Pharmacological Properties Research Articles

Withania somnifera as a potential nanomedicine: A review

Withania somnifera, commonly known as Ashwaganda, is an important medicinal plant for a long time. Roots, seeds and other parts of Ashwaganda have clinically important pharmacological properties. The phytochemicals present in the plant include flavonoids, alkaloids, phenols and withanolids which make it useful in treatment of cancer, cardiovascular diseases and diabetes. Withania somnifera possess anti-inflammatory, anticancer, antioxidant, antimicrobial and anti-aging activities. Nanobiotechnology is an emerging field as nanoparticles allow targeted and controlled drug delivery. Green synthesis of nanoparticles involves the use of plants for their ability to reduce harmful impacts associated with chemically synthesized nanoparticles. The green synthesis approach has been applied for the synthesis of nanoparticles form plant extracts obtained from Withania somnifera. Silver, gold, selenium, platinum and many more nanoparticles have been synthesized by mixing the root extracts of Ashwaganda and metal salts. Another approach involves the use of plant extracts encapsulated in niosomes and in combination with solid lipid nanoparticles which is pharmacologically helpful. The nanoparticles from Withania somnifera utilize anti-inflammatory, anticancer, antioxidant, antimicrobial and anti-aging activities of Ashwaganda and help in targeted delivery of the drug. The plant-based nanoparticles show better characteristics including bioavailability, solubility and improved shelf life. This approach can be developed further for agricultural and technological uses like sensors and imaging technology.

The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.

Orally bioavailable, synthetic nonpeptide agonists (NPAs) of the glucagon-like peptide-1 receptor (GLP-1R) may offer an effective, scalable pharmacotherapy to address the metabolic disease epidemic. One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron, which is in clinical development for treating type 2 diabetes and obesity. Here, we characterized the pharmacological properties of orforglipron in comparison with peptide-based GLP-1R agonists and other NPAs. Competition binding experiments using either [125I]GLP-1(7-36)NH2 or [3H]orforglipron indicated that orforglipron is a high-affinity [inhibition constant (Ki) = 1 nM], selective ligand of the human GLP-1R. Signal transduction assays showed that orforglipron has low intrinsic efficacy for effector activation and negligible β-arrestin recruitment. To evaluate GLP-1R engagement in vivo, mice expressing the human GLP-1R were administered orforglipron and subjected to a glucose tolerance test. Predicted receptor occupancy was calculated using the receptor Ki value of orforglipron and its unbound concentration in vivo that reduces hyperglycemia. These experiments revealed that low GLP-1R occupancy by orforglipron is sufficient to yield a full biological response. Moreover, in a model where CRISPR-Cas9 gene editing was used to sensitize the rat GLP-1R (Glp1rS33W) to GLP-1R NPAs, target engagement by orforglipron in the pancreas and brain was consistent with peptide-based GLP-1R agonists. Diet-induced obesity in Glp1rS33W rats enabled studies showing weight loss in animals orally administered orforglipron versus subcutaneous injection of GLP-1R agonist semaglutide. Furthermore, crossover studies indicated oral orforglipron can sustain efficacy initiated by parenteral semaglutide. The pharmacological properties of orforglipron may inform targeting of other peptide receptors with NPAs.

Unlocking the pharmacological potential of Brennnesselwurzel (Urtica dioica L.): an in-depth study on multifaceted biological activities

