Pharmacological Potential Research Articles

Impact of geographical distribution on polyphenol compostion, antioxidant, antimicrobial and cytotoxic potential of Rhynchostylis retusa (L.) Blume roots

IntroductionRhynchostylis retusa (L.) Blume lies in the heart of majestic Himalayan mountains and is well-documented in Traditional System of Medicine. R. retusa roots are used to treat rheumatic disease, asthma, tuberculosis, epilepsy, kidney, and menstrual disorders. Besides earlier reports, current study was focused to investigate locational variations of polyphenols, antioxidant, antimicrobial and cytotoxicity activities of R. retusa roots. MethodR. retusa roots of four locations of Himachal Pradesh, India were used in the current study. The targeted polyphenols were determined using UPLC-PDA while total phenolic and total flavonoid contents were by spectroscopic method. The antioxidant activity was assessed by DPPH ֹ and ABTS ֗+ assays. Antimicrobial activity was performed against gram-positive (Bacillus subtilis and Staphylococcus aureus) and gram-negative bacteria (Salmonella typhimurium and Escherichia coli) while cytotoxicity activity was against HT29 cancer cell line. ResultIn present study, 50 % ethanol revealed higher yield in Kangra region (1375 m; 32.1109° N, 76.5363° E) sample followed by water and ethanol. Among all extracts, gallic acid and protocatechuic acid were most abundant phenolic acids. The highest TPC and TFC were found in the ethanol extract of Bilaspur (680 m; 31.33°N 76.75°E) sample (155.58±6.92 mg GAE/g and 262.25±8.32 mg RE/g) and Kangra (135.64±4.36 mg GAE/g and 281.75±4.38 mg RE/g) regions, respectively. The ethanol extract from Hamirpur (790 m 31.6862° N, 76.5213° E), exhibited highest antioxidant activity (IC50 33.31±0.72 µg/mL and 12.45±0.68 µg/mL), in DPPH ֹ and ABTS ֗+ assays, respectively. The ethanol extract from Bilaspur (5 mm and 3 mm ZOI for B. subtilis and S. aureus), Kangra (4 mm and 2.5 mm for B. subtilis and S. aureus), and Hamirpur showed most potent antimicrobial activity. Whereas, Mandi (760 m; 31.7087° N, 76.9320° E) samples showed least potential as compared to other targeted locations. Further, ethanol extracts of all locations were found most effective in terms of their cytotoxic activity against HT29 cancer cell lines. ConclusionCurrent investigations illuminate ethanol's pivotal role in extracting polyphenols and unleashing the pharmacological potential of R. retusa root extract. Thus, ethanol may be considered as a suitable solvent to extract, fractionate and isolate the bioactive compounds for health perspectives. Findings also suggested that Kangra region (1375 m; 32.1109° N, 76.5363° E) sample has highest potential and can be focused for further study.

A comprehensive review on pharmacological, phytochemical and anticancer potential of Tragia species

Genus Tragia is a member of Euphorbiaceae family and is frequently found in tropical environments. There are more than 150 species in Tragia. Tragia plant is widely distributed in India and East Africa peninsula. Tragia has been designated for multiple medicinal properties including anti-bacterial, anti-inflammatory, anti-fungal, reproductive, diarrhoea, scorpion bite, whooping cough, diabetes etc. These are few medicinal benefits of Tragia. Tragia is also used in ethno medical research. Tragia involucrata, Tragia spathulata, Tragia benthamii, Tragia pluknetii, Tragia urens, Tragia nepetifolia and Tragia urticifolia are the principal species being researched worldwide. By the conventional wisdom, Tragia would be a component in siddha and ayurvedic medicine. Pharmacologically, many phytochemicals including lignans, alkaloids, flavonoids, terpenoids and phenolic substances, have been linked to these characteristics. The combined effects of these phytoconstituents greatly enhance their potential as medicinal agents. Moreover, this review discusses the challenges and future prospects in harnessing the full therapeutic potential of Tragia species. Issues such as standardization of extracts, elucidation of specific active compounds and clinical translation are addressed, highlighting areas that require further research.

