Effects In Guinea Pigs Research Articles

Mellisa officinalis Leaf Extract Green-Synthesized AgNPs: Investigation of Its Anaesthetic and Analgesic Activities

Investigating and studying natural origin agents, such as nanocompounds obtained from plants that have less harmful effects, is the main research aim in the field of treatment of diseases. For this goal, extensive research have been performed on several medicinal herbs and their nanoparticles, and their cytotoxic and therapeutic properties have been determined. In the current experiment, the Ag nanoparticles green-synthesis were carried out by the Mellisa officinalis extract. The formulated NPs were analyzed by FESEM, TEM, and UV-Vis. In the in vivo design, after oral administration, paw edema was significantly decreased in mice. CH3COOH-induced writhing episodes were dose-dependently and significantly decreased. The results of anesthetic activity were indicated that the nanoparticles made the local anesthetic effects in guinea pig and frog models. In addition, the analgesic and anti-inflammatory properties were determined in several doses.

Maternal Vitamin C Intake during Pregnancy Influences Long-Term Offspring Growth with Timing- and Sex-Specific Effects in Guinea Pigs.

Our previous work in guinea pigs revealed that low vitamin C intake during preconception and pregnancy adversely affects fertility, pregnancy outcomes, and foetal and neonatal growth in a sex-dependent manner. To investigate the long-term impact on offspring, we monitored their growth from birth to adolescence (four months), recorded organ weights at childhood equivalence (28 days) and adolescence, and assessed physiological parameters like oral glucose tolerance and basal cortisol concentrations. We also investigated the effects of the timing of maternal vitamin C restriction (early vs. late gestation) on pregnancy outcomes and the health consequences for offspring. Dunkin Hartley guinea pigs were fed an optimal (900 mg/kg feed) or low (100 mg/kg feed) vitamin C diet ad libitum during preconception. Pregnant dams were then randomised into four feeding regimens: consistently optimal, consistently low, low during early pregnancy, or low during late pregnancy. We found that low maternal vitamin C intake during early pregnancy accelerated foetal and neonatal growth in female offspring and altered glucose homeostasis in the offspring of both sexes at an age equivalent to early childhood. Conversely, low maternal vitamin C intake during late pregnancy resulted in foetal growth restriction and reduced weight gain in male offspring throughout their lifespan. We conclude that altered vitamin C during development has long-lasting, sex-specific consequences for offspring and that the timing of vitamin C depletion is also critical, with low levels during early development being associated with the development of a metabolic syndrome-related phenotype, while later deprivation appears to be linked to a growth-faltering phenotype.

A Bilayer Microneedle for Modulated Sequential Release of Adrenaline and Lidocaine for Prolonged Local Anesthesia.

Chronic pain emerges as a major global health issue, significantly impacting individuals' health and quality of life. In this study, we designed a bilayer microneedle loaded with lidocaine nanocomposites in the inner layer and adrenaline (Adr) in the outer layer (HCP MNs) for modulated sequential release to achieve prolonged local anesthesia. The obtained HCP MNs featured an intact structure with adequate mechanical strength for efficient skin penetration. The bilayer structure of MNs was evidenced by loading two fluorescent dyes in each layer. Furthermore, these HCP MNs were capable of inducing rapid as well as prolonged local anesthetic effects in guinea pigs. Hence, the bilayer MN coloaded with Adr and lidocaine nanocomposite serves as a promising transdermal delivery platform for chronic pain management.

Evaluation of the analgesic and anesthetic properties of silver nanoparticles supported over biodegradable acacia gum-modified magnetic nanoparticles

