Optimization of induction and hairy root culture establishment in two mullein species, Verbascum erianthum and Verbascum stachydiforme.

The genus Verbascum, belonging to the family Scrophulariaceae, has a significant center of diversity in Iran. Two of its species, V. erianthum and V. stachydiforme, originate in the Iranian-Turanian region, but no studies have been conducted on the induction of their hairy roots. This genus is a valuable source of biologically active compounds such as iridoid glycosides and flavonoids. Hairy root culture is a suitable technique for the production and accumulation of secondary metabolites. Three different studies were conducted to optimize the induction and establishment of hairy roots. In the first experiment, the influence of explant type (leaf and hypocotyl), six infection methods, and co-culture time (48 and 72 h) on the efficiency of hairy root induction was investigated. The results showed that the highest hairy root induction (68.18%) was observed in the leaf explants inoculated by direct infection with three wounds within 72 h co-culture time. In the second experiment, the effect of four Agrobacterium rhizogenes strains (ATCC 15834, A4, A7, and A13) and leaf age (14, 21, and 28 days) on transformation efficiency and some morphological traits examined in both species were studied. The high transformation efficiency of hairy root (80.55%) was detected in the 21-day-old leaf explant of V. erianthum species that was inoculated with the A13 strain. The transformed hairy root colons were confirmed by PCR using rolB gene-specific primers. To optimize hairy root growth and avoid tissue browning, hairy roots were cultured in various media containing different antioxidants and improver agents (including ascorbic acid, citric acid, and NAA). The results showed that the highest fresh growth index (20.42) and the lowest tissue browning (9%) as well as total phenol (8.51 mg GA/g DW), and total flavonoid content (4.42 mg QUE/g DW) were obtained in medium B5 with 1.5 mg/l NAA.

Caccinia macranthera Brand var. macranthera: Phytochemical analysis, phytotoxicity and antimicrobial investigations of essential oils with concomitant in silico molecular docking based on OPLS force-field.

This study was conducted to extract the essential oils (EOs) of Caccinia macranthera identify their phytochemicals, evaluate their phytotoxicity, antimicrobial activity and enzyme inhibition effects using in silico molecular docking technique. EOs of aerial parts, seeds, and roots of C. macranthera were extracted and analyzed via Gas chromatography-Mass Spectrometry. The antibacterial activity of EOs were determined on nine microorganisms via disk diffusion and microbroth dilution assays. In addition, the allelopathic properties of EOs were investigated by calculating the IC50s for inhibition of germination, seedling length and seedling weight growth of Cuscuta campestris seeds. In order to assess the possible inhibitory effect of major components of C. macranthera EOs on enzymes inhibiting germination and plant growth, molecular docking was employed against the glutamine synthetase (GS), acetohydroxyacid synthetase (AHAS), and 4-hydroxyphenyl pyruvate dioxygenase (HPPD) enzymes. The main compounds of EOs from aerial parts, seeds, and roots EOs were dihydrocarveol (29.5%), Trimethyl-2-Pentadecanone (13.6%), and Palmitic acid (16.8%), respectively. The maximum antibacterial effect was related to the aerial parts EO against Staphylococcus epidermidis. Phytotoxicity analysis exhibited a concentration-dependent increase (p ≤ 0.05) activity. The aerial parts EO demonstrated a substantial allelopathy effect, with IC50 values of 0.22 ± 0.026, 0.39 ± 0.021, and 0.20 ± 0.025 mg/mL, respectively, on inhibitory germination, seedling length and seedling weight growth of Cuscuta campestris seeds. Molecular docking analyzes showed that Oleic acid was suitable for dynamic stabilization of HPPD (-6.552 kJ/mol) and GS (-7.265 kJ/mol) and Eupatoriochromene had the inhibitory potential against AHAS, with docking score of -4.189 kJ/mol. The current research demonstrated that C. macranthera EOs from its aerial parts have an acceptable phytotoxic activity against Cuscuta campestris weed. The major components of EOs, Oleic acid and Eupatoriochromene, presented the strongest binding with HPPD, GS, and AHAS active sites causing disturbance in germination, photosynthesis and weed growth suggesting it as a natural herbicide for controlling the weeds.

Electrosprayed Nanoparticles Containing Hydroalcoholic Extract of Echinacea purpurea (L.) Moench Stimulates Immune System by Increasing Inflammatory Factors in Male Wistar Rats.

