The effects of hydroxysafflor yellow A on blood pressure and cardiac function

Aim of the study

This work aims to investigate the effects of HSYA on cardiac function and blood pressure.

Materials and methods

To evaluate changes in mean arterial pressure (MAP) and heart rate (HR), different groups of pentobarbitone-anesthetized normotensive and spontaneously hypertensive rats (SHR) were treated with intravenous HSYA (0.1-3 mg/kg). Isolated WKY rat hearts in Langendorff system were employed for examining the effect of HSYA on hemodynamic. After 30 min equilibration time the isolated hearts were perfused with HSYA (30 μmol/L) in a stepwise fashion. Potassium channel inhibitors were used to determine the role of potassium channel activation in HSYA effect.

Results

Intravenous injection of the HSYA significantly reduced MAP and HR in both normotensive rats and SHR in a dose-dependent manner. HSYA reduced left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of increase of left ventricular pressure (+dp/dt_max) and heart rate (HR) in a dose-dependent manner. HSYA had no remarkable effect on the maximum rate of decrease of left ventricular pressure (−dp/dt_max); BK_Ca and K_ATP blocker can weakened the inhibitory effect of HSYA on heart function and HR, but K_V and K_ACh blocker did not significantly weaken the HSYA effects.

Conclusion

Our results show that HSYA could significantly reduce blood pressure and heart rate, which may be related to activation of BK_Ca and K_ATP channels.     

Medicinal and therapeutic potential of Sea buckthorn (Hippophae rhamnoides L.)

Ethnopharmacological context

This review explores the medicinal and therapeutic applications of Sea buckthorn (Hippophae rhamnoides L.) in curtailing different types of acute as well as chronic maladies. The plant is being used in different parts of the world for its nutritional and medicinal properties.

Materials and methods

Sea buckthorn based preparations have been extensively exploited in folklore treatment of slow digestion, stomach malfunctioning, cardiovascular problems, liver injury, tendon and ligament injuries, skin diseases and ulcers. In the recent years, medicinal and pharmacological activities of Sea buckthorn have been well investigated using various in vitro and in vivo models as well as limited clinical trials.

Results

Sea buckthorn has been scientifically analyzed and many of its traditional uses have been established using several biochemical and pharmacological studies. Various pharmacological activities such as cytoprotective, anti-stress, immunomodulatory, hepatoprotective, radioprotective, anti-atherogenic, anti-tumor, anti-microbial and tissue regeneration have been reported.

Conclusion

It is clear that Sea buckthorn is an important plant because of its immense medicinal and therapeutic potential. However, several knowledge gaps identified in this paper would give impetus to new academic and R&;D activities especially for the development of Sea buckthorn based herbal medicine and nutraceuticals.     

Anti-diabetic activity of Chiliadenus iphionoides

Ethnopharmacological relevance

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

Materials and methods

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

Results

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

Conclusions

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

Proanthocyanidin-enriched extract from Myrothamnus flabellifolia Welw. exerts antiviral activity against herpes simplex virus type 1 by inhibition of viral adsorption and penetration

Aim of the study

Extracts from the aerial parts of the South African resurrection plant Myrothamnus flabellifolia Welw. have been used traditionally against infections of the upper respiratory tract and skin diseases. A polyphenol-enriched extract was investigated for potential antiviral effects against herpes simplex virus type 1 (HSV-1) and adenovirus, and the underlying mode of action was to be studied.

Materials and methods

Antiviral effects of an acetone-water extract (MF) from Myrothamnus flabellifolia on HSV-1 and adenovirus type 3 were tested in infected Vero cells by plaque reduction assay, MTT test and immunofluorescence. The influence of the extract on the HSV-1 envelope glycoprotein D was shown by Western blot. Organotypic full thickness skin models consisting of multilayer skin equivalents were used for the investigation of MF effects on HSV-1 replication.

Results

MF exhibited strong antiviral activity against HSV-1. The HSV-1-specific inhibitory concentration (IC₅₀) was determined as 0.4 μg/mL and the cytotoxic concentration (CC₅₀) against Vero cells as 50 μg/mL. A selectivity index (SI) (ratio of CC₅₀ to IC₅₀) of approximately 120 was calculated when MF was added to the virus inoculum for 1 h at 37 °C prior to infection. The replication of adenovirus 3 was not affected by MF.MF abolished virus entry into the host cell by blocking viral attachment to the cell surface. When added after attachment at a concentration of >6 μg/mL, the extract also inhibited penetration of HSV-1 into the host cell. Polyphenolic compounds from MF directly interacted with viral particles, leading to the oligomerisation of envelope proteins as demonstrated for the essential viral glycoprotein D (gD). Using organotypic full thickness tissue cultures, it was shown that treatment of HSV-1 infected cultures with the MF resulted in reduced viral spread.

