Essential oil of the leaves of psychotria asiatica L.: chemical composition, antioxidant, anti-inflammatory, and cytotoxic properties.

This study is focused on investigating the chemical composition and bioactive properties of the essential oil extracted from Psychotria asiatica L., a plant species known for its medicinal properties. Utilising gas chromatography-mass spectrometry (GC-MS) analysis, the essential oil from P. asiatica was found to contain 53 distinct constituents. Major compounds identified include (E)-citral (20.6%), 10-epi-γ-eudesmol (15.9%), (Z)-citral (10.5%), geraniol (7.4%), α-cadinol (6.7%), 7-epi-α-eudesmol (4.4%), linalool (3.7%), and α-muurolol (3.4%). The essential oil did not exhibit antioxidant activity, as indicated by an IC50 value of > 100 µg/mL, whereas the positive control L-Ascorbic acid had an IC50 of 7.37 ± 0.27 µg/mL in the DPPH model. Assessment of its anti-inflammatory potential revealed an inhibitory effect on NO production, with an IC50 value of 29.08 ± 1.54 µg/mL in Lipopolysaccharide-induced RAW264.7 macrophage cells. Furthermore, the essential oil demonstrated significant cytotoxicity against the SK-LU-1 cancer cell line, with an IC50 value of 39.75 ± 1.79 µg/mL according to the sulforhodamine B (SRB) assay.

In Vitro Anti-Diabetic, Anti-Inflammatory, Antioxidant Activities and Toxicological Study of Optimized Psychotria malayana Jack Leaves Extract.

Psychotria malayana Jack (Family: Rubiaceae, local name: Salung) is a traditional herb used to treat diabetes. A previous study by our research group demonstrated that P. malayana methanolic and water extract exhibits significant potential as an effective agent for managing diabetes. Further research has been performed on the extraction optimization of this plant to enhance its inhibitory activity against α-glucosidase, a key enzyme associated with diabetes, and to reduce its toxicity. The objectives of this study are to evaluate the anti-diabetic, anti-inflammatory, and antioxidant properties of the optimized P. malayana leaf extract (OE), to evaluate its toxicity using a zebrafish embryo/larvae model, and to analyze its metabolites. The anti-diabetic effects were assessed by investigating α-glucosidase inhibition (AGI), while the inflammation inhibitory activity was performed using the soybean lipoxygenase inhibitory (SLOXI) test. The assessment of antioxidant activity was performed utilizing FRAP and DPPH assays. The toxicology study was conducted using the zebrafish embryo/larvae (Danio rerio) model. The metabolites present in the extracts were analyzed using GC-MS and LC-MS. OE demonstrated significant AGI and SLOXI activities, represented as 2.02 and 4.92 µg/mL for IC50 values, respectively. It exhibited potent antioxidant activities as determined by IC50 values of 13.08 µg/mL (using the DPPH assay) and 95.44 mmol TE/mg DW (using the FRAP assay), and also demonstrated an LC50 value of 224.29 µg/mL, which surpasses its therapeutic index of 111.03. OE exhibited a higher therapeutic index compared to that of the methanol extract (13.84) stated in the previous state of the art. This suggests that OE exhibits a lower level of toxicity, making it safer for use, and has the potential to be highly effective in its anti-diabetic activity. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) demonstrated the presence of several constituents in this extract. Among them, several compounds, such as propanoic acid, succinic acid, D-tagatose, myo-inositol, isorhamnetin, moracin M-3'-O-ß-D-glucopyranoside, procyanidin B3, and leucopelargonidin, have been reported as possessing anti-diabetic and antioxidant activities. This finding offers great potential for future research in diabetes treatment.

Chemico-pharmacological and computational studies of Ophiorrhiza fasciculata D. Don and Psychotria silhetensis Hook. f. focusing cytotoxic, thrombolytic, anti-inflammatory, antioxidant, and antibacterial properties.

