In vitro antimicrobial and antibiofilm screening of eighteen Iranian medicinal plants.

BACKGROUND: Natural products are one of the best candidates for controlling drug-resistant pathogens, the advantages of which include low production costs and low side effects. In this study, as potential antimicrobials, the anti-bacterial and antibiofilm activities of several Iranian native medicinal plants were screened. METHODS: The antibacterial/antifungal and anti-biofilm activities of 18 medicinal plants including Reseda lutea L., Nepeta sintenisii Bunge., Stachys turcomanica Trautv., Stachys lavandulifolia Vahl, Diarthron antoninae (Pobed.) Kit Tan., Ziziphora clinopodioides Lam., Euphorbia kopetdaghi Prokh, Euphorbia serpens Kunth., Hymenocrater calycinus Benth., Scutellaria pinnatifida A.Ham., Viola tricolor L., Hypericum helianthemoides (Spach) Boiss., Hypericum scabrum L., Convolvulus lineatus L., Scabiosa rotata M.Bieb Greuter & Burdet, Delphinium semibarbatum Bien. Ex Boiss., Glycyrrhiza triphylla Fisch. & C.A.Mey., and Ziziphus jujuba Mill., against two Gram-positive bacteria, Staphylococcus aureus, Bacillus cereus, as well as two Gram-negative bacteria, Pseudomonas aeruginosa, Escherichia coli; and Candida albicans as a fungal strain, were evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) values of the extracts against tested microorganisms were reported and we investigated their effect on the biofilm inhibition of Pseudomonas aeruginosa PAO1, Staphylococcus epidermis, Staphylococcus aureus and Streptococcus mutans. In addition, the effect of the extracts on the eradication of the biofilms of these bacteria was evaluated. RESULTS: In this study, H. scabrum was found to exhibit potentially significant activity against Gram-positive bacteria with the MIC range of 6.25-25 µg/mL. This extract also showed a significant effect on inhibiting the biofilm of S. aureus, S. mutans, and S. epidermidis and eradicating the biofilm of S. epidermidis DSMZ 3270. In addition, Hymenocrater calycinus root extract had moderate antibacterial activity against B. cereus with the MIC and MBC 62.5 µg/mL, respectively. CONCLUSIONS: The results of this study showed that the root extracts of two plants, Hypericum scabrum and Hymenocrater calycinus, had antimicrobial and anti-biofilm effects. Based on the observed anti-biofilm effects, these two plants may be considered in future studies to find responsible antimicrobial compounds.

Diverse diterpenoids and a triterpenoid from Euphorbia spinidens Bornm. ex Prokh.

Four previously unreported diterpenoids including three ent-atisanes (1-3) and one ent-abietane (4), along with one known linear triterpenoid (5) and five known diterpenoids including four myrsinanes (6-9), and one abietane (10) have been isolated from the roots of Euphorbia spinidens Bornm. ex Prokh. The structures were determined on the basis of extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR and comparison of the data with those reported in the literature. Antimicrobial potential of isolated compounds were also evaluated. Guionianol B (10) showed good antibacterial activity against Staphylococcus aureus and Bacillus subtilis with MIC value of 6.25 µg/mL.

Neuroprotective Effects of Sesamum indicum, Sesamin and Sesamolin Against 6-OHDA-induced Apoptosis in PC12 Cells.

BACKGROUND: Sesamum indicum L. (sesame) is one of the most widely used herbs in the world. Sesame oil contains lignans such as sesamin and sesamolin, which are known to possess anti-inflammatory, antioxidant, and anti-apoptotic properties. Parkinson's disease (PD) is recognized as the most common neurodegenerative disease after Alzheimer's disease; however, the exact molecular mechanism of the progression of neural death is not clear yet. In this study, the effect of sesame seed extracts and their main bioactive components (sesamin and sesamolin) on in vitro model of Parkinson's disease has been compared. METHODS: Cell viability, the number of reactive oxygen species (ROS), and apoptosis were determined using resazurin assay, ROS assay, propidium iodide (PI) staining and flow cytometry, and western blot analysis. RESULTS: 6-OHDA caused cellular death and apoptosis but pretreatment with sesame seed extracts, sesamin, and sesamolin significantly increased cell viability (p<0.001) and decreased ROS (p<0.001) and apoptosis. ERK1/2 is activated by 6-OHDA in PC12 cells, and the level of survivin decreased. Pretreatment with sesame significantly reversed the entire cell death induced by 6- OHDA. Sesame seed extracts at 5 and 10 µg/ml, sesamin and sesamolin at 5 and 10 µM increased surviving (p<0.01), and reduced P-ERK1/2/ERK1/2 (p<0.05) levels close to the control values. CONCLUSIONS: Overall, compounds in sesame seed extract and sesamin may assist as adjuvant therapeutics in PD. It seems sesame seeds have more potent protection effects against neural death compared with individual components, which might reflect the synergism among different phytochemicals present in the extract.