Brennnesselwurzel (Urtica dioica L.) is recognized for its diverse pharmacological properties. With a range of chemical constituents, such as vitamins, minerals, phenolic compounds, fibers, and amino acids, Brennnesselwurzel (BWE) has a long history of traditional medicinal use in Europe and Asia. The correlation between a plant's metabolite composition and its activity can vary depending on considerations such as geographic location, environmental conditions, and genetic variations. In the present study, we explore the phytochemical profile and biological activity of the 70% acetone extract of the BWE plant. The chemical profile of the BWE extract was explored using several techniques, including amino acid analyzer, HPLC, GC–MS, and other colorimetric analysis. The antioxidant activity of the BWE extract was assessed by evaluating the total antioxidant, free radical scavenging activity (DPPH, ABTS, H2O2), and metal chelating scavenging activity (FRAP, CUPRAC, metal chelating). Furthermore, we assessed the antimicrobial and antiproliferation activities of the BWE extract against 29 microbial strains and 15 cell lines, respectively. Our phytochemical analyzes revealed that the BWE extract has a unique profile of metabolites including amino acids, flavonoids, phenolics, volatile oils, lipids, and vitamins. The BWE extract showed a total antioxidant capacity of 30.94 ± 1.58 mg GAE/g, together with potential free radical scavenging activity towards ABTS (IC50 = 153.51 ± 3.97 µg/ml), DPPH (IC50 = 195.75 ± 5.91 µg/ml), and H2O2 (IC50 = 230.67 ± 5.98 µg/ml). Although the BWE extract showed no significant antifungal activity, our findings revealed that the BWE extract possesses substantial antibacterial activity against Staphylococcus epidermidi, Streptococcus mutants, Enterococcus faecalis, Micrococcus sp., Klebsiella pneumonia and Porphyromonas gingivalis. Furthermore, the BWE extract demonstrated potential antiproliferative activity toward a panel of cancer cell lines with a high selectivity index. Among the cells examined, the BWE extract exhibited significant cytotoxic activity toward HCT-116, A-549, MDA-MB-231 cells with IC50 of 15.11, 15.32, 15.79 µg/mL, respectively, while it possessed no significant cytotoxic activity towards WI-38 cells (IC50 119.62 µg/mL). Taken together, our findings reveal that BWE extract possesses a wide spectrum of biological activities, including antioxidant, antibacterial, and antitumor activities, and could be considered for further research to explore its potential as a natural plant-based supplement for human diseases.

Crystallization of n-Alkanes under Anisotropic Nanoconfinement in Lipid Bilayers.

Understanding crystallization behavior is integral to the design of pharmaceutical compounds for which the pharmacological properties depend on the crystal forms achieved. Very often, these crystals are based on hydrophobic molecules. One method for delivering crystal-forming hydrophobic drugs is by means of lipid nanoparticle carriers. However, so far, a characterization of the potential crystallization of fully hydrophobic molecules in a lipid environment has never been reported. In this work we investigate the crystallization behavior of two model hydrophobic chains, n-eicosane (C20) and n-triacontane (C30), in phospholipid bilayers. We combine static 2H nuclear magnetic resonance (NMR) spectroscopy and differential scanning calorimetry (DSC) and show that C30 molecules can indeed crystallize inside DMPC and POPC bilayers. The phase transition temperatures of C30 are slightly reduced inside DMPC, and rotator phase formation becomes a two-step process: Preorganized n-alkane chains assemble in rotator-phase crystallites just as fast as bulk C30, but further addition of molecules is notably slower. Under the same isothermal conditions, different crystal forms can be obtained by crystallization in the membrane and in bulk. In excess water conditions, homogeneous nucleation of C30 is observed. The initial anisotropic molecular arrangement of C30 molecules in the membrane is readily recovered upon reheating, showing reversibility. The shorter C20 molecules on the other hand become trapped in the DMPC membrane gel-phase upon cooling and do not crystallize. This work marks the first observation of the crystallization of hydrophobic chains inside a lipid bilayer environment. As such, it defines a fundamental starting point for studying the crystallization characteristics of various hydrophobic molecules in lipid membranes.

The current state of research on the pharmacological properties of melanins and the prospects for their use in medicine

Introduction. This article discusses the basic physico-chemical properties of melanins, their biosynthesis, and the potential for their use in medicine. As a result of the review, based on a number of scientific studies, it was revealed that melanins are characterized by a wide range of biological activity. They have photoprotective, radioprotective, immunomodulatory, stress-protective, antioxidant, detoxification and anti-inflammatory effects. The presented information indicates the promising use of melanins in medical practice in the treatment of diseases of the immune, central nervous, cardiovascular systems, and some oncological diseases. The purpose of the study was to review the Russian and foreign literature on melanins, their biosynthesis, functional properties and prospects for their use in medicine. Methods. content analysis of scientific publications to identify the structure, biosynthesis, and biopharmacological properties of melanins in the databases: CyberLeninka, eLibrary, PubMed, Article, SAGE Premier, Scopus over the past 12 years (2013–2024); comparative analysis of various properties of melanins based on current scientific literature data Conclusion. The information obtained and the justification of the prospects for the use of melanins in clinical practice allow us to speak about the relevance of the development of formulations and technology for the production of drugs based on it, including in the form of combined drugs with a multifunctional effect in various dosage forms. Melanin nanoparticles are promising as a multifunctional nanoplatform for use in oncology, cardiology and restorative medicine.

