In vitro effects of active components of Polygonum Multiflorum Radix on enzymes involved in the lipid metabolism

Ethnopharmacology relevance

Raw and processed Polygoni Multiflori Radix (PMR and PMRP) are used in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD), hyperlipidemia or related diseases. In our previous research, 2, 3, 5, 4′-tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG) displayed the most important role in the total cholesterol (TC) lowering effect among all the chemical constituents of Polygonum multiflorum. Emodin and physcion displayed more favorable triglyceride (TG) reducing effects than TSG. However, there are few researches focus on the approach and mechanism of how do Polygonum multiflorum exhibit good lipid regulation activity. The targeted sites of active substances of Polygonum multiflorum are still not clearly elucidated. This research pays close attention to how major chemical components of Polygonum multiflorum affect the TC and TG contents in liver cells.

Materials and methods

In this research, a sensitive, accurate and rapid in vitro model, steatosis hepatic L02 cell, was used to explore target sites of active chemical substances of Polygonum multiflorum for 48 h. Steatosis hepatic L02 cell was exposed to emodin, physcion and TSG, respectively. The contents of four key enzymes in the pathway of synthesis and decomposition of TC and TG were investigated after exposure. Meanwhile, the contents of lipid transfer protein were also tested. The diacylgycerol acyltransferase 1 (DGAT1) controlled the biosynthesis of TG from free fatty acids while 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) limited the biosynthesis of TC. Hepatic triglyceride lipase (HTGL) and cholesterol 7α-hydroxylase (CYP7A) played the key role in the lipolysis procedure of TG and TC.

Results

The synthesis of TC and TG in steatosis L02 cells were apparently increased in the model group compared to the control group. Intracellular contents of HMG-CoA reductase and DGAT1 increased 32.33% and 56.52%, while contents of CYP7A and HTGL decreased 21.61% and 47.37%. Emodin, physcion and TSG all showed down-regulation effects on HMG-CoA reductase, while up-regulation effects on CYP7A. The most remarkable effect on HMG-CoA reductase was found on emodin. Emodin could reduce the DGAT1 content from 438.44±4.51 pg/mL in model group to 192.55±9.85 pg/mL (100 μm). The content of HTGL in 300 μm physcion group was 3.15±0.15 U/mL, which was more significantly effective than the control, lovastatin and fenofibrate group.

Conclusions

TSG could raise the content of CYP7A and then promote the lipolysis of cholesterol. Moreover, TSG also showed the best LDL-reducing effect. Emodin could inhibit HMG-CoA reductase and DGAT1, which were key enzymes in the synthesis of TC and TG. Physcion increased the content of HTGL, and then could boost the lipolysis of triglyceride. At the same time, physcion showed the best VLDL-reducing effect. In view of the above conclusions, we contributed the lipid regulation activity to an overall synergy of TSG, emodin and physcion.     

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.     

Phaleria macrocarpa (Scheff.) Boerl fruit aqueous extract enhances LDL receptor and PCSK9 expression in vivo and in vitro

Ethnopharmacological relevance

Phaleria macrocarpa (Scheff.) Boerl (Pm) has been shown to reduce cholesterol level in vitro and in vivo experiment.

Aim of the study

This study investigated the effects of Pm fruit on weight control and mechanistic basis of its anti-hypercholesterolemic effect in both in vivo and in vitro.

Materials and method

In the in vivo study, thirty six male Sprague Dawley were randomized to six groups. Five groups were induced into hypercholesterolemia by giving 3% cholesterol enriched-diet for 52 days while one group acted as control. The rats were then treated with Pm extract (0, 20, 30 and 40 mg/ml) or simvastatin for 84 days. The following parameters were determined: (1) body weight, (2) blood lipid profile (total cholesterol, triglyceride, HDL and LDL) and (3) hepatic LDL receptor (160 kDa and 120 kDa) and PCSK9 proteins. In the in vitro study, HepG2 cells were cultured in serum-free RPMI supplemented with 0.2% BSA with or without LDL and in the presence of Pm extract (0, 0.1, 2, 40 and 1000 μg/ml) or simvastatin (4.60 μg/ml) for 24 h. The abundance of both LDL receptor and PCSK9 proteins and mRNA were investigated.