Abstract An ecofriendly and green procedure was adopted to immobilize Ag NPs over acacia gum (GA)-modified magnetic nanoparticles (Fe3O4-GA/Ag NPs) with analgesic and anesthetic properties. In the stepwise modification method, the pre-synthesized Fe3O4 NPs were coated by the gum acacia (GA) that has hydroxyl groups on its backbone and can be used for as a capping, reducing, and stabilizing agent for immobilized Ag nanoparticles. The capped Ag ions were reduced and immobilized over the acacia gum because of hydrogen bonding of the hydroxyl groups. The final bio-material was characterized by various analytical techniques such as X-ray diffraction, energy dispersive X-ray spectroscopy, inductively coupled plasma-optical emission microscope, transmission electron microscopy, field emission scanning electron microscopy, and fourier transformed infra red spectroscopy. In the in vivo design, the results of anesthetic activity indicated that the Fe3O4-GA/Ag NPs made local anesthetic effects in guinea pig and frog models. After oral administration of Fe3O4-GA/Ag NPs, paw edema was significantly decreased in mice. Acetic acid-induced writhing episodes were dose-dependently and significantly decreased in all groups treated with Fe3O4-GA/Ag NPs. In addition, the analgesic and anti-inflammatory properties were determined in several doses of Fe3O4-GA/Ag NPs. The above results protect the analgesic and anesthetic properties of silver nanoparticles supported over biodegradable acacia gum-modified magnetic nanoparticles for the next research or clinical trial studies in human.

Identification of a New Pyrrolyl Pyridoindole Alkaloid, Melpyrrole, and Flazin from Honey and Their Cough-Suppressing Effect in Guinea Pigs.

The cough-suppressing effect of honey was demonstrated for the first time using a guinea pig model whereby cough was induced by citric acid and capsaicin, and a new pyrrolyl pyridoindole, 1-(5-(hydroxymethyl)-1H-pyrrol-2-yl)-9H-pyrido[3,4-b]indole-3-carboxylic acid (1), named melpyrrole, and flazin (2) were identified as the active principle components. The structures of 1 and 2 were estimated using a combination approach of an activity-guided survey and LC-MS/MS multivariate analysis and were finally established by total synthesis of 1 and comparison with an authentic standard for 2. Both compounds showed antitussive activity comparable to that of dextromethorphan in guinea pigs. Their antitussive effects were unaffected by an opioid antagonist and reversed by a nitric oxide (NO) synthase inhibitor, indicating that these natural products do not act directly on opiate receptors but through the NO signaling pathway.

Silver nanoparticles (Ag NPs) adorned starch-functionalized magnetite nanocomposite: Investigation of cytotoxicity, analgesic and anaesthetic activities

In current days, the biosynthesis of magnetic bio-nanocomposites have emerged incredibly as the new-generation catalytic materials. This report demonstrates the devising of a hybrid Ag NP decorated starch biomolecule modified Fe3O4 (Fe3O4@starch/Ag) bio-nanomaterial. Physicochemical features of the material were further characterized over a range of advanced methods like SEM, TEM, EDX, XRD and ICP-OES. For investigating the antioxidant potentials of AgNO3, Fe3O4@starch, and Fe3O4@starch/Ag, the DPPH analysis was applied in the BHT presence as the positive control. The IC50 of the Fe3O4@starch/Ag was 160 μg/mL. To survey the cytotoxicity activities of AgNO3, Fe3O4@starch, and Fe3O4@starch/Ag, MTT way was applied on normal cell. After oral administration, paw edema was significantly decreased in mice. The results of anesthetic activity were indicated that the nanoparticles made the local anesthetic effects in guinea pig and frog models. CH3COOH-induced writhing episodes were dose-dependently and significantly decreased. In addition, the analgesic and anti-inflammatory properties were determined in several doses.

Toxicological evaluation of a nonlethal riot control combinational formulation upon dermal application using animal models

Numerous adverse effects on human health have been reported in epidemiological studies of oleoresin capsicum (OC) and other riot control agents (RCAs). Importantly, the daunting risk of such RCAs can be neutralized by optimizing the desired concentration of such agents for mob dispersal. Hence, a nonlethal riot control combinational formulation (NCF) was prepared for dispersing rioters without imparting fatal outcomes. However, for desired utilization of NCF, it is essential to recognize its extent of potential toxicity. Therefore, the current investigation evaluated the dermal toxicity of NCF using experimental animals in compliance with the OECD guidelines. Additionally, few essential metal ions were analyzed and found non -significantly different in the test rats as compared to control rats. Moreover, abnormal dermal morphology and lesions ultrastructural tissue defects were not noticed as evinced by different studies like ultrasonography, histology, and scanning electron microscopy (SEM) respectively. Further, Doppler ultrasonography exhibited non-significantly different blood flow velocity in both groups, whereas miles test demonstrated a significantly increased Evans blue concentration in test rats compared to the control rats, which might be due to an initial increase in blood flow via an instant action of the NCF at the cutaneous sensory nerve endings. However, our results demonstrated NCF can produce initial skin irritating and sensitizing effects in guinea pigs and rabbits without the antecedence of acute toxicity (≤2000 mg/kg) in Wistar rats.