Conclusions

A polyphenol-enriched extract from Myrothamnus flabellifolia strongly acts against HSV-1 by blocking viral entry into the cells.     

Cardioprotective effect of water and ethanol extract of Salvia miltiorrhiza in an experimental model of myocardial infarction

Ethnopharmacological relevance

Salvia miltiorrhiza has long been used in the traditional Chinese formulations for the treatment of heart ischemic diseases.

Aim of the study

We investigated the cardioprotective effect of purified Salvia miltiorrhiza extract (SME) in an experimental model of acute myocardial infarction.

Materials and methods

Following induction of acute myocardial infarction in rats by adminstration of isoproterenol, hemodynamic and electrocardiographic parameters were monitored and recorded continuously, cardiac enzymes and parameters of oxidative stress were measured, and histopathological examination of heart tissue was performed. Experiments were performed in rats treated with SME or vehicle, as well as in those treated with Fufang Danshen Tablet (FDT) as a positive control which has previously been shown to prevent myocardial ischemia.

Results

Isoproterenol-treated rats showed reductions in left ventricular systolic pressure as well as in maximum and minimum rate of developed left ventricular pressure, together with an increase in left ventricular end-diastolic pressure. They also demonstrated ST-segment elevation, together with increases in serum levels of lactate dehydrogenase, glutamic oxalacetic transaminase, creatine kinase and malondialdehyde, as well as decreases in serum activities of glutathione peroxidase and superoxide dismutase. Oral administration of SME (29.76 or 59.52 mg/kg) blunted all of the hemodynamic and biochemical changes induced by isoproterenol, as did FDT (1210 mg/kg). The protective effect of SME on isoproterenol-induced myocardial damage was further confirmed by histopathological examination.

Conclusions

Our results suggest that SME affords protection against isoproterenol-induced myocardial infarction.     

Hepatoprotective effect and its possible mechanism of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced chronic liver hepatotoxicity in rats

Ethnopharmacological relevance

Coptidis rhizoma is traditionally used for heat-clearing and toxic-scavenging and it belongs to liver meridian in Chinese medicine practice. Clinically, Coptidis rhizoma can be used for hepatic and biliary disorders, yet details in the therapies of liver diseases and underlying mechanism(s) remain unclear. Our previous study demonstrated that Coptidis rhizoma aqueous extract (CRAE) against CCl₄-induced acute liver damage was related to antioxidant property. In the present study, the protection of CRAE on chronic liver damage induced by carbon tetrachloride (CCl₄) in rats and its related mechanism were explored.

Materials and methods

The CCl₄-induced chronic liver damage model was established, and CRAE's protective effect was examined. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, serum and liver superoxide dismutase (SOD) activity were then measured. The histological changes were observed under microscopy and then computed in numerical score. The normal or damaged cells were isolated and related signaling pathway was evaluated.

Result

Serum AST and ALT activities were significantly decreased in rats treated with different doses of CRAE, indicating its protective effect against CCl₄-induced chronic liver damage. Observation on serum SOD activity revealed that CRAE might act as an anti-oxidant agent against CCl₄-induced chronic oxide stress. Histological study supported these observations. Erk1/2 inhibition may take part into CRAE's effect on preventing hepatocyte from apoptosis when exposed to oxidative stress.

Conclusion

CRAE showed protective effect against CCl₄-induced chronic liver damage in rats and its potential as an agent in the treatment of chronic liver diseases by protecting hepatocyte from injury.     

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

Etnopharmacological relevance

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

Aim of the study

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

Material and methods

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

Results

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

Conclusions

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

Procyanidin-rich fractions from Parkia biglobosa (Mimosaceae) leaves cause redox-sensitive endothelium-dependent relaxation involving NO and EDHF in porcine coronary artery

Aim of the study

Parkia biglobosa leaves are traditionally used as an antihypertensive agent in Benin. The present study assessed the vasorelaxant activity of different Parkia biglobosa leaf extracts using isolated porcine coronary artery rings.

Materials and methods

A hydroalcoholic leaf extract was submitted to a multi-step liquid-liquid fractionation with solvents of increasing polarity and the polyphenolic content of the different fractions was analyzed. Vascular reactivity of the different extracts was assessed using porcine coronary artery rings, in the presence or absence of specific pharmacological inhibitors.

