Antifatigue Effects of the Aqueous Extracts of Myrtle Berries, Apple and Clove: An Animal Study.

Background: Fatigue is one of the most prevalent symptoms, increasing worldwide with no specific medication for fatigue. Iranian traditional medicine (ITM), or Persian medicine, is a reliable source for discovering natural medicine for diseases and their symptoms. Myrtus communis L. (Myrtle), Malus domestica Borkh. (Apple), and Syzygium aromaticum (L.) Merr. & L. M. Perry (Clove) have been utilized as brain and heart tonics in ITM. Based on ITM, cardiac tonics decrease fatigue by enhancing heart function and increasing blood flow to tissues. These plants, particularly myrtle berries, have been utilized as potent enlivening agents that reduce mental fatigue. Objectives: This study aims to investigate the effects of aqueous extracts of these plants on weight-loaded forced swimming (WLFS) tests and three doses of aqueous myrtle extract in an animal model of chronic sleep deprivation-induced fatigue. Methods: Five groups of rats (n = 6) were evaluated: Sham, control, apple-treated, clove-treated, and myrtle-treated groups. After 28 days of treatment, the WLFS test was performed, and swimming time was recorded. Subsequently, central fatigue was induced in rats by chronic sleep deprivation for 21 days. Five groups of rats (n = 6) were evaluated: Sham, control (sleep-deprived, which received water), and three sleep-deprived + treatment groups, which received aqueous myrtle extract (350, 700, and 1000 mg/kg). An open field test on the 20th day and a WLFS test on the 21st day were performed. Results: The myrtle berries significantly increased glucose, reduced lactate dehydrogenase (LDH) levels, and enhanced swimming time. Fatigue caused by chronic sleep deprivation increased malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and LDH while decreased superoxide dismutase (SOD), glucose, and swimming time. In all treatment groups, SOD levels and swimming time were increased, whereas MDA, IL-1ß, and TNF-α levels were decreased significantly. Only the 1000 mg/kg dose significantly reduced LDH levels (P < 0.001). The treatment significantly improved the velocity and the total distance moved in the open-field test. Conclusions: According to the results, the myrtle berries reduced fatigue in two animal models, probably due to its phenolic compounds, flavonoids, and polysaccharides.

Synthesis, characterization, molecular docking, antimalarial, and antiproliferative activities of benzyloxy-4-oxopyridin benzoate derivatives.

Background and purpose: Malaria and cancer are two major health issues affecting millions of lives annually. Maltol complexes and derivatives have been extensively investigated as chemotherapeutic and antimalarial activities. In this study, the design, synthesis, biological activities, and docking study of a novel series of pyridinones derivatives were reported. Experimental approach: The chemical structures of synthesized compounds were approved by FTIR, 1HNMR, 13CNMR, and mass spectroscopies. The antimalarial activity was evaluated through ß-hematin inhibition assay and the cytotoxicity activities were evaluated against PC12 and fibroblast cell lines via MTT and cell uptake assays. To theoretically investigate the ability of compounds to inhibit hemozoin formation, the synthesized compounds were docked in a heme sheet to explore their binding mode and possible interactions. Findings/Results: ß-Hematin inhibition assay showed acceptable activity for 7f, 7c, and 7d compounds and the molecular docking study showed 7h and 7f had effective interactions with the heme sheet. The cytotoxic study revealed compound 4b (IC50 = 18 µM) was significantly more active against PC12 cells than docetaxel (IC50 = 280 µM). The observations of cell uptake images were also shown both cell penetration and monitoring potential of synthesized compounds. Conclusion and implications: The compounds showed a moderate ability to inhibition of heme polymerization and also good interaction with heme through molecular docking was observed. Additionally, some of them have a good cytotoxic effect on the study2 cell line. So further study on these compounds can lead to compounds that can be considered as anti-malarial and/or anticancer agents.

Side effects of omeprazole: a system biology study.

AIM: To assess the effects of omeprazole on the human cardiovascular system is the main aim of this study. BACKGROUND: Omeprazole as a proton pump inhibitor is widely consumed to inhibit gastric acid secretion. METHODS: Gene expression profiles of "human coronary artery endothelial cells" in the absence and presence of omeprazole were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) interacted as an interactome, and the hub nodes are determined. The DEGs were enriched via gene ontology (GO) analysis. The critical hubs were identified based on the GO findings. RESULTS: Among 103 queried DEGs, 61 individuals were included in the main connected component. CTNNB1, HNRNPA1, SRSF4, TRA2A, SFPQ, and RBM5 genes were identified as critical hub genes. Six clusters of biological terms were introduced as deregulated elements in the presence of omeprazole. CONCLUSION: In conclusion, long-term consumption of omeprazole may be accompanied with undesirable effects, however more evidence is required.

