Cellular neurobiology of hyperforin.

Hyperforin is a phloroglucinol derivative isolated from the medicinal plant Hypericum perforatum (St John's wort, SJW). This lipophilic biomolecule displays antibacterial, pro-apoptotic, antiproliferative, and anti-inflammatory activities. In addition, in vitro and in vivo data showed that hyperforin is a promising molecule with potential applications in neurology and psychiatry. For instance, hyperforin possesses antidepressant properties, impairs the uptake of neurotransmitters, and stimulates the brain derived neurotrophic factor (BDNF)/TrkB neurotrophic signaling pathway, the adult hippocampal neurogenesis, and the brain homeostasis of zinc. In fact, hyperforin is a multi-target biomolecule with a complex neuropharmacological profile. However, one prominent pharmacological feature of hyperforin is its ability to influence the homeostasis of cations such as Ca2+ , Na+ , Zn2+ , and H+ . So far, the pathophysiological relevance of these actions is currently unknown. The main objective of the present work is to provide an overview of the cellular neurobiology of hyperforin, with a special focus on its effects on neuronal membranes and the movement of cations.

Assessment of Ferula hermonis Boiss fertility effects in immature female rats supported by quantification of ferutinin via HPLC and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferula hermonis is a small shrub renowned for its aphrodisiac abilities. Middle East herbalists have utilized Ferula hermonis seed and root as an aphrodisiac folk medicine to treat women's frigidity and male erectile and sexual dysfunction. AIM OF THE STUDY: Assessment of follicle-stimulating hormone-like (FSH), luteinizing hormone-like (LH), and estrogenic activities of the methanolic extract (ME) of the roots of Ferula hermonis on female reproductive function. MATERIALS AND METHODS: The methanolic extract was prepared from the root of F. hermonis and studied at dose level 6 mg/kg in immature female rats for FSH-like, LH-like, and estrogenic activities. These activities were determined by analyzing gross anatomical features, relative organ weight, and serum level of FSH, LH, progesterone and estrogen hormones, and histopathological characteristics. Quantification of the main phytoestrogenic component ferutinin carried out by HPLC. In addition, molecular docking for the binding affinity of ferutinin inside active sites of both estrogen receptor alpha (ERα) and FSH receptor (FSHR) was performed to predict the potential role of ferutinin in regulating the female reproductive process. RESULTS: Ferula hermonis (ME) showed potent FSH-like, LH-like activities and moderate estrogenic effect at the dose of 6 mg/kg. The content of ferutinin in F. hermonis was estimated to be 92 ± 1.33 mg/g of the methanolic extract. Molecular docking of ferutinin with ERα and FSHR displayed strong interaction with target proteins. CONCLUSIONS: Based on results, it can be concluded that Ferula hermonis can be considered as a suitable female fertility improving agent.

In vitro evaluation of ferutinin on proliferation and osteogenesis differentiation in human unrestricted Somatic stem cells.

Osteoporosis is a common disease in post-menopausal women. The increased risk of breast cancer and malignancy with hormone replacement, hampers its wide-usage. Phytoestrogens are known to have selective estrogen receptor modulator activity. The present study aims to determine how ferutinin affects unrestricted human Somatic Stem Cells (USSCs) osteogenic differentiation. The effect of ferutinin on USSCs proliferation was assessed by MTT assay while osteogenesis was evaluated using Alkaline Phosphatase Activity (ALP), calcium deposition and Alizarin Red Staining. Quantitative real-time PCR was applied to examine the expression of bone specific genes such as osteocalcin, Runx2, and BMP-2. Ferutinin (5-15 µg/mL) could positively impact on the proliferation of cells in a dose-dependent manner. Also, ALP enzyme activity and calcium deposition were enhanced in the presence of ferutinin. Based on real-time PCR results, ferutinin could increase the expression of bone marker genes. The pattern of ferutinin effect on gene expression is similar to standard synthetic estrogen, 17-ß-estradiol. In the presence of the estrogen activity inhibitor (ICI), the effect of ferutinin on ALP and gene level was diminished. In conclusion, ferutinin may be considered as a potential candidate for the stem cell therapy in osteoporosis.