Early bactericidal activity of sitafloxacin against pulmonary tuberculosis.

Sitafloxacin is a quinolone broad-spectrum antimicrobial agent, and its pharmacologic properties and in vitro data demonstrate that sitafloxacin has a potent killing effect against Mycobacterium tuberculosis, including drug-resistant strains, which is superior to that of other available quinolones. However, its efficacy in patients with primary-sensitive tuberculosis is unclear. This study aims to evaluate the early bactericidal activity (EBA) of sitafloxacin in patients with primary drug-susceptible tuberculosis. In this early bactericidal activity study, 30 patients with primary smear-positive tuberculosis were randomized to the once-daily oral administration of 200 mg sitafloxacin, 500 mg levofloxacin, or 300 mg isoniazid (INH) for 7 days. Sputum for quantitative culture was collected 2 days before the study of drug administration, followed by 16 hours of overnight sputum collected daily for 7 days of monotherapy. Colony-forming units (CFU) of Mycobacterium tuberculosis were counted from the collected overnight sputum on agar plates to calculate the EBA, defined as log10 CFU/mL sputum/day. The bactericidal activity was measured by measuring the first 2 days (early bactericidal activity 0-2) and the last 5 days (prolonged early bactericidal properties 2-7) of study drug administration. The EBA 0-2 of INH (0.39 ± 0.22 log10CFU/mL/day) was higher than that of levofloxacin (0.26 ± 0.27 log10CFU/mL/day) and sitafloxacin (0.22 ± 0.25 log10CFU/mL/day), with no statistically significant difference (P = 0.08). EBA 0-2 was similar for the three drugs. INH prolonged early bactericidal activity (2-7) (0.17 ± 0.16 log10CFU/mL/day) was higher than levofloxacin (0.14 ± 0.10 log10CFU/mL/day) and lower than sitafloxacin (0.26 ± 0.31 log10CFU/mL/day), with no statistically significant difference (P = 0.59). The EBA 2-7 of sitafloxacin showed higher activity than INH and levofloxacin. Sitafloxacin exhibits comparable early bactericidal activity and higher extended early bactericidal activity relative to levofloxacin. In addition, this novel fluoroquinolone has a good safety profile. The study data highlights the potential of sitafloxacin in the clinical management of drug-susceptible tuberculosis, as well as drug-resistant tuberculosis.IMPORTANCESitafloxacin is a quinolone broad-spectrum antimicrobial agent, and its pharmacologic properties and in vitro data demonstrate that sitafloxacin has a potent killing effect against Mycobacterium tuberculosis. However, its efficacy in patients with primary-sensitive tuberculosis is unclear. We investigated the early bactericidal activity of sitafloxacin in primary susceptible tuberculosis. The results showed that sitafloxacin exhibited comparable early bactericidal activity and higher extended early bactericidal activity relative to levofloxacin. In addition, this novel fluoroquinolone has a good safety profile. Our study data highlights the potential of sitafloxacin in the clinical management of drug-susceptible tuberculosis, as well as drug-resistant tuberculosis.

PROXIMATE, MINERAL AND PHYTOCHEMICAL ANALYSIS OF SOME MEDICINAL PLANTS COLLECTED FROM ORATHUR VILLAGE, THIRUPORUR TALUK KANCHEEPURAM DISTRICT TAMILNADU, INDIA

The use of medicinal plants has a long tradition as part of the human diet and has therapeutic agents. That is why they are well accepted by consumers and are generally considered to be environmentally friendly, efficient and generally considered to be safe alternative to antibiotics due to the presence of phytochemicals found in the leaves, stem bark, roots, flowers amongst others. Medicinal plant also possesses nutritional properties and play multiple pharmacological roles such as anti-inflammatory, antioxidant, anti-cancer, antimicrobial, anti-viral, anti-fungal, anti-helminthic, hepato-protective activity amongst others. This study was aimed at accessing the proximate, mineral and phytochemical composition of Tephrosia purpurea, Adhatoda vasica, Crataeva nurvala, Bauhinia racemose, Holarrhena antidysenterica and Aegle marmelos. Result on proximate analysis showed that moisture content varied from 13.57 – 16.02 %, dry matter (83.98 – 86.43 %), crude protein (5.06 – 7.12 %), ash (9.90 – 12.04 %), crude fibre (12.74 – 14.32 %), crude fat (0.10 – 0.22 %) and carbohydrates (40.30 – 50.17 %). Concentrations of calcium, phosphorus, potassium, magnesium, zinc, manganese, sodium and copper ranged from 120 – 148.0 mg/100g, 180.0 – 300 mg/100g, 66.8 – 94.2 mg/100g, 41.8 – 69.8 mg/100g, 27.9 – 44.6 mg/100g, 119 – 133 mg/100g and 8.21 – 13.1 mg/100g respectively. Quantitative evaluation of tannins showed that values varied from 39.00 – 46.50 mg/g, alkaloids (26.35 – 35.09 mg/g), saponins (20.05 – 30.40 mg/g), flavonoids (66.10 – 86.11 mg/g), terpenoids (40.71 – 45.88 mg/g) and phenols (106.8 – 125.4 mg/g). In conclusion, it was discovered that it contained some essential nutrients in significant quantities. However, values obtained varied due to age of plant, specie, processing method among others. The presence of phytochemicals in these plant suggests that it has pharmacological properties. Accessing the constituent’s in this plants could lead to a novel drug discovery and curb the increasing cases in antimicrobial resistance.

