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Cytotoxic activities of methanolic crude extract of Stachys parviflora (Lamiaceae family) and its sub-fractions were primarily evaluated against human breast adenocarcinoma (MCF-7 and MDA-MB-231) and prostate (PC3) cell lines. The methanolic extract exhibited the highest activity, and was chosen for the isolation procedure. Four diterpenoid qui- nones, namely miltirone [1], tanshinone IIA [2], 1-hydroxy-tanshinone IIA [3], and cryptotanshinone [4] were isolated. Notably, this is the first report on the isolation and/or characterization of the mentioned diterpenoids from the Stachys genus. In this study, 1-hydroxy-tanshinone IIA [3] displayed the highest cytotoxicity among the isolated compounds. The mechanism of the cytotoxicity of methanolic extract and isolated compounds was further investigated by the utilization of propidium iodide staining (PI) assay. The results showed that the methanolic extract and 1-hydroxy-tanshinone IIA [3] enhanced DNA fragmentation in PC3 and MCF-7 cells. Moreover, the western blotting analysis demonstrated increasing and decreasing protein levels of Bax and Bcl2, respectively, and cleaved poly ADP-ribose polymerase (PARP). Further bioassay-guided phytochemical assessments of S. parviflora can be suggested as a promising approach for discovering potent bioactive secondary metabolites.

Background. In-stent restenosis (ISR) is an important clinical complication that occurs following stent implantation. The application of drug-eluting stents (DES) and even consumption of drugs such as antiplatelet agents and statins are not completely effective in reducing ISR risk. Since the number of these patients continues to rise, it is pivotal to detect patients who are at a higher risk of ISR. In addition, identification of biochemical markers of ISR could give the right perspective on choosing the proper strategy to treat these patients. Several pathophysiological pathways including oxidative stress (OS) are implicated in the progression of ISR. Hence, this study aimed to evaluate the association between oxidative/anti-oxidative markers and ISR. Methods. This was a case-control study which comprised 21 ISR, 26 NISR (non-ISR), and 20 healthy subjects. The serum levels of OS markers including malondialdehyde (MDA), thiol groups (GSH), total antioxidant capacity (TAC), and the activity of serum antioxidant enzymes such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assessed by colorimetric methods. The overall oxidative burden was assessed using a pro-oxidant-antioxidant balance (PAB) assay. Results. MDA levels were considerably higher in the ISR group when compared to healthy subjects ( P = 0.004 ). PAB also indicated significantly higher values in both ISR ( P < 0.001 ) and NISR ( P < 0.001 ) groups related to healthy subjects. No significant differences were observed between the studied groups regarding thiol levels, antioxidant enzyme activities, and TAC. Multinomial logistic regression analysis showed that elevated serum levels of MDA (OR: 1.028, 95% CI: 1.008-1.048; P = 0.006 ) and PAB (OR: 1.076, 95% CI: 1.017-1.139; P = 0.011 ) were significantly associated with higher ISR risk; however, increased values of TAC (OR: 0.990, 95% CI: 0.982-0.999; P = 0.030 ) were significantly associated with decreased ISR risk, while after adjustment for confounders, only SOD activity (OR: 0.0, 95% CI: 0.0-0.0; P < 0.001 ) and PAB value (OR: 1.866, 95% CI: 1.856-1.900; P < 0.001 ) showed association with ISR risk. Conclusion. According to the present findings, some oxidative and antioxidative markers like PAB and SOD activity showed the potential in the prediction of ISR risk.