Ferutinin: A phytoestrogen from ferula and its anticancer, antioxidant, and toxicity properties.

This study was performed to evaluate the antioxidant, anticancer, and toxicity properties of ferutinin, a phytoestrogen derived from Ferula species. The human Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line and normal human fibroblast (HDF) were cultured and treated with different ferutinin concentrations. The cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell death-defining tests (a comparative real-time polymerase chain reaction [for Bax and Bcl-2 genes], flow cytometry, and acridine orange/propidium iodide cell staining). Moreover, 15 white male balb/c mice were divided into three groups of five (one untreated control group and two groups), which received different doses of ferutinin-supplemented water (500 and 1000 µg/kg mice weight) to check the mice liver and kidney pathomorphological alterations and to determine the antioxidant enzymes' expression profile (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase) in the mentioned tissues. Finally, the liver lipid peroxidation of mice was analyzed. The results of MTT and cell death-defining tests indicate the significant reduction in cell viability and induction of apoptotic death in MCF-7 cells (enhanced sub-G1 peaks, Bax overexpression, Bcl-2 downregulation, and increased apoptotic cells). The antioxidant enzymes (SOD and CAT) in the mice liver and kidney cells were found to be upregulated (p < .05) in response to the increasing doses of ferutinin. Besides, the lipid peroxidation of the liver tissue of mice was significantly reduced. According to the results, we suggest that ferutinin has the potential to be served as a selective anticancer compound for breast cancer treatment.

Bicyclic Ligand-Biased Agonists of S1P1: Exploring Side Chain Modifications to Modulate the PK, PD, and Safety Profiles.

Sphingosine-1-phosphate (S1P) binds to a family of sphingosine-1-phosphate G-protein-coupled receptors (S1P1-5). The interaction of S1P with these S1P receptors has a fundamental role in many physiological processes in the vascular and immune systems. Agonist-induced functional antagonism of S1P1 has been shown to result in lymphopenia. As a result, agonists of this type hold promise as therapeutics for autoimmune disorders. The previously disclosed differentiated S1P1 modulator BMS-986104 (1) exhibited improved preclinical cardiovascular and pulmonary safety profiles as compared to earlier full agonists of S1P1; however, it demonstrated a long pharmacokinetic half-life (T1/2 18 days) in the clinic and limited formation of the desired active phosphate metabolite. Optimization of this series through incorporation of olefins, ethers, thioethers, and glycols into the alkyl side chain afforded an opportunity to reduce the projected human T1/2 and improve the formation of the active phosphate metabolite while maintaining efficacy as well as the improved safety profile. These efforts led to the discovery of 12 and 24, each of which are highly potent, biased agonists of S1P1. These compounds not only exhibited shorter in vivo T1/2 in multiple species but are also projected to have significantly shorter T1/2 values in humans when compared to our first clinical candidate. In models of arthritis, treatment with 12 and 24 demonstrated robust efficacy.

Ferula L. Plant Extracts and Dose-Dependent Activity of Natural Sesquiterpene Ferutinin: From Antioxidant Potential to Cytotoxic Effects.

The employment studies of natural extracts in the prevention and treatment of several diseases highlighted the role of different species of genus Ferula L., belonging to the Apiaceae family, dicotyledonous plants present in many temperate zones of our planet. Ferula communis L. is the main source of sesquiterpene ferutinin, a bioactive compound studied both in vitro and in vivo, because of different effects, such as phytoestrogenic, antioxidant, anti-inflammatory, but also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. The present review will focus on the molecular mechanisms involved in the different activities of Ferutinin, starting from its antioxidant potential at low doses until its ionophoric property and the subsequent mitochondrial dysfunction induced through administration of high doses, which represent the key point of its anticancer action. Furthermore, we will summarize the data acquired from some experimental studies on different cell types and on several diseases. The results obtained showed an important antioxidant and phytoestrogenic regulation with lack of typical side effects related to estrogenic therapy. The preferential cell death induction for tumor cell lines suggests that ferutinin may have anti-neoplastic properties, and may be used as an antiproliferative and cytotoxic agent in an estrogen dependent and independent manner. Nevertheless, more data are needed to clearly understand the effect of ferutinin in animals before using it as a phytoestrogen or anticancer drug.

