Evaluation of the anti-neuraminidase activity of the traditional Chinese medicines and determination of the anti-influenza A virus effects of the neuraminidase inhibitory TCMs in vitro and in vivo

Etnopharmacological relevance

Neuraminidase (NA) inhibitors are currently the most effective drugs to treat influenza A viruses infection. Many traditional Chinese medicines (TCMs) have been used in the clinics to treat influenza. The anti-viral mechanisms of these TCMs and their inhibitory effects towards NA need to be systematically tested.

Aim of the study

To evaluate the anti-NA activity of the TCMs and the anti-influenza A virus effects of the NA inhibitory TCMs in vitro and in vivo.

Material and methods

We tested the inhibitory activity of water extracts from 439 TCMs towards NA. The in vitro anti-influenza virus activities of the 5 TCMs were evaluated using the strain A/California/7/2009 (H1N1) NYMC X-179A of influenza A virus. A randomly selected TCM with NA inhibitory activity, Melia toosendan extract, was further evaluated using a mouse model infected with influenza A virus.

Results

Five TCMs, Duchesnea indica (Andr.) Focke [Fragaria indica Andr.], Liquidambar formosana Hance., Lithospermum erythrorhizon Sieb. et Zucc., Melia toosendan Sieb. et Zucc., and Prunella vulgaris L., exerted potent inhibitory activity towards NA. These TCMs in the range of 25-250 μg/mL had the ability to reduce virus-induced cytopathic effect (CPE) and the virus yield in MDCK cells. Melia toosendan significantly reduced death rate and prolonged mean day to death (MDD) of the viral infected mice.

Conclusions

This study describes five TCMs exerted strong inhibitory activities towards NA, and exhibited antiviral effect against influenza A virus by reducing viral reproduction and reduced CPE of the viral infected cells. Melia toosendan, significantly reduced death rate and prolonged survival of the H1N1 viral infected mice.     

Activation of the nuclear receptor PPARγ by metabolites isolated from sage (Salvia officinalis L.)

Ethnopharmacological relevance

Salvia officinalis has been used as a traditional remedy against diabetes in many countries and its glucose-lowering effects have been demonstrated in animal studies. The active compounds and their possible mode of action are still unknown although it has been suggested that diterpenes may be responsible for the anti-diabetic effect of Salvia officinalis.

Aim of the study

To investigate whether the reported anti-diabetic effects of Salvia officinalis are related to activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ and to identify the bioactive constituents.

Materials and methods

From a dichloromethane extract of Salvia officinalis able to activate PPARγ several major metabolites were isolated by chromatographic techniques. To assess bioactivity of the isolated metabolites a PPARγ transactivation assay was used.

Results

Eight diterpenes were isolated and identified including a new abietane diterpene being the epirosmanol ester of 12-O-methyl carnosic acid and 20-hydroxyferruginol, which was isolated from Salvia officinalis for the first time, as well as viridiflorol, oleanolic acid, and α-linolenic acid. 12-O-methyl carnosic acid and α-linolenic acid were able to significantly activate PPARγ whereas the remaining metabolites were either unable to activate PPARγ or yielded insignificant activation.

Conclusions

Selected metabolites from Salvia officinalis were able to activate PPARγ and hence, the anti-diabetic activity of this plant could in part be mediated through this nuclear receptor.     

Effect of Chinese herbs on CYP3A4 activity and expression in vitro

Ethnopharmacological relevance

Traditional Chinese Medicine (TCM) has become more popular among cancer patients in the Western world, who often use Chinese herbs as adjuvant therapy to reduce the adverse effects of conventional chemotherapy. However, pharmacokinetic (PK) interactions between Chinese herbs and anticancer drugs can occur and have dramatic consequences for these patients. Currently, only a few possible PK interactions between Chinese herbs and conventional Western drugs have been documented.

Aim of the study

Since the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) contributes to most of the PK interactions with (anticancer) drugs, the effect of four Chinese herbs (Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus) on the activity and expression of CYP3A4 was investigated in vitro.