Purpose: Echinacea purpurea (L.) Moench is a member of the Asteraceae family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of E. purpurea. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of E. purpurea using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. Methods: The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. Results: In vivo studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-ß (IL1-ß) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (P<0.05) whereas other CBC parameters remained unchanged. Conclusion: The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of E. purpurea.

Bioactivity assays and phytochemical analysis upon Alcea glabrata; focusing on xanthine oxidase inhibitory and antimalarial properties.

Alcea glabrata from the family Malvaceae, was selected for evaluating its xanthine oxidase inhibitory, anti-malarial, and antioxidant activities. In addition, some phytochemical analysis upon different extracts of A. glabrata were performed. Aerial parts of the collected A. glabrata plant material were dried and solvent extracted via soxhlet apparatus using different solvents. Various chromatographic techniques were used for extra fractionation of the achieved extracts. Xanthine oxidase (XO) inhibitory, antimalarial and antioxidant activity assays upon different A. glabrata extracts and fractions were carried out and reported in terms of IC50s. Total phenolic and flavonoid contents of the A. glabrata methanol extract (MeOH) were determined using the 2,2-Di Phenyl-1-Picryl Hydrazyl (DPPH) assay, aluminum chloride colorimetric, and Folin-Ciocalteu reagents, respectively. In addition, A. glabrata essential oil was obtained through hydrodistillation by a Clevenger apparatus. Analysis and identification of essential oil compounds were carried out through gas chromatography mass spectrometry (GC-MS) analysis. MeOH extract showed the highest XO inhibitory activity with the IC50 of 0.37 ± 0.12 mg/mL antioxidant activity with the RC50 of 0.24 ± 0.06 mg/mL. While, chloroform extract revealed the strongest antimalarial activity with the IC50 of 0.4 ± 0.05 mg/mL. The total flavonoid and phenolic contents of the A. glabrata methanol extract were 39.8 mg quercetin equivalent and 6.1 g gallic acid equivalent per 100 g of dry plant material, respectively. GC-MS analysis showed that the monoterpenes were prevailing in A. glabrata essential oil where the major constituents: octacosane (30.7%), eugenol (12.3%), and anethole (12.0%). Concerning the results of this study, A. glabrata extracts and its ingredients could be considered as a novel promising herbal medicine in the design and also treatment of new drugs for the relief of gout and malaria diseases.

Anti-inflammatory Properties of the Genus Symphytum L.: A Review.

The Symphytum genus has been mainly used in traditional medicine, containing its anti-inflammatory activity. Symphytum spp.'s active components, such as allantoin, polyphenols, flavonoids, and alkaloids, can act on several intentions in the signaling pathway, constrain pro-inflammatory enzymes, reducing the construction of inflammatory chemokine's and cytokines, and decreasing oxidative stress, which afterward suppresses inflammation procedures. Preclinical and clinical trials have reported the prevailing anti-inflammatory effect of several Symphytum species. This review presents an overview of the anti-inflammatory activities of different products and bioactive constituents in this genus. The papers with the English language were gathered from 2000 to 2021. This review may provide a scientific base for establishing innovative and alternative techniques for isolating a single individual from this genus to attenuate inflammatory disorders. The Symphytum genus is waiting for researchers to develop safe and effective anti-inflammatory agents for additional investigation of other different mechanisms of action.

Nanoencapsulation of n-butanol extract of Symphytum kurdicum and Symphytum asperrimum: Focus on phytochemical analysis, anti-oxidant and antibacterial activity.

Objectives: The current study's objectives were to obtain different extracts and essential oils of Symphytum kurdicum and Symphytum asperrimum and to determine the chemical composition, as well as to evaluate free radical scavenging activity (IC50) and minimum bactericidal concentration (MBC), and the effect of liposomal formulation on antimicrobial properties. Materials and Methods: Air-dried powdered aerial parts of S. kurdicum and S. asperrimum were used. The antioxidant and antibacterial properties, essential oil compositions, total phenol, and flavonoid contents of different fractions were determined by DPPH test, disk diffusion assay, gas chromatography-mass spectrometry, Folin-ciocalteu reagent, and colorimetric assay method, respectively. The film hydration method was used to fabricate nanoparticles. Results: GC-MS analysis indicated that hexafarnesyl acetone was a major essential oil component. n-butanol and ethyl acetate extracts of S. kurdicum had the highest anti-oxidant activity. Extracts of both plants showed antimicrobial activity. The extracts' maximum inhibition zones against Staphylococcus epidermidis were established. A particle size analyzer detected the formulation size of 140 nm. The optimum formulation of liposomes contains the ratio of 75 mg lecithin, 25 mg cholesterol, and 50 mg herbal extract. Despite the nanoparticles' appropriate particle size, the liposomal extract's antimicrobial effect was lower than that of the free form. Conclusion: Our findings demonstrated that extracts have significant antibacterial and anti-oxidant activities, attributed to their bioactive constituents.

