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Ginkgolide B, one of the important components of Ginkgo biloba extracts, has been revealed to exhibit great potential in therapy of cerebrovascular diseases. However the lack of permeability greatly limited it from further clinical application. Based on the prediction model for blood brain barrier (BBB) permeation, herein a potential brain-targeting analog ginkgolide B cinnamate (GBC) was successfully synthesized and characterized. After intravenous administration of GBC or GB, liquid chromatography tandem mass spectrometry (LC–MS/MS) was conducted to determine the analog in rat plasma and brain. The results showed that GBC had a significant increase in BBB permeability. A significant 1.61-times increase in half-life was observed for GBC and the drug targeting index (DTI) value was calculated to be 9.91. The experiment results matched well with the predicted one, which revealed that BBB permeability prediction model combined with in vivo study could be used as a quick, feasible and efficient tool for brain-targeting drug design. [ABSTRACT FROM AUTHOR]

In this research, a sensitive and reliable LC–MS/MS method was developed and applied to determine the concentration of pristimerin in rat plasma, cell incubation media and metabolism incubation mixtures. The absolute oral bioavailability of pristimerin is 28.4% at a dose of 1 mg · kg − 1 , and the bioavailability was poor. The bidirectional transport of pristimerin across Caco-2 cells was studied in vitro . A markedly higher transport of pristimerin across Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. The result indicated that P-gp might be involved in the transport of pristimerin in intestine. The phase I and phase II metabolic stability was also investigated using human liver microsomes (HLM) and S9 fractions, respectively. Pristimerin was stable in S9 fractions but metabolized in HLM with a half-life of 20.4 min, which indicated that pristimerin could be mainly metabolized by phase I enzymes. In conclusion, the absolute oral bioavailability of pristimerin in plasma, transport across Caco-2 cell monolayers, and metabolic stability in HLM and S9 fractions were systematically investigated by using a sensitive and reliable LC–MS/MS method. [ABSTRACT FROM AUTHOR]

Psoralea corylifolia L. is a traditional Chinese medicine for the treatment of various skin diseases such as psoriasis, vitiligo and chronic graft-versus-host. Bakuchiol, isolated from the seeds of P. corylifolia L., is one of the most important active compounds. To study the metabolic fate of bakuchiol in rats, an ultra performance liquid chromatography/electrospray ionization–photo diode array–quadrupole time of flight–mass spectrometry (UPLC/ESI–PDA–QTOF–MS) combined with MetaboLynx XS software was used, peak area–time curves of major metabolites in plasma from bakuchiol were determined. A total of 11 metabolites were identified after a single oral administration of bakuchiol, including 6 in plasma, 10 in bile, 8 in urine and 2 in feces, the metabolic transformation pathways of bakuchiol in rats included oxidation, hydroxylation, methylation, O-glucuronide conjugation and O-sulfate conjugation. In conclusion, this study expands our knowledge about the metabolism of bakuchiol which will be conducive to reveal its in vivo pharmacological and toxicological material basis, in addition, UPLC/ESI–PDA–QTOF–MS coupled with MetaboLynx XS software can be adopted as a useful tool for quick detection and identification of metabolites from medicine in vivo. [ABSTRACT FROM AUTHOR]

Two new triterpenoid estersaponins ( 1, 2 ) were isolated from the leaves of Pittosporum tobira ‘Variegata’ (Thunb.) W. T. Aiton, along with one known saponin ( 3 ) and one known flavonoid glycoside ( 4 ). Their structures were established by different spectroscopic methods including 1D and 2D NMR, UV, as well as ESI-MS analysis. The investigated 80% aqueous methanol extract showed significant dose dependent inhibition of acetic acid induced abdominal writhing in mice. The n -butanol fraction exerted moderate antimicrobial activity against Staphylococcus aureus and Escherichia coli . In addition, it showed in vitro antioxidant activity with IC 50 value (7.3 μg/ml) lower than that of the positive control ascorbic acid (11.2 μg/ml), using DPPH free radical scavenging activity method. Evaluation of its in vitro cytotoxicity showed strong activity against breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and colon carcinoma (HCT) cell lines. [ABSTRACT FROM AUTHOR]

The effects of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) were studied in the mouse maximal electroshock seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Total brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay to ascertain any pharmacokinetic contribution to the observed anticonvulsant effects. Results indicate that xanthotoxin (50 and 100 mg/kg, i.p.) significantly potentiated the anticonvulsant activity of carbamazepine against maximal electroshock-induced seizures (P < 0.05 and P < 0.001, respectively). Similarly, xanthotoxin (100 mg/kg, i.p.) markedly enhanced the anticonvulsant action of valproate in the maximal electroshock seizure test (P < 0.001). In contrast, xanthotoxin (100 mg/kg, i.p.) did not affect the protective action of phenobarbital and phenytoin against maximal electroshock-induced seizures in mice. Moreover, xanthotoxin (100 mg/kg, i.p.) significantly increased total brain concentrations of carbamazepine (P < 0.001) and valproate (P < 0.05), but not those of phenytoin and phenobarbital, indicating pharmacokinetic nature of interactions between drugs. In conclusion, the combinations of xanthotoxin with carbamazepine and valproate, despite their beneficial effects in terms of seizure suppression in mice, were probably due to a pharmacokinetic increase in total brain concentrations of these antiepileptic drugs in experimental animals. [ABSTRACT FROM AUTHOR]

Fargesin displayed similar chromatographic retention peak to metoprolol in the cardiac muscle/cell membrane chromatography (CM/CMC) and β 1 adrenergic receptor/cell membrane chromatography (β 1 AR/CMC) models. To provide more biological information about fargesin, we investigated the effects of fargesin on isoproterenol-(ISO-) induced cells injury in the high expression β 1 adrenergic receptor/Chinese hamster ovary-S (β 1 AR/CHO-S) cells and occluding the left coronary artery- (LAD-) induced myocardial ischemia/reperfusion (MI/R) injury in rats. The results in vitro showed that ISO-induced canonical cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) levels were decreased by fargesin in β 1 AR/CHO-S cells. Fargesin attenuated the serum creatine kinase (CK), lactate dehydrogenase (LDH), and improved histopathological changes of ischemic myocardium compared with the I/R rats. Similar results were obtained with Evans Blue/TTC staining, in which fargesin notably reduced infarct size. Moreover, compared with the I/R group, fargesin increased COX release and the activities of some endogenous antioxidative enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), but suppressed malondialdehyde (MDA), and intracellular ROS release. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated fargesin suppressed myocardial apoptosis, which may be related to inhibition of caspase-3 activity. Taken together, these results provided substantial evidences that fargesin as a potential β 1 AR antagonist through cAMP/PKA pathway could protect against myocardial ischemia/reperfusion injury in rats. The underlining mechanism may be related to inhibiting oxidative stress and myocardial apoptosis. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a chronic condition that is difficult to be treated. Current therapies available are either ineffective or non-specific thus requiring newer treatment approaches. In this study, we investigated the antiallodynic and antihyperalgesic effects of zerumbone, a bioactive sesquiterpene from Zingiber zerumbet in chronic constriction injury (CCI)-induced neuropathic pain animal model. Our findings showed that single and repeated dose of intra-peritoneal administration of zerumbone (5, 10, 50, 100 mg/kg) significantly attenuated the CCI-induced neuropathic pain when evaluated using the electronic von Frey anesthesiometer, cold plate, Randall–Selitto analgesiometer and the Hargreaves plantar test. Zerumbone significantly alleviated tactile and cold allodynia as well as mechanical and thermal hyperalgesia. Our findings are in comparison to the positive control drugs thatused gabapentin (20 mg/kg i.p.) and morphine (1 mg/kg i.p.). Together, these results showed that the systemic administration of zerumbone produced marked antiallodynic and antihyperalgesic effects in the CCI-induced neuropathic pain in mice and may serve as a potential lead compound for further analysis. [ABSTRACT FROM AUTHOR]

Oxysophocarpine (OSC), an active and toxic quinolizidine alkaloid, is highly valued in Sophora flavescens Ait. and Subprostrate sophora Root. OSC is used to treat inflammation and hepatitis for thousands of years in China. This study aims to investigate the CYP450-mediated reduction responsible for metabolizing OSC and to evaluate the absorption and metabolism of OSC in rat in situ. Four metabolites were identified, with sophocarpine (SC) as the major metabolite. SC formation was rapid in human and rat liver microsomes (HLMs and RLMs, respectively). The reduction rates in the liver are two fold higher than in the intestine, both in humans and rats. In HLMs, inhibitors of CYP2C9, 3A4/5, 2D6, and 2B6 had strong inhibitory effects on SC formation. Meanwhile, inhibitors of CYP3A and CYP2D6 had significant inhibition on SC formation in RLMs. Human recombinant CYP3A4/5, 2B6, 2D6, and 2C9 contributed significantly to SC production. The permeability in rat intestine and the excretion rates of metabolites were highest in the duodenum (p < 0.05), and the absorbed amount of OSC in duodenum and jejunum was concentration-dependent. The metabolism could be significantly decreased by CYP3A inhibitor ketoconazole. In conclusion, the liver was the main organ responsible for OSC metabolism. First-pass metabolism via CYP3A4/5, 2B6, 2D6, and 2C9 may be the main reason for the poor OSC bioavailability. [ABSTRACT FROM AUTHOR]

Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia , had been proved to be effective in hyperuricemic control. Allopurinol is a commonly used medication to treat hyperuricemia and its complications. In this study, we evaluated whether Pallidifloside D could enhance allopurinol's effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. We found that, compared with allopurinol alone, the combination of allopurinol and Pallidifloside D significantly decreased the serum uric acid level and increased the urine uric acid level (both P < 0.05), leading to the normalized serum and urine uric acid concentrations. Data on serum, urine creatinine and BUN supported these observations. Our results showed that the synergistic effects of allopurinol combined with Pallidifloside D were linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions. [ABSTRACT FROM AUTHOR]