Materials and methods

Ethanol and water–ethanol extracts of the four Chinese herbs were prepared from raw material. CYP3A4 inhibition was assessed by the use of Supersomes^™ in a fluorescence assay. Furthermore, CYP3A4 induction was evaluated in a human pregnane X receptor (hPXR)-mediated CYP3A4 reporter gene assay and a quantitative real time PCR assay, both in human colon adenocarcinoma-derived LS180 cells (LS180).

Results

Extracts of Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus inhibited CYP3A4 in human CYP3A4 Supersomes^™ (IC₅₀ values: 17–83 µg/mL). Oldenlandia diffusa and Rehmannia glutinosa significantly induced PXR-mediated CYP3A4 (p<0.001). Oldenlandia diffusa also significantly induced CYP3A4 mRNA levels (p<0.001 at 250 µg/mL).

Conclusions

Concomitant use of Oldenlandia diffusa and Rehmannia glutinosa could result in induction of CYP3A4, leading to a reduced efficacy of drugs that are CYP3A4 substrates and have a narrow therapeutic window. Because of the possible enhanced toxicity caused by CYP3A4 inhibition, clinical effects of CYP3A4 inhibition by Astragalus propinquus and Codonopsis tangshen must also be taken into account. In conclusion, herb–drug interactions between Chinese herbs and various CYP3A4 substrates can occur. Further research to investigate the clinical relevance of the interactions caused by Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus is required.     

Hypnotic effects and binding studies for GABAA and 5-HT2C receptors of traditional medicinal plants used in Asia for insomnia

Aim of the study

Many medicinal plants have been used for treatment of insomnia in Asia. However, scientific evidence and precise mechanism for their sedative-hypnotic activity have not been fully investigated. Thus, we investigated the binding activity of the oriental plant extracts (mainly from Korea and Japan) to the well-known molecular targets for sleep regulation, GABA_A and 5-HT_2C receptors. Following the binding assay, sedative-hypnotic effects of the extracts with high affinity were examined in an animal model of sleep.

Materials and methods

Aqueous and ethanol extracts of 15 medicinal plants were tested for binding at the benzodiazepine site of GABA_A receptor and 5-HT site of 5-HT_2C receptor. The sedative-hypnotic effects of selected extracts were evaluated by measuring the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of extracts.

Results

In the GABA_A assay, the ethanol extracts of licorice and danshen displayed concentration-dependent, high affinity binding, whereas in the 5-HT_2C assay, the ethanol extracts of ginseng and silk tree showed high affinity. Among these extracts we tested previously uncharacterized licorice and silk tree for hypnotic effects. We found the ethanol extracts of licorice and silk tree significantly decreased sleep latency and increased sleep duration in pentobarbital-induced sleep.

Conclusions

We demonstrate for the first time that licorice and silk tree have the sedative-hypnotic activity possibly by modulating GABA_A and 5-HT_2C receptors. We propose that licorice and silk tree might be effective candidates for treatment of insomnia.     

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.     

Effect of panaxytriol on cytochrome P450 3A4 via the pregnane X receptor regulatory pathway

Panaxytriol (PXT) is one of the major effective components of red ginseng and Shenmai injection. The present study aimed to explore the effect of PXT on cytochrome P450 3A4 (CYP3A4) based on the pregnane X receptor (PXR)–CYP3A4 regulatory pathway in HepG2 cells and hPXR‐overexpressing HepG2 cells treated with PXT for different time periods using quantitative polymerase chain reaction, Western blot, and dual‐luciferase reporter gene assays. PXT could upregulate the levels of PXR and CYP3A4 mRNA in HepG2 cells treated with PXT for 1 hr, with no impact on the expression of their protein levels. The expression levels of both PXR and CYP3A4 mRNA and protein in HepG2 cells treated with PXT for 24 hr increased in a concentration‐dependent manner. The effects of PXT on the expression of PXR and CYP3A4 mRNA and protein in hPXR‐overexpressing HepG2 cells were similar to those in HepG2 cells. Moreover, the influence trend of PXT on CYP3A4 was consistent with that of PXR in HepG2 cells and hPXR‐overexpressing HepG2 cells. The dual‐luciferase reporter gene assay in HepG2 cells further demonstrated that PXT treatment for specific time periods could significantly induce the expression of CYP3A4 mediated by the PXR regulatory pathway.     