Results

Pm extract significantly (P < 0.05) reduced body weight gain, total cholesterol, triglycerides, HDL LDL levels and upregulated hepatic LDL receptor as well as PCSK9 proteins of hypercholesterolemic rats. These results were supported by studies in HepG2 cells whereby Pm extract also significantly upregulated both LDL receptor and PCSK9 at protein and mRNA levels.

Conclusion

This study enhances the potential usage of Pm fruit for controlling the body weight of obese people and for treating hypercholesterolemia.     

Effects of lignans extracted from Eucommia ulmoides and aldose reductase inhibitor epalrestat on hypertensive vascular remodeling

Aim of the study

To investigate the effects of lignans extracted from Eucommia ulmoides and epalrestat on vascular remodeling in spontaneously hypertensive rats.

Materials and methods

Ten-week-old male spontaneously hypertensive rats were randomly divided into 3 groups (12 rats each group), and treated orally with 100 mg/kg/d of captopril (an angiotensin-converting enzyme inhibitor), 100 mg/kg/d of epalrestat (an aldose reductase inhibitor) and 300 mg/kg/d of lignans by gavage daily for 16 weeks, respectively. Sex-, age-, and number-matched spontaneously hypertensive rats and normotensive Wistar Kyoto rats, were treated with distilled water (vehicle) as controls. The rats were weighed weekly. Mean arterial blood pressure and heart rate were measured periodically by non-invasive blood pressure monitoring. They were sacrificed at the end of experiment (26-week-old). Superior mesenteric artery and aorta were isolated for determination of histomorphometry and the expression of aldose reductase by immunohistochemistry.

Results

Captopril and lignans, but not epalrestat, decreased mean arterial blood pressure in spontaneously hypertensive rats. Vascular remodeling was improved in all three treated groups by histomorphometry.

Conclusions

Both lignans and epalrestat reversed hypertensive vascular remodeling. Aldose reductase played a vital role in the pathologic process of hypertensive vascular remodeling rather than elevation of blood pressure. These data suggested that aldose reductase could be a new therapeutic target for the treatment of cardiovascular diseases.     

Evaluation of cholesterol absorption and biosynthesis by decoctions of Annona cherimola leaves

Ethnopharmacological relevance

Decoctions of the leaves of Annona cherimola Mill. are traditionally used in Azores to treat hypercholesterolemia. Although they are sold and consumed by people in order to improve their health, these are products that cannot be sold with claims for health benefits as they have never been studied scientifically.

Materials and methods

The activities of decoctions from Annona cherimola leaves were analysed for the two therapeutic approaches currently used to reduce plasma cholesterol: inhibition of dietary cholesterol uptake and inhibition of HMG-CoA reductase activity. Furthermore, the composition of the decoction was elucidated by LC–MS and the permeability of the active components was analysed using Caco-2 cell monolayers as a model of the intestinal barrier (dietary cholesterol uptake).

Results

The chemical composition of the Annona cherimola leaves' extract revealed that rutin was its main component. The in vitro gastrointestinal digestion did not modify the chemical composition of the extract. This extract was able to originate a slight reduction in cholesterol absorption through Caco-2 cells lines and to reduce the HMG-CoA reductase activity in 50% when using 137.3 μg of the extract/mL. Rutin, when used in the same concentration as that found in the extract, was able to reduce cholesterol absorption through Caco-2 cells monolayer in approximately 47%. This flavonoid had an IC₅₀ of 17.85 μM relatively to the HMG-CoA reductase activity.

Conclusions

The traditional use of decoctions from the leaves of Annona cherimola may be justified, at least by the inhibition of HMG-CoA reductase activity.     

A plasma metabonomic investigation into the intervention of volatile oil of Magnolia biondii Pamp on rat model of acute inflammation

Ethnopharmacological relevance

The dried flower buds of Magnolia biondii Pamp (Magnoliaceae) possesses significant anti-inflammatory activities.

Aim of the study

Volatile oil in Magnolia biondii Pamp (VOMbP) is considered to be important pharmacologically active individuals against acute inflammation, but its exact anti-inflammatory mechanism remains elusive. In this study, we aimed to investigate the intervention of VOMbP on rats with acute inflammation and explore the possible anti-inflammatory mechanisms of VOMbP with metabonomic strategy.

