Alkaloid Fraction Research Articles

Bioactivity Enhanced Isolated Carpaine from Carica papaya Leaves for Platelet Stimulating Activity

Carica papaya leaves are used in folklore medicine for the treatment of different types of thrombocytopenia associated with diseases and drugs. There are several scientific studies carried out on humans and animal models to confirm the efficacy of papaya leaves extract for the treatment of thrombocytopenia. In the present study, the alkaloid, carpaine extracted from papaya leaves was found to have platelet stimulating activity. Papaya leaves powder was extracted by microwave with a mixture of methanol: glacial acetic acid: water (180:2:1.6 v/v/v). The extract was treated with suitable solvent to obtain alkaloid fraction. From the total alkaloids, carpaine was further separated by preparative thin layer chromatography, purified and analyzed. Carpaine was complexed with beta-cyclodextrin and mixed with piperine. The complex was administered in thrombocytopenia induced rats. The results showed that bioavailability enhanced carpaine exhibits potent activity of increasing platelet count.

Effect of habitat variations on the chemical composition, antioxidant, and antimicrobial activities of Achillea fragrantissima (Forssk) Sch. Bip

Achilea fragmentisma plant is widely distributed along northern regions of Saudi Arabia with various traditional medical uses. The plant was collected from Tabuk and Arar regions to study the effect of the variation in habitat on the chemical compositions, antimicrobial and antioxidant activities of the plant. The results showed significant differences between the two studied region regarding the parameters of the weather in years from 2010–2016.The antioxidant and antimicrobial of the plant showed significant variation in two habitats. Plant collected from Arar showed high antioxidant activity with IC50 (0.21 ± 0.01 g/L) by DPPH radical scavenging methods, and good antibacterial activity with gram-positive bacteria (Staphylococcus epidermidis, Bacillus cereus and Staphylococccus aureus clinical isolate), antibacterial activity ranging between high to no activity (between 14.5 ± 0.5–6.0 ± 0.0 mm zone of inhibition), On the other side the tested plant extracts showed no effect on, all gram-negative bacteria. GC/MS data showed marked variation in chemical compositions of both phenolic and alkaloid compounds in plants collected from both regions. Phenolic compounds were accumulated with higher amounts(Ferulic acid, Eugenol and Salicylic acid ester) in Arar region, while the alkaloid fractions (Ethyl isoallocholate, Pterin 6-carboxylic-acid and kadain) showed higher concentrations in plants collected from Tabuk region. The results reflect the variation in of weather parameter, affect on chemical compositions and biological activities of the plant in two studied regions.

Metabolic profiling of monoterpenoid indole alkaloids from Tabernaemontana catharinensis (A. DC) latex by GC-MS

Abstract Latex from Tabernaemontana catharinensis contains synthesized bioactive compounds known as monoterpenoid indole alkaloids (MIAs). Such compounds have several biological activities, including as cholinesterase inhibitors, and have analgesic, anti-inflammatory, bactericidal, antileishmanial, antitumoral andestrogenic properties, as well as acting as stimulants and depressants of the central nervous system. The objective of the present study was to perform the metabolite profiling of alkaloidal extracts from T. catharinensis latex. The alkaloidal fraction obtained from T. catharinensis latex was analyzed by Gas Chromatography coupled to Mass Spectrometry (GC–MS). The T. catharinensis latex was obtained after cutting the stem and allowing it to flow into tap water that was submitted to an acid-basic procedure for total MIA extraction, which was then analyzed by GC–MS. The total MIA extract was directly subjected to GC–MS without a derivatization step, allowing the detection and identification of ten known and three unknown MIAs. The described method resulted in effective separation and analysis by GC-EI-MS, which permitted the identification of known bioactive MIAs, as well as the structural elucidation of new MIAs with potential biological activities.

1,6-Dehydropinidine Is an Abundant Compound in Picea abies (Pinaceae) Sprouts and 1,6-Dehydropinidine Fraction Shows Antibacterial Activity against Streptococcus equi Subsp. equi.