South African plants used in traditional medicine to treat epilepsy have an antagonistic effect on NMDA receptor currents

Ethnopharmacological relevance

Several Searsia species (Anacardiaceae), including Searsia dentata and Searsia pyroides, are used in South Africa traditional medicine to treat epilepsy. Ethanol leaf extracts of these plants have been shown to act as possible antagonists of N-methyl-d-aspartate (NMDA)-type glutamate receptors.

Materials and methods

Leaf material of three Searsia species were collected from the Botanical Garden at the University of KwaZulu-Natal, Pietermaritzburg; dried and extracted with ethanol in an ultrasound bath. Filtered and dried extracts were resuspended in DMSO (100 mg/ml) and diluted in the recording solution. The effect of Searsia dentata, Searsia pyroides and Searsia glauca extracts was investigated in dissociated cerebellar granule cells (CGCs) from 8-day-old rats and in transiently transfected HEK (human embryonic kidney) 293 cells (HEK), expressing either NR1a/NR2A or NR1a/NR2B receptors. In both systems we measured whole-cell currents elicited by 0.5 mM NMDA (CGCs) or 50 μM glutamic acid (HEK) at −60 mV in 0 Mg and 30 μM glycine and NMDA driven Ca influx in Fura2-loaded CGC.

Results

Searsia dentata and Searsia pyroides ethanol extracts caused a dose-dependent decrease of NR current with ED₅₀ close to 0.03 mg/ml in CGC and a similar inhibition (80% with 1 mg/ml) in HEK cells, while Searsia glauca was much less effective. The inhibition was dependent on time of incubation and slightly favored by opening of the NR channel. It was hardly reversible during the recording time, but was not caused by accelerated run-down or by interaction with the modulatory redox site. Searsia pyroides ethanol extract also depressed the NMDA stimulated increase in intracellular Ca.

Conclusions

The data confirm the specificity of Searsia dentata and Searsia pyroides and justify their use in traditional medicine. These plants may combine one or more γ-aminobutyric acid (GABA)_A agonists with one or more NMDA antagonists, thus representing an efficient treatment for epilepsy.     

Toxicity of medicinal plants used in traditional medicine in Northern Peru

Ethnopharmacological relevance

The plant species reported here are traditionally used in Northern Peru for a wide range of illnesses. Most remedies are prepared as ethanol or aqueous extracts and then ingested. The aim of this study was to evaluate the potential toxicity of these extracts.

Materials and methods

The toxicity of ethanolic and water extracts of 341 plant species was determined using a brine-shrimp assay.

Results

Overall 24% of the species in water extract and 76% of the species in alcoholic extract showed elevated toxicity levels to brine-shrimp. Although in most cases multiple extracts of the same species showed very similar toxicity values, in some cases the toxicity of different extracts of the same species varied from non-toxic to highly toxic.

Conclusions

Traditional preparation methods take different toxicity levels in aqueous and ethanol extracts into account when choosing the appropriate solvent for the preparation of a remedy.     

Anti-inflammatory effect of a methanolic extract of leaves of Dregea volubilis

Aim of study

The aim of this study was to establish the anti-inflammatory activity of the methanolic extract of Dregea volubilis leaves (MEDV) with its fractions and to delineate the possible mechanism of action for MEDV.

Materials and methods

The anti-inflammatory activities of MEDV along with its petroleum ether and chloroform fractions were evaluated in a carrageenan induced model of acute inflammation. The effect of MEDV on lipopolysaccharide induced production of nitric oxide (NO) in macrophages was also studied.

Results

MEDV (100, 200 and 400 mg/kg body weight) significantly reduced carrageenan induced paw edema; chloroform fraction was most potent (66%, p < 0.001). MEDV was non-toxic up to 125 μg/ml in mouse peritoneal macrophages wherein it (0-100 μg/ml) reduced lipopolysaccharide induced NO production.

