Hypoglycemic effect of a leaf extract of Pseuderanthemum palatiferum (Nees) Radlk. in normal and streptozotocin-induced diabetic rats

Ethnopharmacological relevance

Pseuderanthemum palatiferum (Nees) Radlk (Acanthaceae) was first found in Northern Vietnam and expanded throughout the country including the Mekong Delta region. The leaves of this plant are recommended in folk medicine of Vietnam and Thailand for promoting and treating various diseases including hypertension, diarrhea, arthritis, hemorrhoids, stomachache, tumors, colitis, bleeding, wounds, constipation, flu, colon cancer, nephritis, and diabetes.

Aim of the study

The hypoglycemic effect of an 80% ethanolic leaf extract from the leaves of Pseuderanthemum palatiferum (PPE) was investigated in normal and streptozotocin (STZ)-induced diabetic rats.

Materials and methods

The PPE was administered daily and orally to the rats at the doses of 250, 500, and 1000 mg/kg body weight (b.w.) for 14 days. The levels of fasting plasma glucose (FPG), serum insulin, and biochemical data such as blood urea nitrogen (BUN), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and alkaline phosphatase (ALP) were evaluated. The hypoglycemic effect of PPE was compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.).

Results

FPG and serum insulin in normal rats were not significantly different from the control and test groups in all dosages. The treated diabetic rats which had received PPE and glibenclamide showed significantly (p < 0.05) decreased FPG and increased serum insulin levels at the end of the experiment. The hypoglycemic effect of PPE at the dose of 250 mg/kg b.w. was significantly (p < 0.05) more effective than that of glibenclamide. The serum insulin in PPE fed diabetic rats at the dose of 250 mg/kg b.w. was not different from those which had received glibenclamide, and this dose was significantly (p < 0.05) more effective than PPE at the doses of 500 and 1000 mg/kg b.w. while PPE increased HDL and decreased TC, TG, LDL, BUN and ALP in the diabetic rats.

Conclusions

PPE has a beneficial effect in hyperglycemic rats and may prevent the complication of diabetes.     

Antidiabetic and antioxidant effects of extracts from Potentilla discolor Bunge on diabetic rats induced by high fat diet and streptozotocin

Aim of the study

Potentilla discolor Bunge, commonly found at the north temperate and boreal zone, has been used for diabetes in China for a long time. Flavonoids and triterpenoids are two major types of compounds in P. discolor. This study was designed primarily to investigate the effects of total flavonoids extract (TFE) and total triterpenoids extract (TTE) of P. discolor Bunge on blood glucose, lipid profiles and antioxidant parameters on diabetic rats induced by high fat diet and streptozotocin.

Materials and methods

High fat diet-fed and streptozotocin-induced diabetic rats were treated with the TFE and TTE for 15 days, respectively. A range of parameters were tested including fasting blood glucose (FBG), serum insulin (SI), blood lipid profile, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glycosylated serum protein (GSP), and nitric oxide (NO).

Results

Diabetic rats treated with TFE or TTE had decreased concentration of FBG and GSP compared with the control group. Meanwhile, the levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-c) in the TFE or TTE treated diabetic rats were lower, and the high-density lipoprotein cholesterol (HDL-c) level was higher than in the control diabetic rats. Furthermore, the extracts treatment decreased the MDA and NO level, while increased SOD and GSH levels in diabetic rats. Histopathologic examination also showed that the extracts have protective effects on β-cells in diabetic rats which are supported by the increase of SI.

Conclusions

All these experimental results highlighted the hypoglycemic and hypolipidemic properties of the two extracts from Potentilla discolor Bunge on diabetes and its complications, possibly through a strong antioxidant activity and a protective action on β-cells.     

Antidiabetic effect of Symplocos cochinchinensis (Lour.) S. Moore. in type 2 diabetic rats

Aim

Symplocos cochinchinensis (Lour.) S. Moore. is used in Indian system of traditional medicine to treat diabetes mellitus. The present study aims to investigate the antidiabetic efficacy of the hexane extract of Symplocos cochinchinensis leaves in high fat diet-low streptozotocin (STZ) induced type 2 diabetic rats.

Materials and methods

The doses for the study were fixed based on Irwin test. The hypoglycemic effect of the hexane extract of Symplocos cochinchinensis leaves were studied in normal rats. Oral glucose and insulin tolerance tests were carried out. The antihyperglycemic effect of the hexane extract at 250 and 500 mg/kg was studied in high fat diet-low STZ induced type 2 diabetic rats for 28 days.

