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BACKGROUND: Despite remarkable advances, cancer has remained the second cause of death, which shows that more potent novel compounds should be found. Ethnobotanical compounds have a long history of treating diseases, and several approved chemotherapeutic compounds were isolated from plants. OBJECTIVE: The research aimed to evaluate the cytotoxic effects of Dorema hyrcanum root extract on ovarian, breast, and glioblastoma cells while examining its selectivity towards normal cells. Additionally, the study is directed to investigate cell death mechanisms, delineate modes of cell death, and explore intracellular ROS production. METHODS: Cytotoxic effects of alcoholic, dichloromethane, and petroleum ether fractions of Dorema hyrcanum were investigated on cancer and normal cells by using MTT assay, and the concentration around IC50 values was used for flow cytometric assessment of apoptosis, evaluation of the expression of selected genes via RT-qPCR and production of ROS. RESULTS: Methanolic extract exhibited the highest cytotoxicity, impacting A2780CP and MDA-MB-231. All fractions showed comparable effects on U251 cells. Notably, extracts displayed higher IC50 values in normal HDF cells, indicating cancer cell specificity. Flow cytometry revealed induction of apoptosis and non-apoptotic death in all three cancer cell lines. QPCR results showed upregulation of related genes, with RIP3K prominently increased in U251 glioblastoma. The DCFH-DA assay demonstrated ROS induction by the PE fraction exclusively in A2780CP cells after 30 minutes and up to 24 hours. CONCLUSION: Dorema hyrcanum root extracts exhibited potent anti-tumor effects against all studied cell lines. The methanolic extract demonstrated the highest cytotoxicity, particularly against A2780CP and MDA-MB-231 cells. Importantly, all fractions displayed selectivity for cancer cells over normal HDF cells. Unique modes of action were observed, with the petroleum ether fraction inducing significant non-apoptotic cell death. These findings suggest promising therapeutic potential for Dorema hyrcanum in cancer treatment with subject to further mechanistic studies.
Assuntos
Antineoplásicos Fitogênicos , Apoptose , Neoplasias da Mama , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioblastoma , Neoplasias Ovarianas , Extratos Vegetais , Raízes de Plantas , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Apoptose/efeitos dos fármacos , Feminino , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Células Tumorais Cultivadas , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrine disorder that disrupts the menstrual cycle and causes infertility. Considering the increasing use of medicinal plants, the present study aimed to evaluate the effects of Teucrium polium L. on letrozole-induced PCOS in female rats. METHODS: Six groups of rats (n=7 each) were evaluated. The control group received 1% carboxy methyl cellulose as vehicle, while the five other groups received letrozole 1 mg/kg orally for 21 days. After PCOS induction, the rats were orally administered T. polium extract (50, 100, and 200 mg/kg) or metformin (200 mg/kg) for 28 days. Subsequently, body and ovarian weights and serum levels of follicle stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, and testosterone were measured. Finally, the ovarian tissues were isolated for histological examination. RESULTS: There were no significant changes in weekly body weight in any group. After 21 days of letrozole administration, PCOS induction was confirmed by estrous cycle irregularities and increased LH and testosterone levels. After treatment with the hydroalcoholic extract of T. polium, testosterone and LH levels were significantly reduced in all groups (P<0.05). Histological studies of ovaries in the metformin and T. polium groups exhibited normal follicular development with fewer and smaller cystic follicles than those in the PCOS group. CONCLUSION: The hydroalcoholic extract of T. polium improves serum levels of sex hormones, restores ovarian morphology in PCOS-induced rats, and is a good candidate for further clinical trials.
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Based on the long history of Scutellaria plants in east traditional medicines, several species of Scutellaria showed promising antioxidant, anti-inflammation and neuroprotection effects in pharmacological researches. Using bioassay-guided fractionation of various extract of Scutellaria nepetifolia, an endemic species that grows widely in Iran, based on on nitric oxide (NO) inhibitory activity against H2O2 induced NO production in PC12 pheochromocytoma cells led to the isolation of two iridoid compounds namely, as 6ß-hydroxy 8-epiboshnaloside (1) and 1,5,9-epideoxy loganic acid (2) and Verbascoside (3). Finally, the interaction of isolated compounds with inducible nitric oxide synthase (iNOS) protein was simulated by molecular docking study. It is the first report of these two iridoid glycosides from Scutellaria spp. All three isolated compounds showed strong interaction with iNOS enzyme in molecular docking simulations. So, they possibly contributed in the NO inhibitory effect of S. nepetifolia.
