Teratogen Potential Evaluation of the Aqueous and Hydroalcoholic Leaf Extracts of Crataegus oxyacantha in Pregnancy Rats.

Crataegus oxyacantha is used in the treatment of cardiovascular diseases. The aim of this study was to evaluate the transplacental genotoxicity effect of aqueous (AE) and hydroalcoholic extract (HE) of leaves C. oxyacantha in a rat model and the quantification of malondialdehyde (MDA) in the liver. Three different doses of the AE and HE of the C. oxyacantha leaf were administered orally (500, 1000 and 2000 mg/kg) to Wistar rats during 5 days through the pregnancy term (16-21 days), and sampling in rats occurred every 24 h during the last 6 days of gestation, while only one sample was taken in neonates at birth. A sample of the mother's and the neonate's liver was taken for the determination of MDA. The results show that, at the hepatic level, the evaluated doses of extracts C. oxyacantha in pregnant rats and their pups did not show cytotoxicity. However, the AE and HE generated cytotoxic and genotoxic damage in the short term. On the other hand, only the AE showed a teratogenic effect. Based on these results, the AE and HE of the C. oxyacantha leaf should not be administered during pregnancy.

In Vitro Anti-cancer Effect of Crataegus oxyacantha Berry Extract on Hormone Receptor Positive and Triple Negative Breast Cancers via Regulation of Canonical Wnt Signaling Pathway.

Breast cancer treatment strategy depends mainly on the receptor status. Our aim was to identify a herbal preparation, effective against breast cancer, irrespective of hormone sensitivity, and to understand its molecular mechanism. The rich antioxidant composition of hawthorn (Crataegus oxyacantha) makes it a promising anti-cancer drug candidate. Polyphenol-rich methanolic extract of C. oxyacantha berry (M.Co) was found to be cytotoxic on hormone receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines, at a dose (75 µg/ml) safe on normal cells. It could effectively inhibit tumor cell proliferation and arrest cell cycle at G1/S transition in both cell lines. Molecular targets were selected from different levels of canonical Wnt signaling pathway (such as autocrine and antagonistic ligands, receptor, effector, cytoplasmic components, downstream targets, and pathway antagonist), since they are frequently found dysregulated in all breast cancers and their aberrant activation is associated with cancer stem cell expansion. M.Co could significantly downregulate the expression of Wnt pathway agonists and upregulate that of Wnt antagonists at transcriptional and translational levels, in both cell lines. To conclude, C. oxyacantha berry extract is effective against breast cancer irrespective of its hormone dependency, and cancer growth inhibition at stem cell level can be expected.

Crataegus oxyacantha Extract as a Biostimulant to Enhance Tolerance to Salinity in Tomato Plants.

Salinity is a severe abiotic problem that has harmful impacts on agriculture. Recently, biostimulants were defined as bioprotectant materials that promote plant growth and improve productivity under various stress conditions. In this study, we investigated the effect of Crataegus oxyacantha extract as a biostimulant on tomato plants (Solanum lycopersicum) grown under salt stress. Concentrations of 20 mg/L, 30 mg/L, and 70 mg/L of C. oxyacantha extract were applied to tomato plants that were grown under salt stress. The results indicated that plants that were treated with C. oxyacantha extract had a higher ability to tolerate salt stress, as demonstrated by a significant (p < 0.05) increase in plant growth and photosynthetic pigment contents, in addition to a significant increase in tomato soluble sugars and amino acids compared to the control plants. In the stressed tomato plants, malondialdehyde increased and then decreased significantly with the different concentrations of C. oxyacantha extract. Furthermore, there was a significant improvement in the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and glutathione reductase (GR) in the stressed plants, especially after treatment with 70 mg/L of the extract. Overall, our results suggest that C. oxyacantha extract could be a promising biostimulant for treating tomato plants under salinity stress.

Cytotoxic and Genotoxic Evaluation of the Aqueous and Hydroalcoholic Leaf and Bark Extracts of Crataegus oxyacantha in Murine Model.

