Beetle (Ulomoides dermestoides) fat improves diabetes: effect on liver and pancreatic architecture and on PPARgamma expression

Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect.

Evaluation of cytogenotoxicity, antioxidant and hypoglycemiant activities of isolate compounds from Mansoa hirsuta D.C. (Bignoniaceae)

ABSTRACT Mansoa hirsuta (Bignoniaceae) is a native plant from caatinga in Brazilian semiarid. This plant has been locally used as antimicrobial and hypoglycemiant agents, but their action mechanisms and toxicity remain largely unknown. Therefore, we evaluated the composition and antioxidant, cytoprotective and hypoglycemiant effects of raw extract, fractions and compounds from leaves of M. hirsuta. The cytogenotoxic effects of ursolic and oleanolic acids, the main phytotherapic components of this plant, were assessed. The raw extract and fractions presented steroids, saponins, flavonols, flavanonols, flavanones, xanthones, phenols, tannins, anthocyanins, anthocyanidins and flavonoids. The ethyl acetate fraction inhibited efficiently the cascade of lipid peroxidation while the hydroalcoholic fraction was richer in total phenols and more efficient in capturing 2,2-diphenyl-1-picrylhydrazyl (·DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS·+) radicals. The isolated fraction of M. hirsuta also inhibited the α-amylase activity. Cytotoxic effects were absent in both raw extract and fractions while ursolic+oleanolic acids were efficient in protecting cells after exposure to hydrogen peroxide. Moreover, this mixture of acid shad no significant interference on the mitotic index and frequency of nuclear and/or chromosomal abnormalities in Allium cepa test. Therefore, M. hirsuta represents a potential source of phytochemicals against inflammatory and oxidative pathologies, including diabetes.

Trichuris trichiura in a post-Colonial Brazilian mummy

Trichuris trichiura is a soil-transmitted helminth which is prevalent in warm, moist, tropical and subtropical regions of the world with poor sanitation. Heavy whipworm can result either in Trichuris dysenteric syndrome - especially in children - or in a chronic colitis. In heavy infections, worms can spread proximally and may cause ileitis. Here we provide first microscopic evidence for a T. trichiura adult worm embedded in the rectum of a post-Colonial Brazilian adult mummy. During Colonial and post-Colonial times, many European chroniclers described a parasitic disease named Maculo whose symptomatology coincides with heavy helminthiasis. Based on our findings and on comparison of ancient textual evidence with modern description of heavy whipworm, we feel confident in considering that the two syndromes are expressions of the same pathological condition.

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. .

Beneficial effects of Lagenaria siceraria (Mol.) Standley fruit epicarp in animal models.

Lagenaria siceraria (Mol.) Standley fruit (bottle gourd), a commonly used vegetable in India is described as cardiotonic and as a general tonic in Ayurveda. Keeping in view the presence of free radical scavenging activity in L. siceraria and involvement of free radicals in the development of various disorders, present studies were designed to evaluate the ethanolic extract of L. siceraria fruit against the disorders where free radicals play a major role in pathogenesis. The extract was found effective as hepatoprotective, antioxidant, antihyperglycemic, immunomodulatory, antihyperlipidemic and cardiotonic agent. The results showed that the radical scavenging capacity of L. siceraria fruit may be responsible for various biological activities studied.

Preliminary studies on antihyperglycemic effect of aqueous extract of Brassica nigra (L.) Koch in streptozotocin induced diabetic rats.

In the streptozotocin induced diabetic rats treated separately with aqueous, ethanol, acetone and chloroform extracts of the seeds of B. nigra, the increase in serum glucose value between 0 and 1 hr of glucose tolerance test (GTT) was the least (29 mg/dl) in aqueous extract treated animals while it was 54, 44 and 44 mg/dl with chloroform, acetone and ethanol extracts respectively. In further studies carried out with aqueous extract, the effective dose was found to be 200 mg/kg body weight in GTT. Administration of 200 mg/kg body weight of aqueous extract to diabetic animals daily once for one month brought down fasting serum glucose (FSG) levels while in the untreated group FSG remained at a higher value. In the treated animals the increase in glycosylated hemoglobin (HbA1c) and serum lipids was much less when compared with the levels in untreated diabetic controls. These findings suggest that further studies with the aqueous extract of B. nigra seeds on its antidiabetic activity would be useful.

