Synergistic interaction between the Ligusticum chuanxiong constituent butylidenephthalide and the nitric oxide donor sodium nitroprusside in relaxing rat isolated aorta

Ethnopharmacological relevance

Ligusticum chuanxiong Hort. (Umbelliferae), a traditional Chinese medicinal herb, is often prescribed together with nitric oxide donors for treating coronary heart diseases such as angina in China; however, studies concerning their pharmacological interaction are scarce.

Aim of the study

The objective of the present study was to examine the interaction between the Ligusticum chuanxiong major active constituent butylidenephthalide (BDPH) and the nitric oxide donor sodium nitroprusside (SNP) in vasorelaxation.

Materials and methods

Vasorelaxation was examined in rat isolated aorta using an organ bath system.

Results

BDPH and SNP interacted synergistically under 9,11-dideoxy-9α,11α-methanoepoxyprostaglandin H₂ (U-46619)-induced tone. This synergism became greater with increasing U-46619 concentrations where Ca²⁺ sensitization contributed more significantly, and less when U-46619 was replaced with phenylephrine where participation of Ca²⁺ sensitization was minimal. BDPH-SNP synergism remained intact in the absence of external Ca²⁺, indicating that regulation of Ca²⁺ influx was not a requirement for the manifestation of this interaction.

Conclusions

The present study demonstrated the synergistic relaxation between BDPH and SNP in rat isolated aorta. This interaction is related to an enhancement of the effectiveness of SNP in producing relaxation under tone induced mainly by Ca²⁺ sensitization.     

An LC/MS/MS method for simultaneous quantitation of two homoisoflavones: Protosappanin B and brazilin with hypoglycemic activity in rat plasma and its application to a comparative pharmacokinetic study in normal and streptozotocin-treated rats

Ethnopharmacological relevance

The heartwood of Caesalpinia sappan L. (Leguminosae), a widely used Chinese medicine in folk, has been used for the treatment of traumatic injury, stasis pain, amenorrhea, dysmenorrheal, as well as stabbing pain in the chest, abdomen and so on. Protosappanin B and brazilin, as the major bioactive homoisoflavones of Sappan Lignum, are used as the marker components for the quality control of the herb in China Pharmacopoeia.

Aim of the study

To establish a sensitive LC/MS/MS method for investigating the pharmacokinetic properties of protosappanin B and brazilin in rats after oral administration of Sappan Lignum extract, and compare their pharmacokinetics difference between normal and streptozotocin-treated rats.

Material and methods

A rapid, selective and sensitive LC/MS/MS method was developed and validated for the simultaneous quantification of protosappanin B and brazilin in rat plasma. Normal and streptozotocin-treated rats were orally administered with the Sappan Lignum extract at the same dose of 2.83 g extract/kg body weight (equivalent to 35.56 mg/kg of protosappanin B and 52.25 mg/kg of brazilin), respectively.

Results

After oral administration of Sappan Lignum extract, a remarkable increase (p<0.05) in the value of AUC_0–24 h, AUC_0–∞, C_max and T_1/2 associated with protosappanin B and brazilin was observed in the streptozotocin-treated group. Compared with the normal rats, elimination of both compounds in the streptozotocin-treated rats was slower.

Conclusion

The established method was successfully applied to compare the pharmacokinetic behaviors of protosappanin B and brazilin in rat plasma after oral administration of Sappan Lignum extract between normal and streptozotocin-treated groups; the results might suggest the accumulation of both compounds in diabetic pathologic states and the adverse reaction should be considered when it was used.     

In vivo metabolites and plasma exposure of TongMai Keli analyzed by UHPLC/DAD/qTOF-MS and LC/MS/MS

Ethnopharmacological relevance

TongMai Keli (TM) is a widely used traditional Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular diseases. It is composed of Puerariae Lobatae Radix (roots of Pueraria lobata (Willd.) Ohwi), Salviae Miltiorrhizae Radix (roots of Salvia miltiorrhiza Bge.), and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort.). The aim of this study is to identify the in vivo metabolites of TM, and to elucidate the pharmacokinetics of TM constituents and their metabolites.

Materials and methods

For metabolites identification, TM was orally administered to rats (n=3), and the metabolites in plasma were identified by UHPLC/DAD/qTOF-MS analysis and β-glucuronidase hydrolysis. For pharmacokinetic study, rats (n=10) were treated with TM at a clinical dose, and the plasma was analyzed by LC/MS/MS.

