Pharmacological Activities Research Articles

Unveiling the Potential of Ent-Kaurane Diterpenoids: Multifaceted Natural Products for Drug Discovery.

Natural products hold immense potential for drug discovery, yet many remain unexplored in vast libraries and databases. In an attempt to fill this gap and meet the growing demand for effective drugs, this study delves into the promising world of ent-kaurane diterpenoids, a class of natural products with huge therapeutic potential. With a dataset of 570 ent-kaurane diterpenoids obtained from the literature, we conducted an in silico analysis, evaluating their physicochemical, pharmacokinetic, and toxicological properties with a focus on their therapeutic implications. Notably, these natural compounds exhibit drug-like properties, aligning closely with those of FDA-approved drugs, indicating a high potential for drug development. The ranges of the physicochemical parameters were as follows: molecular weights-288.47 to 626.82 g/mol; number of heavy atoms-21 to 44; the number of hydrogen bond donors and acceptors-0 to 8 and 1 to 11, respectively; the number of rotatable bonds-0 to 11; fraction Csp3-0.65 to 1; and TPSA-20.23 to 189.53 Ų. Additionally, the majority of these molecules display favorable safety profiles, with only 0.70%, 1.40%, 0.70%, and 46.49% exhibiting mutagenic, tumorigenic, reproduction-enhancing, and irritant properties, respectively. Importantly, ent-kaurane diterpenoids exhibit promising biopharmaceutical properties. Their average lipophilicity is optimal for drug absorption, while over 99% are water-soluble, facilitating delivery. Further, 96.5% and 28.20% of these molecules exhibited intestinal and brain bioavailability, expanding their therapeutic reach. The predicted pharmacological activities of these compounds encompass a diverse range, including anticancer, immunosuppressant, chemoprotective, anti-hepatic, hepatoprotectant, anti-inflammation, antihyperthyroidism, and anti-hepatitis activities. This multi-targeted profile highlights ent-kaurane diterpenoids as highly promising candidates for further drug discovery endeavors.

Simultaneous determination of five constituents of areca nut extract in rat plasma using UPLC-MS/MS and its application in a pharmacokinetic study

Areca nuts have been used as a traditional Chinese medicine (TCM) for thousands of years. Recent studies have shown that it exhibits good pharmacological activity and toxicity. In this study, the pharmacokinetics of five major components of areca nut extract in rats were investigated using a highly sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method. Arecoline, arecaidine, guvacoline, guvacine, and catechin were separated and quantified accurately using gradient elution with mobile phases of (A) water containing 0.1 % formic acid-10 mM ammonium formate, and (B) methanol. The constituents were detected under a timing switch between the positive and negative ion modes using multiple reaction monitoring (MRM). Each calibration curve had a high R2 value of >0.99. The method accuracies ranged −7.09–11.05 % and precision values were less than 14.36 %. The recovery, matrix effect, selectivity, stability, and carry-over of the method were in accordance with the relevant requirements. It was successfully applied for the investigation of the pharmacokinetics of these five constituents after oral administration of areca nut extract. Pharmacokinetic results indirectly indicated a metabolic relationship between the four areca nut alkaloids in rats. For further clarification of its pharmacodynamic basis, this study provided a theoretical reference.

Comprehensive Experimental and Computational Analysis of the Structural and HSA Binding Properties of Newly Synthesized Coumarin-Trimethoxybenzohydrazide Derivative

