An Update on Promising Agents against COVID-19: Secondary Metabolites and Mechanistic Aspects.

BACKGROUND: Coronavirus disease 2019 (COVID­19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is associated with a high level of mortality. OBJECTIVE: This updated review aims to present the most important traditional medicinal plants and some of their secondary metabolites that have previously and more recently been shown to affect viruses and may represent a beneficial contributory step against SARS-CoV-2 as the cause of COVID-19. Moreover, the mechanism aspects of these secondary metabolites were discussed, which may help find more reliable drugs against SARSCoV- 2. METHODS: Articles were searched on scientific websites including Google Scholar, Scopus, Web of Science, PubMed, and IranMedex using the search terms herbal medicine and traditional medicine with coronavirus, SARS-CoV-2, or COVID-19. Human, animal, and in vitro studies were identified in the search. RESULTS: Medicinal plants and their secondary metabolites may possess a potential role in combating this disease, and researchers suggest that some of these plants and their constituent compounds have inhibitory activity on coronaviruses. Numerous medicinal plants, their extracts, and secondary metabolites have been investigated over a period of time for antiviral activity. Among them, kaempferol, silybin, myricitrin, licoleafol, and curcumin are promising agents with potential activity against SARS-CoV-2. Natural compounds can form strong bonds with the active sites of SARS-CoV-2 protease. Structural and non-structural SARS-CoV-2 proteins such as Spike protein, PLpro, and 3CLpro are inhibited by these phytochemicals. CONCLUSION: Prospective treatments targeted at the life cycle stages of the virus may eventuate from research endeavors, and it must not be discounted that therapy originally derived from plant secondary metabolite sources may potentially have a part to play.

Effect of fennel on primary dysmenorrhea: a systematic review and meta-analysis.

BACKGROUND: One of the most common complaints for women is dysmenorrhea. Several studies investigated the treatment effects of medicinal plants on primary dysmenorrhea. OBJECTIVES: This systematic review and meta-analysis investigates the effect of Foeniculum vulgare (Fennel) on pain in primary dysmenorrhea in comparison to non-steroidal anti-inflammatory drugs such as mefenamic acid. METHODS: PubMed, EMBASE, EBSCO Web of Science, Scopus, Cochrane library, Cochrane Central Register of Controlled Trials (CENTRAL), Science Direct, ProQuest, ISI Web of Science, Google Scholar, Magiran, SID, Iran Medex, and Irandoc were searched up to January 2019. Quality assessment of clinical trials was conducted using Jadad scoring system. Totally, 12 studies were entered in the meta-analysis. I 2 was calculated to determine heterogeneity. Fixed effects and/or random effects models were applied. RESULTS: Meta-analysis of these trials showed that F. vulgare intake decreased significantly the intensity of dysmenorrhea compared to the placebo (SMD -0.632; CI: -0.827 to -0.436; p<0.001; heterogeneity p=0.807; I 2=0%; fixed effect model; seven articles). However, the effect of Mefenamic acid with F. vulgare was not different from each other (SMD=-0.214; CI: -0.446 to 0.017; p=0.07; heterogeneity p=0.58; I 2=0%; fixed effect model; six trials). CONCLUSION: The F. vulgare alleviates dysmenorrhea. Regarding the same effect of F. vulgare with NSAIDs, it is highly recommend to the women suffered from dysmenorrhea specifically the ones who have high tendency toward herbal medicine.

Hydroalcoholic Extract of Anchusa Italica Protects Global Cerebral Ischemia-Reperfusion Injury Via a Nitrergic Mechanism.

INTRODUCTION: In stroke models, Inducible Nitric Oxide Synthase (iNOS) expression initiates cellular toxicity due to excessive Nitric Oxide (NO) generation. Anchusa italica is a medicinal herb with anti-inflammatory, antioxidant and neuroprotective properties. This study evaluated the antioxidant activity and NOS mRNA expression of the Hydroalcoholic Extract Of Anchusa Italica (HEAI) in an experimental stroke model in rats. METHODS: The stroke model was induced by bilateral occlusion of both common carotid arteries for 60 min. Twenty-four hours after surgery, HEAI (50 and 100 mg/kg i.p.) was injected daily for 10 consecutive days. mRNA expression levels of NOS subtypes and hippocampal Brain-Derived Neurotrophic Factor (BDNF) were studied using real-time PCR. Besides, hippocampal tissue plus serum concentrations of NO and Malondialdehyde (MDA) were measured. RESULTS: HEAI decreased MDA in both serum and hippocampal tissue and also reduced serum NO levels. Additionally, in the HEAI-treated groups, a down-regulation of iNOS mRNA expression, and an up-regulation of BDNF mRNA expression were observed. CONCLUSION: The results indicated that the administration of HEAI even after the onset of ischemia protects the brain from free radical injury and inflammation via a down-regulation of iNOS expression inhibiting NO production and an up-regulation of BDNF mRNA.