Protective effects of naringenin against methamphetamine-induced cell death in dopaminergic SH-SY5Y cells

ABSTRACT Background: Methamphetamine is a psychoactive substance that competes with the dopamine transporter, disrupting its flow and storage. This can trigger oxidative stress, finally resulting in neural cell death. Due to the increasing prevalence of methamphetamine use, extensive research has been devoted to finding treatments that ameliorate its detrimental effects. Naringenin, a dietary flavonoid found in citrus fruits, has shown several neuroprotective and pharmacological properties. Objectives: This study was aimed to assess the protective effects of naringenin against methamphetamine-induced dopaminergic cell death. Methods: Before exposure to methamphetamine, human neuroblastomaSH-SY5Y cells were either pretreated or not treated (controls) with naringenin. Cell viability, level of oxidative stress markers, and expression of some genes involved in apoptosis and autophagy processes were then assessed using MTT, ROS, and MMP assays, and qRT-PCR and Western blotting techniques. Results: Naringenin pretreatment significantly enhanced cell viability following methamphetamine exposure (p < .01). It significantly decreased ROS levels (p < .001), preserved mitochondrial membrane potential, and moderated upregulation of apoptotic (CytC, Casp3, and Bax) and autophagic genes (Beclin-1, and LC-3) and down-regulation of Bcl-2 as an anti-apoptotic gene. Similar naringenin-mediated patterns were observed for cytochrome C and caspase 3 proteins. Conclusion: Naringenin administration can be considered for treating the neurotoxic effects of methamphetamine.

Quercetin alleviates ulcerative colitis through inhibiting CXCL8-CXCR1/2 axis: a network and transcriptome analysis

IntroductionUlcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract in which mucosal healing is a crucial measure of therapeutic efficacy. Quercetin, a flavonoid prevalent in various foods and traditional Chinese medicines, exhibits notable pharmacological properties, including antioxidant and anti-inflammatory activities. Consequently, it warrants investigation to determine its potential therapeutic effects on UC. The objective of this study was to investigate the effects and underlying mechanisms of quercetin in a murine model of UC.MethodsA comprehensive approach integrating network predictions with transcriptomic analyses was employed to identify the potential targets and enriched pathways associated with quercetin in UC. Subsequently, the effects of quercetin on pathological morphology, inflammatory mediators, and mucosal barrier-associated proteins, as well as the identified potential targets and enriched pathways, were systematically investigated in a murine model of dextran sulfate sodium (DSS)-induced UC.ResultsNetwork analyses identified CXCL8 and its receptors, CXCR1 and CXCR2, as primary target genes for therapeutic intervention in UC. Further validation through transcriptomic analysis and immunofluorescence staining demonstrated significant upregulation of the CXCL8-CXCR1/2 axis in the intestinal tissues of patients with UC. Experimental investigations in animal models have shown that quercetin markedly alleviates DSS-induced symptoms in mice. This effect includes the restoration of colonic crypt architecture, normalization of goblet cell structure and density, reduction of inflammatory cell infiltration, and decreased concentrations of inflammatory mediators. Quercetin enhanced the expression of tight junction (TJ) proteins, including ZO-1, MUC2 (Mucin 2), and occludin, thereby preserving the integrity of the intestinal mucosal barrier. Additionally, it significantly diminished the levels of IL-17A, NF-κB, CXCL8, CXCR1, and CXCR2 in the colonic tissues of mice with UC.DiscussionThe ameliorative effects of quercetin on colon tissue damage in DSS-induced UC mice were significant, possibly due to its ability to inhibit the CXCL8-CXCR1/2 signaling axis. These findings provide a solid foundation for the clinical application and pharmaceutical advancement of quercetin.