IntroductionBackground: This study aimed to investigate the trehalose-induced alterations in serum expression levels of miRNAs associated with vascular inflammation in patients with coronary artery disease (CAD) in order to evaluate the effectiveness of intravenous (IV) trehalose administration in reducing arterial wall inflammation.Material and methodsMethods: This trial enrolled 14 men with a history of myocardial infarction (MI) and systemic inflammation. The patients were randomized in a 2:1 ratio to trehalose (15g/week, IV administration) (N=10) or placebo (equal volume 0.9% normal saline) (N=4) for a period of 12-weeks. The relative serum expression levels of miRNA-126, miRNA-24, miRNA-181b, miRNA-10a and miRNA-92a were assessed.ResultsResults: IV trehalose administration significantly increased the serum level of miRNA-24 (2.473±0.72; P=0.037) compared to the baseline, but did not alter the other miRNA serum levels. However, at the end of the study, miRNA-24 (4.58±0.99; P=0.002), miRNA-181b (4.08±1.75; P=0.009) and miRNA-10a (3.68±0.63; P=0.013) showed notably higher serum levels in the trehalose relative to the placebo group. Furthermore, the reduction (normalized to baseline) in serum levels of miRNA-126 (P=0.042) and miRNA-92a (P=0.001) were reduced in the trehalose versus placebo group, while the serum level of miRNA-24 (P=0.007) was notably higher than that in the placebo group.ConclusionsConclusion: Serum levels of miRNAs associated with vascular inflammation were altered following IV trehalose administration. The alterations in serum miRNAs, especially miRNA-126 and miRNA-24, could be considered as helpful biomarkers for the evaluation of trehalose potency in reducing arterial wall inflammation in patients with CAD.

Background: Obesity is one of the most important public health problems worldwide. Stem cells are primary cells capable of differentiating into different types of cells, and can be used to treat various diseases. Thymoquinone (TQ) has antioxidant, anti-inflammatory, anti-diabetic and anti-obesity properties. Herein, we aim to investigate the effect of TQ on the process of lipid differentiation in human adipose tissue-derived stem cells (ADSCs). Methods and Results: Quantification of cell surface markers was used by Flow-Cytometry and then, the effect of TQ on cell viability was assessed using alamarBlue test. ADSCs were then subjected to induction of differentiation in the presence of non-cytotoxic concentrations of TQ (6.25, 12.5 and 25 μg/mL). ADSCs differentiation was assessed using Oil-Red staining technique. Moreover, expression of PPARγ (Peroxisome proliferator activated receptor γ) and FAS (Fatty Acid Synthetase) proteins was evaluated using Western blotting analysis. Flow-cytometric analysis demonstrated the expression of CD44 and CD90 markers as mesenchymal stem cells markers on the surface of ADSCs. At concentrations≤100 μg/mL of TQ, no significant difference in cell viability of ADSCs was observed compared to the control. Adipocyte differentiation process significantly decreased at 25 μg/mL (PConclusions: This study showed that TQ can reduce the process of differentiation of fat stem cells into fat cells and might be considered as an anti-obesity compound.

Background: Flaxseed (Linum usitatissimum) is an oil-based seed that contains high amounts of alpha-linolenic acid, linoleic acid, lignans, fiber and many other bioactive components which is suggested for a healthier life. Nowadays, flaxseed is known as a remarkable functional food with different health benefits for humans and protects against cardiovascular disease, diabetes, dyslipidemia, obesity and altogether metabolic syndrome. Methods: To review the bioactive components of flaxseed and their potential health effects, PubMed and Scopus were searched from commencement to July 2019. Keywords including: "flaxseed", "Linum usitatissimum", "metabolic syndrome", "obesity", "inflammation", "insulin resistance", "diabetes", "hyperlipidemia" and "menopause" were searched in the databases with varying combinations. Conclusions: Consumption of flaxseed in different forms has valuable effects and protects against cardiovascular disease, hypertension, diabetes, dyslipidemia, inflammation and some other complications. Flaxseed can serve as a promising candidate for the management of metabolic syndrome to control blood lipid levels, fasting blood sugar, insulin resistance, body weight, waist circumference, body mass and blood pressure.

Cinnamon (Cinnamomum verum and C. cassia) is a medicinal plant, widely-used as a culinary spice. It possesses various therapeutic effects and can slow down the progression of neurological disorders impressively. In this article, the effects of hydro-alcohol extract and essential oil of C. verum and C. cassia and its main bioactive component cinnamaldehyde, has been examined on 6-OHDA-exposed PC12 cells as an in vitro model of Parkinson's disease. The cytotoxicity and cell apoptosis has been induced by 6-OHDA in PC12 cells. The protective effect was determined by measuring cell viability, the amount of reactive oxygen species (ROS), and apoptosis. Cell viability and apoptosis were assessed using resazurin assay, flow cytometry of propidium iodide (PI) stained cells, and western blot analysis. 6-OHDA resulted in the death and apoptosis of cells while, pretreatment with the extract and essential oil of C. verum and C. cassia at 20 µg/ml and cinnamaldehyde at 5 and 10 µM for 24 h could significantly increase the viability (p