Invitro Antibacterial, Antioxidant and XRF Analysis of <i>Commelina Diffusa Burm.F. </i>Plant Extracts

Ethiopia has a long history of using medicinal herbs for treating both human and animal illnesses. Nonetheless, not enough research has been done on the antibacterial properties and possible bioactive components of the majority of medicinal plants. Therefore, this study deals with the evaluation of phytochemical, antimicrobial, antioxidant activities, phenol content and XRF analysis of <i>Commelina Diffusa Burm.F. </i>plant extracts. Mean values of the antimicrobial activity, MIC, antioxidant activities, phenol content and XRF analysis were reported as mean ± standard deviation. The chloroform leaf extracts of the plant gave the highest yield 23.4% followed by methanol 22.27%. The presence of several metabolite components, including alkaloids, diterpenes, flavonoids, glycosides, phenol, protein, saponin, steroids, tannins, terpenoids, tri-terpenoids and amino acids, has been shown by qualitative phytochemical analysis of plant parts. Significant antibacterial activity against the test bacterial strains was demonstrated by steam extracts of<i> Commelina Diffusa Burm.F. </i>Moreover, the methanolic extract of the plant demonstrated notable antioxidant activity. The highest value of phenolic content was obtained in <i>Commelina Diffusa Burm.F. </i>steam methanol extract followed by leaf extract while <i>Commelina Diffusa Burm.F. </i>root extract shows lower phenolic content. In this study, threaten elements were determined in the <i>Commelina Diffusa Burm.F. </i>plant part by using XRF spectroscopy. Overall, this research contributes to the understanding of pharmacological potential of <i>Commelina Diffusa Burm.F. </i>and highlights the importance of further exploring its medicinal properties. The findings provide valuable insights into utilizing medicinal plants for disease treatment and support the development of natural therapeutic agents.

Physicochemical Evaluation and Pharmacological Screening of Fernando Adenophylla Steenis Fruits.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200 mg/kg extract dose exhibited %age pain inhibition of 55.12 % and reduced body temperature from 39.78±0.03 °C to 37.22±0.02 °C in hyperthermic rats. A decrease in blood glucose levels up to 57.88 % was observed on the 21st day of the treatment with 500 mg/kg ethanolic extract.

Exploring the pharmacological potential of Lepionurus sylvestris blume: from folklore medicinal usage to modern drug development strategies using in vitro and in silico analyses

BackgroundLepionurus sylvestris Blume has a long history of folklore medicinal usage against various ailments. However, studies on these plants were neglected particularly their pharmacological potential.MethodsThe crude extract was identified using LC-MS analysis. In vitro assays were carried out to determine the properties of antioxidant, anti-microbial, and anti-cancer. Further, network pharmacology was proposed to evaluate the potential targets of the compounds against breast cancer and type II diabetes. Molecular docking and molecular dynamic simulation were used to determine the potential compounds for the drug formulation of diabetes.ResultsVarious bioactive compounds were identfied using LC-MS and Galiposin, Fujikinetin, Boeravinone B, 4-Deoxybryaquinone, and Norbaeocystin were described for the first time from the plant. Determination of antioxidant potential showed that the IC50 value of ABTS, DPPH, and phosphomolybdate was 24.33 µg/ml, 37.81 µg/ml, 60.35 µg/ml, and reducing power assays 1.185. The antibacterial activity against Streptococcus pyogenes, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was determined, and the minimum inhibition concentration (MIC) was found to be 5.3 mg/ml, 3.47 mg/ml, 3.33 mg/ml, and 2.7 mg/ml respectively, revealing the extracts as effective antibacterial agents. The IC50 values for the plant extract were determined to be 26 µg/ml, 30.52 µg/ml, and 24.39 µg/ml for HeLa, MCF-7, and K-562 cells, respectively, and the increasing concentration of the plant extract increased LDH release. Furthermore, the in silico network pharmacology, molecular docking which had the highest docking score for GAPDH and HIF-1 target proteins of -9.3 kcal/mol, and − 11.3 kcal/mol binding affinities, and molecular dynamic simulation analysis revealed the bioactive compound Boeravinone B present in the plant was significant for the treatment of various ailments.ConclusionBased on our findings, plant extracts could be a promising option for developing new drug formulations.

