Turpentine Ointment for the Treatment of Folliculitis: An Open, Prospective, Randomized, Placebo- and Comparator-Controlled Multicenter Trial.

INTRODUCTION: Folliculitis is a painful infection and inflammation of the hair follicles, mostly caused by bacterial, fungal, or, more rarely, viral infections. Turpentine derivatives have been used traditionally to treat various skin infections and could thus also be effective in treating folliculitis. We carried out an open, prospective, randomized, placebo- and comparator-controlled multicenter trial to evaluate the efficacy and safety of an ointment containing pine turpentine oil, larch turpentine, and eucalyptus oil in the treatment of acute folliculitis. METHODS: Seventy outpatients with acute folliculitis were treated with the turpentine ointment, a comparator (povidone iodine solution), or a placebo (Vaseline) for 7 days. Photographs of the affected skin areas were taken by the physicians at four visits and by the patients on a daily basis. Photographs were evaluated by blinded observers. Primary efficacy endpoint was the change in total hair follicle lesion counts. Secondary endpoints included the evolution of the lesion counts in the course of the study, responder rate (improvement of follicle lesions by at least one count), and the patient's global assessment. Safety endpoints were the tolerability of the treatments and adverse event recording. RESULTS: A decrease of follicle lesions counts was detected for both active treatments but not for placebo, but the differences among groups were not statistically significant. As for the secondary endpoints, the ointment showed statistically significant superiority over placebo for the evolution of the lesions during the course of the study (p = 0.017), the responder rate (p = 0.032), and the subjective efficacy assessment by patients (p = 0.029). All treatments were equally well tolerated, with a similar number of treatment-emergent adverse events. CONCLUSION: The turpentine ointment is an effective and safe option for the treatment of folliculitis.

The history, stereochemistry, ethnopharmacology and quality assessment of borneol.

ETHNOPHARMACOLOGICAL RELEVANCE: Borneol (BO) represents a global trade-driven spreading of ethnic medicine traceable to the classical age, and won its name specific to its original habitat "Borneo". BO shows broad spectral pharmacological effects, such as anti-inflammatory, analgesic, antipyretic, inducing resuscitation, and widely applied in the protection and treatment of cardiovascular and cerebrovascular diseases, used singly or mostly in compound formulae. AIM OF THE STUDY: Three stereoscopic configuration forms of BO, l-borneol (LB), d-borneol (DB), and dl-borneol (synthetic, SB), are formulated in broad spectral application, yet their diverse pharmacodynamic and pharmacokinetic properties caused by configurations, and accurate assay and quality assessment are often overlooked. A systematic review and analysis of lumped studies and applications is necessary to clarify the relationship between configuration and its original plant, analysis method, activity and side effect BO in order to guarantee the efficacy and safety during their application. MATERIALS AND METHODS: The public databases including PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure were referenced to summarize a comprehensive research and application data of BO published up to date. RESULTS: This review includes following sections: History and current status, Stereochemistry, Ethnopharmacology, and Quality assessment. In the section of history, the changes of the plant origins of the two isomeric forms of natural BO were described respectively, and the methods for synthetic racemate SB were also included. The section of stereochemistry deals with the stereoscopic structures, physical/chemical property, optical rotation of the three forms of BO, as well as the main related substances like isoborneol, obtained in SB via chemical transformation of camphor and turpentine oil. In the section of Ethnopharmacology, pharmacological activities and pharmacokinetics of different forms of BO were discussed. BO is usually used as an "adjuvant", by enhancing the permeability of the blood-brain barrier and intervene the ADME/T pathways of the other ingredients in the same formulation. In the section of quality assessment, the analytical methods, including chromatography, especially GC, and spectroscopy were addressed on the chiral separation of the coexisting enantiomers. CONCLUSIONS: This overview systematically summarized three forms of BO in terms of history, stereochemistry, ethnopharmacology, and quality assessment, which, hopefully, can provide valuable information and strategy for more reasonable application and development of the globally reputed ethnic medicine borneol with characteristics in stereochemistry.