Alpha-bisabolol (α-bisabolol), an unsaturated monocyclic sesquiterpene alcohol, is known as one of the "most-used herbal constituents" in the world. Various therapeutic and biological properties of α-bisabolol in preventing oxidative stress, inflammatory disorders, infections, neurodegenerative diseases, cancers, and metabolic disorders have been reported. In this review, we evaluated new findings regarding the molecular mechanisms of α-bisabolol published from 2010 until 2021 in PubMed, Science Direct, and Scopus. The antioxidant mechanism of α-bisabolol is mainly associated with the reduction of ROS/RNS, MDA, and GSH depletion, MPO activity, and augmentation of SOD and CAT. Additionally, upregulating the expression of bcl-2 and suppression of bax, P53, APAF-1, caspase-3, and caspase-9 activity indicates the anti-apoptotic effects of α- bisabolol. It possesses anti-inflammatory effects via reduction of TNF-α, IL-1β, IL-6, iNOS, and COX-2 and suppresses the activation of ERK1/2, JNK, NF-κB, and p38. The antimicrobial effect is mediated by inhibiting the viability of infected cells and improves cognitive function via downregulation of bax, cleaved caspases-3 and 9 levels, β-secretase, cholinesterase activities, and upregulation of bcl-2 levels. Finally, due to multiple biological activities, α-bisabolol is worthy to be subjected to clinical trials to achieve new insights into its beneficial effects on human health.

Due to many therapeutic effects, Ginger (Zingiber officinale) is the most widely used spice around the world, including in Iran. Due to its potent anti-inflammatory and antioxidant effects, ginger may protect against neurodegenerative disorders. Here, we investigated the effects of 6-gingerol (the main bioactive compound in ginger) on 6-hydroxydopamine (6-OHDA)-induced cell death in PC12 cells. Cell viability, cell apoptosis, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and survivin expression were measured using resazurin, propidium iodide (PI) and flow cytometry, and western blot analysis. 6-OHDA (100 μM) reduced the cell viability, increased apoptosis, increased the active form of SAPK/JNK, and decreased survivin protein level in PC12 exposed cells in a dose and time-dependent manner. Pretreatment with 6-gingerol significantly increased the viability and reduced apoptosis (2.5 and 5 µM). Also, pretreatment with 6-gingerol at 2.5 and 5 µM increased survivin whereas, 6-gingerol at 2.5 µM reduced (P-SAPK/JNK):(SAPK/JNK) levels to a level near that of the related control. According to the results, 6-gingerol blocks 6-OHDA-induced cell damage by suppressing oxidative stress and anti-apoptotic activity. Thus, 6-gingerol may process beneficial protective effects in slowing the progression of Parkinson's disease.

Neuroprotection using compounds with dual functions of anti-apoptotic and antioxidant effects fight against neurodegeneration. Vitamin K2 acts as a cofactor in many biochemical pathways, including sphingolipid synthesis in the nervous system, which is involved in many cellular events, including proliferation, differentiation, cellular communication, and alteration. This study aimed to investigate the protective effects of vitamin K2 in PC12 cells as an in vitro model of Parkinson's disease. The protective effects of vitamin K2 against 6-OHDA-induced apoptosis in PC12 cells were assessed using resazurin for viability, DCF-DA for ROS level, DTNB for glutathione level, flow cytometry for sub G1, and western blot analysis for detecting bax and pro-caspase-3 expression level. The results showed that 6-OHDA significantly decreased cell viability, glutathione and pro-caspase-3 levels, and increased ROS, the amount of bax in PC12 cells, while the pretreatment with 5 μM vitamin K2 significantly decreased the cell death induced by 6-OHDA. Generally, the results may present a new insight about the potential protective action of vitamin K2 against the progression of Parkinson's disease. Further studies may warrant the use of vitamin K2 as an antioxidant and anti-apoptotic agent in slowing nerve injury in neurodegenerative disease, particularly in Parkinson's disease.

