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 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.     

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 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.     

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.     

南非传统草药Sutherlandia 抗糖尿病作用的研究

目的：观察南非传统草药Sutherlandia水提物对糖脂代谢的影响。方法：腹腔注射链脲佐菌素（STZ）并高脂饲料喂养诱导2型糖尿病大鼠模型。随机分为正常组、模型组、吡格列酮组、Sutherlandia组。观察体质量、口服糖耐量试验（OGTT）、血甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白-胆固醇（LDL-C）、高密度脂蛋白-胆固醇（HDL-C）指标的改变,Western Blot法检测各组大鼠骨骼肌胰岛素受体底物（IRS-1）表达情况。结果：与正常组比较,模型组大鼠体质量降低,OGTT、TG、TC、LDL-C指标明显升高（P<0.05）,多饮、多食、多尿症状明显,IRS-1 蛋白表达明显降低（P<0.05）;治疗后,与模型组比较,Sutherlandia组及吡格列酮组的体质量未见明显增长,Sutherlandia组及吡格列酮组血糖、TG、TC均明显降低（P<0.05或P<0.01）,二者之间无统计学差异,Sutherlandia组及吡格列酮组骨骼肌中IRS-1蛋白表达明显升高（P<0.05）,二者之间无统计学差异。结论：腹腔注射STZ并高糖高脂饲料喂养诱导2 型糖尿病大鼠模型存在糖脂代谢紊乱;南非传统草药Sutherlandia可明显降低其血糖水平,改善血脂代谢,提高胰岛素水平;Sutherlandia可提高IRS-1骨骼肌中的表达水平,进而改善胰岛素抵抗,降低血糖,其确切的作用途径有待进一步深入研究。     

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.     

Punica granatum flower extract, a potent alpha-glucosidase inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats

Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and has been proposed as an independent risk factor for cardiovascular diseases. The flowering part of Punica granatum Linn. (Punicaceae) (PGF) has been recommended in Unani literature as a remedy for diabetes. We investigated the effect and action mechanism of a methanolic extract from PGF on hyperglycemia in vivo and in vitro. Oral administration of PGF extract markedly lowered plasma glucose levels in non-fasted Zucker diabetic fatty rats (a genetic model of obesity and type 2 diabetes), whereas it had little effect in the fasted animals, suggesting it affected postprandial hyperglycemia in type 2 diabetes. In support of this conclusion the extract was found to markedly inhibit the increase of plasma glucose levels after sucrose loading, but not after glucose loading in mice, and it had no effect on glucose levels in normal mice. In vitro, PGF extract demonstrated a potent inhibitory effect on alpha-glucosidase activity (IC50: 1.8 microg/ml). The inhibition is dependent on the concentration of enzyme and substrate, as well as on the length of pretreatment with the enzyme. These findings strongly suggest that PGF extract improves postprandial hyperglycemia in type 2 diabetes and obesity, at least in part, by inhibiting intestinal alpha-glucosidase activity.     

Effect of Sclerocarya birrea (Anacardiaceae) stem bark methylene chloride/methanol extract on streptozotocin-diabetic rats

Sclerocarya birrea (Anacardiaceae) is used as a traditional treatment of diabetes in Cameroon. In this study, we investigated the possible antidiabetic effect of the stem bark extract in diabetic rats. Diabetes was induced by intravenous injection of streptozotocin (STZ, 55 mg/kg) to male Wistar rats. Experimental animals (six per group), were treated by oral administration of plant extract (150 and 300 mg/kg body weight) and metformin (500 mg/kg; reference drug) for comparison, during 21 days. The stem bark methanol/methylene chloride extract of Sclerocarya birrea exhibited at termination, a significant reduction in blood glucose and increased plasma insulin levels in diabetic rats. The extract also prevented body weight loss in diabetic rats. The effective dose of the plant extract (300 mg/kg) tended to reduce plasma cholesterol, triglyceride and urea levels toward the normal levels. Four days after diabetes induction, an oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats. The results showed a significant improvement in glucose tolerance in rats treated with Sclerocarya birrea extract. Metformin, a known antidiabetic drug (500 mg/kg), significantly decreased the integrated area under the glucose curve. These data indicate that Sclerocarya birrea treatment may improve glucose homeostasis in STZ-induced diabetes which could be associated with stimulation of insulin secretion.     