Evaluating of Gene Expression Alteration after Garlic Consumption, Analyzing through Bioinformatics Approach.

Molecular study of garlic as a popular food ingredient could better understand its health benefits such as immunological effects. For this aim, effects of garlic on the spleen and possible side effects including oxidative stress increment, the molecular mechanism is investigated through network analysis of differentially expressed genes in the treatment of garlic. Protein-protein interaction (PPI) network analysis of spleen gene expression profile of Mus musculus (8-week old male C57BL/6J mice) in garlic treatments from a microarray study with the code of GSE10344 was analyzed via GEO2R software. Furthermore, Cytoscape V 3.7.1 was applied to construct and analyze a network of up- and down-regulated genes. The differentially expressed genes (DEGs) were analyzed via the CluePedia plugin of Cytoscape to determine expression patterns. After the identification of central nodes, an action map was created. A total of 77 DEGs were achieved which were including 40 up-regulated and 37 Down-regulated. The centrality analysis of the network indicated that Vcan, Lamb1, and Ltbp1 are hubs and Glra1, Wdr17, Nefl, and Becn1 are bottlenecks. Mutual regulatory connections between hubs and Alb and App (as two non-queried hubs) were determined. The findings indicate that garlic effect on the spleen and its mechanism may be involved mostly with App dysregulation.

Antimalarial Activities of (Z)-2-(Nitroheteroarylmethylene)-3(2H)-Benzofuranone Derivatives: In Vitro and In Vivo Assessment and ß-Hematin Formation Inhibition Activity.

A series of (Z)-2-(nitroheteroarylmethylene)-3(2H)-benzofuranones possessing nitroheteroaryl groups of nitroimidazole, nitrofuran, and nitrothiophene moieties was screened for antiplasmodium activity against a drug-sensitive strain (3D7 strain) and a multidrug-resistant (chloroquine [CQ] and pyrimethamine) strain (K1 strain) of Plasmodium falciparum. 5-Nitroimidazole and 4-nitroimidazole analogs were highly selective and active against resistant parasites, while 5-nitrofuran and 5-nitrothiophene derivatives were more potent against the 3D7 strain than against the K1 strain. Among the synthetic analogues, (Z)-6-chloro-2-(1-methyl-5-nitroimidazol-2-ylmethylene)-3(2H)-benzofuranone (compound 5h) exhibited the highest activity (50% inhibitory concentration [IC50], 0.654 nM) against the K1 strain and (Z)-7-methoxy-2-(5-nitrothiophen-2-ylmethylene)-3(2H)-benzofuranone (10g) showed the highest activity (IC50, 0.28 µM) against the 3D7 strain in comparison with the activities of CQ (IC50s of 3.13 and 206.3 nM against 3D7 and K1 strains, respectively). The more active compounds, with IC50s lower than 5 µg/ml (∼20 µM), were further studied for their cytotoxicity responses using KB cells. From these studies, 5-nitroimidazole, 4-nitroimidazole, and 5-nitrofuran analogues were shown to be cytotoxic against KB cells, while 5-nitrothiophene analogues were shown to have the least cytotoxic effects. To gain some insight into their potential contributing mechanisms of action, three derivatives, 10e, 10g, and 10h (from the nitrothiophene subgroup, possessing 6-methoxy, 7-methoxy, and 6,7-dimethoxy substituents, respectively, on their benzofuranone moieties), showing the least toxicity and highest selectivity indices were assessed for their ß-hematin formation inhibition activity. Compound 10g demonstrated the highest inhibition activity (IC50, 10.78 µM) in comparison with that of CQ (IC50, 2.63 µM) as the reference drug. Finally, these three analogues (10e, 10g, and 10h) were further evaluated for their in vivo activities against the Plasmodium berghei/albino mouse model (Peter's test). The tested analogues were shown to be active, reducing the percentages of erythrocytes that contained parasites by 53.4, 48.8, and 32.4%, respectively.