Comparison by Life-Cycle Assessment of Alternative Processes for Carvone and Verbenone Production.

Verbenone and carvone are allylic monoterpenoid ketones with many applications in the fine chemicals industry that can be obtained, respectively, from the allylic oxidation of α-pinene and limonene over a silica-supported iron hexadecachlorinated phthalocyanine (FePcCl16-NH2-SiO2) catalyst and with t-butyl hydroperoxide (TBHP) as oxidant. As there are no reported analyses of the environmental impacts associated with catalytic transformation of terpenes into value-added products that include the steps associated with synthesis of the catalyst and several options of raw materials in the process, this contribution reports the evaluation of the environmental impacts in the conceptual process to produce verbenone and carvone considering two scenarios (SI-raw-oils and SII-purified-oils). The impact categories were evaluated using ReCiPe and IPCC methods implemented in SimaPro 9.3 software. The environmental impacts in the synthesis of the heterogeneous catalyst FePcCl16-NH2-SiO2 showed that the highest burdens in terms of environmental impact come from the use of fossil fuel energy sources and solvents, which primarily affect human health. The most significant environmental impacts associated with carvone and verbenone production are global warming and fine particulate matter formation, with fewer environmental impacts associated with the process that starts directly from turpentine and orange oils (SI-raw-oils) instead of the previously extracted α-pinene and limonene (SII-purified-oils). As TBHP was identified as a hotspot in the production process of verbenone and carvone, it is necessary to choose a more environmentally friendly and energy-efficient oxidizing agent for the oxidation of turpentine and orange oils.

Characterization of Turpentine nanoemulsion and assessment of its antibiofilm potential against methicillin-resistant Staphylococcus aureus.

Turpentine essential oil (TEO) is a commercially available product having application as food additive, due to its ethno-botanical and ethnopharmacological properties. In the present study, we performed chemical composition of TEO by Gas Chromatography-Mass Spectrometry (GC-MS). Further, TEO was nanoemulsified, encapsulated and characterized by droplet size, PDI, Zeta potential and transmittance. The obtained turpentine nanoemulsion (TNE) was investigated for its antibacterial and antibiofilm potentiality against methicillin-resistant Staphylococcus aureus (MRSA), a model biofilm-forming microorganism. Small micellar TEO nanoparticles were succesfully formed with a mean droplet size ranging from 22.52 to 26.54 nm. Thermodynamic stability studies revealed homogeneous dispersion of the droplets size confirming the stability of TNEs. The developed nano-emulsions displayed two fold enhanced antagonistic activity against S. aureus in comparison with TEOs, with minimum inhibitory concentration (MIC) values at 0.039% (v/v) against MRSA. Additionally, TNEs displayed potent antibiofilm activity against MRSA strains with percent biofilm disruption of around 70.83%. Findings from this study validates the phytomedicinal significance of turpentine nanoemulsions and envisage its exploration as a natural and cost-effective strategy against bacterial biofilms in medical and industrial sectors.

Modulation of volatile release and antimicrobial properties of pink pepper essential oil by microencapsulation in single- and double-layer structured matrices.