Knowledge about the defensive chemistry of coniferous trees has increased in recent years regarding a number of alkaloid compounds; in addition to phenolics and terpenes. Here, we show that Norway spruce (Picea abies (L.) H. Karst.), an important boreal zone tree species; accumulates 1,6-dehydropinidine (2-methyl-6-(2-propenyl)-1,6-piperideine) in its needles and bark. We reanalyzed previously published GC-MS data to obtain a full picture of 1,6-dehydropinidine in P. abies. 1,6-dehydropinidine appeared to especially accumulate in developing spring shoots. We used solid-phase partitioning to collect the alkaloid fraction of the sprouts and thin-layer chromatography to purify 1,6-dehydropinidine. The antibacterial properties of the 1,6-dehydropinidine fraction were tested using a broth microdilution method; with Streptococcus equi subsp. equi as a model organism. Based on our results 1,6-dehydropinidine is common in alkaloid extractions from P. abies (0.4 ± 0.03 mg g−1 dw in mature needles) and it is especially abundant in young spruce shoots (2.7 ± 0.5 mg g−1 dw). Moreover; 1,6-dehydropinidine extracted from P. abies sprouts showed mild antibacterial potential against Streptococcus equi subsp. equi (MIC 55 µg mL−1). The antibacterial activity of a plant compound thought of as an intermediate rather than an end-product of biosynthesis calls for more detailed studies regarding the biological function of these coniferous alkaloids

Anti-malarial activity and toxicity of Aspidosperma nitidum Benth: a plant used in traditional medicine in the Brazilian Amazon

The objective of this work was to evaluate the antiplasmodial activity and toxicity of the extract and fractions obtained from the bark of Aspidosperma nitidum. The ethanol extract obtained from the powdered bark of plants was acid-base partitioned and phytochemically analyzed. The antiplasmodial activity, in vivo antimalarial activity and in vitro cytotoxicity were acessed. The selectivity index (SI) was calculated. The acute oral toxicity and pathological effects, of the ethanol extract was evaluated in mice. The major constituent of the ethanol extract was suggestive of a β-carboline chromophore. The alkaloid and neutral fractions contained compounds with an aspidospermine core as the major constituent. The ethanol extract (IC50 = 3.60 µg/mL), neutral fraction (IC50 = 3.34 µg/mL) and alkaloid fraction (IC50= 2.32 µg/mL) showed high activity against P. falciparum (W2 strain). The ethanol extract and the alkaloid fraction reduced 80% of the parasitemia of P. berghei (ANKA)-infected mice (dose of 500 mg/kg) in the 5th day, which was not sustainable at the 8th day. A similar result was obtained for chloroquine. The ethanol extract (CC50 = 410.65 µg/mL; SI = 114.07), neutral fraction (CC50 = 452.53 µg/mL; SI = 135.49), and alkaloid fraction (CC50 =346.73 µg/mL; SI 149.45) demonstrated low cytotoxicity and high SI. The ethanol extract (5000 mg/kg; gavage) presented low acute oral toxicity, with no clinical or anatomopathological modifications being observed (in comparison to the control group). In vitro studies with a chloroquine-resistant clone of P. falciparum confirmed the antiplasmodial activity of the A. nitidum ethanol extract, and its fractions had low cytotoxicity for HepG2 cells. In vivo studies with P. berghei–infected mice and acute toxicity studies corroborated these results.

The Bioassay-Guided Fractionation and Identification of Potent Acetylcholinesterase Inhibitors from Narcissus c.v. 'Hawera' Using Optimized Vacuum Liquid Chromatography, High Resolution Mass Spectrometry and Bioautography.

Bioassay-guided isolation of bioactive compound is a modern and efficient technique in metabolites screening. It may shorten the total time of the entire process and reduce some costs of it. The aim of this paper was to fractionate and isolate alkaloids by developing an innovative vacuum liquid chromatography method for a species of Narcissus c.v. ‘Hawera’ rarely investigated so far and establishing the inhibitory activity of acetylcholinesterase (AChE). The studies consisted of the extraction of plant material by modern pressurized liquid extraction (PLE), followed by the isolation of alkaloidal fractions. For this purpose, the pioneering gradient vacuum liquid chromatography (gVLC) technique was employed by using two sorbents in various proportions packed in polypropylene cartridges for the first time. This step was performed in order to pre-clean the samples but also to establish the best combination of sorbents which permits obtaining potentially strong AChE inhibitors. The collected fractions were examined by HPLC/ESI-QTOF-MS in order to compare which combination of sorbents would allow us to obtain the highest concentration of alkaloids. The combination of these techniques confirmed the presence of the alkaloids and enabled the development of a modern method for the fractionation and isolation of the compounds with strong anti-AChE activity.