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Scutellaria , Peróxido de Hidrogênio , Simulação de Acoplamento Molecular , Óxido Nítrico , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Scutellaria/químicaRESUMO
BACKGROUND AND OBJECTIVES: NF-kB, SIRT1 and systemic inflammation factors including hs-CRP, IL-6 and TNF-α accelerate atherosclerosis pathogenesis. Our purpose was to evaluate the effect of daily supplementation of three-gram cinnamon on plasma levels of NF-kB, SIRT, hs-CRP, IL-6 and TNF-α among type 2 diabetes patients. SUBJECTS AND METHODS: A randomized, double blind, and controlled clinical trial was performed with 44 adult patients who were 25 to 70 years old with type 2 diabetes, randomized to two intervention (n = 22) and control (n = 22) groups differing by daily three grams cinnamon supplementation and placebo for 8 weeks, respectively. The plasma levels of NF-kB, SIRT, hs-CRP, IL-6 and TNF-α were measured by ELISA assay at the beginning and end of the study. RESULTS: After 8-week intervention, 39 subjects (n = 20 in the cinnamon and n = 19 in the placebo groups) ended up the trial. It was not observed significant difference in levels of hs-CRP (P = 0.29), TNF-α (P = 0.27), IL-6 (P = 0.52), and Sirtuin-1 (P = 0.51) in between group comparison. While, the result showed significant difference in levels of NF-kB (P = 0.02) between groups. As well as, in among group comparison, there was not observed significant differences except in hs-CRP (P = 0.008) in placebo group. CONCLUSIONS: This study elucidated that cinnamon supplementation has no beneficial effects in reduction of NF-kB, SIRT1, hs-CRP, IL-6 and TNF-α levels in type 2 diabetes patients which have a considerable role in development of atherogenesis.
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Cinnamomum zeylanicum , Diabetes Mellitus Tipo 2/sangue , Suplementos Nutricionais , Inflamação/sangue , Inflamação/tratamento farmacológico , NF-kappa B/sangue , Sirtuína 1/sangue , Adulto , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Humanos , Inflamação/etiologia , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Soluble forms of vascular adhesion molecules, ICAM-1 and VCAM-1, accelerate atherosclerosis pathogenesis. The present study was conducted to evaluate the effect of daily supplementation of 3 g cinnamon on the plasma levels of ICAM-1 and VCAM-1 among patients with type 2 diabetes. This randomized double-blind placebo-controlled trial was performed on 44 adult patients with type 2 diabetes aged 25-70 years. The patients were randomized to two groups of intervention (n = 22) and control (n = 22), differing by daily cinnamon supplementation or placebo (3 g) for 8 weeks. Plasma levels of ICAM-1 and VCAM-1 were measured at the beginning and end of the study. After 8 weeks, 39 subjects (n = 20 in the cinnamon and n = 19 in the placebo groups) completed the trial. There was a significant reduction in the mean levels of ICAM-1 and VCAM-1 within cinnamon and placebo groups (P < 0.001). But there was no significant difference in ICAM-1 (P = 0.75) and VCAM-1 (P = 0.72) between the groups at the end of the trial. According to the results, cinnamon supplementation has no beneficial effect on the reduction of ICAM-1 and VCAM-1 levels in patients with type 2 diabetes, which have a role in the development of atherogenesis.