Materials and methods

Acute inflammation was induced by subcutaneously injection of carrageenan in the rats. Plasma was analyzed using gas chromatography-mass spectrometry (GC-MS), based on which the principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) models were established for metabonomic analysis.

Results

It was revealed that the pretreatment of VOMbP in acute inflammatory rats induces a substantial and characteristic change in their metabolic profiles. Some significantly changed metabolites, including hexadecanoic acid, linoleic acid, oleic acid, stearic acid, and cholesterol, were found to be reasonable in explaining the anti-inflammatory mechanism of VOMbP.

Conclusions

In all, it is likely that VOMbP intervenes the metabolic process of inflammatory rats by affecting the fatty acid and cholesterol metabolism. Our work also indicated that the metabonomics method is a promising tool for performing intervention and mechanism research of traditional Chinese medicines.     

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.     

Hypolipidemic Activity of Okra is Mediated Through Inhibition of Lipogenesis and Upregulation of Cholesterol Degradation

Little is known about the hypolipidemic activity of okra; therefore, we investigated the hypolipidemic activity of okra and its interaction with gene expression of several key components involved in lipid homeostasis. Male C57BL/6 mice were randomly divided into three groups and fed with hyperlipidemic diet or two hyperlipidemic diets supplemented with 1% or 2% okra powder for eight weeks. Results demonstrated that okra dose‐dependently decreased serum and hepatic total cholesterol and triglyceride, and enhanced fecal excretion of bile acids. Gene expression analysis revealed that okra upregulated cholesterol 7α‐hydroxylase (CYP7A1) expression, downregulated expression of sterol regulatory element‐binding protein 1c (SREBP1c) and fatty acid synthase (FAS), with no effect on sterol regulatory element‐binding protein 2 (SREBP2), 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGR), low‐density lipoprotein receptor (LDLR) and carnitine palmitoyltransferase‐1A (CPT1A). It was suggested that hypolipidemic activity of okra was mediated most likely by upregulation of cholesterol degradation through CYP7A1 and by inhibition of lipogenesis through SREBP1c and FAS. Okra raw and fractionated polysaccharide showed strong bile acid binding capacity in vitro, which may contribute to the hypolipidemic activity observed. In conclusion, okra has potential application in the management of hyperlipidemia and its associated metabolic disorders. Copyright © 2013 John Wiley & Sons, Ltd.     

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.     

Curculigo orchioides (Xian Mao) modifies the activity and protein expression of CYP3A in normal and Kidney-Yang Deficiency model rats

Aim of the study

In Chinese medicine clinics, traditional Chinese herbs are used to treat disorders of Yin and Yang balance, including Kidney-Yang Deficiency. The activity of the hepatic cytochrome P450 3 A (CYP3A) is closely associated with body status. The aim of the present study is to investigate CYP3A enzymatic activity and CYP3A4 protein expression using a Kidney-Yang Deficiency rat model and furthermore to investigate the intervention effects of the Pungent-hot herb Xian Mao. This work contributes rationale for personalized medicine and enhances our understanding of herb–drug interactions.

Materials and methods

Rats were randomly divided into three groups: the model group, the Xian Mao group and the intervention group (model rats treated with Xian Mao). The model rats were given an intramuscular injection of hydrocortisone for 14 days, and the control rats were given normal saline. The Xian Mao group consisted of normal rats treated with Xian Mao by oral gavage for 7 days. The intervention group was given Xian Mao for 7 days after treatment with hydrocortisone. The activity of CYP3A was detected by using the erythromycin-N-demethylase method. CYP3A4 protein expression level was detected by Western-blot.

Results

CYP3A enzymatic activity in the Kidney-Yang Deficiency rat was decreased by 44% compared to normal animals. The relative CYP3A4 protein expression level of the Kidney-Yang Deficiency rat (mean value 0.663±0.188) was 20% lower than that of normal rat (0.830±0.199). The in vitro data showed that CYP3A activity was significantly (P<0.001) inhibited (decreased by 59%) by Xian Mao concentrations of 1 mg/mL. The in vivo data also showed that CYP3A activity was significantly decreased in the rats treated with the three doses of Xian Mao. The CYP3A4 protein expression was significantly decreased by Xian Mao treatment at the high and intermediate doses (30 and 20 g/kg, respectively) compared with the normal group. However, the intervention group (the Kidney-Yang Deficiency rat treated with Xian Mao at 20 and 30 g/kg) showed an increased CYP3A activity and CYP3A4 protein expression compared with the herb-untreated model rats.

