Antipyretic and antinociceptive effects of methanolic extract of C. iria L. tuber.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus iria L. is a sedge belongs to Cyperaceae family. Tuber of this plant is traditionally used in fever. AIM OF THE STUDY: This study aimed to verify the effectiveness of this plant part against fever. Additionally, antinociceptive effect of the plant was evaluated. MATERIALS AND METHODS: Antipyretic effect was evaluated by yeast induced hyperthermia experiment. Antinociceptive effect was determined by acetic acid induced writhing test and hot plate test. Four different doses of plant extract were used in mice model. RESULTS: Extract at dose of 400 mg/kg.bw produced greater effect than paracetamol; reduction of elevated mice body temperature was observed by 2.6 °F and 4.2 °F after 4 h by paracetamol and 400 mg/kg.bw extract respectively. In acetic acid writhing test, extract at 400 mg/kg.bw and diclofenac were found to have equivalent effects producing percentage inhibition of writhing of 67.68% and 68.29% respectively. In hot plat test, significant reduction in latency was also observed after administration of plant extracts. Mean percent maximal effect was 83.55% and 67.26% for ketorolac and extract (400 mg/kg.bw) respectively. CONCLUSION: Our study endorsed the traditional use of C. iria tuber in fever with possible antinociceptive effects.

A methanolic extract of Eclipta prostrata (L.) L. decreases inflammation in a murine model of chronic allergic asthma via inhibition of the NF-kappa-B pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals. A methanolic extract of E. prostrata (MEEP), the major components of which are wedelolactone (WED) and demethylwedelolactone (DMW), exhibited anti-inflammatory activity in acute asthma models but the effects on lung inflammation and the mechanisms of action of MEEP in a chronic asthma model are not known. AIM OF THE STUDY: To study the effects of MEEP in vivo using a chronic ovalbumin (OVA)-induced allergic asthma model in mice. MATERIALS AND METHODS: The identities of WED and DMW in MEEP were confirmed and the concentrations determined by liquid chromatography and tandem mass spectrometry. Male Balb/c mice were sensitized and challenged with OVA and experimental animals were treated with MEEP (100, 250 or 500 mg/kg) while control animals were treated with dexamethasone (2 mg/kg) or normal saline. Bronchial hyperresponsiveness, total and differential cell counts in bronchoalveolar lavage (BAL), and the production of Th2 cytokines in lung homogenates were assessed. Lung inflammation and mucus production were evaluated by histological analysis while nuclear factor kappa-B (NF-κB) activation was assessed immunohistochemically. RESULTS: Concentrations of WED and DMW in MEEP were 5.12% and 1.04%, respectively. Treatments with MEEP (250 or 500 mg/kg) significantly decreased bronchial hyperresponsiveness, reduced total cell and eosinophil counts in BAL and IL-4 concentrations in lung homogenate, and inhibited NF-κB activation. Treatment with MEEP at 500 mg/kg reduced the level of IL-5 in lung homogenates but did not decrease IL-13 concentration or mucus production. CONCLUSIONS: MEEP attenuated bronchial hyperresponsiveness and decreased lung and airway inflammation in a chronic asthma model in mice. The mechanism of action involves inhibition of NF-κB activation, most likely associated with the presence of the coumestans WED and DMW. These results support the ethnopharmacological evidence for the use of E. prostrata against asthma and other respiratory inflammatory diseases.

Simultaneous quantification of nirmatrelvir/ritonavir in human serum by LC-HRMS.

In December 2021, the U.S. Food and Drug Administration (FDA) granted emergency authorization for Paxlovid® as an antiviral treatment for COVID-19. Paxlovid® is composed of two tablets, nirmatrelvir and ritonavir. Dose adjustment is necessary in cases of renal insufficiency. The aim of present study is to establish a LC-HRMS method for simultaneous determination of nirmatrelvir/ritonavir in human serum for therapeutic drug monitoring. Internal standard saquinavir was added in 25 µL human serum samples, and then the samples were precipitated with methanol. The analytes were separated by gradient elution on a C18 column, using a mobile phase of 0.1 % formic acid-water and methanol, at a flow rate of 0.4 mL/min. The injection volume was 2 µL, and the analysis time was 5 min. The determination of the analytes was performed by electrospray ionization in positive mode by full mass monitoring. The detected ions of nirmatrelvir, ritonavir and saquinavir were m/z 500.24792, 721.32004 and 671.39155, respectively. The linear concentration range for nirmatrelvir was 78.13-20000 ng mL-1, for ritonavir was 15.63-4000 ng mL-1 (r2＞0.9900). The accuracy ranged from 87.45 %∼104.63 %, and the intra-day and inter-day precision RSD was <15 %. The recovery of nirmatrelvir ranged from 98.72 %∼109.83 %, and that of ritonavir was 95.41∼112.36 %. The matrix effect of nirmatrelvir was 88.31∼97.73 %, and that of ritonavir was 85.17∼103.05 %. This method was used to measure the trough concentrations of nirmatrelvir/ritonavir in 17 patients. The trough concentration of nirmatrelvir was 1331.7-8352.5 ng/mL, and that of ritonavir was 53.4-1325.5 ng mL-1, with large individual differences. The method is simple, sensitive, specific, and reproducible, and can be used for monitoring the blood concentration and pharmacokinetic study of nirmatrelvir/ritonavir in COVID-19 patients.