Results

The hydroalcoholic, ethyl acetate and butanolic extracts contained mainly procyanidins and monomeric flavonoids. Parkia biglobosa leaf crude extract induced a redox-sensitive endothelium-dependent relaxation mediated by both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The fractionation of the butanolic extract generated 6 fractions, two of which induced stronger vasorelaxation than the original extract and they had a higher phenolic content.

Conclusions

Parkia biglobosa leaf extract is able to induce endothelium-dependent NO- and EDHF-mediated relaxation in porcine coronary artery rings. The vasorelaxant activity is dependent on their phenolic content and appears to involve mainly procyanidins.     

The absorption characterization effects and mechanism of Radix Angelicae dahuricae extracts on baicalin in Radix Scutellariae using in vivo and in vitro absorption models

Ethnopharmacological relevance

Angelicae Dahurica(Hoffm.)Benth.&Hook.f.ex Franch.&Sav combined with Scutellaria baicalensis Georgi. has been widely used as herb-pairs in traditional Chinese medicine (TCM) to treat migraine headache and cataract, but the underlying compatibility mechanism of the two herbs remains unknown.

Aim of study

In the present work, we investigated the additive or synergistic effects of absorption behavior of Radix Angelicae dahuricae extracts on baicalin, and the absorption-enhancing mechanism of Radix Angelicae dahuricae extracts on baicalin.

Materials and methods

Total coumarins (Cou) and volatile oil (VO), as the two main components of Radix Angelicae dahuricae, were extracted by supercritical fluid extraction (SFE) further treated with liquid-liquid separation method. The absorption behavior was investigated by applying the everted gut sac technique and in situ single-pass intestinal perfusion method.

Results and conclusions

The results showed that both the Cou and the VO could improve the intestinal absorption of baicalin in vivo, and had synergistic action the enhanced absorption of baicalin. Since verapamil did not affect the P_app and K_a of baicalin significantly, we concluded that the absorption of Baicalin could not be an active transportation in dependent of P-glycoprotein-Mediated efflux systems. Based on intestinal absorption of drug studying was one of the efficacious methods to clarify the compatibility of principles of herb-pairs. The everted gut sac technique and in situ single-pass intestinal perfusion technique model were the effective methods to study the absorption of drug, the application of the animal model to investigating the absorption of herb-drug interactions or other relevant research purposes is envisioned.     

An ethnomedicinal, phytochemical and pharmacological profile of Desmodium gangeticum (L.) DC. and Desmodium adscendens (Sw.) DC

Ethnopharmacological relevance

Desmodium gangeticum (L.) DC. and Desmodium adscendens (Sw.) DC. are two important and well explored species of genus Desmodium (Fabaceae (alt. Leguminosae) subfamily: Faboideae). Desmodium gangeticum is used as a tonic, febrifuge, digestive, anticatarrhal, antiemitic, in inflammatory conditions of chest and in various other inflammatory conditions in the Ayurvedic System of Medicine while Desmodium adscendens is widely used for the treatment of asthma in Ghana, Africa.

Aim of the review

The aim of this review is to provide comprehensive information on the botany, traditional uses, phytochemistry, pharmacological research and toxicology of Desmodium gangeticum and Desmodium adscendens to explore their therapeutic potential and future research opportunities.

Materials and methods

All the available information on Desmodium gangeticum and Desmodium adscendens was collected via electronic search (using Pubmed, SciFinder, Scirus, Google Scholar, JCCC@INSTIRC and Web of Science) and a library search for articles published in peer-reviewed journals.

Results

About 25 different species of Desmodium including Desmodium gangeticum and Desmodium adscendens are used ethnomedicinally all over the world. Phytochemical research on Desmodium gangeticum and Desmodium adscendens has led to the isolation of alkaloids, pterocarpans, phospholipids, sterols, flavones and flavonoid glycosides from Desmodium gangeticum and triterpenoid saponins, phenylethylamines and indole-3-alkyl amines from Desmodium adscendens. Crude extracts, fractions and isolated components of Desmodium gangeticum and Desmodium adscendens showed a wide spectrum of in vitro and in vivo pharmacological activities like antileishmanial, immunomodulatory, antiasthmatic, smooth muscle relaxant, anti-inflammatory, anti-ulcer, cardio-protective, antidiabetic, antiamnesic, antiviral, antioxidant and hepatoprotective activities.