Polycyclic aromatic compounds encompass a diverse array of molecules that exhibit remarkable chemical activity and play pivotal roles across various scientific domains. Coumarins represent a diverse class of heterocyclic compounds, which exhibit a wide range of significant biological and pharmacological activities, while containing at least two aromatic rings in their structure. Because chemical, biological, as well as pharmacological properties and activities are highly dependent on the structural characteristics of the molecule, in this paper a detailed structural investigation of the monocrystal structure of newly synthesized (E)-N′-(1-(2,4-dioxochroman-3-ylidene)ethyl)-3,4,5-trimethoxybenzohydrazide was performed. The DFT model that is best suited for describing the structural parameters of coumarin-benzohydrazides was determined. Out of three tested models which were previously proven to be excellent in describing structures of organic compounds, B3LYP-D3BJ was found to be the best in describing the structure of investigated coumarin derivative in regard to the obtained X-ray and spectroscopic data. Determination of the best theoretical model allows for better structural characterization of the coumarin-benzohydrazides for which monocrystals and consequently X-ray structure cannot be obtained. Finally, both experimental and computational analysis indicated (with high mutual correlation) that investigated compound showed excellent binding potential toward the albumin, indicating good distribution through the organism.

Therapeutic Potential of Dicentrine in Human Disorders: A Review On Medicinal Importance and Pharmacological Activities of Aporphine Alkaloid

Backgrounds: Plants have always been an important source of food and drugs, in addition to their application in medical and cosmetic sectors. The popularity of herbal remedies has increased in many countries in recent decades. Herbal medicines contain numerous active phytocomponents with different biological activities. Alkaloid class phytochemicals have diverse chemical structures and pharmacological activities in nature. Additionally, Aporphinoids are an important class of plant secondary metabolites that have been used for the treatment of numerous human disorders for a long time in traditional medicine. Dicentrine is an aporphine class phytochemical isolated from numerous medicinal plants, including Actinodaphne sesquipedalis and Lindera megaphylla. Methods: The biological potential of dicentrine, an aporphine alkaloid derivative, has been described in the present work. Scientific data on dicentrine were collected here from different scientific databases and presented in this paper in order to know the biological importance of dicentrine in medicine for the treatment of human complications. Further, detailed pharmacological activities and scientific data on dicentrine were also analyzed in order to determine its therapeutic potential in medicine. Moreover, its analytical aspects were also described in this work to understand its separation and isolation methods. Results: The present work described the biological potential of dicentrine in medicine and its analytical aspects. It signified the biological potential of dicentrine in cancer, breast cancer, oral squamous cell carcinoma, lung adenocarcinoma, blood pressure, inflammatory disorders, hyperlipidaemia, arrhythmia, stomach muscle, and glomerulonephropathy. Further, its effectiveness in medicine was found to be mainly because of its antiplatelet, alpha 1-adrenoceptor, epidermal growth factor, antiprotozoal, larvicidal, antimicrobial, topoisomerase II, and acetylcholinesterase inhibitory potential. Moreover, other scientific data also signified its metabolism and pharmacokinetic parameters in terms of its analytical aspects in medicine. Conclusion: The present review gives us an updated summary of the scientific information for pharmacological activities and analytical aspects of dicentrine in medicine. It also signified the potential contribution of dicentrine in medicine for the development of a newer class of drug molecules for human disorders.

New Era’s of Artificial Intelligence in Pharmaceutical Industries

Artificial Intelligence (AI) is the future of pharmaceutical industries. We make our tasks easier with help of Artificial Intelligence in future. With help of Artificial Intelligence we can also increase in production in pharmaceutical industry, can be save of dangerous and risky works in the production or manufacturing. Artificial Intelligence can drugs designing in future and discover new drugs and determine the chemical structure of drugs. Artificial Intelligence is very important role play in clinical research. For the pharmacological action drugs are works with the target protein. Than this target proteins are show the pharmacological action and Artificial Intelligence is help in determination of target protein and Artificial Intelligence can easier the drug discovery related work. Artificial Intelligence will used in the marketing such as the patient or customer related information or data collection and deposition. Creation of essential and specialized advertisement for increase product Sell. Different type application will in pharmaceutical industry of Artificial intelligence. And AI will change the pharmaceutical industry or drug associated work and that is come new revolution in pharmacy. Many types AI robots are invented in various pharmacy fields for the help of human being in manufacturing or production in pharmaceutical industry. Artificial Intelligence will advantages and disadvantage for the human beings. This review aims that drug delivery nanosystems design, characterization, and production stand to benefit greatly from artificial intelligence (AI). Furthermore, the ability to perform reverse engineering and ongoing system optimisation is becoming possible with the help of big data.