Background Red clover is an important source of isoflavones; which has been made commercially available as dietary supplements for the treatment of menopausal symptoms. Bioavailability and metabolism of these red clover isoflavones (RCI) have not been studied in detail. Fructooligosaccharides (FOS) stimulate the growth of intestinal bacteria and play an important role in the formation of certain isoflavone metabolites, such as equol and O -desmethylangolensin. Objective To determine the bioavailability of RCI metabolites and analyse whether FOS supplementation could influence their bioavailability. Methods Seventeen healthy adults were enrolled in the study carried out in two periods. In the first, compound bioavailability was determined after consumption of 80 mg of RCI (MF11RCE). In the second, a 6-day supplementation of 2 × 3000 mg/day of FOS was administered before isoflavone consumption. Results Biochanin A and formononetin were rapidly absorbed and both reached maximum concentrations at an average of 5–7 h. Demethylation was a major reaction in the metabolic pathway. Daidzein serum level peaked after about 12.6 h. Supplementation with FOS led to a significant decrease in the bioavailability of daidzein, dihydroformononetin, dihydrogenistein and dihydrodaidzein. An increase in equol production was also observed which did not reach statistical significance ( p > 0.05). Conclusion This study is the first to provide detailed data on RCI bioavailability in humans and determine no influence of FOS yet a trend toward increased equol production. More research is warranted involving a greater sample size. [ABSTRACT FROM AUTHOR]

Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, C max and AUC 0–10h values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the C max and AUC 0–10h values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Garcinia kola is a medicinal plant traditionally used for malaria therapy in Central Africa. Aim of the study To evaluate the antimalarial potencies in vitro and in vivo of pure biflavanones from G. kola . Materials and methods The pure biflavanones were obtained by bioassay-guided fractionation of a 70% ethanol extract of G. kola seeds and their chemical structures were elucidated by comparison of their NMR ( 1 H and 13 C) and mass spectral data with those provided in the literature. Plasmodium falciparum (FCR-3, cycloguanil-resistant strain from Gambia) was used for in vitro assessments of antimalarial activities. Growth inhibition, intraerythrocytic development and parasite morphology were evaluated in culture by the microscopic observation of Giemsa-stained thin blood films. The cytotoxicity of the antimalarial compounds was evaluated against KB 3-1 (human epidermoid carcinoma) cells by MTT assay. In vivo antimalarial activities were determined in mice infected with Plasmodium berghei (ANKA strain) following a four-day suppressive test. Results The bioassay-guided fractionation of an extract of G. kola resulted in the isolation of three biflavanones (GB-1a, GB-1, and GB-2) as its active principles. These three biflavanones displayed not only potent inhibitory activity in vitro against P. falciparum proliferation but also antimalarial potency through oral administration in mice infected with P. berghei without signs of acute toxicity. GB-1 was found to exhibit the strongest in vitro antimalarial potency on P. falciparum with an IC 50 of 0.16 μM, whereas it exhibited a very low in vitro cytotoxicity on KB 3-1 cells with an IC 50 of greater than 150 μM. During an in vivo antimalarial assay in mice infected with P. berghei , GB-1 was found to exhibit biological potency with an approximate ED 50 of 100 mg/kg following oral administration. GB-1 was also shown to increase the average life span of the infected mice significantly compared to that of control mice ( p <0.01 Student’s t -test). Conclusions The antimalarial outcome of GB-1a, GB-1, and GB-2 may be related to the traditional utilization of this crude drug against malaria judging from their significant content in G. kola nuts. GB-1 showed the most potent antimalarial activity with a high selectivity index and, therefore could be exploited to identify the molecular target, which subsequently could be helpful to design novel therapeutics against malaria. GB-1 may be considered a promising antimalarial candidate for trial in vivo using higher animals infected with P. falciparum . [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Preparation of Lannea barteri is used in the treatment of epilepsy, gastritis, childhood convulsions among other uses in northern Nigeria for many years. The popularity of its efficacy is well established among the Traditional Medical Practitioners. Aim of the study The present study aimed at screening the ethanol stem bark extract of Lannea barteri for possible anticonvulsant action. Materials and method Anticonvulsant screening was carried out using pentylenetetrazole (PTZ), strychnine (STN) and picrotoxin (PTC) induced seizures in mice while Maximal electroshock (MES) test was carried out in day old chicks. Preliminary phytochemical screening of the extract was performed on the extract. The intraperitoneal median lethal dose (LD 50 ) was carried out in mice. Results The intraperitoneal ( i.p. ) LD 50 of the extract was estimated to be 567.70 mg/kg in mice. Lannea barteri (160 mg/kg) significantly ( p ≤0.05) delayed the mean onset of seizures induced by PTZ when compared with normal saline treated group. Similarly, the extract at 160 mg/kg significantly ( p ≤0.05) prolonged the latency of convulsion induced by STN. Lannea barteri (40 mg/kg) significantly ( p ≤0.05) delayed the mean onset of seizures induced by picrotoxin in mice. The extracts at all the doses tested showed no observable effect in decreasing the mean recovery time of convulsed chicks in MEST. Flavonoids, alkaloids, tannins, saponins and glycosides were found present in the stem bark extract. Conclusion Our findings revealed that the ethanol stem bark extract of Lannea barteri contained bioactive constituents that may be useful in the management of petit mal epilepsy and supports the ethnomedical claim for the use of its stem bark in the management of epilepsy. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Marsilea quadrifolia Linn. (MQ) has been used for insomnia and epileptic disorders in traditional Indian medicine. The present study is to isolate the active component responsible for antiepileptic property of MQ by evaluating its ability to minimize the reactive oxidative damage in brain due to chronic epilepsy in rat. Materials and methods 1-Triacontanol cerotate (1TAC) was isolated after chromatography on a silica gel from dried petroleum ether fraction of methanolic extract of MQ. Acute oral toxicity studies of 1TAC were carried out and efficacy of 1TAC on malondialdehyde (MDA) and reduced glutathione (GSH) production in different brain areas of chronic pentylenetetrazole (PTZ) induced epileptic rats were evaluated. Results Our results showed that PTZ-kindled chronic epileptic rats had an increase MDA and decreased GSH concentration in the frontal cortex as well as hippocampus, compared to the normal control. MDA and GSH concentrations in those brain areas were normalized after treatment with sodium valproate (SV) in 200 mg kg −1 bw; as well as 1TAC in 40 and 80 mg kg −1 bw doses. Conclusion Production of reactive oxygen species ( ROS) is known to worsen epileptogenesis. The isolated component 1TAC which reduced the reactive oxidative damage in hippocampus and frontal cortex of PTZ kindled rats could be responsible for antiepileptic property of MQ. Its action is found to be dose dependent, with 80 mg kg −1 bw showing even better efficacy than 200 mg kg −1 bw of SV. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Spilanthes africana is a plant used in several countries for the treatment of toothache, malaria, fracture, pneumonia, and dysentery. In order to establish the safety of aerial part of the plant extract, the acute and sub-acute toxicity of the aqueous extract of this plant has been evaluated in male and female young rats. Material and methods In acute toxicity, the effects of a single oral dose (2000 mg/kg and 5000 mg/kg) of the lyophilised aqueous extract have been determined. General behaviour, adverse effects and mortality were determined for up to 14 days. In sub-acute treatment, the effects of the extract in daily single oral administration at the doses of 250, 500 and 1000 mg/kg during 28 days were evaluated. One group treated at the dose of 1000 mg/kg for 28 days was let without treatment during 14 days to assess the possible reversibility of the harmful effects of the extract. Body weight, food and water intakes, biochemical and haematological parameters were recorded. Histopathological examination of liver, kidney and lungs were assessed. Results In acute study, a single administration of the aqueous extract at the doses of 2000 mg/kg or 5000 mg/kg did not induce mortality. Thus, the LD 50 of the aqueous extract of S. africana has been estimated higher than 5000 mg/kg. Four hours after administration of the extract, a reduction of the mobility, sensitivity to the noise and to touch has been observed. In sub-acute study, the administration of the extract during 28 days at all doses did not significantly modify the body weight. On the haematological analysis, a decrease of the rate of monocytes and a rise of lymphocytes counts were observed among the male group. In both sexes, it appeared a decrease of the rate of granulocytes two weeks after stopping the treatment. It has also been observed in different groups among the females, an increase of the mean corpuscular content and the mean concentration in haemoglobin as well as an increase of platelets. A significant decrease of transaminases, alkaline phosphatase, triglycerides, and a significant increase of total bilirubin compared to the normal group has been observed. There was a significant decrease in renal catalase in both sexes compared with different control groups. Besides, a significant increase of the kidney rates of glutathione and malondialdehyde have also been observed in the female treated at the doses of 1000 mg/kg. Histopathological analysis has shown vascular congestion and leucocyte infiltrations in the liver of animals treated at the dose of 1000 mg/kg. This congestion has been marked in satellite group. In the kidney female satellite group, tubular clarifications have been observed and disappear when stopping the treatment. Conclusion These results show that the aqueous extract of S. africana given by the oral route is slightly toxic. However in sub-acute treatment, higher doses could provoke functional and structural changes in the organism which could in part reversible. Thus the extract should be used with caution. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Danshen and Sanqi Prescription (Dan-Qi) is commonly used to treat cardiovascular diseases (CVD) in China. Since Danshen and Sanqi are reported to ameliorate lipid metabolism disorders at treatment of cardiovascular diseases. Meanwhile, it is reported that co-administration of Danshen and Sanqi exhibited significant pharmacokinetic herb–herb interactions. We reasoned that Danshen and Sanqi combination could be potentially function synergistically in treating diet induced insulin resistance. Materials and methods Using high calori food induced Drosophila and mice models, we assessed Danshen and Sanqi treatment for their anti-diabetic effects. Results The combination of Danshen and Sanqi (Dan-Qi) effectively improved fat and glucose metabolism of the high-sugar and high-fat diet fed fruit flies. More importantly, Dan-Qi significantly ameliorated hyperlipidemia and hyperglycemia phenotype caused in high-fat diet induced obesity (DIO) mouse model. The Dan-Qi treated DIO mice showed lower fasting insulin, triglycerides, total and low-density lipoprotein cholesterol (LDL-C) levels in plasma, much better than Danshen or Sanqi treated alone. It was shown that Dan-Qi prescription reduced fat accumulation in the liver with Sanqi playing the major role. Interestingly, it was not Danshen or Sanqi alone, but the combination markedly increased glycogen deposition in mice liver. Quantitative RT-PCR showed Dan-Qi increased liver glycogen synthesis gene like Glut-1, GK, and Glut-4, reduced fat and cholesterol anabolism genes such as SREBP-1c, ACC, ATP-CL, ACS. Meanwhilpose tissues and muscle tissues, the glucose and fat metabolism genes are changed accordingly to pro-catabolism status. Notably, endogenous plasma metabolites of Dan-Qi treated mice displayed much better overral rectifying effects than the Danshen or Sanqi alone. Conclusions Our data demonstrated that Danshen and Sanqi combination exerted significant anti-diabetic efficacy, and Dan-Qi prescription could be potentially considered as a therapeutic application in diabetes. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Solanum cernuum Vell. (Solanaceae) is a Brazilian medicinal plant, traditionally known as “panaceia”. Its folk name is probably due to its wide range of applications in traditional medicine including the treatment of ulcers. Aim of the study To evaluate the gastroprotective activities of the hydroethanolic extract (ESC) of S. cernuum and its major isolated compounds using in vivo gastric ulcer models. Material and methods The ESC extract was obtained by maceration followed by percolation of the dried and powdered leaves of S. cernuum in ethanol:water (7:3). The major compounds in the extract were isolated by applying various preparative chromatographic techniques. The gastroprotective activity was evaluated in mice using different gastric ulcer-induced models. The anti- Helicobacter pylori activity was performed using the agar-well diffusion and broth microdilution methods. Results The ESC extract showed gastroprotective effects in the assay of acute gastric ulcer-induced by HCl/EtOH, nonsteroidal anti-inflammatory drug, and acetic acid-induced chronic ulcer protocols. The results also demonstrated that the gastroprotection induced by ESC extract is related to the activity of nitric oxide and endogenous sulfhydryls, which are important gastroprotective factors. The ESC extract and the alkaloid cernumidine did not show activity against H. pylori in the concentrations tested. Conclusions The present study showed that the crude extract of S. cernuum possessed gastroprotective activity which corroborating the traditional use of this plant for the treatment of gastric ulcers. The isolated flavonoids, quercitrin and afzelin as well as the phenylpropanoid, isoferulic acid are suggested to be the compounds responsible for the gastroprotective activity of S. cernuum extract. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Gentiana scabra root extract (GS) is frequently prescribed as an internal remedy in traditional Korean medicine for treatment of diabetes mellitus. GS contains bitter iridoid glycosides including loganic acid, gentiopicrin, trifloroside, and rindoside. We previously reported that the intestinal bitter taste sensation stimulates GLP-1 secretion, and thereupon hypothesized that the blood glucose regulatory effect of GS is due to its GLP-1 secreting effect in enteroendocrine L cells. Materials and method We studied GLP-1 secreting effect of GS treatment and its cellular downstream mechanism in human enteroendocrine NCI-H716 cells using the G protein-coupled receptor (GPCR) pathway inhibitors. Intracellular calcium assay also demonstrated the signal transduction pathway stimulated by the GS treatment. Using db/db mice, we performed oral glucose tolerance test (OGTT) to examine the blood glucose lowering effect of GS administration. We also collected the mouse plasma during the OGTT to measure the GLP-1 and insulin levels. Result We demonstrated dose-dependent GLP-1 secreting effect of GS on the NCI-H716 cells. The GLP-1 secreting effect of GS is mediated by the G protein βγ-subunit and inositol triphosphate. Using db/db mice, we found that the effect of GS on lowering blood glucose is due to its GLP-1 secretion, and consequential insulinotropic effect. The chemical fingerprint of GS was obtained through a direct analysis in realtime mass spectrometry (DART-MS) and high-performance liquid chromatography (HPLC)/MS. Through the GLP-1 secretion study, we found that loganic acid, an iridoid glycoside, contributes to the GLP-1 secreting effect of GS. Conclusion The findings of this study highlight the potential of exploiting the antidiabetic effect of GS on type 2 diabetes mellitus patients. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Ludwigia octovalvis is an aquatic plant widely distributed throughout the tropical and sub-tropical regions. It is commonly consumed as a health drink and traditionally used for treating various ailments such as dysentery, diarrhea, diabetes, nephritisn and headache. No information is available on its in vivo antibacterial activity against an important foodborne pathogen, Shiga toxin producing Escherichia coli O157:H7. Materials and methods Male Balb/c mice were orally administered with the extract at doses of 200 or 400 mg/kg body weight for one week before the infection with E. coli O157:H7 and continued for 14 consecutive days after infection. Serum antibody (IgA, IgG and IgM) levels were quantified at days 7 and 14 post-challenge by an ADVIA ® 2400 Clinical Chemistry Auto Analyzer. Nitroblue tetrazolium (NBT) and Ceruloplasmin, as nonspecific immune parameters, were determined enzymatically. Results A significant increase ( p <0.05) in IgA serum level was indicated on the 7th day post-challenge with the pathogen in the experimental group received 400 mg/kg of the extract in comparison with other groups. Total IgA serum levels on day 7 post-challenge in groups of PBS negative control, E. coli O157:H7 positive control, E. coli O157:H7+200 mg/kg extract group and E. coli O157:H7+400 mg/kg extract group were 709.4±149.6, 1655.8±139.7, 1728.6±64.3 and 1971.4±135.6 µg/ml, respectively. Serum IgG and IgM did not significantly change among different groups. The extract administered orally to infected Balb/c mice did not affect the NBT as well as ceruloplasmin levels. Conclusions The extract of L. octovalvis contains biologically active principles which increased systemic immune response to E. coli O157:H7 via potentiating the synthesis of IgA antibodies. [ABSTRACT FROM AUTHOR]

Aim of the study Asthma is an ailment of airways characterized by activation of the T helper (Th) 2 lymphocytes and subsequent movement of inflammatory cells. Boerhavia procumbens of family Nyctaginaceae is locally used for the treatment of asthma, cough, hemorrhoids, dropsy, cardiac, eyes and kidney problems. We have evaluated its methanol extract (BPM) as a therapeutic candidate for asthma against toluene diisocyanate (TDI) allergic model in rat. The BPM extract was obtained from the whole plant of B. procumbens in methanol. Sprague-Dawley male 36 rats (200–250 g) were categorized into 6 groups having six rats in each category. The animals were provoked (10%) and sensitized (5%) by TDI. Animals of groups I–III were vehicle control (ethyl acetate), diseased control (TDI) and reference control (TDI+dexamethasone {2.5 mg/kg bw}), respectively. Animals of group IV (TDI+200 mg/kg bw) and group V (TDI+400 mg/kg bw) were administered with BPM whereas group VI was administered with 400 mg/kg bw alone of BPM. Protective effects of BPM were determined by counting the number of leucocytes and estimation of interleukines in blood, bronchoalveolar lavage (BAL) and in in vitro culture of spleen cells. Estimation of antioxidant enzymes, lipid peroxides and H 2 O 2 and histopathology of lungs were carried out for antioxidant potential of plant extract used. Results Methanol extract of B. procumbens suppressed the asthmatic symptoms and inhibited the infiltration of eosinophils and lymphocytes in lungs of TDI provoked rats. Administration of BPM to TDI provoked rats, dose dependently, inhibited the release of interleukins (IL)-2 in serum and IL-4, IL-6 interferon gamma (IFN-γ) in bronchoalveolar lavage (BAL) and in in vitro culture of spleen cells, and ameliorated the oxidative stress in lung tissues. Quantitative scoring of the lung histopathology exhibited protective effects of BPM and the inflammation, mucus, thickening of peribronchial smooth muscle layer and subepithelial deposition of collagen induced with TDI were ameliorated. The BPM has the anti-inflammatory properties that may be used to treat the asthma and inflammatory related ailments. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Scutia buxifolia , a native tree popularly known as “coronilha”, is widely used in Brazilian folk medicine for diuretic and anti-hypertensive purposes. Aim of the study We investigated the effects of a butanolic (BuOH) soluble fraction of the hydroethanolic extract (HESB) of bark of Scutia buxifolia on both blood pressure and urinary excretion of rats. The involvement of the nitric oxide/guanylate cyclase pathway in the hypotensive effect found was also explored. Material and methods We tested the effect of the BuOH soluble fraction of HESB on the mean arterial pressure (MAP) of anesthetized rats. The fraction was administered at doses of 1, 3 and 10 mg/kg (i.v.) in normotensive rats during continuous infusion of vehicle (10 μl/min), or phenylephrine (4 μg/kg/min), or l -NAME (7 mg/kg/min), two approaches able to induce a sustained hypertensive state. In some experiments, a bolus injection of ODQ (2 mg/kg) was administered in animals infused with phenylephrine before the administration of the BuOH soluble fraction of HESB. We also measured the effects of the BuOH soluble fraction on the MAP of spontaneously hypertensive rats (SHR). Separate groups of rats were treated orally with either HESB (10, 30 or 100 mg/kg), or its BuOH soluble fraction (3, 10 or 30 mg/kg), and were subjected to measurement of diuresis and blood pressure. Results The BuOH soluble fraction of HESB (10 mg/kg, i.v.) reduced the MAP of both phenylephrine-infused and SHR rats by 20.6±6.0 and 41.8±8.3 mm Hg, respectively. However, no hypotensive effect was found in normotensive animals infused with l -NAME, a non-selective inhibitor of nitric oxide synthase, or animals previously treated with the soluble guanylate cyclase inhibitor ODQ. The urinary excretion was increased by 70% at 6–8 h after a single oral administration of the BuOH soluble fraction of HESB (10 mg/kg), without change in urinary density, pH, or Na + and K + concentrations. In addition, MAP was lower 3 h after the acute oral treatment with the BuOH soluble fraction (82.1±3.8 mm Hg), compared with MAP of animals from the control group (97±3.2 mm Hg). Conclusion This study demonstrates that the BuOH soluble fraction of the hydroethanolic bark of Scutia buxifolia , which has its bark used in folk medicine for the treatment of hypertension mainly by its presumed diuretic properties, possesses both diuretic and hypotensive effects in rats, and that at least the hypotensive effect is fully dependent on activation of the nitric oxide/guanylate cyclase pathway. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Trichilia catigua preparations have antinociceptive, antiinflammatory, and neuroprotective activity. Recently, a neuroprotective role for T. catigua was proposed using an in vitro model of ischemia–reperfusion in rat hippocampal slices. The aim of the present study was to evaluate the effects of an ethyl-acetate fraction (EAF) of T. catigua , which has potent antioxidant activity, in mice subjected to an in vivo model of cerebral ischemia. Material and methods Male Swiss mice were subject to the bilateral common carotid occlusion (BCCAO) model of cerebral ischemia. The animals were orally administered the T. catigua EAF (200, 400, or 800 mg/kg) 30 min before and once per day for 7 days after BCCAO. Histological and behavioral outcomes were assessed using Nissl staining and the Morris water maze test of cognition, respectively. Results Mice that were subjected to BCCAO exhibited cognitive impairments in the Morris water maze. The spatial cognitive deficits were counteracted by T. catigua EAF administration (200–800 mg/kg). The T. catigua EAF significantly increased the number of intact-appearing Nissl-stained cells in the hippocampus in BCCAO mice. Conclusions These results show that the T. catigua EAF promoted functional recovery, decreased the delayed hippocampal cell loss, and mitigated the ongoing neurodegenerative processes induced by BCCAO in mice. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Rhizoma Anemarrhenae has been used in Asian countries for thousands of years to treat diabetes. Insulin resistance (IR) is the primary cause responsible for type 2 diabetes. The aim of this study was to to assess the hypoglycemic and insulin sensitizing properties of Rhizoma Anemarrhenae extract (TFA) in animal models of insulin resistance and/or diabetes and to delineate modes of action. Materials and methods In-vivo studies were performed on STZ-induced diabetic mice and KK-Ay mice, the former of which were given the extract alone or in combination with insulin for 7 days, and the latter of which were given the extract for 8 consecutive weeks. Fasting blood glucose and serum insulin levels were measured. Pancreatic tissue sections were examined using transmission electron micrographs. Further, hyperinsulinemic–euglycemic clamping study was conducted in BCG vaccine-induced insulin resistance rats, and glucose infusion rate was examined. Mechanisms of action were investigated in 3T3-L1 and Hela cells using Western blot analysis. Results Our study showed that TFA enhanced the glucose-lowering effects of exogenous insulin administration in STZ-induced diabetic mice. Therapeutic administration of TFA significantly reduced fasting blood glucose, and serum insulin levels, and markedly increased the size and the number of insulin-producing beta cells in KK-Ay mice. Further, hyperinsulinemic–euglycemic clamping study showed that glucose infusion rate was significantly improved in TFA-treated BCG vaccine-induced insulin resistance rats. Study of mechanism of action revealed that TFA increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in 3T3-L1 cells. It activates AMPK in a LKB1-independent manner, providing a unified explanation for the beneficial effects of TFA. Conclusions This study that TFA mediates activation of AMPK and improves overall glucose and lipid metabolism in diabetic rodents, highlights the potential utility of TFA for the management of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Helicteres angustifolia L. ( H. angustifolia L.) has been used as traditional medicine in the treatment of cancer in China and Laos. Its medical benefits, however, are still lacking of scientific evidence. Two extracts successively obtained from the root of H. angustifolia L., namely the aqueous root extract (ARE) and the ethanolic root extract (ERE), were used to evaluate the antioxidant and anticancer activities in vitro , and the antitumor efficacy of ARE was examined in vivo , respectively. Materials and methods ARE and ERE were extracted successively from H. angustifolia L. root with water and ethanol. In vitro antioxidant activities were assessed by radicals scavenging assay, ferrous chelating assay and reducing power assay. In vitro anticancer activities of ARE and ERE were evaluated by their cytotoxic effects against three human cancer cell lines. In addition, the anti-tumor activities of ARE in vivo were assessed by using Ht1080 (human fibrosarcoma cell line Ht1080) tumor xenografts mice. BALB/c nude mice were orally administrated with 200 mg/kg/d of ARE. The tumor inhibition rate was determined on day 42 after treatment by using histopathology analysis of the tumor tissues. Furthermore, relevant biochemical parameters in blood were analyzed to monitor their cytotoxic effect. Results In vitro assays indicated that ARE possessed relatively higher antioxidant and anticancer activities than ERE, with IC 50 values of 82.31±9.62, 62.50±6.99, and 127.49±2.9 μg/mL against DLD-1, A549, and HepG2 cells, respectively. In vivo tumor inhibition experiments suggested that ARE possessed significant antitumor efficacy in BALB/c nude mice with a tumor inhibition rate of 49.83±14.38% ( p <0.05) and little toxicity was observed to the host. Conclusion ARE from H. angustifolia L. possessed high antioxidant activities is active against liver cancer HepG2, lung cancer A549 and colon cancer DLD-1 cells in vitro and tumor xenografts bearing BALB/c nude mice in vivo . Further studies on elucidation of the mechanisms involved and isolation of the active components may provide more valuable information for the development of functional products from H. angustifolia L. and their application in cancer treatment. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Dendrobium aurantiacum var. denneanumis widespread in southern China, locally known as “Shihu”, “Huangcao” or “Fengdou”, has long been used in traditional Chinese medicine for antipyretic, immunomodulatory, anti-aging effects and eye benefiting. Aim of this study To investigate the effects of gigantol extracted from the stem of D. aurantiacum var. denneanum on the formation of galactose-induced cataractogenesis and the potential mechanisms underlying these effects. Materials and methods Cataract lens models were induced by d -galactose both in vitro and in vivo . The transparency of the rat lenses in vitro and in vivo was observed with an anatomical microscope and a slit lamp microscope. The differential protein and action targets of gigantol were determined and compared among the control group, model group, and gigantol group using two-dimensional electrophoresis and mass spectrometry (MS). Enzyme kinetics was used to show the ability of gigantol to respress aldose reductase (AR) and inducible nitric oxide synthase (iNOS). Quantitative real-time PCR (RT-qPCR). was used to detect repression of the expression of AR and iNOS genes. Molecular docking and dynamic simulation were used to predict the interaction points and combination patterns between gigantol, AR, and iNOS. Results Gigantol was found to prevent galactose-induced damage to the rat lenses both in vitro and in vivo , to delay lens turbidity, and to keep the lenses transparent. Differential proteomes, MS, and RT-qPCR showed AR and iNOS to be the target proteins of gigantol. Gigantol reduced the galactose-induced AR and iNOS mRNA expression by 51.2% and 60.9%, respectively. The IC50 of gigantol for inhibition of AR and iNOS activities were 65.67 μg/mL and 8.768 μg/mL, respectively. Gigantol–AR binding sites were Trp111, His110, Tyr48, and Trp20, and gigantol–iNOS binding sites were Ile195 and Gln257. The main forms of interaction were hydrophobic forces, hydrogen bonds, and van der Waals forces. Conclusion Gigantol extracted from D. aurantiacum var. denneanum was found to inhibit galactose-induced formation of cataracts through repression of the gene expression and activity of AR and iNOS. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Polyalthia longifolia var. pendula is a very popular herb in Bangladesh due to its traditional uses in treatment of rheumatism, bone fracture and gastric ulcer. The present study was conducted to investigate the antinociceptive activity of ethanol extract of P. longifolia (EEPL) bark. Materials and methods Hot plate and tail immersion tests, acetic acid-induced writhing test, glutamate and formalin-induced paw licking tests in mice were employed in this study. In all the experiments EEPL was administered orally at the doses of 50, 100 and 200 mg/kg body weight. To investigate the possible participation of opioid system in EEPL-mediated effects, naloxone was used to antagonize the action. Results EEPL showed a significant antinociceptive activity against both heat and chemical-induced nociception. The effects were dose-dependent and significant at the doses of 100 and 200 mg/kg of EEPL. Besides, pretreatment with naloxone caused significant inhibition of the antinociceptive activity induced by EEPL, revealing the possible involvement of the opioid receptors. Conclusion These results indicate the antinociceptive activity of the bark of P. longifolia and support the ethnomedical use of this plant in treatment of different painful conditions. [ABSTRACT FROM AUTHOR]