The current study sought to examine the pharmacological potentials of crude methanolic extracts of Ophiorrhiza fasciculata and Psychotria silhetensis, as well as their various solvent fractionates, with a focus on cytotoxic, thrombolytic, membrane stabilizing, antioxidant, and antibacterial activities via in vitro and in silico approaches. The extensive chromatographic and spectroscopic analyses confirmed and characterized two compounds as (±)-licarin B (1) and stigmasterol (2) from O. fasciculata and P. silhetensis, respectively. Petroleum ether soluble fraction of O. fasciculata and the aqueous soluble fraction of P. silhetensis showed the lowest 50% lethal concentrations (1.41 and 1.94 µg/mL, respectively) in brine shrimp bioassay. Likewise, petroleum ether soluble fraction of O. fasciculata and aqueous soluble fraction of P. silhetensis showed the highest thrombolytic activity with 46.66% and 50.10% lyses of the clot, respectively. The methanol and dichloromethane soluble fractions of O. fasciculata reduced erythrocyte hemolysis by 64.03% and 37.08%, respectively, under hypotonic and heat-induced conditions, compared to 81.97% and 42.12% for standard acetylsalicylic acid. In antioxidant activity test, aqueous soluble fraction O. fasciculata (IC50 = 7.22 µg/mL) revealed promising antioxidant potentialities in comparison to standard butylated hydroxytoluene (IC50 = 21.20 µg/mL). In antibacterial screening, chloroform, and dichloromethane soluble fractions of P. silhetensis showed a mild antibacterial activity compared with the standard drug ciprofloxacin. Additionally, the molecular docking study corroborated the current in vitro findings, and the isolated two constituents had higher binding affinities toward epidermal growth factor receptor, tissue plasminogen activator, vFLIP-IKK gamma stapled peptide dimer, glutathione reductase, and dihydrofolate reductase enzyme than their corresponding standard drugs. In addition, the both isolated compounds exerted favorable pharmacokinetics (absorption, distribution, metabolism, excretion) and toxicological profiles with drug-like qualities in computational-based ADMET and drug likeliness analyses. The current research suggests that both plants have potential as a natural treatment for treating thrombosis, inflammation, and oxidative stress. However, more thorough research is required to thoroughly screen for phytochemicals and pinpoint the precise mechanisms of action of the bioactive metabolites derived from these plants against a broad range of molecular targets.

Bioactive-Guided Phytochemical Investigations, In Vitro and In Silico Alpha-Glucosidase Inhibition of Two Vietnamese Medicinal Plants Dicranopteris linearis and Psychotria adenophylla.

Little is known about the chemical and biological profiles of Dicranopteris linearis and Psychotria adenophylla. No previous studies have investigated alpha-glucosidase inhibition using extracts from D. linearis and P. adenophylla. In this paper, bioactive-guided isolation procedures were applied to the plants D. linearis and P. adenophylla based on alpha-glucosidase inhibition. From the most active fractions, 20 compounds (DL1-DL13 and PA1-PA7) were isolated. The chemical structures were elucidated using spectroscopic data and compared with those available in the literature. These compounds were evaluated for alpha-glucosidase inhibition, while a molecular docking study was performed to elucidate the mechanisms involved. Consequently, D. linearis and P. adenophylla might serve as a good potential for developing new antidiabetic preparations.

Biochemical responses in leaf tissues of alkaloid producing Psychotria brachyceras under multiple stresses.

Under natural conditions plants are generally subjected to complex scenarios of combined or sequential environmental stresses. Among the various components of plant biochemistry modulated by abiotic variables, a pivotal role is played by antioxidant systems, including specialized metabolites and their interaction with central pathways. To help address this knowledge gap, a comparative analysis of metabolic changes in leaf tissues of the alkaloid accumulating plant Psychotria brachyceras Müll Arg. under individual, sequential, and combined stress conditions was carried out. Osmotic and heat stresses were evaluated. Protective systems (accumulation of the major antioxidant alkaloid brachycerine, proline, carotenoids, total soluble protein, and activity of the enzymes ascorbate peroxidase and superoxide dismutase) were measured in conjunction with stress indicators (total chlorophyll, ChA/ChB ratio, lipid peroxidation, H2O2 content and electrolyte leakage). Metabolic responses had a complex profile in sequential and combined stresses compared to single ones, being also modified over time. Different stress application schemes affected alkaloid accumulation in distinct ways, exhibiting similar profile to proline and carotenoids, constituting a complementary triad of antioxidants. These complementary non-enzymatic antioxidant systems appeared to be essential for mitigating stress damage and re-establishing cellular homeostasis. The data herein provides clues that may aid the development of a key component framework of stress responses and their appropriate balance to modulate tolerance and yield of target specialized metabolites.

The complete organellar genomes of the entheogenic plant Psychotria viridis (Rubiaceae), a main component of the ayahuasca brew.