Conclusions

Desmodium gangeticum and Desmodium adscendens have emerged as a good source of traditional medicine. Desmodium gangeticum possesses the ability to scavenge the free radicals generated during ischaemia and ischaemia reperfusion thereby preserving the mitochondrial respiratory enzymes that eventually lead to cardio-protection and has potential prophylactic and therapeutic efficacy against Leishmania infection. Desmodium adscendens is useful against chronic bronchitis and asthma. However, there is a need to search for individual secondary metabolites responsible for these actions and study their mode of actions, bioavailability, pharmacokinetics and physiological pathways in sufficient detail. The promising results should be further substantiated by clinical trials.     

Gastric antisecretory and antiulcer activities of Cedrus deodara (Roxb.) Loud. in Wistar rats

Ethnopharmacological relevance: Cedrus deodara (Roxb.) Loud. is used in Ayurvedic medicine to treat peptic ulcer.

Aim of the study

To evaluate the gastric antisecretory and antiulcer activity of Cedrus deodara.

Materials and methods

The volatile oil extracted by steam distillation of Cedrus deodara wood was examined for its gastric antisecretory and antiulcer effect in the pylorus-ligated rat model and ethanol induced gastric lesions in rats.

Results

The volatile oil showed significant antisecretory activity as evidenced by decreased gastric fluid volume, total acidity, free acidity and increase in the pH of the gastric fluid in pylorus-ligated rats. Our studies also revealed that pretreatment with Cedrus deodara significantly reduced the number of ulcer, ulcer score and ulcer index in pylorus-ligated and ethanol treated rats. The antiulcer activity of Cedrus deodara is further supported by histopathological study which showed protection of mucosal layer from ulceration and inflammation.

Conclusion

The present findings conclude that volatile oil of Cedrus deodara wood has potent antisecretory and antiulcer effects and justify the traditional usage of this herb to treat peptic ulcers.     

Wound healing and anti-inflammatory activities of the Michauxia L'Hérit (Campanulaceae) species native to Turkey

Ethnopharmacological relevance

The leaves of Michauxia species are used for the treatment of wounds in Turkish traditional medicine. In the present study, wound healing, anti-inflammatory and antioxidant activities of the extracts obtained from the root and herb of 5 species of Michauxia collected in different parts of Turkey were evaluated.

Material and methods

In vivo incision and excision wound models were used in order to assess the wound healing effects of the methanolic extracts of the plants. Skin samples were also evaluated histopathologically. In vivo inhibitory effect of the extracts on acetic acid-induced increase in capillary permeability was studied for the assessment of anti-inflammatory activity. TBA (thiobarbituric acid) test, qualitative and quantitative DPPH (2,2-diphenyl-1-picrylhydrazyl) tests were used to evaluate the antioxidant activity.

Results

Noteworthy wound healing activity was observed for the ointment formulation prepared with 1% Michauxia nuda (root) and Michauxia tchihatchewii (herb) extracts. The results of histopathological evaluation supported the outcome of incision and excision wound models. Moreover, the Michauxia nuda (root) exerted remarkable anti-inflammatory effect. The highest antioxidant activity was observed with the ethyl acetate extract of Michauxia tchihatchewii herb.

Conclusion

The experimental study revealed that Michauxia displays remarkable wound healing and anti-inflammatory and antioxidant activities.     

Therapeutic effects of total coumarins from Urtica dentata Hand on collagen-induced arthritis in Balb/c mice

Ethnopharmacological relevance

Urtica dentata Hand (UDH), the root of Laportea bulbifera (Sieb. et. Zucc.) Wedd, has long been utilized in traditional Chinese medicine for the treatment of rheumatoid arthritis and some other autoimmune diseases. Coumarins are the main active principles contributing to UDH's efficacy, but the mechanisms have not been fully clarified.

Aim of study

To explore effects of total coumarins (TC) isolated from UDH on the development of type II collagen (CII)-induced arthritis (CIA) in Balb/c mice.

Materials and methods

Arthritis was induced in Balb/c mice by immunization with an emulsion of 200 mg CII and complete Freund's adjuvant (CFA). The CIA mice were then given with a suspension of TC or saline by intragastric (i.g.) administration every other day. The incidence and severity of disease and histopathology of inflammation were assessed. Inflammatory response was determined by measuring the levels of different inflammation mediators in serum. The effect of TC on differentiation of CD4⁺CD25⁺ Foxp3⁺Treg cells was examined by flow cytometry. The phenotype of bone marrow-derived dendritic cells (DCs), T-bet mRNA level and IL-12p70 secretion by DCs were also detected.