Background: In this study, the essential oil composition and cytotoxic activities of five Artemisia species were determined. Methods: The collected plants were water-distilled separately to obtain oils which were then subjected to gas chromatography (GC) and gas chromatography/mass spectrometry GC/MS analyses to identify their compositions. Cancer cells were exposed to different concentrations of samples and cell viability was measured using AlamarBlue® assay. Apoptotic cells were analyzed by propidium iodide (PI) staining and flow cytometry. Results & Conclusion: To study the amount of pro-apoptotic proteins and the apoptosis mechanism, Western blot method was used. Although all samples were cytotoxic at the highest concentration, the oil of A. kulbadica showed the strongest activity among other plants. Carvacrol (IC50 21.11 μg/ml) had the most cytotoxic effects among other components. Carvacrol, 1,8-cineole and 4-terpineole caused an increase in the amount of Bax protein and cleaved peroxisome proliferator-activated receptors (PPAR) and caspase proteins in DU 145 cells.

Background: Crocin is a known compound with the antioxidant and anti-inflammatory properties which may help to reduce the progression of neurological disorders. In this study, we aimed to investigate the protective effects of crocin on beta-amyloid peptide Aβ (1-40) and hydrogen peroxide (H2O2) induced neurotoxicity in PC12 cells. Methods: PC12 cells were pretreated with crocin and donepezil (5 and 10 μM) for 2 h and then treated with Aβ (1-40) (25 μM) for 24 h. In parallel, after pretreatment with crocin (5 and 10 μM) and donepezil (5 and 10 μM) for 24 h, cells were treated with H2O2 (800 μM) for 4 h. Finally, the cell viability and intracellular reactive oxygen species (ROS) generation were evaluated using Alamar- Blue® and 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. The western blot test was done to compare the protein level of phospho SAPK/JNK, SAPK/JNK, PI3 Kinase P85, Phospho-PI3 Kinase P85, caspase-3 and cytochrome c) cyt c). Results: Crocin and donepezil could significantly decrease the Aβ toxicity and ROS level. While treatment with Aβ increased Cyt c release from mitochondria to cytosol, cleaved form of caspase-3 (17 kDa) and activated form of SAPK/JNK p44/4 decreased the activated form of PI3 Kinase P85 protein, indicating that crocin could significantly block the apoptosis initiated with Aβ. Conclusions: According to the results, crocin could be a promising candidate for further evaluations against the development of Alzheimer's disease through mitogen-activated protein kinases (MAPK) and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling (PI3 K/AKT) pathways.

Breast cancer is the most common malignancy in women worldwide. Unfortunately, current therapeutic methods are not completely efficient. Hence, combination therapy with medicinal plants has attracted several kinds of research. In the current study, we aimed to investigate the apoptotic and anti-cancer effect of Parthenolide in combination with Epirubicin in the MDA-MB-468 breast cancer cell line. In this study, the anti-proliferative and pro-apoptotic effect of Parthenolide in combination with Epirubicin and without it, in the MDA-MB-468 cell line have been assessed by MTT test, Hoescht staining and flow cytometry methods. Our outcomes showed that Parthenolide treatment in the present of Epirubicin led to a decrease in the minimum toxic concentration of Parthenolide and Epirubicin in comparison with individual treatments. Then, to achieve a likely molecular mechanism of mentioned drugs Bax and Bcl2 expression level evaluated by Real-time PCR and subsequently, Western blotting has been estimated the protein level of Caspase 3. Our data indicated that the treatment of cells with Parthenolide led to up-regulation of Bax and downregulation of Bcl2 at mRNA level. Moreover, Parthenolide treatment led to the obvious alternation of Caspase3 protein level. These results indicated that Parthenolide in combination with Epirubicin have significant cytotoxicity due to targeting the main regulators of apoptosis. Hence, according to lack of cytotoxicity of Parthenolide on normal cells that lead to reduction of drug side effects, it could be suggested as an adjuvant therapy with Epirubicin after complementary research on animal model and clinical trial.

The purpose of this study is cytotoxicity-guided isolation of the petroleum ether fraction from the roots of Salvia atropatana for the first time, which has shown to growth inhibition and apoptosis induction in MCF-7 and PC3 cells. Bioassay-guided isolation method was conducted for finding compounds with highest cytotoxicity. Different extracts were prepared from the roots of Salvia atropatana. All extracts were tested for their cytotoxic activity against three cancer cell lines (PC3, MCF-7, and MDA-MB-231). The most cytotoxic extract was chosen for further isolation by column chromatography and HPLC. The chemical structures were determined by spectroscopic methods including 1D and 2D NMR. From the petroleum ether extract, four abietane-type diterpenoids, including a new abietane-type diterpenoid, named atropatanene (1), together with three known diterpenoids, 7α-acetoxyroyleanone (2), and a mixture of two isomers, saprorthoquinone and aethiopinone (3+4), were isolated. The latter exhibited substantial cytotoxicity with IC50 value of 8.73 μg/ml against PC3 cells and led to an increasing number of cells in the subG1 region and an increase in the amount of Bax and cleavage of PARP protein, indicating apoptotic cell death. Owing to its numerous biological activities, Salvia species could be represented as a natural potential source against several cancer cell lines.