Insights the dominant contribution of biomass burning to methanol-soluble PM2.5 bounded oxidation potential based on multilayer perceptron neural network analysis in Xi'an, China.

Atmospheric fine particulate matter (PM2.5) is associated with cardiorespiratory morbidity and mortality due to its ability to generate reactive oxygen species (ROS). Ambient PM2.5 samples were collected during heating and nonheating seasons in Xi'an, China, and the ROS-generation potential of PM2.5 was quantified using the dithiothreitol (DTT) assay. Additionally, positive matrix factorization combined with multilayer perceptron was employed to apportion sources contributing to the oxidation potential of PM2.5. Both the mass concentration of PM2.5 and the volume-based DTT activity (DTTv) were higher during the heating season than during the nonheating season. The primary contributors to DTTv were combustion (biomass and coal) sources during the heating season (>52 %), whereas secondary formation dominated DTT activity during the nonheating season (35.7 %). In addition, the secondary reaction process promoted the generation of intrinsic oxidation potential (OP) of sources. Among all the sources investigated (traffic source, industrial emission, mineral dust, biomass burning, secondary formation and coal combustion), the inherent oxidation potential of biomass burning was the highest, whereas that of mineral dust was the lowest. Our study indicates that anthropogenic sources, especially biomass burning, should be prioritized in PM2.5 toxicity control strategies.

Evaluation of the anti-inflammatory and antioxidant properties and isolation and characterization of a new bioactive compound, 3,4,9-trimethyl-7-propyldecanoic acid from Vitex negundo.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicines derived from plant extraction are affordable, more therapeutically effective, and have fewer side effects than contemporary medications. Vitex negundo L. (V. negundo). is a medicinal shrub, which contains numerous phytoconstituents. In ancient medicinal practices, V. negundo was primarily prescribed as an analgesic and anti-inflammatory drug. AIM OF THE STUDY: This study aims to evaluate the anti-inflammatory and antioxidant characteristics of crude extracts from V. negundo leaves, including those derived from petroleum ether (P), methanol (M), and aqueous (A) solvents. Additionally, the research seeks to identify the specific bioactive compounds responsible for these observed properties. MATERIALS AND METHODS: The nitric oxide scavenging study was performed to evaluate the V. negundo crude extract's ability to function as a nitric oxide scavenger. Protein denaturation and proteinase inhibition experiments were employed to study the ability of extracts to suppress proteolysis and inhibit the enzymes that cause tissue injury. The membrane-stabilizing potency of plant extracts were examined through the process of heat-induced hemolysis. The ability of the extracts to neutralize free radicals showed a dose-dependent response, and the aqueous extract exhibited substantially higher activity in both FRAP and DPPH. The GC-MS analysis of V. negundo extracts revealed a vast array of pharmacologically active metabolites. Based on this Bioassay-guided fractionation approach, the optimal extract was selected for the potent molecule isolation and characterization. RESULTS: The findings demonstrated that the aqueous extract of V. negundo exhibited markedly superior radical scavenging and anti-inflammatory capabilities compared to the other two extracts. Furthermore, a new molecule, 3,4,9-trimethyl-7-propyldecanoic acid was isolated from this extract, and its chemical structure was successfully determined. CONCLUSION: This study revealed that the aqueous extract of V. negundo demonstrated notably stronger in vitro anti-inflammatory and antioxidant properties in comparison to the methanol and petroleum ether extracts. The identified active compound, 3,4,9-trimethyl-7-propyldecanoic acid is likely responsible for the extract's free radical scavenging and anti-inflammatory effects. Furthermore, conducting both in vitro and in vivo studies is crucial to substantiate the potential of this active constituent for the development of an anti-inflammatory drug derived from V. negundo.