Stachys schtschegleevii tea, matrix metalloproteinase, and disease severity in female rheumatoid arthritis patients: a randomized controlled clinical trial.

BACKGROUND: Stachys schtschegleevii (SSC) is a herbal medicine used to treat infections. To date, this is the first study aimed to investigate the effects of SSC tea on disease activity score (DAS), serum inflammatory biomarkers and matrix metalloproteinases (MMP-1 and MMP-3) among women with rheumatoid arthritis (RA). METHODS: This pilot, triple-blind, randomized controlled clinical trial was conducted among forty-four women (age: 30-65 years) diagnosed with moderately active RA. Subjects were randomly assigned (1:1 ratio) into either SSC group (2.4 g/day SSC + 2.4 g/day black tea, n=22) or placebo (2.4 g/day black tea, n=22) for 8 weeks. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-1 beta (IL-1ß), and MMPs were measured using ELISA. According to the American College of Rheumatology guideline considering hs-CRP, DAS28 was assessed. RESULTS: Both study groups had respondent rates above 94.9%. The SSC intervention caused significant reductions in the number and the percent changes of the tender joints (SSC: -74.39% vs. placebo: -57.15%, mean differences= -0.77; P<0.05) and DAS28 [SSC: -32.44% vs. placebo: -22.32%, mean differences= -0.41, P<0.05). Unlike the intervention within SSC group that showed significant reductions in the mean serum levels of hs-CRP, IL-1ß, and MMP-3, SSC caused significant MMP-3 reductions (SSC: -20.59% vs. placebo: 1.29%, P<0.05). CONCLUSION: The SSC intervention showed an appropriate clinical efficacy for female RA patients, accompanying remarkable reductions in the number of tender and swollen joints, DAS28, and serum levels of MMP-3. This can provide additional insights to the interventional studies controlling RA-related pathological and inflammatory outcomes. Trial registration Prospectively registered at the Iranian Registry of Clinical Trials (IRCT), linked to the WHO Registry Network ( https://en.irct.ir/trial/11602 , IRCT registration number: IRCT2015032011335N5, Registration date:2015-05-12). Key Points • Stachys schtschegleevii improved clinical outcomes and attenuated disease severity in RA patients. • Stachys schtschegleevii ameliorated serum level of MMP-3 in RA patients.

Preconcentration of digoxin using a synthetic imprinted polymer deposited upon the surface of double-layered hydroxides on porous anodised aluminium wire a triple solid-phase microextraction fibre.

INTRODUCTION: A new solid-phase microextraction fibre is fabricated through polymerisation of molecularly imprinted polymer on the surface of a layered double hydroxide framework that has been fabricated via the in situ synthesis on a non-porous anodic aluminium oxide/aluminium wire as both the substrate and the aluminium source. OBJECTIVE: The synthesized SPME fiber was performed to analyze trace digoxin in real samples. MATERIAL AND METHOD: A one-at-a-time optimization strategy was applied for optimizing the important extraction parameters such as extraction solvent, extraction time, stirring rate, pH, ionic strength, and desorption time. RESULT: Aluminum surface before and after anodizing and LDH structure reveal that anodizing and preparation LDH increases the surface area and adsorption capacity of aluminum wire. CONCLUSION: Under optimum conditions, the repeatability for one fibre (n = 3), expressed as relative standard deviation (RSD %), was 5.2%.

Biological Activities and Phytochemical Study of Pedicularis wilhelmsiana Fisch Ex. From Iran.