The bioactivity of essential oils applied in foods to act as natural preservatives can be reduced due to interactions with other components of the food matrix. Microencapsulation can help to increase the functionality of these compounds. In addition, the electrostatic interaction between proteins and polysaccharides can result in double-layered encapsulating structures, ensuring greater protection to essential oils than using only protein as surface active agent. In this work, pink pepper essential oil was microencapsulated by spray drying of single-layer emulsions, stabilized by soy protein isolate (SPI), and of double-layer emulsions, stabilized by soy protein isolate/high methoxyl pectin (SPI/HMP). Pink pepper essential oil showed predominance of α-pinene, ß-pinene, ß-mircene, δ-3-carene, d-limonene, and germacrene D. Compared to SPI microcapsules, SPI/HMP microcapsules better preserved the total volatile content identified in pure oil, showed less water adsorption during storage at relative humidity ≥75% and improved antimicrobial properties. When stored for 20 days (25 °C/RH = 52.8%), both microcapsules allowed more gradual release of volatiles compared with non-encapsulated oil. Microencapsulation by spray drying did not have negative effects on the antioxidant activity of the encapsulated oil, as the microcapsules showed similar results to the non-encapsulated oil, around 11 µg Trolox/mg of oil. After storage, however, the non-encapsulated oil showed greater losses of its antioxidant activity due to higher rates of volatile release. In the in vitro antimicrobial activity assay, both microcapsules inhibited growth of Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes and Listeria innocua, although no inhibition was observed against Gram-negative bacteria. When added in milk, both microcapsules reduced bacterial growth, whereas non-encapsulated oil showed no satisfactory inhibition. Faster reduction of microbial growth in milk was observed for SPI/HMP microcapsules. Inhibition results were better for skim milk than for whole milk, suggesting that the interaction of essential oil with other lipids present in milk decreased its bioactivity. Microencapsulation positively affected the functionality of pink pepper essential oil, highlighting its potential for application as a natural preservative in food products.

Remarkable rutin-rich Hypericum capitatum extract exhibits anti-inflammatory effects on turpentine oil-induced inflammation in rats.

BACKGROUND: Natural extracts with beneficial biological activities are nowadays of high interest, in various treatment or prophylaxis. Hypericum capitatum has been known for its curative effects for centuries and its extracts have become of interest due to their distinct activity among other Hypericaceae members. In this study, further light is aimed to be shed on the secondary-metabolites composition of H. capitatum extracts, using chromatographic techniques and Electron paramagnetic resonance profiles in alkaline medium. Considering that no previous works explored the anti-inflammatory activity of H. capitatum, here, an in vivo study is also designed in order to evaluate this property by assessing the impact of one of H. capitatum extracts in ameliorating turpentine oil-induced inflammation on rats and to quantify their blood antioxidants level. METHODS: Chromatographic techniques and Electron paramagnetic resonance spectroscopy were used in order to describe the chemical profile in different parts of the plant. The in vivo study on turpentine-oil induced inflammation in rats included three doses of H. capitatum extract expressed in rutin concentration. Oxidative stress was measured using total oxidative status, total antioxidant capacity, oxidative stress index, 3-nitrotyrosine, nitric oxide, malondialdehyde, superoxide dismutase, catalase and the inflammatory response was evaluated by performing a complete blood cells count and C reactive protein. RESULTS: The extract was remarkably rich in rutin; however, other polyphenolic-like minor components appeared important in explaining the observed biological properties. The tested extract prevents the increase of inflammation-induced white blood cell count, number of neutrophils, and serum nitric oxide, and did so in a dose-dependent manner, similarly to the positive control-diclofenac. In addition, the same extract appeared to be a good alternative to diclofenac to restore total oxidative status, thiobarbituric active reactive species, total proteins and C reactive proteins. Moreover, antioxidant enzymes such as catalase, superoxide dismutase and total serum thiol concentration were significantly increased by the tested extract. CONCLUSIONS: Due to its powerful reservoir rich in rutin, H. capitatum extract depicted its in vivo antioxidant and anti-inflammatory effects indicating it to be a good alternative to conventional drugs for oxidative stress protection.

Comparison of topical capsaicin and topical turpentine Oil for treatment of painful diabetic neuropathy.