Nanoemulsions with oleoresin of Copaifera reticulata (Leguminosae) improve anthelmintic efficacy in the control of monogenean parasites when compared to oleoresin without nanoformulation.

This study compared the in vitro anthelmintic activity of Copaifera reticulata oleoresin (200, 400, 600, 800 and 1,000 mg/L) and of nanoemulsions prepared with this oleoresin (50, 100, 150, 200 and 250 mg/L) against monogeneans on the gills of Colossoma macropomum. The major compounds present in the oleoresin of C. reticulata were γ-macrocarpene (14.2%), α-bergamotene (13.6%), ß-selinene (13.4%) and ß-caryophyllene (11.7%). All concentrations of the nanoemulsion and the oleoresin without nanoformulation showed anthelmintic efficacy against monogeneans, and higher concentrations led to more rapid parasite mortality. Structural damages to the tegument of the parasites exposed to C. reticulata oleoresin were observed with scanning electron microscopy. At two hours of exposure, fish showed 100% tolerance to all nanoemulsion concentrations used in the in vitro assays, whereas 100% mortality was shown in the fish exposed to the oleoresin without nanoformulation after one hour. The results of this study suggest that nanoemulsions with oleoresin of C. reticulata have advantages in the control and treatment of monogenean infections in C. macropomum when compared to the oleoresin without nanoformulation. In addition, since nanoemulsions with the C. reticulata oleoresin are safe to control monogeneans, the efficacy of these nanoformulations may be assayed in therapeutic baths to treat C. macropomum infected by monogeneans.

Extending the Specificity of DRL 72-s Behavior for Screening Antidepressant-Like Effects of Glutamatergic Clinically Validated Anxiolytic or Antidepressant Drugs in Rats.

Both an agonist and its associated prodrug for metabotropic glutamate2/3 (mGlu2/3) receptors demonstrated anxiolytic efficacy in large, randomized, multicenter, double-blind, placebo-controlled trials studying patients with generalized anxiety disorder (GAD). These mGlu2/3 receptor agonists produced robust preclinical anxiolytic-like effects in rodent models. Several different metabotropic glutamate2 receptor positive allosteric modulators have been found to produce antidepressant-like effects on several preclinical screening paradigms, including differential-reinforcement-of-low-rate 72-second (DRL 72-s) behavior [increased reinforcers, decreased response rate, and cohesive rightward shifts in inter-response time distributions]. Although mGlu2/3 receptor agonists have not been tested formally for therapeutic effects in treating patients with major depressive disorder, these compounds generally fail to exert antidepressant-like effects in preclinical screening paradigms and did not improve depressive symptoms in GAD trials. Thus, the present studies were designed to test the potential antidepressant-like effects of the mGlu2/3 receptor agonist 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-bicarboxylate monohydrate (LY354740) on the DRL 72-s schedule. LY354740 did not test similarly to clinically validated antidepressant drugs when administered alone or when coadministered with the selective serotonin reuptake inhibitor fluoxetine in rats. Another glutamate-based antidepressant drug, the uncompetitive N-methyl-D-aspartate channel blocker racemic ketamine, exerted antidepressant-like effects when administered at subanesthetic doses in rats. The findings further support the specificity of rat DRL 72-s behavior when screening for anxiolytic versus antidepressant drugs and extend testing of compounds with glutamatergic mechanisms of action. SIGNIFICANCE STATEMENT: The metabotropic glutamate2/3 receptor agonist and clinically validated anxiolytic drug 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-bicarboxylate monohydrate did not test similar to antidepressant drugs (increased reinforcers, decreased response rate, and cohesive rightward shifts in the inter-response time distribution) when tested on differential-reinforcement-of-low-rate 72-second (DRL 72-s) behavior and also did not enhance the antidepressant-like effects of the serotonin reuptake inhibitor fluoxetine. The uncompetitive N-methyl-D-aspartate receptor antagonist ketamine increased the reinforcement rate, decreased the response rate, and induced a rightward shift in the inter-response time distribution similar to antidepressant drugs; these results confirm the utility of DRL 72-s schedule of reinforcement when testing clinically validated anxiolytic versus antidepressant glutamatergic drugs.