Neurotoxicity study of ethyl acetate extract of Zanthoxylum armatum DC. on SH-SY5Y based on ROS mediated mitochondrial apoptosis pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum armatum DC. (ZADC) is a traditional medicinal plant with various pharmacological activities and is widely used in China, Japan, India, and other regions. Previous studies have revealed that the methanol extract of ZADC can cause neurotoxicity symptoms in rats, such as drooling, decreased appetite, decreased movement, and increased respiratory rate. However, the basis of these toxic substances and the mechanism of neurotoxicity remain unclear. AIM OF THE STUDY: To evaluate the effects of ZADC on nerve cells and their damage mechanisms and discuss the possible toxic substance basis. MATERIALS AND METHODS: The ethyl acetate extract of ZADC is obtained by extracting the methanol extract of ZADC with ethyl acetate. The Q-Orbitrap LC-MS/MS method was employed to analyze the chemical composition of the EA extract of ZADC. SH-SY5Y cells were incubated with different concentrations of the ethyl acetate extract of ZADC. The cytotoxicity of the extract was evaluated using CCK-8, LDH, and ROS assays, and the oxidative stress status of cells was assessed using MDA, GSH, and SOD. Cell apoptosis was detected using flow cytometry. Damage to mitochondrial function was evaluated by labeling mitochondria, ATP, and MMP with fluorescence. Cyto-C, Caspase-3, Caspase-9, Apaf-1, Bax, and reduced Bcl2 expression were measured to evaluate the activation of the mitochondrial apoptosis pathway. Finally, NAC intervention was used to detect changes in the relevant indicators. The activation of mitochondrial apoptosis pathway was evaluated by measuring Cyto-C, Caspase-3, Caspase-9, Apaf-1, and Bax and Bcl2 expression. Finally, NAC intervention was utilized to detect changes in the relevant indicators. RESULTS: After treating SY-SY5Y cells with EA extract from ZADC, cell viability decreased significantly, and the intracellular ROS level increased in a dose-dependent manner. Meanwhile, ZADC can cause cellular oxidative stress and increase MDA and SOD concentrations while decreasing GSH concentrations. It can also shorten the mitochondrial cristae and decrease the number of mitochondria. In contrast, it can reduce ATP synthesis in the mitochondria and mitochondrial membrane potential (MMP). Furthermore, it increased the apoptosis rate and the expression of Cyto-C, Caspase-3, Caspase-9, Apaf-1, and Bax and reduced Bcl2 expression. NAC intervention alleviated the reduction in SH-SY5Y cell survival and the accumulation of reactive oxygen species induced by the EA extract in ZADC. It also inhibits signaling pathways dominated by proteins, such as Cyto-C, reducing cell apoptosis and cytotoxicity. A total of 46 compounds were identified in the extracts. CONCLUSIONS: The results suggest that EA extract of ZADC can induce the mitochondrial apoptotic pathway by accumulating ROS in cells, leading to apoptosis. Antioxidants had a good inhibitory and protective effect against cell damage caused by the EA extract of ZADC. The neurotoxic components of ZADC may be organic acids and compounds containing amino groups.

Effects of combustion temperature on the optical properties of brown carbon from biomass burning.

Biomass burning has been known as one of main sources of Brown Carbon (BrC) in atmosphere. In this study, by controlling the combustion temperature at 250°C, 350°C, and 450°C, the methanol soluble organic carbon (MSOC) and methanol insoluble carbon (MISC) from pine wood burning was collected by impinger. UV-Vis, excitation emission matrix (EEM), TEM and FTIR spectra were applied to investigate the properties of BrC collected. For MSOC at 250°C and 350°C, all the spectral profiles of UV-Vis absorption and excitation emission matrix are almost the same, while the EEM of MSOC at 450°C are different from that of the other two. For MISC fluorescence was observed only in the case of 450°C. In the FTIR spectra, with the temperature increasing the peaks associated to the oxygen-contained functions was weakened, indicating the formation of the fluorophores with larger conjugated system, especially aromatic hydrocarbons. Our results show that biomass combustion at low temperature produces more oxygen-riched BrC, which possesses relatively lower light absorption, while at high temperature produces more aromatics hydrocarbons with relatively strong light absorption. The results of this work are helpful to trace the source of brown carbon and optimize biomass energy utilization.

A review on high-pressure heterogeneous catalytic processes for gas-phase CO2 valorization.

This review discusses the importance of mitigating CO2 emissions by valorizing CO2 through high-pressure catalytic processes. It focuses on various key processes, including CO2 methanation, reverse water-gas shift, methane dry reforming, methanol, and dimethyl ether synthesis, emphasizing pros and cons of high-pressure operation. CO2 methanation, methanol synthesis, and dimethyl ether synthesis reactions are thermodynamically favored under high-pressure conditions. However, in the case of methane dry reforming and reverse water-gas shift, applying high pressure, results in decreased selectivity toward desired products and an increase in coke production, which can be detrimental to both the catalyst and the reaction system. Nevertheless, high-pressure utilization proves industrially advantageous for cost reduction when these processes are integrated with Fischer-Tropsch or methanol synthesis units. This review also compiles recent advances in heterogeneous catalysts design for high-pressure applications. By examining the impact of pressure on CO2 valorization and the state of the art, this work contributes to improving scientific understanding and optimizing these processes for sustainable CO2 management, as well as addressing challenges in high-pressure CO2 valorization that are crucial for industrial scaling-up. This includes the development of cost-effective and robust reactor materials and the development of low-cost catalysts that yield improved selectivity and long-term stability under realistic working environments.

Diuretic activity evaluation and chemical composition analysis of Hedyotis scandens extract from Mizoram, India, in rat models.