Effect of Zingiber officinale Roscoe rhizome (ginger) capsule on postpartum pain: Double-blind randomized clinical trial.

BACKGROUND: Postpartum pain contributes to increased irritability and excessive stress in the mother and consequently may inhibit successful breastfeeding, reduce a mother's ability to take care of her baby, and cause an imperfect mother-baby interaction. Evidence suggests the positive effect of ginger on reduction in uterus-associated pain. The objective of this study is to investigate the effect of ginger capsules on postpartum pain. MATERIALS AND METHODS: The present double-blinded, randomized, placebo-controlled trial was conducted in Mahdiyeh Educational Hospital, Tehran. One hundred and twenty-eight mothers having moderate-to-severe pain following vaginal delivery were included. The participants were divided into two groups (A and B). Interventions were performed every 8 h in 24 h. In the first intervention (2 h after the delivery), Group A received 500 mg of placebo capsules (containing chickpea flour) and Group B received 500 mg of Zintoma (ginger rhizome) capsules. In the second and third interventions, Group A received 250 mg placebo capsules and Group B received 250 mg Zintoma capsules. All participants received 250 mg capsules of mefenamic acid in each intervention in addition to ginger or placebo capsules. The pain severity was measured before and half an hour, an hour, and 2 h after each intervention. Statistical analysis was performed using the SPSS software version. 22. The Chi-square, Fisher's, and t tests and the GEE model were applied to assess the pain severity. RESULTS: The average pain severity was not statistically significant between the groups in the beginning of the intervention (P = 0.623). The mean score of pain significantly decreased within the duration of intervention in both groups (P < 0.001); however, the pain severity was significantly lower in the intervention group as compared to the control group at any point after the intervention (P = 0.006). CONCLUSION: Ginger can be used as an effective remedy for postpartum pain relief.

Immunological reactions by T cell and regulation of crucial genes in treated celiac disease patients.

AIM: To assess the immunological reactions and gene expression level in the celiac disease (CD) patients under a gluten-free diet (GFD). BACKGROUND: CD is an autoimmune disorder in genetic susceptible individuals and lifelong gluten free diet is the effective treatment method. It seems that treated patients will experience a normal life style though there are documents about some potential damages. METHODS: Gene expression profiles of treated CD patients and healthy samples were obtained from Gene Expression Omnibus (GEO) and compared to find the differentially expressed genes (DEGs). The identified DEGs were introduced in the network and gene ontology (GO) analysis. RESULTS: Ten differentially expressed genes (DEGs) including CCR2, IRF4, FASLG, CCR4, ICOS, TNFSF18, BACH2, LTF, PRM1, and PRM2 were investigated via network analysis. Seven clusters of biological processes (BP) were determined as the affected BP. PThe finding led to introduction of CCR2, IRF4, FASLG, CCR4, and ICOS as the potential immunological markers that are still active despite GFD in the treated CD patients. CONCLUSION: The results of this study indicated that the immune system is already active in treated CD patients despite GFD treatment and exposure to gluten causes potential immunological reactions in these patients.

Evaluation of long-term consumption of omeprazole disadvantages: a network analysis.

AIM: Evaluation of deregulated genes after long-term consuming of omeprazole via network analysis. BACKGROUND: Proton pump inhibitors (PPIs) are used to inhibit gastric high rate of acid secretion in patients. Omeprazole as a PPI is a common drug in this regard. Evaluation of long-term consumption of omeprazole is studied in the present study via its effects on the gene expression of "human coronary artery endothelial cells". METHODS: Net effect of the presence of omeprazole on gene expression profiles of "human coronary artery endothelial cells" was evaluated through data from gene expression omnibus (GEO). Results of protein-protein interaction (PPI) network analysis were assessed via biological process examination to find the critical deregulated genes after long-term consumption of omeprazole. RESULTS: "Negative regulation of muscle cell apoptotic process", "negative regulation of DNA binding", "telencephalon cell migration", "forebrain cell migration" "response to cadmium ion", "cell-cell recognition", "positive regulation of protein targeting to mitochondrion", and "central nervous system neuron development" were the clusters of biological processes that were associated to the long -term presence of omeprazole. The final critical deregulated genes were JAK2, PTK2, and NRG1. CONCLUSION: It can be concluded that cell cycle, proliferation, and apoptosis and several essential biological processes are affected and nervous system is a possible target related to the long-term consumption of omeprazole.