This research paper presents findings of an investigation about antibacterial effect of methanol/water fractions as well as cytotoxic activity of the extracts obtained from Pedicularis wilhelmsiana (Scrophulariaceae) which grows in Azarbaijan/Iran by agar well diffusion method and brine shrimp lethality test successively. Phytochemical study of this plant was determined as well. A combination of solid-phase extraction (SPE), preparative reversed-phase HPLC analysis and spectroscopic means were applied for fractionation, purification, and identification of ingredients respectively. Antimicrobial test demonstrated that 40% and 60% methanol/water fractions were more active than methanolic extract and other SPE fractions. No cytotoxic effect was detected from the extracts of this plant by brine shrimp lethality assay. Phytochemical study of aerial parts of Pedicularis wilhelmsiana (P. wilhelmsiana) afforded two phenylethanoids (verbascoside and martynoside), three iridoids (Aucubin, ipolamiid, 5-hydroxy-8-epi-loganin) and two flavonoids (luteolin, luteolin-7-glucoside) along with mannitol on the basis of spectral evidences (UV, 1H and 13CNMR) as well as comparison with literature data. The findings of this research supported further studies related to antibiotic potential of methanolic extract of P. wilhelmsiana.

Triterpenoid corosolic acid attenuates HIF-1 stabilization upon cobalt (II) chloride-induced hypoxia in A549 human lung epithelial cancer cells.

Hypoxia-inducible factor-1 is a target for the management of cancer. Here, the anti-proliferation properties of corosolic acid (CA) against A549 human lung epithelial cancer cells in CoCl2-induced hypoxia is reported. CA was isolated from the roots of Salvia syriaca based on a bioassay-guided isolation platform and identified by 1D and 2D NMR experiments. Several cytotoxicies and genotoxicity analyses were performed using MTT, DAPI, cell cycle, DNA ladder, and annexin V/PI detection. Cobalt chloride (CoCl2) was used to stimulate hypoxia. The adaptation of A549 cells to a stimulated hypoxic condition in the presence of CA was evaluated. CA decreased the growth of A549 cells with an IC50 of 12 µg/mL at 48 h. Also, chromatin condensation and DNA fragmentation were detected as signs of apoptosis occurrence. CA induced ~85% apoptosis and even 1% necrosis. The expression of hypoxia-inducible factor-1 α (HIF-1α), HIF-1ß and downstream genes was strongly suppressed in the presence of CA in CoCl2-stimulated hypoxia condition. Results indicated that CA has remarkable cytotoxicity against the cancerous cell in hypoxia condition and may be regarded for preparation of new formulations for possible uses as supplement and medicine in cancer therapy.

Evaluation of Phytochemical, Antioxidant and Antibacterial Activity on Astragalus Chrysostachys Boiss. Roots.

Astragalus is a well-known genus in Leguminosae family that represented more than 800 species growing in Iran. Nevertheless, there are a few reports on Astragalus plants endemic to Iran. The roots of Astragalus plants are rich in saponins, flavonoids and polysaccharides that possess various pharmacological activities. In the present study, chemical components, antioxidant and antibacterial activity of Astragalus chrysostachys Boiss. roots were evaluated. For determination of phytochemicals in Astragalus chrysostachys Boiss. roots, total hydroalcoholic extract was fractionated with ethyl acetate and n-butanol. Ethyl acetate extract as a flavonoid rich extract was analyzed using vacuum liquid chromatography and preparative TLC and consequently a major flavonoid was isolated. The structure of the obtained compound was elucidated with 1D and 2D NMR experiments. Additionally, the essential oil of the roots was analyzed by GC-MS. Antioxidant activity of all extracts was evaluated by different assays. Moreover, antibacterial activities of the extracts were also investigated against 2 Gram-positive and 2 Gram-negative bacteria using Micro-dilution Broth method. Apigenin-6, 8-di-C-glucoside was detected in ethyl acetate extract for the first time in genus Astragalus. In addition, m-tolualdehyde, acetophenone, croweacin were found to be characteristics of the volatile oil of roots. Ethyl acetate extracts revealed notable antioxidant activity in DPPH scavenging assay with IC50 value of 14.6 µg/mL. Evaluation of antibacterial activity on the tested extracts showed mild activity against Gram-positive bacteria. Since there have been no reports on Astragalus chrysostachys Boiss. to date, the present data might be promising for application of this plant derivatives in phytotherapeutic practice.

Effect of Cucurbita Maxima on Control of Blood Glucose in Diabetic Critically Ill Patients.