Mechanisms of Medicinal Plant Activity on Nitric Oxide (NO) Bioavailability as Prospective Treatments for Atherosclerosis.

BACKGROUND AND OBJECTIVE: Atherosclerosis is one of the leading causes of human morbidity globally and reduced bioavailability of vascular nitric oxide (NO) has a critical role in the progression and development of the atherosclerotic disease. Loss of NO bioavailability, for example via a deficiency of the substrate (L-arginine) or cofactors for endothelial nitric oxide synthase (eNOS), invariably leads to detrimental vascular effects such as impaired endothelial function and increased smooth muscle cell proliferation, deficiency of the substrate (Larginine) or cofactors for eNOS. Various medicinal plants and their bioactive compounds or secondary metabolites with fewer side effects are potentially implicated in preventing cardiovascular disease by increasing NO bioavailability, thereby ameliorating endothelial dysfunction. In this review, we describe the most notable medicinal plants and their bioactive compounds that may be appropriate for enhancing NO bioavailability, and treatment of atherosclerosis. METHODS: The material in this article was obtained from noteworthy scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar. RESULTS: Medicinal plants and their bioactive compounds influence NO production through diverse mechanisms including the activation of the nuclear factor kappa B (NF-κB) signaling pathway, activating protein kinase C (PKC)-α, stimulating protein tyrosine kinase (PTK), reducing the conversion of nitrite to NO via nitrate-nitrite reduction pathways, induction of eNOS, activating the phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase B (AKT) (PI3K/AKT/eNOS/NO) pathway and decreasing oxidative stress. CONCLUSION: Medicinal plants and/or their constituent bioactive compounds may be considered as safe therapeutic options for enhancing NO bioavailability and prospective preventative therapy for atherosclerosis.

Review of Phytochemical Compounds as Antiviral Agents Against Arboviruses from the Genera Flavivirus and Alphavirus.

Arboviruses are a diverse group of viruses that are among the major causes of emerging infectious diseases. Arboviruses from the genera flavivirus and alphavirus are the most important human arboviruses from a public health perspective. During recent decades, these viruses have been responsible for millions of infections and deaths around the world. Over the past few years, several investigations have been carried out to identify antiviral agents to treat these arbovirus infections. The use of synthetic antiviral compounds is often unsatisfactory since they may raise the risk of viral mutation; they are costly and possess either side effects or toxicity. One attractive strategy is the use of plants as promising sources of novel antiviral compounds that present significant inhibitory effects on these viruses. In this review, we describe advances in the exploitation of compounds and extracts from natural sources that target the vital proteins and enzymes involved in arbovirus replication.

Effective Antiviral Medicinal Plants and Biological Compounds Against Central Nervous System Infections: A Mechanistic Review.

BACKGROUND AND OBJECTIVE: Infectious diseases are amongst the leading causes of death in the world and central nervous system infections produced by viruses may either be fatal or generate a wide range of symptoms that affect global human health. Most antiviral plants contain active phytoconstituents such as alkaloids, flavonoids, and polyphenols, some of which play an important antiviral role. Herein, we present a background to viral central nervous system (CNS) infections, followed by a review of medicinal plants and bioactive compounds that are effective against viral pathogens in CNS infections. METHODS: A comprehensive literature search was conducted on scientific databases including: PubMed, Scopus, Google Scholar, and Web of Science. The relevant keywords used as search terms were: "myelitis", "encephalitis", "meningitis", "meningoencephalitis", "encephalomyelitis", "central nervous system", "brain", "spinal cord", "infection", "virus", "medicinal plants", and "biological compounds". RESULTS: The most significant viruses involved in central nervous system infections are: Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), West Nile Virus (WNV), Enterovirus 71 (EV71), Japanese Encephalitis Virus (JEV), and Dengue Virus (DENV). The inhibitory activity of medicinal plants against CNS viruses is mostly active through prevention of viral binding to cell membranes, blocking viral genome replication, prevention of viral protein expression, scavenging reactive Oxygen Species (ROS), and reduction of plaque formation. CONCLUSION: Due to the increased resistance of microorganisms (bacteria, viruses, and parasites) to antimicrobial therapies, alternative treatments, especially using plant sources and their bioactive constituents, appear to be more fruitful.