Results

A total of 25 metabolites from TM were identified in rats plasma. Glucuronide and sulfate conjugations were the major metabolic reactions, and produced 14 metabolites. The analytical method for pharmacokinetic study was fully validated with good linearity (r>0.99), wide dynamic ranges (6–6000 ng/mL), and low variations (<14.3%). The plasma concentration–time curves of puerarin and nine metabolites were profiled.

Conclusion

Isoflavones from Puerariae Lobatae Radix were the major metabolites in rat plasma after oral administration of TM. Puerarin and other isoflavone glycosides could reach their first C_max within 30 min, and were then rapidly eliminated, followed by their phase II metabolites.     

Comparative study of pharmacokinetics and tissue distribution of osthole in rats after oral administration of pure osthole and Libanotis buchtormensis supercritical extract

Ethnopharmacological relevance

Libanotis buchtormensis is the source of an important traditional medicine from Shaanxi province of China used in the treatment of many illnesses. Libanotis buchtormensis supercritical extract (LBSE) has analgesic, sedative and anti-inflammatory qualities. Osthole is one of the major bioactive components of LBSE; it is known for its significant anti-tumor, analgesic, and anti-inflammatory properties, it also alleviates hyperglycemia.

Aim of the study

The purpose of the present study was to compare the pharmacokinetics and tissue distribution of osthole in Sprague-Dawley (SD) rats after oral administration of pure osthole and LBSE. The two preparations were administered at the same osthole dose (approximately 130 mg/kg). The results should provide some guidance for the clinical applications of Libanotis buchtormensis.

Materials and methods

Comparative pharmacokinetics and tissue distribution of osthole in SD rats after oral administration of pure osthole and LBSE were analyzed using reversed-phase high-performance liquid chromatography (RP-HPLC). All pharmacokinetic data were analyzed using 3P97 software. Samples of blood and internal organs (heart, liver, spleen, lungs and kidney) were collected and pretreated according to the experimental schedule. After pretreatment, plasma and tissue samples were extracted using ether–ethyl acetate mixture (3:1, v/v). The concentration of osthole in the plasma and tissues were determined using the RP-HPLC method.

Results

The procedure described in this paper shows good precision and stability and is suitable for the osthole assays in biological samples. We found that the average plasma concentration-time profile of osthole after oral administration of osthole and LBSE showed a single peak. There were also clear differences between plasma concentrations of osthole after oral administration of pure osthole and LBSE. Non-osthole ingredients in LBSE showed some pharmacokinetic interactions with osthole and hence decreased its absorption levels (p<0.05). Our results show different tissue distribution of osthole in the single and composite administration regimens.

Conclusions

This study compares the pharmacokinetic characteristics and tissue distribution of osthole in rats after oral administration of pure osthole and LBSE; the results might be useful in clinical application of this traditional Chinese herbal medicine.     

Analgesic activity of DaChuanXiongFang after intranasal administration and its potential active components in vivo

Ethnopharmacological relevance

DaChuanXiongFang was a well-known formula originated from Jin Dynasty, China. It has been used in both China and Japan to treat migraine. In the present study, the analgesic and sedative efficacy of DaChuanXiongFang ethanol extract (DCXFEE) after intranasal administration was tested and compared with that by intragastric route.

Materials and methods

Three mice experimental models: acetic acid-induced writhing response test, hot-plate latent pain response test and pentobarbital-induced sleep model were used to evaluate DCXFEE activity. To further explore the in vivo potential active components of DCXFEE that contribute to the difference of activity induced by different administration route, ultra performance liquid chromatography–mass spectrometer (UPLC–MS) was utilized to analyze components in rat brain after given DCXFEE (60 mg/kg).

Results

DCXFEE showed analgesic efficacy after intranasal administration (15, 30 and 60 mg/kg) in acetic acid-induced writhing response in mice. While after intragastric administration, DCXFEE only showed analgesic efficacy at high dose (60 mg/kg). Moreover, the analgesic potency was weaker after intragastric administration compared with that after intranasal administration at the same dose (60 mg/kg). Similar results were obtained in hot-plate latent pain response test in mice. DCXFEE (60 mg/kg) had no sedative effect after intranasal and intragastric administration. No components originated from DCXFEE were identified in rat brain 15 min after oral administration. One major parent component ligustilide was detected in rat brain after intranasal administration.