Purpose: Cucurbita maxima Duchense (C. maxima) has been widely used in China and Mexico as a hypoglycemic plant for controlling blood glucose in diabetic patients. Furthermore, in northwest of Iran, this plant is used traditionally for controlling of diabetes. We examined the effect of C. maxima pulp besides insulin on control of hyperglycemia in diabetic patients admitted to Intensive care unit (ICU). Methods: Twenty critically ill patients who were admitted to the ICU were enrolled in this study. 5g lyophilized powder of C. maxima was administrated every 12 hours for 3 days. Moreover, blood glucose level and insulin dose were measured every 1-4 hours during 3 days before administration and 3days at the time of C. maxima administration. Results: The average of glucose level in 3 days before C. maxima administration was 214.9 ± 55.7 mg/dl, while in 3 days during C. maxima administration it was decreased to 178.4 ± 36.1 mg/dl (P<0.001). Additionally, the average insulin dose during 3 days before intervention was 48.05 ± 36.5 IU and during the 3 days of C. maxima administration was decreased to 39.5 ± 27.8 IU (P=0.06). Conclusion: It seems that C. maxima may decrease high blood glucose level fast and effective in diabetic critically ill patients.

Anti-proliferative activity-guided isolation of clerodermic acid from Salvia nemorosa L.: Geno/cytotoxicity and hypoxia-mediated mechanism of action.

The adaptation of solid tumors to the low oxygen/nutrient environment is mediated by the pivotal transcription role of hypoxia-inducible factor-1 (HIF-1). Thus, the HIF-1 and its subunits have been considered to be hopeful anti-cancer targets. Various natural compounds were reported to persuade cell cytotoxicity through targeting and downregulation of the HIF-1. The genus Salvia is a rich source of bioactive terpenoids which show promising anti-cancer activities. Here, the identification of natural anti-proliferative compound targeting the HIF-1α expression was reported. A bioassay-guided isolation was employed for the discovery of natural anti-proliferative compounds from Salvia extracts using MTT assay against A549 cells. In this direction, clerodermic acid (CDA) as a potent cytotoxic compound was purified from Salvia nemorosa and identified using 1D and 2D NMR analysis. Results indicated that CDA has anti-proliferation activity (IC50 value of 35 µg/mL) which was confirmed by genotoxicity and apoptosis detection analyses. The quantitative qPCR analysis showed that the expression level of HIF-1 alpha was strongly inhibited in the hypoxic cells treated with CDA compared to the untreated cells tolerated hypoxia. Findings exhibited that S. nemorosa and clerodermic acid have significant potential for reducing HIF-1α expression and could be considered for further studies for cancer therapy.

Herbal Medicine for Oligomenorrhea and Amenorrhea: A Systematic Review of Ancient and Conventional Medicine.

INTRODUCTION: Menstrual bleeding cessation is one of the most frequent gynecologic disorders among women in reproductive age. The treatment is based on hormone therapy. Due to the increasing request for alternative medicine remedies in the field of women's diseases, in present study, it was tried to overview medicinal plants used to treat oligomenorrhea and amenorrhea according to the pharmaceutical textbooks of traditional Persian medicine (TPM) and review the evidence in the conventional medicine. METHODS: This systematic review was designed and performed in 2017 in order to gather information regarding herbal medications of oligomenorrhea and amenorrhea in TPM and conventional medicine. This study had several steps as searching Iranian traditional medicine literature and extracting the emmenagogue plants, classifying the plants, searching the electronic databases, and finding evidences. To search traditional Persian medicine references, Noor digital library was used, which includes several ancient traditional medical references. The classification of plants was done based on the repetition and potency of the plants in the ancient literatures. The required data was gathered using databases such as PubMed, Scopus, Google Scholar, Cochrane Library, Science Direct, and web of knowledge. RESULTS: In present study of all 198 emmenagogue medicinal plants found in TPM, 87 cases were specified to be more effective in treating oligomenorrhea and amenorrhea. In second part of present study, where a search of conventional medicine was performed, 12 studies were found, which had 8 plants investigated: Vitex agnus-castus, Trigonella foenum-graecum, Foeniculum vulgare, Cinnamomum verum, Paeonia lactiflora, Sesamum indicum, Mentha longifolia, and Urtica dioica. Conclusion. Traditional Persian medicine has proposed many different medicinal plants for treatment of oligomenorrhea and amenorrhea. Although just few plants have been proven to be effective for treatment of menstrual irregularities, the results and the classification in present study can be used as an outline for future studies and treatment.