Neurotransmitter, Antioxidant and Anti-neuroinflammatory Mechanistic Potentials of Herbal Medicines in Ameliorating Autism Spectrum Disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental issue that disrupts behavior, nonverbal communication, and social interaction, impacting all aspects of an individual's social development. The underlying origin of autism is unclear, however, oxidative stress, as well as serotonergic, adrenergic and dopaminergic systems are thought to be implicated in ASD. Despite the fact that there is no effective medication for autism, current pharmacological treatments are utilized to ameliorate some of the symptoms such as selfmutilation, aggression, repetitive and stereotyped behaviors, inattention, hyperactivity, and sleep disorders. METHODS: In accord with the literature regarding the activity of herbal medicines on neurotransmitter function, we aimed to review the most worthy medicinal herbs possessing neuroprotective effects. RESULTS: Based on the outcome, medicinal herbs such as Zingiber officinale, Astragalus membranaceu, Ginkgo biloba, Centella asiatica and Acorus calamus, have antioxidant activity, which can influence neurotransmitter systems and are potentially neuroprotective. CONCLUSION: Consequently, these herbs, in theory at least, appear to be suitable candidates within an overall management strategy for those on the autism spectrum.

Antioxidants and Atherosclerosis: Mechanistic Aspects.

Atherosclerosis is a chronic inflammatory disease which is a major cause of coronary heart disease and stroke in humans. It is characterized by intimal plaques and cholesterol accumulation in arterial walls. The side effects of currently prescribed synthetic drugs and their high cost in the treatment of atherosclerosis has prompted the use of alternative herbal medicines, dietary supplements, and antioxidants associated with fewer adverse effects for the treatment of atherosclerosis. This article aims to present the activity mechanisms of antioxidants on atherosclerosis along with a review of the most prevalent medicinal plants employed against this multifactorial disease. The wide-ranging information in this review article was obtained from scientific databases including PubMed, Web of Science, Scopus, Science Direct and Google Scholar. Natural and synthetic antioxidants have a crucial role in the prevention and treatment of atherosclerosis through different mechanisms. These include: The inhibition of low density lipoprotein (LDL) oxidation, the reduction of reactive oxygen species (ROS) generation, the inhibition of cytokine secretion, the prevention of atherosclerotic plaque formation and platelet aggregation, the preclusion of mononuclear cell infiltration, the improvement of endothelial dysfunction and vasodilation, the augmentation of nitric oxide (NO) bioavailability, the modulation of the expression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells, and the suppression of foam cell formation.

A Review on the Most Important Medicinal Plants Effective in Cardiac Ischemia-Reperfusion Injury.

Ischemia, referring to reduction and restriction of perfusion to myocardial tissue which involves coronary artery through the formation of misplaced clots and thrombosis, is one of the most important cardiovascular diseases. Plant-based compounds help to improve or prevent disease by affecting the factors involved in the disease. This review was conducted to report the medicinal plants and factors effective in cardiac ischemiareperfusion (I/R) injury to supplement the knowledge about this disease and its prevention and treatment using certain medicinal plants and their active compounds. For this purpose, medicinal plants and their potential antioxidant activities, effects on lipid levels and plaque formation, atherosclerosis and development of cardiovascular diseases and ischemia were reviewed. METHODS: To conduct this review, relevant articles published between 1983 and 2018 were retrieved from the Google Scholar, PubMed, Scientific Information Database, Web of Science, and Scopus using search terms antioxidant, ischemia, reperfusion, heart, infarct, inflammation, cholesterol and medicinal plants. Then, the eligible articles were reviewed. RESULTS: The active compounds of plants, including phenolic compounds, flavonoids, and antioxidant compounds, can be effective on certain pathogenic factors particularly in decreasing cholesterol and blood pressure, preventing an increase in free radicals and ultimately reducing blood clots and vascular resistance to reduce and prevent ischemic disease and its harmful effects. CONCLUSION: Medicinal plants discussed in this article seem to be able to prevent cardiac damage and the disease progression via affecting the factors that are involved in ischemia.