Psychotria viridis (Rubioideae: Rubiaceae), popularly known as chacrona, is commonly found as a shrub in the Amazon region and is well-known to produce psychoactive compounds, such as the N,N-dimethyltryptamine (DMT). Together with the liana Banisteropsis caapi, P. viridis is one of the main components of the Amerindian traditional, entheogenic beverage known as ayahuasca. In this work, we assembled and annotated the organellar genomes (ptDNA and mtDNA), presenting the first genomics resources for this species. The P. viridis ptDNA exhibits 154,106 bp, encoding all known ptDNA gene repertoire found in angiosperms. The Psychotria genus is a complex paraphyletic group, and according to phylogenomic analyses, P. viridis is nested in the Psychotrieae clade. Comparative ptDNA analyses indicate that most Rubiaceae plastomes present conserved ptDNA structures, often showing slight differences at the junction sites of the major four regions (LSC-IR-SSC). For the mitochondrion, assembly graph-based analysis supports a complex mtDNA organization, presenting at least two alternative and circular mitogenomes structures exhibiting two main repeats spanning 24 kb and 749 bp that may symmetrically isomerize the mitogenome into variable arrangements and isoforms. The circular mtDNA sequences (615,370 and 570,344 bp) encode almost all plant mitochondrial genes (except for the ccmC, rps7, rps10, rps14, rps19, rpl2 and rpl16 that appears as pseudogenes, and the absent genes sdh3, rps2, rsp4, rsp8, rps11, rpl6, and rpl10), showing slight variations related to exclusive regions, ptDNA integration, and relics of previous events of LTR-RT integration. The detection of two mitogenomes haplotypes is evidence of heteroplasmy as observed by the complex organization of the mitochondrial genome using graph-based analysis. Taken together, these results elicit the primary insights into the genome biology and evolutionary history of Psychotria viridis and may be used to aid strategies for conservation of this sacred, entheogenic species.

The complete chloroplast genome of Psychotria asiatica, Linnaeus 1759 (Rubiaceae).

Psychotria asiatica is a typical traditional medicinal plant. Herein, we acquired and characterized the complete chloroplast (cp) genome sequence of P. asiatica to provide genomic resources for conservation genetics and phylogenetic studies of P. asiatica. The cp genome of P. asiatica is 154,652 bp in length and consists of a large single-copy (LSC) region with 85,106 bp, a small single-copy (SSC) region with 17,960 bp, and two inverted repeat regions (IRs) with 25,793 bp. The cp genome of P. asiatica comprises 127 genes, including 82 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic result confirmed that P. asiatica was closely related to Psychotria kirkii within the Rubiaceae.

Azepine-Indole Alkaloids From Psychotria nemorosa Modulate 5-HT2A Receptors and Prevent in vivo Protein Toxicity in Transgenic Caenorhabditis elegans.

Nemorosine A (1) and fargesine (2), the main azepine-indole alkaloids of Psychotria nemorosa, were explored for their pharmacological profile on neurodegenerative disorders (NDs) applying a combined in silico-in vitro-in vivo approach. By using 1 and 2 as queries for similarity-based searches of the ChEMBL database, structurally related compounds were identified to modulate the 5-HT2A receptor; in vitro experiments confirmed an agonistic effect for 1 and 2 (24 and 36% at 10 µM, respectively), which might be linked to cognition-enhancing properties. This and the previously reported target profile of 1 and 2, which also includes BuChE and MAO-A inhibition, prompted the evaluation of these compounds in several Caenorhabditis elegans models linked to 5-HT modulation and proteotoxicity. On C. elegans transgenic strain CL4659, which expresses amyloid beta (Aß) in muscle cells leading to a phenotypic paralysis, 1 and 2 reduced Aß proteotoxicity by reducing the percentage of paralyzed worms to 51%. Treatment of the NL5901 strain, in which α-synuclein is yellow fluorescent protein (YFP)-tagged, with 1 and 2 (10 µM) significantly reduced the α-synuclein expression. Both alkaloids were further able to significantly extend the time of metallothionein induction, which is associated with reduced neurodegeneration of aged brain tissue. These results add to the multitarget profiles of 1 and 2 and corroborate their potential in the treatment of NDs.

Preliminary Phytochemical Screening, In Vitro Antidiabetic, Antioxidant Activities, and Toxicity of Leaf Extracts of Psychotria malayana Jack.

