This study investigates the anticancer potential of ethanol and ethyl acetate extracts from Avicennia marina leaves against breast (MCF-7), ovarian (OVCAR3), and cervical (HeLa) cancer cell lines through in vitro and in silico approaches. Phytochemical analyses revealed high phenolic and flavonoid contents, with ethanol extracts showing greater yields. In vitro assays demonstrated that ethanol extracts significantly inhibited MCF-7 proliferation via S-phase cell cycle arrest, while ethyl acetate extracts induced apoptosis in HeLa and OVCAR3 cells. Western blot analysis confirmed upregulated pro-apoptotic proteins (BAX, cleaved caspases-1, -3, -7) and downregulated anti-apoptotic proteins (BCL-2, pro-caspases). In silico molecular docking and dynamics simulations identified key compounds, including alpha amyrin, stigmasterol, and vitamin E, with strong binding affinities to apoptosis-related receptors (e.g., TNFR1, PPAR gamma, Adenosine A1). Bioavailability assays indicated favorable lipophilicity but poor aqueous solubility, suggesting the need for advanced delivery systems. These findings highlight A. marina as a promising source of anticancer compounds, warranting further in vivo and formulation studies.

Nowadays, major attention is being paid to curing different types of cancers and is focused on natural resources, including oceans and marine environments. Jellyfish are marine animals with the ability to utilize their venom in order to both feed and defend. Prior studies have displayed the anticancer capabilities of various jellyfish. Hence, we examined the anticancer features of the venom of Cassiopea andromeda and Catostylus mosaicus in an in vitro situation against the human pulmonary adenocarcinoma (A549) cancer cell line. The MTT assay demonstrated that both mentioned venoms have anti-tumoral ability in a dose-dependent manner. Western blot analysis proved that both venoms can increase some pro-apoptotic factors and reduce some anti-apoptotic molecules that lead to the inducing of apoptosis in A549 cells. GC/MS analysis demonstrated some compounds with biological effects, including anti-inflammatory, antioxidant and anti-cancer activities. Molecular docking and molecular dynamic showed the best position of each biologically active component on the different death receptors, which are involved in the process of apoptosis in A549 cells. Ultimately, this study has proven that both venoms of C. andromeda and C. mosaicus have the capability to suppress A549 cells in an in vitro condition and they might be utilized in order to design and develop brand new anticancer agents in the near future.

Sea cucumber extracts and their bioactive compounds have the potential for stem cell proliferation induction and for their beneficial therapeutic properties. In this study, human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs) were exposed to an aqueous extract of Holothuria parva body walls. Proliferative molecules were detected using gas chromatography-mass spectrometry (GC-MS) analysis in an aqueous extract of H. parva. The aqueous extract concentrations of 5, 10, 20, 40, and 80 µg/mL and 10 and 20 ng/mL of human epidermal growth factor (EGF) as positive controls were treated on hUC-MSCs. MTT, cell count, viability, and cell cycle assays were performed. Using Western blot analysis, the effects of extracts of H. parva and EGF on cell proliferation markers were detected. Computational modeling was done to detect effective proliferative compounds in the aqueous extract of H. parva. A MTT assay showed that the 10, 20, and 40 µg/mL aqueous extract of H. parva had a proliferative effect on hUC-MSCs. The cell count, which was treated with a 20 µg/mL concentration, increased faster and higher than the control group (p < 0.05). This concentration of the extract did not have a significant effect on hUC-MSCs’ viability. The cell cycle assay of hUC-MSCs showed that the percentage of cells in the G2 stage of the extract was biologically higher than the control group. Expression of cyclin D1, cyclin D3, cyclin E, HIF-1α, and TERT was increased compared with the control group. Moreover, expression of p21 and PCNA decreased after treating hUC-MSCs with the extract. However, CDC-2/cdk-1 and ERK1/2 had almost the same expression as the control group. The expression of CDK-4 and CDK-6 decreased after treatment. Between the detected compounds, 1-methyl-4-(1-methyl phenyl)-benzene showed better affinity to CDK-4 and p21 than tetradecanoic acid. The H. parva aqueous extract showed proliferative potential on hUC-MSCs.