Depression and Treatment with Effective Herbs.

Depression is a common psychiatric disease and one of the main causes of disability worldwide. In spite of certain developments in this field, chemical and synthetic drugs used for the treatment of depression disrupt the treatment process due to numerous side effects and high cost. Today, the goal of using a potential method for treating depression involves the use of medicinal and phytochemical plants, which have many therapeutic benefits. Studies have shown that medicinal plants affect the nervous system and exert antidepressant effects in various ways, including synaptic regulation of serotonin, noradrenaline and dopamine, and inflammatory mediators. In this study, depression as well as the factors and mechanisms involved in its development are first addressed, and then medicinal plants effective in the treatment of depression along with their mechanisms of actions are reported.

Medicinal Plants and Atherosclerosis: A Review on Molecular Aspects.

Atherosclerosis is an inflammatory vascular disease that is characterized by progressive accumulation of cholesterol in the arterial walls and it is a major cause of cardiovascular disease. Issues related to the side effects of synthetic drugs have in recent times, led to the misuse of drugs, a lack of patient consultations, and consequently, a disruption in meticulous disease control. Therefore, a new insight into medicinal plants has recently emerged and much research has been conducted on these herbs in an attempt to prepare novel naturally based drugs. The aim of this review article was to scrutinize the molecular mechanisms of medicinal plants possessing effectiveness against atherosclerosis. To conduct the review, electronic searches were performed to retrieve potentially relevant publications, indexed within internet databases and reference textbooks concerning the effects and underlying molecular mechanisms of plants or their constituents used to treat atherosclerosis. Overall, medicinal plants facilitate atherosclerosis treatment through a variety of mechanisms which include the regulation of expression of inflammatory factors, stimulation of peroxisome proliferator-activated receptors (PPARs), inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), promotion of ATP-binding cassette transporter A1 (ABCA1) as well as ATP-binding cassette transporter G (ABCG), facilitation of adiponectin activity, reduction of sterol regulatory element-binding proteins (SREBPs) and antioxidant activity. An increased perception of these herbal mechanistic links is an important prelude to the design of novel plant based drugs.

Immunosuppression-lipid Metabolism Interplay and Medicinal Plants in Atherosclerosis: A Review.

Atherosclerosis is a chronic arterial disease responsible for the majority of vascular-related deaths throughout the world. Immune cells and inflammation in conjunction with hyperlipidemia play a key role in atherosclerosis development. Regarding the low efficacy of the synthetic drugs and also the associated negative side effects which can adversely influence health-related quality of life, looking for natural, affordable and non-toxic substances seem necessary. Plant-derived natural products play a critical role in the prevention and treatment of atherosclerosis. In this review, we aimed to outline the most important medicinal herbs effective for atherosclerosis through the impact on immune system.

Medicinal Plants with Multiple Effects on Diabetes Mellitus and Its Complications: a Systematic Review.

PURPOSE OF REVIEW: This systematic review describes evidence concerning medicinal plants that, in addition to exerting hypoglycemic effects, decrease accompanying complications such as nephropathy, neuropathy, retinopathy, hypertension, and/or hyperlipidemia among individuals with diabetes mellitus (DM). RECENT FINDINGS: Studies on the antidiabetic mechanisms of medicinal plants have shown that most of them produce hypoglycemic activity by stimulating insulin secretion, augmenting peroxisome proliferator-activated receptors (PPARs), inhibiting α-amylase or α-glucosidase, glucagon-like peptide-1 (GLP-1) secretion, advanced glycation end product (AGE) formation, free radical scavenging plus antioxidant activity (against reactive oxygen or nitrogen species (ROS/RNS)), up-regulating or elevating translocation of glucose transporter type 4 (GLUT-4), and preventing development of insulin resistance. Not only are medicinal plants effective in DM, but many of them also possess a variety of effects on other disease states, including the complications of DM. Such plants may be appropriate alternatives or adjuncts to available antidiabetic medications.

Synthetic and natural antioxidants attenuate cisplatin-induced vomiting.