Molecular dynamics simulation and 3D-pharmacophore analysis of new quinoline-based analogues with dual potential against EGFR and VEGFR-2.

Epidermal growth factor and vascular endothelial growth factor-2 are important targets of tyrosine kinase for the treatment of various cancerous diseases. Combination of inhibition of both targets to produce synergy in the signal pathway is a critical approach to identify novel tyrosine kinase inhibitors. In this study, a series of new compounds derived from the 4-aminoquinoline as dual inhibitors were synthesized. The obtained results of cytotoxicity assay against human carcinoma cell lines indicated 0.8 µM for 4c against A549 showing its high efficiency in comparison to erlotinib. Pharmacophore modeling as a structure-based method was investigated on dual inhibitors and 4c which was compared with co-crystallized in the active site of EGFR and VEGFR-2. They have shown the same binding orientation as vandetanib, erlotinib and sorafenib. Molecular dynamics simulation results approved that Met769, Lys721, Asp1046, and Lys868 are key residues in two binding sites for dual activity. Ala1050 and Pro968 were identified as new amino acid interaction sites for dual inhibition. 4c showed more favorable stability than vandetanib in VEGFR-2 receptor for a 50 ns dynamic simulation. The high correlation between essential pharmacophoric features of designed compounds and lead inhibitors interactions provided a deeper insight into the structural basis of 4-aminoquinoline inhibition.

Assessment of Cytokine-Mediated Signaling Pathway Dysregulation in Arm Skin After CO2 Laser Therapy.

Introduction: Laser therapy is known as an efficient approach in dermatology surgery. CO2 laser therapy is a gold standard treatment in skin surgery. This study aimed to evaluate the interferons change after CO2 laser surgery Methods: Significant differentially-expressed genes (DEGs) of arm skin after 7 days of treatment by the CO2 laser relative to the controls are downloaded from Gene Expression Omnibus (GEO) and are included in the protein-protein interaction network via a STRING database (an application of Cytoscape software). The central DEGs were identified and enriched via gene ontology by using Clue GO software. Results: A network including 78 DEGs and 100 neighbors was constructed and STAT1, MX1, ISG15, OAS1, IFIT1, IRF8, OASL, OAS2, and RSAD2 as hubs and STAT1, PTPRC, MX1, IRF8, ISG15, IL6, RORC, SAMSN1, and IFIT1 as bottlenecks were introduced. The cytokine-mediated signaling pathway, interferon gamma signaling, hepatitis C, interferon alpha/beta signaling, and the type I interferon signaling pathway were identified as 5 clusters of biological terms which are related to the central nodes. Conclusion: It can be concluded that the cytokine-mediated signaling pathway is the major pathway that is dysregulated after laser application in the treated skin.

Pharmacophore Modeling, Synthesis, Scaffold Hopping and Biological ß- Hematin Inhibition Interaction Studies for Anti-malaria Compounds.

Backgound: Exploring potent compounds is critical to generating multi-target drug discovery. Hematin crystallization is an important mechanism of malaria. METHODS: A series of chloroquine analogues were designed using a repositioning approach to develop new anticancer compounds. Protein-ligand interaction fingerprints and ADMET descriptors were used to assess docking performance in virtual screenings to design chloroquine hybrid ß-hematin inhibitors. A PLS algorithm was applied to correlate the molecular descriptors to IC50 values. The modeling presented excellent predictive power with correlation coefficients for calibration and cross-validation of r2 = 0.93 and q2 = 0.72. Using the model, a series of 4-aminoquinlin hybrids were synthesized and evaluated for their biological activity as an external test series. These compounds were evaluated for cytotoxic cell lines and ß-hematin inhibition. RESULTS: The target compounds exhibited high ß-hematin inhibition activity and were 3-9 times more active than the positive control. Furthermore, all the compounds exhibited moderate to high cytotoxic activity. The most potent compound in the dataset was docked with hemoglobin and its pharmacophore features were generated. These features were used as input to the Pharmit server for screening of six databases. CONCLUSION: The compound with the best score from ChEMBL was 2016904, previously reported as a VEGFR-2 inhibitor. The 11 compounds selected presented the best Gold scores with drug-like properties and can be used for drug development.

Methanolic Extract from Aerial Parts of Artemisia Annua L. Induces Cytotoxicity and Enhances Vincristine-Induced Anticancer Effect in Pre-B Acute Lymphoblastic Leukemia Cells.