Evaluation of the effect of Peganum harmala extracts on the in vitro viability of Leishmania tropica promastigotes in comparison to Glucantime.

Cutaneous leishmaniasis is a skin disease that pretends with skin lesions, mainly ulcers, on exposed parts of the body. It's caused mainly by parasites belonging to the genus Leishmania, such as L. tropica. Medicinal plants, which have sparked recent researches attention, consider one of the richest sources of active compounds against the Leishmania parasite including Peganum harmala. This study was conducted to investigate the antileishmanial effect of different extracts of Peganum harmala grown in Syria, particularly the methanolic extract of seeds and roots as well as its alkaloid fractions on Leishmania tropica promastigotes growth in vitro. After culturing promastigotes and incubating with extracts for 72h, the surviving promastigotes were counted. The half maximal (50%) inhibitory concentration (IC50) was determined. The experiments were repeated at least three times. The in vitro experiment has demonstrated a concentration-dependent decrease of parasites number caused by the extracts with an IC50 value of 18.61 ± 0.87µg/mL and 16.41 ± 0.71µg/mL for the methanolic extract of seeds and roots respectively. While the IC50 of the alkaloid fractions of seeds and roots were 4.97 ± 0.43μg/mL and 9.23 ± 0.86μg/mL respectively. There was a significant difference between all extracts and Glucantime which had IC50 = 32.62 ± 0.66µg/mL.

Antileishmanial activity of Annona species (Annonaceae)

Annona species are widely used in traditional medicine against leishmaniasis. In vitro studies have confirmed their antileishmanial activity. Objective: review the antileishmanial activity of Annona species. Results: This article provides a review Annona species activity against leishmaniasis, in which it suggests that extracts of A. mucosa were active against promastigotes and amastigotes of L. amazonensis. Moreover, extracts of A. crassiflora were active only against promastigotes of L. donovani, whereas the extract, alkaloid fraction and liriodenine of A. foetida were active against promastigotes of L. braziliensis and L. guyanensis. Liriodenine was also very active against L. amazonensis. Furthermore, extracts and fractions from stems of A. muricata were active against Leishmania sp. This activity may be related to the presence of acetogenins, since fractionation contributed to increase activity. The fractionation of A. purpurea extract contributed to antileishmanial activity, and resulted in a fraction with high selectivity. Such activity may be related to alkaloids or acetogenins. Conclusions: In this review article it is suggested that Annona species are promising as leishmanicide and this activity may be related to acetogenins and alkaloids.

Alkaloid and terpenoid fractions from the leaves of Launaea taraxacifolia (Willd.) repressed the proliferation of Plasmodium berghei in mice