Background Alzheimer׳s disease (AD) is the most common cause of dementia. This disease is a progressive and irreversible brain disorder accompanied with severe learning and memory impairment. This study investigated whether treatment with standardized Lycii Fructus Extract (LFE) would improve the cognitive function and the pathological features of AD in 3xTg-AD mice. Ethnopharmacological relevance Lycii Fructus is a fruit of Lycium chinense Miller and widely distributed in East Asia and has been used traditionally for anti-aging purposes. Materials and methods The cognitive function of 3xTg-AD mice was assessed using the Morris water maze test. The levels of the amyloid beta deposits and NeuN in the hippocampus were evaluated with immunohistochemistry. Brain neurotrophic derived factor (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot analysis. Results LFE treatment significantly ameliorated learning and memory deficits in AD mice, as shown by increased time spent in the target zone during probe tests. In addition, LFE significantly decreased Aβ deposits, increased NeuN-positive cells, and upregulated the expression of BDNF and TrkB in the 3xTg AD mice. Conclusions The present study suggests that LFE treatment can be a useful strategy for treating memory impairment induced by several neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Valeriana jatamansi Jones named Zhizhuxiang in China is one of the most popular traditional medicine for varied ailments related to malaise, abdominal distention, insomnia, and rheumatism. Aim of the study Evaluate the safety of iridoids rich fraction from V. jatamansi Jones (IRFV) and to provide data for clinical application. Materials and methods The acute and sub-chronic toxicity of IRFV were investigated by employing established methods. The acute toxicity study was conducted through oral administration of a single dose (3200 mg/kg body weight) of IRFV to adult mice. The vehicle used for dilution of the IRFV was a mixture of 0.5% CMC-Na and 99.5% water. The weight, diet, toxic reaction, and death after 14 days were observed. In the sub-chronic toxicity study, low doses (240 mg/kg bw), middle doses (960 mg/kg bw), and high doses (1200 mg/kg bw) of IRFV were administered daily to adult rats for 6 days a week (except Sunday) for 3 months. The general behavior of the rats was observed and recorded daily. The weight and food consumption of rats were tested weekly. The effect on organs, the hematological and blood biochemical parameters, and the histopathology were assessed after 1.5 months (five males and five females) and after 3 months (10 males and 10 females).The remaining 10 rats (five males and five females) in each group were fed for 2 weeks to observe reversible and delayed toxicity after the medicine was administered. Results In the acute toxicity study, no significant difference was found in the body weight of the mice in the control group and those in the drug group ( p >0.05). The maximum tolerated dose of IRFV on mice was 3200 mg/kg, which is 2666 times of the clinical adult daily dose. In the sub-chronic toxicity study on rats, the daily single oral doses of the IRFV did not result in death nor affected the general behavior, including appearance, activities, discharge, and waste at all tested doses. Moreover, no significant difference was found ( p >0.05) between the body weights of the rats from the drug groups and those from the control group. Food consumption was significantly affected ( p <0.05) only in the first 3 weeks. No statistically significant differences ( p >0.05) were observed in the hematological and blood biochemical parameters, and no abnormality of other organs were noted in both gross and histopathological examinations, except several animal transients ( p <0.05) or spontaneous lesions (abnormality). Conclusion IRFV is extremely safe in the usual clinical dose, and may not have any single dose toxicity. The lethal dose with 50% mortality rate (LD50) on mice is over 2000 mg/kg bw. The no-observed adverse effects level is 1200 mg/kg/day for rats. No direct correlation was found between the hematology, blood biochemical indexes, and organ coefficient of tested rats and the toxicity of IRFV. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Yulangsan polysaccharide (YLSPS) is often used in popular folk medicine in the Guangxi Zhuang Autonomous Region of China as a chief ingredient of Millettia pulchra , which is used as a hepatic protection, anti-aging and memory improving agent. Aim of the study This study was designed to investigate the protective effects of polysaccharides from Millettia pulchra Kurz var.laxior (Dunn) (Yulangsan polysaecharide, YLSPS) against nimesulide-induced hepatotoxicities in mice. Materials and methods Liver injury was induced in mice by administering nimesulide. Simultaneously, YLSPS was administered 2 h prior to the administration of nimesulide. Dimethyl diphenyl bicarboxylate (DDB) was used as a reference drug. Results Compared with the nimesulide group, YLSPS significantly decreased the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and the content of bilirubin in the serum. The anti-oxidative effect of YLSPS was observed from the increase of the superoxide dismutase (SOD) and catalase and glutathione peroxidase (GSH-Px) activities in the liver, both of which were decreased by nimesulide. Moreover, the content of malondialdehyde (MDA) was reduced, and histological findings also confirmed the anti-hepatotoxic activity. In addition, YLSPS significantly inhibited proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, YLSPS also enhanced the mitochondrial antioxidant and inhibited dead cells by preventing the down-regulation of Bcl-2, up-regulation and release of Bax along with caspase 9 and 3 activity, confirming the involvement of mitochondria in the nimesulide-induced apoptosis. Conclusion The protective effect of YLSPS against nimesulide-induced hepatic injury may rely on its ability to reduce oxidative stress and prevent nimesulide-induced hepatotoxicity by inhibiting critical control points of apoptosis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Areca catechu Linn. (Arecaceae) nut is a popular folk remedy for the treatment of migraine in Kerala and Tamil Nadu states of India. Aim of the study This study was designed to investigate the effect of hydroalcoholic extract of A. catechu L. nut (ANE) treatment on migraine pain in rat models to strengthen its use as an anti-migraine therapy. Materials and methods Bradykinin (0.1 μmol/kg) injection in to left femoral vein of rat produced PPE which was measured with luminescence spectrometer. Vocalizations were produced in rats with 10 μg of bradykinin infusion into common carotid artery. Phonogram was recorded before, during and for 5 min after bradykinin injection and sumatriptan was used as a standard anti-migraine drug. In both models, the ANE was orally administered at doses of 250 and 500 mg/kg, 60 min before bradykinin infusion. Results The PPE was reduced in both ANE treated groups of rats. The percent fluorescein was significantly increased in positive control group (97.00±1.7%; p <0.0001) compared to negative control (63.87±1.2%). With ANE treatments (250 and 500 mg/kg) PPE was significantly decreased to 88.88±1.4% ( p <0.01) and 83.55±0.1% ( p <0.0001) compared to positive control group, respectively. On the other hand in the model of vocalization, with 250 and 500 mg/kg ANE treatment, vocalization was significantly reduced to 33.33% and 16.66%, respectively, compared to saline treated rats. The reduction in vocalization is comparable to the reference drug sumatriptan. Conclusion The findings provide the strong evidence for anti-migraine potential of ANE in rat models of migraine. In summary, therapeutic intervention with ANE treatment could be a promising strategy for prevention of migraine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Schefflera octophylla (Lour.) Harms, a traditional Chinese herb mainly distributed in Southeast Asia, is extensively prescribed to alleviate pain and treat rheumatoid arthritis (RA), influenza, throat swelling, pain, etc. In this paper, the antinociceptive and anti-inflammatory activities of the ethanol extract and its five different polar fractions of this plant were evaluated. Furthermore, the anti-rheumatoid arthritis activity of the ethanol extract and its active fraction (CHCl 3 fraction) were evaluated. And the chemical constituents of the CHCl 3 active fraction displayed significant antinociceptive and anti-inflammatory activities were investigated. Materials and methods Antinociceptive and anti-inflammatory activities were investigated by hot plate test, acetic acid-induced abdominal writhing test and formalin test, xylene-induced ear edema test. The anti-rheumatoid arthritis activity was evaluated through the model of adjuvant-induced arthritis (AA) in rats, paw swelling, pain response, arthritis index and histopathological changes of ankle, the levels of TNF-α, IL-1β, IL-6 and rheumatoid factor (RF) of rats were detected. The chemical constituents of the CHCl 3 fraction were isolated using chromatographic techniques. Their structures were elucidated by spectroscopic data analysis. Results The results showed that the ethanol extract of S. octophylla has significant dose-dependent anti-inflammatory and antinociceptive activities. And its five different polar fractions especially the CHCl 3 fraction significantly inhibited the abdominal writhing induced by acetic acid and ear edema induced by xylene, also increased pain threshold in hot plate test in 120 min and reduced ticking times in formalin test. The ethanol extract of S. octophylla and the CHCl 3 fraction demonstrated an anti-RA effect in a dose-dependent manner. The levels of TNF-α, IL-1β and IL-6 in ethanol extract (600 mg/kg) and CHCl 3 fraction (300 mg/kg) groups were significantly lower than those of the model group. The chemical constituents study of the CHCl 3 fraction from S. octophylla led to six triterpenoids which were identified as taraxerone ( 1 ), 3-epi-taraxerol ( 2 ), aleuritolic acid ( 3 ), 3-oxofriedelan-28-oic acid ( 4 ), 3β,19α -dihydroxy-urs-12-ene- 24,28-dioic acid ( 5 ) and asiatic acid ( 6 ). Compounds 1 – 5 were obtained from this plant for the first time. Conclusion This study proved the antinociceptive, anti-inflammatory and anti-rheumatoid arthritis activities of S. octophylla. Triterpenoids obtained from its CHCl 3 fraction may be responsible for those activities. These results could support the fact that S. octophylla is used traditionally to cure inflammatory and pain diseases. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Centaurium erythraea Rafn (CE), Artemisia herba-alba Asso (AHA) and Trigonella foenum-graecum L. (TFG) are traditionally used to treat type 2 diabetes in Algeria, previous studies have found that extracts of these plants were effective to treat or prevent experimental diabetes induced by high-fat diet (HFD). Aim of the study Describe the additional effects of these extracts on lipid tissue deposition in HFD. Materials and methods Male C57BL/6J mice were fed with HFD to induce type 2 Diabetes. Groups of mice were given plant extracts orally at 2 g/kg/bodyweight daily for 20 weeks during establishment of diabetes, or for 18 weeks after confirmation of diabetes at the 17th week. Liver and other tissue samples were stained with Oil Red O. Results Liver steatosis was confirmed with HFD. CE, AHA and TFG extracts improved liver steatosis by the end of the preventive (20 weeks) and curative periods (35 weeks). This was most marked for CE extract ( p <0.05), less so with TFG and AHA. No steatosis was found in other tissues. Conclusion CE extract had a clear hepatoprotective effect in this mouse model of diet-induced type 2 diabetes. AHA and TFG had a minimal or no significant effect on steatosis. Beyond its effect as an antidiabetic agent, CE may also be promising to prevent or treat non-alcoholic liver steatosis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Myrianthus arboreus P. Beauv (Cecropiaceae) is a shrub or a tree plant widely distributed in Tropical Africa. In the South Eastern part of Nigeria, the leaves are used in traditional medicine as an analgesic for muscular pains, and also as an enema to relieve pain in the back and loins. Although no scientific study has been performed to validate its traditional use in pain management, this study therefore aims at investigating the anti-nociceptive activity of M. arboreus leaves extract in mice. Materials and methods Anti-nociceptive activity of M. arboreus was investigated using acetic acid induced writhing, formalin induced paw licks, hot plate, and tail flick tests. Acute toxicity was determined using a slightly modified Lorkes method. Results The extract of M. arboreus produced a significant dose-dependent [ F (4, 20)=13.48 p <0.001] inhibition of abdominal writhings induced by acetic acid. In the formalin paw licking test, it produced a significant dose-dependent inhibition of neurogenic and inflammatory pain [ F (4, 17.5)=60.13 p <0.001]. It also produced a significant dose dependent [ F (4, 20)=30.5 p <0.001; F (4, 20)=0.321 p <0.0001] prolongation of the latency and reaction time in the hot plate and tail immersion tests. Peak effect was observed at the highest dose (40 mg/kg). LD 50 of the plant was found to be 894 mg/kg. Conclusion M. arboreus possesses potent antinociceptive activity mediated centrally and peripherally, an effect which may justify its traditional use in the management of pain. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Bitter and cold Chinese medicines have been long used for the treatment for diabetes mellitus (DM) for thousands of years in China. The roots of Sophora flavescens Ait., one of bitter and cold Chinese medicines commonly used to remove lung heat have been used to counteract DM and exerted good clinical effects for diabetic patients in some folk hospitals in Fujian province, PR China. However, the corresponding active principles and antidiabetic mechanism of this Traditional Chinese Medicine remain unclear. Therefore, in this study, we aim at chemical profiling of the active principles, validating the potential antidiabetic effects of the active EtOAc extract (SF-EtOAc) in vitro and in vivo , and elucidating its probable antidiabetic mechanism as well as evaluating its acute oral toxicity. Materials and methods An off-line semi-preparative LC-NMR and LC-UV-ESI MS protocol was developed to determine the chemical principles of the active EtOAc extract rapidly and unambiguously. The effect of SF-EtOAc on the glucose transporter type 4 (GLUT4) translocation in L6 myotubes was examined. T2DM KK-Ay mice were induced by high-fat diet. SF-EtOAc was orally administration at the dose of 30, 60 and 120 mg/kg/d, for 21 days. Metformin was used as positive control. Body weight, plasma glucose, oral glucose tolerance test, serum insulin and blood–lipid indexes were measured. Phosphorylation of the AMP-activated protein kinase (AMPK) expression in liver was measured. Results We found that SF-EtOAc significantly improved oral glucose tolerance, increased serum high density lipoprotein cholesterol ( HDL-C) and reduced body weight, blood glucose levels and other related blood–lipid indexes. Mechanistically, SF-EtOAc elevated phosphorylation of AMP-activated protein kinase (AMPK) and stimulated membrane translocation of GLUT4. Moreover, it was unveiled that oral median lethal dose (LD 50 ) of SF-EtOAc was more than 7500 mg/kg, suggesting that SF-EtOAc was practically non-toxic for mice. Conclusions SF-EtOAc improves glucose tolerance, reduces hyperglycemia and resumes insulin levels, at least in part, by activating GLUT4 translocation which may be modulated by AMPK pathway. According to the results of the present study, SF-EtOAc possesses a potent antidiabetic activity and could be used as a safe remedy for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Combretum leprosum Mart. is a native species of the Caatinga, an important biome in the Brazilian semi-arid region. This species is commonly used in Brazil as a healing agent, as well as for the treatment of skin diseases. Aim of the study This study investigated the healing potential of the ethanolic extract (EECL) and the bioactive triterpene 3β, 6β, 16β-trihydroxylup-20 (29)-ene (CLF-1) isolated from the leaves of C. leprosum . Materials and methods Skin wounds (1 cm 2 ) were created in the dorsal zone of mice with a scalpel blade number 15. The treatment consisted in a daily topical application of 100 μl of 150 mM NaCl, EECL and CLF-1 (at 10 μg/100 μl) for 12 days. The lesions were then macro and microscopically evaluated. Results On postoperative day (POD) 2, the lesions treated with EECL and CLF-1 showed a moderate presence of vessels of the granulation tissue progressing in the dermis. The same effect was not observed in the control group. The treatment with EECL and CLF-1 stimulated angiogenesis, resulting in a rapid deposition of extracellular matrix (ECM). Moreover, the animals treated with EECL and CLF-1 showed smaller lesions on POD 7, primarily due to the contraction in the reticular dermis induced by organization of myofibroblasts, which was not observed in the group treated with NaCl. In addition, the lesions treated with EECL and CLF-1 showed ECM restructuration and presence of epithelium coating, which was not observed in the group treated with NaCl, in which the lesions showed no epithelial lining, suggesting delayed healing. Conclusion CLF-1 isolated from the leaves of C. leprosum may be considered to be an important molecule for the treatment of skin lesions. However, further investigations are necessary to establish its role in chronic lesions and to elucidate the mechanism of action involved in the cutaneous healing process. To the best of our knowledge, this is the first report describing the pro-healing activity of the ethanolic extract and the triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene isolated from leaves of C. leprosum . [ABSTRACT FROM AUTHOR]

Jasminum lanceolarium Roxb is an important traditional Chinese medicine. Its stems and roots have been used for the treatment of rheumatism and fever while the leaves are used as an anti-inflammatory agent to relieve pain. In order to support its traditional Chinese medicinal uses, five animal models were designed and the anti-inflammatory and analgesic properties of the 70% EtOH–H 2 O extracts of J. lanceolarium (EJL) were investigated. Meanwhile, biochemical parameters such as cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) in blood serum of rats exposed to acute (carrageenan) inflammation model were evaluated. At doses of 400 mg/kg, EJL exhibited higher anti-inflammation effect than that of indomethacin and better analgesic activity than that of aspirin ( P <0.001). Furthermore, eleven isolated compounds including six lignanoids ( 1 , 2 , 6 , 7 , 8 , and 11 ) and five iridoids ( 3 , 4 , 5 , 9 , and 10 ) were isolated from the active extracts and showed significant anti-inflammatory activities with the IC 50 values of 1.76–5.22 mg/mL, respectively, when testing their inhibitory effects on phospholipase A 2 in vitro . The results demonstrated that the possible anti-inflammatory mechanisms might be attributed to inhibit the hydrolysis of membrane phospholipids, production on both COX-2 and 5-LOX, and then finally inhibit the release of prostaglandins (PGs), which suggested that EJL had a non-selective inhibitory effect on the release or actions of these mediators, and might be a dual LOX–COX inhibitor for the treatment of inflammation from the natural resource. The studies on the animals and the inflammatory mediators, along with the bioactive compounds presumed that the existences of iridoids and lignanoids could be response for their bioactivities of the whole plants. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Lonicera japonica Thunberg, a widely used traditional Chinese medicine, possesses antibacterial, antiviral, and antiendotoxin activities. This study investigated the molecular mechanisms of HS-23, the ethanol extract of the dried flower buds of L. japonica, on sepsis-induced immunosuppression. Materials and methods Male ICR mice were intravenously administered HS-23 (10, 20, and 40 mg/kg) immediately (0 h) and 22 h after cecal ligation and puncture (CLP). The spleen was isolated for biochemical assays 24 h after CLP. Results HS-23 improved sepsis-induced mortality. CLP induced a marked decrease in the number of splenocytes, B cells, and natural killer cells, which was attenuated by HS-23. HS-23 also attenuated CLP-induced apoptosis in CD4 + and CD8 + T cells and inhibited both the intrinsic and extrinsic apoptotic pathway in the spleen. HS-23 attenuated the CLP-induced decrease in interleukin (IL)-17 production. CLP significantly decreased splenic production of tumor necrosis factor-α and IL-2, and these effects were attenuated by HS-23. Conclusion Our findings suggest that HS-23 reverses immunosuppression during the late phase of sepsis by inhibiting lymphocyte apoptosis and enhancing Th1 cytokine production. HS-23 warrants further evaluation as a potential therapeutic agent for the treatment of sepsis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Through one-to-one interaction with the traditional healers, the present study has identified 15 medicinal plant species traditionally used as remedies to control diabetes. Materials and methods The methanolic extracts were screened for their α-glucosidase inhibitory activity. Hypoglycemic activity was assessed following glucose, sucrose and starch tolerance test on normal and STZ induced diabetic rats. Results Ficus cunia extract had the highest α-glucosidase inhibitory potency with IC 50 1.39±0.74 µg mL −1 followed by Schima wallichi (IC 50 1.43±0.20 µg mL −1 ) and Wendlandia glabrata (IC 50 1.67±0.33 µg mL −1 ). In STZ induced diabetic rat model, F. cunia and W glabrata extracts reduced blood glucose concentration to near normal up to 14 days when administered 48 h after STZ. Conclusion The present study supports the traditional use of some of these medicinal plants in anti-diabetic remedies. The present study contributes to evidence for use of traditional medicine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance C. mexicana A. Gray (Asteraceae) is a native of North America plant. In Mexico׳s folk medicine it is used for the fever, rheumatism and as a diuretic, antispasmodic, general tonic or adaptogenic herb, and as a stimulant agent. The aim of the study was to examine the antidepressant-like properties of an aqueous extract of C. mexicana (Cm), in order to scientifically describe its potential value in the management of depressive disorders. To evaluate the acute and subacute toxic effects of Cm and effects on hepatic and biochemical functions in mice. Materials and methods Antidepressant-like effects of Cm were evaluated in the Forced swimming and suspension tail tests (FST and TST), the ambulatory activity was measure in the Open Field Test (OFT), motor coordination was evaluated in the inverted screen and gyratory roller (IST and Rota-rod), the biochemical and histopathological analysis were carried out. Phytochemical studies of organic and aqueous extracts of Cm were thoroughly conducted. Results Cm produced a significant reduction of the immobility time both FST and in TST, without affect the ambulatory activity of experimental mice. Cm did not produce any damage in the hepatic functions, nor produce any significant change in the morphological tissue of organs examined. Conclusions Chrysactinia mexicana induces a clear antidepressant-like effect in mice, without affect any basic functions. The consumption of this medicinal plant does not represent risk for health. The chemical analysis showed the flavonoids free and glycosides mainly. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Decoctions prepared from the bark of Margaritaria discoidea (Baill.) G. L. Webster (Euphorbiaceae) are used in Nigeria and other parts of West Africa in the treatment of wounds and ulcers. The study was conducted to investigate the gastric ulcer protective effect of ethanolic stem bark extract of M. discoidea in rats. Materials and methods Antiulcer assays were performed using ethanol, indomethacin and pylorus ligation-induced ulcer models at the dose of 50, 100 and 150 mg/kg, p.o. The antioxidant effect of the extract was evaluated in vitro and by studying its effect on antioxidant enzymes (superoxide dismutase, catalase, and reduced glutathione) and lipid peroxidation in the stomach tissue of rats in ethanol-induced model. Solvent fractions (hexane, dichloromethane, ethyl acetate, butanol and aqueous) from the crude extract were investigated for antiulcerogenic effects in ethanol-induced ulcer model at the dose of 150 mg/kg. GC–MS analysis of the active hexane fraction was also carried out. Results The extract significantly ( P <0.05) reduced gastric lesion in ethanol and indomethacin-induced ulcer models. The extract had significant influence on in vivo antioxidant status in ethanol-induced model. In pylorus ligation-induced model, only the dose of 150 mg/kg showed significant reduction (88.89%, P <0.05) of ulcer lesions. There was no significant reduction in the gastric juice volume and total acidity. The solvent fractions showed ulcer inhibition in varying degrees but significance ( P <0.01) was only observed in the hexane fraction. Ethyl esters of palmitic and linoleic acids were found as the major compounds in the GC–MS analysis of the hexane fraction. Conclusion Our results suggest that M. discoidea possesses gastroprotective activity possibly mediated through antioxidant mechanism. The data obtained in this study provide some support to the traditional use of M. discoidea in the treatment of gastric ulcer. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Isoboldine is one of the major bioactive constituents in the total alkaloids from Radix Linderae (TARL) which could effectively alleviate inflammation and joints destruction in mouse collagen-induced arthritis. To better understand its pharmacological activities, we need to determine its pharmacokinetic and metabolic profiles. Materials and methods In this study, a sensitive and simple UPLC–MS/MS method was developed and validated for determination of isoboldine in rat plasma. Isoboldine in plasma was recovered by liquid–liquid extraction using 1 mL of methyl tert -butyl ether. Chromatographic separation was performed on a C 18 column at 45 °C, with a gradient elution consisting of acetonitrile and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. The detection was performed on an electrospray triple-quadrupole MS/MS by positive ion multiple-reaction monitoring mode. This newly developed method was successfully applied to a pharmacokinetic study after oral and intravenous dosing in rats. For metabolites identification, isoboldine was orally administered to rats and the metabolite in plasma, bile, urine and feces were characterized by the established UPLC–MS/MS method. Results Good linearity ( r 2 >0.9956) was achieved in a concentration range of 4.8–2400 ng/mL with a lower limit of quantification of 4.8 ng/mL for isoboldine. The intra- and inter-day precisions of the assay were 1.7–5.1% and 2.2–4.4% relative standard deviation with an accuracy of 91.3–102.3%. A total of five phase II metabolites in rat plasma, bile, urine and feces were characterized by comparing retention time in UPLC, and by molecular mass and fragmentation pattern of the metabolites by mass spectrometry with those of isoboldine. Conclusion isoboldine has extremely low oral bioavailability due to the strong first-pass effect by the rats, and glucuronidation and sulfonation were involved in metabolic pathways of isoboldine in rats. These results have paved the way for further clarifying therapeutic ingredients and provided new knowledge regarding pharmacokinetic features of this category of isoquinoline alkaloids. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Lafoensia pacari A. St.-Hil. (Lythraceae), known popularly as “pacari” or “mangaba-brava” is popularly used in the state of Goiás, Brazil. The stem bark or leaves are used to treat cancer, gastric disorders, inflammation and as a tonic to treat loss of enthusiasm. Aim of the study Previous results suggest that the ethanol:water 7:3 extract of the stem bark of L. pacari (PEx) has antidepressant-like activity in male mice. Our aim was to perform the PEx׳s bioguided fractionation and evaluate the monoaminergic system involvement in the antidepressant effect as well as progress in the study of L. pacari mechanism of action. Material and methods Mice (30–35 g) orally treated (24, 5 and 1 h) with PEx (100, 300 or 1000 mg/kg), chloroform (ChloF—70 mg/kg), ethyl acetate (180 mg/kg), n -butanol (370 mg/kg) and aqueous (1 g/kg) fractions were submitted to the forced swimming test. To assess the mechanism of action, different groups of mice were pretreated with p -chlorophenylalanine (PCPA—100 mg/kg, 4 days, i.p.) and alpha-methyl- p -tyrosine (AMPT—100 mg/kg, 4 h, i.p.) to assess the involvement of serotoninergic and catecholaminergic systems in the ChloF effects, respectively. A putative in vitro inhibition of monoamine oxidase (MAO) activity as well as the ex vivo hippocampal brain-derived neurotrophic factor (BDNF) quantification were carried out. Phytochemical screening, spectroscopy and chromatography analysis were used for identification of compounds present in ChloF. Results and discussion After the fractionation, the ChloF 70 mg/kg was the most active fraction, reducing the immobility time by 22%. Pre-treatments with both PCPA and AMPT abolished the ChloF effects, suggesting that ChloF antidepressant-like effect is dependent on serotonergic and catecholaminergic systems. ChloF did not inhibited MAO-A or MAO-B activity, excluding this as possible mechanism of action. ChloF augmented hippocampal BDNF level, which could be accounted for its antidepressant-like effect. Phytochemical screening showed the presence of saponins, tannins, steroids and triterpene in the PEx, and the presence of triterpene and steroids in ChloF. The spectroscopy and chromatography analysis identified lupeol, β-sitosterol and stigmasterol in ChloF. Conclusion ChloF is the fraction that better retained the crude extract active constituents. ChloF presents antidepressant-like effect that involves both serotonergic and catecholaminergic systems without inhibiting MAO enzymatic activity; this fraction also increases the hippocampal BDNF levels. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Pholidota articulata Lindley (PA) locally known as Hadjojen (bone jointer) belongs to family Orchidaceae is used for healing fractures in folklore tradition of Kumaon region of Uttarakhand, Himalaya, India. Bone is a dynamic organ and is constantly being remodeled in order to facilitate growth and repair. This process requires the involvement of bone forming osteoblast and bone resorbing osteoclast cells, which function in generating and mineralizing bone, giving strength and rigidity to the skeletal system. Present study was aimed to determine the therapeutic potential of ethanolic extract of PA and its isolated compound oxoflavidin, by characterizing their fracture healing properties. Materials and methods Ovariectomized (Ovx) estrogen deficient adult female Balb/c mice were used for in vivo evaluation of osteogenic or bone healing potential of ethanolic extract of PA. Further, its isolated compounds were tested for their osteogenic efficacy using alkaline phosphatase assay and mineralization assay in vitro in mice calvarial osteoblasts. Results The ethanolic extract of PA exhibited significant restoration of trabecular micro-architecture in both femoral and tibial bones. Additionally, treatment with PA extract led to better bone quality and devoid of any uterine estrogenicity in ovariectomized estrogen deficient mice. One of the isolated compound, oxoflavidin enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen, RUNX-2 and osteocalcin. Conclusion These results warrant that ethanolic extract of PA and it’s pure compound oxoflavidin have fracture healing properties. The extract and oxoflavidin exhibit a strong threapeutical potential for the treatment and management of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Wutou (WT, Radix Aconiti ), the mother root of Aconitum carmichaelii Debx., is a famous Chinese herb against rheumatoid arthritis. In Chinese clinics, PWT is often prepared as a decoction in combination with other herbs, such as Wutou decoction (WTD). The present study aimed to compare the effects of PWT single herb and WTD on CYP3A activity ex vivo and in vivo . Materials and methods In the ex vivo study, CYP3A activity was determined by using testosterone (Tes) as a specific probe. Levels of Tes and its metabolite 6β-hydroxytestosterone (6β-OH-Tes) were measured using a validated ultra-performance liquid chromatography (UPLC) method. CYP3A protein and mRNA levels were measured by using Western blot and real-time PCR, respectively. In the in vivo study, CYP3A activity was determined by using buspirone (BP) as a specific probe. The plasma concentrations of BP and its primary metabolites, namely, 1-(2-pyrimidinyl) piperazine (1-PP) and 6′-hydroxybuspirone (6′-OH-BP), were determined using a validated UPLC-tandem mass spectrometry (UPLC/MS/MS) method. Results Compared with the control group, the formation rates of 6β-OH-Tes from Tes ex vivo significantly decreased in groups treated with PWT at the tested doses, and this decrease was accompanied by a striking decrease in CYP3A protein and mRNA levels. However, a significant increase was observed in the ratios in the WTD groups compared with PWT single herb groups. In vivo , both formation ratios of 6′-OH-BP and 1-PP from BP showed no significant change in the WTD group. Conclusions PWT can significantly inhibit CYP3A activity ex vivo at the tested doses because of the down-regulation of CYP3A protein and mRNA expression levels. WTD can significantly reverse the inhibition caused by PWT. WTD also had no significant effect on CYP3A activity in vivo . Results implied that the use of PWT as a part of the WTD prescription rather than PWT single herb is more appropriate in clinics. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Scutellariae Radix (SR), the dried root of Scutellariae baicalensis Georgi, has a lot in common with non-steroidal anti-inflammatory drugs (NSAIDs). Their similarities in therapeutic action (anti-inflammation) and metabolic pathways (phase II metabolisms) may lead to co-administration by patients with the potential of pharmacokinetic and/or pharmacodynamic interactions. The current study aims to investigate the potential interactions between SR and an NSAID, mefenamic acid (MEF), on the overall pharmacokinetic dispositions, anti-inflammatory effects and adverse effects in rats. Materials and methods The current study simultaneously monitored the pharmacokinetic and pharmacodynamic interactions in a single animal. Four groups of Sprague-Dawley rats ( n =7 each) received oral doses of a standardized SR extract (300 mg/kg, twice daily), MEF (40 mg/kg, daily), combination of SR extract and MEF, and vehicle control, respectively, for 5 days. On Day 5, blood samples were collected after first dose over 24 h for the determination of (1) plasma concentrations of SR bioactive components, MEF and its metabolites by LC-MS/MS, and (2) prostaglandin E 2 (PGE 2 ) production and cyclooxygenase-2 (COX-2) gene expression by ex vivo analyses using LPS-stimulated RAW264.7 macrophage cells, ELISA and real time-PCR. After the rats were sacrificed, stomachs were isolated to assess their gross mucosal damage. Statistical comparisons were conducted using ANOVA and t -test. Results Minimal pharmacokinetic interaction between SR extract and MEF was observed. Co-administration of SR extract and MEF did not significantly alter the plasma concentration–time profile or the pharmacokinetic parameters such as C max , AUC 0→24 , T max or clearance. Pharmacodynamic interaction via the COX-2 pathway was observed. The PGE 2 level in LPS-stimulated RAW264.7 cells treated with plasma collected from control group over the 24 h sampling (AUC 0→24[PGE2] ) was 191981±8789 pg/ml hr, which was significantly reduced to 174,780±6531 and 46,225±1915 pg/ml hr by plasma collected from rats administered with SR extract and MEF, respectively. Co-administration of SR extract and MEF further potentiated the PGE 2 inhibition, with an AUC 0→24[PGE2] of 37013±2354 pg/ml hr ( p <0.05, compared to SR or MEF group). By analyzing the COX-2 gene expression, SR extract significantly prolonged the COX-2 inhibitory effect of MEF over the 24 h ( p <0.05). Furthermore, the MEF-induced stomach ulcer after the 5-day treatment, as evidenced by the increased gross ulcer index and sum of lesion length ( p <0.05, compared to control), could be alleviated by co-administration with SR extract ( p <0.05). Conclusions Co-administration of SR extract and MEF potentiated the anti-inflammatory effects, alleviated the MEF-induced stomach adverse effect while having minimal pharmacokinetic interactions. Our findings provide insight for combination therapy of SR extract and MEF against inflammatory diseases. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Pseudolysimachion rotundum var . subintegrum (Speedwell, Plantaginaceae) is used as a traditional herbal medicine for treating bronchitis, cough and asthma in Korea, China, Russia, and Europe. Aim of the study In this study, we investigated the protective effects of the novel iridoid glycoside, piscroside C (compound 1) isolated from the methanolic extract of P. rotundum var. subintegrum against inflammatory responses using a cigarette smoke induced chronic obstructive pulmonary disease (COPD) and TNF-α-stimulated human airway epithelial NCI-H292 cells. Materials and methods The novel iridoid glycoside piscroside C was isolated from the methanolic extract of P. rotundum var. subintegrum . The chemical structure was established by NMR, HRESIMS, and optical rotation. In in vivo experiment, the mice received 1 h of cigarette smoke for 3 days. Piscroside C was administered to mice by oral gavage 1 h before cigarette smoke exposure for 3 days. In in vitro experiment, we evaluated the effect of piscroside C on proinflammatory mediators in H292 cells stimulated with TNF-α. Results Piscroside C significantly reduced the neutrophil influx, reactive oxygen species production, IL-6, TNF-α, and elastase activity in bronchoalveolar lavage fluid in COPD animals. In addition, piscroside C attenuated NF-κB and IκB phosphorylation, leading to reduced recruitment of inflammatory cells into the lung tissue. Consistent with the results of in vivo experiment, piscroside C significantly inhibited the expression of inflammatory cytokines (IL-6, IL-8 and IL-1β) by inhibiting NF-κB activation, as resulting decrease in the phosphorylation of IKKβ, IκBα and TAK1 in TNF-α-stimulated H292 cells. Conclusion These findings indicate that piscroside C effectively inhibits inflammatory responses, which is an important process in the development of COPD through suppression of IKK/NF-κB activation. Our study suggest that piscroside C might represent a useful therapeutic for the treatment of inflammatory airway disease. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance In Kenya, 22 million people are at risk of malaria, 70% of them are in rural areas and most of these people use traditional plant based medicines to treat malaria. The aim of the study was to escalate documentation, from an earlier study of medicinal plants, traditionally used to treat malaria by the Digo community of Kwale County, taking cognizance of their pharmacological information by evaluating their antiplasmodial efficacies. Materials and methods The study was carried out in Kwale County at Shimba Hills Game Reserve and adjoining part of Kinango. Traditional health practitioners (THP) were interviewed with a standard questionnaire to obtain information on medicinal plants traditionally used for management of malaria. Group interviews were also held among THPs and members of the community. The plant samples collected were tested for antiplasmodial activity against chloroquine sensitive (D6) and resistant (W2) Plasmodium falciparum using the ability of extracts, prepared from the plant species, to inhibit the incorporation of [G-3H] hypoxanthine into the malaria parasites. Results Fifty seven (57) species in forty eight (48) genera and thirty (30) families were documented and evaluated for in vitro antiplasmodial activity. Apocynaceae, Euphorbiaceae, and Rubiaceae families had each about 12% of the plant species reported as antimalarial remedy and represented the species that are most commonly used. Twelve species (21.1%) showed antiplasmodial efficacy of IC 50 <5 µg/ml and these were Boscia salicifolia , Cissampelos mucronata , Clerodendrum myricoides , Commiphora schimperi , Flueggea virosa , Maytenus undata , Maytenus senegalensis , Maytenus putterlickioides , Vernonia amygdalina , Warburgia stuhlmannii , Zanthoxylum chalybeum and Tabernaemontana pachysiphon. Conclusions These results seem to indicate that ethnopharmacological inquiry used in search for new herbal remedies as predictive and could form the basis of an ethnopharmacopoeia and search for new active principles. This is the first report on traditional use of T. pachysiphon for malaria and its antiplasmodial activity. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Eupafolin, a major bioactive compound found in Phyla nodiflora, has the anti-inflammatory property. Upregulation of cell adhesion molecules in the lung airway epithelium is associated with the epithelium–leukocyte interaction and plays a critical role in the pathogenesis of lung airway inflammatory disorders. To investigate the effects of eupafolin on tumor necrosis factor-α (TNF-α)-induced intercellular cell adhesion molecule-1 (ICAM-1) expression in A549 human lung airway epithelial cells and the underlying mechanisms. Materials and methods The effect of eupafolin on ICAM-1 expression in A549 cells were examined by Western blotting and immunofluorescent staining. The mice were injected intraperitoneally with or without eupafolin and then were left untreated or were injected intratracheally with TNF-α. To detect the effect of eupafolin on ICAM-1 expression, the lung tissues were also examined by Western blotting and immunohistochemical staining. Results Eupafolin pretreatment reduced the TNF-α-induced ICAM-1 expression and also the ERK1/2, JNK, p38, and AKT/PI3K phosphorylation. However, the increase in ICAM-1 expression with TNF-α treatment was unaffected by p38 and PI3K inhibitors. Eupafolin decreased the TNF-α-induced NF-κB p65 activation and its nuclear translocation. Furthermore, eupafolin reduced ICAM-1 expression in the lung tissues of TNF-α-treated mice. Conclusions Eupafolin exerts its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via AKT/ERK1/2/JNK phosphorylation and nuclear translocation of NF-κB p65. These results suggest that eupafolin may represent a novel therapeutic agent targeting epithelial activation in lung inflammation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Impatiens textori Miq. ( I. textori, Balsaminaceae) is a traditional medicinal herb used for centuries to treat several inflammatory related skin infections and allergic disorders in Asian countries. Aim of the study In this study, we elucidated the effects of whole plant extracts of I. textori on inflammasome activation using in vitro and in vivo models. Materials and methods LPS-stimulated murine bone marrow macrophages were used to study the regulatory effect of I. textori extract (IT) on inflammasome activation. ATP, nigericin and MSU were used as danger-associated molecules to activate the NLRP3 inflammasome. An LPS-induced acute lung injury (ALI) mouse model was used to study the in vivo effect of IT on inflammasome activation. Results IT treated at 25, 50, and 100 μg/mL concentrations suppressed interleukin-1β secretion through the attenuation of NLRP3 inflammasome activation ( p <0.001 at 100 μg/mL) leading to the decreased amount of ASC oligomerization and caspase-1 maturation. For the in vivo model, IT inhibited the NLRP3 expression and cell recruitment at the lung tissue in the ALI mouse model. Conclusion IT exhibited potent anti-inflammatory effects via the attenuation of NLRP3 inflammasome activation supporting the traditional claims and may provide a valuable therapeutic strategy in treating various inflammation-related disorders. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Jiegeng (Radix Platycodi), the dried root of Platycodon grandiflorum A. DC (Campanulaceae), has been used to treat cough, sore throat, bronchitis, and bronchial asthma for thousands of years. It is commonly prescribed with Gancao (Radix et Rhizoma Glycyrrhizae ) as a herbal combination in traditional Chinese medicine (TCM) to produce synergistic effects. Aim of the study To elucidate the herbaceous compatibility of Jiegeng and Gancao, we investigated the comparative pharmacokinetics, intestinal absorption, and microbial metabolism of platycodin D (PD) and deapio-platycodin D (DPD), the platycodins contained in Jiegeng. Materials and methods In the comparative pharmacokinetic study, the concentrations of PD and DPD in Jiegeng extract (JE) and the Jiegeng–Gancao herb pair (JGHP) were determined in rat plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS). In addition, the main pharmacokinetic parameters were calculated using data analysis software (DAS). Furthermore, in vitro studies using Caco-2 cells and fecal lysates were performed to contradistinguish the intestinal absorption and microbial metabolism of PD and DPD in JE from those in JGHP. Results The peak concentration ( C max ) and area under the plasma concentration curve ( AUC ) of PD in rats orally administrated JGHP significantly increased compared to that in rats treated with JE. In addition, the time to reach peak concentration ( T max ) and half-life ( t 1/2 ) of PD and DPD in combination with JGHP were all prolonged compared with those of JE. There was no significant difference in the absorption of PD between JE and JGHP in Caco-2 cells. However, the hydrolysis of both PD and DPD in JGHP were weaker than that in JE after a 2-h incubation in fecal lysate which might be responsible for the different pharmacokinetic profiles of the platycodins in JE and JGHP. Conclusion In this study, we discovered that Gancao might influence the pharmacokinetic profiles of PD and DPD in Jiegeng. Furthermore, the difference in profiles may be attributable to the inequable microbial metabolism rather than intestinal absorption of the platycodins in JE and JGHP. The results of this study elucidated the pharmacokinetic compatibility and rationale for the use of JGHP. [ABSTRACT FROM AUTHOR]