Ferula hermonis: A Review of Current Use and Pharmacological Studies of its Sesquiterpene Ester Ferutinin.

Ferula hermonis Boiss, is an endemic plant of Lebanon, locally known as "shilsh Elzallouh". It has been extensively used in the traditional medicine as an aphrodisiac and for the treatment of sexual impotence. Crude extracts and isolated compounds of ferula hermonis contain phytoestrogenic substances having a wide spectrum of in vitro and in vivo pharmacological properties including anti-osteoporosis, anti-inflammatory, anti-microbial and anti-fungal, anti-cancer and as sexual activity enhancer. The aim of this mini-review is to highlight the traditional and novel applications of this plant's extracts and its major sesquiterpene ester, ferutinin. The phytochemical constituents and the pharmacological uses of ferula hermonis crude extract and ferutinin specifically will be discussed.

Comparison the Effect of Ferutinin and 17ß-Estradiol on Bone Mineralization of Developing Zebrafish (Danio rerio) Larvae.

There is an urgent need to develop novel drugs for osteoporosis which occurs due to estrogen deficiency. Phytoestrogens derived from medicinal plants would be the best alternative to chemical drugs with harmful side effects. The main purpose of the present study was to investigate the effect of ferutinin compared to 17ß-estradiol (E2) on bone mineralization of zebrafish larvae. Regarding the lack of publications, the histology analysis was performed after exposure to E2 to find effective treatment on bone mineralization of developing zebrafish larvae. Then, the larvae were exposed to four concentrations of ferutinin at three time points to assess the mortality, the expression of some related genes and histology of the ceratohyal and hyomandibular of treated larvae. The RT-PCR result of the treatment groups demonstrated the similar expression pattern in the larvae which were exposed to 1.25 µg/mL of ferutinin and 2 µM of E2 at 2 dpf, which confirmed the result of histology analysis. In addition, RT-qPCR of high concentration of ferutinin and E2 demonstrated that bmp2a/b and esr1 were downregulated and upregulated when the larvae were exposed to 5 µg/mL of ferutinin and 10 µM of E2, respectively.

Residual inhibition: From the putative mechanisms to potential tinnitus treatment.

Neurons in various sensory systems show some level of spontaneous firing in the absence of sensory stimuli. In the auditory system spontaneous firing has been shown at all levels of the auditory pathway from spiral ganglion neurons in the cochlea to neurons of the auditory cortex. This internal "noise" is normal for the system and it does not interfere with our ability to perceive silence or analyze sound. However, this internal noise can be elevated under pathological conditions, leading to the perception of a phantom sound known as tinnitus. The efforts of many research groups, including our own, led to the development of a mechanistic understanding of this process: After cochlear insult the input to the central auditory system becomes markedly reduced. As a result, the neural activity in the central auditory system is enhanced to compensate for this reduced input. Such hyperactivity is hypothesized to be interpreted by the brain as a presence of sound. This implies that suppression of hyperactivity should reduce/eliminate tinnitus. This review explores research from our laboratory devoted to identifying the mechanism underlying residual inhibition of tinnitus, a brief suppression of tinnitus following a sound stimulus. The key mechanisms that govern neural suppression of spontaneous activity in animals closely resemble clinical psychoacoustic findings of residual inhibition (RI) observed in tinnitus patients. This suppression is mediated by metabotropic glutamate receptors (mGluRs). Lastly, drugs targeting mGluRs suppress spontaneous activity in auditory neurons and reduce/eliminate behavioral signs of tinnitus in mice. Thus, these drugs are therapeutically relevant for tinnitus suppression in humans.

Towards green drugs against cestodes: Effectiveness of Pelargonium roseum and Ferula gummosa essential oils and their main component on Echinococcus granulosus protoscoleces.