Background Besides the first-line medication for the treatment of type 2 diabetes, the growth inhibitory activity of metformin alone or in combination with conventional chemotherapeutics has been addressed on a panel of cell lines. In this study, we investigated the cytotoxicity and apoptosis of the metformin alone and in combination with dacarbazine in Raji and Ramos lymphoma cell lines. Methods Cell viability and apoptosis measured using resazurin assay, flow cytometry of PI stained cells and western blot analysis. Results Metformin showed synergistic cytotoxic effects in combination with dacarbazine, reduced cell viability, and increased apoptosis in Raji and Ramos lymphoma cells in comparison with the use of each drug alone. The activation of MAPK and SAPK/JNK (P-SAPK/JNK) were shown in both cells. Conclusion Overall, the result verified the synergistic effect of the metformin-dacarbazine combination, which has the value in reducing the chemotherapeutic agent dose, adverse effect and the burden of treatment for the community and patients.

Alzheimer’s is an age-related disease with a hallmark of progressive loss of memory formation followed by a damage in the brain function due to the neural degeneration and extracellular beta-amyloi...

Auraptene (AUR) is a bioactive antioxidant coumarin with valuable pharmacological properties; however, poor water solubility is a substantial issue for the topical application of AUR. Therefore, we sought to prepare solid lipid nanoparticles (SLNs) containing AUR (AUR-SLNs) to enhance its anti-inflammatory effect. The prepared formulations were optimized by applying the response surface method. Furthermore, AUR-SLNs were compared to conventional cream containing AUR regarding both the permeation rate of the nanoparticles and the anti-inflammatory effect through both in vitro and in vivo studies. Particle size and entrapment efficiency of the optimized formulation were 140.9 ± 3.55 nm and 84.11% ± 3.30, respectively. Transmission electron microscopy revealed that the nanoparticles were spherical. Differential scanning calorimetry (DSC) analysis demonstrated no drug-lipid incompatibility in the formulation. Fourier transform-infrared spectroscopy (FTIR) spectra revealed the amorphous state of AUR and the encapsulation of this agent in SLNs. The in vitro permeation studies exhibited that AUR-SLNs could significantly enhance cutaneous uptake of AUR and skin targeting. The anti-inflammatory and histopathological studies exhibited no significant differences between AUR-SLNs and indomethacin. AUR-SLNs did not induce skin sensitization in guinea pigs. The results suggest that SLNs could be appropriate carriers for the topical application of AUR as a natural anti-inflammatory agent.

Parkinson's disease is a neurodegenerative disorder which accompanied with cognitive decline, chorei form moves and behavioral difficulties. Oxidative stress which promote the apoptotic cell death are responsible for neurodegeneration in Parkinson. The purpose of this study is to evaluate the protective effects of betanin against toxicity and oxidative damage induced by 6-hydroxydopamine (6-OHDA) and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Parkinson's cell damage. PC12 cells pretreated with betanin (1-200 µM) for 24 h, and exposed to either 6-OHDA (100 µM) or H2O2 (150 µM) for 24 h. Cell survival and intracellular reactive oxygen species (ROS) production analyzed by resazurin and DCF-DA assay. The anti-apoptotic effects of betanin in PC12 cells were studied using flow cytometry of PI stained cells. Also, western blot analysis of survivin, Cyt c, Phospho SAPK/JNK, SAPK/JNK, Phospho-PI3 kinase P85, PI3 kinase P85 was performed for detection of apoptosis. Betanin (1-200 µM) significantly decreased the 6-OHDA and H2O2 cytotoxicity also attenuated the ROS level. Cell apoptosis significantly increased after 6-OHDA (100 µM) treatment, compared to the control. However, pretreatment with betanin (20 and 50 µM), protected against apoptosis. Western blot analysis of PC12 cells showed that 100 µM 6-OHDA could increase the proteins involved in apoptosis signaling and betanin (20 and 50 µM), could decrease the apoptosis. The results show that betanin has antioxidant and anti-apoptotic effects and may have the ability to prevent or delay the progress of neural death in Parkinson's disease.