Medicinal plants play a major role in the treatment and prevention of malaria in many communities across the world. The aim of the study was to validate the ethno pharmacological claims of L. taraxacifolia, traditionally used to treat malaria in western part of Nigeria by evaluating its antiplasmodial efficacies. A maceration of dried leaves of L. taraxacifolia was prepared in ethanol. Alkaloid and terpenoid fractions of L. taraxacifolia were extracted using solvent-solvent extraction methods. Antiplasmodial activities of crude extract, alkaloid and terpenoid fractions of L. taraxacifolia were assessed by suppressive, curative and prophylaxis assays against chloroquine-sensitive P. berghei (NK-65) infected mice. Enzyme activities (AST, ALT, ALP and gamma-GT) were evaluated in serum of P. berghei infected mice. Radical scavenging activity of the extract was measured using DPPH, hydroxyl radical and FRAP FRPAS assays. Phytochemical analysis of the extract and fractions were done using GC system. The results of this study showed that the crude extract and fractions inhibited the proliferation of P. berghei with varying degrees. Crude extract displayed a significant (p < 0.05) chemosuppression effects at 200 and 400 mg/kg body weight. Alkaloid and terpenoid fractions were relatively potent than the crude extract at 10 mg/kg body weight. The extract and fractions of L. taraxacifolia significantly (p < 0.05) reversed the increase in activities of enzymes caused by P. berghei infection in mice. In addition, oral administration of L. taraxacifolia extract and fractions significantly normalized the concentration of urea and creatinine in the serum of treated mice. Some known alkaloids and terpenoids identified from the leaves of L. taraxacifolia are β-sitosterol 3-0-β-D-glucopyranoside, 16-carbaldehyde, 7a-Hexahydro 6H-indol-6-one, 3,4-Dimethoxyphenyl, octahydro-1-methyl and β-carboline-3-carboxylic acid. The results of this study support the ethno medical use of L. taraxacifolia leave as antimalarial remedies. Further studies on the mechanism of actions of the antiplasmodial components of L. taraxacifolia may lead to the discovery of a more potent antimalarial drug.

Intestinal anti-inflammatory activity of the total alkaloid fraction from Fumaria capreolata in the DSS model of colitis in mice

Fumaria genus has been traditionally used for managing inflammatory and gastrointestinal disorders. The study evaluates the immunomodulatory potential of the total alkaloid fraction from Fumaria capreolata L. (AFC) in primary macrophages and the intestinal anti-inflammatory effect in a dextran sodium sulphate-induced colitis in mice. AFC inhibited LPS-stimulated bone marrow-derived macrophages gene expression program dose-dependently. In vivo, AFC markedly reduced macroscopic and microscopic signs of intestinal inflammation. Besides, it restored the colonic expression of pro-inflammatory and anti-inflammatory mediators, as well as enhanced the expression of intestinal barrier markers. These results demonstrate the potential of AFC extract as a therapeutic tool for the management of inflammatory bowel disease.

Nanosecond pulsed electrical fields enhance product recovery in plant cell fermentation

The potential of pharmacologically active secondary plant metabolites is limited by the low yield from often rare plants, and the lack of economically feasible chemical synthesis of these complex compounds. Plant cell fermentation offers an alternative strategy to overcome these constraints. However, the efficiency of this approach is limited by intracellular sequestration of the products, such that continuous bioprocessing is not possible. As a precondition for such a, more attractive, continuous process, it is of great importance to stimulate the export of the product into the medium without impairing viability and, thus, the productivity of the cells. Using nicotine alkaloids of tobacco as a case study, an alternative strategy is explored, where nanosecond pulsed electric fields (nsPEFs) are applied for the efficient downstream recovery of the products. To maintain cell viability and allow for the further use of biomass, cells were exposed to strong (1–20 kV·cm−1), but very short (10–100 ns) electric pulses, which leads to a temporary permeabilisation of cell membranes. Using two transgenic cell lines, where two key genes involved in the metabolism of the anti-Alzheimer compound nornicotine were overexpressed, we could show that this nsPEF treatment improved the partitioning of some nicotine alkaloids to the culture medium without impairing viability, nor the synthesis of alkaloids. However, this release was only partial and did not work for nornicotine. Thus, nsPEFs produced a fractionation of alkaloids. We explain this electrofractionation by a working model considering the differential intracellular compartmentalization of nicotineic alkaloids.

Acute and Sub-Acute Toxicological Evaluations of Bioactive Alkaloidal Extract from Melodinus henryi and Their Main Chemical Constituents

Melodinus henryi is a good source of terpenoid indole alkaloids, and traditionally used as a folk medicine in the treatment of meningitis and fracture. In order to further exploit their potential uses, its anti-inflammatory and immunosuppressive activities, safety evaluations and chemical profiles have been illustrated. Compared to the crude methanol extract from M. henryi and its non-alkaloidal fraction, the total alkaloidal fraction (MHTA) had the strongest anti-inflammatory and immunosuppressive activities. In the acute oral toxicity assay, the half lethal dose (LD50) of MHTA was more than 2000 mg/kg. The sub-acute toxicity assay for consecutive 28 days exhibited MHTA at a lower concentrations of less than 500 mg/kg might be regarded as safe, and might damage spleen, liver, kidney, and heart when the dose is higher than 1000 mg/kg. In addition, a phytochemical investigation on MHTA led to the isolation of 15 monoterpenoid indole alkaloids. Thus, in regard with the potent side effects of MHTA, it should be used with caution in the development of phytomedicine.Graphic