Background: Nowadays, remarkable attention has been drawn towards the effective therapeutic characteristic of natural products targeting cancerous cells. This study aimed to investigate the anti-cancer effect of Artemisia annua extract (AAE), a Chinese herbal medicine alone and in combination with a microtubule binding agent used in ALL treatment, vincristine (VCR), in B-Acute lymphoblastic leukemia (ALL) Nalm-6 and Reh cells. Materials and Methods: Cytotoxic activity of AAE and VCR was determined using MTT assay in Nalm-6, and Reh cell lines and synergism was evaluated using the CompuSyn software. Caspase 3 activity and Annexin/PI staining were performed for apoptosis assessment. The expression level of apoptosis-related genes, caspase 3, Bax and Bcl-2 were determined using real time-PCR. One-way ANOVA and post hoc Tukey multiple comparisons were used for statistical analysis. Results: Our findings revealed that a single administration of AAE exerted an anti-leukemic effect in both ALL-derived cells in a time- and dose-dependent manner. Interestingly, the growth inhibitory activity of the extract was more potentiated when combined with 0.1 and 1 nM VCR through caspase 3-dependent apoptosis. Moreover, real-time PCR analysis showed that VCR-induced cytotoxicity was augmented by AAE through alteration of Bax, and Bcl-2 mRNA expression. Conclusion: Overall, owing to the nontoxic nature of AAE and its explicit role in enhancing VCR effectiveness, our study provided new insight into the development of a novel combinatorial approach in ALL using natural herbs. The practical implication of the research requires further investigation through clinical trials, opening avenues for forthcoming treatment improvements.

Investigating the Effect of Melissa Officinalis on After-Pains: A Randomized Single-Blind Clinical Trial.

Introduction: Regarding high prevalence of postpartum pain and side-effects of pharmaceutical analgesics on maternal and neonatal health, the present study aimed to explore the effect of Melissa officinalis on after-pain among mothers hospitalized in Asgariyeh Hospital, Isfahan, 2016. Methods: In this single-blind clinical trial, 110 women with moderate to severe after-pain were divided into two M.officinalis and mefenamic acid groups by random allocation. Samples in the first group received 250mg of mefenamic acid and the second group received 395mg of M.officinalis oral capsules every 6hours for 24hours following childbirth. The primary outcome (After-pain) was assessed using a numeric 10-point scale before intervention, 1,2 and 3hours after the first intervention and every 6hours to 24hours after delivery for each of second, third and fourth interventions. Data were analyzed, using SPSS by independent t-test, Mann-Whitney and chi-square test. Results: The demographic and obstetric variables and after-pain severity before the intervention in both groups were homogenous. Pain intensity wasn't significantly different between the two groups during first and second hours after the first intervention, but there was a significant difference in the third hour, The severity of pain was significantly different between the two groups in different assessments including: an hour after the second, third and fourth intervention (P<0.05). A significant difference was found between mefenamic acid and M.officinalis in pain relief. Conclusion: M.officinalis can reduce the severity of after-pain, because it eliminates the need for pharmaceutical analgesics and works much better than mefenamic acid.

Isopentenyl Transferase (IPT) Gene Transfer to Perennial Ryegrass Through Sonication-Assisted Agrobacterium-Mediated Transformation (SAAT), Vacuum and Heat Treatment.

The successful introduction of isopentenyl transferase (IPT) gene into perennial ryegrass, cultivars Numan and Grassland using Agrobacterium tumefaciens via three explants (callus, seed and meristem tip) under three individual experiment was evaluated. In the first experiment, the calli were inoculated with LBA4404 Agrobacterium strain under vacuum, heat and in combination of both at 42 °C for 5 min followed by vacuum treatment (390 mm Hg pressure) for 15 min. Sonication-assisted Agrobacterium-mediated transformation (SAAT) was applied for seed and meristem tip transformation of perennial ryegrass for the first time. Results showed positive effects of heat treatment on transformation efficiency during Agro-infection in both cultivars. However, heat shock treatment was more effective in 'Grassland' than 'Numan' (14.2% vs 9.2%). In addition, high transformation efficiency of about 46.65% and 29.15% was observed using meristem tip explants of 'Grassland' and 'Numan' based on IPT and RD29A positive PCR results, respectively. Seed transformation efficiency in 'Grassland' and 'Numan' under SAAT method reached to 37.5% and 16.65%, respectively. Results of these experiments revealed that LBA4404 strain was more efficient than GV3101 in transformation of both perennial ryegrass cultivars. The DNA-blot analysis confirmed that a single T-DNA copy of the IPT gene was integrated into the genomic DNA of the positive transgenic T0 plants which obtained from callus and meristem tip explants of 'Grassland' after heat and SAAT treatment, respectively. Because monocots are not the host of Agrobacterium tumefaciens, this novel protocol can be used in further experiments on genetic transformation of perennial ryegrass cultivars.