ETHNOPHARMACOLOGICAL RELEVANCE: Diuretics play a crucial role in addressing various medical conditions such as hypertension and edema. Across numerous communities, plants have served as diuretic agents, leveraging their abundant phytochemical composition. In certain instances, plant-based remedies have gained preference over synthetic drugs due to their affordability and ready availability. Hedyotis scandens Roxb., commonly recognized as Laikingtuibur/Kelhnamtur in Mizoram, belongs to the Rubiaceae family. This plant has been harnessed worldwide within diverse societies as a medicinal resource to combat a spectrum of ailments. Notably, in Mizoram, the leaves are employed in creating a decoction with diuretic properties. The ethnopharmacological exploration of plant diuretics not only preserves cultural traditions but also contribute to the potential discovery of novel therapeutic agents. AIM OF THE STUDY: Our study endeavours to explore the traditional employment of this plant as a diuretic in Mizoram. Furthermore, we seek to elucidate the plant's chemical composition through the utilization of GC-MS analysis. MATERIALS AND METHODS: In this investigation, we conducted plant extraction using methanol and distilled water as solvents within a soxhlet apparatus. Prior to commencing the main experiment, we conducted an acute toxicity test to ensure the safety of the plant extract. For the assessment of diuretic activity, we adopted the methodology outlined by Lipschitz et al. (1943). All in vivo experiments were conducted in strict accordance with the guidelines set forth by the OECD. Based on the outcomes of the acute toxicity evaluation, we opted for three dosage levels: a high dose (1000 mg/kg), a medium dose (500 mg/kg), and a low dose (250 mg/kg). Furosemide, recognized as a loop diuretic, was employed as the standard reference, while the control group received distilled water. RESULTS: Our investigation unveiled the presence of several uncharacterized bioactive compounds within the plant. Of particular interest, the GC-MS analysis identified a specific compound named 'phytol,' which has previously been associated with diuretic properties. Notably, the acute toxicity assessment demonstrated the plant extract's safety even at a high dose of 5000 mg/kg, as no toxic effects were observed. The diuretic evaluation of the H. scandens extract exhibited a dose-dependent increase in diuresis, with the methanolic extract yielding notably superior outcomes compared to the aqueous extract. Moreover, the treated animals displayed an elevated output of electrolytes and an enhanced glomerular filtration rate in comparison to the control group. Notably, the histological examination of the kidneys from the treated animals depicted a normal structural configuration, devoid of any cellular-level modifications attributed to the plant extract across all tested doses. CONCLUSION: The Hedyotis scandens extract demonstrated a pronounced diuretic effect in contrast to the control group. As such, our study substantiates the traditional employment of this plant as a diuretic within the Mizoram region.

Identification of bioactive components on antihemorrhoidal activity of Cistus laurifolius L. using RP-HPLC and LC-QTOF-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistus laurifolius is widely used in folk medicine in Anatolia for the treatment of many ailments. The leaves of the plant are used in the form of tea in the treatment of hemorrhoids in the Western Black Sea Region and Central Anatolia. AIMS OF THE STUDY: It was aimed at evaluating the anti-hemorrhoidal effects of C. laurifolus leaves in croton oil-induced hemorrhoid model in rats. MATERIALS AND METHODS: The methanolic and aqueous extracts of C. laurifolius were tested for in vivo anti-hemorrhoidal efficacy using an experimental hemorrhoid model, followed by histological and biochemical analysis. Hemorrhoid was created by using croton oil on the anal region of the rats. TNF-α and VEGF mRNA expression levels were assessed using real-time PCR detections. The extract was also tested for anti-inflammatory properties, which are based on the suppression of an increase in capillary permeability caused by acetic acid. LC-QTOF-MS and RP-HPLC were used for the phytochemical analysis. RESULTS: In comparison to the control, histological and biochemical assessment showed that the methanolic extract of C. laurifolius is particularly effective against hemorrhoids. The same extract group's TNF-α mRNA expression was found to be the lowest. Additionally, the methanolic extract showed a strong inhibitory effect on the increase in capillary permeability resulted on by acetic acid. Three phenolic compounds were discovered in the extracts by phytochemical analyses, while more than eighteen compounds were found by LC-QTOF-MS analysis. Five of these compounds are phenolic acid derivatives, and flavonoids constitute the majority of the group. CONCLUSION: This is the first evidence from the research that C. laurifolius possesses strong anti-inflammatory and anti-hemorrhoidal properties.

Annickia affinis (Exell) Versteegh & Sosef methanol stem bark extract, potent fractions and isolated Berberine alkaloid target both blood and liver stages of malaria parasites.