Conclusion

CYP3A enzymatic activity and CYP3A4 protein expression could be inhibited by Xian Mao. The CYP3A activity and CYP3A4 expression in the Kidney-Yang Deficiency model rat were lower than that of normal rat but this deficiency could be rescued by treatment with Xian Mao.     

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.     

Effects of Juniperus oxycedrus ssp. oxycedrus on tissue lipid peroxidation, trace elements (Cu, Zn, Fe) and blood glucose levels in experimental diabetes

Ethnopharmacological relevance

Juniperus oxycedrus L. (Cupressaceae) fruits and leaves are used internally and pounded fruits are eaten for diabetes in Turkey.

Aim of the study

To evaluate the interrelationships between the levels of chosen trace elements (copper, iron, and zinc) and hepatic, renal lipid peroxidation (TBARS) in streptozotocin-induced diabetic rats treated with Juniperus oxycedrus ssp. oxycedrus (J.o.s.o.) leaf and fruit extracts for 10 days.

Materials and methods

J.o.s.o. fruit and leaf extracts were administered in STZ-induced diabetic rats, at doses of 500 and 1000 mg/kg. The blood glucose levels were measured in the 1st, 4th, 7th and 10th day of experiment. Fe, Cu, and Zn contents and lipid peroxidation levels of liver and kidney tissues were determined by atomic absorption spectrophotometry and ultraviolet spectrophotometry, respectively.

Results

Treatment of diabetic rats with the J.o.s.o. fruit and leaf extracts decreased the blood glucose levels and both the levels of lipid peroxidation in liver and kidney tissues. J.o.s.o. extracts have augmented Zn concentrations in liver of STZ-induced diabetic rats.

Conclusions

Results indicated that J.o.s.o. fruit and leaf extracts might be beneficial for diabetes and its complications.     

Aqueous extract of Gleditsia sinensis Lam. fruits improves serum and liver lipid profiles and attenuates atherosclerosis in rabbits fed a high-fat diet

Ethnopharmacological relevance

Gleditsia sinensis Lam. has been used in the traditional Chinese medicine as a chief ingredient of many polyherbal formulations for the treatment of obesity and thrombosis.

Aim of the study

To evaluate the effects of Gleditsia sinensis Lam. fruit aqueous extract (GAE) on hyperlipidemia and atherosclerosis in Japanese white rabbits on a high fat diet.

Materials and methods

Rabbits were divided into four groups: the normal control with a normal diet, and high-fat diet-fed model group and GAE-treated groups supplemented with GAE (6 or 12 mg/kg/day, p.o.), respectively. The groups fed high-fat diets were given i.v. with bovine serum albumin (BSA) on the 4th week to induce atherosclerosis. The serum lipid profile, including triglycerides (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), was determined on the 0th, 4th, 8th and 14th week, respectively. And the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) were measured simultaneously. At the end of the experiment, the rabbits were sacrificed, and the atherosclerotic plaques as well as the histopathological changes of aorta and liver were assessed by oil-red or HE staining, respectively, and the aorta and liver lipid profiles were also assayed.

Results

Results showed that the prophylactic treatment with GAE could significantly decrease the lipid levels of serum, aorta and liver, attenuate aortic atherosclerosis and improve aortic remodeling without the significant liver and muscle toxicity.

Conclusion

The present findings suggest that GAE can effectively attenuate the atherosclerotic at least through anti-hyperlipidemic activity and thus has the therapeutic potential in treating hyperlipidemia-related cardiovascular diseases.     

Src/NF-κB-targeted inhibition of LPS-induced macrophage activation and dextran sodium sulphate-induced colitis by Archidendron clypearia methanol extract

Ethnopharmacological relevance

Raw and processed Polygoni Multiflori Radix (PMR) are used in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD), hyperlipidemia or related diseases. However, few researches compared the activities of raw and processed PMR on lipid metabolism regulation. Moreover, the active substances of Polygonum multiflorum are still not clearly elucidated.