BACKGROUND: Synthetic and natural antioxidants including Bacopa monnieri (L.) Pennell (Scrophulariaceae) which also possess anti-dopaminergic properties, have been proposed to be useful for emetogenic chemotherapy. In this study, synthetic [N-(2-mercaptopropionyl) glycine (MPG), vitamin C (Vit-C)] and natural [grape seed proanthocyanidin (GP), B. monnieri n-butanolic fraction (BM-ButFr)] antioxidants and their combinations were evaluated against cisplatin-induced emesis in pigeons during a 24 h observation period. METHODS: Emesis was induced using cisplatin (7.0 mg/kg, i.v). MPG (10, 20, 30 mg/kg), Vit-C (100, 200, 300 mg/kg), GP (50, 100, 150 mg/kg) and BM-ButFr (5, 10, 20 mg/kg) and their combinations were administered i.m., 15 min before cisplatin administration. The number of vomiting bouts, retching, emetic latency and % weight loss were recorded to assess antiemetic potential. Antioxidant activity was evaluated by the DPPH free radical scavenging assay (FRSA). RESULTS: Significant attenuation of vomiting bouts, retching, % weight loss along with an increase in latency was produced by all the antioxidants and their combinations compared to cisplatin alone and this is the first report of this activity of GP in pigeons. Low EC50 values in the FRSA for MPG (67.66 µg/mL), Vit-C (69.42 µg/mL), GP (6.498 µg/mL) and BM-ButFr (55.61 µg/mL) compared to BHT standard (98.17 µg/mL) demonstrated their radical scavenging capacity. Correlation between the antioxidant activity and antiemetic efficacy disclosed a high degree of correlation for the tested antioxidants. CONCLUSION: The selected synthetic and natural antioxidants and their combinations were able to attenuate cisplatin-induced vomiting, which correlated with their potent in vitro antioxidant activity.

Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms.

BACKGROUND: Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocin-induced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms. METHODS: PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia. RESULTS: GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency. CONCLUSIONS: These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain. The antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and GABAergic mechanisms though a potential oleamide-sourced cannabimimetic involvement is also discussed.

Thymoquinone Inhibition of Acquisition and Expression of Alcohol-Induced Behavioral Sensitization.

Repeated low doses of alcohol have been shown to progressively enhance locomotor activity in mice, and this phenomenon is designated as behavioral sensitization. Thymoquinone, a major active component of Nigella sativa oil has been investigated in a number of studies for its neuroprotective effects against a variety of ailments. This study was conducted to explore the therapeutic potential of thymoquinone on the acquisition and expression of alcohol-induced behavioral sensitization. Mice treated with alcohol (2.2 g/kg/day) or saline for 13 days and subsequently challenged with an acute alcohol dose (2.2 g/kg) 5 days later were orally administered acute doses of thymoquinone (10, 20 and 30 mg/kg). Thymoquinone subacute treatment with all doses throughout alcohol exposure significantly inhibited both the development and expression phases of alcohol behavioral sensitization in a dose-dependent manner. However, acute treatment with thymoquinone (30 mg/kg) only reversed the expression phase of sensitization. These findings are explained in terms of the known GABA promoting action of thymoquinone in relation to the motive circuit within the limbic component of the basal ganglia. It is concluded that thymoquinone may be a potential therapeutic option for the treatment and prevention of alcohol induced behavioral sensitization.

Attenuation of cisplatin-induced emetogenesis by standardized Bacopa monnieri extracts in the pigeon: behavioral and neurochemical correlations.

Nausea and vomiting are the most distressing and common side effects of cancer chemotherapy which often result in patient noncompliance. In the present study, standardized methanolic and n-butanolic fractions of Bacopa monnieri were evaluated against cisplatin-induced emesis in the pigeon in relation to their activity on central and intestinal neurotransmitters levels. Cisplatin (7.0 mg/kg, i. v.) induced reproducible emesis without lethality in healthy pigeons. The methanolic (10-40 mg/kg) and the bacoside-rich n-butanolic fractions of B. monnieri (5-20 mg/kg), as well as the antioxidant N-(2-mercaptopropionyl) glycine (10 mg/kg), attenuated cisplatin-induced emesis by 66.3% (p < 0.05), 71.6% (p < 0.001), and 76.5% (p < 0.001), respectively, where the standard antiemetic metoclopramide (30 mg/kg) produced a 48.9% reduction (p < 0.01). The methanolic and n-butanolic fractions of B. monnieri at all of the doses tested significantly reduced the serotonin concentration (p < 0.001) in the brain stem and intestine 3 h after cisplatin administration, while at the 18th h, B. monnieri treatments attenuated not only the dopamine upsurge in the area postrema and brain stem (p < 0.05-0.001), but also the intestinal 5-HT concentration (p < 0.01-0.001). B. monnieri treatments alone did not alter the basal neurotransmitters or their metabolites in the brain areas and intestine. The prolonged suppressive effect of B. monnieri treatments on the behavioral signs of cisplatin-induced emesis, the subsequent supportive neural evidence, and the safety and tolerability profile suggest that B. monnieri methanolic and bacoside-rich n-butanolic fractions might be a valuable adjunct in the treatment of emetogenic chemotherapy, and this warrants further study in other models of emesis.