Isolation and intracellular localization of insulin-like proteins from leaves of Bauhinia variegata

Evidence based on immunological cross-reactivity and anti-diabetic properties has suggested the presence of insulin-like peptides in plants. The objective of the present study was to investigate the presence of insulin-like proteins in the leaves of Bauhinia variegata ("pata-de-vaca", "mororó"), a plant widely utilized in popular medicine as an anti-diabetic agent. We show that an insulin-like protein was present in the leaves of this plant. A chloroplast protein with a molecular mass similar to that of bovine insulin was extracted from 2-mm thick 15 percent SDS-PAGE gels and fractionated with a 2 x 24 cm Sephadex G-50 column. The activity of this insulin-like protein (0.48 mg/mL) on serum glucose levels of four-week-old Swiss albino (CF1) diabetic mice was similar to that of commercial swine insulin used as control. Further characterization of this molecule by reverse-phase hydrophobic HPLC chromatographic analysis as well as its antidiabetic activity on alloxan-induced mice showed that it has insulin-like properties. Immunolocalization of the insulin-like protein in the leaves of B. variegata was performed by transmission electron microscopy using a polyclonal anti-insulin human antibody. Localization in the leaf blades revealed that the insulin-like protein is present mainly in chloroplasts where it is also found associated with crystals which may be calcium oxalate. The presence of an insulin-like protein in chloroplasts may indicate its involvement in carbohydrate metabolism. This finding has strengthened our previous results and suggests that insulin-signaling pathways have been conserved through evolution.

Hypoglycemic activity of polysaccharide fractions containing ß-glucans from extracts of Rhynchelytrum repens (Willd.) C.E. Hubb., Poaceae

ß-Glucans are soluble fibers with physiological functions, such as interference with absorption of sugars and reduction of serum lipid levels. The objective of the present study was to analyze the distribution of ß-glucans in different tissues of the African grass species Rhynchelytrum repens and also to evaluate their hypoglycemic activity. Leaf blades, sheaths, stems, and young leaves of R. repens were submitted to extraction with 4 M KOH. Analysis of the fractions revealed the presence of arabinose, glucose, xylose, and traces of rhamnose and galactose. The presence of ß-glucan in these fractions was confirmed by hydrolyzing the polymers with endo-ß-glucanase from Bacillus subtilis, followed by HPLC analysis of the characteristic oligosaccharides produced. The 4 M KOH fractions from different tissues were subjected to gel permeation chromatography on Sepharose 4B, with separation of polysaccharides with different degrees of polymerization, the highest molecular mass (above 2000 kDa) being found in young leaves. The molecular mass of the leaf blade polymers was similar (250 kDa) to that of maize coleoptile ß-glucan used for comparison. The 4 M KOH fraction injected into rats with streptozotocin-induced diabetes showed hypoglycemic activity, reducing blood sugar to normal levels for approximately 24 h. This performance was better than that obtained with pure ß-glucan from barley, which decreased blood sugar levels for about 4 h. These results suggest that the activity of ß-glucans from R. repens is responsible for the use of this plant extract as a hypoglycemic drug in folk medicine.

Phytochemical determination and extraction of Momordica charantia fruit and its hypoglycemic potentiation of oral hypoglycemic drugs in diabetes mellitus (NIDDM).