Materials and methods

In this research, a sensitive, accurate and rapid in vitro model, steatosis hepatic L02 cell, was applied to compare the relative activities of raw and processed PMR on lipid metabolism regulation. Furthermore, the lipid regulation activities of emodin, physcion and 2,3,5,4′-tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG) were evaluated. The steatosis L02 cells were obtained after cultured with 1% fat emulsion-10% fetal bovine serum (FBS)-RPMI 1640 medium for 48 h. Contents of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in L02 cells are evaluated after exposure.

Results

The intracellular TG contents were increased from 16.50 ± 1.29 mmol/L to 34.40 ± 1.36 mmol/L in steatosis L02 cells, while the intracellular contents of TC were increased from 5.07 ± 1.80 mmol/L to 11.79 ± 0.54 mmol/L. Water extract of raw PMR showed much remarkable TG-regulation and TC-regulation effects than its processed products. Emodin displayed the best TG regulation activity while TSG showed the best TC regulation activity. At the same time, the exposure of emodin and physcion could reduce the LDL-C contents in steatosis L02 cells.

Conclusions

On account of these in vitro results, raw PMR might have more satisfactory effects in clinic treatment of NAFLD or hyperlipidemia characterized by the elevation of cholesterol than processed PMR.     

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.     

Preliminary study of antidiabetic activity of the methanolic leaf extract of Axonopus compressus (P. Beauv) in alloxan-induced diabetic rats

Ethnopharmacological relevance

Axonopus Compressus is commonly used by the people of Southern Nigeria to treat different ailment such as common cold and diabetes. This study therefore, evaluated the anti-diabetic effect of the methanolic leaf extract of the plant.

Materials and methods

Diabetes was induced in the rats by intraperitoneal (i.p.) injection of alloxan monohydrate at the dose of 180 mg/kg. Three test doses of the extract (250, 500 and 1000 mg/kg) administered per os through gastric gavage to the rats were used in the study. The activity was compared to a standard reference drug (glibenclamide, 2 mg/kg) and a negative control. Blood from the tail snip was used to measure the effects of the extract and drug at 0, 1, 3 and 6 h using autoanalyzer (AccuCheck Active^®) glucose kit.

Results

Methanolic leaf extract of Axonopus compressus at all the doses (250, 500 and 1000 mg/kg) used caused a respective time dependent and significant (p < 0.0001) reduction (by 31.5%, 19.8% and 24.5%) of the blood glucose levels in the diabetic rats when compared to the negative control group at the 6th hour. However, the reference drug (glibenclamide, 2 mg/kg) decreased the blood glucose levels by 69.9% and the tween 20 solution (negative control) increased the blood glucose level by 15.2% at the 6th hour. Moreso, the extract at the different test doses caused various degrees of reduction of the blood glucose levels of the test rats at 1st, 3rd and 6th hours when compared to the negative control rats.

Conclusion

The findings suggest that Axonopus compressus may possess antidiabetic property.     

Identification of novel pregnane X receptor activators from traditional Chinese medicines

Aim of the study

To investigate the ability of traditional Chinese medicines (TCMs) and their bioactive compounds to activate pregnane X receptor (PXR) signalling pathway.

Materials and methods

We screened ethanol extracts of 28 commonly used TCMs for their capability to induce cytochrome P450 3A4 (CYP3A4) via PXR signalling pathway using a cell-based reporter gene assay combined with RT-PCR analysis. In addition, 34 bioactive components from these TCMs were examined for their potential to activate PXR.

Results

Our observations showed that 22 ethanol extracts and 8 compounds could activate human PXR and induce CYP3A4 reporter construct in HepG2 cells. Among them, Ginkgo biloba, Ligusticum chuanxiong, Chinese angelica, prepared Rehmannia root, Epimedium brevicornum, Atractylodes macrocephala, Schisandra chinensis, Paeonia lactiflora, Ophiopogon japonicus, Polygonum multiflorum, Coptis chinensis, Artemisia scoparia, Trichosanthes kirilowii, Silybum marianum, Gardenia fruit and Lycium chinense could strongly trans-activate PXR. Moreover, ligustilide, schisantherin A, berberine hydrochloride and trans-resveratrol were identified for the first time as efficacious PXR agonists.

Conclusions

Twenty-two TCM ethanol extracts and eight bioactive compounds could activate PXR signalling pathway and induce CYP3A4 reporter gene. Therefore, caution should be taken when these PXR activators are used in combination with prescribed drugs metabolized by CYP3A4.