Novel α7 nicotinic acetylcholine receptor modulators as potential antitussive agents

A novel series of α7 nicotinic acetylcholine receptor (nAChR) modulators was designed and evaluated for antitussive activity in an in vivo guinea pig model of chemically induced cough. Compound 16 at all tested doses (9.5, 3 and 1 mg/kg) significantly (p < 0.01) reduced the cumulative number of coughs and showed similar results to a positive control (codeine at 30 mg/kg). Among three different administration routes (intraperitoneal, oral and inhalation), compound 16 exerted a significant antitussive effect in guinea pigs at an inhaled dose as low as 0.4 mg/kg (p < 0.05). α7 nAChR modulators may provide a novel, non-narcotic approach to therapy in patients with acute and chronic cough.

Hot spring bathing accelerates wound healing and enhances heat retention effect in guinea pigs.

This study aimed to demonstrate the effects of hot springs on wound healing and heat retention by performing comparative experiments with tap water. The hot spring water used in this study was from an alkaline hot spring that was rich in sodium and chloride ions and exhibited high reducibility. Guinea pigs were divided into a hot spring bathing group and a tap water bathing group, and a bathing test was conducted for eight consecutive days. A comparison of the plasma amino acid composition between the two groups after the bathing test revealed differences in the concentrations of several amino acids associated with wound healing. Image analysis demonstrated that wounds made on the abdominal skin of guinea pigs were significantly contracted by hot spring bathing compared to that by tap water bathing, and histopathological findings showed that wound healing was accelerated. In the thermography test, changes in body surface temperature after bathing were investigated in both groups. The heat retention effect was not observed in the tap water bathing group after bathing, whereas it was enhanced in the hot spring bathing group until 30 min after bathing. In conclusion, this study demonstrated that hot spring bathing accelerates wound healing and has a more significant heat retention effect than tap water bathing.

Biological Evaluation of Medical Devices in the Form of Suppositories for Rectal and Vaginal Use

Background. Programs of preclinical safety studies of the health care products depend on the regulatory status of the investigated products. The classification of such products, in particular suppositories for rectal and vaginal use, is a critical step of developing tactics for their biological evaluation. Adaptation of biological evaluation methods for the medical devices based on the combination of biologically active substances, as well as evaluation of the results of such studies is urgent task of biomedicine. Objective. To substantiate the regulatory status and to carry out a biological evaluation of medical devices in the form of vaginal suppositories based on octenidine dihydrochloride ("Prodexyn") and in the form of rectal suppositories based on Saw palmetto, Levisticum officinale and Calendula officinalis extracts ("Pravenor"). Methods. Biological evaluation was conducted according to the requirements of ISO 10993 standards using in vitro and in vivo biological test systems (cytotoxicity in cell culture and the MTT test, sensitizing and irritating effect in guinea pigs). Results. The cytotoxicity (СС50) of the medical device "Prodexyn" extract in Vero cell culture was 8.35 μg/ml calculated as octenidine dihydrochloride and 416.65 μg/ml calculated as dexpanthenol. "Pravenor" medical device was found to be non-toxic in Vero cell culture. According to the results of MMT assay CC50 for octenidine dihydrochloride was 1.67 μg/ml, and 83.33 μg/ml – for dexpanthenol. CC50 indicators calculated for the different active ingredients of the medical device "Pravenor" were the following: 50 mg/ml for the dwarf palm berries extract (Saw palmetto), 16.67 mg/ml for the lovage roots extract (Levisticum officinale), and 16.67 mg/ml for the calendula flowers extract (Calendula officinalis). No sensitizing or skin irritating effects were observed in guinea pigs. Conclusions. Biological evaluation of medical devices in the form of rectal suppositories "Pravenor" and vaginal suppositories "Prodexyn" performed using in vitro and in vivo biological systems. It was demonstrated an acceptable level of safety of the products. The MTT test was 5 times more sensitive than the Vero cell culture method in determination of cytotoxicity.