Assuntos
Cinnamomum zeylanicum , Diabetes Mellitus Tipo 2/metabolismo , Molécula 1 de Adesão Intercelular/sangue , Preparações de Plantas/farmacologia , Molécula 1 de Adesão de Célula Vascular/sangue , Idoso , Glicemia/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
In Iranian traditional medicine, Inula species have been used for the treatment of seizure. In this study we decided to investigate the anticonvulsant activity of seven species from this genus to find an effective remedy for seizure with less adverse effects compared to the available medicines. Aqueous and methanolic extracts of Inula britannica, Inula helenium, Inula viscidula, Inula oculus-christi, Inula aucheriana, Inula thapsoides, and Inula salicina were prepared and their antiepileptic activity was investigated by maximal electroshock (MES) and pentylentetrazole (PTZ) tests on Male NMRI Albino mice. Diazepam was used as positive control in both tests. In addition, two extracts with the best anticonvulsant activities were selected and their sedative and hypnotic effects were evaluated using open field and righting reflex tests, respectively. The effects of the both extracts on memory and motor coordination were also assessed by step-through passive avoidance and rotarod tests, respectively. Aqueous extract of Inula britannica and Inula viscidula showed the best activity in MES model and their ED50 (with 95% confidence interval) was 19.5 (7.9~48.5) mg/kg and 12.7(10.0~16.3) mg/kg, respectively. None of the extracts showed noticeable anticonvulsant effects in the PTZ model. The active extracts also showed sedative-hypnotic effects in righting reflex and open field tests. Furthermore, both extracts did not affect the memory and motor coordination in the experimental models. The anticonvulsant and sedative activities of the extracts were antagonized by flumazenil, indicating that benzodiazepine receptors are probably involved in the effects. This study indicates that Inula britannica and Inula viscidula are good candidates for further phytochemical and mechanistic studies in order to find anticonvulsant and sedative-hypnotic compounds with less adverse effect on memory and motor coordination.
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Allium hirtifolium Boiss and Astragalus hamosus L. are mentioned in Iranian traditional medicine documentation as therapy for a kind of dementia with the features and symptoms similar to those of Alzheimer's disease (AD). In the present study, the effects of these herbs on neuro-inflammation and memory have been evaluated as new therapies in amyloid beta (Aß)-induced memory impairment model. Separate groups of rats were fed with A. hirtifolium or A. hamosus extract (both 100 mg/(kg·day)-1) started 1 week before stereotaxic surgery to 24 h before behavioral testing (totally, for 16 successive days). The effects of oral administration of mentioned extracts on the memory and neuro-inflammation were assessed in the Aß-injected rats. The results of this study showed that oral administration of both A. hirtifolium and A. hamosus improved the memory, examined by using Y-maze test and shuttle box apparatus. Also, Western blotting analysis of cyclooxygenase-2, interleukin-1ß, and tumor necrosis factor-α showed that these herbs have ameliorating effects against the neuro-inflammation caused by Aß. These findings suggest that the use of A. hirtifolium and A. hamosus as herbal therapy may be suitable for decreasing AD-related symptoms and treatment of other neurodegenerative disorders.
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Allium/química , Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Astrágalo/química , Comportamento Animal/efeitos dos fármacos , Suplementos Nutricionais , Hipocampo/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Memória/efeitos dos fármacos , Nootrópicos/farmacologia , Extratos Vegetais/farmacologia , Administração Oral , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Nootrópicos/administração & dosagem , Nootrópicos/isolamento & purificação , Fragmentos de Peptídeos , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos WistarRESUMO
The aim of the current study was to determine the effect of a daily intake of three grams of cinnamon over eight weeks on glycemic indicators, advanced glycation end products, and antioxidant status in patients with type 2 diabetes. In a double-blind, randomized, placebo controlled clinical trial study, 44 patients with type 2 diabetes, aged 57 ± 8 years, were randomly assigned to take either a three g/day cinnamon supplement (n = 22) or a placebo (n = 22) for eight weeks. We measured the fasting blood glucose, insulin, hemoglobinbA1c, homeostasis model assessment for insulin resistance (HOMA-IR), carboxymethyl lysine, total antioxidant capacity, and malondialdehyde levels at the beginning and the end of the study. Thirty-nine patients (20 in the intervention group and 19 in the control group) completed the study. After an eight-week intervention, changes in the level of fasting blood glucose, insulin, hemoglobinbA1c, HOMA-IR, carboxymethyl lysine, total antioxidant capacity, and malondialdehyde were not significant in either group, nor were any significant differences between groups observed in these glycemic and inflammatory indicators at the end of the intervention. Our study revealed that cinnamon supplementation had no significant effects on glycemic and inflammatory indicators in patients with type 2 diabetes.