Chemical compositions and biological activities of Scutellaria pinnatifida A. Hamilt aerial parts.

Phytochemical analysis of the methanolic and dichloromethane extracts of the aerial parts of Scutellaria pinnatifida led to the isolation of a phenylpropanoid, 1-o-feruloyl-ß-D-glucose (1), two known flavonoids including luteolin-7-o-glucoside (2) and apigenin-7-o-glucoside (3), three known phenylethanoid glycosides composed of phlomisethanoside (4), syringalide A (5), and verbascoside (6), and oleic acid (7). Isolation and structural elucidation of compounds were accomplished by HPLC and spectroscopic methods (UV, 1H-NMR, 13C-NMR). The extracts were also evaluated for their radical scavenging activity and insecticidal property by 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay and contact toxicity method, respectively. Among the extracts, the methanol extract showed the most potent free radical scavenging activity with a RC50 value of 0.044 ± 0.350 mg/mL which could be attributed to the presence of the isolated phenolic compounds. In the case of insecticidal activity, the n-hexane extract displayed the most potent activity and caused 10%, 15%, and 40% mortality to Oryzaephilus mercator at the concentration of 5, 10, and 15 mg/mL after 4 h of exposure.

A Survey on Phytochemical Composition and Biological Activity of Zygophyllum fabago from Iran.

Purpose: Zygophyllum fabago L. (Z. fabago) is a widespread perennial herb which is used as a medicinal plant in traditional medicine of Iran, Turkey and China. The present study was a survey on phytochemical constituents and biological activities of this plant. Methods: Methanolic extract of the roots was fractionated over a C-18 pre-packed cartridge (Sep-pak) and chromatographic separation was performed on a reversed-phase preparative HPLC. Structural elucidation of the isolated compounds was carried out using UV, 1H-NMR and 13C-NMR spectral analyses. Furthermore, the chemical compositions of the essential oil of the aerial parts were identified by GC-MS analysis. Antiproliferative and antioxidant activities of all extracts from aerials were determined by MTT and DPPH assays, respectively. Results: Phytochemical investigation on the plant roots led to the isolation and identification of two the 60% methanol-water Sep-pak fraction, a prenylated flavone glycoside, 6-C-prenyl-7-O-[ ß -D-4'''-O-acetyl-glucopyranosyl-(1'''→2'')-ß-D-glucopyranosyl] apigenin, which was named as a Zygocaperoside and also, other flavonoid, was named as the Isorhamnetin -3-O glucoside. None of the extracts showed antiproliferative effect against cancerous cells. However, among the extracts, methanolic extract indicated antioxidant activity. Moreover, essential oils of flowers and leaves of plant have high amounts of sesquiterpene hydrocarbons and diterpenoides. Conclusion: The results of present study introduce Z. fabago roots as a new source of flavonoid glycosides and suggest it as an appropriate candidate for further pharmacological studies.

Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells.

Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions. An imbalance in oxygen content within the cellular microenvironment activates a cascade of molecular events that are often compensated, otherwise pathologic condition occurs through a complexed network of biomolecules. Hypoxia inducible factor-1 (HIF-1) plays a key transcriptional role in the adaptation of cell physiology in relation with the oxygen content within a cell. In this current study, we provide a comprehensive review on the molecular mechanisms of oxygen sensing and homeostasis and the impacts of HIF-1 in hypoxic/anoxic conditions. Moreover, different molecular and biochemical responses of the cells to the surrounding environment are discussed in details. Finally, modern technological approaches for targeting the hypoxia related proteins are articulated.

Evaluation of the Effect of Psyllium on the Viability of Lactobacillus Acidophilus in Alginate-Polyl Lysine Beads.