Results

Pharmacologically, treatment with TC for type II collagen induced arthritis in mice through oral administration displayed significant and dose-dependent drop of clinical arthritis score and paw swelling, compared with the untreated CIA mice. Pathologic changes showed that TC protected tissues against bone destruction, whereas an almost complete destruction occurred in the CIA model group. The protective status was associated with a substantial decrease in the production of IFN-γ and IL-2, an increase of IL-10 and TGF-β and suppressive expression of T-bet in DCs. TC also induced the generation of CD4⁺CD25⁺ Treg cells with a Treg phenotype Foxp3. TC-treated DCs were characterized as low expression of MHC class II and CD86 molecules, as well as a reduction of IL-12p70.

Conclusions

Our data suggest that TC provides substantial therapeutic protection against CIA by eliciting immune tolerance and it would be a valuable candidate for further investigation as a new anti-arthritic agent.     

Neuroprotective effect of Alpinia galanga (L.) fractions on Aβ(25-35) induced amnesia in mice

Ethnopharmacological relevance

The rhizomes of Alpinia galanga (L.) Willd (Zingiberaceae), a ginger substitute for flavouring food was traditionally used as nervine tonic and stimulant.

Aim of the study

This investigation is designed to screen cognitive improvement of Alpinia galanga (AG) fractions in Alzheimer's type of amnesia in mice induced by Aβ_(25-35).

Materials and methods

Alzheimer's disease induced mice treated with fractions (n-hexane, chloroform and ethyl acetate) of AG in 200 and 400 mg/kg. Neurotoxicity was induced by intracerebroventricular injection of Aβ_(25-35) on the 14th day of 21 days drug treatment. Open field and water maze were carried to determine habituation memory and hippocampal memory. Na⁺/K⁺-ATPase, acetylcholinesterase (AChE) and antioxidant enzymes (SOD, GPx, catalase and vitamin C) were determined in brain tissue homogenate to estimate the brain biochemical changes and its anti-amnesic potential with intensity of oxidative stress signaling. Further bioactive (chloroform) fraction was eluted through column chromatography to identify the lead molecules.

Results

Increased habituation memory and decreased escape latency in behavioral parameter are the indicative of the cognitive enhancement after treatment with Alpinia galanga fractions. Increment in Na⁺/K⁺-ATPase and antioxidant activity depicts brain membrane integrity improvement and free radical scavenging property. AChE level was decreased to improve the cognition by enhancing cholinergic transmission.

Conclusion

Anti-amnesic effect was exerted by various fractions of Alpinia galanga. Among all fractions, preeminent neuroprotection was exerted by chloroform fraction, which has compound, 1′δ-1′-acetoxyeugenol acetate and it may be a potential therapeutic agent for Alzheimer's type of amnesia. These results further motivate us to explore the activity of lead compound's anti-amnesic effect on transgenic mice model of AD.     

Ge-Gen-Tang has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

Ethnopharmacological relevance

Ge-Gen-Tang (GGT) has been used against adult respiratory tract infection for thousand years in ancient China. However, GGT is unable to inhibit influenza virus. The effect of GGT to manage respiratory tract viral infection has been questioned. Several ingredients of GGT and their constituents are able to inhibit various viruses. Therefore, GGT might have antiviral activity against other viruses causing respiratory tract illness. Human respiratory syncytial virus (HRSV) is one of the most important airway viruses. However, it is unknown whether GGT is effective against HRSV.

Aim of the study

HRSV contributes considerably to respiratory tract illness of the elderly and immunocompromised adults. There is no effective therapeutic modality for HRSV infection. In order to find a readily available agent to manage HRSV infection, the authors tested the hypothesis that GGT can effectively minimize airway pathology by preventing HRSV-induced plaque formation in respiratory mucosal cell lines.

Materials and methods

Effect of the hot water extract of GGT on HRSV was tested by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Ability of GGT to stimulate anti-viral cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA).

Results

GGT dose-dependently inhibited HRSV-induced plaque formation in both cell lines (p < 0.0001), especially in A549 cells. GGT was more effective when given before viral infection (p < 0.0001). GGT could dose-dependently inhibit viral attachment (p < 0.0001) with or without heparin. GGT could further inhibit HRSV internalization time-dependently and dose-dependently (p < 0.0001). GGT could stimulate mucosal cells to secrete IFN-β to counteract viral infection before and after viral inoculation.

Conclusions

GGT is effective against HRSV-induced plaque formation in airway epithelium.     