Crataegus oxyacantha has been mainly used in traditional medicine for the treatment of cardiovascular diseases. However, its safety profile has not been fully established, since only the genotoxic effects of C. oxyacantha fruit have been described. Therefore, the objective of this work was evaluating the cytotoxicity and genotoxicity of the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha by means of the micronucleus test in a murine model. Doses of 2000, 1000, and 500 mg/kg of both extracts were administered orally for 5 days in mice of the Balb-C strain. Peripheral blood smears were performed at 0, 24, 48, 72, and 96 h after each administration. The number of polychromatic erythrocytes (PCEs), micronucleated polychromatic erythrocytes (MNPCEs), and micronucleated erythrocytes (MNEs) was determined at the different sampling times. Our results showed that the leaf and bark of C. oxyacantha increase the number of MNEs at the 2000 mg/kg dose, and only the aqueous leaf extract decreases the number of PCEs at the same dose. Therefore, the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha showed genotoxic effects, and only the aqueous leaf extract exhibited cytotoxic effects.

Polyphenolic content and bioactivities of Crataegus oxyacantha L. (Rosaceae).

Solid-Liquid Extraction (SLE) using solvent of different polarities (CHCl3, EtOAc, and n-BuOH) has been applied to leaves and fruits from (Crataegus oxyacantha L.), a deciduous shrub with an expected rich phytochemical profile. The total polyphenols content and the radical scavenging activity of each extract were evaluated. These extracts were analyzed by HPLC-DAD and rutin, quercetin-3-glucoside, caftaric and caffeic acid had been positively identified. The phytochemical study of the ethyl acetate extract of C. oxyacantha, led to the isolation and structural elucidation of quercetin (1); quercetin-3-O-ß-glucoside (2); epicatechin (3); naringenin (4), reported for the first time from this species except caffeic acid and epicatechin. These compounds were identified by 1D and 2D NMR combined analysis as well as by MS and UV.The antimicrobial activity of these extracts has also been tested, showing strong antibacterial activity-solvent dependent-against Gram positive bacteria. Additionally, bactericidal power was demonstrated in fruit extracts.

Green synthesis of silver and gold nanoparticles using Crataegus oxyacantha extract and their urease inhibitory activities.

This study reports the green synthesis and urease inhibitory activities of Ag and Au nanoparticles (NPs) using Crataegus oxyacantha extract. The synthesized NPs were characterized by UV-visible, FT-IR spectroscopy, atomic force microscopy, and scanning electron microscopy. The obtained NPs were spherical in shape, and their size was around 85 nm. A strong correlation between the phytochemicals present in the extract and their capability for the synthesis of NPs was observed. Furthermore, the shape, size, stability, and bioactivity of the NPs were strongly influenced by the stabilizing phytochemicals. The experimental analysis suggested that these NPs have substantial stability in a diverse range of physiological conditions such as pH, salinity, and temperature. The NPs exhibited potent urease enzyme inhibitory activities with percent inhibition of 99.25 and IC50 value of 1.38 ± 0.3, comparable to the standard (thiourea percent inhibition, that is, 98.2% and IC50 value 5.3 ± 0.04). These results suggested that the proposed NPs could be used in the homeopathic and pharmaceutical industries for biomedical applications.

Hepatoprotective Effects of Algerian Crataegus oxyacantha Leaves.