Efficacy of orally administered montmorillonite in myoglobinuric acute renal failure model in male rats.

Objectives: Acute kidney injury can be associated with serious consequences and therefore early treatment is critical to decreasing mortality and morbidity rate. We evaluated the effect of montmorillonite, the clay with strong cation exchange capacity, on the AKI model in rats. Materials and Methods: Glycerol (50% solution, 10 ml/kg) was injected in the rat hind limbs to induce AKI. 24 hr after induction of acute kidney injury, the rats received oral doses of montmorillonite (0.5 g/kg or 1 g/kg), or sodium polystyrene sulfonate (1 g/kg) for three consecutive days. Results: Glycine induced acute kidney injury in rats with high levels of urea (336.60± 28.19 mg/dl), creatinine (4.10± 0.21 mg/dl), potassium (6.15 ± 0.28 mEq/L), and calcium (11.52 ± 0.19 mg/dl). Both doses of montmorillonite (0.5 and 1 g/kg) improved the serum urea (222.66± 10.02 and 170.20±8.06, P<0.05), creatinine (1.86±0.1, 2.05± 0.11, P<0.05), potassium (4.68 ± 0.4, 4.73 ± 0.34, P<0.001) and calcium (11.15 ± 0.17, 10.75 ± 0.25, P<0.01) levels. Treatment with montmorillonite especially at a high dose reduced the kidney pathological findings including, tubular necrosis, amorphous protein aggregation, and cell shedding into the distal and proximal tubule lumen. However, administration of SPS could not significantly decrease the severity of damages. Conclusion: According to the results of this study, as well as the physicochemical properties of montmorillonite, such as high ion exchange capacity and low side effects, montmorillonite can be a low-cost and effective treatment option to reduce and improve the complications of acute kidney injury. However, the efficacy of this compound in human and clinical studies needs to be investigated.

Therapeutic potency of curcumin for allergic diseases: A focus on immunomodulatory actions.

In light of increasing research evidence on the molecular mechanisms of allergic diseases, the crucial roles of innate and acquired immunity in the disease's pathogenesis have been well highlighted. In this respect, much attention has been paid to the modulation of unregulated and unabated inflammatory responses aiming to suppress pathologic immune responses in treating allergic diseases. One of the most important natural compounds with a high potency of immune modulation is curcumin, an active polyphenol compound derived from turmeric, Curcuma longa L. Curcumin's immunomodulatory action mainly arises from its interactions with an extensive collection of immune cells such as mast cells, eosinophils, epithelial cells, basophils, neutrophils, and lymphocytes. Up to now, there has been no detailed investigation of curcumin's immunomodulatory actions in allergic diseases. So, the present review study aims to prepare an overview of the immunomodulatory effects of curcumin on the pathologic innate immune responses and dysregulated functions of T helper (TH) subtypes, including TH1, TH2, TH17, and regulator T cells (Tregs) by gathering evidence from several studies of In-vitro and In-vivo. As the second aim of the present review, we also discuss some novel strategies to overcome the limitation of curcumin in clinical use. Finally, this review also assesses the therapeutic potential of curcumin regarding its immunomodulatory actions in allergic diseases.

Structural Diversity of Complex Phloroglucinol Derivatives from Eucalyptus Species.

Several species of the genus Eucalyptus are used in many traditional medicine systems for the treatment of respiratory tract infections, colds, flu, sore throats, and bronchitis. The genus Eucalyptus (Myrtaceae) is a well-known natural source of bioactive phloroglucinols. These polyphenolic compounds bear an aromatic phenyl ring with three hydroxy groups (1,3,5-trihydroxybenzene) which have been exhibiting a variety of biological activities such as antimicrobial, anticancer, anti-allergic, anti-inflammatory, and antioxidant activities. This review summarizes the literature published from 1997 until the end of 2021 and addresses the structure diversity of phloroglucinols isolated from Eucalyptus species and their biological activities. Phloroglucinol-terpene adducts are the main class of compounds that have been reported in this genus.

Cytotoxic sesquiterpene lactones and lignans from Cousinia turkmenorum Bornm (Asteraceae).