Comparative Transcriptome Analysis of Artificially Induced Rough-Mutant Brucella Strain RM57 and Its Parent Strain Brucella melitensis M1981.

Brucellosis is one of the most common zoonotic epidemics with a serious threat to public health and livestock development in many countries across the world. Vaccination is a key control strategy toward preventing brucellosis in high-prevalence regions. Recently, a rough-type Brucella melitensis mutant strain (RM57) induced from a B. melitensis strain M1981 showed protective effects in guinea pigs indicating that it is a good vaccine candidate. In this study, stress response assays were performed to reveal the mechanisms underlying virulence attenuation of RM57. In addition, a genome-wide transcriptome profile of RM57 was analyzed relative to the parent strain M1981 in order to reveal genetic factors controlling the phenotypes. Our results indicated a similar sensitivity to various stress conditions in RM57 owing to a lack of significant differences from its parent strain. Transcriptome analysis showed that a total of 1,205 genes were differentially expressed between RM57 and M1981 with gene ontology terms revealing that these genes are involved in energy production and conversion, translation, ribosomal structure, and biogenesis. Pathway enrichment analysis revealed that genes involved in oxidative phosphorylation, ribosome, nitrogen metabolism, tyrosine metabolism, and two-component system were significantly affected. As a result of these differences at the molecular level, the function of type IV secretion system in RM57 was found to be affected leading to reduced virulence of the RM57 mutant strain in both macrophage and mice infection models.

Discovery of a novel niacin-lipoic acid dimer N2L attenuating atherosclerosis and dyslipidemia with non-flushing effects

Niacin has been widely used as an antihyperlipidemic drug, but the flushing effect restricted its clinical application. Here, we developed novel niacin-lipoic acid dimers which lead to better lipid modulation, higher synergistic effects and less side effects. We utilized molecular docking simulation to design a novel series of niacin-lipoic acid dimers. The compound N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide (N2L) was selected for the in vitro and in vivo evaluation, including the agonist activity in CHO-hGPR109A cells, cell protective effects in HT22 and HUVECs cells, flushing effect in guinea pigs and rats, lipid modulation in C57BL/6 mice and high fat diet-rats and atherosclerotic lesions regulation in apolipoprotein E null mice. N2L worked as potent and selective agonists for the high affinity niacin receptor GPR109A. N2L retained antioxidation and cytoprotection of lipoic acid. In addition, N2L displayed a good therapeutic index regarding lipid modulation and atherosclerotic lesions regulation, and minimized niacin-induced vasodilation (flushing) effect in vivo. N2L showed effective treatment regarding to lipid regulation and atherosclerosis inhibition effects, also with excellent antioxidant effects, safety profiles and non-flushing. All these results suggest N2L promising application prospects in the drug development for the treatment of atherosclerosis.

Evaluation of the anti-asthmatic and antitussive potentials of methanol leaf extract of Napoleona vogelii in rodents