Effects of 1H-1,2,3-Triazole Derivatives of 3-O-Acetyl-11-Keto-Beta-Boswellic Acid from Boswellia sacra Resin on T-Cell Proliferation and Activation

Background: 3-O-acetyl-11-keto-β-boswellic acid (β-AKBA), a triterpene natural product, is one of the main natural products of Boswellia sacra resin (BSR) and has reported biological and immunomodulatory effects. 1H-1,2,3-triazole derivatives of β-AKBA (named 6a–6d) were synthesized from β-AKBA. The 1H-1,2,3-triazole compounds are also known to have a wide range of biological and pharmacological properties as demonstrated by in vitro and in vivo studies. This study aimed to investigate the effects of these 1H-1,2,3-triazole derivatives of β-AKBA on human T-cell proliferation and activation. Methods: PBMCs isolated from healthy donors were activated by anti-CD3/CD28 monoclonal antibodies in the presence of β-AKBA (1) or 1H-1,2,3-triazole derivatives of β-AKBA or DMSO controls. Results: We found that similar to the parent compound β-AKBA (1), derivatives 6a, 6b, and 6d significantly inhibited T-cell expansion/proliferation and reduced the levels of CD25 activation marker on CD4+ and CD8+ T cells without exerting significant cytotoxic effects on T-cell viability at a concentration of 25 µM. However, compound 6c further inhibited T-cell expansion/proliferation and CD25 expression, but had a significant cytotoxic effect on cell viability at similar concentrations of 25 µM. Conclusions: These findings demonstrate the immunoinhibitory effects of β-AKBA (1) and its corresponding triazole derivatives on T-cell proliferation and activation, highlighting the promising therapeutic potential of these compounds in T-cell-mediated diseases.

Current Status and Perspectives of Novel Radiopharmaceuticals with Heterologous Dual-targeted Functions: 2013-2023.

Radiotracers provide molecular- and cellular-level information in a noninvasive manner and have become important tools for precision medicine. In particular, the successful clinical application of radioligand therapeutic (RLT) has further strengthened the role of nuclear medicine in clinical treatment. The complicated microenvironment of the lesion has rendered traditional single-targeted radiopharmaceuticals incapable of fully meeting the requirements. The design and development of dual-targeted and multitargeted radiopharmaceuticals have rapidly emerged. In recent years, significant progress has been made in the development of heterologous dual-targeted radiopharmaceuticals. This perspective aims to provide a comprehensive overview of the recent progress in these heterologous dual-targeted radiopharmaceuticals, with a special focus on the design of ligand structures, pharmacological properties, and preclinical and clinical evaluation. Furthermore, future directions are discussed from this perspective.

Pharmaceutical and therapeutic utility of Hingula

Rasashastra is a branch of Ayurveda which deals with the various pharmaceutical processes viz. Shodhana, Marana, etc. and gives detailed description regarding the Metals, Minerals, Poisonous herbal drugs and Animal products commonly used as therapeutically in practice of Ayurveda. Hingula, a significant component in Rasashastra, is categorized as a Sadharana Rasa, meaning a common yet potent substance used in various Ayurvedic formulations. Known in the modern context as cinnabar, Hingula primarily contains mercury sulfide and has been utilized for centuries in the many preparations. Its importance in Rasashastra lies in its ability to enhance the potency and efficacy of formulations, particularly those aimed at rejuvenation, longevity, and the treatment of complex diseases. The careful detoxification and processing of Hingula is crucial, as it is a potent substance that can be toxic if not properly handled. This paper explores the traditional methods of Hingula purification, its pharmacological properties, and its role in the preparation of various Ayurvedic medicines.