Understanding Antithrombotic Agents for Rehabilitation Therapy: A Comprehensive Narrative Review.

In rehabilitation medicine, attention must be paid to the medication. Among them, antithrombotic drugs are used for the initial treatment and secondary prevention of stroke, so as a basic knowledge, the pharmacological actions, characteristics, indications, and precautions for the use of antithrombotic drugs should be known. Antithrombotic agents are divided into antiplatelet agents and anticoagulants, and the appropriate antithrombotic agent is selected according to the main disease or condition. Antiplatelet agents include aspirin, clopidogrel, ticlopidine, prasugrel, ticagrelor, and cilostazol. Each antiplatelet agent has a different mechanism of action, characteristics, and indications, and should be prescribed with due consideration. Anticoagulants include heparin, synthetic Xa inhibitors, direct oral anticoagulants (DOACs), synthetic antithrombin agents, and warfarin. Knowledge of the mechanism of action, characteristics, and indications of each anticoagulant is necessary, as well as monitoring and dose adjustment. With regard to ischemic cerebrovascular disease (ICD) and antithrombotic agents, the first step is to classify cerebral infarction and to determine whether antiplatelet agents or anticoagulants should be used. Bleeding and recurrence prevention are important considerations in the selection of appropriate antithrombotic agents for the pathophysiology of ICD.

Obacunone, a Promising Phytochemical Triterpenoid: Research Progress on Its Pharmacological Activity and Mechanism.

Obacunone, a natural triterpenoid, is an active component of the herbs Dictamnus dasycarpus Turcz. and Phellodendron amurense Rupr, and an indicator of the herbs' quality. Owing to its multiple health benefits, several studies have investigated the multi-targeting potential action mechanisms of obacunone. To summarize recent developments on the pharmacological actions of obacunone and focus on the underlying molecular mechanisms and signaling networks, we searched PubMed, Europe PMC, Wiley Online Library, Web of Science, Google Scholar, Wanfang Medical Network, and China National Knowledge Infrastructure for articles published prior to March 2024. Existing research indicates obacunone has great potential to become a promising therapeutic option against tumors, fibrotic diseases, bone and cholesterol metabolism diseases, and infections of pathogenic microorganisms, among others. The paper contributes to providing up-to-date references for further research and clinical applications of obacunone.

A Novel Approach of Polyvinyl Alcohol/Acrylic Acid Based Hydrogels for Controlled Delivery of Diclofenac Sodium.

The aim of this study was to prepare polyvinyl alcohol/acrylic acid (PVA/AA) hydrogels for the controlled release of diclofenac sodium and to develop PVA/AA hydrogels as controlled release carriers to overcome not only the side effects of diclofenac sodium but also sustain its release for an extended period. Diclofenac sodium is employed for relieving pain and fever. The half-life of diclofenac sodium is very short (1-2 h). Hence, multiple intakes of diclofenac sodium are required to maintain a constant pharmacological action. Multiple GI adverse effects are produced as a result of diclofenac sodium intake. A free radical polymerization technique was used for crosslinking PVA with AA in the presence of APS. EGDMA was used as a cross-linker. FTIR and XRD confirmed the preparation and loading of the drug by prepared hydrogels. An increase in the thermal stability of PVA was shown by TGA and DSC analysis. Surface morphology was investigated by SEM. Similarly, water penetration and drug loading were demonstrated by porosity and drug loading studies. The pH-sensitive nature of PVA/AA hydrogels was investigated at different pH values by swelling and drug release studies. The development and drug loading of PVA/AA hydrogels were confirmed by FTIR and XRD analysis. TGA and DSC indicated high thermal stability of prepared hydrogels as compared to unreacted PVA. SEM indicated a hard and compact network of developed hydrogels. The swelling and drug release studies indicated maximum swelling and drug release at high pH as compared to low pH values, indicating the pH-sensitive nature of prepared hydrogels. Moreover, we demonstrated that drug release was sustained for a prolonged time in a controlled pattern by prepared hydrogels by comparing the drug release of the developed hydrogels with the commercial product Cataflam. The results indicated that prepared PVA/AA hydrogels can be used as an alternative approach for the controlled delivery of diclofenac sodium.