Salvia is the largest genus of the Lamiaceae family, with over 900 species in the world which about 60 species are distributed in Iran, 17 of them are endemic. In Iran, Salvia species have been used to treat various diseases with a wide spectrum of pharmacological activity in vitro and in vivo. The present review summarizes the phytochemistry and pharmacology of medicinal Iranian Salvia species in order to describe their therapeutic potential for a range of diseases. . Phytochemical investigations reveal that the Iranian Salvia has a varied range of metabolites including terpenoids, flavonoids and phenolic acids. The most important pharmacological activities are antidiabetic, antioxidant, antimicrobial, cytotoxic and anti-inflammatory. Iranian Salvia traditionally used as carminatives, analgesics, digestive aids, antiseptics, sedative, anxiolytic, hypnotic, pain reduction and antidiabetic. Among the endemic species, the most interesting for human health are treating a variety of diseases.

The widespread use of plants as accessible anticancer agents leads to the identification of many natural source chemotherapeutic agents. Scutellaria one of the popular genus of flowering plants has been used for various human illnesses for thousands of years. Scutellaria has anti-metastatic, anti-proliferative, anti-invasion, anti-angiogenic and apoptosis effects in vitro as well as in vivo. Despite numerous reports on the cytotoxic-antitumor activity of the plant, there are still some issues need further consideration. Issues such as unjustified interpretations, lack of attention to the pharmacokinetics profile and weak study design may affect the final decision about the use of plants as anticancer agents and possibly needs reconsideration. In this review, we have summarized the potential health benefits of Scutellaria and its active components also the underlying mechanism of cytotoxicity and antitumor activity. Meanwhile we have discussed concerns may interfere with the precise conclusion.

A phytochemical investigation of the root extracts of Salvia tebesana Bunge led to the isolation of two new diterpenoids, tebesinone A (1) and tebesinone B (2), along with two known compounds, aegyptinone A (3) and aegyptinone B (4). The structures were established by spectroscopic analysis including 1D and 2D NMR and HRESIMS. The cytotoxic activities of the crude extracts and isolated compounds were evaluated against MCF-7, B16F10, PC-3 and C26 human cancer cell lines, in which compounds 2 and 3 showed significant cytotoxic activities (IC50 2.1–10.3 μM).

Scutellaria comprises many species traditionally used for cognitive and neurological conditions. In vitro and in vivo studies have supported the value of bioactive compounds of the genus Scutellaria for CNS disorders such as Alzheimer, cerebral ischemia, depression and anxiety. In particular, the effects of plants belonging to the genus Scutellaria and their components are detailed on cognitive ability such as memory, attention and learning. In this review, the pharmacology of CNS effect and the related molecular mechanisms of the plants belonging to the genus Scutellaria and active constituents have been discussed.

In vitro antiproliferative activities of some pyrimido[4,5-e][1,3,4]oxadiazine and [1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine derivatives were examined in human malignant cancer cell lines. All synthesized compounds inhibited the growth of malignant cells in a dose dependent manner, but among them 1,5,7-trimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine and [(1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazin-7-yl)sulfanyl]acetonitrile, both with triazole moiety, were found to be more effective than other compounds; they also induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to controls, indicating that apoptotic cell death is involved in toxicity they induce. The results showed that compounds with triazole moiety fused to pyrimido[4,5-e] [1,3,4]oxadiazine derivatives are more active than those bearing chlorine or pyrrolidine groups at C-7 position.

Modern medicine owes much to the invaluable heritage of the practices of past generations and their achievements that have now become medical rules. In the case of vaccination, there is evidence that the nomads of Baluchistan (Southeast Iran) demonstrated natural immunization against cowpox, a practice that was later introduced to the medical community by Edward Jenner. Although the discoveries of scientists cannot be ignored, they are certainly based on the traditional and indigenous experiences that have been transferred from generation to generation until reaching us.