Momordica charantia (MC) fruit was subjected to phytochemical and pharmacological interaction studies with oral hypoglycemis in NIDDM patients. Phytochemical, chromatographical analysis and extraction of methanolic MC fruit soft (semi-solid form) in CCl4 + C6H6 solvent system yielded 15 diverse chemical constituents--alkaloids, glycosides, aglycone, tannin, sterol, phenol and protein. The CCl4 + C6H6 MC soft extract was used orally in a dose of 200 mg twice daily (BD) for pharmacological interactions with two diversely acting oral hypoglycemic agents--1) metformin BD and 2) glibenclamide BD in 15 patients of either sex (52-65 years of age) of NIDDM. It was observed that with CCl4 + C6H6 MC soft extract plus half doses of metformin or glibenclamide or both in combination caused hypoglycemia greater than that caused by full doses used in the study with 7 days treatment. Conclusively the extract acts in synergism with oral hypoglycemics and potentiates their hypoglycemia in NIDDM.

Mechanism of action of a hypoglycemic principle isolated from fenugreek seeds.

Mechanism of action of an orally active hypoglycemic principle isolated from water extract of seeds of Trigonella foenum graecum (fenugreek) was investigated in alloxan induced subdiabetic and overtly diabetic rabbits of different severities. The active principle was orally administered to the subdiabetic and mild diabetic rabbits (five in each group) at a dose of 50 mg/kg body weight for 15 days. The treatment produced significant attenuation of the glucose tolerance curve and improvement in the glucose induced insulin response, suggesting that the hypoglycemic effect may be mediated through stimulating insulin synthesis and/or secretion from the beta pancreatic cells of Langerhans. Prolonged administration of the same dose of the active principle for 30 days to the severely diabetic rabbits (n = 5) lowered fasting blood glucose significantly, but could elevate the fasting serum insulin level to a much lower extent, which suggests an extra-pancreatic mode of action for the active principle. The effect may also be by increasing the sensitivity of tissues to available insulin. The hypoglycemic effect was observed to be slow but sustained, without any risk of developing severe hypoglycemia.

Hypoglycemic effect of Hibiscus rosa sinensis L. leaf extract in glucose and streptozotocin induced hyperglycemic rats.

Investigations were carried out to evaluate the effect of aqueous extract of H. rosa sinensis leaves on blood glucose level and glucose tolerance using Wistar rats. Repeated administration of the extract (once a day for seven consecutive days), at an oral dose equivalent to 250 mg kg(-1), significantly improved glucose tolerance in rats. The peak blood glucose level was obtained at 30 min of glucose load (2 g kg(-1)), thereafter a decreasing trend was recorded up to 120 min. The data exhibit that repeated ingestion of the reference drug tolbutamide, a sulphonylurea and the extract brings about 2-3 fold decrease in blood glucose concentration as compared to single oral treatment. The results clearly indicate that tolbutamide improves the glucose tolerance by 91% and extract does so only by 47%. At 250 mg kg(-1), the efficacy of the extract was 51.5% of tolbutamide (100mg kg(-1)). In streptozotocin diabetic rats, no significant effect was observed with the extract, while glibenclamide significantly lowered the glucose level up to 7 hr. These data suggest that hypoglycemic activity of H. rosa sinensis leaf extract is comparable to tolbutamide and not to glibenclamide treatment.

Hypoglycemic activity of bio-tea in mice.

Administration of bio-tea (1.71 ml/kg) to normal albino mice caused hypoglycemia after 30 min which reached to maximum after 2 hr with a significant decrease in blood sugar level (BSL) and became normal beyond 8 hr. In alloxan-induced diabetic albino mice, repeated treatments of bio-tea for 3 days (five doses) brought about a significant fall in mean BSL. Continuous decrease in BSL was observed after 4 hr of administration of last dose of bio-tea. Hypoglycemic effect was persistent in alloxan-induced diabetic mice. Effect on glucose tolerance test showed a significant fall in BSL of bio-tea treated animals after 1 hr of glucose treatment indicating hypoglycemic effect of bio-tea.

Hypoglycaemic activity of extracts from soft corals of Andaman and Nicobar coasts in rats.