Plumeran Indole Alkaloids From Aspidosperma pyrifolium Flowers

Aspidosperma pyrifolium Mart., Apocynaceae, is a species popularly known with the popular Brazilian names of “pereiro” and “pau-pereiro.” It is a native tree from the Caatinga biome, and the flowers frequently attract bees. The species is known for the presence of plumeran indole alkaloids. In this study, the alkaloidal fraction of A. pyrifolium flowers resulted in the characterization of eighteen plumeran indolic alkaloids via ultra-performance liquid chromatography coupled with diode array and quadrupole time-of-flight mass spectrometry. Four of these alkaloids were isolated, and their structures were established by different spectroscopic methods. The novel indole alkaloid N-formyl-15-methoxy-aspidofractinin, in addition to the known alkaloids pyrifoline, aspidospermine, and 15-methoxy-aspidospermine, was identified from the analyzed plant.

High-performance countercurrent chromatography fractionation of epimeric pairs intermedine/lycopsamine and amabiline/supinine by an off-line electrospray mass spectrometry injection profiling of the roots of Lappula squarrosa

The toxicity of pyrrolizidine alkaloids (PAs) and how they endanger the health of livestock and humans have been known for decades. However, quantitative measurements of these toxic PAs in food sources and herbal products are still hindered by poor availability of some authenticated reference standards. In this study, a PA fortified extract from a lyophilized Lappula squarrosa root sample (564 g) was separated using high-performance countercurrent chromatography (HPCCC) with the solvent system n-hexane − n-butanol − 1% aqueous ammonia (1:1:2, v/v/v). The HPCCC fractions were initially monitored by an off-line electrospray ionization mass-spectrometry (ESI-MS), and the targeted alkaloid fractions were subsequently elucidated by GC-EI-MS, ESI-MS/MS injection profiling, coupled with 1D/2D-NMR analysis. This approach led to accurate fractionation of some L. squarrosa PAs, while high recovery rates were reached since adsorptive losses of sample is neglected as countercurrent chromatography is an all-liquid chromatographic technique.

Variability of the Chemical Composition of the Essential Oils of Flowers and the Alkaloid Contents of Leaves of Sophora secundiflora and Sophora tomentosa

GC/MS analyses of the essential oils isolated from the fresh flowers of Sophora secundiflora and Sophora tomentosa had led to the identification of fifty components (97.43 %) and seventeen components (85.08 %), respectively. The Major components were 2-pentadecanone (32.91 %), 2-tridecanone (14.98 %) from S. secundiflora and n-pentacosane (36.83 %), n-heptacosane (19.03 %) from S. tomentosa. Additionally, volatile alkaloids from the leaves’ alkaloid fraction of both species analyzed by GC/MS with the identification and quantification of 10 major alkaloids.

Viability of and germination test conditions for Schoenocaulon officinale seeds

ABSTRACT Schoenocaulon officinale , commonly known as Sabadilla, is a new world species, which has been an important medicinal plant for Native Americans, and it is currently economically important for the production of some homeopathic medicines. At present, research regarding Sabadilla has mainly been focused on systematics, quantitative analysis of alkaloid fraction, and its insecticidal and medicinal properties. A search in academic databases produced no literature on seed germination of S. officinale. Therefore, the main objectives of this research were to determine suitable germination test conditions and to assess the storability of S. officinale seeds. Triphenyl tetrazolium chloride method was used to determine the viability of the seeds. Owing to the lack of methodology for this species, the International Seed Testing Association (ISTA)’s rules for Allium cepa were used as the starting point. Seeds were stored at 6°C, and germination tests were carried out at 20°C, with permanent light. A thermo-gradient table was used to identify the optimum temperature for germination. Sabadilla seeds started to germinate 18 days after planting, and complete germination was achieved in 42 days. Best germination rates were achieved using constant temperatures between 19.2°C and 30.7°C and alternating temperatures between 10.0°C and 28.4°C. Results of the storability assessment indicated that loss of total viability was expected to occur in 2.5 years. We recommend a temperature of 25°C and permanent light and first and final count after 15 and 45 days to determine, respectively, germination and viability with the ISTA method described for A. cepa using longitudinally dissected seeds.

Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: applicability to Parkinson's disease

Ethnopharmacology relevanceAyahuasca is a tea produced through decoction of Amazonian plants. It has been used for centuries by indigenous people of South America. The beverage is considered to be an ethnomedicine, and it is traditionally used for the treatment of a wide range of diseases, including neurological illness. Besides, some scientific evidence suggests it may be applicable to Parkinson's disease (PD) treatment. Thus, Ayahuasca deserves in depth studies to clarify its potential role in this disease. Aim of the studyThis study aimed to use an untargeted metabolomics approach to evaluate the neuroprotective potential of the Ayahuasca beverage, the extracts from its matrix plants (Banisteriopsis caapi and Psychotria viridis), its fractions and its main alkaloids on the viability of SH-SY5Y neuroblastoma cells in an in vitro PD model. Material and methodsThe cytotoxicity of Ayahuasca, crude extracts, and fractions of B. caapi and P. viridis, as well as neuroprotection promoted by these samples in a 6-hydroxydopamine (6-OHDA)-induced neurodegeneration model, were evaluated by the MTT assay at two time-points: 48 h (T1) and 72 h (T2). The main alkaloids from Ayahuasca matrix plants, harmine (HRE) and N,N-dimethyltryptamine (DMT), were also isolated and evaluated. An untargeted metabolomics approach was developed to explore the chemical composition of samples with neuroprotective activity. Ultra-Performance Liquid Chromatography coupled to Electrospray Ionisation and Time-of-Flight (UPLC-ESI-TOF) metabolome data was treated and further analysed using multivariate statistical analyses (MSA): principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The metabolites were dereplicated using the Dictionary of Natural Products and an in house database. The main alkaloids were also quantified by UPLC-MS/MS. ResultsThe samples did not cause cytotoxicity in vitro and three of samples intensely increased cell viability at T1. The crude extracts, alkaloid fractions and HRE demonstrated remarkable neuroprotective effect at T2 while the hydroalcoholic fractions demonstrated this neuroprotective effect at T1 and T2. Several compounds from different classes, such as β-carbolines and monoterpene indole alkaloids (MIAs) were revealed correlated with this property by MSA. Additionally, a total of 2419 compounds were detected in both ionisation modes. HRE showed potent neuroprotective action at 72 h, but it was not among the metabolites positively correlated with the most efficacious neuroprotective profile at either time (T1 and T2). Furthermore, DMT was statistically important to differentiate the dataset (VIP value > 1), although it did not exhibit sufficient neuroprotective activity by in vitro assay, neither a positive correlation with T1 and T2 neuroprotective profile, which corroborated the MSA results. ConclusionThe lower doses of the active samples stimulated neuronal cell proliferation and/or displayed the most efficacious neuroprotection profile, namely by preventing neuronal damage and improving cell viability against 6-OHDA-induced toxicity. Intriguingly, the hydroalcoholic fractions exhibited enhanced neuroprotective effects when compared to other samples and isolated alkaloids. This finding corroborates the significance of a holistic approach. The results demonstrate that Ayahuasca and its base plants have potential applicability for PD treatment and to prevent its progression differently from current drugs to treat PD.