Seven sesquiterpene lactones, chlorophyssopifolin E (1), aguerin B (2), repdiolide triol (3), solistitiolide (4), aitchisonolide (5), sinicin B (6), cynaropicrin (7), along with four lignans arctigenin (8), arctiin (9), matairesinol (10), and matairesinoside (11) were isolated for the first time from the aerial parts of Cousinia turkmenorum Bornm. Among the isolated compounds, aguerin B (2) showed the most cytotoxic activity against MCF7 cell lines with IC50 value of 18.9 µM. Findings of this study could be useful for the development of new anticancer agents from nature.

Quercetin and its role in modulating endoplasmic reticulum stress: A review.

The endoplasmic reticulum (ER) is the place where proteins and lipids are biosynthesized and where transmembrane proteins are folded. Both pathological and physiological situations may disturb the function of the ER, resulting in ER stress. Under stress conditions, the cells initiate a defensive procedure known as the unfolded protein response (UPR). Cases of severe stress lead to autophagy and/or the induction of cell apoptosis. Many studies implicate ER stress as a major factor contributing to many diseases. Therefore, the modulation of ER stress pathways has become an attractive therapeutic target. Quercetin is a plant-derived metabolite belonging to the flavonoids class which presents a range of beneficial effects including anti-inflammatory, cardioprotective, anti-oxidant, anti-obesity, anti-carcinogenic, anti-atherosclerotic, anti-diabetic, anti-hypercholesterolemic, and anti-apoptotic activities. Quercetin also has anti-cancer activity, and can be used as an adjuvant to decrease resistance to cancer chemotherapy. Furthermore, the effect of quercetin can be increased with the help of nanotechnology. This review discusses the role of quercetin in the modulation of ER stress (and related diseases) and provides novel evidence for the beneficial use of quercetin in therapy.

From plants to antimicrobials: Natural products against bacterial membranes.

Bacterial membrane barrier provides a cytoplasmic environment for organelles of bacteria. The membrane is composed of lipid compounds containing phosphatide protein and a minimal amount of sugars, and is responsible for intercellular transfers of chemicals. Several antimicrobials have been found that affect bacterial cytoplasmic membranes. These compounds generally disrupt the organization of the membrane or perforate it. By destroying the membrane, the drugs can permeate and replace the effective macromolecules necessary for cell life. Furthermore, they can disrupt electrical gradients of the cells through impairment of the membrane integrity. In recent years, considering the spread of microbial resistance and the side effects of antibiotics, natural antimicrobial compounds have been studied by researchers extensively. These molecules are the best alternative for controlling bacterial infections and reducing drug resistance due to the lack of severe side effects, low cost of production, and biocompatibility. Better understanding of the natural compounds' mechanisms against bacteria provides improved strategies for antimicrobial therapies. In this review, natural products with antibacterial activities focusing on membrane damaging mechanisms were described. However, further high-quality research studies are needed to confirm the clinical efficacy of these natural products.

Protective Effects of Curcumin against Iron-induced Toxicity.

Iron is an essential element in cellular metabolism that participates in many biochemical reactions. Nevertheless, iron overload in the body is the cause of damage in some organs including the liver, glands, brain, heart, gastrointestinal tract and lung. Iron chelation therapy could be considered an effective approach for removing excess iron. Deferoxamine, deferiprone and deferasirox are three common iron chelators in clinical practice but cause several side effects. In this context, the use of curcumin, a dietary phytochemical derived from turmeric, as a natural and safe antioxidant with iron-chelating activity may be a useful strategy for the management of iron overload. This review focuses on the deleterious effect of iron accumulation in different organs of the body as well as the therapeutic potential of curcumin against iron-induced toxicity.

A Review of the Phytochemistry and Antimicrobial Properties of Origanum vulgare L. and Subspecies.

Origanum vulgare L. (O. vulgare) is an important medicinal herb of the family Lamiaceae. In the current study, we explained the critical evaluation of traditional uses, the phytochemistry and the antimicrobial properties of O. vulgare and its subspecies, with a focus on the mechanisms of actions of the most important phytochemicals from O. vulgare subspecies. The most important phytochemicals of O. vulgare are volatile (essential oil) and non-volatile phenolic compounds (phenolic acids & flavonoids). The constituents of the O. vulgare essential oil (EO) include high percentages of thymol and carvacrol with excellent antimicrobial activity alone or in combination with other antibiotics. Interesting results have been reported the remarkable antimicrobial activities of infusion or tea products of O. vulgare with a high amount of EO against multidrug-resistant bacterial and fungal microorganism (such as Escherichia coli, Staphylococcus aureus, Candida albicans and Pseudomonas aeruginosa). The most important antibacterial mechanisms of O. vulgare are enzyme inhibition, efflux pump inhibition, ATP depletion, biofilm formation inhibition and cytoplasmic membrane damage. The antimicrobial activity of the hirtum subspecies has been confirmed in different in-vitro and in-vivo studies. The present review confirms the clinical and preclinical research showing the O. vulgare and its subspecies antimicrobial effects.