ETHNOPHARMACOLOGICAL RELEVANCE: Having identified Annickia affinis as the most potent antiplasmodial plant constituent in a hepta-herbal Agbo-iba (HHA) formula commonly used to manage malaria in Benin city, Nigeria, we have in this study attempted to identify the specialized metabolites responsible for antiplasmodial activity of A. affinis through anti-blood stage malaria parasite activity guided isolation of potent molecules from its stem bark methanol extract. After that, phenotypic effects, including stage-specific kill kinetics, were investigated. Further, the crude extract, its potent fractions, and specialized metabolites were also tested against the liver-stage malaria parasite. MATERIALS AND METHODS: A. affinis was subjected to molecular PCR-based analysis to confirm its identity. Thereafter, extraction of its stem bark with methanol was carried out. Alkaloid enriched fractions from this stem bark extract were obtained using the acid-base-solvent extraction method. These alkaloid-enriched fractions were subjected to various chromatographic techniques that led to the isolation of two protoberberine alkaloids identified as berberine and palmatine based on NMR and mass spectrometry analysis. The efficacy of crude extract, fractions and purified alkaloids was tested against the malaria parasite's blood and liver stages, respectively. RESULTS AND DISCUSSION: Annickia affinis methanol extract, fractions, and the isolated protoberberine alkaloids showed excellent antiplasmodial activity with good selectivity against blood-stage malaria parasite. Thus, their IC50 against various strains of the parasite ranged from 0.95 to 18.65 µg/ml, while CC50 against Human embryonic kidney (HEK) and the human hepatoma (HUH-7) cell lines ranged between 10 and > 100 µg/ml. Interestingly, the crude extract and the alkaloid enriched fractions showed promising activity against the liver-stage malaria parasite. Between berberine and palmatine isolated from the potent fractions, only the former showed ∼100% and 90% inhibitions of liver stage parasite at 5 µg/ml and 1 µg/ml, respectively, while the latter showed no inhibition even at 20 µg/ml. CONCLUSION: This study reports that the ethnomedicinal use of HHA to manage malaria can be attributed to the presence of promising antiplasmodial protoberberine alkaloids together with synergistic effects via either enhancement of bioavailability or improved pharmacokinetics by other phytoconstituent(s) coming from other HHA constituent plants. The protoberberine alkaloids isolated have been identified as fast-acting antiplasmodial agents, with activity against all erythrocytic stages of the malaria parasite. Further, A. affinis methanol stembark extract and the protoberberine alkaloid berberine isolated from it also displayed excellent activity (>90% inhibition at 1 µg/ml) against the liver-stage malaria parasite. A. affinis and HHA can thus be useful as both liver-stage prophylactic and blood-stage curative agents.

Triazole Antifungal Quantification for Therapeutic Drug Monitoring in Serum by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS): Posaconazole, Voriconazole, Itraconazole, and Hydroxyitraconazole.

Antifungal therapy with triazole drugs including posaconazole, voriconazole, itraconazole, and its active metabolite hydroxyitraconazole is routinely accompanied by therapeutic drug monitoring to ensure optimal dosing. The method presented here simultaneously quantitates these compounds in serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Specimen preparation includes protein precipitation with a methanol and acetonitrile mixture, centrifugation, and filtration. Analyte separation is achieved by reverse-phase chromatography using a dC18 column and a linear gradient of methanol in water. Analytes are detected by multiple reaction monitoring mass spectrometry and quantitated by comparison to a standard curve.

Evaluation of anti-inflammatory potential and GC-MS profiling of leaf extracts from Clerodendrum infortunatum L.

ETHNOPHARMACOLOGICAL RELEVANCE: Clerodendrum infortunatum L. is commonly distributed in tropical and subtropical countries and is widely used in the indigenous systems of medicine including Ayurveda, Unani, and Homeopathy. The plant has important uses in the treatment of various inflammatory disorders which includes asthma, cough, chest complaints, pain, rheumatism, osteoarthritis, gastric ulcer, cancer, diabetes, skin diseases etc. AIM OF THE STUDY: Regarding the extensive healing properties of C. infortunatum in folk medicine, we aimed to explore the anti-inflammatory activity of the plant and analyze its bioactive components. MATERIALS AND METHODS: Sequential extracts were prepared from C. infortunatum leaves using n-hexane, dichloromethane, ethyl acetate, methanol, ethanol and water. In vitro anti-inflammatory activity of these extracts were evaluated using membrane stabilization and protein anti-denaturation assays. Toxicity of the extracts was tested using brine shrimp lethality assay. GC-MS analysis has been carried out to analyze and characterize various bioactive constituents present in the plant. RESULTS: Each of the tested extracts showed significant (p < 0.05) in vitro anti-inflammatory activity. Sequential ethyl acetate extract demonstrated the strongest membrane stabilization and protein anti-denaturation activities with IC50 values of 331.3, 308.3 and 279.2 µg/mL for heat and hypotonicity induced membrane stabilization and protein anti-denaturation assays, respectively. Sequential methanol extract also exhibited strong activity in heat and hypotonicity induced membrane stabilization and protein anti-denaturation assays with IC50 values of 371.5, 331.6 and 284.6 µg/mL, respectively. The extracts demonstrated a range of toxicity in the brine shrimp lethality assay with LC50 values of 51.4, 59.7, 47.3, 37.1, 68.1 and 77.3 µg/mL for n-hexane, dichloromethane, ethyl acetate, methanol, ethanol and water extracts respectively. The GC-MS analysis of direct n-hexane, ethyl acetate and methanol extracts detected 32 different compounds. The major compounds (> 5%) were phenol, 3,5-bis(1,1-dimethylethyl)-, hexadecanoic acid methyl ester, estragole, methyl stearate, lanosterol, 9-methoxybicyclo[6.1.0]nona-2,4,6-triene, benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl) 4 hydroxy methyl ester, 22,23-dibromostigmasterol acetate, 3-methyl-4-(phenylthio)-2-prop-2-enyl-2,5-dihydrothiophene 1,1-dioxide, benzenemethanol, α-methyl-α-propyl- and 9-octadecenoic acid (Z)- methyl ester. CONCLUSIONS: The findings of our study revealed that C. infortunatum is rich with diverse bioactive phytoconstituents and the scientific evidences support the anti-inflammatory potential of the plant.