Abstract Avicennia marina, the gray mangrove, is an herbal source of bioactive anticancer compounds. In the current study, the anticancer activity of ethanol and ethyl acetate extracts of A. marina leaves were aimed to be evaluated. To do that, some assessments including phytochemical, GC-MS, cell proliferation, viability, cycle, western blot and computational modeling analysis were performed for evaluation of their anticancer activity on breast, ovarian and cervical cancer cell lines. The results demonstrated ethanol and ethyl acetate extracts of A. marina leaves had high phenolic and flavonoid contents. In GC-MS analysis of the extracts, anticancer compounds were detected. Moreover, the MTT and cell viability assays showed anti-proliferative activity and decrease in cell viability after treatment of MCF-7, OVCAR3, and HeLa cell lines with both extracts, separately. In addition, in the cell cycle analysis the cell cycle arrest was observed in MCF-7. Moreover, the western blot analysis showed that the pro-apoptotic cell effectors such as Bax and caspase-1, -3, and -7 increased. Computational results of affinity of ligands detected by GC-MS compounds and stimulated apoptosis effectors detected by western blot showed five molecules in A. marina leaves playing role in OVCAR3 and HeLa apoptosis. In conclusion, the ethanol and ethyl acetate extracts of A. marina leaves have anticancer effects. The ethanol extract induced cell cycle arrest in the breast cancer cell line and the ethyl acetate extract induced apoptotic mechanisms in ovarian and cervical cancer cell lines; that’s how they decreased cancer cells’ survival and viability.

Background: Avicennia marina , the gray mangrove, is an herbal source of bioactive anti-cancer compounds. Purpose: The present study aimed to evaluate phytochemical compositions of ethanol and ethyl acetate extracts of A. marina leaves and experimental study and computational modeling of their anti-cancer activity on breast, ovarian and cervical cancer cell lines. Study design: Phytochemical analysis, computational modeling and experimental in vitro evaluation Methods: Phytochemical analysis and GC-MS analysis were used to detect phenolic and flavonoid contents in ethanol and ethyl acetate extracts of A. marina leaves. Cell proliferation, viability, cycle and western blot assays of the extracts were performed on MCF-7, OVCAR3, and HeLa. Computational modeling done to detect effective compounds. Results: The extracts of A. marina leaves had high phenolic and flavonoid contents. In GC-MS analysis of the extracts, anti-cancer and anti-proliferative compounds were detected. Moreover, after treatment of MCF-7, OVCAR3, and HeLa, separately, the MTT assay, cell proliferation assay, and cell viability assays showed anti-proliferative activity, decreasing of cell population and decreasing cell viability, respectively. In addition, the cell cycle analysis showed that the S phase of the cell cycle increased in MCF-7. Moreover, the western blot analysis showed that the pro-apoptotic cell effectors such as Bax and caspase-1, -3, and -7 increased. Computational results of affinity of ligands detected by GC-MS compounds and stimulated apoptosis effectors detected by western blot showed five molecules in A. marina leaves playing role in OVCAR3 and HeLa apoptosis. Conclusion: The extracts of A. marina leaves have anti-cancer effects on breast, ovarian and cervical cancer cells via cell cycle arrest or apoptotic mechanisms.

Sea cucumber has antiviral activities against various viruses including herpes simplex virus type 1 (HSV-1). The purpose of the current study was to determine the chemical profile and inhibitory effects of tegument ethanolic extract of Holothuria parva on HSV-1 infection and to elucidate the mechanism of antiviral action of this marine invertebrate. Cytotoxic activity of the extract on Vero cell line was determined using the methyl thiazolyl tetrazolium (MTT) method. The different components in H. parva were determined by GC-MS analysis. To assess the antiviral activity of the extract, MTT and 50% tissue culture infective dose (TCID50) were applied. Finally, computational molecular docking was performed to screen the potential binding ability of extract contents with HSV-1 surface glycoproteins and host cell surface receptors. Using MTT assay, the non-cytotoxic concentration of the extract was measured 46.5 mu g/mL. Octadecanoic acid 2-hydroxy-1-(hydroxymethyl) ethyl ester and 2',6'-acetoxylidide were two major constituents in the H. parva extract. Pre-treatment of HSV-1 with the ethanolic extract of H. parva led to a 2.1 log10 TCID50 reduction in virus titers when compared to the control group (P = 0.002). The log10 TCID50 reductions relative to the control group for co-penetration and post-penetration assays were 1.5 (P = 0.009) and 0.7 (P = 0.09), respectively. The tegument ethanolic extract of H. parva has significant antiviral properties against HSV-1. Docking analysis demonstrated that compounds of the extract [lidocaine and 2-hydroxy-1-(hydroxymethyl) ethyl ester octadecanoic acid] may cover similarly both virus and host cells binding domains leading to interference in virus attachment to cell receptors.