BACKGROUND: Hawthorn (C. oxyacantha), a common edible plant, is widely used for the preparation of a different foodstuff and is also used in traditional medicine to treat heart problems and gastrointestinal ailments. Recently, a few patents of Crataegus preparation for protective effects (prevention of cardiovascular and hepatic diseases) have been developed. OBJECTIVE: The current study aimed to explore the antioxidant and hepatoprotective effects of nbutanol extract of Crataegus oxyacantha leaves in acute liver damage induced by Doxorubicin (DOX). METHODS: Crataegus oxyacantha (100 mg/kg body weight) or vitamin E as a standard antioxidant (100 mg/kg body weight) were administered orally to female rats for 10 days, in the presence or absence of hepatotoxicity induced by a single intraperitoneal (i.p.) injection of DOX (15 mg/kg on the 8th day). On day 11, blood and liver samples were analyzed for biomarker levels and histopathological changes. Liver homogenates were used for determination of oxidative stress parameters that include Malondialdehyde (MDA), Glutathione (GSH) level and Glutathione Peroxidase (GPx) activity. RESULTS: Treatment with n-butanol extract of C. oxyacantha leaves significantly improved the altered liver enzyme activities and oxidative stress markers. The histopathological observations confirm the results of biochemical parameters. CONCLUSION: The obtained results support the traditional use of C. oxyacantha to cure gastrointestinal ailments and highlighted its possible use in the food and pharmaceutical industries as a source of natural antioxidant.

Cardioprotective effect of resistance training and Crataegus oxyacantha extract on ischemia reperfusion-induced oxidative stress in diabetic rats.

Discovering an effective approach to limit infarction size after ischemia-reperfusion has a clinical importance in diabetics. We investigated the anti-myocardial ischemia-reperfusion injury effect of resistance training and Crataegus oxyacantha extract on diabetic rats. To this end, 50 male Wistar rats were randomly divided into 5 groups: the sedentary control (SC), sedentary diabetic (SD), resistance trained diabetic (RD), diabetic plus C. oxyacantha extract treatment (CD) and resistance trained diabetic plus C. oxyacantha extract treatment (RCD) groups. Animals in trained groups were subjected to progressive resistance training program with the use of a ladder (5 days/week, for 10 weeks). C. oxyacantha extract rats were treated with 100 mg/kg body weight of the extract using a gavage every day for 10 weeks. After treatments, rats were subjected to ischemia via LAD artery ligation for 30 min followed by 90 min reperfusion. The heart was collected following the ischemia-reperfusion and analyzed for oxidative stress and ischemia-reperfusion injury. Compared to the SC group, LDH, CK-MB and infarction size in the SD group were significantly higher, whereas injury indices in the RCD group were significantly lower than those in the SD group. GPx and MPO levels after reperfusion increased and decreased, respectively in response to training and C. oxyacantha. These findings suggest that 10 weeks resistance training and C. oxyacantha can synergistically decrease ischemia-reperfusion injury, and this mechanism may be related to a reduction in oxidative stress which is normally associated with ischemia-reperfusion.

Phytochemical and Pharmacological Activity Profile of Crataegus oxyacantha L. (Hawthorn) - A Cardiotonic Herb.

Crataegus oxyacantha L. (syn. C. rhipidophylla Gand.) (Rosac-eae) is one of the two medicinally recognized hawthorn species in European Pharmacopeia. Standardization of the extract prepared from the berry and flowers of the plant is required according to its oligomeric procyanidins. C. oxyacantha is well-known for its use in the treatment of various heart problems particularly, including heart failure in cases of declining cardiac performance equivalent to stages I and II of the New York Heart Association classification, angina pectoris, hypertension with myocardial insufficiency, mild alterations of cardiac rhythm, and atherosclerosis. C. oxyacantha has been reported to exert several other pharmacological activities such as hypotensive, antihyperlipidemic, antihyperglycemic, anxiolytic, immunomodulatory, and antimutagenic. Oligomeric procyanidins and flavone/flavonol types of flavonoids, which are considered to be the chief groups of active substances, phenolic acids, triterpenes, fatty acids, and sterols are present in the plant. The present review aims mainly to outline cardiotonic effect of C. oxyacantha as well as its brief phytochemistry. Numerous experiments and clinical studies have underlined cardiovascular efficacy of the plant through various mechanisms including positive inotropic and negative chronotropic effects, escalation in coronary blood flow and exercise tolerance, inhibition of the enzymes such as angiotensinconverting enzyme (ACE) and phosphodiesterase, anti-inflammatory and antihyperlipidemic effects, improving status of antioxidant enzymes, etc., which support its cardioactive efficacy. The plant possesses several other bioactivities for human health usually concomitant to its rich polyphenolic content.