Hammerhead-type FXR agonists induce an enhancer RNA Fincor that ameliorates nonalcoholic steatohepatitis in mice

The nuclear receptor, farnesoid X receptor (FXR/NR1H4), is increasingly recognized as a promising drug target for metabolic diseases, including nonalcoholic steatohepatitis (NASH). Protein-coding genes regulated by FXR are well known, but whether FXR also acts through regulation of long non-coding RNAs (lncRNAs), which vastly outnumber protein-coding genes, remains unknown. Utilizing RNA-seq and global run-on sequencing (GRO-seq) analyses in mouse liver, we found that FXR activation affects the expression of many RNA transcripts from chromatin regions bearing enhancer features. Among these we discovered a previously unannotated liver-enriched enhancer-derived lncRNA (eRNA), termed FXR-induced non-coding RNA (Fincor). We show that Fincor is specifically induced by the hammerhead-type FXR agonists, including GW4064 and tropifexor. CRISPR/Cas9-mediated liver-specific knockdown of Fincor in dietary NASH mice reduced the beneficial effects of tropifexor, an FXR agonist currently in clinical trials for NASH and primary biliary cholangitis (PBC), indicating that amelioration of liver fibrosis and inflammation in NASH treatment by tropifexor is mediated in part by Fincor. Overall, our findings highlight that pharmacological activation of FXR by hammerhead-type agonists induces a novel eRNA, Fincor, contributing to the amelioration of NASH in mice. Fincor may represent a new drug target for addressing metabolic disorders, including NASH.

Bridging Tradition and Modern Pharmacology of Bergenia ciliata (Haw.) Sternb: A Review

Bergenia ciliata, a perennial rhizomatous herb holds a special place in the traditional herbal healthcare system due to its diverse therapeutic uses and potentials. Validation of its efficacy with scientific investigation is a prerequisite of any prospective herbal resource. The plant is a rich source of various bioactive chemical compounds. The present review is an attempt to consolidates comprehensive information sourced from 100 different literatures, exploring the plant's distribution, phytochemistry, traditional medicinal uses, and pharmacological activities specially focusing on some prevalent diseases of present day. The herb’s antimicrobial, anticancer, antiulcer and antidiabetic properties signify its potential in modern pharmacology. The review underscores B. ciliata's relevance in drug development and nutraceutical formulations, bridging age-old wisdom with contemporary healthcare solutions. Further exploration into its bioactive compounds and clinical applications promises innovative avenues in therapeutic intervention.
 Keywords: Bergenia ciliata, perennial rhizomatous herb, traditional herbal healthcare, age-old wisdom

Icariin accelerates bone regeneration by inducing osteogenesis-angiogenesis coupling in rats with type 1 diabetes mellitus

BACKGROUND Icariin (ICA), a natural flavonoid compound monomer, has multiple pharmacological activities. However, its effect on bone defect in the context of type 1 diabetes mellitus (T1DM) has not yet been examined. AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM. METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining, alizarin red S staining, quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis. A bone defect model was established in T1DM rats. The model rats were then treated with ICA or placebo and micron-scale computed tomography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area. RESULTS ICA promoted bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation. The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers (alkaline phosphatase and osteocalcin) and angiogenesis-related markers (vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1) compared to the untreated group. ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs. In the bone defect model T1DM rats, ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation. Lastly, ICA effectively accelerated the rate of bone formation in the defect area. CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and β-Tricalcium Phosphate (β-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. Statement of significanceInjectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into β-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.

Hammerhead-type FXR agonists induce an enhancer RNA Fincor that ameliorates nonalcoholic steatohepatitis in mice.