Antidepressant- and anxiolytic-like activities and acute toxicity evaluation of the Psilocybe cubensis mushroom in experimental models in mice.

ETHNOPHARMACOLOGY RELEVANCE: Central nervous system (CNS) diseases can be diverse and usually present with comorbidity, as in the case of depression and anxiety. Despite alternatives like Psilocybe mushrooms for mental health there is no basic research to evidence their CNS benefits. AIM OF THE STUDY: To evaluate the anxiolytic- and antidepressant-like effects, as well as the acute toxicity of P. cubensis mushroom. MATERIAL AND METHODS: First, the acute toxicity (LD50) of P. cubensis (2000 mg/kg) was determined after the esophageal (p.o.) and intraperitoneal (i.p.) route of administration. The rota-rod test and electroencephalogram (EEG) were included to assess CNS toxicity in free moving mice. Anxiolytic (ambulatory or exploratory and rearing behaviors) and antidepressant behavioral responses were assayed in the open-field, plus-maze, and forced swimming test, respectively, after administration of 1000 mg/kg, p.o., of the whole P. cubensis mushroom or the polar aqueous (AQ) or methanolic (MeOH) extractions (1, 10, and/or 100 mg/kg, i.p.) in comparison to the reference drugs buspirone (4 mg/kg, i.p.), fluoxetine and/or imipramine (10 mg/kg, s.c. and i.p., respectively). A chemical analysis of the AQ and MeOH extractions was performed to detect psilocybin and/or psilocin by using UHPLC. RESULTS: Neurotoxic effects of P. cubensis mushroom administered at high doses were absent in mice assessed in the rota-rod test or for EEG activity. A LD50 > 2000 mg/kg was calculated by p.o. or i.p. administration. While significant and/or dose-response antidepressant-like effects were produced with the whole P. cubensis mushroom, p.o., and after parenteral administration of the AQ or MeOH extractions resembling the effects of the reference drugs. Behavioral responses were associated with an anxiolytic-like effect in the open-field as corroborated in the plus-maze tests. The presence of psilocybin and psilocin was mainly characterized in the AQ extraction. CONCLUSION: Our results provide preclinical evidence of the anxiolytic- and antidepressant-like effects of the P. cubensis mushroom without producing neurotoxicity after enteral or parenteral administration, where psilocybin and psilocin were identified mainly after AQ extraction. This study reinforces the benefits of the P. cubensis mushroom in mental health and therapy for anxiety and depression.

GC-MS analysis and potential therapeutic efficacy of extracts from Allium humile Kunth in lowering dyslipidemia in wistar rat models.

ETHNOPHARMACOLOGICAL RELEVANCE: Small Alpine onion Allium humile (Alliaceae) is a common traditional Indian medicine used for blood purification, anti-inflammatory, anti-asthmatic, anti-diabetic and seasoning agents. It is also used for the treatment of asthma, jaundice, stomach problems, cardiovascular disorders and anti-cancer agent. AIM OF THE STUDY: In this study, various extracts from the A. humile were taken and their therapeutic activity against dyslipidemia was evaluated in wistar rat models. MATERIALS AND METHODS: The extraction was done by Soxhlet extraction and the extracts (hexane, ethyl acetate, methanol, ethanol and aqueous) obtained were then tested for nitric oxide radical scavenging activity. The effective extracts i.e., methanol and ethyl acetate were then selected for in vivo studies in wistar rats. Dyslipidemia was induced in rats by feeding them high fat diet, and extracts of varying concentrations were administered to assess their potential for decreasing dyslipidemia. Statin was used as a positive control. After treatment, the blood was drawn and serum was separated for tests such as lipid profile, atherogenic index, lipid peroxidation and histopathological study. GC-MS analysis was carried out to identify the types of compounds present in A. humile extracts and FTIR analysis of extracts was done to determine the types of chemical bonds and functional groups. RESULTS: The phytochemical screening of A. humile extracts revealed a high concentration of flavonoids, alkaloids, phenols, terpenoids, and saponins. Different extracts were evaluated to inhibit the nitric oxide at different concentrations. At the concentration of 700 µg/ml, methanol extract showed maximum inhibition of 78.26%, followed by ethyl acetate, ethanol, aqueous and hexane have shown 62.25%, 54.26%, 47.59% and 36.99% respectively. The GC-MS analysis of methanol and ethyl acetate extracts revealed many compounds. The FTIR analysis showed the presence of many functional groups pertaining to various compounds. The methanolic extract (100 mg/kg) was more active (P < 0.0001) than the ethyl acetate extract in lowering lipid levels, lipid peroxidation, and the decreasing development of the lipoidal layer in aortic wall and rupture of the intima and media confirmed by histopathological study. CONCLUSION: The results indicate that A. humile methanolic extract was more active than the ethyl acetate extract in lowering lipid levels, lipid peroxidation, inhibiting NOS production and the decreasing development of the lipoidal layer in aortic wall and thus could serve potential antihyperlipidemic agent to enhance cardiovascular health.