Psychotria malayana Jack belongs to the Rubiacea and is widespread in Southeast Asian countries. It is traditionally used to treat diabetes. Despite its potential medicinal use, scientific proof of this pharmacological action and the toxic effect of this plant are still lacking. Hence, this study aimed to investigate the in vitro antidiabetic and antioxidant activities, toxicity, and preliminary phytochemical screening of P. malayana leaf extracts by gas chromatography-mass spectrometry (GC-MS) after derivatization. The antidiabetic activities of different extracts of this plant were investigated through alpha-glucosidase inhibitory (AGI) and 2-NBDG glucose uptake using 3T3-L1 cell line assays, while the antioxidant activity was evaluated using DPPH and FRAP assays. Its toxicological effect was investigated using the zebrafish embryo/larvae (Danio rerio) model. The mortality, hatchability, tail-detachment, yolk size, eye size, beat per minute (BPM), and body length were taken into account to observe the teratogenicity in all zebrafish embryos exposed to methanol extract. The LC50 was determined using probit analysis. The methanol extract showed the AGI activity (IC50 = 2.71 ± 0.11 µg/mL), insulin-sensitizing activity (at a concentration of 5 µg/mL), and potent antioxidant activities (IC50 = 10.85 µg/mL and 72.53 mg AAE/g for DPPH and FRAP activity, respectively). Similarly, the water extract exhibited AGI activity (IC50 = 6.75 µg/mL), insulin-sensitizing activity at the concentration of 10 µg/mL, and antioxidant activities (IC50 = 27.12 and 33.71 µg/mL for DPPH and FRAP activity, respectively). The methanol and water extracts exhibited the LC50 value higher than their therapeutic concentration, i.e., 37.50 and 252.45 µg/mL, respectively. These results indicate that both water and methanol extracts are safe and potentially an antidiabetic agent, but the former is preferable since its therapeutic index (LC50/therapeutic concentration) is much higher than for methanol extracts. Analysis using GC-MS on derivatized methanol and water extracts of P. malayana leaves detected partial information on some constituents including palmitic acid, 1,3,5-benzenetriol, 1-monopalmitin, beta-tocopherol, 24-epicampesterol, alpha-tocopherol, and stigmast-5-ene, that could be a potential target to further investigate the antidiabetic properties of the plant. Nevertheless, isolation and identification of the bioactive compounds are required to confirm their antidiabetic activity and toxicity.

Polygamous breeding system identified in the distylous genus Psychotria: P. manillensis in the Ryukyu archipelago, Japan.

Distyly is a genetic polymorphism composed of long-and short-styled flowers in a population. The evolutionary breakdown of distyly has been reported in many taxa, and mainly involves a shift toward monomorphism or dioecism. However, a shift toward monoecism has not been reported in distylous species. Psychotria (Rubiaceae), one of the world largest genera, consists of distylous species and their derivatives. In our preliminary study, however, we identified some monoecious individuals in a population of Psychotria manillensis. To understand the breeding system and reproductive biology of P. manillensis, we investigated floral traits, open fruit set, and flower visitors, and performed hand pollination and bagging experiments in five populations of Okinawa and Iriomote islands, Ryukyu Islands, Japan. The populations of P. manillensis were composed mainly of monoecious individuals (54%), followed by female (30%), male (14%), and hermaphroditic (2%) individuals at the time of flower collection. Of the collected flowers, 93% were functionally unisexual (male or female), whereas only 6.5% were perfect (hermaphroditic). However, some individuals changed sex mainly towards increasing femaleness during the flowering period. Moreover, 35% of the studied plants changed their sexual expression over the years. P. manillensis showed self-compatibility and no agamospermy. The fruit set under open pollination varied among populations and years (1.8-21.9%), but it was significantly higher than that of auto-selfing (0.68-1.56%). Wasps and flies were the main flower visitors and probably the main pollinators of the species. In conclusion, P. manillensis was revealed to be polygamous, involving monoecious, female, male, and hermaphroditic individuals. This is the first report of the polygamous breeding system not only in the genus Psychotria, but also in all heterostylous taxa.

Inhibition Effect of Extract of Psychotria viridiflora Stem on α-Amylase and α-Glucosidase and Its Application in Lowering the Digestibility of Noodles.