Conclusion

These data demonstrate that DCXFEE had faster onset of action as well as better analgesic efficacy after intranasal administration than that after intragastric administration. DCXFEE has no sedative activity on potentiation of pentobarbital-induced sleep in mice given by both routes. Ligustilide might represents the potential major bioactive component of DCXFEE after intranasal administration and contribute to its analgesic activity in vivo.     

Comparative pharmacokinetics of swertiamarin in rats after oral administration of swertiamarin alone,Qing Ye Dan tablets and co-administration of swertiamarin and oleanolic acid

Ethnopharmacological relevance

Qing Ye Dan is a well-known herbal drug that is widely used to treat viral hepatitis in the Yi and Hani minority regions in the Yunnan province of China.

Materials and methods

An LC–MS/MS method was developed to determine the levels of swertiamarin in rat plasma. Swertiamarin and naringin (internal standard, IS) were extracted from rat plasma using solid-phase extraction (SPE) to purify the samples. The pharmacokinetics of the following different administration methods of swertiamarin in rats were studied: oral administration of swertiamarin alone, a Qing Ye Dan tablet (QYDT) and co-administration of swertiamarin and oleanolic acid, with each method delivering approximately 20 mg/kg of swertiamarin. Non-compartmental pharmacokinetic profiles were constructed by using the software DAS (version 2.1.1), and the pharmacokinetic parameters were compared using an unpaired Student's t-test.

Results

The results showed that the pharmacokinetic parameters C_max, AUC_0–∞, V_z/F and CL_z/F were significantly different (P<0.05) among the three types of swertiamarin administration.

Conclusions

The data indicate that oleanolic acid and the other ingredients present in QYDT could affect the pharmacokinetic behaviour of swertiamarin in rats.     

A Chinese herbal medicine, Gexia-Zhuyu Tang (GZT), prevents dimethylnitrosamine-induced liver fibrosis through inhibition of hepatic stellate cells proliferation

Ethnopharmacological evidence

Gexia-Zhuyu Tang (GZT), also called Gexiazhuyu decoction (GXZYD), is a traditional Chinese herbal medicine for chronic liver diseases such as cirrhosis and liver fibrosis.

Aim of the study

In this study, we have investigated the affects of GZT on a rat model of dimethylnitrosamine (DMN)-induced liver fibrosis.

Materials and methods

In this study, the protective effects of GZT on DMN-induced liver fibrosis were measured using a rat model. Following 5 weeks of DMN-treatment (8 mg/kg, i.p., given 3 consecutive days each week), oral administration of GZT at 1.8 g/kg daily via oral gavage for 2 weeks beginning at week 13.

Results

Both body and liver weights were significantly decreased. The reductions in body and liver weights corresponded with increasing liver damage severity. Furthermore, GZT-treatment remarkably decreased the levels of serum GOT (glutamate oxaloacetate transaminase) and GPT (glutamic pyruvic transaminase), and the mRNA expression levels of collagen alpha-1(I) and alpha-smooth muscle actin (alpha-SMA) in DMN-induced hepatic fibrosis. In addition, hepatic stellate cells (HSCs) play a major role in various types of liver fibrosis through initial myofibroblast transformation. The proliferation of HSCs was inhibited by GZT. Treatment with GZT also induced HSC apoptosis in a dose- and time-dependent manner. GZT treatment induced HSC apoptosis by facilitating Ca²⁺ release from the mitochondria within 6 h. Subsequently, caspases 3 and 12 were elevated by 72 h after treatment.

Conclusions

Our studies indicate that GZT exhibited both hepatoprotective and antifibrogenic effects in DMN-induced hepatic injury. These findings suggest that GZT may be useful in preventing the development of hepatic fibrosis.     

Ligusticum chuanxiong as a potential neuroprotectant for preventing serum deprivation-induced apoptosis in rat pheochromocytoma cells: Functional roles of mitogen-activated protein kinases

Ethnopharmacological relevance

Ligusticum chuanxiong (LC) as a common component in many traditional Chinese medicinal formulas and decoctions has been used to treat different central nervous diseases, suggesting a neuroprotective function.

Aim of the study

To investigate the functional roles of mitogen-activated protein kinases (MAPKs) in mediating the neuroprotection of LC.

Materials and methods

Different extractions of LC were applied with or without MAPK inhibitor to test their protection against serum deprivation-induced apoptosis in rat neuronal-like pheochromocytoma (PC12) cells as revealed by an MTT assay or Hoechst staining. Western blot was used to identify the activations of MAPKs.