Conclusion

MEDV possesses significant anti-inflammatory activity. Chloroform fraction of MEDV showed best anti-inflammatory activity.     

Up-regulatation of CYP3A expression through pregnent X receptor by praeruptorin D isolated from Peucedanum praeruptorum Dunn

Ethnopharmacological relevance

Qianhu, the dried roots of Peucedanum praeruptorum DUNN (Umbelliferae), is a well-known traditional Chinese medicinal herb which was officially listed in the Chinese Pharmacopoeia. Praeruptorin D (PD) is one of the major active constituents of Peucedanum praeruptorum Dunn (Qianhu). The Pregnane X receptor (PXR) is an orphan nuclear receptor and plays a pivotal role in the activation of human cytochrome P450 3A4 (CYP3A4) gene.

Aim of the study

The purpose of this study was to investigate the effect of PD on the PXR-mediated transactivation of CYP3A4, and thus to predict potential herb–drug interactions between PD, Qianhu, and the other co-administered drugs that metabolized by CYP3A4.

Materials and methods

The effect of PD on the Cyp3a11, mPXR mRNA expression in mice primary hepatocytes was measured using real-time PCR. The gene expression, protein expression, and catalytic activity of CYP3A4 in the LS174T cells after transfected with PXR expression plasmids were determined by real-time PCR, Western blot analysis, and LC–MS/MS based CYP3A4 substrate assay.

Results

The results revealed that the level of Cyp3a11 gene expression in mice primary hepatocytes was significantly increased by PD, but PD cannot induce the mPXR gene expression. On the other hand, CYP3A4 mRNA, protein expression and functional activity in PXR-over-expression LS174T cells were significantly increased by PD through PXR-mediated pathway; conversely, no significant change was found in the untransfected cells.

Conclusions

These findings suggest that PD can significantly up-regulate CYP3A4 expression and activity via the PXR-mediated pathway and this should be taken into consideration to predict any potential herb–drug interactions when PD and Peucedanum praeruptorum Dunn are co-administered with other drugs.     

Apoptotic activity of ethanol extract from Styrax Japonica Siebold et al Zuccarini in HepG2 cells

Ethnopharmacological relevance

Styrax japonica Siebold et al Zuccarini (SJSZ) has been used to heal inflammation and bronchitis as an herbal plant in Korea.

Aims of the study

The purpose of the present study is to determine whether the ethanol (EtOH) extract of SJSZ induces the programmed cell death (apoptosis) in human hepatoma HepG2 cells.

Materials and methods

It was evaluated cytotoxicity using MTT assay, amount of intracellular reactive oxygen species (iROS) and Ca²⁺ using fluorescence. Activities of apoptotic relevant factors [Bid, cytochrome c, caspase-9, -3, and poly-(ADP-ribose) polymerase (PARP)] were measured by Western blot.

Results

The results in this study indicated that ethanol extract of SJSZ (75 μg/ml) stimulates to increase amount of iROS, Ca²⁺, and the apoptotic relevant factors [Bid, cytochrome c, caspase-9, -3, and poly-(ADP-ribose) polymerase (PARP) in the HepG2 cells.

Conclusion

The results in this study indicated that ethanol extract of SJSZ (75 μg/ml) induces programmed cell death (apoptosis) in the HepG2 cells. Therefore, we speculate that ethanol extract of SJSZ could be used for healing of hepatocarcinoma as one of chemotherapeutic agents.     

Antiosteoporotic compounds from seeds of Cuscuta chinensis

Ethnopharmacological relevance

The seeds of Cuscuta chinensis (Tu-Si-Zi, TSZ) have long been used for the treatment of osteoporosis in China and some Asian countries. The compounds in TSZ responsible for the antiosteoporotic activity are still poorly understood.

Aim of the study

The present study was designed to investigate the osteogenic compounds in TSZ, and to evaluate their antiosteoporotic effects in osteoblastic cells.