ANTIOXIDANT AND CYTOTOXIC ACTIVITIES OF ARECA CATECHU SEED EXTRACT IN SWISS ALBINO MICE USING EAC CELL LINE IN DIFFERENT CULTURE MEDIUM

Objective: Areca nut is the dried ripe seeds of Areca catechu, belonging to family Palmae. Areca nut contains a number of alkaloids, belonging to pyridine and piperidine groups, derived from amino acid lysine. Arecoline a nicotinic acid-based alkaloid present which exerts sialagogue property. But the habit of chewing marketed gutka may cause oral leukoplakia, sometimes lead to squamous cell carcinoma. However, Based on the phytochemical compounds present, it is predicted that it must show antioxidant and may show cytotoxic activities.&#x0D; Methods: The antioxidant activity (nitrite scavenging and hydrogen peroxide scavenging) and cytotoxic activity in two different medium were checked in EAC cell line using the swiss albino mice model.&#x0D; Results: The study was also postulated an idea about the qualitative and quantitive analysis of Areca catechu. The plant extract showed good Nitrite and Hydrogen peroxide scavenging activity. The cytotoxicity study conducted in swiss albino mice, cell viability and IC50 value was checked. The cytotoxic activity of different concentrations of different fractions of plant extract was checked in two different medium, i.e., PBS and RPMI 1640. IC50 values for following fractions which were studied in PBS; as, 91.73±73 (µg/ml), 183±36.24 (µg/ml), 53.74±1.562 (µg/ml) for crude ethanolic extract, alkaloid fraction and flavonoid fraction respectively. IC50 value in RPMI 1640 medium obtained as; 44.18±1.09µg/ml, 54.27±0.2279µg/ml and 51.24±2.461µg/ml for crude ethanolic extract, Alkaloid and Flavonoid fraction, respectively.&#x0D; Conclusion: Areca nut extract showed good scavenging activity depending on concentration. Relatively RPMI 1640 medium showed better cytotoxic activity than other mediums.

Effect of indole alkaloids from roots of Rauvolfia ligustrina in the noradrenergic neurotransmission

The new glucosyl sarpagan alkaloid designated as 21(R*)-(O-β-glucosyl)-hydroxy-sarpagan-17-oic acid, along with eleven known alkaloids were isolated from a soluble alkaloidal fraction from the ethanol extract of Rauvolfia ligustrina. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiment, GIAO 13C NMR calculations, and comparison with literature data. All the isolated alkaloids were screened by their neuroinhibitory effects using the electrically stimulated mice vas deferens bioassay. Compounds 1, 2 and 9 presented a potent inhibitory effect in the neurotransmission while 3 and 11 showed an acute neuroexcitatory effect. Compound 10 exhibited a very effective post-synaptic inhibitory activity.

Stephalagine, an aporphine alkaloid from Annona crassiflora fruit peel, induces antinociceptive effects by TRPA1 and TRPV1 channels modulation in mice

Pain relief represents a critical unresolved medical need. Consequently, the search for new analgesic agents is intensively studied. Annona crassiflora, a native species of the Brazilian Savanna, represents a potential source for painful treatment. This study aimed to investigate the antinociceptive potential of A. crassiflora fruit peel, focusing on its major alkaloid, stephalagine, in animal models of pain evoked by the activation of transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) channels. Male C57BL/6/J mice were submitted to formalin-, cinnamaldehyde-, and capsaicin-induced nociception tests to assess nociceptive behavior, and to the open-field and rotarod tests for motor performance analyses. Moreover, the stephalagine's effect was tested on capsaicin- and cinnamaldehyde-induced Ca2+ influx in spinal cord synaptosomes. In silico assessments of the absorption, distribution, metabolism and central nervous system permeability of stephalagine were carried out. The ethanol extract and alkaloidal fraction reduced the nociception induced by formalin. When administered by oral route (1mg/kg), stephalagine reduced the spontaneous nociception and paw edema induced by TRPV1 agonist, capsaicin, and by TRPA1 agonists, cinnamaldehyde- and formalin, without altering the animals' locomotor activity. The prediction of in silico pharmacokinetic properties of stephalagine suggests its capacity to cross the blood-brain barrier. Furthermore, this alkaloid reduces the capsaicin- and cinnamaldehyde-mediated Ca2+ influx, indicating a possible modulation of TRPV1 and TRPA1 channels, respectively. Together, our results support the antinociceptive and anti-edematogenic effects of the A. crassiflora fruit peel and suggest that these effects are triggered, at least in part, by TRPV1 and TRPA1 modulation by stephalagine.