Results

The most effective butanol extraction (LC-BuOH) was used in the following experiments. LC-BuOH reversed serum deprivation-induced decreased phosphorylation of extracellular signal-regulated kinase (ERK) and increased phosphorylation of c-Jun NH₂-terminal kinase (JNK) and p38, the family of MAPKs. A PKA inhibitor, blocked the protection of LC-BuOH and partially blocked LC-BuOH-induced alterations in MAPKs, suggesting that the LC-BuOH regulates MAPKs through both PKA-dependent and -independent pathways. Although PD 98059, an inhibitor of MEK which activates ERK, blocked LC-BuOH-induced ERK phosphorylation, it did not block the protection of LC-BuOH.

Conclusions

LC-BuOH mediates protection by suppressing JNK/p38 instead of activating ERK activity.     

Anti-inflammatory effects and acute toxicity of hydroethanolic extract of Jacaranda decurrens roots in adult male rats

Ethnopharmacological relevance

Jacaranda decurrens subsp. symmetrifoliolata Farias and Proença (Bignoniaceae) is a species traditionally used for the treatment of inflammatory diseases. However, until this moment, there is no scientific evidence of these effects.

Aim of study

To evaluate the anti-inflammatory effects of hydroethanolic root extract of Jacaranda decurrens in rats and to determine the safe of this plant after acute exposure.

Materials and methods

The acute toxicity of Jacaranda decurrens root extract (EJD) was evaluated by oral administration to male rats as single doses of 0; 500; 1000 or 2000 mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in carrageenan-induced inflammatory paw edema and myeloperoxidase activity in male rats.

Results

No signs of acute toxicity were observed, indicating that the LD₅₀ is greater than 2000 mg/kg. EJD (100 and 300 mg/kg) significantly reduced edema formation and at higher dose, the reduction was similar to dexamethasone. A significant decrease in myeloperoxidase activity was also observed.

Conclusions

The present study shows that Jacaranda decurrens extract has anti-inflammatory properties in rats without causing acute toxicity. These properties observed may be due to the presence of bioactive constituents such as ursolic acid.     

Acute toxicity studies of the leaf extract of Ficus exasperata on haematological parameters,body weight and body temperature

Introduction

The plant, Ficus exasperata is popularly used in Nigeria and in several parts of Africa for a variety of ailments.

Aim of study

This study was thus mapped out to investigate the toxicity profile of the aqueous leaf extract (AET) on haematological parameters, body weight and body temperature in mice.

Methodology

In the present study, AET was evaluated for acute toxicity over 24 h and 14-day periods. The LD₅₀ was assessed via oral and intraperitoneal administration.

Results

The LD₅₀ was indeterminable via the oral route but was determined to be 0.54 g/kg i.p. In the 24 h and 14 days single dose study, oral administration of 2.5, 5, 10 and 20 g/kg of AET produced neither mortality nor changes in behavior or any other physiological activity in mice. Body weights and body temperatures were not significantly altered. Haematological analysis showed no marked differences in any of the parameters examined (WBC count, platelet and haemoglobin estimation) in either the control or treated groups. However, the 14 days daily dose study showed significant increase in body temperature (p < 0.05) and a significant decrease in the red blood cell count, haemoglobin count and haematocrit values (p < 0.05), while other parameters remained unchanged.

Conclusion

In summary, AET was found to be relatively safe on short-term oral administration. However, chronic toxicity studies are required for the support of the safe use of this plant.     

Analysis of the chemical composition,acute toxicity and skin sensitivity of essential oil from rhizomes of Ligusticum chuanxiong

Ethnopharmacological relevance

Ligusticum chuanxiong Hort. (Umbelliferae) is a plant used as medicine and food in China. The essential oil (EO) extracted from its rhizomes possesses many pharmacological activities. However, there have been no scientific reports in the modern literature on the safety of EO.

Aims of the study

The objective of this study was to conduct a chemical composition analysis and evaluate acute toxicity and skin sensitivity of EO from rhizomes of Ligusticum chuanxiong.

Materials and methods

The chemical composition of hydrodistilled EO was analyzed by gas chromatography-mass spectrometry (GC–MS) and was evaluated in animals for acute toxicity, skin irritation and sensitization tests.