Clinical use of zoledronate is accompanied by osteonecrosis of the jaw but the pathogenesis is not well understood. We assumed that zoledronate may have cytotoxicity against stem cells of the oral cavity and in this way helps to initiate or promote osteonecrosis. Dental pulp stem cells (DPSCs) and gingival fibroblasts (GFs) were isolated from volunteers who were undergoing a third molar extraction. The proliferation of DPSCs and GFs was evaluated using the thiazolyl blue tetrazolium bromide assay. The effect of zoledronate on apoptosis was determined by propidium iodide staining and Western blotting analysis. Incubation with zoledronate for 72 h and 7 days significantly decreased proliferation of DPSCs and GFs at concentrations of more than 0.4 μmol/L (p < 0.001). The IC50 of zoledronate was lower for DPSCs than for GFs (0.92 versus 3.5 μmol/L for 7 days of treatment). After 72 h of treatment with zoledronate, the percentage of apoptotic DPSCs significantly increased, which was accompanied by an increased level of pro-apoptotic proteins caspase-3 and Bax and decreased the level of the anti-apoptotic protein Bcl-2. In conclusion, zoledronate has anti-proliferative and pro-apoptotic effects in DPSCs. These effects may be involved in promoting zoledronate-induced osteonecrosis and suggest an unfavorable impact of this drug on regenerative potentials of the body stem cells.

Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec). We evaluated their inhibitory activities against pan HDAC and HDAC1 isoform. Four compounds (8f, 8q, 8r and 8u) showed significant cytotoxicity with IC50 in the range of 0.53–57.59 μM on cancer cells and potent pan-HDAC inhibitory activity (consists of HDAC isoenzymes) (IC50 = 0.80–14.81 μM) and HDAC1 inhibitory activity (IC50 = 0.47–0.87 μM and also, had no effect on Huvec (human normal cell line) viability (IC50 > 100 μM). Among them, 8u displayed a higher potency for HDAC1 inhibition with IC50 value of 0.47 ± 0.02 μM near equal to the reference drug Entinostat (IC50 = 0.41 ± 0.06 μM). Molecular docking studies and Molecular dynamics simulation of compound 8a displayed possible mode of interaction between this compound and HDAC1enzyme.

Artemisiais an important genus of Iranian flora. Cytotoxic activities for some species of the genus have already been reported. In this study, we have investigated the cytotoxic effects ofn-hexane, CH2Cl2, EtOAc, EtOH, and EtOH/H2O (1 : 1) extracts ofA. turanicaKrasch. on two human leukemic cancer cell lines (K562 and HL-60) and J774 as normal cells using alamarBlue (resazurin) assay. PI staining of the fragmented DNA and western blot analysis were used to evaluate the possible apoptotic effect of the extract. The CH2Cl2extract ofA. turanicashowed the most antiproliferative effect on cancer cells among all tested extracts with IC50values of 69 and 104 μg/mL on K562 and HL-60 cells, respectively, whereas the normal cells were not affected significantly by this extract. Sub-G1 peak in the flow cytometry histogram of the cells treated with CH2Cl2extract ofA. turanicaand cleavage of PARP protein confirmed the induction of apoptosis with CH2Cl2extract. Taken together, the findings of the present work suggest the anticancer potential of CH2Cl2extract ofA. turanicaon human leukemic cancer cell lines.

Islamic medicine is regarded as a comprehensive medical school with a long, glorious and worldwide reputation. Some of the physicians of this school are famous worldwide and have contributed valuable services to the scientific world. Given the dramatically increasing prevalence of cancer and the relative inefficacy of current medications, there is a great demand for the introduction of effective therapeutic approaches. To this end, integration of traditional medicine with modern medical treatments represents a promising option. In this essay, methods of diagnosis and treatment of cancer have been mentioned from the viewpoint of five famous physicians before the Mongolian attack who used Islamic medicine, namely Rhazes, Akhaveyni, Ahwazi, Avicenna and Jorjani. The ideas discussed dates back to a period between the eighth and fourteenth centuries.