Purpose: Psylliumseeds are used in traditional herbal medicine to treat various disorders. Moreover, as a soluble fiber, psyllium has potential to stimulate bacterial growth in digestive system. We aimed to substitute alkali-extractable polysaccharides of psyllium for alginate in beads with second coat of poly-l-lysine to coat Lactobacillus acidophilus. Methods: Beads were prepared using extrusion technique. Poly-l-lysine as second coat was incorporated on optimum alginate/psyllium beads using immersion technique. Beads were characterized in terms of size, encapsulation efficiency, integrity and bacterial survival in harsh conditions. Results: Beads with narrow size distribution ranging from 1.85 ± 0.05 to 2.40 ± 0.18 mm with encapsulation efficiency higher than 96% were achieved. Psyllium concentrations in beads did not produce constant trend in bead sizes. Surface topography by SEM showed that substitution of psyllium enhanced integrity of obtained beads. Psyllium successfully protected the bacteria against acidic condition and lyophilization equal to alginate in the beads. Better survivability with beads of alginate/psyllium-poly-l-lysine was achieved with around 2 log rise in bacterial count in acid condition compared to the corresponding single coat beads. Conclusion: Alginate/psyllium (1:2) beads with narrow size distribution and high encapsulation efficiency of the bacteria have been achieved. Presence of psyllium produced a much smoother and integrated surface texture for the beads with sufficient protection of the bacteria against acidic condition as much as alginate. Considering the health benefits of psyllium and its prebiotic activity, psyllium can be beneficially replaced in part for alginate in probiotic coating.

Formulation and Physicochemical Characterization of Lycopene-Loaded Solid Lipid Nanoparticles.

PURPOSE: Lycopene belongs to the carotenoids that shows good pharmacological properties including antioxidant, anti-inflammatory and anticancer. However, as a result of very low aqueous solubility, it has a limited systemic absorption, following oral administration. METHODS: Here, we prepared a stable lycopene-loaded solid lipid nanoparticles using Precirol® ATO5, Compritol 888 ATO and myristic acid by hot homogenization method with some modification. The size and morphological characteristics of nanoparticles were evaluated using Scanning Electron Microscopy (SEM). Moreover, zeta potential and dispersity index (DI) were measured using zeta sizer. In addition, encapsulation efficiency (EE%), drug loading (DL) and cumulative drug release were quantified. RESULTS: The results showed that the size and DI of particles was generally smaller in the case of SLNs prepared with precirol when compared to SLNs prepared with compritol. Scanning electron microscopy (SEM) and particle size analyses showed spherical SLNs (125 ± 3.89 nm), monodispersed distribution, and zeta potential of -10.06 ± 0.08 mV. High EE (98.4 ± 0.5 %) and DL (44.8 ± 0.46 mg/g) were achieved in the case of nanoparticles prepared by precirol. The stability study of the lycopene-SLNs in aqueous medium (4 °C) was showed that after 2 months there is no significant differences seen in size and DI compared with the fresh formulation. CONCLUSION: Conclusively, in this investigation we prepared a stable lycopene-SLNs with good physicochemical characteristic which candidate it for the future in vivo trials in nutraceutical industries.

Co-treatment by docetaxel and vinblastine breaks down P-glycoprotein mediated chemo-resistance.

OBJECTIVES: Chemoresistance remains the main causes of treatment failure and mortality in cancer patients. There is an urgent need to investigate novel approaches to improve current therapeutic modalities and increase cancer patients' survival. Induction of drug efflux due to overexpression of P-glycoproteins is considered as an important leading cause of multidrug resistance. In this study, we investigated the role of combination treatments of docetaxel and vinblastine in overcoming P-glycoprotein mediated inhibition of apoptosis and induction of cell proliferation in human non-small cell lung carcinoma cells. MATERIALS AND METHODS: Cell proliferation and apoptosis were assessed using MTT assay and DAPI staining, respectively. P-glycoprotein expression was evaluated in gene and protein levels by Real-time RT-PCR and Western blot analysis, respectively. RESULTS: Combination treatment of the cells with docetaxel and vinblastine decreased the IC50 values for docetaxel from (30±3.1) to (15±2.6) nM and for vinblastine from (30±5.9) to (5±5.6) nM (P≤0.05). P-glycoprotein mRNA expression level showed a significant up-regulation in the cells incubated with each drug alone (P≤0.001). Incubation of the cells with combined concentrations of both agents neutralized P-glycoprotein overexpression (P≤0.05). Adding verapamil, a P-glycoprotein inhibitor caused a further increase in the percentage of apoptotic cells when the cells were treated with both agents. CONCLUSION: Our results suggest that combination therapy along with P-glycoprotein inhibition can be considered as a novel approach to improve the efficacy of chemotherapeutics in cancer patients with high P-glycoprotein expression.