Napoleona vogelii is used in ethnomedicine for the treatment of asthma and cough. This study evaluated antiasthmatic and antitussive properties of its methanol leaf extract (NVE) in rodents. Phytochemical screening was conducted using established methods. Acute oral toxicity test was done in mice and guinea pigs. Ovalbumin (OA)-sensitized guinea pigs were orally pretreated with 100, 200 or 400 mg/kg/day of NVE or 0.5 mg/kg/day of salbutamol for 14 days before exposure to 0.2% histamine aerosol. Latency to preconvulsive dyspnea (PCD), tracheal fluid volume (TFV), flow rate (FR), and tracheal morphometry (TM) were evaluated. Tracheal rings from sensitized guinea pigs were tested in organ baths for antispasmodic and spasmolytic effects. Citric acid and ammonium hydroxide cough models were used to evaluate antitussive effects in guinea pigs and mice respectively. Tannins, alkaloids, flavonoids, and phenolic substances were found in NVE. LD50 values in mice and guinea pigs were greater than 5000 mg/kg. NVE caused a significant (P < 0.05) increase in the latency to PCD and a decrease in TFV in the group treated with 200 mg/kg. TM indicated a reduction in airway narrowing in NVE-treated groups. The presence of NVE significantly attenuated responses of tracheal rings to carbachol. Its addition to carbachol precontracted rings resulted in significant relaxation. Emax for calcium concentration-response was significantly (P < 0.01) decreased in the presence of NVE. Cough bouts dose-dependently decreased significantly (P < 0.05) in guinea pigs and mice. We conclude that NVE seems safe and possesses anti-asthmatic effect that involves inhibition of calcium influx. It also has antitussive properties that may be peripherally mediated.

Pharmacokinetics of buprenorphine after intravenous and oral transmucosal administration in guinea pigs (Cavia porcellus).

OBJECTIVE To determine pharmacokinetics and sedative effects of buprenorphine after IV and oral transmucosal (OTM) administration in guinea pigs. ANIMALS 14 male guinea pigs (6 adults for preliminary experiment; eight 8 to 11-week-old animals for primary study). PROCEDURES A preliminary experiment was conducted to determine an appropriate buprenorphine dose. In the primary study, buprenorphine (0.2 mg/kg) was administered IV or OTM, and blood samples were obtained. The pH of the oral cavity was measured before OTM administration. Sedation was scored for 6 hours on a scale of 0 to 3 (0 = no sedation and 3 = heavy sedation). After a 7-day washout period, procedures were repeated in a crossover manner. Plasma buprenorphine concentration was quantified, and data were analyzed with a noncompartmental pharmacokinetic approach. RESULTS Mean peak plasma buprenorphine concentrations were 46.7 and 2.4 ng/mL after IV and OTM administration, respectively. Mean time to maximum plasma buprenorphine concentration was 1.5 and 71.2 minutes, and mean terminal half-life was 184.9 and 173.0 minutes for IV and OTM administration, respectively. There was a range of sedation effects (0 to 2) for both routes of administration, which resolved within the 6-hour time frame. CONCLUSIONS AND CLINICAL RELEVANCE On the basis of pharmacokinetic parameters for this study, buprenorphine at 0.2 mg/kg may be administered IV every 7 hours or OTM every 4 hours to maintain a target plasma concentration of 1 ng/mL. Further studies are needed to evaluate administration of multiple doses and sedative effects in guinea pigs with signs of pain.

The neuronal stem cells effect on inner ear structure in experimental gentamicin ototoxicity

Objective. To examine the effectiveness of suspensions of embryonic stem cells in experimentally induced aminoglycoside ototoxicity in Guinea pigs.Materials and methods. The study involved 35 adult Guinea pigs. The hearing loss was caused by administration of gentamicin 100 mg per KBW. Intratympanal suspension of 2 million neuronal steam cells in 0.5 mg and sub occipital suspension of 2 million cells in 0.5 mg were administered on the 1st and 15th day.Results. The methodology of using and preparation of the suspension from neuronal stem cells enables to provide their necessary number for transplantation in vivo, remaining the cell characteristics.Aminoglycoside ototoxity caused by a 14-day administration of gentamicin to Guinea pigs in a dose of 100 mg/KBW was accompanied by general intoxication: reduced appetite, weight loss, frequent urination, hair falling out. The administration of neuronal stem cells on the first day, before and after aminoglycoside administration, completely, and on 15 partially neutralizes the symptoms.Fourteen-day administration of gentamicin to Guinea pigs causes a violation of the architectonics and morphology of inner ear microcirculation in psalterial cords.NSC administration on the first day of simulated aminoglycoside ototoxicity prevented its development if 14-day injections of gentamycin, that is confirmed by ABR and morphologically.Conclusions. The conducted experiments show the feasibility of the chosen direction to explore the potential use of neuronal stem cells for the prevention of aminoglycoside ototoxic effects in Guinea pigs.