Antidiabetic activity of alcoholic stem extract of Coscinium fenestratum in streptozotocin-nicotinamide induced type 2 diabetic rats

The antidiabetic potential of the alcoholic stem extract of Coscinium fenestratum Colebr. (Menispermaceae), a medicinal plant widely used in the traditional Ayurveda and Siddha systems of medicine for the treatment of diabetes mellitus was evaluated in the STZ-nicotinamide induced type 2 diabetic model. Graded doses of the alcoholic stem extract were administered to normal and experimental diabetic rats for 12 days. Significant (p < 0.05) reduction in fasting blood glucose levels were observed in the normal as well as in the treated diabetic animals. Serum insulin levels were not stimulated in the animals treated with the extract. In addition, changes in body weight, serum lipid profiles, thiobarbituric acid reactive substance levels, glycosylated hemoglobin and liver glycogen levels assessed in the extract treated diabetic rats were compared with diabetic control and normal animals. Significant results were observed in the estimated parameters, thereby justifying the use of the plant in the indigenous system of medicine.     

Hypoglycaemic activity of Anthocleista vogelii (Planch) aqueous extract in rodents

The hypoglycaemic effect of Anthocleista vogelii was studied in mice, rats and rabbits. Aqueous extract of the plant obtained by infusion from finely pulverized root was used. The extract (100, 400 and 800 mg/kg) induced significant hypoglycaemic activity in a dose-related fashion at 2 h after oral administration in mice and rats with ED₂₅ of 250 mg/kg and 350 mg/kg respectively. The extract (800 mg/kg, orally) similarly induced statistically significant lowering of blood glucose levels at 8 h in normoglycaemic rabbits. The extract (400 mg/kg and 800 mg/kg, orally) also caused reduction of blood glucose levels in alloxan-induced diabetic animals. The results of this study indicate that the aqueous extract of the roots of Anthocleista vogelii possess favourable hypoglycaemic activity both in normo and hyperglycaemic animals compared to chlorpropamide as a standard.     

Antihyperglycemic and antihyperlipidemic activities of wild musk melon (Cucumis melo var. agrestis) in streptozotocin-nicotinamide induced diabetic rats

Objective: Wild musk melon (Cucumis melo var. agrestis, CMA) is one of the edible plants form Tamil Nadu. Traditionally, this plant was used as diabetic diet (leaves of CMA with Momordica charantia leaves), but there is no scientific report on antidiabetic action of this plant material. Hence, the current research work was designed to evaluate its evaluate the anti-hyperglycemic and antihyperlipidemic effect of hydroalcoholic extract of CMA leaves (HALEC) in streptozotocin (STZ)-nicotinamide (NIC)-induced diabetic rats. Methods: Diabetes was induced by administration of STZ (60 mg/kg, i.p.) after 15 min of NIC (120 mg/kg i.p.) administration. The diabetic rats were treated with HALEC (300 and 600 mg/kg, p.o., respectively) for 21 d. Results: After the management with HALEC, blood glucose, HbA1c levels, total cholesterol, LDL cholesterol, triglycerides levels, glycogen phosphorylase and glucose-6-phosphatase levels were significantly diminished in diabetic rats. However, haemoglobin level, HDL cholesterol, liver glycogen, total protein, hexokinase, glucose-6-phosphate dehydrogenase levels were significantly increased in HALEC treated diabetic rats. The histopathological studies of the pancreas in HALEC-treated diabetic rats showed almost normal appearance. L6 cell line study revealed the increased glucose uptake activity of HALEC. High performance thin layer chromatography (HPTLC) analysis confirms the presence of active principles such as rutin, gallic acid and quercetin in HALEC. Conclusion: The results indicated that HALEC possess significant antihyperglycemic and antihyperlipidemic activity in STZ-NIC-induced type II diabetic rats with protective effect. This research work will be useful for the isolation of active principles and development of herbal formulation in phytopharmaceuticals.     

Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism in type 2 diabetic rats

This study investigated the effect of aqueous and ethanol soluble solid extracts of guava (Psidium guajava Linn.) leaves on hypoglycemia and glucose metabolism in type 2 diabetic rats. Low-dose streptozotocin (STZ) and nicotinamide were injected into Sprague-Dawley (SD) rats to induce type 2 diabetes. Acute and long-term feeding tests were carried out, and an oral glucose tolerance test (OGTT) to follow the changes in plasma glucose and insulin levels was performed to evaluate the antihyperglycemic effect of guava leaf extracts in diabetic rats.The results of acute and long-term feeding tests showed a significant reduction in the blood sugar level in diabetic rats fed with either the aqueous or ethanol extract of guava leaves (p < 0.05). Long-term administration of guava leaf extracts increased the plasma insulin level and glucose utilization in diabetic rats. The results also indicated that the activities of hepatic hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase in diabetic rats fed with aqueous extracts were higher than in the normal diabetic group (p < 0.05). On the other hand, diabetic rats treated with the ethanol extract raised the activities of hepatic hexokinase and glucose-6-phosphate dehydrogenase (p < 0.05) only. The experiments provided evidence to support the antihyperglycemic effect of guava leaf extract and the health function of guava leaves against type 2 diabetes.     