Materials and methods

Osteoblast-like UMR-106 cells were used for bioactivity-guided isolation of the active compounds. The activity of alkaline phosphatase (ALP) in UMR-106 cells was measured by p-nitrophenyl sodium phosphate assay. The proliferation of UMR-106 cells was assayed by Alamar-Blue method. Estrogenic activity of the extracts and isolated compounds was evaluated by activation of estrogen response element (ERE) luciferase reporter expression in HeLa cells co-transfected with human estrogen receptor subtypes (ERα or ERβ) expression vectors and 5 × ERE luciferase reporter plasmid. Antiestrogenic activity of the extracts and isolated compounds were evaluated by activation of activator protein-1 (AP-1) luciferase reporter expression in HeLa cells co-transfected with human estrogen receptor subtypes (ERα or ERβ) expression vectors and 6 × AP-1 luciferase reporter plasmid.

Results

ALP-guided fractionation led to the isolation of five known flavonoids, quercetin, kaempferol, isorhamnetin, hyperoside and astragalin from the crude ethanolic extract of TSZ. Further study showed that kaempferol and hyperoside significantly increased the ALP activity in UMR-106 cells. Astragalin promoted the proliferation of UMR-106 cells whereas other compounds had no such effect. The isolated compounds showed estrogenic activity but quercetin, kaempferol and isorhamnetin showed more potent ERβ agonist activity. However, compared with their ER agonist activity, only quercetin and kaempferol showed potent ER antagonist activity by activating ERα/β-mediated AP-1 reporter expression.

Conclusions

Our findings validated the clinical use of TSZ in the treatment of osteoporosis, and demonstrated that kaempferol and hyperoside are the active compounds in TSZ for the osteogenic effect.     

Drynaria fortunei J. Sm. promotes osteoblast maturation by inducing differentiation-related gene expression and protecting against oxidative stress-induced apoptotic insults

Aim of the study

Drynaria fortunei J. Sm. is one variety of the traditional Chinese medical herb Gusuibu. This study was aimed to evaluate the effects of water extracts of Kunze on regulation of osteoblast maturation and its possible mechanisms.

Materials and methods

Primary osteoblasts prepared from neonatal rat calvarias were exposed to the water extracts of Kunze (WEK), and the cytotoxicity was assayed. Osteoblast maturation was evaluated by analyzing cell mineralization. RT-PCR was executed to determine the effects of WEK on regulation of osteoblast differentiation-related gene expression. Nitrosative stress and apoptotic cells were quantified using flow cytometry.

Results

Exposure of rat calvarial osteoblasts to WEK did not affect cell viability, but significantly promoted osteoblast mineralization. WEK induced osteoprogenitor proliferation-related insulin-like growth factor-1 mRNA, but did not affect collagen type 1 mRNA expression. Treatment with WEK likewise induced the expression of matrix maturation-related bone morphogenetic protein (BMP)-2 and BMP-6 mRNA. Consequently, WEK enhanced the levels of mineralization-related alkaline phosphatase, ostepontin, and osteocalcin mRNA in osteoblasts. In addition, exposure of osteoblasts to WEK alleviated nitrosative stress-caused apoptotic insults.

Conclusions

This study shows that WEK can promote osteoblast maturation by regulating bone differentiation-related gene expression and defending against nitrosative stress-induced apoptotic insults.     

Action mechanism of Zuo Gui Yin Decoction's promotion on estradiol production in rats during the peri-menopausal period

Aim of the study

Although Zuo Gui Yin Decoction has long been used in Traditional Chinese Medicine to treat menopausal symptoms, the underlying mechanism(s) by which these effects are induced remains to be defined. The aim of this study was to investigate the action mechanism of Zuo Gui Yin Decoction on estradiol production in the rat ovary during peri-menopause.

Materials and methods

The peri-menopausal animal model was established by natural aging. Peri-menopausal rats were treated by intragastric administration (ig) with low (13.78 g kg⁻¹), middle (20.67 g kg⁻¹) or high (31 g kg⁻¹) dose of Zuo Gui Yin Decoction per day for 8 weeks. At the 8th weekend, the rats were sacrificed for sampling. Estradiol (E₂) levels in rats’ serum were evaluated by radioimmunoassay (RIA). RT-PCR, in situ hybridization and immunohistochemistry were used to determine mRNA and protein expression of relevant genes.