In silico molecular screening of bioactive natural compounds of rosemary essential oil and extracts for pharmacological potentials against rhinoviruses

Rhinoviruses (RVs) cause upper respiratory tract infections and pneumonia in children and adults. These non-enveloped viruses contain viral coats of four capsid proteins: VP1, VP2, VP3, and VP4. The canyon on VP1 used cell surface receptor ICAM-1 as the site of attachment and for the internalization of viruses. To date, there has been no drug or vaccine available against RVs. In this study, bioactive natural compounds of rosemary (Salvia rosmarinus L.), which are known for their pharmacological potential, were considered to target the VP1 protein. A total of 30 bioactive natural compounds of rosemary were taken as ligands to target viral proteins. The PkCSM tool was used to detect their adherence to Lipinski’s rule of five and the ADMET properties of the selected ligands. Further, the CB-Dock tool was used for molecular docking studies between the VP1 protein and ligands. Based on the molecular docking and ADMET profiling results, phenethyl amine (4 methoxy benzyl) was selected as the lead compound. A comparative study was performed between the lead compound and two antiviral drugs, Placonaril and Nitazoxanide, to investigate the higher potential of natural compounds over synthetic drugs. Placonaril also targets VP1 but failed in clinical trials while Nitazoxanide was examined in clinical trials against rhinoviruses. It was discovered from this study that the (4 methoxy benzyl) phenethyl amine exhibited less toxicity in comparison to other tested drugs against RVs. More research is needed to determine its potential and make it a good medication against RVs.

Crystallographic analysis, Hirshfeld surface investigation, and DFT calculations of 2-phenoxy-triazoloquinazoline molecule: Implications for drug design

This study presents a comprehensive structural and computational investigation of 2-phenoxy-1,2,4-triazolo[1,5-a]quinazoline (PTQ), a compound with promising pharmacological potential. Single-crystal X-ray diffraction (SCXRD) analysis revealed the molecular geometry and crystal packing, while density functional theory (DFT) calculations provided insights into electronic properties and reactivity. Hirshfeld surface analysis elucidated intermolecular interactions, highlighting hydrogen bonding, van der Waals forces, and π–π stacking as crucial factors in crystal stability. Fingerprint analysis quantified these interactions, revealing the dominance of hydrogen contacts and the significance of hydrogen bonds and C–H···π interactions. Void analysis identified potential areas for inclusion complex formation. Frontier molecular orbital analysis and molecular electrostatic potential (MEP) mapping identified potential electrophilic and nucleophilic sites, guiding future reactivity studies. Furthermore, in silico ADMET and molecular docking studies were performed to assess the drug-likeness and potential antihistamine activity of PTQ.

Isolation and In Vitro Biological Evaluation of Triterpenes from Salacia grandifolia Leaves.

Salacia grandifolia is naturally found in the Atlantic Forest regions of Brazil. Despite the pharmacological potential of plants from the Salacia genus, phytochemical studies on this species have not been reported in literature. A new triterpene, 28-hydroxyfriedelane-3,15-dione (1), and seven known compounds (friedelan-3-one (2), friedelan-3β-ol (3), friedelane-3,15-dione (4), 15α-hydroxyfriedelan-3-one (5), 28-hydroxyfriedelan-3-one (6), 30-hydroxyfriedelan-3-one (7), and 29-hydroxyfriedelan-3-one (8)) were obtained from the hexane extract of Salacia grandifolia leaves. These isolated compounds and three extracts, hexane (EH), chloroform (EC), and ethyl acetate (EAE), were assessed for their potential biological activities, which consisted in the evaluation of antiviral activity against a murine coronavirus, mouse hepatitis virus 3 (MHV-3), antibacterial activity against the susceptible and methicillin-resistant Staphylococcus aureus (MRSA), and antileukemia activity against the THP-1 and K-562 cell lines. The extracts EH and EAE along with the triterpenes 1 and 6 exhibited moderate to high antiviral activity, with emphasis on 6, which presented an EC50 value of 2.9 ± 0.3 μM. None of the compounds presented antibacterial activity against the tested strains. The evaluated compounds 1, 4, 6 and 7 exhibited low cytotoxic activity against the tested leukemia cell lines. Taken together, this study comprises an overview for the potential of the Salacia grandifolia biological activities, including a new isolated triterpene.

Chemical Composition, Antioxidant, and Cytotoxic Effects of Senna rugosa Leaf and Root Extracts on Human Leukemia Cell Lines.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was carried out by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins, and DNA. Cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extracts contained catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile showed obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with an IC50 of 4.86 ± 0.51 μg/mL and 8.33 ± 0.90 μg/mL in the ABTS assay for ELSR and ERSR, respectively. Furthermore, in the DPPH• assay, the IC50 was 19.98 ± 1.96 μg/mL for ELSR and 13.37 ± 1.05 μg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 μg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 h of treatment. After 48 h, results against the K562 cell line demonstrate an IC50 of 242.54 ± 2.38 μg/mL and 223.00 ± 2.34 μg/mL for ELSR and ERSR, respectively. While against the Jurkat cell line, these extracts showed an IC50 of 171.45 ± 2.25 μg/mL and 189.30 ± 2.27 μg/mL, respectively. The results pertaining to PBMC viability demonstrated that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions and expand their significant pharmacological potential in oxidative stress and leukemia conditions.