Protective Effects of a Brassica nigra Sprout Hydroalcoholic Extract on Lipid Homeostasis, Hepatotoxicity, and Nephrotoxicity in Cyclophosphamide-Induced Toxicity in Rats

Background: Brassica nigra possesses a significant concentration of bioactive compounds and has been demonstrated to have a variety of pharmacological properties, although its sprout has not been extensively studied. Thus, the protective effects of Brassica nigra sprout hydroalcoholic extract (BNSE) on lipid homeostasis, hepatotoxicity, and nephrotoxicity in cyclophosphamide (CYP)-induced toxicity in rats were examined in this study. Methods: Four experimental rat groups (n = 8 for each group) were examined as follows: NR, normal rats that received normal saline by oral gavage daily; CYP, injected with a single dose of CYP at 250 mg kg−1 intraperitoneally (i.p.) and did not receive any treatment, receiving only normal saline by oral gavage daily; CYP + BNSE250, injected with a single dose of CYP at 250 mg kg−1 i.p. and treated with BNSE at 250 mg kg−1 by oral gavage daily for three weeks; and CYP + BNSE500, injected with a single dose of CYP at 250 mg kg−1 i.p. and treated with BNSE at 500 mg kg−1 by oral gavage daily for three weeks. Results: The results indicated a significant increase (p &lt; 0.05) in triglyceride (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), and very low-density lipoprotein cholesterol (VLDL-c) levels in CYP-induced toxicity rats. The administration of BNSE at 250 and 500 mg kg−1 significantly (p &lt; 0.05) attenuated TG, CHO, LDL-c, and VLDL-c at values comparable with the NR group. The most efficient treatment for improving the lipid profile and atherogenicity complication was BNSE at 500 mg kg−1, performing even better than 250 mg kg−1. Administrating BNSE at 250 or 500 mg kg−1 improved the liver’s function in a dose-dependent manner. Comparing the lower dose of 250 mg kg−1 of BNSE with 500 mg kg−1 showed that administrating 250 mg kg−1 attenuated alanine transaminase (ALT) by 28.92%, against 33.36% when 500 mg kg−1 was given. A similar trend was observed in aspartate aminotransferase (AST), where 19.44% was recorded for BNSE at 250 mg kg−1 and 34.93% for BNSE at 500 mg kg−1. Higher efficiency was noticed for BNSE at 250 and 500 mg kg−1 regarding alkaline phosphatase (ALP). An improvement of 38.73% for BNSE at 500 mg kg−1 was shown. The best treatment was BNSE at 500 mg kg−1, as it markedly improved liver function, such as total bilirubin (T.B.), in a dose-dependent manner. The administration of BNSE attenuated the total protein (T.P.), albumin, and globulin levels to be close to or higher than the typical values in NR rats. Conclusions: BNSE might be used for its promising hypolipidemic, hepatoprotective, and nephroprotective potential and to prevent diseases related to oxidative stress. Further research on its application in humans is highly recommended.

Attenuating Oxidative Damage with Macelignan in Glutamate-Induced HT22 Hippocampal Cells

Macelignan, from Myristica fragrans (nutmeg), is a bioactive compound with various pharmacological properties, including anti-inflammatory and neuroprotective activities. The purpose of this work was to investigate the antioxidant and anti-apoptotic effects of macelignan in glutamate-treated HT22 mouse hippocampal neurons. Macelignan was extracted and identified in a methanol extract of M. fragrans seeds. The DPPH was used to assess the antioxidative activity of macelignan. Glutamate (5 mM) was used to induce neurotoxicity in the HT22 cells. Neuroprotective effects were measured using relevant biochemical and imaging assays, including cell viability, ROS production, nuclear staining, apoptotic cell death, and protein expression. Macelignan markedly and concentration-dependently enhanced DPPH radical scavenging activity. In the HT22 cell model, glutamate induced cell damage by decreasing cell viability, promoting ROS generation, and increasing apoptotic cell death according to cell morphological changes. However, macelignan treatment restored cell viability, inhibited ROS generation concentration-dependently, and reduced apoptosis. Moreover, glutamate significantly up-regulated the phosphorylation of MAPK-pathway-related proteins, which was reversed by macelignan treatment. In conclusion, macelignan shows notable neuroprotective effects on oxidative stress and apoptotic cell death in glutamate-induced cells, and this study provides useful information on its potential therapeutic implications in neurological disorders.