Matrix solid-phase dispersion as a tool for phytochemical and bioactivities characterisation: Crataegus oxyacantha L._A case study.

The use of a matrix solid-phase dispersion (MSPD) process to extract polyphenols from hawthorn (Crataegus oxyacantha L.) a deciduous shrub with an expected rich phytochemical profile, has been evaluated. MSPD extracts of fruits and leaves have an outstanding content of polyphenols, although the particular phenolic profile is solvent dependent. The extracts were analysed by HPLC-DAD for the accurate identification of the major bioactive polyphenols, some of which have never been described for this species. MSPD has proven to be a good alternative to the classic methods of obtaining natural extracts, fast and with low consumption of organic solvents, therefore, environmentally friendly. The bioactivities can be considered also very remarkable, revealing extracts with high levels of antioxidant activity.

Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents.

Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha (Co) and Rosmarinus officinalis (Ro) extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); (c) Ro extract-treated myocardial infarction (MI-Ro); (d) Co extract-treated myocardial infarction (MI-Co); or (e) Ro+Co-treated myocardial infarction (MI-Ro+Co). Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD)-Cu2+/Zn2+, SOD-Mn2+, and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1), increased vasodilators agents (angiotensin 1-7 and bradikinin) and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators.

Neurologically Potent Molecules from Crataegus oxyacantha; Isolation, Anticholinesterase Inhibition, and Molecular Docking.

Crataegus oxyacantha is an important herbal supplement and famous for its antioxidant potential. The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer's disease. The compounds isolated from C. oxyacantha were evaluated for cholinesterases inhibitory activity using Ellman's assay with Galantamine as standard drug. Total of nine (1-9) compounds were isolated. Compounds 1 and 2 were isolated for the first time from natural source. Important natural products like ß-Sitosterol-3-O-ß-D-Glucopyranoside (3), lupeol (4), ß-sitosterol (5), betulin (6), betulinic acid (7), oleanolic acid (8), and chrysin (9) have also been isolated from C. oxyacantha. Overall, all the compounds exhibited an overwhelming acetylcholinesterase (AChE) inhibition potential in the range 5.22-44.47 µM. The compound 3 was prominent AChE inhibitor with IC50 value of 5.22 µM. Likewise, all the compounds were also potent in butyrylcholinesterase (BChE) inhibitions with IC50s of up to 0.55-15.36 µM. All the compounds, except 3, were selective toward BChE. Mechanism of the inhibition of both the enzymes were further studied by docking procedures using Genetic Optimization for Ligand Docking suit v5.4.1. Furthermore, computational blood brain barrier prediction of the isolated compounds suggest that these are BBB+.

Traditional herbs: a remedy for cardiovascular disorders.

BACKGROUND: Medicinal plants have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, venous insufficiency and arrhythmia since centuries. A recent increase in the popularity of alternative medicine and natural products has revived interest in traditional remedies that have been used for the treatment of cardiovascular diseases. AIM: The purpose of this review is to provide updated, comprehensive and categorized information on the history and traditional uses of some herbal medicines that affect the cardiovascular system in order to explore their therapeutic potential and evaluate future research opportunities. METHODS: Systematic literature searches were carried out and the available information on various medicinal plants traditionally used for cardiovascular disorders was collected via electronic search (using Pubmed, SciFinder, Scirus, GoogleScholar, JCCC@INSTIRC and Web of Science) and a library search for articles published in peer-reviewed journals. No restrictions regarding the language of publication were imposed. RESULTS: This article highlights the cardiovascular effects of four potent traditional botanicals viz. Garlic (Allium sativum), Guggul (Commiphora wightii), Hawthorn (Crataegus oxyacantha) and Arjuna (Terminalia arjuna). Although these plants have been used in the treatment of heart disease for hundreds of years, current research methods show us they can be utilized effectively in the treatment of cardiovascular diseases including ischemic heart disease, congestive heart failure, arrhythmias and hypertension. CONCLUSION: Although the mechanisms of action are not very clear, there is enough evidence of their efficacy in various cardiovascular disorders. However, for bringing more objectivity and also to confirm traditional claims, more systematic, well-designed animal and randomized clinical studies with sufficient sample sizes are necessary. Multidisciplinary research is still required to exploit the vast potential of these plants. Potential synergistic and adverse side effects of herb-drug interactions also need to be studied. These approaches will help in establishing them as remedies for cardiovascular diseases and including them in the mainstream of healthcare system.