Comparative evaluation of gastroulcerogenic potential of nitrogen isoforms of salicyl alcohol and aspirin in rats: biochemical and histological study.

The aim of the current study was to explore in vivo any relative gastroulcerogenic prospective propensity of newly synthesized nitrogen containing derivatives of salicyl alcohol; compound (I) [1-(2-hydroxybenzyl)piperidinium chloride], compound (II) [4-carbamoyl-1-(2-hydroxybenzyl)piperidinium chloride] and aspirin in albino rats. The experimental groups received the following oral treatments daily for 6 days: group I saline control; group II, standard (aspirin) treatment group [150 mg/kg of body weight]; group III, test (compound I) treatment group [100, 150 mg/kg]; group IV, test (compound II) treatment group [100, 150 mg/kg]. The results showed that in the case of the aspirin treated group and compound (I) [150 mg/kg], there was a significant increase in gastric volume, free acidity, total acidity, ulcer score and a decrease in gastric pH. Furthermore, histopathological examination of gastric mucosa of these treated groups revealed detectable morphological changes. Utilizing the same protocol, synthetic compound (I) [100 mg/kg] and (II) [100, 150 mg/kg] exhibited no statistically significant ulcerogenic or cytotoxic properties. A cyclooxygenase (COX) selectivity test indicated the preferential inhibition of COX-I and COX-II enzymes by compounds (I) and (II). This study therefore indicates that these synthetic compounds may possess reduced ulcerogenic potential and could be a functional substitute to aspirin.

The use of local anaesthesia for intrauterine device insertion by health professionals in the UK.

BACKGROUND: Pain associated with the insertion of an intrauterine device (IUD) is a known barrier to intrauterine contraception use in the UK. It is good practice for health professionals to discuss pain relief and use with women prior to the insertion of an IUD. OBJECTIVES: This study aimed to determine the prevalence of and reasons for and against the use of local anaesthesia (LA) for IUD insertion. METHODS: A survey was undertaken using paper questionnaires to determine LA use for IUD insertion by UK health professionals. RESULTS: Overall, approximately one quarter (n=129) of all respondents use LA routinely, one quarter hardly ever or never use LA, while the remaining half use it sometimes. Use of LA was more prevalent among health professionals who worked in integrated sexual and reproductive health and contraception-only services, compared to general practice. UK health professionals who hardly ever or never used LA for the insertion of IUDs were more likely to be working in general practice. CONCLUSIONS: The results of this survey suggest that more UK health professionals need to routinely discuss pain relief and offer this to their patients prior to IUD insertion as part of the care pathway for patients who choose to use intrauterine contraception.

A Bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover.

Bacopa monnieri (BM) has been used in Ayurvedic medicine as a nootropic, anxiolytic, antiepileptic and antidepressant. An n-butanol extract of the plant (nBt-ext BM) was analysed and found to contain Bacoside A (Bacoside A3, Bacopaside II and Bacopasaponin C). The effects of the BM extract were then studied on morphine-induced hyperactivity as well as dopamine and serotonin turnover in the striatum since these parameters have a role in opioid sensitivity and dependence. Mice were pretreated with saline or nBt-ext BM (5, 10 and 15 mg/kg, orally), 60 min before morphine administration and locomotor activity was subsequently recorded. Immediately after testing, striatal tissues were analysed for dopamine (DA), serotonin (5HT) and their metabolites using HPLC coupled with electrochemical detection. The results indicated that nBt-ext BM significantly (p < 0.001) decreased locomotor activity in both the saline and morphine treated groups. Additionally, nBt-ext BM significantly lowered morphine-induced dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-H1AA) upsurges in the striatum but failed to affect DA, 5-HT and their metabolites in the saline treated group. These findings suggest that nBt-ext BM has an antidopaminergic/serotonergic effect and may have potential beneficial effects in the treatment of morphine dependence.