Natural Compounds Research Articles

EXTH-20. EXPLORING EUPHOL’S THERAPEUTIC EFFECT IN ADULT AND PEDIATRIC BRAZILIAN HIGH-GRADE GLIOMAS PRE-CLINICAL MODELS

Abstract High grade gliomas (HGG) are among the most aggressive brain tumors affecting both adults and children. Adult HGG (aHGG) account for almost 25% of all brain tumors in adults, with glioblastoma (GBM) being the predominant subtype. Pediatric HGG (pHGG), though less common, accounts for 3-15% of primary brain tumors in children and exhibits distinct genetic profiles compared to aHGG. Standard treatment for HGG in both adults and pediatric patients includes maximal surgical resection followed by temozolomide (TMZ)-based chemotherapy and radiation therapy. Our group previously reported that euphol, a natural compound derived from the sap of Euphorbiaceae family plants, exerts cytotoxicity effects on glioma cells. In this study, we investigated the therapeutic potential of euphol in primary cell cultures and xenograft models derived from six Brazilian HGG patients, including three adults and three pediatrics. In vitro, euphol exposure significantly reduced cell viability reduction, clonogenic capacity, and migration, while enhancing apoptosis in all six primary cultures. Additionally, euphol sensitized glioma cells to TMZ, resulting in a synergistic cytotoxic effect. In vivo, euphol reduced tumor growth in both GBM and pHGG models, and prolonged the survival of mice in the GBM orthotopic experiment. These findings highlight the promising therapeutic potential of euphol for treating high-grade gliomas in both adult and pediatric populations.

Preparation and Characterization of Ozonated Liposomes Loaded with Curcumin: A Potential Approach for Diabetic Retinopathy Treatment

Background: Limitations in drug penetration are overcome by nanotechnology, particularly liposomes, which enhance targeted administration of ocular medications. Liposomes can augment the therapeutic effects of curcumin, a natural compound with positive impacts on the retina. Treatments for eye diseases can also benefit from the antibacterial properties of ozonated oil liposomes. Objectives: This study aims to develop and evaluate ozonated liposomes loaded with curcumin for ocular drug delivery applications, specifically targeting diabetic retinopathy (DR). Methods: Liposomal nanoparticles were prepared using thin-film hydration, incorporating phospholipids, lecithin, cholesterol, ozonated oil, and curcumin. We assessed physicochemical properties including particle size, zeta potential, encapsulation efficiency (EE), and morphology. Drug release profiles and stability studies were also conducted. Results: The optimized liposomes showed a particle size of 84.77 nm, a zeta potential of -16.8 mV, and an EE of 94.73%. The formulation exhibited sustained curcumin release over 24 hours, reaching 82.09% cumulative release. Stability studies indicated minimal changes in key parameters over three months at room temperature. Conclusions: The developed ozonated liposomal formulation demonstrates promising characteristics for curcumin delivery, potentially enhancing its therapeutic efficacy in ocular applications, particularly for DR.

The Therapeutic Management of Chemical and Herbal Medications on Uric Acid Levels and Gout: Modern and Traditional Wisdom

Background: Gout is a chronic inflammatory condition characterized by elevated uric acid levels in the blood, which can precipitate acute gout attacks in individuals with genetic susceptibility, existing medical conditions, and dietary influences. Genetic predispositions, comorbid medical conditions, nutritional choices, and environmental factors increasingly recognize the multifactorial etiology of the disease. Methods: Recent research has highlighted the potential of phytochemicals, particularly flavonoids, saponins, and alkaloids, to manage hyperuricemia (HUA) and its associated complications. Results: Plant’s natural compounds have garnered attention for their anti-inflammatory, antioxidant, and uric acid-lowering properties, suggesting their role in alternative and complementary medicine. Phytochemicals have demonstrated promise in mitigating gout symptoms and potentially modifying the disease course by addressing different aspects of hyperuricemia and inflammation. Herbal remedies, with their complex phytochemical profiles, offer a unique advantage by potentially complementing conventional pharmacological treatments. The integration of herbal therapies with standard medications could lead to enhanced therapeutic outcomes through synergistic effects, optimizing disease management, and improving patient quality of life. Conclusions: This review examines the current understanding of the multifaceted etiology of gout, explores the role of phytochemicals in managing hyperuricemia, and discusses the potential benefits of combining herbal remedies with conventional treatments to improve patient care and therapeutic efficacy.

Efficacy of Nigella sativa seed oil against psychophysical stress induced irritable bowel syndrome and anxiety-like symptoms in Wistar rats.