Inhibition of differentiation of monocyte to macrophages in atherosclerosis by oligomeric proanthocyanidins -In-vivo and in-vitro study.

Monocyte to macrophage differentiation is a key event in the progression of atherosclerosis. An understanding on the fundamental molecular mechanisms and the identification of regulatory mechanisms behind this differentiation may aid in the identification of new therapeutic strategies. Inhibition of this phenomenon will form first line of defense in the prevention and treatment of atherosclerosis. In the current study we explored hypercholesterolemia induced monocyte to macrophage differentiation in-vivo (Wistar rats) leading to atherosclerosis and OxyLDL, M-CSF induced monocyte differentiation in-vitro (U937 cells). Oligomeric proanthocyanidin (OPC) isolated from Crataegus oxyacantha was tested for its efficacy in downregulating this differentiation and in preventing atherogenic disturbances. Cholesterol cholic acid diet induced an increased monocyte to macrophage differentiation by upregulating MCP1 and VCAM1 which induced the inflammatory cytokines that further substantiated the monocyte conversion and infiltration into the vascular walls. On addition of OxyLDL and M-CSF to U937 cells, macrophage markers CD36 and CD 68, PPARγ, MMP2 and 9 were elevated, suggesting differentiation. OPC downregulated this differentiation and thus could prevent the initiation of atherosclerosis.

Ethnomedicinal and phytopharmacological potential of Crataegus oxyacantha Linn. - A review

Traditional herbal medicines are practiced in the entire world and their ethnopharmacological records reveal that most of the people of the world have been using plants, animals, micro-organisms and minerals for treating various diseases. Crataegus oxyacantha (C. oxyacantha) Linn. (Rosaceae) commonly known as Hawthorn is an official plant in Homeopathic System of Medicine to treat various conditions of cardiovascular system. In recent times, this drug has been subjected to phytochemical, pharmacological, pre-clinical and clinical investigations and many new investigations have been indicated. Current review finds ethnomedicinal and phytopharmacological potential of leaves, flowers, berries, bark etc. for exploring the immense medicinal potential of Hawthorn. At the same time, studies to evaluate the dosage, toxicity and interactions with drugs and herbs on simultaneous use, which is imperative for optimal and safe utilization of this plant, are explained. There are few comprehensive reports available on clinical use of Hawthorn in chronic heart failure patients have shown promising results.

Pharmacological evaluation of a phytotherapeutic product - CPV (dry extract of Crataegus oxyacantha L., Passiflora incarnata L. and Valeriana officinalis L.) in laboratory animals / Avaliação farmacológica do produto fitoterápico - CPV (extrato seco de Crataegus oxyacantha L., Passiflora incarnata L. e Valeriana officinalis L.) em animais de laboratório

O presente estudo teve por objetivo avaliar em modelos animais, os possíveis efeitos do produto fitoterápico CPV (extrato seco de Crataegus oxyacantha, Passiflora incarnata e Valeriana officinalis) quanto à sua ação ansiolítica avaliada no modelo do labirinto em cruz elevado (LCE). Outros efeitos como neuroléptico (bloqueio da estereotipia por apomorfina), analgésico (testes: placa quente; retirada da cauda e contorções abdominais), bem como sobre a memória (esquiva passiva) também foram considerados. O extrato CPV (430 e 860 mg/kg) apresentou um efeito ansiolítico (aumento do número de entradas nos braços abertos do LCE) em ratos e uma tendência de efeito amnésico para ambas as doses (430 e 860 mg/kg), embora menos intenso quando comparado com o diazepam (1,5 mg/kg). O extrato não apresentou efeitos neuroléptico ou analgésico.