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Antioxidantes/metabolismo , Glicemia/fisiologia , Cinnamomum zeylanicum , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Idoso , Método Duplo-Cego , Hemoglobinas Glicadas/metabolismo , Produtos Finais de Glicação Avançada , Homeostase/efeitos dos fármacos , Humanos , Insulina/sangue , Lisina/análogos & derivados , Lisina/metabolismo , Malondialdeído , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Corylus avellana L. (hazelnut) is known to be a delicious and nutritious food. This study was carried out to evaluate the use of hazelnut as a therapy for memory impairment because in Iranian traditional medicine, it is recommended for those suffering from a particular type of dementia, with symptoms of Alzheimer's disease. METHODS: In this study, rats were fed with hazelnut kernel [(without skin) 800â mg/kg/day] during 1 week before stereotaxic surgery to 24â hours before behavioral testing (in general, for 16 consecutive days) and the effect of hazelnut eating on memory, anxiety, neuroinflammation and apoptosis was assessed in the amyloid beta-injected rat. RESULTS: The results of this study showed that feeding with hazelnut improved memory, (which was examined by using Y-maze test and shuttle box apparatus), and reduced anxiety-related behavior, that was evaluated using elevated plus maze. Also, western blotting analysis of cyclooxygenase-2, interleukin-1ß, tumor necrosis factor-α, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, and caspase-3 showed that hazelnut has an ameliorating effect on the neuroinflammation and apoptosis caused by Aß. DISCUSSION: These ï¬ndings suggest that hazelnut, as a dietary supplement, improves healthy aging and could be a beneficial diet for the treatment of AD.
Assuntos
Doença de Alzheimer/prevenção & controle , Corylus , Modelos Animais de Doenças , Alimento Funcional , Memória , Neuroproteção , Nozes , Doença de Alzheimer/imunologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Ansiedade/etiologia , Ansiedade/prevenção & controle , Apoptose , Aprendizagem da Esquiva , Comportamento Animal , Corylus/crescimento & desenvolvimento , Etnobotânica , Hipocampo/imunologia , Hipocampo/metabolismo , Humanos , Irã (Geográfico) , Aprendizagem em Labirinto , Medicina Tradicional , Proteínas do Tecido Nervoso/metabolismo , Neurônios/imunologia , Neurônios/metabolismo , Nozes/crescimento & desenvolvimento , Distribuição Aleatória , Ratos WistarRESUMO
BACKGROUND: Many plants have been introduced in Iranian traditional medicine for treatment of different joint problems including knee pain. Topical application of the mixture of Lawsonia inermis L. leaves (Henna) with aqueous extract of Ricinus communis L. leaves have been mentioned to have significant effects on reducing knee pain. The present study was designed to evaluate the analgesic and anti-inflammatory effects of the mixture of these two herbs in male rats. METHODS: We induced knee osteoarthritis as a model of chronic pain by intra-articular injection of mono sodium iodoacetate (MIA). Mechanical allodynia, hotplate latency test, spontaneous movements and gait analysis were used for the evaluation of analgesic activity. Anti-inflammatory activity was evaluated by measuring the diameter and the volume of the injected paw compared to contralateral paw. These tests were monitored at days 1, 3, 7, 14 and 21 of MIA administration. Histopathological evaluations were also used to assess the efficacy of the treatment on inflammation and lesions in knee tissue. In all tests, diclofenac topical gel was used as a positive control. The herbal extracts, their mixture, and vehicle or diclofenac gel were administered daily for 14 days by topical route. RESULTS: The mixture of these two extracts significantly reduced the knee joint width and volume of the injected paws and also improved foot prints in gait analysis after 3 days of MIA injection. Analysis of mechanical allodynia (after 21 days), hotplate latency test (after 10 days), spontaneous movements (after 7 days) and in positive control group (after 3 days in all tests and in mechanical allodynia after 14 days) compared to the vehicle group, showed significant effects. Topical usage of the selected formulation made significant histopathological changes on the knee of the rats. Compared to the vehicle group, the tests and diclofenac groups showed less reactions characterized by negligible edema and a few scattered inflammatory lymphoid cells. CONCLUSION: The present findings showed that the present formulation not only was able to mitigate pain and inflammation in the paws but also made significant histopathological changes on the knee of the rats. Further studies are necessary to confirm the effect of the formulation.