Stressors play a critical role in the progression of irritable bowel syndrome (IBS). Heterogenous stress causes alterations in our bowel movements which can further cause anxiety and depression-like symptoms, decreasing the ability of individuals worldwide to function in social, academic, and employment settings. This study was aimed to investigate the effect of orally administered Nigella sativa (0.2mL/kg b.wt.) seed oil (NSSO) on stress-induced IBS, anxiety, and depression-like symptoms in Wistar rats. In the present study, modelling IBS induced anxiety and depression-like symptoms in rodents have been employed to correlate the pathophysiological mechanisms behind this disorder. Moreover, evaluation of ameliorative potential of traditionally used NSSO in IBS was also carried out. Present investigation indicated that acute stress of 1.5h daily for 20days induced hyper cortisol, gastrointestinal (GI) hypermotility, diarrhoea, altered levels of short chain fatty acids (SCFAs), and inflammation which are common symptoms of IBS. Furthermore, depression and anxiety-like symptoms were validated in test groups by various behavioral tests and decreased levels of 5-HT-Transporter mRNA gene expression, which are clear indicators of cognitive impairment. It is possible that these IBS-like symptoms may have contributed to the pathogenesis of cognitive deficits and depression. However, the anti-oxidative, anti-inflammatory, anti-spasmodic, and possibly the anti-anxiolytic properties of NSSO helped in the mitigation of altered gut-brain axis. Because the concurrent treatment of NSSO alleviated the symptoms of modified GI function and consequently, the anxious & depressive behavior of the animals. Overall, this research explored the protective efficacy of NSSO against stress-induced IBS and depression-like symptoms, shedding light on the potential of this natural compound as a therapeutic option in the field of gastroenterology and psychiatry.

Unlocking Neuraminidase Inhibitors: Insights from Natural Products through Pharmacophore Modeling, Virtual Screening, and Molecular Docking

Background: Neuraminidase enzyme plays a major role in the life cycle of influenza viruses. Targeting neuraminidases is a key strategy in preventing and treating influenza A and B spread by inhibiting the release of new viral particles from infected cells. Developing new neuraminidase inhibitors with enhanced efficacy and reduced risk of resistance is the ultimate of ongoing research. Objective: In this study, we tried to shed light on molecules of natural origin that inhibit neuraminidase enzyme by utilizing different aspects of in silico studies. Methods: The work started by generating structure-based pharmacophore, later used for the virtual screening of electronic libraries constructed from chemical and natural compounds. Hits raised from virtual screening were subjected to molecular docking to assess and explain different modes of interactions with the neuraminidase enzyme. Drug likeness and ADME filters were applied to choose compounds that may be taken effectively by oral route with good gastrointestinal absorption and acceptable pharmacokinetics with respect to Lipinski and Ghose rules. The hits were also inspected for toxicity risks, including mutagenic, tumorigenic, irritant, and reproductive effects. Results: 7 features of the generated pharmacophore from the potent inhibitor Oselatamiver were the base for virtual screening. The results obtained by database screening highlighted 4 natural compounds listed in the COCONUT library (CNP 0125691 (Penicitrinol K), CNP0256196 (Frenolicin D), CNP 0138184, and CNP 0206296) as potential neuraminidase inhibitors. The compounds showed a similar interaction profile to Oseltamivir by molecular docking with high binding affinity. The key residue TYR 406 hydrogen bonded to Penicitrinol and Frenolicin D as well as to Oseltamevir. The 4 natural compounds exerted drug-like properties and promising pharmacokinetic characters. Toxicity risks estimations put Penicitrinol K and Frenolicin as devoted to mutagenic, tumorigenic, irritant and reproductive potentials. Penicitrinol K and Frenolicin are assigned for further in vitro and in vivo studies as promising neuraminidase inhibitors. Conclusion: Penicitrinol K, and Frenolicin D are promising natural neuraminidase inhibitors, exhibiting favourable drug-like properties and low toxicity risks in addition to showing the pattern of interaction profiles with neuraminidase enzymes similar to the known drug Oseltamivir contributing to the development of effective antiviral therapies against influenza, suggesting further in vitro and in vivo evaluation.