Burn injury is one of the most destructive events in the world. The Pergularia tomentosa L. is a medicinal plant that traditionally, applies for treatment of burning, in Bushehr province, Iran. Various bioactive compounds such as steroid glycosides, tannins, various vitamins, saponins, cardenolides and anthraquinones were identified into extract of the plant, which can be effective in burn wound healing. Twenty-one rats weighting every one 200±5 grams were divided equally into three groups. The second-degree burning induced on all groups. One of groups did not receive any treatment (The control group) and was treated locally with saline and eucerin. The Second group received the P. tomentosa L. as a topical ointment, and the third group received locally, a thin layer of silver sulfadiazine ointment 3% after washing the wound with saline. Afterward treatment period, the microscopic slides from histological sections were prepared. At that point, amounts of the fibroblast cells, blood vessels, wound area, necrotic tissues, and diameter of epidermis rate of wound healing were determined. Also the exterior status of wound in different days was considered. Results obtained from current study have revealed that the extract of P. tomentosa L. can significantly, cause qualitative and quantitative acceleration in healing of second degree burn wounds, due to their bioactive and vasoactive properties. In conclusion the P. tomentosa L. can is used as an overborne medicine with lower cost and side effect than the similar chemical medicines. Although, the further studies are needed on these plants, due to their some toxic effects.

The aim of the present article was to study the healing of wounds using spider silk. Eight New Zealand female rabbits were selected as animal model. First, 3 identical wounds with length of 15 mm and a depth of 4 mm on the back of each rabbit were created. The first group, as standard control, did not receive any special treatment, they were treated only with saline and Vaseline locally. The second group, as positive control, received a thin film of phenytoin 1% ointment locally. The third group, as treated group, received a thin film of spider silk protein. At the end of the study, a biopsy of skin was done. After tissue preparation, all sections were evaluated. Some morphometrical parameters such as counting cells, fibroblasts, blood vessels, determination of the area of the wound closure, necrotic tissue, speed of wound healing, and epidermal thickness were done, and for data statistical analysis, SPSS software and Excel software were used. The results of this study showed that spider silk dressing may benefit as a possible effect of nanoparticles in the test preparation in wound healing.

OBJECTIVES:Diabetes is a metabolic syndrome which is associated with the worldwide major public health problems. There are many natural compounds from the sea-market, as a valuable aquatic source, along with the variety of health and therapeutic benefits. In the present research, with respect to the traditional and ethnic uses of Sargassum oligocystum algae for healing of some diseases which have similar metabolic mechanism to the diabetes, its anti-diabetic effects in animal model was proposed.MATERIALS AND METHODS:The animals (rat) were divided into the normal control, diabetic control, positive control and, the test groups. The test groups were gavaged with oral doses of 150 and 300 mg/kg of algae hydroalcoholic extracts. After 30 days of intervention the serum glucose, cholesterol, triglyceride, HDLC, LDLC, insulin, insulin resistance, β-cells function and, the histopathology of pancreatic tissue were evaluated.RESULTS:In animals that were fed with algae extracts a significant decrease in the fasting blood glucose, triglyceride and HOMA-IR and an increase in the HOMA-B with no significant impacts on the insulin, cholesterol and HDL were observed. Also, the histopathology evaluations in the groups which were treated with algae extract revealed the regeneration and reconstitution of damaged pancreatic β-cells.CONCLUSION:The results give evidence that, the S. oligocystum algae extract has a healing effect on diabetes which can be considered as a new research prospect for the natural therapy of diabetes.