The nuclear receptor, farnesoid X receptor (FXR/NR1H4), is increasingly recognized as a promising drug target for metabolic diseases, including nonalcoholic steatohepatitis (NASH). Protein-coding genes regulated by FXR are well known, but whether FXR also acts through regulation of long non-coding RNAs (lncRNAs), which vastly outnumber protein-coding genes, remains unknown. Utilizing RNA-seq and global run-on sequencing (GRO-seq) analyses in mouse liver, we found that FXR activation affects the expression of many RNA transcripts from chromatin regions bearing enhancer features. Among these we discovered a previously unannotated liver-enriched enhancer-derived lncRNA (eRNA), termed FXR-induced non-coding RNA (Fincor). We show that Fincor is specifically induced by the hammerhead-type FXR agonists, including GW4064 and tropifexor. CRISPR/Cas9-mediated liver-specific knockdown of Fincor in dietary NASH mice reduced the beneficial effects of tropifexor, an FXR agonist currently in clinical trials for NASH and primary biliary cholangitis (PBC), indicating that amelioration of liver fibrosis and inflammation in NASH treatment by tropifexor is mediated in part by Fincor. Overall, our findings highlight that pharmacological activation of FXR by hammerhead-type agonists induces a novel eRNA, Fincor, contributing to the amelioration of NASH in mice. Fincor may represent a new drug target for addressing metabolic disorders, including NASH.

Dicoumarol attenuates NLRP3 inflammasome activation to inhibit inflammation and fibrosis in knee osteoarthritis.

Knee osteoarthritis (KOA) is a major cause of disability in elderly individuals. Dicoumarol is a coumarin‑like compound derived from sweet clover [Melilotus officinalis (L.) Pall]. It has been suggested that dicoumarol exhibits various types of pharmacological activities, including anticoagulant, antitumor and antibacterial effects. Due to its various biological activities, dicoumarol has a potential protective effect against OA. Therefore, the present study aimed to assess the effects of dicoumarol on knee osteoarthritis. In the present study, dicoumarol was found to protect rat synoviocytes from lipopolysaccharide (LPS)‑induced cell apoptosis. Western blot analysis showed that dicoumarol significantly reduced the protein expression levels of fibrosis‑related markers and inflammatory cytokines (Tgfb, Timp, Col1a, Il1b and Il18). The inhibitory rates of these proteins were all >50% (P<0.01) compared with those in the LPS and ATP‑induced group. Consistently, the mRNA expression levels of these markers and cytokines were decreased to normal levels by dicoumarol after the treatment of rat synovial fibroblasts with LPS and ATP. Mechanistic studies demonstrated that dicoumarol did not affect NF‑κB signaling, but it did directly interact with NOD‑like receptor protein 3 (NLRP3) to promote its protein degradation, which could be reversed by MG132, but not NH4Cl. The protein half‑life of NLRP3 was accelerated from 26.1 to 4.3 h by dicoumarol. Subsequently, dicoumarol could alleviate KOA in vivo; knee joint diameter was decreased from 11.03 to 9.93 mm. Furthermore, the inflammation and fibrosis of the knee joints were inhibited in rats. In conclusion, the present findings demonstrated that dicoumarol could impede the progression of KOA by inhibiting NLRP3 activation, providing a potential treatment strategy for KOA.

Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo.

Glioblastoma multiforme is a universally lethal brain tumor that largely resists current surgical and drug interventions. Despite important advancements in understanding GBM biology, the invasiveness and heterogeneity of these tumors has made it challenging to develop effective therapies. Therapeutic oligonucleotides-antisense oligonucleotides and small-interfering RNAs-are chemically modified nucleic acids that can silence gene expression in the brain. However, activity of these oligonucleotides in brain tumors remains inadequately characterized. In this study, we developed a quantitative method to differentiate oligonucleotide-induced gene silencing in orthotopic GBM xenografts from gene silencing in normal brain tissue, and used this method to test the differential silencing activity of a chemically diverse panel of oligonucleotides. We show that oligonucleotides chemically optimized for pharmacological activity in normal brain tissue do not show consistent activity in GBM xenografts. We then survey multiple advanced oligonucleotide chemistries for their activity in GBM xenografts. Attaching lipid conjugates to oligonucleotides improves silencing in GBM cells across several different lipid classes. Highly hydrophobic lipid conjugates cholesterol and docosanoic acid enhance silencing but at the cost of higher neurotoxicity. Moderately hydrophobic, unsaturated fatty acid and amphiphilic lipid conjugates still improve activity without compromising safety. These oligonucleotide conjugates show promise for treating glioblastoma.