A collection of tropical medicinal plants from East Malaysia's rainforests are used by indigenous tribes for their curative properties. Despite their purported healing properties, these forest plant species are largely unexplored and hence remain virtually unknown to the outside world. In this study, antidiabetic properties of Psychotria viridiflora, a plant used to treat diabetes by a local community in Sarawak, Malaysia were investigated. Ethyl acetate (EA) extract of P. viridiflora stem was found to exhibit high starch hydrolase inhibition activity with an IC50 value of 15.4 ± 2.1 µg/ml against porcine α-amylase and an IC50 value of 32.4 ± 3.7 µg/ml against rat intestinal α-glucosidase. A complex mixture of A-type oligomeric proanthocyanidins containing (epi)fisetinidol, (epi)afzelechin, (epi)guibourtinidol, and (epi)catechin were found. These compounds may be responsible for the starch hydrolase inhibition activity. Ethyl acetate (EA) extract of P. viridiflora stem was incorporated into wheat and rice flour to reformulate noodles with slow digestibility and was assessed under in vitro simulated gastrointestinal conditions. A dose-dependent effect on digestibility was observed for both noodles upon incorporation of 1-6% (w/w) of EA extract, with noodles containing 6% (w/w) extract exhibiting the greatest reduction in digestibility. As compared to rice noodles containing 6% extract (31.16% inhibition), wheat noodles with the same extract concentration had a smaller decline in digestibility (27.25% inhibition) after 180 min. Overall, our findings highlight the potential of P. viridiflora in the prevention of postprandial hyperglycaemia.

The antioxidant and neuroprotective effects of the Psychotria camptopus Verd. Hook. (Rubiaceae) stem bark methanol extract contributes to its antiepileptogenic activity against pentylenetetrazol kindling in male Wistar rats.

A substantial number of epileptic patients are resistant to the current medication thus necessitating the search for alternative therapies for intractable forms of the disease. Previous studies demonstrated the acute anticonvulsant properties of the methanol extract of the stem bark of Psychotria camptopus (MEPC) in rats. This study investigated the effects of MEPC on pentylenetetrazole-kindled Wistar rats. Kindling was induced by intraperitoneal injection of pentylenetetrazole (37.5 mg/kg) on every alternate day, 1 h after each daily oral pretreatment of rats (8 ≤ n ≤ 10) with MEPC (40, 80 and 120 mg/kg), vehicle or diazepam (3 mg/kg) for 43 days. The kindling development was monitored based on seizure episodes and severity. Rats' brains were collected on day 43 for the determination of oxidative stress parameters. The histomorphological features and neuronal cell viability of the prefrontal cortex (PFC) and hippocampus were also assessed using H&E and Cresyl violet stains. Chronic administration of pentylenetetrazole time-dependently decreased the latency to myoclonic and generalized seizures, and increased seizure scores and the number of kindled rats. MEPC and diazepam significantly increased the latencies to myoclonic jerks and generalized tonic-clonic seizures. These substances also reduced seizure score and the number of rats with PTZ-kindling. MEPC improved glutathione status and decreased lipid peroxidation in the brains of kindled rats. MEPC also exhibited neuroprotection against pentylenetetrazole-induced hippocampal and PFC neuronal damages. These results suggest that P. camptopus has antiepileptogenic activity, which might be related to the augmentation of antioxidant and neuroprotective defense mechanisms, and further confirm its usefulness in the management of epilepsy.

Anticonvulsant effects of the aqueous and methanol extracts from the stem bark of Psychotria camptopus Verdc. (Rubiacaea) in rats.

ETHNOPHARMACOLOGY RELEVANCE: The decoction from the stem bark of Psychotria camptopus (Rubiaceae) is used in the Cameroonian pharmacopoeia to treat neurological pathologies including epilepsy. AIM: The present work was undertaken to study the anticonvulsant properties of the aqueous (AE) and methanol (ME) extracts from the stem bark of P. camptopus in acute models of epileptic seizures in Wistar rats. METHOD: AE and ME were obtained by decoction and maceration of the stem bark powder in water and methanol, respectively. They were tested orally at the doses of 40, 80 and 120 mg/kg, on the latency of onset and duration of epileptic seizures induced by pentylene tetrazole (PTZ, 70 mg/kg, i.p.). The kinetic effect of both extracts at 120 mg/kg was evaluated. Their effects on diazepam (50 mg/kg) induced sleep and strychnine (STR, 2.5 mg/kg, i.p.) induced seizures were determined. ME was further tested on picrotoxin (PIC, 7.5 mg/kg, i.p.) and thiosemicarbazide (TSC, 50 mg/kg, i.p.) induced seizure models. The phytochemical composition of ME was assessed using LC-MS method, as well as its acute toxicity. RESULTS: AE and ME significantly (p < 0.001) reduced the duration of seizures in both PTZ and STR models. Their maximal effect was observed at 1 h after administration, though their effect at 120 mg/kg was maintained (p < 0.05) up to 24 h post-treatment. Both extracts significantly (p < 0.01) reduced sleep duration. ME significantly (p < 0.001) increased the latency of rat death on PIC-induced convulsions. In TSC rats, ME significantly (p < 0.001) delayed the latency to the first convulsion, and decreased the duration and frequency of convulsions. ME showed no acute toxicity while its phytochemical screening revealed the presence of two flavonoids (Rutin and Butin), two triterpenoid saponins (Psycotrianoside B and Bauerenone) and four alkaloids (10-Hydroxy-antirhine, 10-hydroxy-iso-deppeaninol, Emetine and Hodkinsine). In conclusion, AE and ME from the stem bark of P. camptopus have comparable anticonvulsant properties. The effect of ME is likely due to the presence of flavonoids and alkaloid and the activation of GABA pathway. These results further justify and support the use of P. camptopus in traditional medicine for the treatment of epilepsy.