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Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Lawsonia (Planta)/química , Osteoartrite do Joelho/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Ricinus/química , Administração Tópica , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Esquema de Medicação , Combinação de Medicamentos , Marcha/efeitos dos fármacos , Ácido Iodoacético/efeitos adversos , Masculino , Osteoartrite do Joelho/induzido quimicamente , Osteoartrite do Joelho/patologia , Manejo da Dor , Extratos Vegetais/farmacologia , Folhas de Planta/química , Distribuição Aleatória , Ratos , Resultado do TratamentoRESUMO
Fruits of Olea europaea L. have been used for centuries in folk medicine to treat many inflammatory diseases. In order to evaluate the anti-nociceptive activities of the methanolic and aqueous extracts of defatted fruits of O. europaea, formalin test was used and for evaluation of anti-inflammatory effects of the extract, the volume of paw edema was measured. The results revealed that both extracts did not exhibit significant analgesic activity in the first phase of formalin test, whereas methanolic extract at the 600 mg/Kg dose and aqueous extract at the 450 and 600 mg/Kg doses could inhibit induced pain in the second phase of formalin test. Furthermore, the results of paw edema volume measurement indicated that the aqueous extract has anti-inflammatory effects at dose of 600 mg/Kg. Induced anti-nociception by aqueous olive extract was not reversed by naloxone, which indicates that the opioid receptors are not involved in the analgesic effects of the extracts. The present data pointed out that the extracts of olive defatted fruit have anti-nociceptive and anti-inflammatory effects in rats but further studies are needed to elucidate the mechanism(s) of action and active components which are involved in analgesic and anti-inflammatory effects.
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Antiepileptic drugs used to treat epilepsy can cause severe, life threatening side effects. In Iranian traditional medicine, herbal remedies have been used for centuries to treat seizures. In this study, the five most important herbals in Iranian traditional medicine, namely Canon, al-Hawi, al-Abniah 'an Haqaeq al Adwia, Tuhfat al-Mu'minin, and Makhzan ul-Adwia, were searched for the term "sar-e", which means epilepsy, to identify the herbs used for treatment in ancient times. We also searched scientific literature for pharmacological evidence of their effectiveness. Twenty-five plants were identified as herbal remedies to treat epilepsy. Pharmacological data related to the antiepileptic activity of eleven of these plants exists. A large number of these plants which have not been investigated pharmacologically for antiepileptic activity would be good candidates for study in exploring new herbal anticonvulsant remedies.
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Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Medicina Tradicional , Fitoterapia , Plantas Medicinais , Animais , Humanos , Irã (Geográfico)RESUMO
Phytochemical investigation of the chloroform extract of BRYONIA ASPERA roots resulted in the isolation and structure elucidation of two new cucurbitacins (1, 2) together with eight known cucurbitane derivatives (6-13), the pentacyclic triterpene bryonolic acid (5) and two hydroxybenzoic acid amides (3, 4). Their structures were elucidated by spectroscopic analysis, including 2D NMR techniques.
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Bryonia/química , Extratos Vegetais/química , Triterpenos/isolamento & purificação , Ácido Benzoico/isolamento & purificação , Glicosídeos/isolamento & purificação , Estrutura Molecular , Raízes de Plantas , Triterpenos/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: An investigation of plants was undertaken through interviews and literature surveys on plants used to treat malaria or cancer or microbial diseases in Iran. AIM OF STUDY: In vitro and in vivo antiplasmodial tests were carried out on selected plants traditionally used in Iran. MATERIALS AND METHODS: Thirty-two plants were extracted with methanol and tested for their in vitro (pLDH assay) activity against Plasmodium falciparum, in vivo activity against Plasmodium berghei and assessed for any cytotoxicity against the human cancer cell line MCF7 and the normal cell MDBK. RESULTS: Extracts from four plants, Buxus hyrcana Pojark. (Buxaceae), Erodium oxyrrhnchum M. Bieb. (Geraniaceae), Glycyrrhiza glabra L. (Fabaceae) and Ferula oopoda (Boiss and Bushe) Boiss. (Apiaceae) were found to have significant antiplasmodial activity (IC50 ranging from 4.7 to 26.6 microg/ml). These findings lend support to the use of Buxus hyrcana and Glycyrrhiza glabra in traditional medicine. The chloroformic fraction also was active against K1 and 3D7 strains. The chloroformic fraction was studied at 10 mg per kg body weight mouse per day. This fraction reduced parasitaemia by 86.1% compared to untreated control mice. CONCLUSION: Glycyrrhiza glabra showed antiplasmodial activity and has selectivity for Plasmodium falciparum and Plasmodium berghei when tested on mammalian cells. This is the first report that mentioned in vitro and in vivo antiplasmodial activity of Glycyrrhiza glabra.