Results

The extracts showed no adverse effects up to 5 g/kg concentration. In hypoglycemic study, after treatment with hexane extract at 250 and 500 mg/kg the blood glucose was mildly reduced. In oral glucose tolerance test, the treatment with the hexane extract at 250 and 500 mg/kg showed a highly significant reduction of 12.07% and 23.58% in plasma glucose levels, respectively 30 min after glucose load. The insulin tolerance test also showed improved insulin sensitivity after 60 min of insulin treatment. In high fat diet-low STZ induced type 2 diabetic rats, after 28 days treatment with the hexane extract at 250 and 500 mg/kg reduced the plasma glucose level by 17.04% and 42.10%, respectively. A significant reduction in plasma insulin, plasma and hepatic total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) and a significant increase in liver glycogen were observed in treated diabetic rats.

Conclusion

This study demonstrated the potential antidiabetic property of hexane extract of Symplocos cochinchinensis leaves on type 2 diabetes mellitus, thus justifying its traditional usage.     

Antihyperglycemic activity of Selaginella tamariscina (Beauv.) Spring

Aim of the study

The present study was designed to investigate the effects of the EtOH and H₂O extracts of Selaginella tamariscina (Beauv.) Spring on hyperglycemia in diabetic rats and HepG2 cells, and to confirm the active fractions of EtOH extract in HepG2 cells.

Materials and methods

HepG2 cells and type II diabetic rats induced by low-dose streptozotocin (STZ) and high-fat diet (HFD) were used to evaluate the hypoglycemic effect of EtOH and H₂O extracts of Selaginella tamariscina. HepG2 cells were used to evaluate the promotive effect of different fractions of EtOH extract obtained from a polyamide column on glucose utilization.

Results

The results in HepG2 cells indicated that the EtOH extract had a better hypoglycemic effect than the H₂O extract. The results in diabetic rats indicated that both EtOH extract and H₂O extract were able to ameliorate the fasting blood glucose (FBG) level and improve oral glucose tolerance (OGTT). Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c), free fatty acids (FFA), tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and malondialdehyde (MDA) levels in serum were lowered. High density lipoprotein (HDL-c), insulin and superoxide dismutase (SOD) levels in serum were elevated as well as the hepatic glycogen content in diabetic rats. Compared with H₂O extract, the effects of EtOH extract were more marked. The 80% ethanol fraction exhibited a stronger hypoglycemic effect than the aqueous and 50% ethanol fractions, but the 95% ethanol fraction did not show any appreciable effects in HepG2 cells.

Conclusions

The results suggested that the EtOH extract had a better hypoglycemic effect than the H₂O extract; the 80% ethanol fraction from polyamide column had a strong hypoglycemic activity in HepG2 cells.     

Identification of trans-tiliroside as active principle with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinesis

Aim of the study

The present study was carried out to isolate and identify trans-tiliroside as principal compound with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinesis.

Materials and methods

A bioactive compound, trans-tiliroside was isolated from the ethanol extract of Potentilla chinesis and its administration dose was optimized and patented. The normal, alloxan-induced diabetic mice and streptozotocin-induced diabetic rats were used to evaluate the anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects of trans-tiliroside from Potentilla chinesis. Biochemical parameters were assayed in blood samples of different groups of alloxan-induced diabetic mice and streptozotocin-induced diabetic rats.

Results

The level of fasting serum glucose levels, triglycerides (TG) and total cholesterol (TC) in alloxan-induced diabetic mice were significantly decrease after daily oral administration of trans-tiliroside in normal and diabetic mice at doses of 0.4, 0.8 and 1.6 mg/kg/day, for 15 days. Blood glucose level was significant decrease in STZ induced diabetic rats by trans-tiliroside (1.2 and 0.3 mg/kg body weight for 10 weeks). The content of TC, low density lipoprotein (LDL-C) and TG levels were decreased and high density lipoprotein (HDL-C) content was increased, so lipid metabolism was improved. Moreover, trans-tiliroside revealed antioxidant activity as shown by increased activities of superoxide dismutase (SOD), decreased level of malondialdehyde (MDA) in diabetic rats. Histological morphology examination showed that the trans-tiliroside restored the damage of pancreas tissues in rats with diabetes mellitus.

Conclusion

Trans-tiliroside, a constituent from Potentilla chinesis, revealed significant anti-hyperglycemic, anti-hyperlipidemic and antioxidant activities.     