A new hexenoic acid glycoside with cytotoxic activity from the leaves of Psychotria luzoniensis.

A new hexenoic acid glycoside (1) together with known compounds, flavonol glycosides (2-4), iridoid glycoside (5), megastigmane glycoside (6), and amino acid (7) were isolated from the leaves of P. luzoniensis by resin column chromatography and preparative HPLC. Their structures were determined based on spectroscopic analysis, including HRFABMS and NMR (1H and 13C, 1H-1H COSY, HMQC, and HMBC) data. All compounds tested for cytotoxicity were active (IC50 < 50 µM) with IC50 values ranging from 1.97 to 32.85 µM against human colon adenocarcinoma cell line, compared to etoposide (IC50 1.19 µM).

In Vitro Potential of the Acetone Leaf Extract and Fractions of Psychotria capensis (Eckl.) Vatke (Rubiaceae) to Combat Co-Infection of Tuberculosis and Helminthiasis.

Tuberculosis (TB) is a disease of global importance that affects millions of people. Approximately a quarter of the world's population is currently infected with M. tuberculosis, and about 10% of those infected will develop into active disease, particularly immune compromised individuals. Helminthiasis is of global health importance, affecting over 2 billion people mostly in resource-poor countries. Co-infection with tuberculosis (TB) and helminths (worms) is an emerging global public health concern with both affecting about one-third of the global population. Chronic infection with helminths can result in impaired immune responses to TB as well as enhancing failure to TB therapy and BCG vaccination. Antimycobacterial and anthelmintic activities of the acetone extract and fractions of Psychotria capensis were evaluated, including their in vitro safety. In addition, the anti-inflammatory and immunomodulatory effect of the fractions and crude extract of P. capensis were assessed. Antimycobacterial activity of the extract and fractions was tested against four non-tuberculous mycobacteria (Mycobacterium smegmatis, M. fortuitum, M. aurum, M. bovis BCG) and pathogenic M. tuberculosis H37Rv while the Egg Hatch Assay (EHA) was used for the anthelmintic test on eggs of Haemonchus contortus. Cytotoxicity was determined against Vero kidney cells while in vitro immune modulation via cytokine production was determined on activated macrophages. The minimum inhibitory concentration (MIC) values of the Psychotria capensis acetone extract and fractions ranged from 39 to 1,250 µg/ml with the crude extract and hexane fraction having the best MIC values (both 39 µg/ml). In the EHA, the inhibitory concentration (IC50) ranged from 160 to 630 µg/ml with the hexane fraction having the best activity. The hexane and chloroform fractions were relatively non-toxic with LC50 values of 290 and 248 µg/ml respectively, while the acetone crude extract (64 µg/ml) and n-butanol fraction (71 µg/ml) were moderately toxic. The SI values (LC50/MIC) ranged from 0.1 to 7.4 with the hexane fraction having the highest value against M. smegmatis (7.4). The hexane fraction had the best dual anthelmintic and antimycobacterial activity. This fraction had the best NO inhibitory activity and was the least cytotoxic, indicating that its activity was not due to general metabolic toxicity, with 96.54% cell viability. Pro-inflammatory cytokines such as IL-12p70 were upregulated while IL-10 expression was inhibited by the extracts. Compounds were detected using GC-MS analysis, and in both the crude acetone extract and the hexane fraction was the diterpene neophytadiene, which has anti-inflammatory and antimicrobial activity. Finding alternative or complementary approaches to dealing with TB infections by, amongst other things, reducing the incidence of helminth infestations may lessen the burden of TB, contributing to slowing the spread of multi-drug resistance.