Hypotensive effect of aqueous extract of Averrhoa carambola L. (Oxalidaceae) in rats: an in vivo and in vitro approach

Aim of the study

Averrhoa carambola L. (Oxalidaceae) leaves are used in Brazilian traditional medicine to treat hypertension. This study was conducted to evaluate the hypotensive effect of the aqueous extract of Averrhoa carambola (AEAc) and its underlying mechanisms in the isolated rat aorta.

Materials and methods

The effect of AEAc on the mean arterial pressure (MAP) was determined in vivo in anesthetized rats. In vitro, thoracic aortic rings were isolated and suspended in organ baths, and the effects of AEAc were studied by means of isometric tension recording experiments. In HPLC analysis, the fingerprint chromatogram of AEAc was established.

Results

In normotensive rats, AEAc (12.5-50.0 mg/kg, i.v.) induced dose-dependent hypotension. In vitro, AEAc caused a depression in the E_max response to phenylephrine without a change in sensibility. Also, in a depolarized Ca²⁺-free medium, AEAc inhibited CaCl₂-induced contractions and caused a concentration-dependent rightward shift of the response curves, indicating that AEAc inhibited the contractile mechanisms involving extracellular Ca²⁺ influx.

Conclusions

These results demonstrate the hypotensive effects of AEAc, and these effects may, in part, be due to the inhibition of Ca²⁺, which supports previous claims of its traditional use.     

Anti-inflammatory and antinociceptive effects of the stem bark of Byrsonima intermedia A. Juss

Ethnopharmacological relevance

Byrsonima intermedia A. Juss. is popularly known as “murici pequeno” and is native to the Brazilian Cerrado. This species has been used as an antimicrobial, anti-hemorrhagic, anti-diarrheal and anti-inflammatory. Nevertheless, scientific information regarding Byrsonima intermedia is limited; there are no reports related to its possible anti inflammatory and antinociceptive effects. This study employed in vivo inflammatory and nociceptive models to evaluate the scientific basis for the traditional use of Byrsonima intermedia.

Materials and methods

Carrageenan-induced paw edema, peritonitis and fibrovascular tissue growth induced by s.c. cotton pellet implantation tests were used to investigate the anti-inflammatory activity of Byrsonima intermedia aqueous extract (BiAE) in rats. Mechanical nociceptive paw, formalin and hot plate tests were used to evaluate the antinociceptive activity in mice. High-performance liquid chromatography (HPLC), phytochemistry screening and determination of total phenolics and flavonoids were used to determine the chemical profile of the BiAE.

Results

BiAE at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced carrageenan-induced paw edema, by inhibited leukocyte recruitment into the peritoneal cavity and, in the model of chronic inflammation, by using the cotton pellet-induced fibrovascular tissue growth in rats. The extracts at test doses of 30-300 mg/kg p.o. clearly demonstrated antinociceptive activity in all tests. Administration of the opioid receptor antagonist naloxone completely inhibited the antinociceptive effect induced by BiAE (100 mg/kg).

Conclusion

BiAE markedly exhibits anti-inflammatory action in rats and antinociceptive activity in mice. Thus, it may be useful in the treatment of inflammatory hyperalgesic disorders, which supports previous claims of its traditional use.     

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

Ethnopharmacological relevance

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

Materials and methods

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

Results

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

Conclusions

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

The neuroprotective effects of an extract of Gastrodia elata

Ethnopharmacological relevance

Gastrodia elata (GE) Blume (family Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, and epilepsy, indicating neuronal protective functions.

Aim of the study

To evaluate the neuroprotection of GE and its molecular mechanism in preventing serum deprivation-induced PC12 cell apoptosis.

Materials and methods

An MTT assay and Hoechst staining were used to respectively validate serum deprivation-induced cell death and apoptosis. Cyclic (c)AMP formation and protein kinase (PK)A activity were also measured after GE treatment. Western blotting was used to detect the phosphorylation of the cAMP response element-binding (CREB) protein. Transient transfection of a dominant negative CREB was used to validate the importance of CREB.

Results

GE targeted the adenosine A_2A receptor (A_2A-R). GE increased cAMP formation, PKA activity, and phosphorylation of the CREB protein. GE-induced CREB protein phosphorylation and protection was blocked by a PKA inhibitor and overexpression of the dominant negative CREB, respectively.

Conclusions

These results support the neuroprotective effects of GE. The protective mechanism might be mediated through an A_2A-R/cAMP/PKA/CREB-dependent pathway.