Effect of aqueous extract of the leaves of Acalypha wilkesiana 'Godseffiana' Muell Arg (Euphorbiaceae) on the hematology, plasma biochemistry and ocular indices of oxidative stress in alloxan induced diabetic rats

Ethnopharmacological relevance

The leaves of Acalypha wilkesiana are used in Southern Nigeria for the management of hypertension and diabetes mellitus. In this study, the effect of aqueous extract of the leaves of Acalypha wilkesiana on the hematology, plasma biochemistry and ocular indices of oxidative stress was investigated in alloxan induced diabetic rats.

Methodology

Diabetes mellitus was induced by injection of alloxan (80 mg/kg body weight), via the tail vein. The extract was administered orally at 100, 200 and 300 mg/kg (both to normal and diabetic rats), and metformin at 50 mg/kg.

Results

On gas chromatographic analysis of the extract, twenty nine known flavonoids were detected, consisting mainly of 29.77% apigenin, 14.97% quercetin, 11.12% naringenin, 10.62% kaempferol, 9.05% (−)-epicatechin and 4.04% (+)-catechin. Tannic acid and β-sitosterol were also detected. Compared to test control, the treatment lowered (significantly, P < 0.05) plasma glucose, triglyceride, conjugated bilirubin levels, atherogenic index of plasma, plasma alanine transaminase activity, total protein and total bilirubin, aspartate transaminase activity and unconjugated bilirubin, plasma urea, blood urea nitrogen and ocular malondialdehyde contents, lymphocyte and monocyte counts, and not significantly, plasma very low density lipoprotein cholesterol, but increased (significantly, P < 0.05) plasma calcium contents, total white cell and platelet counts, mean cell volume and ocular ascorbic acid content, and (though not significantly) plasma high density lipoprotein cholesterol level, red cell and neutrophil counts.

Conclusions

This study showed that the extract was hypoglycemic, positively affected the hemopoietic system and integrity and function (dose dependently) of the liver and kidney of the diabetic rats; improved the lipid profile and had no deleterious effect on red cell morphology. It also protected against oxidative stress in ocular tissues. This study also revealed the presence of pharmacologically active compounds in the leaf extract. All of these highlights the cardioprotective potential of the leaves of Acalypha wilkesiana and support its use in traditional health practices for the management of diabetes mellitus.     

Evaluation of antihyperglycemic activity of Cocos nucifera Linn. on streptozotocin induced type 2 diabetic rats

Ethnopharmacological relevance

The plant Cocos nucifera Linn. (Arecaceae) is commonly known as coconut. Traditionally the juice of the young spadix when fresh is used in diarrhea and diabetes.The objective of the present study was to investigate the effect of antidiabetic activity and effect on lipid profile as well as cardioprotective effect of hydro-methanol extract of Cocos nucifera (HECN) on streptozotocin (STZ)-induced diabetic rats.

Materials and methods

After 72 h of STZ (50 mg/kg, b.w. i.p.) administration, animals showing plasma sugar level more than 250 mg/dl were considered as diabetic rat. Fasting blood glucose (FBG) levels were measured on 0th (after 72 h of STZ), 5th, 10th, and 15th day. On the 15th day all the animals were sacrificed and the serum biochemical parameters and antioxidant enzyme status were measured.

Results

HECN treated animals showed a significant reduction in FBG level as compared with diabetic control group. Serum enzyme level (SGOT, SGPT, SALP), lipid peroxidation and antioxidant enzyme level such as CAT, GSH, SOD and cholesterol and triglycerides in the HECN treated groups were restored towards normal level as compared to diabetic control groups and the values were comparable with the standard groups (glibenclamide).

Conclusion

Improvement in the FBG and the restoration of all other biomarker as well as enzymes indicates that HECN has very good antidiabetic activity with very low side effects and provides a scientific rationale for the use as an antidiabetic agent.     

Anti-diabetic activity of Chiliadenus iphionoides

Ethnopharmacological relevance

Chiliadenus iphionoides (Boiss. & Blanche) Brullo (Asteraceae), a small aromatic shrub found throughout Israel, is used traditionally in the treatment of diabetes mellitus. In this study, Chiliadenus iphionoides anti-diabetic activity was characterized using cellular and animal models.

Materials and methods

Pancreatic β cells, adipocytes, and skeletal myotubes were treated with an ethanolic extract of Chiliadenus iphionoides to study the extract's effects on insulin secretion and glucose uptake. The sand rat (Psammomys obesus) was used to study Chiliadenus iphionoides acute and long term effects in vivo. An oral starch tolerance test was performed as well as a 30 day feeding study.

Results

Chiliadenus iphionoides extract increased insulin secretion in β cells as well as glucose uptake in adipocytes and skeletal myotubes. The extract also displayed hypoglycemic activity in the diabetic sand rat.