BACKGROUND: Diabetes Mellitus is a pandemic of the modern era owing to our rapidly deteriorating lifestyle. Painful diabetic neuropathy is one of the costliest and disabling complications of diabetes mellitus. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Topical Capsaicin and Turpentine Oil are found to be effective in treatment of painful diabetic neuropathy. METHODS: Patients of either gender with ages between 18 and 70 years having painful diabetic neuropathy already taking one oral drug for painful neuropathy and treatment for diabetes mellitus and an HbA1C less than 8.5% were included while Pregnant or lactating mothers, patients with chronic liver disease and patients with renal insufficiency (creatinine >3.0 mg/dl) and peripheral arterial disease were excluded from study. Patients were randomly divided into two groups (A & B) using computer generated random number table. Group A was given topical application of capsaicin while Group B was given topical application of commercially available turpentine oil over painful site on feet. RESULTS: 300 patients were equally divided in two groups. The patients in group A had a Visual Analog Pain Score of 7.91±5.10 at baseline and 5.10±1.343 after 3 months of treatment (p-value 0.0001). The patients in group B had a Visual Analog Pain Score of 7.83±1.012 at baseline and 5.20±1.187 after 3 months of treatment (p-value 0.0001). Chi Square test was applied to compare efficacy of both groups. It was noted that 71 (53%) had efficacy in group A and 63 (47%) had efficacy in the group B but the difference was not statistically significant. (p-value=0.399). CONCLUSIONS: It has been concluded that turpentine oil is effective in managing diabetic neuropathic pain similar to capsaicin cream.

Anti-arthritic activity of aqueous-methanolic extract and various fractions of Berberis orthobotrys Bien ex Aitch.

BACKGROUND: The roots and stem bark of Berberis orthobotrys (Berberidaceae) have long been used traditionally to treat joint pain. Though, it has not been pharmacologically assessed for rheumatoid arthritis. The current study explores anti-arthritic activity and phytochemical analysis of aqueous-methanolic extract (30:70) and fractions (ethyl acetate, n-butanol, and aqueous) of Berberis orthobotrys roots. METHODS: Anti-arthritic potential was evaluated in vitro using protein denaturation (bovine serum albumin and egg albumin) and membrane stabilization methods at 12.5-800 µg/ml concentration and in vivo via turpentine oil, formaldehyde and Complete Freund Adjuvant (CFA) models at 50, 100 and 150 mg/kg doses. Also, in vitro antioxidant ability was appraised by reducing power assay. Moreover, total flavonoid content, Fourier transform infrared spectroscopy and High performance liquid chromatography of n-butanol fraction were performed. RESULTS: The results revealed concentration dependent inhibition of albumin denaturation and notable RBC membrane stabilization, with maximum results obtained at 800 µg/ml. Similarly, plant exhibited dose dependent anti-arthritic effect in turpentine oil and formaldehyde models, with maximum activity observed at 150 mg/kg. The results of CFA model depicted better protection against arthritic lesions and body weight alterations. Also, B.orthobotrys remarkably ameliorated altered hematological parameters, rheumatoid factor and positively modified radiographic and histopathological changes. Additionally, plant exhibited remarkable anti-oxidant activity. Moreover, phytochemical analysis revealed polyphenols and flavonoids. CONCLUSION: Taken together, these results support traditional use of B.orthobotrys as potent anti-arthritic agent that may be proposed for rheumatoid arthritis treatment.

Sulfate turpentine: a resource of tick repellent compounds.

Compounds with tick (Ixodes ricinus) repellent properties were isolated from sulfate turpentine consisting of Norway spruce (80%) and Scots pine (20%) from southern Sweden. The turpentine was divided into two fractions by distillation under reduced pressure resulting in one monoterpene hydrocarbon fraction and a residual containing higher boiling terpenoids. The monoterpene fraction was further oxidized with SeO2 to obtain oxygenated monoterpenes with potential tick repellent properties. The oxidized fraction and the high boiling distillation residual were each separated by medium pressure liquid chromatography. The fractions were tested for tick repellency and the compounds in those with highest tick repellency were identified by GC-MS. The fractions with highest repellency contained, mainly (-)-borneol, and mixtures of (+)- and (-)-1-terpineol and terpinen-4-ol. The enantiomers of borneol showed similar tick repellent properties.

Effect of solvents on apically extruded debris and irrigant during root canal retreatment using reciprocating instruments.