In Vitro Evaluation, Chemical Profiling, and In Silico ADMET Prediction of the Pharmacological Activities of Artemisia absinthium Root Extract

Artemisia absinthium L., is a plant with established pharmacological properties, but the A. absinthium root extract (AARE) remains unexplored. The aim of this study was to examine the chemical composition of AARE and assess its biological activity, which included antidiabetic, antibacterial, anticancer, and antioxidant properties. GC-MS was used to analyze the chemical components. The antioxidant activity of the total phenolic and flavonoid content was evaluated. Antibacterial activity and cytotoxic effects were identified. Enzyme inhibition experiments were performed to determine its antidiabetic potential. Molecular docking was utilized to evaluate the potential antioxidant, antibacterial, and anticancer activities of the compounds from AARE using Maestro 11.5 from the Schrödinger suite. AARE exhibited moderate antioxidant activity in DPPH (IC50: 172.41 ± 3.15 μg/mL) and ABTS (IC50: 378.94 ± 2.18 μg/mL) assays. Cytotoxicity tests on MCF-7 and HepG2 cancer cells demonstrated significant anticancer effects, with IC50 values of 150.12 ± 0.74 μg/mL and 137.11 ± 1.33 μg/mL, respectively. Apoptotic studies indicated an upregulation of pro-apoptotic genes (caspase-3, 8, 9, Bax) and a downregulation of anti-apoptotic markers (Bcl-2 and Bcl-Xl). AARE also inhibited α-amylase and α-glucosidase, suggesting potential antidiabetic effects, with IC50 values of 224.12 ± 1.17 μg/mL and 243.35 ± 1.51 μg/mL. Antibacterial assays revealed strong activity against Gram-positive bacteria. Molecular docking and pharmacokinetic analysis identified promising inhibitory effects of key AARE compounds on NADPH oxidase, E. coli Gyrase B, and Topoisomerase IIα, with favorable drug-like properties. These findings suggest AARE’s potential in treating cancer, diabetes, and bacterial infections, warranting further in vivo and clinical studies.

A Review on Hepatoprotective Effect of Chrysin: Preclinical Implications and Molecular Cascades Came into Focus.

Chrysin, a flavone nutraceutical, possesses several beneficial pharmacological properties, which has gained much emphasis in recent years. The biological effects of chrysin are exerted due to impeding or activating multifarious cellular and molecular pathways. Our findings indicated that chrysin inhibited tumor progression in various cancer cell lines by repressing the formation of a sphere and upregulated protein expression of Src homology region 2 domain-containing phosphatase-1 (SHP-1), alleviating phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) and transaction workflow innovation standards team1 (Twist1), sustaining phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and endorsing mitogen-activated protein kinase kinase1 (MEK1) overexpression, increasing the cytochrome c release, mitochondrial reactive oxygen species (ROS) formation, matrix metalloproteinases (MMP) collapse, and caspase-3 activity, modulating p53/ B-cell lymphoma-2 (Bcl-2)/caspase-9 cascade, cyclooxygenase- 2 (COX-2), nuclear factor kappa B proposition 65 (NF-kB p65) expression and also decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Chrysin prevented cyclophosphamide, doxorubicin, cisplatin, methotrexate, paracetamol, alcohol, carbon tetrachloride, tert-butyl hydroperoxide (tBHP) and thioacetamide. Chrysin has protective properties against oxidative stress, inflammation, hepatotoxicity, liver fibrosis, steatosis, and hepatocellular carcinoma. Chrysin's most common hepatoprotective biochemical and molecular mechanisms involve the ability to control enzyme synthesis, scavenge free radicals, boost the antioxidant response, induce apoptosis, and modify the synthesis of proinflammatory and profibrotic cytokines.Chrysin is a valuable nutraceutical with broad therapeutic feasibility, but to confirm its representative hepatoprotective potential, clinical studies are advised. It would also be interesting to use cutting-edge drug delivery techniques or include bio-enhancers.

A Review of Synthesis and Therapeutic Applications of Coumarin Derivatives

Coumarins (2H-1-benzopyran-2-ones) are heterocyclic compounds widely distributed in plants, fruits, and vegetables, exhibiting significant pharmacological properties. The coumarin scaffold acts as a good template for drug development due to its structural simplicity and broad spectrum of biological activities. Modern synthetic approaches including gold-catalyzed cyclization, rhodium-catalyzed annulation, palladium-mediated coupling, and green chemistry methods have enabled efficient production of structurally diverse coumarin derivatives. The biological significance of coumarins encompasses anti-inflammatory, anticoagulant, antimicrobial, antiviral, and anticancer properties. Natural coumarins such as imperatorin and osthole show therapeutic effects against inflammation, microbial infections, and cancer. Structure-activity relationship studies have led to the development of synthetic derivatives with enhanced pharmacological profiles. The coumarin nucleus allows strategic modifications at multiple positions, resulting in compounds with improved efficacy and reduced toxicity. Recent synthetic methodologies emphasize sustainable protocols and efficient routes to complex coumarin derivatives. Emerging applications include the development of antidiabetic, neuroprotective, and antituberculosis agents. The low toxicity, natural abundance, and synthetic accessibility of coumarins position them as potential entities for drug discovery and development.