Effects of high fat medium conditions on cellular gene expression profile: a network analysis approach.

AIM: This study aimed to evaluate high fat medium (HFM) effect on the gene expression profile of human Sk-hep1 cells and to determine critical differential proteins. BACKGROUND: There is a correlation between high fat diet (HFD), obesity, and non-alcoholic fatty liver disease. Despite wide range of investigations, understanding molecular mechanism of HFD effect on onset and progression of NAFLD warrants further examination. In this study, network analysis is applied to obtain a clear perspective about HFD effects and NAFLD. METHODS: Gene expression profiles of human Sk-hep1 cells treated with HFM versus controls were extracted from GEO. Data were analyzed by GEO2R where the significant and characterized DEGs were included in the PPI network. The top 10 nodes of query DEGs based on four centrality parameters were selected to determine central nodes. The common hub nodes with at least other one central group were identified as central nodes. Action map was provided for the introduced central nodes. RESULTS: Heterogeneous nuclear ribonucleoprotein family including A1, A2/B1, D, R, and D-like, and five proteins (PRPF40A, SRSF1, PCF11, LSM8, and HSP90AA1) were introduced as differential proteins. CONCLUSION: mRNA processing and several biological terms including hypoxia and oxidative stress, apoptosis, regulation of cell morphology and cytoskeletal organization, and differentiation of micro tubes were introduced as dysregulated terms under HFM condition.

Centaurea albonitens extract enhances the therapeutic effects of Vincristine in leukemic cells by inducing apoptosis.

Drug-induced toxicities and dose-related side effects are the major challenges in the conventional cancer therapy by the chemo drugs. On the other hand, herbal derivatives have obtained a great research interest in the field of therapeutic applications because of their more favorable specifications including less toxicity, cost-effective and more physiologically compatible than the chemical drugs. For this purpose, we evaluated methanolic extract prepared from Centaurea albonitens Turrill alone and in combination with Vincristine (VCR) for its potential cytotoxic effects in NALM-6, REH, NB4 and KMM-1 cell lines by using the various approaches. Centaurea genus is one of the current medicinal plants, which has used in traditional medicine, However, there are rare studies to examine its anticancer properties against hematologic malignant cells. In this study, we demonstrated Centaurea albonitens extract (CAE) induces cytotoxicity through G0/G1 phase arrest followed by apoptosis in a dose- and time- dependent manner, although with varying efficiency. Interestingly, normal cells didn't exhibit significant cytotoxicity after CAE treatment. Moreover, we found that low dose of CAE enhances anti-cancer effects of VCR in pre-B ALL cell lines (NALM-6 and REH). Further investigations validated synergistic anticancer activities of VCR and CAE through inducing apoptosis without significant cell cycle arrest. Taken together, our results demonstrated for the first time that the methanolic extract of Centaurea albonitens can be considered as a potential anticancer agent and/or an enhancer of chemotherapeutic sensitivity of VCR.

Traditional and modern aspects of hemorrhoid treatment in Iran: a review.

Hemorrhoidal disease is a prevalent anorectal condition which is generally not managed well with current pharmacologic interventions. However, in Iranian traditional medicine (ITM) there are numerous plants with hemorrhoid-healing properties. The present research assembled plants with hemorrhoid-healing properties in ITM; their related pharmacological effects, phytochemical constituents and mechanisms of action in the modern medicine were also gathered. For this purpose, leading ITM textbooks were searched for plants with hemorrhoid-healing effects. Further, in vitro, in vivo and clinical studies on the most cited species were considered using scientific databases. Studying ITM textbooks revealed 37 medicinal plants with hemorrhoid-healing effects. Among the mentioned herbal medicines, six species, including Allium ampeloprasum, Phyllanthus emblica, Aloe vera, Terminalia chebula, Vitis vinifera and Commiphora mukul, had the largest number of related pharmacological effects documented in scientific databases. These herbs from ITM should be considered as important resources for producing novel drugs for hemorrhoid treatment.