Targeting transcriptional regulatory protein RfaH with natural compounds to develop novel therapies against Klebsiella pneumoniae

The growing threat of antibiotic-resistant K. pneumoniae infections demands novel treatment strategies. This study focuses on the transcriptional regulatory protein RfaH, a protein crucial for the bacteria’s virulence by promoting gene expression for its capsule, cell wall, and pilus. As K. pneumoniae becomes resistant to existing antibiotics, targeting RfaH with specific inhibitors offers a promising alternative. The diverse benefits of natural compounds, including efficacy against microbial diseases, modulation of inflammatory processes, and potential in cancer therapy, have led to their increasing use in medicine. Through natural compound screening, we aimed to identify potential RfaH inhibitors and understand their interactions with the active site pocket of RfaH. Disrupting interactions of specific residues in RfaH by ligand binding could offer a means to interfere with its function selectively. We found that Naringenin and Quercetin have a strong binding affinity for RfaH β′CH binding pocket and form stable complexes, as evident from the MD simulation studies. The binding affinity of Naringenin and Quercetin was further validated experimentally by fluorescence measurements. This knowledge can be used to design potent and selective RfaH inhibitors for a new therapeutic approach to combat K. pneumoniae infections and address the urgent need for effective treatments.

The Cardiovascular Protective Function of Natural Compounds Through AMPK/SIRT1/PGC‐1α Signaling Pathway

ABSTRACTCardiovascular disease (CVD) poses a major risk to human health and exert a heavy burden on individuals, society, and healthcare systems. Therefore, it is critical to identify CVD's underlying mechanism(s) and target them using effective agents. Natural compounds have shown promise as antioxidants with cardioprotective functions against CVD injuries due to their antioxidative solid capacity and high safety profile. Several CVDs, such as heart failure, ischemia/reperfusion, atherosclerosis, and cardiomyopathies, are closely linked to mitochondrial dysfunction. It is well established that activating the AMPK/SIRT1/PGC‐1α pathway during CVD promotes mitochondrial function. Therefore, targeting the AMPK/SIRT1/PGC‐1α pathway provides a foundation for novel therapeutic strategies to combat CVD. A key goal of our search was to find natural compounds that target this biological pathway and have beneficial effects on CVD.

Synergistic effect of Ca/Zn main stabilizer and maltitol auxiliary stabilizer on the thermal stability, mechanical properties, and transparency of poly(vinyl chloride)

AbstractMaltitol, a natural compound, offers a potentially eco‐friendly alternative to conventional auxiliary thermal stabilizers. Its auxiliary stabilization effect was studied by discoloration tests, Congo red tests, thermogravimetric analysis, and UV–visible spectroscopy. Additionally, x‐ray photoelectron spectroscopy and discoloration tests were used to study the stabilizing mechanisms of maltitol. Compared to dipentaerythritol, commonly used in the PVC industry, maltitol as an auxiliary stabilizer exhibits better improvement in thermal stability. This improvement is related to its melting point, ability to complex with zinc chloride, and content of hydroxyl groups. Furthermore, the addition of maltitol in PVC not only maintains good transparency of PVC basically unchanged but also improves the mechanical properties. Maltitol, as a natural, eco‐friendly, and efficient auxiliary thermal stabilizer, exhibits a promising application prospect in PVC materials.

PNSC5325 prevents acute respiratory distress syndrome by alleviating inflammation and inhibiting extracellular matrix degradation of alveolar macrophages

BackgroundAcute respiratory distress syndrome (ARDS) is characterized by severe inflammation and significant extracellular matrix (ECM) degradation in the lungs. Our prior research identified the CtBP2-p300-NF-κB (C-terminal-binding protein 2-histone acetyltransferase p300-nuclear factor kappa B) transcriptional complex as critical in ARDS by activating pro-inflammatory cytokine genes. MethodsAn ARDS mouse model was established using intratracheal instillation of lipopolysaccharide (LPS). Small molecules that inhibit the CtBP2-p300 interaction were identified through AlphaScreen. RNA sequencing (RNA-Seq) was conducted to determine differential gene expression. Immunoprecipitation and co-immunoprecipitation analyzed protein interactions. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunoblotting detected gene and protein expression. Histological staining evaluated tissue damage. ResultsThrough AlphaScreen, two natural compounds, PNSC2477 and PNSC5325, were identified for their ability to inhibit the CtBP2-p300 interaction. While PNSC2477 demonstrated toxicity and was deemed unsuitable for further research, PNSC5325 exhibited minimal toxicity. PNSC5325 effectively inhibited the CtBP2-p300 interaction and reduced pro-inflammatory cytokine gene expression. RNA-Seq analysis of PNSC5325-treated cells indicated significant suppression of pro-inflammatory cytokine genes and matrix metalloproteinases (MMPs). Further molecular studies revealed that the CtBP2-p300 complex, in conjunction with activator protein 1 (AP1), activates MMP expression. PNSC5325 simultaneously suppressed both pro-inflammatory cytokines and MMPs by targeting the CtBP2-p300 complex. In LPS-injected mice, PNSC5325 administration significantly reduced ARDS incidence by inhibiting inflammatory and MMP genes. ConclusionThese findings suggest that PNSC5325 protects against ARDS by inhibiting key inflammatory and ECM degradation pathways, highlighting its potential as a novel therapeutic agent for ARDS and paving the way for further clinical investigations.