The ethylacetate extract of soft corals collected from Andaman and Nicobar Coasts were screened for hypoglycaemic activity in fasting rats. Rats were divided into 5 groups. Group I received 0.5 ml of 5% gum acacia suspension (control). Group II received the extract of Cladiella australis (CAS), at a dose of 250 mg/kg. Group III received the extract of Sinularia new species (SNS), at a dose of 75 mg/kg. Group IV received the extract of Lamnalia new species (LNS), at a dose of 400 mg/kg and Group V received the extract of 250MF-CBR-13 at a dose of 250 mg/kg. All extracts were administered orally. Blood samples, collected before the administration of test extracts and also at 2, 4, 6, and 8 hr after treatment, were analysed for glucose content. The percentage blood glucose reduction from that of control was also calculated. A very promising hypoglycaemic activity was observed in rats with CAS at 8 hr (42.3%), with SNS at 4 hr (28.34%) and 6 hr (40.6%), with LNS at 6 hr (32.38%) and with MF-CBR-13 at 6 hr (20.25%).

Diuretic, hypotensive and hypoglycaemic effect of Phyllanthus amarus.

Diuretic, hypotensive and hypoglycaemic effects of Phyllanthus amarus (syn. Phyllanthus niruri) on human subjects were assessed. Nine mild hypertensives (four of them also suffering from diabetes mellitus) were treated with a preparation of the whole plant of P. amarus for 10 days. Suitable parameters were studied in the blood and urine samples of the subjects, along with physiological profile and dietary pattern before and after the treatment period. Significant increase in 24 hr urine volume, urine and serum Na levels was observed. A significant reduction in systolic blood pressure in non-diabetic hypertensives and female subjects was noted. Blood glucose was also significantly reduced in the treated group. Clinical observations revealed no harmful side effects. These observations indicate that P. amarus is a potential diuretic, hypotensive and hypoglycaemic drug for humans.

Mechanism of blood sugar lowering by a swerchirin-containing hexane fraction (SWI) of Swertia chirayita.

Mechanism of blood sugar lowering by the crude/impure swerchirin (SWI) isolated from the hexane fraction of Swertia chirayita was investigated. Single oral administration of SWI (50 mg/kg, body wt) to fed CF rats induced about 60% (max.) fall in blood glucose by 7 hr post-treatment. This was associated with marked depletion of aldehyde-fuchsin stained beta-granules and immunostained insulin in the pancreatic islets. In vitro, glucose uptake and glycogen synthesis by muscle (diaphragm) was significantly enhanced by the serum of SWI-treated rat. At 100, 10 and 1 microM final concentration, SWI greatly enhanced glucose (16.7 mM)-stimulated insulin release from isolated islets. It is therefore concluded that SWI lowers blood glucose level by stimulating insulin release from islets of Langerhans.

Hypoglycemic effects of Coccinia indica: inhibition of key gluconeogenic enzyme, glucose-6-phosphatase.

Coccinia indica (Family: Cucurbitaceae, locally known as telakucha) leaves were extracted with 95% ethanol. Following evaporation of the solvents, the residue was suspended in distilled water. When this suspension was fed orally to male normal-fed and 48-hr starved rats, the blood glucose was lowered 21% (P less than 0.01) in normal-fed and 24% (P less than 0.001) in 48-hr starved animals respectively. Starvation had induced a 3-fold increase in the activity of glucose-6-phosphatase and this activity was depressed 19% (P less than 0.05) by extract feeding while basal activity of the enzyme in normal-fed rats remained unaffected. Consistent with the depression of glucose-6-phosphatase, urea cycle enzyme arginase was also depressed 21% (P less than 0.001) and 12% (P less than 0.01) in the liver of 48 hr-starved and normal-fed animals respectively. Unlike glucose-6-phosphatase, starvation induced levels of gluconeogenic enzymes alanine aminotransferase and aspartate aminotransferase were not affected by Coccinia extract. These results suggest that the hypoglycemic effect of C. indica is partly due to the repression of the key gluconeogenic enzyme glucose-6-phosphatase.