Results

Dozens of compounds were detected and the major components of EO were ligustilide and butylidenephthalide with relative contents of 67.46 and 5.06%, respectively. The oral and intra-peritoneal lethal doses of 50% (LD₅₀) in mice were 7.23 g/kg (approximately 14,606 times of clinical dose used) and 2.25 g/kg (approximately 5091 times of clinical dose used), respectively. The doses of 0.115 and 0.23 g/kg EO (approximately 232.5 and 465 times of the respective clinical doses used) revealed slight irritation effects on rabbit skin, but 1 g/kg EO (approximately 2020 times of clinical dose used) had no observable effect on guinea pig skin in the skin sensitization test.

Conclusions

These experimental results indicate that short term application of EO is probably safe within the range of its clinical doses, but the dose should be controlled for external use due to its slight skin irritation.     

Ethnoveterinary knowledge in pastoral Karamoja,Uganda

Ethnopharmacological relevance

The people of Karamoja of northern Uganda chiefly rely on ethnoveterinary knowledge (EVK) to control common livestock health problems. In spite of cattle's central role in Karamojong culture and livelihoods, there has been no systematic recording of their ethnoveterinary plant-based cures to date.

Aim of study

To document the remedies used to treat livestock diseases, their preparation and administration.

Methods

Data were collected using semi-structured interviews, guided questionnaires, group discussions, direct observations and collection trips.

Results

We present information on 209 plant species and 18 non-plant materials. Plant species are distributed over 116 genera and 54 families. The most common medicinal use was treatment against anaplasmosis. Balanites aegyptiacus, Carissa spinarum, Warburgia salutaris and Harrisonia abyssinica had the most uses of all species. All different plant parts were used; bark and underground parts were exploited more frequently than other plant parts. Most remedies listed used a single ingredient, typically soaked in water; only 12.8% remedies used multiple plants. The route of administration was primarily oral followed by topical applications. Almost all plants are collected from the wild; none of the few cultivated plants used had been planted for medicinal purposes.

Conclusions

The pastoralists in the study site possess a wealth of EVK which they use to maintain animal health. Their rich knowledge and high diversity of plants were recorded here for the first time.     

Cardioprotection by Guanxin II in rats with acute myocardial infarction is related to its three compounds

Aim

We tested the hypothesis that cardioprotection afforded by traditional Chinese Guanxin II (GXII) formula is related to absorbed bioactive compounds (ABCs).

Methods

Sprague–Dawley rats with acute myocardial infarction (AMI) were induced by coronary occlusion. ABCs including ferulic acid (F), hydroxyl safflor yellow A (A), tanshinol (T), protocatechualdehyde (P) and paeoniflorin (E) were measured in blood after oral GXII. The effects of GXII and FATPE, alone and in combination, and of some components of FATPE on infarct size, myocardial apoptosis and caspase-3 activity were determined. Myocardial blood flow (MBF) in AMI rat was detected 2 h after oral GXII and FAT.

Results

FATPE was found in rat blood. FAT was similar to FATPE and GXII in decreasing infarct size, myocardial apoptosis and caspase-3 activity of AMI. Both FAT and GXII were similar in increasing of MBF.

Conclusion

GXII and FAT protect the heart from ischemic injury by increasing MBF, and decrease infarct size by inhibiting myocardial apoptosis and caspase-3 activity. These findings provide a potential cardioprotective cocktail.     

Influence of processing on pharmacokinetic of typical constituents in radix polygoni multiflori after oral administration by LC–ESI–MS/MS

Ethnopharmacological relevance

The processed radix polygoni multiflori (P-RPM) are produced from the raw radix polygoni multiflori (R-RPM) steamed with black bean juice, but the two traditional Chinese medicines are used to treat the different diseases in clinic. In order to clarify the influence of processing on pharmacological properties of radix polygoni multiflori, an investigation was carried out to compare the pharmacokinetics of typical constituents after oral administration of P-RPM and R-RPM extracts

Materials and methods

A simple, rapid and sensitive high performance liquid chromatography–tandem mass spectroscopy (LC–MS/MS) was developed and validated for the simultaneous determination of gallic acid, polydatin, 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (PM-SG), resveratrol, and emodin in rat plasma. Male Sprague-Dawley rats were orally administered the two extracts with approximately the same dosage.