Background: SIRT1 and FGF21 are known to regulate glucose metabolism and moderate diabetes complications. Sargassum oligocystum extract has therapeutic characteristics. This study aimed to evaluate the effects of hydroalcoholic extract of sargassum oligocystum on serum levels of SIRT1 and FGF21in diabetic rats. Materials and methods: In this experimental study, 48 male Wistar rats were randomly assigned into six groups: the non-diabetic control, the diabetic control, the diabetic treated with 150mg/kg of the extract, the diabetic treated with 300mg/kg of extract, the diabetic treated with 450mg/kg of the extract and the diabetic treated with 100mg/kg of Metformin. After 30 days of treatment, serum levels of SIRT1 and FGF21 of rats were measured. The data was analyzed in SPSS software version 22. Results: The extract of sargassum at the dose of 450mg/kg significantly reduced the SIRT1 serum level, but no changes were observed in the serum level of FGF21 and insulin at any of the doses. Moreover, serum glucose and insulin resistance were decreased at the doses of 300mg/kg of the extract. Conclusion: The results of this study suggest that the algae extract did not significantly change SIRT1 and FGF21 levels in order to regulate the glucose metabolism.

ObjectivesThe aim of this study was to investigate the potential effects of Sargassum oligocystum extract on the pentylenetetrazole (PTZ) seizure and the contribution of antioxidant capacity of this alga to its antiepileptic effect.MethodsA dose of 100mg/kg PTZ was used to induce the seizure in the male albino mice. Extract of Sargassum oligocystum in four doses (100, 200, 400 and 600mg/kg), diazepam (5mg/kg) and the vehicle were used 30min before the injection of PTZ (n=8). The onsets of clonic and tonic-clonic seizures, as well as the latency of death of animals, were recorded and the total antioxidant capacity (TAC), Superoxide dismutase (SOD) activity and catalase level were measured. Data were analyzed using one-way ANOVA or Kruskal-Wallis tests.ResultsSargassum oligocystum extract at the doses of 400 and 600mg/kg significantly increased the latency of clonic and tonic-clonic seizures. Also, at the doses of 100, 200 and 400mg/kg significantly increased the TAC. Moreover, Sargassum oligocystum at the doses of 200 and 400mg/kg increased the SOD activity and at the doses of 400 and 600mg/kg increased the catalase level in neural cells compared with the vehicle-treated group.ConclusionSargassum oligocystum extract inhibited PTZ-induced seizure. Attenuation of oxidative stress may partly be responsible for the anticonvulsant effects of this alga in the PTZ-induced seizures. Therefore, marine algae, especially Sargassum oligocystum, may be a valuable target to discover new antiepileptic drugs.

Diabetes is a major public health problem worldwide and associated with serious side effects. Given the role of medicinal plant in controlling diabetes, this study aimed to compare the effects of silymarin with metformin on serum glucose, insulin, insulin resistance (HOMA. IR), pancreatic function (HOMA. B) and pancreatic tissue in diabetic rats. In this experimental study, frothy male Wistar rats weighing 180-240 g were randomly divided into 5 equal groups as follows: the healthy control (HC), the diabetic control (DC), the silymarin100 (S-100), the silymarin 200 (S-200) and the metformin 100 (M-100). Groups DC, S-100, S-200 and M-100 were injected with intraperitoneally of streptozotocin. Groups S-100, S-200 and M-100 received 100 mg/kg of silymarin, 200 mg/kg of silymarin and 100 mg/kg of metformin respectively. After 30 days of intervention, serum concentrations of glucose and insulin were determined by enzymatic and ELISA method respectively. Also the pancreatic tissue was studied by light microscopy. Serums concentrations of glucose, insulin and HOMA. IR significantly decreased, whereas HOMA. B increased in the S-100, S-200 and M-100 groups compared to the DC group. Glucose and insulin levels significantly decreased in the M-100 group compared to the S-100 and S-200 groups (p < 0.05). Histological analysis demonstrated restoration effects of metformin and silymarin on pancreatic tissue. It seems that efficacy of metformin on diabetes is better than silymarin, however, more researches are needed to survey the effects of different timing (longer) and different concentrations of silymarin on diabetes.

Background: Remote Ischemic Preconditioning (RIPC) improves exercise performance, and since this phenomenon has two phases, the aim of the current study was to investigate the delayed effects of remote ischemic preconditioning on cardiopulmonary function in athletes and non-athletes. Materials and Methods: 25 male and female students were studied in two main athletes and non-athletes groups. RIPC was induced by using 3 cycles of alternative 5 minutes ischemia and 5 minutes reperfusion at arms of participants. Cardiopulmonary tests were measured before, after and 24 hours after inducing remote ischemic preconditioning. Maximum oxygen consumption (VO2max) estimated by using queen steps test. Results: Analysis of data demonstrated that delayed RIPC in non-athletes group caused significant improvement in Forced Expiratory Volume in one second (FEV1) and Maximum Voluntary Ventilation (MVV) and noticeable improvement in some other parameters of pulmonary function tests. Moreover, it decreased systolic blood pressure and heart rate and decreased lactate release in both groups especially athletes group but it had no significant effect on VO2max of both groups. Conclusion: Delayed RIPC improves cardiovascular function of athletes and pulmonary function of non-athletes subjects. Thus, it can be considered as a good replacement for doping to improve sports performance of subjects in sports tournaments.