Characterization of α-Glucosidase Inhibitors from Psychotria malayana Jack Leaves Extract Using LC-MS-Based Multivariate Data Analysis and In-Silico Molecular Docking.

Psychotria malayana Jack has traditionally been used to treat diabetes. Despite its potential, the scientific proof in relation to this plant is still lacking. Thus, the present study aimed to investigate the α-glucosidase inhibitors in P.malayana leaf extracts using a metabolomics approach and to elucidate the ligand-protein interactions through in silico techniques. The plant leaves were extracted with methanol and water at five various ratios (100, 75, 50, 25 and 0% v/v; water-methanol). Each extract was tested for α-glucosidase inhibition, followed by analysis using liquid chromatography tandem to mass spectrometry. The data were further subjected to multivariate data analysis by means of an orthogonal partial least square in order to correlate the chemical profile and the bioactivity. The loading plots revealed that the m/z signals correspond to the activity of α-glucosidase inhibitors, which led to the identification of three putative bioactive compounds, namely 5'-hydroxymethyl-1'-(1, 2, 3, 9-tetrahydro-pyrrolo (2, 1-b) quinazolin-1-yl)-heptan-1'-one (1), α-terpinyl-ß-glucoside (2), and machaeridiol-A (3). Molecular docking of the identified inhibitors was performed using Auto Dock Vina software against the crystal structure of Saccharomyces cerevisiae isomaltase (Protein Data Bank code: 3A4A). Four hydrogen bonds were detected in the docked complex, involving several residues, namely ASP352, ARG213, ARG442, GLU277, GLN279, HIE280, and GLU411. Compound 1, 2, and 3 showed binding affinity values of -8.3, -7.6, and -10.0 kcal/mol, respectively, which indicate the good binding ability of the compounds towards the enzyme when compared to that of quercetin, a known α-glucosidase inhibitor. The three identified compounds that showed potential binding affinity towards the enzymatic protein in molecular docking interactions could be the bioactive compounds associated with the traditional use of this plant.

Antileishmanial and cytotoxic activities of four Andean plant extracts from Colombia.

BACKGROUND AND AIM: Licania salicifolia (L.S) Cuatrec., Persea ferruginea (P.F) Kunth, Oreopanax floribundus (O.F), and Psychotria buchtienii (P.B) belong to the families Chrysobalanaceae, Lauraceae, Araliaceae, and Rubiaceae, respectively, which have been used as medicines by communities in the Andes. This study evaluated the leishmanicidal and cytotoxic activities of alcohol and non-alcohol extracts from four Andean plant extracts (L.S, O.F, P.F, and P.B). MATERIALS AND METHODS: Extracts were obtained by percolation with solvents of different polarities - hexane, dichloromethane, ethyl acetate, and ethanol. Phytochemical screening was conducted based on reported methods. All products were evaluated in vitro to determine the leishmanicidal activity against amastigotes of Leishmania panamensis and cytotoxicity against U937 cells. RESULTS: Flavonoids, triterpenes, and tannins were the main secondary metabolites found. From the results, dichloromethane extracts from O.F and P.B, ethanol extract from P.B, and ethyl acetate extracts of all plants were active, with EC50 <30 µg/mL. Ethyl acetate was the most active extract, which showed EC50 values of 9.8, 14.1, 23.7, and 25.5 µg/mL, for L.S, P.B, O.F, and P.F, respectively. Hexane extracts from P.B and O.F exhibited moderate activity with EC50 values of 84.8 and 87.4 µg/mL, respectively. Hexane and ethanol extracts from O.F, ethyl acetate, and ethanol extracts from L.S, and all extracts from P.F were not toxic. Alternatively, hexane and dichloromethane extracts from L.S and P.B as well as dichloromethane and ethyl acetate extracts from O.F displayed high toxicity. CONCLUSION: Based on the activity we observed, ethyl acetate extract can continue in its usage in the search for new antileishmanial drugs, mainly ethyl acetate extract from L.S showed activity comparable to meglumine antimoniate and was not cytotoxic.

Ethanol leaf extract of Psychotria microphylla rich in quercetin restores heavy metal induced redox imbalance in rats.