Results

It was found that gallic acid was distributed as opened one-compartment model while polydatin, PM-SG and emodin were fitted to an open two-compartment model after oral administration of raw and processed radix polygoni multiflori extract. Cmax and AUC of gallic acid were increased (P<0.01), but C_max and AUC of PM-SG were descreased (P<0.05). AUC of polydatin and emodin were similar with that of PM-SG. However, resveratrol was not detected in plasma collected at certain intervals following oral administration of the two extracts.

Conclusions

These results indicate that influence of the processing could improve the bioavailability of gallic acid and reduce the absorption of PM-SG, polydatin and emodin in rats. The LC–MS/MS method could be used to evaluate the effect of processing on pharmacokinetic of typical constituents in radix polygoni multiflori after oral administration.     

Comparative pharmacokinetic investigation on baicalin and wogonoside in type 2 diabetic and normal rats after oral administration of traditional Chinese medicine Huanglian Jiedu decoction

Ethnopharmacological relevance

Huanglian Jiedu decoction (HLJDD) is used traditionally in China for the treatment of diabetes mellitus in clinical practice, which has been proved to be effective. The purpose of this study was to investigate the pharmacokinetic characteristics (especially the area under the curve, AUC) of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract and to explore its possible mechanism.

Materials and methods

HLJDD extract and Radix scutellariae extract were prepared and the contents of baicalin and wogonoside contained in two extracts were assayed with high performance liquid chromatography (HPLC). Type 2 diabetic rats were induced by high fat diet and intraperitoneal injection of streptozotocin. Pharmacokinetics of baicalin and wogonoside in type 2 diabetic and normal control rats after oral administration of HLJDD extract or Radix scutellariae extract were investigated. Pharmacokinetics of baicalin in type 2 diabetic and normal rats after oral administration of pure baicalin was also investigated.

Results

The pharmacokinetic parameters (especially AUCs) of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract were remarkably different from those in normal rats. And the alterations of the AUCs of baicalin and wogonoside in type 2 diabetic rats after oral administration of Radix scutellariae extract were similar to those after oral administration of HLJDD extract. Moreover, the increase of the AUC of baicalin in type 2 diabetic rats after oral administration of pure baicalin was similar to that after oral administration of HLJDD extract or Radix scutellariae extract.

Conclusion

The pharmacokinetic behaviors of baicalin and wogonoside (especially the systemic exposure [AUCs] of baicalin and wogonoside) were significantly altered in type 2 diabetic rats after orally administrated HLJDD extract. And the increased AUCs of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract resulted from neither the effects of other herbs contained in HLJDD nor the effects of other components contained in Radix scutellariae. It might result from the effects of the pathological status of type 2 diabetes mellitus.     

Antidiabetic activities of Tecoma stans (L.) Juss. ex Kunth

Ethnopharmacological relevance

Tecoma stans aqueous extract (TAE) is widely used as a traditional antidiabetic remedy in Mexico; its rational use is controversial. We provide evidence of its main antidiabetic activities.

Aim of the study

To evaluate in vivo and in vitro intestinal α-glucosidases inhibition as the possible mode of action of TAE on type 2 diabetes mellitus (DM2) animal models, and to test the effects of its sub-chronic administration on lipids and glucose blood levels.

Materials and methods

In healthy and streptozotocin (STZ)-induced diabetic male Sprague–Dawley rats, glucose or cornstarch was administered after an oral dose of TAE, acarbose, tolbutamide or vehicle, in order to build starch and glucose tolerance curves (STC and GTC). An intestinal brush border preparation was used to evaluate the TAE α-glucosidases inhibitory activity. Moreover, in STZ-induced diabetic rats TAE, tolbutamide or vehicle was administered for 21 days for evaluate their effects on fasting glucose cholesterol and triglycerides. Also, TAE total phenolic compounds were quantified.

Results

In STC, TAE decreased hyperglycemic peak values in both healthy and STZ-treated rats, in a magnitude similar to that of acarbose. The in vitro preparation showed a dose-dependent inhibition of glucose release from starch. Sub-chronic administration of TAE significantly reduced cholesterol and triglycerides levels. Moreover, we confirmed that acute and sub-chronic administration of TAE (500 mg/kg) in both rat models did not diminish fasting glucose and did not modify the GTC.

Conclusions

The study present evidence that the main antidiabetic effect of TAE is due to intestinal α-glucosidase inhibition by decreasing the postprandial hyper-glycaemia peak; in addition, TAE sub-chronic administration reduces triglycerides and cholesterol, without modifying fasting glucose.