Taxodione, a diterpenoid from the roots of Salvia chorassanica Bunge, possesses cytotoxic, apoptotic, and antimicrobial activity. This study was designed to investigate the protective effects of taxodione on serum/glucose deprivation-induced ischemic injury in PC12 cells and related mechanisms. In an in vitro model of ischemia, PC12 cells were exposed to serum and glucose deprivation for 6 and 18 h. The protective effects of the methanol extract of S. chorassanica and taxodione were assessed using alamarBlue(®) assay. Intracellular ROS production was measured by fluorimetry using 2',7'-dichlorofluorescin diacetate (DCFH-DA). The levels of PARP, Bcl-2, and Bax proteins were detected after western blot analysis. It was shown that taxodione (0.2-1.5 μM) significantly increased cell viability in a dose-dependent manner after ischemic insult. Taxodione has antioxidant activity and protects PC12 cells against oxidative stress-induced apoptotic cell death. Meanwhile, pretreatment with taxodione significantly induced an increase in Bcl-2 and a decrease in Bax protein level. The results of this study confirmed the protective effect of taxodione in serum/glucose deprivation-induced ischemic injury and the putative role of apoptosis as a underling mechanisms. Thus, it would be fair to consider taxodione as a promising ingredient of S. chorassanica for the expansion on novel class of anti-ischemic agents.

In the present study, the cytotoxic and apoptogenic properties of hydroalcoholic extract and ethyl acetate (EtOAc),n-butanol, and water fractions (0–800 μg/mL) ofViola tricolorwere investigated in Neuro2a mouse neuroblastoma and MCF-7 human breast cancer cells. In addition, antiangiogenic effect of EtOAc fraction was evaluated on chicken chorioallantoic membrane (CAM). The quality of EtOAc fraction was also characterized using high performance liquid chromatography (HPLC) fingerprint. Cytotoxicity assay revealed that EtOAc fraction was the most potent among all fractions with maximal effect on MCF-7 and minimal toxicity against normal murine fibroblast L929 cells. Apoptosis induction by EtOAc fraction was confirmed by increased sub-G1 peak of propidium iodide (PI) stained cells. This fraction triggered the apoptotic pathway by increased Bax/Bcl-2 ratio and cleaved caspase-3 level. Moreover, treatment with EtOAc fraction significantly decreased the diameter of vessels on CAM, while the number of newly formed blood vessels was not suppressed significantly. Analysis of quality of EtOAc fraction using HPLC fingerprint showed six major peaks with different retention times. The results of the present study suggest thatV. tricolorhas potential anticancer property by inducing apoptosis and inhibiting angiogenesis.

Bioassay-guided fractionation of Salvia chorassanica Bunge roots for the first time led to the isolation of taxodione, ferruginol and 6-hydroxysalvinolone. Cytotoxic studies revealed that all compounds exhibited high cytotoxic activity against apoptosis-proficient HL-60 and apoptosis-resistant K562 cells, with IC 50 values ranging from 7.7 to 60.3 μM with much less cytotoxic effects on normal human lymphocytes. Sub-G1 peak in flow cytometry histogram of treated cells by S. chorassanica and all pure compounds in comparison with control was induced and DNA fragmentation confirmed the cytotoxicity and apoptosis. Taxodione, ferruginol and 6-hydroxysalvinolone (2.5 and 5.0 μM) also enhanced expression of the pro-apoptotic protein Bax, cleaved caspase-3 and cleaved PARP after treatment for 48 h. Collectively, these findings suggest cytotoxic and apoptotic effectiveness of taxodione, ferruginol and 6-hydroxysalvinolone against the leukemic K562 and HL-60 cancer cells.

The compound (IVb) is tested for activity against the cancer cell lines HeLa, MCF-7 and HepG2.

The compound (IXd) is tested on the cancer cell lines MCF-7 and HepG2 and decreases viability of the cells in a concentration-dependent manner.

Scutellaria lindbergii (Lamiaceae) is Iranian species of Scutellaria. Cytotoxic properties of total methanol extract of S. lindbergii and its fractions were investigated on different cancer cell lines including AGS, HeLa, MCF-7, and PC12. Meanwhile the role of apoptosis was explored in this toxicity. Malignant and non-malignant cells were cultured in DMEM medium and incubated with different concentrations of plant extracts. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). S. lindbergii inhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions of S. lindbergii, the methylene chloride fraction was found to be more toxic compared to other fractions. S. lindbergii-induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in S. lindbergii-induced toxicity. In conclusion, S. lindbergii exerts cytotoxic effects in different cancer cell lines in which apoptosis plays an important role. Thus S. lindbergii could be considered as a potential chemotherapeutic agent in cancer treatment.