Regulation of microRNA-21 expression by natural products in cancer.

Natural products have been of much interest in research studies owing to their wide pharmacological applications, chemical diversity, low side effects, and multitarget activities. Examples of these compounds include matrine, sulforaphane, silibinin, curcumin, berberin, resveratrol, and quercetin. Some of the present anticancer drugs, such as taxol, vincristine, vinblastine, and doxorubicin are also derived from natural products. The anti-carcinogenic effects of these products are partly mediated through modulation of microRNA-21 (miR-21) expression. To date, numerous downstream targets of miR-21 have been recognized, which include phosphatase and tensin homolog (PTEN), ras homolog gene family member B (RHOB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), programmed cell death 4 (PDCD4), signal transducer and activator of transcription (STAT)-3, and nuclear factor kappa B (NF-κB) pathways. These signaling pathways, their regulation by oncomiR-21 in cancer, and the modulating impact of natural products are the main focus of this review.

Natural products as safeguards against monosodium glutamate-induced toxicity.

Monosodium glutamate is a sodium salt of a nonessential amino acid, L-glutamic acid, which is widely used in food industry. Glutamate plays an important role in principal brain functions including formation and stabilization of synapses, memory, cognition, learning, as well as cellular metabolism. However, ingestion of foodstuffs rich in monosodium glutamate can result in the outbreak of several health disorders such as neurotoxicity, hepatotoxicity, obesity and diabetes. The usage of medicinal plants and their natural products as a therapy against MSG used in food industry has been suggested to be protective. Calendula officinalis, Curcuma longa, Green Tea, Ginkgo biloba and vitamins are some of the main natural products with protective effect against mentioned monosodium glutamate toxicity through different mechanisms. This review provides a summary on the toxicity of monosodium glutamate and the protective effects of natural products against monosodium glutamate -induced toxicity.

Curcumin and its analogues protect from endoplasmic reticulum stress: Mechanisms and pathways.

The endoplasmic reticulum (ER), a cellular organelle with multiple functions, plays an important role in several biological processes including protein folding, secretion, lipid biosynthesis, calcium homeostasis, and cellular stress. Accumulation of misfolded or unfolded proteins in the ER makes cells undergo a stress response known as the unfolded protein response (UPR). UPR is initially protective. However, prolonged and severe ER stress can lead to autophagy and/or the induction of apoptosis in stressed cell. Many studies have demonstrated that ER stress and the UPR are involved in different diseases such as neurodegenerative diseases, cancer, osteoporosis, diabetes, and inflammatory diseases. Curcumin, a natural polyphenol, has well documented evidence supporting its numerous biological properties including antioxidant, anti-inflammatory, immune-modulatory, anti-microbial, anti-ischemic, anti-angiogenesis, neuroprotective, hepatoprotective, nephroprotective, anti-atherogenic and anti-diabetic activities. In this review, the role of ER stress in several pathological condition and the potential protective effects of curcumin are discussed.

Biological properties of metal complexes of curcumin.

Curcumin, a naturally occurring phenolic compound isolated from Curcuma longa, has different pharmacological effects, including antiinflammatory, antimicrobial, antioxidant, and anticancer properties. However, curcumin has been found to have a limited bioavailability because of its hydrophobic nature, low-intestinal absorption, and rapid metabolism. Therefore, there is a need for enhancing the bioavailability and its solubility in water in order to increase the pharmacological effects of this bioactive compound. One strategy is curcumin complexation with transition metals to circumvent the abovementioned problems. Curcumin can undergo chelation with various metal ions to form metallo-complexes of curcumin, which may show greater effects as compared with curcumin alone. Promising results with metal curcumin complexes have been observed with regard to antioxidant, anticancer, and antimicrobial activity, as well as in treatment of Alzheimer's disease. The present review provides a concise summary of the characterization and biological properties of curcumin-metal complexes. © 2019 BioFactors, 45(3):304-317, 2019.

LC-ESI/LTQOrbitrap/MS/MS and GC-MS profiling of Stachys parviflora L. and evaluation of its biological activities.