Qualitative and Quantitative Phytochemicals Screening of Aqueous, Methanol and Hexane Leaves Extracts of Senna Occidentalis

The Senna occidentalis tree is an incredible plant with incredible antimicrobial, antifungal and antimalarial activities used traditionally. The study was carried out to determine the phytochemical content responsible for these activities Fresh leaves were collected, aqueous, methanolic and hexane extracts of leaves were prepared, and the extracts were screened for phytochemical constituents using standard methods. Results of the phytochemical screening of all the crude extracts revealed the presence of saponins, tannins, steroids, phenol, alkaloid and flavonoid. In aqeuose extract, flavonoid show higher content of 2,47%, followed by tepernoid with 2.27%, methanol with higher content of tepernoid with 2.60%, and hexane with the highest in tepernoid with only 2.38%. Based on the present study, it can be concluded that the extracts of Senna occidentalis are rich source of phytochemicals and F flavonoid is found to be most abundant phytochemical presence of bioactive constituents that could be the reason for pharmacological activity that is used traditionally by many people as an alternative treatment for a variety of health diseases.

Synergistic effects of medicinal plants in combination with spices from algeria: Anticancer, antiangiogenic activities, and embrytoxicity studies

Ethnopharmacological relevanceBryonia dioica Jacq., Evernia prunastri (L.) Ach., Telephium imperati L., and Aristolochia longa L. are species widely used in traditional medicine to treat several diseases including cancer. Conjugation of two or more extracts is an approach to improve the effectiveness of their pharmacological activities. Aim of the studyTo evaluate the synergistic anticancer and anti-angiogenic effects of medicinal plants and edible species combinations. Materials and methodsIn this work, B. dioica, E. prunastri, Telephium imperati, and Aristolochia longa extracts were conjugated to form four mixtures. The antiproliferative effect of mixtures on several carcinoma cells was examined by MTT assay, and the antiangiogenic activity was estimated through Hen's egg test in vivo. Moreover, in an Ovo model, 35 fertilized Ross eggs were used to test the embryotoxicity of mixtures. ResultsAt the highest concentration of 200 μg/mL, both mixtures exerted an important cytotoxic effect against human carcinoma cells. The mixture BETE (Bryonia Evernia Telephium Extract) significantly reduced HT-29, PC-3, and A-549 cell viability. Likewise, this mixture strongly suppressed vascularization in vivo at 200 μg/mL. Interestingly, no signs of toxicity on Perdix embryos were recorded within 21 days of treatment. More importantly, the mixture did not have any cytotoxic effect on non cancerous cells. ConclusionTaken together, our results suggest that the synergy between B. dioica, E. prunastri and T. imperati may be promising for developing new anti-cancer treatments.

An Integrative Study of Scrophularia takesimensis Nakai in an Ovalbumin-Induced Murine Model of Asthma: The Effect on T Helper 2 Cell Activation.

