichilia glabra showed a diminution in both their phagocytic and respiratory burst activities. A decrease in the haemolytic capacity of the human complement was also observed. The significance of the inhibitory effect observed over some components of the human immune system closely related with the inflammatory process is discussed. © 1998 John Wiley & Sons, Ltd.     

Anti-HIV activity of medicinal plant extracts

As part of our screening of anti-AIDS agents from natural sources, ethanolic and aqueous extracts of 15 medicinal plants widely used in the folk medicine of the Iberian Peninsula were evaluated in vitro. Most of the extracts tested were relatively nontoxic to human lymphocytic MT-2 cells, but only the extracts of Tuberaria lignosa and Sanguisorba minor magnolii exhibited anti-HIV activity in an in vitro MTT assay. The aqueous extracts of these plants showed inhibitory effects against HIV-1 induced infections in MT-2 cells at concentrations ranging from 12.5 to 50 microg/ml and 50 microg/ml, respectively. Both extracts showed no appreciable cytotoxicity at these concentrations.     

Antibacterial and antioxidant activity of Sutherlandia frutescens (Fabaceae), a reputed anti-HIV/AIDS phytomedicine

Dried ground leaves of Sutherlandia frutescens were extracted by both sequential extraction with four solvents, starting with the least polar and separately with acetone, ethanol and water. The extracts were tested for antibacterial and antioxidant activity. The hexane extract was, generally, the most active extract against S. aureus, E. faecalis and E. coli with MIC values of 0.31, 1.25 and 2.50 mg/mL, respectively. The second method extracted compounds with antioxidant activity as shown by the DPPH free-radical scavenging assay. The use of Sutherlandia frutescens for topical staphylococcal infections, when formulated in an oily base appears to have a rational basis.     

Sutherlandia frutescens limits the development of insulin resistance by decreasing plasma free fatty acid levels

Intake of high caloric food induces raised plasma free fatty acids, culminating in insulin resistance (IR) and Diabetes mellitus type 2 (DMT2). The present study has shown for the first time that Sutherlandia frutescens reduces plasma free fatty acid levels in rats fed a high fat diet, thereby preventing the development of insulin resistance. A commercially available S. frutescens extract was administered to rats to examine its effects on the progression of high fat diet induced IR. In comparison to rats fed high fat diet only (positive control for IR), levels of plasma free fatty acids (FFA) were significantly reduced after one week (p < 0.025). Twelve weeks of treatment with S. frutescens reduced the level of plasma free fatty acids below that of rats fed a normal diet (negative control) (p < 0.025). QUICKI and HOMA‐IR index confirmed that S. frutescens treated rats did not develop IR when fed a high fat diet for twelve weeks. In addition to preventing IR and reducing plasma FFA, chronic medication over twelve weeks decreased total cholesterol levels and the LDL/HDL ratio. We propose that S. frutescens is an effective medicinal remedy to prevent elevated plasma free fatty acids and IR, and therefore DMT2. Copyright © 2009 John Wiley & Sons, Ltd.     

A review of the taxonomy, ethnobotany, chemistry and pharmacology of Sutherlandia frutescens (Fabaceae)

Sutherlandia frutescens (tribe Galegeae, Fabaceae), a popular plant in traditional medicine, is indigenous to South Africa, Lesotho, southern Namibia and southeastern Botswana. It is chemically, genetically and geographically extremely variable and has been divided into three subspecies and several regional forms. A second species, Sutherlandia tomentosa, is localized along the Cape coast. Sutherlandia is sometimes treated as part of the genus Lessertia. There are numerous vernacular names and a wide diversity of uses, including poor appetite, indigestion, stomach complaints, dysentery, colds, influenza, kidney conditions, fever, diabetes, internal cancers, uterine troubles, liver conditions, backache, rheumatoid arthritis, urinary tract infections, stress and anxiety, dropsy and heart failure. Notable is the use as a bitter tonic ("blood purifier"), anti-stress medication ('musa-pelo) and, at least since 1895, specifically as a cancer tonic (both as treatment and as prophylaxis). Externally it is applied to haemorrhoids, inflamed wounds and eye infections. Recent in vitro and in vivo studies have shown antiproliferative, anti-HIV, anti-diabetic, anti-inflammatory, analgesic, antibacterial, anti-stress, anticonvulsant and antithrombotic activities. Aqueous extracts often differ in activity from organic solvent extracts. The presence of high levels of free amino acids, non-protein amino acids such as canavanine and GABA, the cyclitol pinitol, flavonols and triterpenes (including SU1, a cycloartane-type triterpene saponin) provide plausible hypotheses on how these compounds, individually or collectively, may be responsible for the reputed efficacy in a wide range of ailments. Results of animal studies, as well as a phase I clinical study, have shown no indications of toxicity. Sufficient preclinical data are now available to justify controlled clinical studies.     