A click-chemistry based strategy for synthesizing coumarin piperazine analogues: Assessment of anti-tubercular, anti-cancer, anti-inflammatory and antioxidant potentials

In this study, a novel series of coumarin piperazine analogues were synthesized using Click chemistry approach. Thus synthesized compounds (8a-j) were evaluated for their pharmacological potentialities. These compounds subjected for evaluation of their anti-tubercular, anti-cancer, anti-inflammatory, and antioxidant properties. Results revealed that analogues 8b, 8d, 8i and 8h are found to be the promising drug-like candidates against Mycobacterium tuberculosis H37Rv strain exhibiting more potent activity than isoniazid with MIC of 2.24, 1.04, 3.72, 5.35 µM respectively. Furthermore, the compound 8d displayed better anti-inflammatory and antioxidant activity with IC50 values of 66.43 µM and 69.14 µM respectively. Molecular docking studies insights into the binding affinities and interactions with a target protein. The in silico ADME profiles supported their pharmacokinetic viability. Predominantly, compound 8d exhibited anticancer activity with IC50 values of 12.42 µM and 26.16 µM with reference to HeLa and MCF-7respectively by inhibiting acetyl-CoA synthetase. These findings highlight more specifically the compound 8d as a potent anti-cancer agent.

Appraisal terpenoids rich Boswellia carterri ethyl acetate extract in binary cyclodextrin oligomer nano complex for improving respiratory distress

Boswellia carterii (BC) resins plants have a long historical background as a treatment for inflammation, as indicated by information originating from multiple countries. Twenty-seven diterpenoids have been identified in ethyl acetate and total methanol BC, comprising seventeen boscartins of the cembrane-type diterpenoids and ten boscartols of the prenylaromadendrane-type diterpenoids. Moreover, twenty-one known triterpenoids have also been found, encompassing nine tirucallane-type, six ursane-type, four oleanane-type, and two lupane-type. The cembrane-type diterpenoids hold a significant position in pharmaceutical chemistry and related industries due to their captivating biological characteristics and promising pharmacological potentials. Extraction of BC, creation and assessment of nano sponges loaded with either B. carterii plant extract or DEX, are the subjects of our current investigation. With the use of ultrasound-assisted synthesis, nano sponges were produced. The entrapment efficiency (EE%) of medications in nano sponges was examined using spectrophotometry. Nano sponges were characterized using a number of methods. Within nano sponges, the EE% of medicines varied between 98.52 ± 0.07 and 99.64 ± 1.40%. The nano sponges' particle sizes varied from 105.9 ± 15.9 to 166.8 ± 26.3 nm. Drugs released from nano sponges using the Korsmeyer-Peppas concept. In respiratory distressed rats, the effects of BC plant extract, DEX salt and their nano formulations (D1, D5, P1 and P1), were tested. Treatment significantly reduced ICAM-1, LTB4, and ILβ 4 levels and improved histopathologic profiles, when compared to the positive control group. Boswellia extract and its nano sponge formulation P1 showed promising therapeutic effects. The effect of P1 may be due to synergism between both the extract and the formulation. This effect was achieved by blocking both ICAM-1 and LTB4 pathways, therefore counteracting the effects of talc powder.

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression.