Conclusions

Chiliadenus iphionoides exhibits considerable anti-diabetic activity, although the mechanism of action remains to be determined.     

Hypoglycemic activity of Thai medicinal plants selected from the Thai/Lanna Medicinal Recipe Database MANOSROI II

Ethnopharmacological relevance

Five medicinal plants including Anogeissus acuminata (Roxb. ex DC.) Gills. & Perr. (Combretaceae), Catunaregam tormentosa (Bl. ex DC.) Tirveng (Rubiaceae), Dioecrescis erythroclada (Kurz) Tirveng. (Rubiaceae), Mimosa pudica Linn. var. hispida Bren. (Fabaceae), and Rauwolfia serpentina (L). Benth. ex Kurz. (Apocyanaceae), which have been traditionally used for the treatment of diabetes mellitus and other diseases for several generations by the Thai-Lanna people in the Northern part of Thailand were investigated for their hypoglycemic activity in normoglycemic and alloxan, induced diabetic mice.

Materials and methods

The aqueous extracts of the selected five medicinal plants were tested for their phytochemicals, free radical scavenging activity and hypoglycemic activity on 18 h fasted normoglycemic and alloxan induced diabetic mice over a period of 4 h comparing with the standard anti-diabetic drugs (insulin and glibenclamide) using two way analysis of variance (ANOVA) as analytical tool. Phytochemical analysis was performed using the standard methods while 2,2-diphenyl-1-picrylhydrazine (DPPH) was used to test for free radical scavenging activities of the medicinal plant extracts.

Results

Phytochemicals detected in the extracts were glycosides, xanthones, tannins, alkaloids and saponins. Anogeissus acuminata showed the highest free radical scavenging activity with the IC₅₀ value of 11.00 μg/mL which was 4 folds of the standard ascorbic acid. Significant reduction in fasting blood glucose (FBG) levels of the normoglycemic mice was observed at 4 and 3 h with the extracts of Mimosa pudica (200 mg/kg bw) and Rauwolfia serpentina (100 mg/kg bw), and percentage decreases of 46.15 and 27.94% which were 0.76 and 1.47; 0.53 and 0.91 folds of insulin and glibenclamide, respectively. In alloxan induced diabetic mice, all extracts showed significant (p < 0.05) hypoglycemic activity, with the maximum FBG reduction of 78.96 at 100 mg/kg bw shown by Anogeissus acuminata at the 4 h. The hypoglycemic activity of Anogeissus acuminata was comparable to insulin (1.1 fold), but more potent than glibenclamide (1.76 folds).

Conclusions

Medicinal plants selected from the Thai/Lanna Medicinal Plant Recipe Database MANOSROI II showed hypoglycemic activity in normoglycemic and alloxan induced diabetic mice. This study confirmed the traditional use of these medicinal plants for the treatment of diabetes mellitus and the thiazolidiendiones mimic hypoglycemic effects of the medicinal plants was suggested.     

Mechanism of anti-hyperglycemic action of Vatairea macrocarpa (Leguminosae): Investigation in peripheral tissues

Aim of the study

Previous studies in our laboratory have demonstrated that the treatment of diabetic rats during 21 days with V. macrocarpa stem-bark ethanolic extract (VmE), reduced glycemia, urinary glucose and urea, increased liver glycogen content and improved other parameters diabetes related. The objective of this study was to evaluate if the anti-hyperglicemic mechanisms of VmE could be caused by improvement in the insulin signaling pathway in the peripheral tissues (liver, adipose and skeletal muscle).

Material and methods

Streptozotocin-diabetic rats were separated into two groups: diabetic control (DC) and diabetic treated with VmE (DT) during 21 days. The alterations on the insulin signaling in liver, retroperitoneal adipose tissue (RET) and extensor digitorum longus (EDL) muscles were investigated through determination of insulin receptor (IR), protein kinase B/AKT content and AKT phosphorylation levels using Western blotting analysis. This same methodology was used to evaluate the phosphoenolpyruvate carboxykinase (PEPCK) levels in the liver from these animals.

Results

The treatment with the extract increased the content of IR and the basal phosphorylation of AKT in the three tissues. In the liver from diabetic treated group, the insulin-stimulated AKT phosphorylation was higher and the PEPCK protein levels were reduced.

Conclusions

Data from this work suggest that the anti-hyperglycemic activity of stem-bark extract of V. macrocarpa can occur through stimulation of insulin signaling pathways in peripheral tissues from diabetic rats, mainly in liver and adipose tissue, probably promoting increase in the glucose uptake and liver glycogen synthesis. The concomitant decreasing in hepatic PEPCK levels could be associated to inhibition of gluconeogenesis, which can also contribute to glycemia reduction.     