Antidiabetic activities of aqueous and ethanolic extracts of Piper betle leaves in rats

Leaves of Piper betle (Piperaceae) possess several bioactivities and are used in traditional medicinal systems. However, its antidiabetic activity has not been scientifically investigated so far. The aim of this study therefore, was to investigate the antidiabetic activity of Piper betle leaves. This was tested in normoglycaemic and strepozotocin (STZ)-induced diabetic rats using oral administration of hot water extract (HWE) and cold ethanolic extract (CEE). In normoglycaemic rats, both HWE and CEE significantly lowered the blood glucose level in a dose-dependent manner. In glucose tolerance test, both extracts markedly reduced the external glucose load. The antidiabetic activity of HWE is comparable to that of CEE. Moreover, HWE failed to inhibit the glucose absorption from the small intestine of rats. Both extracts were found to be non-toxic and well tolerated after following chronic oral administration (no overt signs of toxicity, hepatotoxicity or renotoxicity). However, the weight of the spleen had increased in treated groups possibly indicating lymphoproliferative activity. It is concluded that HWE and CEE of Piper betle leaves possess safe and strong antidiabetic activity.     

In vivo and in vitro immunomodulatory activities of Trichilia glabra aqueous leaf extracts

The effects of Trichilia glabra (Meliaceae) aqueous leaf extract on mouse lymphocytes were studied. The in vitro proliferation of T and B lymphocytes was completely impaired. Besides, the extract significantly diminished both antibody and delayed hypersensitivity responses in treated mice. These results suggest that the extract exerts a marked immunomodulatory effect on the murine immune system.     

Mutagenic and antimutagenic activities of aqueous and methanol extracts of Euphorbia hirta

Euphorbia hirta (E. hirta) is a weed commonly found in tropical countries and has been used traditionally for asthma, bronchitis and conjunctivitis. However, one of the constituents in this plant, quercetin, was previously reported to be mutagenic. This work aimed to determine the level of quercetin in the aqueous and methanol plant extracts and to investigate the mutagenic effects of quercetin and the extracts in the Ames test utilising the mutant Salmonella typhimurium TA98 and TA100 strains. The antimutagenic activity of Euphorbia hirta aqueous and methanol extracts was also studied in Salmonella typhimurium TA98. HPLC analyses showed that quercetin and rutin, a glycosidic form of quercetin, were present in the acid-hydrolysed methanol extract and non-hydrolysed methanol extract respectively. The quercetin concentration was negligible in both non-hydrolysed and acid-hydrolysed aqueous extracts. The total phenolic contents in Euphorbia hirta were determined to be 268 and 93 mg gallic acid equivalent (GAE) per gram of aqueous and methanol extracts, respectively. Quercetin (25 μg/mL) was found to be strongly mutagenic in Salmonella typhimurium TA98 in the absence and presence of S-9 metabolic activation. However, both the aqueous and methanol extracts did not demonstrate any mutagenic properties when tested with Salmonella typhimurium TA98 and TA100 strains at concentrations up to 100 μg/mL in the absence and presence of S-9 metabolic activation. In the absence of S-9 metabolic activation, both the extracts were unable to inhibit the mutagenicity of the known mutagen, 2-nitrofluorene, in Salmonella typhimurium TA98. On the other hand, the aqueous extracts at 100 μg/mL and methanol extracts at 10 and 100 μg/mL exhibited strong antimutagenic activity against the mutagenicity of 2-aminoanthracene, a known mutagen, in the presence of S-9 metabolic activating enzymes. The results indicated that these extracts could modulate the xenobiotic metabolising enzymes in the liver at the higher concentrations.     

Diuretic and anti-diuretic activities of the ethanol and aqueous extracts of Alismatis rhizoma

Ethnopharmacological relevance

Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in Asia and Europe. In this paper, we report the diuretic activities of the ethanol extract (EE) and the aqueous extract (AE) of A. rhizoma (AR).

Materials and methods

The EE and AE were orally administered to rats. The urinary excretion rate and pH, and electrolyte excretion were measured in the urine of saline-loaded rats.