Mycobacterium tuberculosis (Mtb) has long posed a significant challenge to global public health, resulting in approximately 1.6 million deaths annually. Pulmonary tuberculosis (TB) instigated by Mtb is characterized by extensive lung tissue damage, leading to lesions and dissemination within the tissue matrix. Matrix metalloproteinases (MMPs) exhibit endopeptidase activity, contributing to inflammatory tissue damage and, consequently, morbidity and mortality in TB patients. MMP activities in TB are intricately regulated by various components, including cytokines, chemokines, cell receptors, and growth factors, through intracellular signaling pathways. Primarily, Mtb-infected macrophages induce MMP expression, disrupting the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thereby impairing extracellular matrix (ECM) deposition in the lungs. Recent research underscores the significance of immunomodulatory factors in MMP secretion and granuloma formation during Mtb pathogenesis. Several studies have investigated both the activation and inhibition of MMPs using endogenous MMP inhibitors (i.e., TIMPs) and synthetic inhibitors. However, despite their promising pharmacological potential, few MMP inhibitors have been explored for TB treatment as host-directed therapy. Scientists are exploring novel strategies to enhance TB therapeutic regimens by suppressing MMP activity to mitigate Mtb-associated matrix destruction and reduce TB induced lung inflammation. These strategies include the use of MMP inhibitor molecules alone or in combination with anti-TB drugs. Additionally, there is growing interest in developing novel formulations containing MMP inhibitors or MMP-responsive drug delivery systems to suppress MMPs and release drugs at specific target sites. This review summarizes MMPs' expression and regulation in TB, their role in immune response, and the potential of MMP inhibitors as effective therapeutic targets to alleviate TB immunopathology.

Phytochemical profile and pharmacological potential of Withania somnifera whole plant extracts.

Withania somnifera belongs to the family Solanaceae, commonly called ashwagandha, and is traditionally used as an astringent, hepatoprotective and antioxidant, and as a treatment for rheumatism. Therefore the current study aimed to explore the dichloromethane fraction of W. somnifera whole plant (DCFWS) and ethyl acetate fraction of W. somnifera (EAFWS) using gas chromatoghraphy-mass spectrometry (GC-MS) analysis and to find the acetylcholinesterase inhibition potential along with spasmolytic activity. The GC-MS-detected phytochemicals were 2,4-bis(1,1-dimethylethyl), hexadecanoic acid, 1-nonadecene and 11-octadecenoic acid. The DCFWS and EAFWS exhibited acetylcholinesterase inhibitory potential with significant inhibitory concentration values. The acute toxicity results of both fractions showed high toxicity, causing emesis at 0.5g and both emesis and diarrhea at 1g/kg. Both fractions exhibited significant (p ≤ 0.01) laxative activity against metronidazole (7mg/kg) and loperamide hydrochloride (4mg/kg) induced constipation. Both DCFWS (66.8 ± 3.85%) and EAFWS (58.58 ± 3.28%) significantly (p ≤ 0.05) increased charcoal movement compared with distal water (43.93 ± 4.34%). Similarly the effect of DCFWS on KCl-induced (80 mm) contraction was more significant as compared with EAFWS. It was concluded that the plant can be used in the treatment of gastrointestinal tract diseases such as constipation. Furthermore, additional work is required in the future to determine the bioactive compounds that act as therapeutic agents in W. somnifera.

In silico research on Novel Derivatives of N-(Acetylphenyl)-N-Ferrocenylmethyl-3-nitroaniline as DNA Binding Agents: Using Diverse Computational Methods, including Molecular Docking and ADME/Toxicity Assessment

This study presents an in silico investigation into the potential DNA binding properties of novel derivatives of N-(Acetylphenyl)-N-Ferrocenylmethylnitroaniline using different computational techniques, including molecular docking and ADME/Toxicity assessment, we explored the interaction between these derivatives and DNA. The results reveal promising candidates with strong binding affinities to DNA, substantiated by robust electrostatic interactions. Furthermore, our study sheds light on the ADME and toxicity profiles of these compounds, providing insights into their pharmacological potential. These findings offer valuable insights into the design and development of DNA-binding agents with potential applications in various biomedical fields.

UHPLC-PDA-ELSD-MS-based simultaneous determination of diterpenoid alkaloids in commercially important Himalayan medicinal plant Aconitum heterophyllum Wall. and network pharmacology-based target prediction

Aconitum heterophyllum Wall., a commercially important Himalayan medicinal plant, is used in various herbal formulations and has high market demand. Given its esteemed medicinal properties, considerable demand, and prioritized status, there’s a pressing requirement for thorough quality assessment methods to ensure high throughput. Genus Aconitum is also well known for its toxicity owing to the presence of diester diterpenoid alkaloids. Hence it is essential to develop a UHPLC-PDA-ELSD-MS based quantification method enabling simultaneous quantification of primary marker compounds alongside toxic diterpenoid alkaloids. The method showcased strong linearity, with detection and quantification limits covering a broad range. Precision was evident with consistently low relative standard deviations both within and across days. Furthermore, accuracy was demonstrated within acceptable bounds. Quantification results revealed the maximum content of atisinium and hetisine in hydroethanolic root extract [atisinium (≅78.88 mg/g) and hetisine (≅50.17 mg/g)] In addition, a network pharmacology-based approach has been applied to predict potential biological targets. The network pharmacology approach suggests the plant’s potential in treating neuralgia, renal fibrosis, diabetes mellitus, lung diseases, cancer, and more, emphasizing the need for scientific validation and indicating future research directions. Overall, the developed method represents a reliable and efficient quality assessment method for the simultaneous quantification of marker compounds and toxic diterpenoid alkaloids in the roots of A. heterophyllum. Network pharmacology predicts pharmacological potentials that require scientific validation highlighting future scope.