Cystic echinococcosis is of great public health importance. Surgery is the efficient treatment for this infection. To minimize the risk of cyst intraoperative leakage, using scolicidals is crucial. To date, any efficacious scolicidal without side effect has not been introduced. Since essential oils of Pelargonium roseum and Ferula gummosa have shown several bioactivities, we evaluated their potential against protoscoleces of E. granulosus using albendazole as positive control. Furthermore, chemical composition of both essential oils was analyzed by gas chromatography-mass spectrometry (GC-MS) analyses, and their main constituents were also evaluated for scolicidal activity. Different concentrations of essential oils and their two main constituents were tested for scolicidal activity. Mortality rate was measured by eosin staining. Results of GC-MS revealed citronellol and ß-pinene as the main constituents of P. roseum and F. gummosa essential oils, respectively. After 60 min of exposure to 50 µg/mL of P. roseum and F. gummosa, mean mortality rate of protoscoleces was 100%. However, ß-pinene and citronellol at the same time point with only 10 µg/mL concentrations resulted in approximately higher than 80% mortality. Essential oils of P. roseum and F. gummosa showed significant toxic effect on E. granulosus with 50% lethal concentration (LC50) values of 8.52 and 17.18 µg/mL, respectively. Based on the LC50 values, ß-pinene (2.20 µg/mL) was the most potent scolicidal agent in the present study. The overall toxicity of ß-pinene and citronellol was significantly higher than the whole essential oils of F. gummosa and P. roseum. Based on these results, ß-pinene and citronellol can be considered as candidate ingredients for the development of green scolicidals.

Anti-Oxidant and Anti-Melanogenic Properties of Essential Oil from Peel of Pomelo cv. Guan Xi.

Here, we investigated the anti-oxidant and anti-melanogenic effects of pomelo peel essential oil (PPEO) from pomelo cv. Guan Xi. The volatile chemical composition of PPEO was analyzed with gas chromatography⁻mass spectrometry (GC/MS). The most abundant component of PPEO was limonene (55.92%), followed by ß-myrcene (31.17%), and ß-pinene (3.16%). PPEO showed strong anti-oxidant activities against 1,1-diphenyl-2-picryhydrazyl (DPPH) (,2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) (, and superoxide anion free radicals. Based on the B16 melanoma cell system, the effects of PPEO on the viability and morphology of B16 cells and the production of melanin were evaluated. The results revealed that PPEO at concentrations below 50 µg/mL could decrease the melanin content without affecting cell viability and morphology. Intracellular tyrosinase (TYR) activity and Western blot analysis showed that PPEO could down-regulate the expression level of TYR in B16 cells and dose-dependently inhibit TYR activity (by a maximum of 64.54%). Meanwhile, the main active components responsible for the effect are citral and ß-myrcene. In conclusion, PPEO has good anti-oxidant and anti-melanogenic activity, and thus can be widely used as a natural antioxidant in the food, pharmaceutical, and cosmetic industries.

Essential Oils of Five Baccharis Species: Investigations on the Chemical Composition and Biological Activities.

This paper provides a comparative account of the essential oil chemical composition and biological activities of five Brazilian species of Baccharis (Asteraceae), namely B. microdonta, B. pauciflosculosa, B. punctulata, B. reticularioides, and B. sphenophylla. The chemical compositions of three species (B. pauciflosculosa, B. reticularioides, and B. sphenophylla) are reported for the first time. Analyses by GC/MS showed notable differences in the essential oil compositions of the five species. α-Pinene was observed in the highest concentration (24.50%) in B. reticularioides. Other major compounds included α-bisabolol (23.63%) in B. punctulata, spathulenol (24.74%) and kongol (22.22%) in B. microdonta, ß-pinene (18.33%) and limonene (18.77%) in B. pauciflosculosa, and ß-pinene (15.24%), limonene (14.33%), and spathulenol (13.15%) in B. sphenophylla. In vitro analyses for antimalarial, antitrypanosomal, and insecticidal activities were conducted for all of the species. B. microdonta and B. reticularioides showed good antitrypanosomal activities; B. sphenophylla showed insecticidal activities in fumigation bioassay against bed bugs; and B. pauciflosculosa, B. reticularioides, and B. sphenophylla exhibited moderate antimalarial activities. B. microdonta and B. punctulata showed cytotoxicity. The leaves and stems of all five species showed glandular trichomes and ducts as secretory structures. DNA barcoding successfully determined the main DNA sequences of the investigated species and enabled authenticating them.