MIL-68 (Ga) for the extraction of derivatized and non-derivatized parabens from healthcare products.

This study was the first-ever attempt to apply MIL-68 (Ga) in developing an analytical method. The method extracts and preconcentrates some parabens from mouthwash and hydrating gel samples. The variable extraction parameters were optimized, and the figures of merit were documented. Avogadro software was used besides discussing intermolecular interactions to clarify the absorption process. ComplexGAPI software was also exploited to assess the greenness of the method. After the derivatization of the parabens using acetic anhydride in the presence of sodium carbonate, sodium chloride was added to the solution and vortexed to dissolve. A few milligrams of MIL-68 (Ga) were added into the solution and vortexed. Centrifugation separated the analyte-loaded absorbent, which was treated with mL volume of methanol through vortexing for desorption aim. A few microliters of 1,2-dibromoethane were merged with the methanolic phase and injected into a sodium chloride solution. One microliter of the extracted phase was injected into a gas chromatograph equipped with a flame ionization detector. High enrichment factors (200-330), reasonable extraction recoveries (40-66%), wide linear ranges (265-30,000 µg L-1), and appreciable coefficients of determination (0.996-0.999) were documented. The applicability of dispersive solid phase extraction for extracting polar analytes, imposing no additional step for performing derivatization, the capability of MIL-68 (Ga) for the absorption of both derivatized and non-derivatized parabens, the use of only 10 mg absorbent, and one-pot synthesis besides no high temperature or long reaction time in the sorbent provision are the highlights of the method.

UPLC/ESI/MS profiling of red algae Galaxaura rugosa extracts and its activity against malaria mosquito vector, Anopheles pharoensis, with reference to Danio rerio and Daphnia magna as bioindicators.

BACKGROUND: Anopheles pharoensis has a major role in transmitting several human diseases, especially malaria, in Egypt?. Controlling Anopheles is considered as an effective strategy to eliminate the spread of malaria worldwide. Galaxaura rugosa is a species of red algae found in tropical to subtropical marine environments. The presence of G. rugosa is indicative of the ecosystem's overall health. The current work aims to investigate UPLC/ESI/MS profile of G. rugosa methanol and petroleum ether extracts and its activity against An. pharoensis and non-target organisms, Danio rerio and Daphnia magna. METHODS: Galaxaura rugosa specimens have been identified using DNA barcoding for the COI gene and verified as G. rugosa. The UPLC/ESI/MS profiling of G. rugosa collected from Egypt was described. The larvicidal and repellent activities of G. rugosa methanol and petroleum ether extracts against An. pharoensis were evaluated, as well as the toxicity of tested extracts on non-target organisms, Dan. rerio and Dap. magna. RESULTS: The UPLC/ESI/MS analysis of methanol and petroleum ether extracts led to the tentative identification of 57 compounds belonging to different phytochemical classes, including flavonoids, tannins, phenolic acids, phenyl propanoids. Larval mortality was recorded at 93.33% and 90.67% at 80 and 35 ppm of methanol and petroleum ether extracts, respectively, while pupal mortality recorded 44.44 and 22.48% at 35 and 30 ppm, respectively. Larval duration was recorded at 5.31 and 5.64 days by methanol and petroleum ether extracts at 80 and 35 ppm, respectively. A decrease in acetylcholinesterase (AChE) level and a promotion in Glutathione-S-transferase (GST) level of An. pharoensis 3rd instar larvae were recorded by tested extracts. The petroleum ether extract was more effective against An. pharoensis starved females than methanol extract. Also, tested extracts recorded LC50 of 1988.8, 1365.1, and 11.65, 14.36 µg/mL against Dan. rerio, and Dap. magna, respectively. CONCLUSIONS: Using red algae derivatives in An. pharoensis control could reduce costs and environmental impact and be harmless to humans and other non-target organisms.