AIM: To evaluate the effect of several solvents on the weight of apically extruded debris and irrigant during retreatment using a novel agar gel model. METHODS: Orange oil, turpentine oil and chloroform were used as solvents. Eighty single straight-rooted extracted human mandibular premolar teeth with a single root canal were divided into four groups (n = 20). All specimens were root canal-filled and weighed prior to their insertion into a prepared 1.5% agar gel model. The mean initial weights were measured by subtracting the weight of the specimen from the weight of the test apparatus and recorded. Following the removal of the coronal 4 mm of root filling, the test solvent was applied onto the root filling. No solvent was used in the control group. A Reciproc R25 instrument was used to remove the root filling in all groups. Apically extruded debris and test solvent were collected during retreatment procedures. The mean weights of apically extruded debris and irrigant were calculated by subtracting the mean initial weights from the weights of test apparatus without the Teflon tape and the specimen following the retreatment procedures. Data were statistically analysed using one-way analysis of variance. RESULTS: Use of solvents resulted in significantly less extruded debris and irrigant compared to the control group (P < 0.05). Chloroform extruded significantly more debris than orange oil and turpentine oil (P < 0.05). CONCLUSION: Use of solvents during root filling removal was associated with less apically extruded debris and irrigant when compared to no solvent.

Essential Oils, Part IV: Contact Allergy.

Nearly 80 essential oils (including 2 jasmine absolutes) have caused contact allergy. Fifty-five of these have been tested in consecutive patients suspected of contact dermatitis, and nine (laurel, turpentine, orange, tea tree, citronella, ylang-ylang, sandalwood, clove, and costus root) showed greater than 2% positive patch test reactions. Relevance data are generally missing or inadequate. Most reactions are caused by application of pure oils or high-concentration products. The clinical picture depends on the responsible product. Occupational contact dermatitis may occur in professionals performing massages. The (possible) allergens in essential oils are discussed. Several test allergens are available, but patients should preferably be tested with their own products. Co-reactivity with other essential oils and the fragrance mix is frequent, which may partly be explained by common ingredients. Patch test concentrations for essential oils are suggested.

[The combined application of yellow turpentine bathtubs and bronchodilators inhalations for the treatment of the patients presenting with chronic obstructive pulmonary disease].

This paper was designed to report the results of comparative clinical and functional studies involving 89 patients who presented with moderately severe chronic obstructive pulmonary disease and were given the combined treatment with yellow turpentine bathtubs and bronchodilators inhalations with the use of a nebulizer. The patients comprising group 1 (n=29) were treated with yellow turpentine bathtubs and bronchodilators inhalations, those making up group 2 (n=30) received monotherapy with yellow turpentine bathtubs alone, and the patients included in group 3 (n=3) served as controls treated with the use of therapeutic physical exercises and symptomatic medications analogous to those given to the patients of the two former groups. The results of the study give evidence of the advantages of the rehabilitative complex including yellow turpentine bathtubs and atrovent inhalations over two alternative therapeutic modalities attributable to its pronounced anti-inflammatory and immune-corrective activity that resulted in the generalized improvement of bronchial patency, reduction of lung hypertension, and enhancement of physical tolerance; taken together, these effects ensured the best clinical results.

The effect of some 4,2 and 5,2 bisthiazole derivatives on nitro-oxidative stress and phagocytosis in acute experimental inflammation.

Nineteen bisthiazoles were tested in order to assess their anti-inflammatory and antioxidant properties. First, we evaluated the in vitro direct antioxidant capacity of the bisthiazoles using the DPPH radical scavenging method. Then, the anti-inflammatory effect was tested in acute rat experimental inflammation by measuring the acute phase bone marrow response, the phagocytic capacity and the serum nitro-oxidative stress status. Although none of the substances showed significant direct antioxidant potential in the DPPH assay, most of them improved serum oxidative status, when administered to rats with inflammation. Four of the bisthiazoles proved to have good anti-inflammatory properties, similar or superior to that of equal doses meloxicam.

Anti-inflammatory effects of Allium schoenoprasum L. leaves.