Background: Considering the importance of the prevalence of diabetes which involves approximately 6% of the world's adult population, the need for low-calorie natural sweetener is felt more than ever. Recent studies have shown that hormones such as vaspin and Angiopoietin-like Protein3 (ANGPTL3) are associated with diabetes. The purpose of this study is to evaluate the effect of Stevia (Stevia rebaudiana ) plant (as a low calorie sugar) on serum concentration of vaspin and ANGPTL3 in diabetic rats. Materials and Methods: In this case-control study, forty male wistar rats weighing 180-250 g were divided into 5 equal groups: control, diabetic control and doses of 250, 500 and 750 mg/kg/BW/day of Stevia extract treatment. Diabetes was induced by intravenous injection of Streptozotocin (60 mg/kg). After 5 days, the rats with glucose above 300 mg/dl were considered as diabetic. The Stevia treatment groups received 250, 500 and 750 mg of Stevia extract for thirty days. At the end of experiment, blood samples were obtained measurement of vaspin, ANGPTL3, triglycerides, cholesterol, HDL, glucose, insulin and ALP. Histological study of the pancreas and liver biopsy were also performed. The results of the treatment and control groups were analyzed by SPSS software and P<0.05 was considered statistically significant. Results: The level of alkaline phosphatase, insulin resistance index, glucose and triglyceride were decreased significantly in the groups 250 and 500 compared with the diabetic control group(p≤0.05). However, insulin levels, HOMA.B, vaspin, ANGPTL3 and weight of the rats in all treatment groups were not significantly different from the control diabetic group. There were no histological changes in pancreatic and liver tissue following Stevia treatment. Conclusion: Administration of Stevia extract via reduction in serum glucose, triglyceride and insulin resistance can be effective in lowering the blood sugar and lipid, also lowering concentrations of serum alkaline phosphatase may have a protective effect on the liver. Howeve it should be considered the appropriate dosage of Stevia etract treatment is very important.

Recently the role of adipocytokines in relationship to incidence of diabetes has been demonstrated. One of the medicinal plants that are used in the treatment of diabetes is stevia. This study investigates the effect of stevia on serum omentin and visfatin levels as novel adipocytokines in diabetic induced rats to find potential mechanisms for the anti hyperglycemic effect of stevia. Forty male wistar rats weighing 180-250 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ). The animals were divided into 5 groups of 8. Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were treated with distilled water, and the rats in the treated groups, group 3 (T250), group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at 9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study significant reductions in fasting blood sugar (FBS), the homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2. Pancreatic histopathology slides demonstrated that stevia extract did not induce any increase in the number of β-cells. The conclusion is that prescription of stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly via activating insulin sensitivity and lowering blood glucose in STZ-induced diabetic rats.

Burns are the most damaging kind of injuries, major global public health crisis and the fourth most common types of trauma. Decision making in the treatment of burns remains a challenge despite existence of improved assessment techniques and treatment procedures. One of the most complications in healing of burn tissues is necrosis. Several medicinal plants were used to treat skin disorders as burn wounds and necrosis so far. In our traditional medicine, one of the non-surgical methods for debridement of necrotic tissues is using toasted barley in sesame oil. Animal was used, because of the lack of previous scientific research about this herbal mixture for debridement of necrotic tissue. After being anesthetized, the second-degree burns were created in rats. Animals were divided into group I, not treated (control group) and group II treated with fibrinolysin ointment 3% (positive control group). Groups III, IV and V were treated with 1, 3 and 5% w/w doses of toasted barley in sesame oil, respectively. Histopathological and clinical findings showed that treated tissues, especially at dose of 5% w/w were more debrided. Therefore, with respect to our results, this herbal based compound can be used as remedy for debridement of necrotic tissue. Key words: Burn, debridement, necrosis, sesame oil, toasted barley.