Anti-diabetic activity and potential mechanism of total flavonoids of Selaginella tamariscina (Beauv.) Spring in rats induced by high fat diet and low dose STZ

Aim of the study

To evaluate the anti-diabetic effects of the total flavonoids of Selaginella tamariscina (Beauv.) Spring (TFST), and to explore the pertinent mechanism.

Materials and methods

High fat diet and STZ (35 mg/kg) induced diabetic rats were administered with TFST at graded oral doses (100, 200 and 400 mg/kg/day, ig.) for 8 weeks. A range of parameters, including blood glucose and lipid, serum insulin and glucagon, glucose tolerance, were tested to evaluate its anti-diabetic effects. The determination of protein expression of peroxisome proliferator activated receptor γ (PPAR-γ) in adipose tissue and insulin receptor substrate 1 (IRS-1) in hepatic and skeletal muscle tissues was used to study the mechanism of TFST. Moreover, the preliminary study of TFST on the antioxidant activity was performed.

Results

The TFST possessed anti-diabetic activities as shown by the decreased serum levels of fast blood glucose (FBG), glycosylated hemoglobulin A1C (HbA1c), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), low density lipoprotein-cholesterol (LDL-C) and glucagon, as well as increased serum levels of high density lipoprotein-cholesterol (HDL-C), insulin and C-peptide. TFST also improved the oral glucose tolerance test (OGTT) to a certain degree. Furthermore, TFST increased the protein expression of PPAR-γ in adipose tissue, and increased the protein expressions of IRS-1 in hepatic and skeletal muscle tissues. These benefits were associated with increased superoxide dismutase (SOD) and decreased malondialdehyde (MDA) in serum.

Conclusions

TFST exert beneficial effects on hyperglycosemia and hyperlipoidemia in diabetic rats possibly through regulating the levers of PPAR-γ in adipose tissue and IRS-1 in hepatic and skeletal muscle tissues.     

The efficacy of Prosopis glandulosa as antidiabetic treatment in rat models of diabetes and insulin resistance

Ethnopharmacological relevance

Diabetes mellitus is rampantly increasing and the need for therapeutics is crucial. In recognition of this, untested antidiabetic agents are flooding the market. Diavite™ which is a product consisting solely of the dried and ground pods of Prosopis glandulosa (Torr.) [Fabaceae] is currently marketed as a food supplement with glucose stabilizing properties. However, these are anecdotal claims lacking scientific evidence. The aim of this study was to determine the efficacy of Prosopis glandulosa as an antidiabetic agent.

Materials and methods

Male Wistar rats were rendered (a) type 1 diabetic after an intraperitoneal injection of STZ (40 mg/kg) and (b) insulin resistant after a 16-week high caloric diet (DIO). Zucker fa/fa ZDF rats were used in a pilot study. Half of each group of animals was placed on Prosopis glandulosa treatment (100 mg/kg/day) for 8 weeks and the remaining animals served as age-matched controls. At the time of sacrifice, blood was collected for glucose and insulin level determination, the pancreata of the STZ rats were harvested for histological analysis and cardiomyocytes prepared from the DIO and Zucker fa/fa hearts for determination of insulin sensitivity.

Results

Type 1 diabetic model: Prosopis glandulosa treatment resulted in significant increased insulin levels (p < 0.001), which was accompanied by a significant decrease in blood glucose levels (p < 0.05). Additionally, Prosopis glandulosa treatment resulted in increased small β-cells (p < 0.001) in the pancreata. The body weight of the STZ animals decreased significantly after STZ injection, with Prosopis glandulosa treatment partially preventing this. Zucker fa/fa rats: Prosopis glandulosa treatment significantly reduced fasting glucose levels (p < 0.01) and improved IPGTT, when comparing treated to untreated animals. DIO insulin resistant model: Prosopis glandulosa treatment resulted in an increased basal (p < 0.01) and insulin-stimulated (p < 0.05) glucose uptake by cardiomyocytes prepared from this group.

Conclusions

The present study showed that Prosopis glandulosa treatment moderately lowers glucose levels in different animal models of diabetes, stimulates insulin secretion, leads to the formation of small β-cells and improves insulin sensitivity of isolated cardiomyocytes.     

The hypoglycemic activity of Lithocarpus polystachyus Rehd. leaves in the experimental hyperglycemic rats

Ethnopharmacological relevance

Leaves of Lithocarpus polystachyus Rehd. are used for the treatment of disorders such as diabetes, hypertension, and epilepsy in folk medicine of South China. The possible antidiabetic effects of the leaves were investigated in experimental type 2 and type 1 diabetic rats.