Difamilast, a Topical Phosphodiesterase 4 Inhibitor, Produces Soluble ST2 via the AHR-NRF2 Axis in Human Keratinocytes.

Difamilast, a phosphodiesterase 4 (PDE4) inhibitor, has been shown to be effective in the treatment of atopic dermatitis (AD), although the mechanism involved remains unclear. Since IL-33 plays an important role in the pathogenesis of AD, we investigated the effect of difamilast on IL-33 activity. Since an in vitro model of cultured normal human epidermal keratinocytes (NHEKs) has been utilized to evaluate the pharmacological potential of adjunctive treatment of AD, we treated NHEKs with difamilast and analyzed the expression of the suppression of tumorigenicity 2 protein (ST2), an IL-33 receptor with transmembrane (ST2L) and soluble (sST2) isoforms. Difamilast treatment increased mRNA and protein levels of sST2, a decoy receptor suppressing IL-33 signal transduction, without affecting ST2L expression. Furthermore, supernatants from difamilast-treated NHEKs inhibited IL-33-induced upregulation of TNF-α, IL-5, and IL-13 in KU812 cells, a basophil cell line sensitive to IL-33. We also found that difamilast activated the aryl hydrocarbon receptor (AHR)-nuclear factor erythroid 2-related factor 2 (NRF2) axis. Additionally, the knockdown of AHR or NRF2 abolished the difamilast-induced sST2 production. These results indicate that difamilast treatment produces sST2 via the AHR-NRF2 axis, contributing to improving AD symptoms by inhibiting IL-33 activity.

Comparative pharmacology and abuse potential of oral dexamphetamine and lisdexamfetamine-A literature review.

To compare the pharmacology and abuse potential of oral dexamphetamine and lisdexamfetamine (LDX). A search of Medline and Embase was conducted to identify relevant articles for this literature review. Dexamphetamine and LDX, a prodrug of dexamphetamine, are indicated for the treatment of attention-deficit/hyperactivity disorder. It has been suggested that LDX may have a reduced potential for oral abuse compared to immediate-release dexamphetamine. As a prodrug, LDX has the same pharmacodynamic properties as dexamphetamine. A study in healthy adults showed that the pharmacokinetic profile of dexamphetamine following oral administration of LDX is essentially identical to that of an equimolar dose of dexamphetamine administered 1h later. In addition, dexamphetamine produced subjective drug liking effects comparable to those produced by LDX. LDX showed linear dose proportional pharmacokinetics up to a dose of 250mg, indicating a lack of overdose protection at supratherapeutic doses. Furthermore, the exposure to dexamphetamine released from LDX may be prolonged by the consumption of alkalizing agents. The available evidence from pharmacodynamic, pharmacokinetic and abuse liability studies suggests a comparable potential for oral abuse of dexamphetamine and LDX.

Preliminary phytochemical and biological activity screening of Sargassum lapazeanum

Algae are exposed to substantial stress. In response, these organisms have developed efficient defense systems, such as protective secondary metabolite synthesis, making algae a primary source of bioactive compounds with a wide spectrum of biological activities. Thus, algae show potential for use in treatments of thrombotic, infectious, and chronic degenerative diseases. Therefore, the objective of this study was to evaluate the phytochemical compounds and pharmacological activity of an extract obtained from Sargassum lapazeanum. Algae were collected in the intertidal zone of Tarabillas beach (Bahía de La Paz, BCS). The biological activities of an ethanolic extract and its fractions were evaluated using chromatographic techniques. In addition, a bioautographic assay of hemolytic activity was conducted, and phytochemical profiles and acute toxicity in Artemia franciscana were evaluated. The relationships among the main extract components were also determined. The ethanolic extract exhibited significant antioxidant and hemolytic activity, which was mainly attributed to its content of anthrones, anthraquinones, and unsaturated triterpenes. Its toxicological activity reached an LC50 value of 225.1 μg mL-1, which was mainly attributed to alkaloids, flavonoids, anthrones, and saponins. The results suggest that Sargassum lapazeanum, which is endemic to the Gulf of California, has great pharmacological potential with biomedical applications.