Psychotria microphylla is a plant found in Africa and many parts of the world where the leaves are locally used in folk medicine for the treatment of toxicity related liver diseases. We investigated the antioxidant potentials of ethanol leaf extract of Psychotria microphylla (ELE-PM) in restoring hepatic redox dysregulations in rats exposed to heavy metals. HPLC was used in quantifying the bioactive compounds in ELE-PM. DPPH (1,1-diphenyl-2 picrylhydrazyl), FRAP (Ferric reducing antioxidant power) and NO (Nitric Oxide) assays were used for in vitro studies. The in vivo studies involved 30 rats randomly divided into 5 groups (n = 6). Group 1 received normal saline (2 mg/kg), group 2, 3, 4 and 5 received a combined solution of Pb(NO3)2 (11.25 mg/kg) and HgCl2 (0.4 mg/kg) respectively. After 7 days of heavy metal exposure, groups 3, 4 and 5 received a daily bolus administration of 200, 400 and 600 mg/kg body weight of EE-PM respectively through oral intubation for 28 days. HPLC quantification revealed a high amount of quercetin (27.43 ± 0.04 mg/100g), lower amounts of gallic acid (7.60 ± 0.06 mg/100g) and rutin (0.38 ± 0.009 mg/100g). Additionally, ELE-PM demonstrated strong inhibitory potentials against free radical scavenging activity generated in vitro. More interestingly, administration of ELE-PM significantly ameliorated hepatic redox dysregulations elicited by the exposure of the rats to heavy metals in a dose dependent pattern. ELE-PM is highly rich in flavonoid compound quercetin and perhaps this may be responsible for the strong antioxidant potentials exhibited in this investigation.

Alpha-Glucosidase Inhibitory Effect of Psychotria malayana Jack Leaf: A Rapid Analysis Using Infrared Fingerprinting.

The plant Psychotria malayana Jack belongs to the Rubiaceae family and is known in Malaysia as "meroyan sakat/salung". A rapid analytical technique to facilitate the evaluation of the P. malayana leaves' quality has not been well-established yet. This work aimed therefore to develop a validated analytical technique in order to predict the alpha-glucosidase inhibitory action (AGI) of P. malayana leaves, applying a Fourier Transform Infrared Spectroscopy (FTIR) fingerprint and utilizing an orthogonal partial least square (OPLS). The dried leaf extracts were prepared by sonication of different ratios of methanol-water solvent (0, 25, 50, 75, and 100% v/v) prior to the assessment of alpha-glucosidase inhibition (AGI) and the following infrared spectroscopy. The correlation between the biological activity and the spectral data was evaluated using multivariate data analysis (MVDA). The 100% methanol extract possessed the highest inhibitory activity against the alpha-glucosidase (IC50 2.83 ± 0.32 µg/mL). Different bioactive functional groups, including hydroxyl (O-H), alkenyl (C=C), methylene (C-H), carbonyl (C=O), and secondary amine (N-H) groups, were detected by the multivariate analysis. These functional groups actively induced the alpha-glucosidase inhibition effect. This finding demonstrated the spectrum profile of the FTIR for the natural herb P. malayana Jack, further confirming its medicinal value. The developed validated model can be used to predict the AGI of P. malayana, which will be useful as a tool in the plant's quality control.

Deciphering the Pharmacological Properties of Methanol Extract of Psychotria calocarpa Leaves by In Vivo, In Vitro and In Silico Approaches.

The present study explores the neuropharmacological, antinociceptive, antidiarrheal, antioxidant, thrombolytic and cytotoxic activity of methanol extract of Psychotria calocarpa leaves (MEPC). In anxiolytic activity testing of MEPC by elevated plus maze test, hole-board test and light-dark test, the extract exhibited a dose-dependent reduction of anxiety while the open field test observed a decreased locomotion. The administration of MEPC revealed a significant dose-dependent reduction of depressant behavior in forced swimming and tail suspension test. Additionally, the antinociceptive and antidiarrheal activity exposed a significant reduction of nociception and diarrheal behavior at the highest dose. In addition, a strong antioxidant activity was observed in DPPH-free radical-scavenging assay (IC50 = 461.05 µg/mL), total phenol content (118.31 ± 1.12 mg) and total flavonoid content (100.85 ± 0.97 mg). The significant clot-lysis activity was also observed with moderate toxicity (LC50 = 247.92 µg/mL) level in the lethality assay of brine shrimp. Moreover, in silico molecular docking study showed that the compound Psychotriasine could offer promising active site interactions for binding proteins. Furthermore, ADME/T and toxicological properties of the compound satisfied the Lipinski's rule of five and Veber rules for drug-like potential and toxicity level. Overall, MEPC had a potential neuropharmacological, antinociceptive, antidiarrheal and antioxidant activity that warranted further investigation.