The use of some Stachys genus as herbal remedies is known and the aerial parts have a pharmaceutical interest, being used in Anatolia and Iran as wild tea. In this study, chemical composition, antimicrobial, antioxidant, and antiproliferative activities of the methanolic extract and essential oil (EO) of Stachys parviflora L. (S. parviflora) were evaluated. Qualitative analysis of metabolites of S. parviflora methanolic extract was studied using liquid chromatography coupled to high resolution mass spectrometry (LC-ESI/LTQOrbitrap/MS), evidencing the presence of phenolic acids and flavonoids derivatives. The EO was analyzed using gas chromatography coupled to mass spectrometry (GC/MS). Eighty-seven compounds were characterized in the EO of S. parviflora, of which α-terpenyl acetate (23.6%), ß-caryophyllene (16.8%), bicyclogermacrene (9.3%), spathulenol (4.9%) and α-pinene (4.2%) were found to be the major components. The highest antimicrobial effect of EO was found to S. aureus and B. cereus (MIC = 0.01 µg/ml), while the highest activity of extract was against B. cereus (MIC = 125 µg/ml). The methanolic extract exhibited strong antioxidant activity in DPPH (IC50 = 76.87 µg/ml) and ß-carotene/linoleic acid assay (BCB, IC50 = 188.47 µg/ml) methods. Furthermore, in vitro cytotoxicity evaluation against three cell lines namely human ovarian carcinoma (A2780), human colon carcinoma (HCT), and mouse melanoma cell line (B16F10), showed an anti-proliferative activity of the EO ranging from IC50 value 30.95 µg/ml to 16.55 µg/ml. The results from this study have demonstrated the promising cytotoxic, antibacterial, and antifungal properties of S. parviflora, which could have wide potential applications in food and pharmaceutical industries.

Anti-Angiogenic Activity of Curcumin in Cancer Therapy: A Narrative Review.

Curcumin is a naturally occurring polyphenol isolated from Curcuma longa that has various pharmacological activities, including, anti-inflammatory, anti-oxidant and anti-cancer properties. The anticancer effect of curcumin is attributed to activation of apoptotic pathways in cancer cells, as well as inhibition of inflammation and angiogenesis in the tumour microenvironment and suppression of tumour metastasis. Angiogenesis, which is the formation of new blood vessels from pre-existing ones, is a fundamental step in tumour growth and expansion. Several reports have demonstrated that curcumin inhibits angiogenesis in a wide variety of tumour cells through the modulation of various cell signaling pathways which involve transcription factors, protein kinases, growth factors and enzymes. This review provides an updated summary of the various pathways and molecular targets that are regulated by curcumin to elicit its anti-angiogenic activity.

Sesquiterpene lactones from Centaurea rhizantha C.A. Meyer.

Two new sesquiterpene lactones, rhizantholide A (1) and rhizantholide B (2), together with five known compounds (3-7) have been isolated from the aerial parts of Centaurea rhizantha (Asteraceae). Sesquiterpene lactones belong to guaianolide class, and rhizantholide B is a rare guaianolide characterized by a free primary alcoholic function at C-10 along with a 3ß,10ß-epoxy function. Their structures have been established on the basis of 1D and 2D NMR experiments, as well as HR-ESIMS. The antimicrobial activity of compounds 1-7 has been evaluated against Gram-positive and Gram-negative strains. Only deacylcynaropicrin 8-O-[3'-hydroxy-2'-methylpropionate] (5) showed moderate antibacterial activity against Staphylococcus aureus with a MIC/MBC value of 500 µg/mL. All isolated compounds have been also evaluated for their cytotoxic activities against cancer cells. Among them, compound 5 showed the highest cytotoxic activity with IC50 values in the range 5.02-16.76 µg/mL.

Curcumin: A naturally occurring autophagy modulator.

Autophagy is a self-degradative process that plays a pivotal role in several medical conditions associated with infection, cancer, neurodegeneration, aging, and metabolic disorders. Its interplay with cancer development and treatment resistance is complicated and paramount for drug design since an autophagic response can lead to tumor suppression by enhancing cellular integrity and tumorigenesis by improving tumor cell survival. In addition, autophagy denotes the cellular ability of adapting to stress though it may end up in apoptosis activation when cells are exposed to a very powerful stress. Induction of autophagy is a therapeutic option in cancer and many anticancer drugs have been developed to this aim. Curcumin as a hydrophobic polyphenol compound extracted from the known spice turmeric has different pharmacological effects in both in vitro and in vivo models. Many reports exist reporting that curcumin is capable of triggering autophagy in several cancer cells. In this review, we will focus on how curcumin can target autophagy in different cellular settings that may extend our understanding of new pharmacological agents to overcome relevant diseases.