Results

The results showed that EE could increase the urine output at 2.5, 5 and 10 mg/kg doses but decrease the urine output at 20, 40 and 80 mg/kg doses compared with the control group. The 5 and 10 mg/kg doses of EE increased the urine electrolyte excretion, but the effects on Na⁺/K⁺ values were too weak to reach statistical significance. The Na⁺ excretion and Cl⁻ excretion were markedly decreased with the 20, 40 and 80 mg/kg doses of EE, but the effect on K⁺ excretion was notably slight. All of the tested doses of AE produced an increase in urinary excretion, but the increase did not reach statistical significance.

Conclusions

This study identified that EE but not AE presents a notable diuretic effect, and EE had diuretic and anti-diuretic effects, which appears to be related to the sodium–chloride co-transporter in the renal distal convoluting tubule. This study demonstrated for the first time that the EE of AR has a dual effect on renal function, including promotion of diuretic activity at lower doses and inhibiting diuretic activity at higher doses, and the AR dose should be given more attention in clinical applications. This study will play a critical and guiding role in the dosing of AR as a diuretic drug in clinical applications.     

Lipid peroxidation and cyclooxygenase enzyme inhibitory activities of acidic aqueous extracts of some dietary supplements

The botanical supplement market is growing at a fast pace with more and more people resorting to them for maintaining good health. Echinacea, garlic, ginkgo, ginseng, Siberian ginseng, grape seed extract, kava kava, saw palmetto and St John's wort are some of the popular supplements used for a variety of health benefits. These supplements are associated with various product claims, which suggest that they possess cyclooxygenase (COX) enzyme and lipid s inhibitory activities. COX enzymes are found to be at elevated levels in inflamed and cancerous cells. To test some of the product claims, selected supplements were analysed for their ability to inhibit COX-1 and -2 enzymes and lipid peroxidation in vitro. The supplements were extracted with acidified water (pH 2) at 37 degrees C to simulate the gastric environment. The supplements tested demonstrated varying degrees of COX enzyme inhibition (5-85% for COX-1 and 13-28% for COX-2). Interestingly, extracts of garlic (Meijer), ginkgo (Solaray), ginseng (Nature's Way), Siberian ginseng (GNC, Nutrilite, Solaray, Natrol), kava kava (GNC, Sundown, Solaray) and St John's wort (Nutrilite) selectively inhibited COX-2 enzyme. These supplements also inhibited lipid peroxidation in vitro (5-99%). The results indicated that the consumption of these botanical supplements studied possess health benefits.     

Antiinflammatory and anti-ulcerogenic activities of the organic extracts of Tanacetum microphyllum DC. in rats

Extracts of Tanacetum microphyllum DC. (Compositae) have been investigated for antiinflammatory and anti-ulcerogenic activity in the rat. In adjuvant-carrageenan-induced inflammation (ACII), orally administered organic extracts of T. microphyllum (hexane, dichloromethane, ethyl acetate and methanol) inhibited both the acute and chronic phases of this experimental model of inflammation, but mainly the chronic phase; the dichloromethane extract was as effective as phenylbutazone. Prior oral administration of T. microphyllum organic extracts prevented the ulcerogenic effect of orally administered indomethacin. Again, the dichloromethane extract exhibited the greatest activity.     

Antioxidant and anticancer activities of organic extracts from Platycodon grandiflorum A. De Candolle roots

This study examined the antioxidant and anticancer activities of the petroleum ether extracts from the roots of Platycodon grandiflorum A. DC, which is a plant used as both a herbal medicine and food in Asia. Extracts from Platycodon grandiflorum in petroleum ether were fractionated (fractions I-V) by silica gel column chromatography using gradient solvents (petroleum ether: ethyl ether, 9:1-5:5, v/v). The antioxidant activities of the fractions were evaluated in terms of their inhibition of lipid peroxidation as well as their free radical scavenging activity. Fraction II, which was extracted at an 8:2 mixture of petroleum ether and ethyl ether, exhibited the greatest antioxidant activity among the fractions. On the other hand, the cytotoxicity of each fraction, which was evaluated by the MTT assay using human cancer cell lines (HT-29, HRT-18 and HepG2), was greatest in fraction III, which was extracted with a 7:3 petroleum ether and ethyl ether mixture. Both fractions, II and III, were sub-fractionated by thin layer chromatography, and the sub-fractions each were screened for their antioxidant and anticancer activities. In addition, the antioxidant activity was closely related to the content of phenolic compounds, and the anticancer active fraction exhibited a typical UV absorbance spectrum of polyacetylene.