Attenuation of ischemia/reperfusion-induced inhibition of the rapid component of delayed rectifier potassium current by Isosteviol through scavenging reactive oxygen species

Isosteviol has been demonstrated to play a protective role during ischemia reperfusion (I/R) myocardial infarction. However, the underlying electrophysiological mechanisms of isosteviol are still unknown. Our previous study showed that the rapid component of the delayed rectifier potassium channel (IKr) plays an important role in the prolongation of I/R-induced QT interval-related arrhythmia. This study aimed to investigate whether isosteviol could attenuate I/R-induced prolongation of the action potential duration (APD) along with inhibition of IKr, and we aimed to clarify the electrophysiological mechanism of isosteviol to determine its cardioprotective effects in guinea pigs. We observed that the APD90 were 298.5±41.6ms in control, 528.6±56.7ms during I/R, and reduced to 327.8±40.5ms after 10μmol/L of isosteviol treatment. The IKr currents were 1.44±0.06 pA·pF−1in the control group, 0.50±0.07pA·pF−1during I/R, and recovered to 1.20±0.12pA·pF−1after 10μmol/L of isoteviol treatment. Moreover, isosteviol reduced the over-production of reactive oxygen species (ROS) during I/R. Importantly, isosteviol does not affect the IKr and human ether-a-go-go-related gene currents of normal cardiomyocytes. It attenuated the I/R-induced inhibition of IKr due to reduced over-production of ROS. Furthermore, isosteviol is safe and has no cardiotoxicity, and it might be beneficial for coronary reperfusion therapy.

In vivo cough suppressive activity of pectic polysaccharide with arabinogalactan type II side chains of Piper nigrum fruits and its synergistic effect with piperine

Piper nigrum L. fruits are not only a prized spice, but also highly valued therapeutic agent that heals many ailments including asthma, cold and respiratory problems. Herein, we have investigated structural features and in vivo antitussive activity of three fractions isolated from Piper nigrum fruits. The water extract (PN-WE) upon fractionation with EtOH yielded two fractions: a soluble fraction (PN-eSf) and a precipitated (PN-ePf) one. The existence of a pectic polysaccharide with arabinogalactan type II side chains (147kDa) in PN-ePf and piperine in PN-eSf were revealed. Moreover, oligosaccharides providing fine structural details of side chains were generated from PN-ePf and then characterized. The parental water extract (PN-WE) that contained both pectic polysaccharide and piperine, after oral administration (50mgkg−1 body weight) to guinea pigs, showed antitussive activity comparable to codeine phosphate (10mgkg−1 body weight). The EtOH precipitated fraction (PN-ePf) containing pectic polysaccharide showed comparatively higher antitussive activity than EtOH soluble fraction (PN-eSf) that contained piperine, but their potencies are lower than the parental water extract. Significantly, the specific airway smooth muscle reactivity of all three fractions remained unchanged. Finally, pectic polysaccharide-piperine combination in parental extract synergistically enhances antitussive effect in guinea pigs.

CRF1 but not glucocorticoid receptor antagonists reduce separation-induced distress vocalizations in guinea pig pups and CRF overexpressing mouse pups. A combination study with paroxetine

RationaleGiven the large number of patients that does not respond sufficiently to currently available treatment for anxiety disorders, there is a need for improved treatment. ObjectivesWe evaluated the anxiolytic effects of corticotropin releasing factor (CRF)1 receptor antagonists and glucocorticoid receptor (GR) antagonists in the separation-induced vocalization test in guinea pigs and transgenic mice with central CRF overexpression. Furthermore, we explored effects of these drugs when given in combination with a suboptimal dose of a selective serotonin re-uptake inhibitor (SSRI). MethodsIn guinea pig pups, the CRF1 receptor antagonists CP-154,526 and DMP695, and the GR antagonists mifepristone and Org34517 (all at 2.5, 10 and 40mg/kg intraperitoneally (IP)) were tested alone or in combination with 0.63mg/kg paroxetine IP. In CRF overexpressing mouse pups and wild type littermates, effects of CP-154,526 (10, 20 and 40mg/kg subcutaneously (SC)) and mifepristone (5, 15, 45mg/kg SC) were studied alone or in combination with 0.03mg/kg paroxetine SC. ResultsCRF1 but not GR antagonists reduced the number of calls relative to vehicle in guinea pigs and mice, independent of genotype. Treatment of CRF1 receptor or GR antagonists with paroxetine had no combined effect in guinea pigs, wild type or CRF overexpressing mice. ConclusionsCurrent results indicate robust anxiolytic properties of CRF1 receptor antagonists in guinea pigs and mice overexpressing CRF, and lack thereof of GR antagonists. Although no combined treatment effects were observed, it would be interesting to study combined treatment of CRF1 receptor antagonists with SSRIs following chronic drug administration.