Alkyne‐ and Azide‐Functionalised Cyclophellitol Derivatives for Selective Glucuronidase Targeting

AbstractHeparanase is an endo‐acting β‐glucuronidase responsible for the degradation of heparan sulfate structures in the extracellular matrix. The enzyme is found to be significantly upregulated in aggressive cancer types, aiding cell proliferation by liberation of growth factors, increasing angiogenesis and metastasis. Despite much interest in the development of inhibitors to control this activity, no compound targeting heparanase has yet been approved as a drug. While mechanism‐based inhibitors derived from the natural product cyclophellitol are very potent enzyme inactivators through their reactive epoxide, one challenge in their development is in achieving selectivity for heparanase over related glycosidases while also maintaining a balance of appropriate pharmacological properties. We present here the synthesis of three cyclophellitol scaffolds presenting azide and alkyne handles at key positions, which are amenable to facile elaboration via copper‐catalysed azide‐alkyne cycloadditions to aid in exploring the structure‐activity relationship for selective inhibitors of heparanase.

Unlocking the biological potential of methyl antcinate A: a new frontier in cancer and inflammation application.

Antrodia camphorata is a valued and scarce parasitic mushroom that exclusively proliferates on the inner cavity wall of the endangered tree Cinnamomum kanehirai Hay (Lauraceae), endemic to Taiwan. Historically, this fungus has been utilized in traditional medicine to treat liver cancer, diarrhea, abdominal pain, hypertension, and food and drug intoxication, among other ailments. Literature searches were performed in scientific databases. The results were compiled from peer-reviewed studies; the search was refreshed through January 2024 to incorporate the most recent research. In vitro studies have revealed that Antrodia camphorata possesses various pharmacological properties that prevent cancer, reduce inflammation, and improve liver function. This medicinal mushroom contains unique ergostane-type triterpenoids known as antcins, which exhibit numerous pharmacological properties. Seven naturally occurring methyl analogs of antcins have been identified so far. In this article, we reviewed and analyzed the properties of methyl antcinate A (MAA), a constituent of Antrodia camphorata and methyl derivative of antcin A. MAA has demonstrated important anti-apoptotic, anti-inflammatory, and gastro-protective properties, as well as significant anti-tumor, anti-cancer, and cytotoxic activities. The anti-cancer effect of MAA in various cancers is attributed to its ability to modulate signaling cascades in apoptotic pathways. A significant challenge is to initiate preclinical and clinical trials to assess its anti-tumor action in vivo, as this data is currently missing. Additionally, future research on the structure-activity relationship of antcins and their derivatives is expected to support their development as therapeutic agents for clinical use.

Bench to Any Side—The Pharmacology and Applications of Natural and Synthetic Alkylated Hydroxy Cinnamates and Cinnamides

Natural alkylated hydroxy cinnamates (AHCs) isolated from medicinal plants and the thereby designed and synthesized cinnamides are derivatives of hydroxy cinnamic acids such as p-coumaric, sinapic, ferulic, and caffeic acids, which are naturally derived from human dietary sources. The pharmacological properties displayed by AHCs based on their inherent structure range include antioxidant, antimicrobial, antiplasmodial, anti-tyrosinase, Alzheimer’s and Parkinson’s disease therapy, anticancer therapy, metabolic disease therapy, and biopesticides, which have not been reviewed together. Based on their inherent antioxidant, antimicrobial, and UV absorption and their structure–activity relationships, these cinnamyl esters and amides can be used for food preservation in emulsions and oils, as sun-protective components of skin care formulations, and in many other multifunctional applications. In conclusion, the fine-tuning of the structural features such as the type of hydroxy cinnamic acid used, the length of alkyl chains for variable lipophilicity, conversion from cinnamic to propanoic for antioxidants, the increase in methoxy or the change to amino groups to increase the molar absorption coefficient and loss of absorption values, the substitution by halides or amino groups for potent biopesticides, and conversion from esters to amide bonds leads to different AHCs for biomedical, cosmetic, and agriculture applications as an emerging field of investigation that can overall provide natural, safe, biodegradable, and sustainable molecules.