Allium schoenoprasum has antimicrobial and antifungal properties and is used to relieve pain from sunburn and sore throat. The aim of the present study was to evaluate the anti-inflammatory effects of the extracts from A. schoenoprasum leaves. A 1:1 (w:v) extract was prepared by a modified Squibb repercolation method. The total phenolic content of 68.5±2 g gallic acid aquivalent (GAE)/g plant was determined using the Folin-Ciocalteu method. The in vitro antioxidant activity was determined using the 1,1-diphenyl-2-picrylhydrazyl bleaching method (6.72±0.44 g/mg DPPH) and the trolox equivalent antioxidant capacity (132.8±23 g trolox eq./g plant) assay. Analysis of the extracts using the hemoglobin ascorbate peroxidase activity inhibition assay or the electron spin resonance did not yield signals above the detection limit. The anti-inflammatory effects of three extract concentrations (25%, 50%, 100%) were evaluated in vivo on a model turpentine oil-induced inflammation in rats. These three extracts were also evaluated in vitro for the ability to inhibit phagocytosis, the accumulation of total nitrites and nitrates in the serum, the total oxidative status, the total antioxidant response and the oxidative stress index. Pure extracts (100% concentration) had the best inhibitory activity on phagocytosis and oxidative stress. In conclusion, these results support the hypothesis that extracts from A. schoenoprasum leaves exert anti-inflammatory activities by inhibiting phagocytosis through the reduction of nitro-oxidative stress.

Excessive nitric oxide impairs wound collagen accumulation.

BACKGROUND: Nitric oxide (NO) plays a major regulatory role in wound collagen synthesis. We hypothesized that this regulatory role is tightly controlled by the levels of NO in the wound environment and that supranormal wound NO generation impairs wound collagen accumulation. MATERIALS AND METHODS: We used the model of turpentine-induced granuloma in male Sprague-Dawley rats as a sterile inflammatory stimulus generating large amounts of NO. In this environment, NO generation increased by 260%, whereas collagen deposition was significantly reduced by 38.5% (729.7 ± 81.5 versus 449.4 ± 76.3 µg hydroxyproline/100 mg sponge, P<0.05). Inhibition of NO synthase activity using 300 mM L-N6-(1-iminoethyl)-lysine, a highly potent and selective inhibitor of inducible NO synthase, significantly reduced NO elevation by 43.3% and increased wound collagen deposition by 37.3% (P<0.05). These effects occurred without any anti-inflammatory effects of L-N6-(1-iminoethyl)-lysine as assessed by the white blood cell counts and levels of interleukins 1 and 6. CONCLUSIONS: The data show that high levels of NO within the wound environment significantly reduce wound collagen deposition. Inhibition of NO generation restores collagen levels to normal levels. The regulatory effects of NO on wound collagen appear to be highly correlated with the amount of NO generated.

An unusual cause of factitious arthritis.

Septic arthritis and toxic synovitis are clinical conditions that can develop in association with various causes and involve symptoms such as pain, swelling, redness, sensitivity and restricted movement in the joint. A 42-year-old male presented to the emergency department with severe joint pain and nausea after injecting a 1-cc mixture of turpentine oil, eucalyptus oil, mint oil and thyme oil, which he purchased from an alternative medicine store, into his right knee with a syringe because of chronic knee pain. Ballottement and sensitivity were present at physical examination. Knee puncture yielded 60 cc of cloudy fluid. There was no growth in the material obtained. Improvement was observed following subsequent arthroscopic washing of the joint space and IV antibiotherapy, and the patient was discharged on day 21 of hospitalization with oral antibiotic and analgesic therapy. Intra-articular injection of foreign bodies into the knee joint space for therapeutic purposes, as in this case report, is a very rare occurrence, but may lead to potentially complicated arthritis.

Inflammation inhibits the expression of phosphoenolpyruvate carboxykinase in liver and adipose tissue.