Study of pH Stability of R-Salbutamol Sulfate Aerosol Solution and Its Antiasthmatic Effects in Guinea Pigs.

Currently, all commercial available nebulized salbutamol in China is in its racemic form. It is known that only R-salbutamol (eutomer) has therapeutic effects, while S-salbutamol (distomer) may exacerbate asthma after chronic use. Therefore, it is an unmet clinical need to develop R-salbutamol as a nebulized product that is more convenient for young and old patients. In our study, a stable aerosol solution of R-salbutamol sulfate was established, and its antiasthmatic effects were confirmed. The decomposition rate and racemization effect of the R-salbutamol sulfate solution were evaluated over a pH range from 1 to 10 (except pH=7, 8) at 60°C. The aerodynamic particle size of the R-salbutamol sulfate solution and commercial RS-salbutamol sulfate solution were both tested in vitro by Next-Generation Impactor (NGI) in 5°C. Laser diffractometer was used to characterize the droplet-size distribution (DSD) of both solutions. We next conducted an in vivo animal study to document the antiasthmatic effect of R-salbutamol aerosol sulfate solution and determine the relationship to RS-salbutamol. The results showed that the R-salbutamol sulfate solution was more stable at pH 6. In vitro comparison studies indicated that there was no distribution difference between R-salbutamol sulfate solution and the commercial RS-salbutamol solution. The animal results showed that R-salbutamol was more potent than RS-salbutamol against the same dose of histamine challenge. Unlike commercial RS-salbutamol, which was acidified to a pH of 3.5 to extend bench life but may cause bronchoconstriction in asthmatic patients, the neutralized R-salbutamol solution was more suitable for clinic use.

Antitussive, anti-pyretic and toxicological evaluation of Ma-Xing-Gan-Shi-Tang in rodents.

BackgroundMa-Xing-Gan-Shi-Tang (abbreviated as MXGST), an important Chinese herbal prescribed for cough, bronchial inflammation and fever from pneumonia, consists of four medicinal herbs, including Ephedrae herb, Semen Pruni Armeniacae, licorice and Gypsum. These components, especially Ephedrae and Semen Pruni Armeniacae, possess antitussive activities, but they have severe adverse effects.MethodsThe pharmacological activities of MXGST extract in clinical use were investigated with citric acid-induced cough, acetylcholine/histamine-induced bronchial contraction and lipopolysaccharide (LPS)-induced fever in rodents. The subacute toxicology of MXGST extract was evaluated after a 28-day repeated oral administration in rats.ResultsEach gram of MXGST extract contained 60 ± 8 μg of ephedrine, 480 ± 40 μg of glycyrrhizic acid and 440 ± 8 μg of amygdalin according to high performance liquid chromatography and a photodiode array detector. MXGST extract produced pronounced, dose-dependent antitussive effects in guinea pigs and reduced hyperthermic syndrome induced by LPS in rats. MXGST extract blocked the bronchial contraction induced by acetylcholine/histamine. Oral administration of MXGST extract for 28 days did not cause any hematological, biochemical or histological changes in rats.ConclusionsMXGST extract is a safer, more effective Chinese prescription with antitussive and anti-pyretic effects. The antitussive mechanism of MXGST is related to partially relaxing the bronchial smooth muscle by blocking acetylcholinergic and histaminergic receptors.