Phytochemistry and Bioactivities of Duguetia furfuracea (A.St.-Hil.) Saff.

Duguetia furfuracea, belonging to the Annonaceae family, is a perennial plant found in the Central-West, Southeast, and Northeast regions of Brazil, known for its various uses in traditional medicine. Used as a hypocholesterolemic, anorexigenic, and for treating various conditions including cancer and infections, its medicinal properties have garnered scientific interest. Studies have identified several bioactive compounds in different parts of the plant. The leaves contain phenolic acids, flavonoids, and alkaloids such as duguetine and dicentrinone, which exhibit antioxidant, anti-inflammatory, and antimicrobial properties. Phytochemical analysis revealed the presence of rare sesquiterpenes such as α-santalene and (-)-ishwarane, strengthening the chemotaxonomic relationship between Annonaceae and Aristolochiaceae. The species has shown larvicidal activity against Aedes aegypti, pediculicidal activity against Pediculus capitis, and antiplasmodial activity against Trypanosoma cruzi. Additionally, it possesses anti-inflammatory, antinociceptive, and cytotoxic activities, being effective against Candida spp. strains and cancer cells. However, its toxicity was observed in studies with Drosophila melanogaster and cellular models, indicating the need for further studies to ensure its safe use. The plant shows potential for therapeutic applications due to its chemical diversity, but it is essential to deepen investigations into its mechanisms of action and develop extraction and isolation methods to maximize its medicinal potential safely and effectively. Continued research is crucial to integrate D. furfuracea into modern phytotherapy and the development of new drugs. The presence of these bioactive compounds highlights the importance of exploring the full pharmacological potential of D. furfuracea for future therapeutic advancements, emphasizing its promising role in natural medicine. the pharmacological properties of D. furfuracea underscore its potential for innovative drug development and traditional medicinal enhancement.

GC-MS analysis and pharmacological potentiality of Lasia spinosa (L.) Thwaites leaves and fruit extracts: an in vitro and in silico studies.

Lasia spinosa (L. spinosa) is widely used in Asian countries for treating various diseases and as a vegetable, yet its bioactive properties remain under-researched. It is traditionally utilized in Ayurveda and the AYUSH system of medicine for its medicinal properties, and commonly used to treat digestive disorders, respiratory issues, and inflammatory conditions. This study aims to identify the phytochemicals in L. spinosa leaves and fruit extracts and evaluate their biological activities. Phytochemicals in methanol extracts of L. spinosa fruits and leaves were identified by GC-MS analysis. Antioxidant and cytotoxic activities were assessed using the DPPH free radical and nitric oxide (NO) scavenging assay and brine shrimp lethality test. Antibacterial activity was evaluated against Shigella boydii, Shigella flexneri, Streptococcus iniae, and Streptococcus dysgalactiae, while antifungal properties were tested against Cercospora beticola and Rhizoctonia solani. Molecular docking was conducted to predict the effectiveness of L. spinosa phytochemicals against NADPH oxidase and the Shigella effector OspG. Nine compounds were detected from both extracts. The methanol leaves extract exhibited superior antioxidant activity compared to the fruit extract, with IC50 values of 111.81 ± 8.99µg/ml and 174.81 ± 4.86µg/ml, respectively, as determined by the DPPH scavenging assay. The nitric oxide (NO) scavenging assay also revealed higher potency in the leaves extract (IC50 = 138.59 ± 1.50µg/ml) compared to the fruit extract (IC50 = 196.47 ± 1.72µg/ml). Both extracts showed significant antimicrobial activity against all tested microorganisms. In silico studies indicated notable inhibitory activity of all phytochemicals against the target proteins, with Linoelaidic acid and 9-Octadecenamide, (Z)- exhibiting the highest activity against NADPH oxidase (PDB: 2cdu) and Shigella flexneri OspG effector kinase (PDB: 4bvu), respectively. These findings suggest that L. spinosa has potent antioxidant and antimicrobial activities. Compounds from this plant could serve as lead compounds for developing antioxidant and antibacterial agents. However, molecular studies should be addressed.