Scrophularia have traditionally been used as herbal medicines to treat neuritis, sore throats, and laryngitis. In particular, S. takesimensis, a Korean endemic species with restricted distribution on Ulleung Island, holds significant resource and genetic value. However, its pharmacological properties have not been thoroughly evaluated. Thus, we provide detailed morphological characteristics and genomic information for S. takesimensis in this study. Moreover, its pharmacological activity was evaluated in an ovalbumin-induced asthma rat model, using extracts of S. takesimensis roots (100 or 200 mg/kg). The distinguishing features of S. takesimensis from related species include the presence or absence of stem wings, leaf shape, and habitat. The chloroplast (cp) genome of this species is 152,420 bp long and exhibits a conserved quadripartite structure. A total of 114 genes were identified, which included 80 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. The gene order, content, and orientation of the S. takesimensis cp genome was highly conserved and consistent with the general structure observed in S. buergeriana and S. ningpoensis cp genomes. Confirming the anti-inflammatory effects of S. takesimensis extract (STE) using an established mouse model of ovalbumin-induced asthma, we observed reduced asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and suppression of T helper 2 (Th2) cell. Furthermore, STE treatment reduced Th2 cell activation and differentiation. This study underscores the medicinal value of S. takesimensis. The importance of preserving S. takesimensis was revealed and crucial insights were provided for further research on its utilization as a medicinal resource.

Pharmacological activation of PDC flux reverses lipid-induced inhibition of insulin action in muscle during recovery from exercise.

Insulin resistance is a risk factor for type 2 diabetes and exercise can improve insulin sensitivity. However, following exercise high circulating fatty acid (FA) levels might counteract this. We hypothesized that such inhibition would be reduced by forcibly increasing carbohydrate oxidation through pharmacological activation of the pyruvate dehydrogenase complex (PDC). Insulin-stimulated glucose uptake was examined with a cross-over design in healthy young men (n = 8) in a previously exercised and a rested leg during a hyperinsulinemiceuglycemic clamp five hours after one-legged exercise with: 1) infusion of saline, 2) infusion of intralipid imitating circulating FA levels during recovery from whole-body exercise, and 3) infusion of intralipid + oral PDC-activator, dichloroacetate (DCA). Intralipid infusion reduced insulin-stimulated glucose uptake by 19% in the previously exercised leg, which was not observed in the contralateral rested leg. Interestingly, this effect of intralipid in the exercised leg was abolished by DCA, which increased muscle PDC activity (130%) and flux (acetylcarnitine 130%) and decreased inhibitory phosphorylation of PDC on Ser293 (∼40%) and Ser300 (∼80%). Novel insight is provided into the regulatory interaction between glucose and lipid metabolism during exercise recovery. Coupling exercise and PDC flux activation upregulated the capacity for both glucose transport (exercise) and oxidation (DCA), which seems necessary to fully stimulate insulin-stimulated glucose uptake during recovery.

Possible interactions between selected food processing and medications.

The impact of food processing on drug absorption, metabolism, and subsequent pharmacological activity is a pressing yet insufficiently explored area of research. Overlooking food-processing-drug interactions can significantly disrupt optimal clinical patient management. The challenges extend beyond merely considering the type and timing of food ingestion as to drug uptake; the specific food processing methods applied play a pivotal role. This study delves into both selected thermal and non-thermal food processing techniques, investigating their potential interference with the established pharmacokinetics of medications. Within the realm of thermal processing, conventional methods like deep fat frying, grilling, or barbecuing not only reduce the enteric absorption of drugs but also may give rise to side-products such as acrylamide, aldehydes, oxysterols, and oxyphytosterols. When produced in elevated quantities, these compounds exhibit enterotoxic and pro-inflammatory effects, potentially impacting the metabolism of various medications. Of note, a variety of thermal processing is frequently adopted during the preparation of diverse traditional herbal medicines. Conversely, circumventing high heat through innovative approaches (e.g., high-pressure processing, pulsed electric fields, plasma technology), opens new avenues to improve food quality, efficiency, bioavailability, and sustainability. However, it is crucial to exercise caution to prevent the excessive uptake of active compounds in specific patient categories. The potential interactions between food processing methods and their consequences, whether beneficial or adverse, on drug interactions can pose health hazards in certain cases. Recognizing this knowledge gap underscores the urgency for intensified and targeted scientific inquiry into the multitude of conceivable interactions among food composition, processing methods, and pharmaceutical agents. A thorough investigation into the underlying mechanisms is imperative. The complexity of this field requires substantial scrutiny and collaborative efforts across diverse domains, including medicine, pharmacology, nutrition, food science, food technology, and food engineering.