Materials and methods

Type 2 diabetic rats received orally three different extracts of Lithocarpus polystachyus Rehd. leaves for 4 weeks (aqueous extract [ST-1], ethanol extract [ST-2], flavonoid-rich fraction [ST-3]). At the end of the experiment biochemical parameters were tested and livers and pancreases were excised for histological study. After the comparison of the pharmacological test results of the three extracts, the one which showed the best bioactivity was further studied to confirm its antidiabetes effect on both type 2 and type 1 diabetic rats.

Results

Compared to ST-1 and ST-2, ST-3 had better effects on regulation of blood glucose, glycosylated serum protein, cholesterol, triglyceride, malondialdehyde, superoxide dismutase and attenuation of liver injury in type 2 diabetic rats (p < 0.01 or p < 0.05). ST-3 administration for four weeks also significantly reduced the fasting serum insulin and C-peptide level and improved the insulin tolerance (p < 0.05). In type 1 diabetic rats, ST-3 supplement for three weeks caused significant reduction in fasting blood glucose, total cholesterol, triglyceride, urea nitrogen, creatinine and liver mass, along with significantly inhibiting the decline of insulin level compared to diabetic control (p < 0.05 or p < 0.01).

Conclusion

The flavonoid-rich fraction of Lithocarpus polystachyus Rehd. leaves (ST-3) had better beneficial effect than that of the ethanol or aqueous extract in experimental diabetic rats, which means that the bioactivity of the herbal leaves is probably due to the presence of flavonoids. The results also strongly suggest that the antidiabetic effect of ST-3 was possibly through multiple mechanisms of action including blood lipid and antioxidant mediation. The results indicated that the aqueous flavonoid-rich fraction of Lithocarpus polystachyus Rehd. leaves possessed significant protective activity in type 2 and type 1 diabetes.     

Lipoxygenase inhibitory activity of crude bark extracts and isolated compounds from Commiphora berryi

Ethnopharmacological relevance

Commiphora berryi is traditionally used for the treatment of cold and fever as well as for wound healing in the southern parts of India.

Aim of study

The present study was designed to investigate in vitro soybean lipoxygenase inhibitory activity of crude extracts and compounds isolated from Commiphora berryi.

Materials and methods

The bark of Commiphora berryi was extracted with different organic solvents and subjected to chromatographic separation for isolation of bioactive compounds. Structures of isolated compounds were elucidated by spectroscopic methods. The anti-inflammatory activity of bark extracts and bioactive compounds were assessed by in vitro soybean lipoxygenase (SBL) assay.

Results

3β-Hydroxyglutin-5-ene (1), friedelin (2), cycloeucaneol (3) nimbiol (4), sugiol (5), surianol (6), daucosterol (7) and ursolic acid (8) were isolated from crude bark extracts of the Commiphora berryi. The structure of nimbiol (4) was also confirmed by single crystal X-ray analysis. The petroleum ether, methanol, chloroform and ethyl acetate extracts of bark of Commiphora berryi showed SBL inhibitory activity with the IC₅₀ values of 15.3, 54.2, 71.5 and 87.8 μg/ml respectively. Among all the isolates, friedelin (2) showed significant SBL inhibitory activity with IC₅₀ 35.8 μM.

Conclusion

The overall results provide evidence that the studied plant might be a potential source of anti-inflammatory agents.     

Cardioprotective effects of aqueous Schizandra chinensis fruit extract on ovariectomized and balloon-induced carotid artery injury rat models: effects on serum lipid profiles and blood pressure

Aim of the study

The fruit from Schizandra chinensis, a member of the Magnoliaceae family, has been used to treat menopause-related symptoms. We have previously reported that an aqueous extract of Schizandra chinensis fruit (ScEx) caused vascular relaxation via the production of endothelial nitric oxide. Estrogen-like molecules are known to play a protective role in cardiovascular diseases through several mechanisms, but the cardioprotective effects of ScEx have not been clearly demonstrated. Therefore, we investigated the vasculoprotective effects of ScEx on ovariectomized (OVX) and balloon-induced carotid artery injury rat models.