Evaluation of the mutagenic and antimutagenic effects of South African plants

Dichloromethane and 90% methanol extracts of 42 South African plants were screened for mutagenicity and antimutagenicity using the Salmonella/microsome mutagenicity assay (Ames) against Salmonella typhimurium TA98 and TA100 bacterial strains in the presence and absence of metabolic activator S9. The methanol extracts from whole plants of Helichrysum simillimum, Helichrysum herbaceum and Helichrysum rugulosum indicated mutagenicity. These are the first reported tests on the mutagenicity of Helichrysum species. Six species indicated antimutagenic properties, all in the presence of S9: methanol leaf extract of Bauhinia galpinii, and dichloromethane leaf extracts of Bauhinia galpinii, Clerodendrum myricoides, Datura stramonium, Buddleja saligna, Millettia sutherlandii and Sutherlandia frutescens.     

Hypoglycemic effect of Suaeda fruticosa in streptozotocin-induced diabetic rats

The purpose of this study was to examine the hypoglycemic activity of the aqueous extract of the aerial part of Suaeda fruticosa (SF) in normal and streptozotocin-induced diabetic rats. The aqueous extract was administered intravenously (i.v.) and the blood glucose changes were determined within 4 h after starting the treatment. Plasma insulin, cholesterol and triglycerides levels were also determined. The aqueous extract at a dose of 192 mg/kg produced a significant decrease in blood glucose levels in normal rats (P < 0.05), and even more in diabetic rats (P < 0.001). This hypoglycemic effect might be due to an extra-pancreatic action of the aqueous extract of SF, since that the levels of plasma insulin were unchanged between the values before and after treatment. In the other hand, the effect of the aqueous extract on the plasma cholesterol were also significant in both normal and diabetic rats (P < 0.05). But, there is no significant effect of SF on plasma triglycerides in both groups. In order to characterize the active principle(s), which could be responsible for the therapeutic effect, preliminary phytochemical analysis of the aqueous extract of the plant has been investigated.     

Anti-hyperglycaemic activity of the aqueous extract of Origanum vulgare growing wild in Tafilalet region

The effect of an aqueous extract of Origanum vulgare (OV) leaves on blood glucose levels was investigated in normal and streptozotocin (STZ) diabetic rats. In normal rats, the blood glucose levels were slightly decreased 6 h after a single oral administration (P<0.05) as well as 15 days after once daily repeated oral administration of aqueous OV extract (P<0.05) (20 mg/kg). After a single dose or 15 daily doses, oral administration of the aqueous extract (20 mg/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (P<0.001). In STZ rats, the blood glucose levels were normalised from the fourth day after daily repeated oral administration of aqueous OV extract (20 mg/kg) (P<0.001). However, this effect was less pronounced 2 weeks after daily repeated oral administration of OV extract. In addition, no changes were observed in basal plasma insulin concentrations after treatment in either normal or STZ diabetic rats indicating that the aqueous OV extract acted without changing insulin secretion. We conclude that an aqueous extract of OV exhibits an anti-hyperglycaemic activity in STZ rats without affecting basal plasma insulin concentrations.     

Antihyperglycaemic effect of Mangifera indica in rat.

The leaves of Mangifera indica are used as an antidiabetic agent in Nigerian folk medicine. To determine whether or not there is a scientific basis for this use, the effect of the aqueous extract of the leaves on blood glucose level was assessed in normoglycaemic, glucose - induced hyperglycaemic and streptozotocin (STZ)-induced diabetic rats. The aqueous extract given orally (1 g/kg) did not alter the blood glucose levels in either normoglycaemic or STZ-induced diabetic rats. In glucose - induced hyperglycaemia, however, antidiabetic activity was seen when the extract and glucose were administered simultaneously and also when the extract was given to the rats 60 min before the glucose. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg) under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity. This action may be due to an intestinal reduction of the absorption of glucose. However, other different mechanisms of action cannot be excluded.     

The effect of Anethum graveolens L. (dill) on corticosteroid induced diabetes mellitus: involvement of thyroid hormones

An investigation was made to evaluate the role of Anethum graveolens L. (dill) leaf extract in the regulation of corticosteroid-induced type 2 diabetes mellitus in female rats. In dexamethasone-treated animals (1 mg/kg for 22 days) an increase in serum concentration of insulin and glucose and in hepatic lipid peroxidation (LPO) was observed. However, there was a decrease in serum concentration of thyroid hormones and in the endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) in liver. In animals treated with an equivalent amount of dexamethasone for a similar period (22 days) when received the leaf extract (100 mg/kg b.wt/d.) for last 15 days a decrease in the concentration of both serum glucose and insulin was observed, indicating the potential of the plant extract in the regulation of corticosteroid-induced diabetes. Dexamethasone-induced alterations in the levels of thyroid hormones as well as in hepatic LPO, SOD, CAT and GSH were also reversed by the plant extract.