Oviposition deterrent activity of basil plants and their essentials oils against Tuta absoluta (Lepidoptera: Gelechiidae).

The leafminer Tuta absoluta Meyrick (Lepidoptera: Gelechiidae) is one of the most important pests of tomato, reducing crop yields by up to 100% in greenhouses and fields, in several countries globally. Because synthetic insecticides lead to resistance and have adverse effects on natural enemies and the health of producers, alternative control methods are needed. In this study, we assessed the oviposition-deterring effect of basil plants, Ocimum gratissimum L. and O. basilicum L. (Lamiaceae), using dual-choice behavioural assays performed in flight tunnels. We found that both plants significantly reduced T. absoluta oviposition behaviour on a tomato plant located nearby. To evaluate the potential effect of basil volatile organic compounds, we formulated essential oils of both plant species in paraffin oil, and observed a similar oviposition-deterring effect. Gas chromatography analyses detected 18 constituents in these essential oils which the major constituents included thymol (33.3%), p-cymene (20.4%), γ-terpinene (16.9%), myrcene (3.9%) in O. gratissimum and estragol (73.8%), linalool (8.6%), ß-elemene (2.9%) and E-ß-ocimene (2.6%) in O. basilicum. Twenty and 33 compounds were identified of the volatiles collected on O. gratissimum and O. basilicum plants, respectively. The main components include the following: p-cymene (33.5%), γ-terpinene (23.6%), α-terpinene (7.2%), α-thujene (6.7%) and E-α-bergamotene (38.9%) in O. gratissimum, and methyl eugenol (26.1%), E-ß-ocimene (17.7%), and linalool (9.4%) in O. basilicum. Four compounds (α-pinene, ß-pinene, Myrcene, Limonene) were common in essential oils and plants. Our results suggest the valuable potential of basil and associated essential oils as a component of integrated management strategies against the tomato leafminer.

Insecticide activity of Baccharis dracunculifolia essential oil against Cochliomyia macellaria (Diptera: Calliphoridae).

The ethnobotanical uses of Brazilian plants for different injuries and diseases conjoined with local rich biodiversity represent an important resource for research and development. This study aimed to characterise BDEO and its in vitro activity on the third instar larvae (L3) of Cochliomyia macellaria. Groups of 20 L3 were placed on filter paper impregnated with increasing concentrations of 5-30% (v/v), equivalent to 0.79-4.77 µL/cm2, solubilised in ethanol or acetone. The major constituents of BDEO were ß-pinene (9.94%), D-limonene (9.59%), ß-nerolidol (7.93%), caryophyllene (7.69%), spathulenol (6.69), α-muurolene (6.74%) and α-pinene (5.31%). Lethal concentrations of 50% for BDEO on C. macellaria (LC50) after 24 and 48 h of exposure were 2.63 and 2.47 µL/cm2 for ethanol and 9.58 and 8.11 µL/cm2 for acetone, respectively. Furthermore, larvae cuticle abnormalities and adult deformity were observed. Our data confirm the effectiveness of BDEO as an ecofriendly product against blowflies.

Evaluation of active ingredients and larvicidal activity of clove and cinnamon essential oils against Anopheles gambiae (sensu lato).