Materials and methods

An aqueous extract of Schizandra chinensis (ScEx) was examined for its cardioprotective effects. To test the arterial response to injury, we applied the balloon-induced carotid artery model to OVX Sprague-Dawley (SD) rats. Rats were subcutaneously administered vehicle, 17β-estradiol (E2; 0.02 or 0.2 mg/kg/day), or ScEx (0.2 or 2.0 mg/kg/day) over the course of the study. Vessel morphology was assessed two weeks after injury. To identify the cardioprotective effects after ScEx treatment, we measured serum lipid profiles and blood pressure levels in the OVX- and sham-operated normotensive and spontaneously hypertensive rats (SHR). Serum lipid profiles were measured in OVX rats after five weeks of treatment with vehicle, E2 (0.5 mg/kg/day), or ScEx (0.5 or 5.0 mg/kg/day). Tail systolic blood pressure in OVX SHR was measured weekly.

Results

In the balloon-induced carotid artery injury model, treatment with E2 (0.2 mg/kg/day) or ScEx (2.0 mg/kg/day) reduced the intimal area and the intima-to-media ratio compared to control animals. Injection of ScEx or E2 reduced body weight gain but did not inhibit the decrease in uterine weight. Treatment with ScEx (5.0 mg/kg/day) or E2 (0.5 mg/kg/day) in OVX SD rats reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C), and TC-(HDL-C)/HDL-C compared to control animals. In OVX rats, treatment with ScEx or E2 also significantly reduced LDL-C compared with the OVX control rats, and systolic blood pressure was significantly attenuated compared to OVX control and the sham control rats.

Conclusions

ScEx treatment restored endothelial function in rats that underwent balloon-induced carotid artery injury, and it reduced serum cholesterol levels in OVX rats. Similar to E2, ScEx exihibited hypotensive effects in OVX SHR. Therefore, ScEx and E2 exhibited similar cardioprotective effects, thereby suggesting that ScEx is a potential candidate to replace estradiol in the prevention and treatment of cardiovascular diseases.     

Polyphenols-rich Vernonia amygdalina shows anti-diabetic effects in streptozotocin-induced diabetic rats

Aim of the study

This study aims to investigate the hypoglycemic properties of Vernonia amygdalina Del. (VA) and its possible mechanisms of action in a single-dose STZ induced diabetic rat model.

Materials and methods

A dose-response study was conducted to determine optimum dose for the hypoglycemic effect of VA in STZ-induced diabetic rats. The optimum dose (400 mg/kg) was used throughout the 28-day chronic study. Body weight, food and water intakes of the rats were monitored daily. Fasting blood serum, pancreas, liver and soleus muscle were collected for biochemical analyses. Chemical composition of VA was analysed using HPLC and LC-ESI-MS.

Results

The study reveals that ethanolic extract of VA contains high level of polyphenols mainly 1,5-dicaffeoyl-quinic acid, dicaffeoyl-quinic acid, chlorogenic acid and luteolin-7-O-glucoside. In an oral glucose tolerance test, 400 mg/kg VA exhibited a significant improvement in glucose tolerance of the STZ-induced diabetic rats. 28-day treatment with 400 mg/kg VA resulted in 32.1% decrease in fasting blood glucose compared to diabetic control. VA also caused significant decrease (18.2% and 41%) in triglyceride and total cholesterol level. Besides, VA showed protective effect over pancreatic β-cells against STZ-induced damage, causing a slight increase in insulin level compared to diabetic control. VA administration also showed positive regulation of the antioxidant system, both enzymatic and non-enzymatic. Furthermore, VA was found to increase expression of GLUT 4 (24%) in rat skeletal muscle. Further tissue fractionation revealed that it can increase the GLUT 4 translocation (35.7%) to plasma membrane as well, suggesting that VA may stimulate skeletal muscle's glucose uptake. This observation is in line with the restoration in skeletal muscle glycogenesis of VA-treated group. However, no alteration was observed in GLUT 1 expression. In addition, VA also suppressed (40% inhibition) one of the key hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase).

Conclusions

VA possesses antihyperglycemic effect, most probably through increasing GLUT 4 translocation and inhibiting hepatic G6Pase. The polyphenols in the extract may be the candidates that are responsible for the above-mentioned biological activities.     

A new TCM formula FTZ lowers serum cholesterol by regulating HMG-CoA reductase and CYP7A1 in hyperlipidemic rats

Ethnopharmacological relevance

Based on a theory of Chinese Medicine, Regulating Gan (liver) to lower lipids that is in brief to regulate the lipid metabolic related factors in the liver will improve serum lipid profile, we have developed Fufang Zhenzhu Tiao Zhi (FTZ) which includes eight herbs that are quality assured. FTZ has been developed with the potential to correct abnormal lipid metabolism. This Chinese herbal medicine has been prescribed for 20 years, which has been issued patent and clinically proven for use in the treatment of dyslipidemia.