Inhibition of adipocyte triglyceride biosynthesis is required for fatty acid mobilization during inflammation. Triglyceride biosynthesis requires glycerol 3-phosphate and phosphoenolpyruvate carboxykinase (PEPCK) plays a key role. We demonstrate that LPS, zymosan, and TNF-α decrease PEPCK in liver and fat. Turpentine decreases PEPCK in liver, but not in fat. The LPS-induced decrease in PEPCK does not occur in TLR4 deficient animals, indicating that this receptor is required. The LPS-induced decrease in hepatic PEPCK does not occur in TNF receptor/IL-1 receptor knockout mice, but occurs in fat, indicating that TNF-α/IL-1 is essential for the decrease in liver but not fat. In 3T3-L1 adipocytes TNF-α, IL-1, IL-6, and IFNγ inhibit PEPCK indicating that there are multiple pathways by which PEPCK is decreased in adipocytes. The binding of PPARγ and RXRα to the PPARγ response element in the PEPCK promoter is markedly decreased in adipose tissue nuclear extracts from LPS treated animals. Lipopolysaccharide and zymosan reduce PPARγ and RXRα expression in fat, suggesting that a decrease in PPARγ and RXRα accounts for the decrease in PEPCK. Thus, there are multiple cytokine pathways by which inflammation inhibits PEPCK expression in adipose tissue which could contribute to the increased mobilization of fatty acids during inflammation.

Antiarthritic activity of majoon suranjan (a polyherbal Unani formulation) in rat.

BACKGROUND & OBJECTIVES: Majoon Suranjan (MS) is a polyherbal formulation used in Unani system of medicine for the treatment of rheumatoid arthritis (RA). The present study evaluates the antiarthritic efficacy of this formulation in three different experimental models. METHODS: The anti-inflammatory activity of MS (in doses of 450, 900 and 1800 mg/kg body wt) was evaluated using the turpentine oil induced paw oedema model and the antiarthritic efficacy was evaluated using the formaldehyde and complete Freund's adjuvant (CFA) induced arthritis models. Aspirin (100 mg/kg body wt) was used as the standard drug in all the models. In order to assess the safety of the test drug, oral acute and 28 day toxicity studies were also carried out. RESULTS: MS produced a dose dependent protective effect in all the experimental models. Its antiarthritic efficacy was comparable to aspirin in formaldehyde induced arthritis and was superior to aspirin in turpentine oil induced paw oedema and CFA induced arthritis. MS also inhibited the delayed increase in joint diameter as seen in control and aspirin treated animals in CFA induced arthritis. Oral LD 50 of MS was found to be >5000 mg/kg in rats. Chronic administration did not produce any significant physiological changes in the tested animals. INTERPRETATION & CONCLUSIONS: Results of the present study suggest that the antiarthritic activity of MS was due to the interplay between its anti-inflammatory and disease modifying activities, thus supporting its use in traditional medicine for the treatment of RA.

Prenatal inflammation-induced hypoferremia alters dopamine function in the adult offspring in rat: relevance for schizophrenia.

Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum non-heme iron, which is common to all types of infections. Adequate iron supply to the fetus is fundamental for the development of the mesencephalic dopamine neurons and disruption of this following maternal infection can affect the offspring's dopamine function. Using a rat model of localized injury induced by turpentine, which triggers the innate immune response and inflammation, we investigated the effects of maternal iron supplementation on the offspring's dopamine function by assessing behavioral responses to acute and repeated administration of the dopamine indirect agonist, amphetamine. In addition we measured protein levels of tyrosine hydroxylase, and tissue levels of dopamine and its metabolites, in ventral tegmental area, susbtantia nigra, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Offspring of turpentine-treated mothers exhibited greater responses to a single amphetamine injection and enhanced behavioral sensitization following repeated exposure to this drug, when compared to control offspring. These behavioral changes were accompanied by increased baseline levels of tyrosine hydroxylase, dopamine and its metabolites, selectively in the nucleus accumbens. Both, the behavioral and neurochemical changes were prevented by maternal iron supplementation. Localized prenatal inflammation induced a deregulation in iron homeostasis, which resulted in fundamental alterations in dopamine function and behavioral alterations in the adult offspring. These changes are characteristic of schizophrenia symptoms in humans.