Phytochemical analysis, antioxidant and hypoglycemic activities of a methanol extract from Stachys brachyclada de Noé ex Coss. leaves.

Stachys brachyclada de Noé ex Coss. (Lamiaceae) is a quite rare medicinal plant endemic to the Mediterranean basin. In this study, seven secondary metabolites from a methanol extract of its leaves have been isolated and identified by a combination of chromatographic and spectroscopic methods (1D and 2D NMR experiments and ESIMS analysis). They include one ethyl 4-hydroxybenzoate (1), three acylated flavone glycosides (2-4), one diapigenin derivative (5) and two flavone aglycones (6-7). Stachysetin (5) was found the major compound of the extract (74.0 mg/g of dry matter). Moreover, the produced extract showed the ability in inhibiting the α-glucosidase enzyme (IC50 = 13.7 µg/mL), in quenching the radical 1,1-diphenyl-2-picrylhydrazyl (EC50 = 74.6 µg/mL), and in reducing the intracellular oxidative stress level in Human Dermal Fibroblast (64% inhibition at 50 µg/mL).

In vitro anti-Trypanosoma cruzi activity of methanolic extract of Bidens pilosa and identification of active compounds by gas chromatography-mass spectrometry analysis.

Chagas disease, caused by Trypanosoma cruzi parasite, is a significant but neglected tropical public health issue in Latin America due to the diversity of its genotypes and pathogenic profiles. This complexity is compounded by the adverse effects of current treatments, underscoring the need for new therapeutic options that employ medicinal plant extracts without negative side effects. Our research aimed to evaluate the trypanocidal activity of Bidens pilosa fractions against epimastigote and trypomastigote stages of T. cruzi, specifically targeting the Brener and Nuevo León strains-the latter isolated from Triatoma gerstaeckeri in General Terán, Nuevo León, México. We processed the plant's aerial parts (stems, leaves, and flowers) to obtain a methanolic extract (Bp-mOH) and fractions with varying solvent polarities. These preparations inhibited more than 90% of growth at concentrations as low as 800 µg/ml for both parasite stages. The median lethal concentration (LC50) values for the Bp-mOH extract and its fractions were below 500 µg/ml. Tests for cytotoxicity using Artemia salina and Vero cells and hemolytic activity assays for the extract and its fractions yielded negative results. The methanol fraction (BPFC3MOH1) exhibited superior inhibitory activity. Its functional groups, identified as phenols, enols, alkaloids, carbohydrates, and proteins, include compounds such as 2-hydroxy-3-methylbenzaldehyde (50.9%), pentadecyl prop-2-enoate (22.1%), and linalool (15.4%). Eight compounds were identified, with a match confirmed by the National Institute of Standards and Technology (NIST-MS) software through mass spectrometry analysis.

Development and Validation a UPLC-MS/MS Method for Quantification of Pentoxifylline in Beagle Plasma: Application for Pharmacokinetic Study of Food Effect.

Purpose: To develop an UPLC-MS/MS method for the quantitative analysis of pentoxifylline in beagle dog plasma and apply it to a pharmacokinetic study of food effect. Methods: Sample separation was achieved using a Kinetex Phenyl-Hexyl column (50 × 2.1 mm, 1.7 µm) with a gradient elution program in 5.5 min after a simple protein precipitation with methanol. Using the mobile phase that made up by 0.2% formic acid and 5mM ammonium formate water (A) and methanol (B). Quantitation was carried out using the positive ionization mode with multiple reaction monitoring (MRM). A randomized, single-dose, two-period crossover study was conducted in six fasted or fed beagles that received 400 mg pentoxifylline sustained-release tablets (Brand name: Shuanling™, CSPC Pharmaceutical Group). WinNonlin® software was used to calculate pharmacokinetic parameters. Results: The linear calibration range was 2-1000 ng/mL (r2> 0.99). Both intra- and inter-batch precision were less than 6.27%, and the accuracy ranged from 88.65% to 97.18%. Pentoxifylline was readily absorbed in fasted and fed dogs administered a dose of 400 mg (tmax:1.54h vs 1.83h). Compared to the fasted group, the AUC0→t and Cmax in the fed group increased by 1.71-fold and 1.30-fold, respectively. In the fasted group, the AUC0→t and Cmax values were 4684.08 h•ng/mL and 2402.33 ng/mL, respectively. In the fed group, these values were 8027.75 h•ng/mL and 3119.67 ng/mL. The difference in AUC0-t between the fed and fasted group was statistically significant. Conclusion: The novel optimized UPLC-MS/MS assay is an effective tool for the determination of pentoxifylline and has been successfully applied in pharmacokinetic studies of pentoxifylline in beagle dogs. The administration of pentoxifylline sustained-release tablets with food significantly increased the area under the time curve, and it is recommended that they should be administered during or shortly after feeding.