BACKGROUND: Mosquitoes are well-known vectors of many diseases including malaria and lymphatic filariasis. Uses of synthetic insecticides are associated with high toxicity, resistance, environmental pollution and limited alternative, effective synthetic insecticides. This study was undertaken to evaluate the larvicidal efficacy of clove and cinnamon essential oils against laboratory Anopheles gambiae (sensu stricto) and wild An. arabiensis larvae. METHODS: The standard WHO guideline for larvicides evaluation was used, and the GC-MS machine was used for active compounds percentage composition analysis and structures identification. Probit regression analysis was used for LC50 and LC95 calculations while a t-test was used to test for significant differences between laboratory-reared and wild larvae populations in each concentration of plant extract. RESULTS: Mortality effect of clove and cinnamon essential oils against wild and laboratory-reared larvae had variations indicated by their LC50 and LC95 values. The mortality at different concentrations of cinnamon and clove post-exposure for wild and laboratory-reared larvae were dosage-dependent and were higher for cinnamon than for clove essential oils. The mortality effect following exposure to a blend of the two essential oils was higher for blends containing a greater proportion of cinnamon oil. In the chemical analysis of the active ingredients of cinnamon essential oil, the main chemical content was Eugenol, and the rarest was ß-Linalool while for clove essential oil, the main chemical content was Eugenol and the rarest was Bicyclo. CONCLUSION: The essential oils showed a larvicidal effect which was concentration-dependent for both laboratory and wild collected larvae. The active ingredient compositions triggered different responses in mortality. Further research in small-scale should be conducted with concentrated extracted compounds.

Phytochemistry and Pharmacology of Ferula hermonis Boiss. - A Review.

Ferula hermonis, a well-known species of the genus Ferula found in Lebanon and Syria, has a brilliant history in traditional medicine as it has been used for the treatment of erectile dysfunction in men and menopausal disturbances in women. Thanks to modern pharmacological and clinical investigations, F. hermonis is a valuable medicinal and condimental plant that may be used for the treatment of impotence and diabetes, the prevention of osteoporosis, and possesses anti-microbial and anti-inflammatory properties. Phytochemical investigations have shown that this plant contains daucane aryl esters such as ferutinin, which has exhibited various biological activities including hypoglycemic and estrogenic activities. Ferutinin is one of the strongest natural phytoestrogen which has agonistic activity on estrogen receptors, particularly α receptor. It seems that ferutinin and its derivatives play an important role in F. hermonis biological activities, mainly the beneficial effects of this plant on impotence, diabetes and osteoporosis. The present review discusses the available data on the active constituents and biological activities of F. hermonis and their possible underlying mechanisms of action.

Yunnaneic Acid B, a Component of Pulmonaria officinalis Extract, Prevents Peroxynitrite-Induced Oxidative Stress in Vitro.

Our work reveals that the aerial parts of Pulmonaria officinalis L. are a new source of yunnaneic acid B. We studied antioxidant activity and cytotoxicity of this compound (1-50 µg/mL) and its contents in various plant extracts. This is the first study confirming the presence of yunnaneic acid B in P. officinalis L. and Pulmonaria obscura Dumort and hence in the Boraginaceae family. Determination of 1,1-diphenyl-2-picrylhydrazyl radical reduction and peroxynitrite-scavenging efficacy in inorganic experimental systems provided EC50 values of 7.14 and 50.45 µg/mL, respectively. Then we examined the antioxidant action of yunnaneic acid B in blood plasma under peroxynitrite-induced oxidative stress in vitro. Yunnaneic acid B effectively diminished oxidative damage to blood plasma proteins and lipids. Furthermore, it was able to prevent the peroxynitrite-induced decrease in nonenzymatic antioxidant capacity of blood plasma. Additionally, cytotoxicity of yunnaneic acid B (at concentrations ≤50 µg/mL) toward peripheral blood mononuclear cells was excluded.

Biological properties of Hertia cheirifolia L. flower extracts and effect of the nopol on α-glucosidase.

In screening for antioxidant and α-glucosidase inhibitors from the extracts of Hertia cheirifolia L. flowers, the petroleum ether extract showed interesting antioxidant activity and inhibitory effect on the activity of α-glucosidase. The fractionation of this extract resulted in the isolation of a compound which is characterized by NMR and ESI-MS as a nopol. The nopol exhibited potent α-glucosidase inhibitory potential with IC50 value of 220µM. The kinetic evaluation indicated that it acts as a non-competitive inhibitor. A molecular docking study proved that the nopol presented a strong affinity with amino acid residues of α-glucosidase.