Cytotoxic and Apoptogenic Activity of Bryonia aspera Extract on Pre-B Acute Lymphoblastic Leukemia Cell Lines.

Background: The natural products and conventional chemotherapeutic drug combinations are believed to increase cure rates of anticancer treatment while reducing its toxicity. The current study investigates cytotoxic and apoptogenic effects of methanolic extract of Beryonia aspera, and also synergistic effects of this extract and Prednisolone on acute lymphoblastic leukemia cell lines. Materials and Methods: The under study populations were NALM-6 and REH cell lines. Cells were treated by Prednisolone and B. aspera extract alone and in combination. The effect of the drugs on survival and apoptosis were examined using MTT and flow cytometry, respectively. Moreover, the effects of the drugs on the mRNA expression levels of Bax and Bcl-2 were studied using RQ-PCR. Finally, both the transcriptional and enzymatic activity of caspase-3 were investigated by caspase-3 assay kit. Results: The B. aspera extract induced cell growth inhibition and triggered apoptosis in a dose- and time-dependent manner. Real-time PCR analysis of apoptotic target genes revealed that this agent shifted the ratio of the death promoter to death repressor genes via alteration of Bax and Bcl-2 expression levels. These changes resulted in caspase-3 activation, which led to DNA fragmentation and subsequent apoptosis. Our study has also demonstrated that the combined treatment of B. aspera extract with Prednisolone did not induce greater cytotoxic effect as compared to treatment series using either Prednisolone alone. Conclusion: Our study demonstrated that the B. aspera extract has anti-leukemic properties on BCP-ALL cell lines and could be regarded as a promising agent for the treatment of ALL.

Naghibione; A Novel Sesquiterpenoid with Antiplasmodial Effect from Dorema hyrcanum Koso-Pol. Root, a Plant Used in Traditional Medicine.

Some Dorema species are used in Persian traditional medicine. In the present study the total extract from the roots of Dorema hyrcanum Koso-Pol. was investigated for its in-vitro (pLDH assay) and in-vivo (Peters' 4-days suppressive test) antiplasmodial effects and assessed for cytotoxicity against the normal cell line MDBK (MTT test). The IC50 values for a chloroquine- sensitive (3D7) and a chloroquine- resistant (K1) strain of Plasmodium falciparum were 28.64 and 9.79 µg/mL, respectively. The inhibition percentage of the rodent parasite, Plasmodium berghei, on day 4 in mice was 77.9% and IC50 value on Madin-Darby bovine kidney cells (MDBK cells) was 59.84 µg/mL. The total extract was subjected to a bioassay-guided fractionation protocol based on the in-vivo model which resulted in the isolation of an acetophenon (compound 1), one new sesquiterpenoid; naghibione (compound 2) and two known sesquiterpenoid derivatives (compounds 3, 4). Their structures were elucidated by spectroscopic analysis, including 1D and 2D NMR experiments and ESI-MS. All compounds were evaluated for in-vivo antiplasmodial effect and the results revealed that naghibione showed good suppression activity, inhibiting 68.1 % of the parasite growth.

Antiplasmodial Activity and Cytotoxicity of Plants Used in Traditional Medicine of Iran for the Treatment of Fever.

Malaria is the most serious parasitic disease and one of the oldest recorded diseases in the world. Because of the resistance of malaria parasites to current drugs, it is necessary to discover new antiplasmodial drugs. Traditional medicine is one of the important sources of new antiplasmodial drugs. In this study, twenty methanolic extracts from different parts of sixteen medicinal plants used in traditional medicine of Iran for the treatment of "Nobeh fever" and/ or fever were screened for in-vivo antiplasmodial activity against Plasmodium berghei and cytotoxic effect on Madin-Darby bovine kidney cells (MDBK). Eleven species (55%) were found to have antiplasmodial activity. Methanolic extract from Rosa damascena Mill. reduced parasitemia by 57.7% compared to untreated control mice at intra-peritoneal (i.p.) injection doses of 10 mg/Kg per day for 4 days. This is the first report that mentioned in-vivo antiplasmodial activity of Rosa damascena Mill.