Results

Medium- and high-dose of Zuo Gui Yin Decoction could significantly increase serum estradiol concentration, ovarian CYP19 mRNA levels, and P450_arom protein expression in rats during peri-menopause. Zuo Gui Yin Decoction at three different dosages all could promote FSHR expression and the effect of low-dose was the greatest. Zuo Gui Yin Decoction could elevate LRH-1 and ER_α expression in a dose dependent manner.

Conclusions

Taken collectively, these findings suggest that Zuo Gui Yin Decoction could promote estradiol production in rat serum during peri-menopausal period through ovarian ER_α → LRH-1 → CYP19 pathway as well as the ovarian classical FSHR → CYP19 mechanism.     

Pharmacokinetic comparisons of rutaecarpine and evodiamine after oral administration of Wu-Chu-Yu extracts with different purities to rats

Ethnopharmacological relevance

Wu-Chu-Yu is a well-known herbal drug used for hypertension. Rutaecarpine and evodiamine are main bioactive components of the medicine.

Materials and methods

A sensitive and specific HPLC method was developed to analyze rutaecarpine (Rut) and evodiamine (Evo) in rat whole blood. The pharmacokinetics of Rut and Evo after oral administration of Wu-Chu-Yu extracts with different purities to rats was compared to evaluate the effect of purity of Wu-Chu-Yu extracts on the absorption of Rut and Evo. Male Sprague-Dawley rats were given Wu-Chu-Yu extracts with different purities (high, medium and low) approximately the same doses of equivalent to Rut (40 mg/kg) and Evo (31 mg/kg). The contents of Rut and Evo were 45 and 35%, 28 and 21%, 9 and 7% in high, medium and low purity extracts, respectively. At different time points (0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3 and 4 h) after administration, the concentrations of Rut and Evo in rat whole blood were determined by HPLC, and main pharmacokinetic parameters were calculated.

Results

The results indicated that the absorption of Rut and Evo in Wu-Chu-Yu extracts was improved when compared with the pure Rut and Evo and there were significant differences among different groups.

Conclusions

The bioavailability of Rut and Evo was increased along with the increasing of purity (16%-80%) in Wu-Chu-Yu extracts.     

Anti-hyperglycemic effect of Opuntia streptacantha Lem

Aim of the study

This experiment studied two extracts of Opuntia streptacantha, a plant used by the Mexican population to treat type 2 diabetes, in different assays to contribute to the understanding of the hypoglycemic mechanism of this plant.

Materials and methods

Two different extracts were prepared and tested: the first extract was a filtrate of the traditional liquefied extract (LE) preparation of the cladode; and the second filtrate extract (FE) is a filtered sample of the first. Both extracts contained a newly identified compound for Opuntia (4-hydroxy)-phenyl acetic acid derivate, they were tested on streptozotocin (STZ)-diabetic rats in a series of two tests. The first test was performed to confirm if STZ-diabetic rats presented a hypoglycemic effect after administration of the extracts (LE 135 mg/kg and FE 27 mg/kg). In the second experiment, the extracts were administered before an oral glucose tolerance test (OGTT) to confirm if they have an anti-hyperglycemic effect (LE 135 mg/kg, FE 12 and 27 mg/kg).

Results

The extracts administered to STZ-diabetic rats did not produce a significant hypoglycemic effect compared to the control group, while the same extracts administered before an OGTT produced an anti-hyperglycemic effect compared to the control group.

Conclusions

The filtered, traditional LE of the cladode of Opuntia streptacantha produces an anti-hyperglycemic effect when administered before a glucose challenge, and this anti-hyperglycemic effect is maintained after filtering the extract.Administration of both plants can improve glycemic control by blocking the hepatic glucose output, especially in the fasting state. These data support the traditional use of the plants as “agua de uso”, a cold infusion of the plant consumed over the course of a day.