Aim of the study

To investigate the cholesterol-lowering effect and the mode of action of FTZ extract on high lipid diet induced hyperlipidemic rats.

Materials and methods

The FTZ was prepared by alcohol and water extraction of eight herbs that have been quality-controlled according to the protocol. The cholesterol-lowering effect of FTZ was evaluated on SD rats fed with high-lipid diet. RT-PCR and western blot were used to analyze the gene expression of cholesterol metabolism-related enzymes including HMG-CoA reductase and cholesterol 7α-hydroxylase (CYP7A1) in the livers of the rats. The activity of HMG-CoA reductase and CYP7A1 were assessed by colorimetrical method and by quantification of the cholesterol metabolite of CYP7A1 using HPLC analysis respectively.

Results and conclusions

FTZ significantly decreased the levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), whilst elevated the serum high-density lipoprotein cholesterol (HDL-C) and decreased serum atherogenic index (A.I.) values in high lipid diet induced hyperlipidemic rats. Furthermore, FTZ showed significant antihyperlipidemic effect by at least three pathways in the high lipid diet induced hyperlipidemic rats: (1) upregulating the gene expression and activity of CYP7A1 which promotes the conversion of cholesterol into bile acid; (2) downregulating the gene expression and activity of HMG-CoA reductase to reduce de novo synthesis of cholesterol; (3) increasing the cholesterol excretion from feces. In these three pathways, HMG-CoA reductase and CYP7A1 are two pivotal enzymes in lipid cholesterol metabolism and are expressed mainly in hepatic cells, which support our new TCM treatment strategy: Modulating Liver to Treat Hyperlipemia.     

Using F-FDG microPET imaging to measure the inhibitory effects of Clematis chinensis Osbeck on the pro-inflammatory and degradative mediators associated with inflammatory arthritis

Aim of the study

This study examined the modulating effects of Clematis chinensis Osbeck (Ranunculaeae) on pro-inflammatory and degradative mediators associated with inflammatory arthritis.

Materials and methods

Primary human chondrocytes (PHC) were stimulated with IL-1β or lipopolysaccharide (LPS) to induce the enhanced release of prostaglandin E₂ (PGE₂), metalloproteinase (MMP-3 and -13), and cyclooxygenase-2 (COX-2) protein expression. The ¹⁸F-FDG microPET imaging system was used to evaluate the anti-arthritic effects of Clematis chinensisin vivo.

Results

The acetone extracted Clematis chinensis (CC6) contained the most total saponins compared to other solvent's extracts and showed significant and dose-dependent inhibitory effects on PGE₂, MMP-3, -13, and COX-2 productions by LPS-stimulated PHC. Furthermore, CC6 also exerted inhibitory effects on 2-¹⁸F-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) uptake when assessed by positron emission tomography (PET) uptake in the joints and serum PGE₂ of rabbits with knee joints injected with LPS.

Conclusion

The results suggest the significant chondroprotective effects of Clematis chinensis are through its anti-inflammatory and MMPs inhibitory abilities. Meanwhile, we established a new analysis method to evaluate the Chinese herbal anti-arthritic effects.     

Trillin, a steroidal saponin isolated from the rhizomes of Dioscorea nipponica, exerts protective effects against hyperlipidemia and oxidative stress

Ethnopharmacological evidence

Numerous efforts have been conducted in searching for effective agents against cardiovascular diseases, in particular from herbal medicines. The rhizome of Dioscorea nipponica (Dioscoreae Nipponicae Rhizoma) is a traditional Chinese herb being prescribed to improve the blood circulation. Here, we identified a steroidal saponin trillin from Dioscorea nipponica, which showed robust anti-hyperlipidemic effects.

Materials and methods

Rats were induced for hyperlipidemia and subjected to the drug treatment. The anti-hyperlipidemic effects of trillin were evaluated by different biochemical assays.

Results

In hyperlipidemic rat model, fed with high-fat diet, the blood levels of cholesterol, triglyceride, low density lipoprotein (LDL) and high density lipoprotein (HDL) were increased. The intra-peritoneal administration of trillin into those rats significantly improved the bleeding and blood coagulation time, and in parallel the treatment restored the levels of cholesterol, glyceride, LDL and HDL back to the normal condition. In addition, the administration of trillin in rats exerted beneficial effects in improving the levels of lipid peroxidation and superoxide dismutase activity.

Conclusion

This was the first time to reveal the anti-hyperlipidemic and anti-oxidative effects of trillin. These results would be important in developing food supplements for health improvements and therapeutic drugs against hyperlipidemia and cardiovascular diseases in future.