The aim of the present study was to evaluate the central effects of the phytotherapeutic product-CPV (dry extract of Crataegus oxyacantha, Passiflora incarnata and Valeriana officinalis) in animals models. In order to investigate the psychopharmacological profile of CPV extract, an evaluation toward anxiolytic effect of this extract on the elevated plus-maze (EPM) was carried out. Other effects such as neuroleptic (blockade of the stereotyped behavior induced by apomorphine), analgesic (hot plate; acetic acid writhing and tail-flick tests) and on the memory (passive avoidance test) were also analyzed. CPV extract (430 and 860 mg/ kg) presented an anxiolytic effect on rats (increased the number of entries into the open arms in the EPM) and, furthermore, a tendency of slight amnesic effect for the doses (430 and 860 mg/kg), but less intense when compared to diazepam (1.5 mg/kg). The extract did not show neuroleptic or analgesic effects.

Estudo de toxicologia clínica de um fitoterápico contendo Passiflora incarnata L., Crataegus oxyacantha L., Salix alba L. em voluntários saudáveis / Clinical toxicology study of an herbal medicine with Passiflora incarnata L., Crataegus oxyacantha L., Salix alba L. in healthy volunteers

O Pasalix® é um produto fitoterápico contendo uma associação de três plantas medicinais: Passiflora incarnata, Salix alba e Crataegus oxyacantha. Sua principal indicação é para o tratamento da ansiedade e insônia. O objetivo desse estudo foi avaliar a toxicologia clínica dessa formulação em voluntários saudáveis. Para isso realizou-se um ensaio clínico não aleatório, aberto, com 24 voluntários sadios do sexo masculino, que receberam ambulatorialmente dois (2) comprimidos revestidos do fitoterápico duas vezes ao dia, durante 28 dias ininterruptos. Os voluntários foram incluídos no estudo somente quando considerados saudáveis após avaliação clínica, exame físico e exames laboratoriais que antecederam o estudo. A avaliação laboratorial incluiu análise hematológica, bioquímica e sorológica. A avaliação clínica e laboratorial foi repetida após a 1ª, 2ª, 3ª e 4ª semanas de tratamento e 7 dias após a última administração. O Pasalix® foi bem tolerado pelos 24 voluntários não apresentando eventos adversos graves. Os exames clínicos, eletrocardiográficos e laboratoriais efetuados antes, durante e após o ensaio não evidenciaram sinais de toxicidade nos diversos órgãos e sistemas avaliados, confirmando a segurança da preparação para utilização em ensaios de eficácia terapêutica.

Pasalix® is an herbal medicine containing a combination of three medicinal plants: Passiflora incarnata, Salix alba and Crataegus oxyacantha. Its main indication is to treat anxiety and insomnia. The purpose of this study was to evaluate the clinical toxicology of that formulation in healthy volunteers. For this, a non-randomized open clinical trial was conducted with 24 healthy male volunteers, who received two (2) coated tablets of the herbal medicine twice a day for 28 uninterrupted days. The volunteers were included in the study only when considered healthy after clinical assessment, physical examination and laboratory tests which preceded the study. The laboratory tests included: hematological, biochemical and serological analysis. The clinical and laboratory evaluation was repeated after the 1st, 2nd, 3rd and 4th weeks of the treatment and 7 days after the last administration. Pasalix® was well tolerated by the 24 volunteers, and it has showed no serious adverse events. The clinical, laboratory, and electrocardiographic data assessed before, during and after the test showed no signals of toxicity in various organs and systems evaluated, confirming the safety of the preparation for use in trials of therapeutic efficacy.