Application of Machine Learning for the Prediction of Absorption, Distribution, Metabolism and Excretion (ADME) Properties from Cichorium intybus Plant Phytomolecules

Drug discovery is the process by which new drug candidates are discovered and drug development takes place. To enhance the efficiency, accuracy, and speed of the drug discovery process, machine learning (ML) could play a transformative role. For this research study, antidiabetic natural compounds from C. intybus, which is commonly known as chicory, were selected, as they have promising antidiabetic properties that can complement conventional diabetes treatments. A bioactive natural compound dataset was retrieved on the chicory plant using Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) public source information. This collected dataset was analyzed for its absorption, distribution, metabolism, and excretion (ADME) properties using the SwissADME online tool. Principal component analysis (PCA) and correlation analysis were performed using trial-version XLSTAT software 2014.5.03 and Python. The obtained dataset from SwissADME was subjected to cleaning, after that, it was used to develop machine learning models, such as support vacuum (SVM) ML, random forest (RF), Naive Bayes (NB), and decision tree (DT). The Lipinski rule of violation was chosen as the target variable. To improve the vitality of the created ADME dataset, PCA, a biplot graph, and correlation analysis were carried out. A large dataset of naturally occurring antidiabetic compounds was used to predict the drug-likeness of ML models that were effectively deployed on heterogeneous ADME datasets. Among all these ML models, DT performed better than the rest of the models.

Caffeine: A Multifunctional Efficacious Molecule with Diverse Health Implications and Emerging Delivery Systems

Natural caffeine is found in many plants, including coffee beans, cacao beans, and tea leaves. Around the world, many beverages, including coffee, tea, energy drinks, and some soft drinks, have this natural caffeine compound. This paper reviewed the results of meta-studies on caffeine’s effects on chronic diseases. Of importance, many meta-studies have shown that regularly drinking caffeine or caffeinated coffee significantly reduces the risk of developing Alzheimer’s disease, epilepsy, and Parkinson’s disease. Based on the health supplements of caffeine, this review summarizes various aspects related to the application of caffeine, including its pharmacokinetics, and various functional health benefits of caffeine, such as its effects on the central nervous system. The importance of caffeine and its use in alleviating or treating cancer, diabetes, eye diseases, autoimmune diseases, and cardiovascular diseases is also discussed. Overall, consuming caffeine daily in drinks containing antioxidant and neuroprotective properties, such as coffee, prevents progressive neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. Furthermore, to effectively deliver caffeine to the body, recently developed nanoformulations using caffeine, for instance, nanoparticles, liposomes, etc., are summarized along with regulatory and safety considerations for caffeine. The U.S. Department of Agriculture (USDA) and the Food and Drug Administration (FDA) recommended that healthy adults consume up to 400 mg of caffeine per day or 5~6 mg/kg body weight. Since a cup of coffee contains, on average, 100 to 150 mg of coffee, 1 to 3 cups of coffee may help prevent chronic diseases. Furthermore, this review summarizes various interesting and important areas of research on caffeine and its applications related to human health.

Exploring the Inhibitory Potential of Phytosterols β-Sitosterol, Stigmasterol, and Campesterol on 5-Alpha Reductase Activity in the Human Prostate: An In Vitro and In Silico Approach

Steroidal 5α-reductase type 2 (S5αR2) is a key enzyme involved in the conversion of testosterone (TST) to dihydrotestosterone (DHT), a crucial process in the development of benign prostatic hyperplasia (BPH). Phytosterols (PSs), natural plant-derived compounds, have been proposed as potential inhibitors of S5αR2, but studies on their efficacy are limited. This study evaluates the inhibitory effects of three PSs (β-sitosterol, stigmasterol, and campesterol) on S5αR2 activity using a combined in vitro and in silico approach. The inhibitory activity of the respective PSs was assessed in vitro, by measuring TST and DHT, while molecular docking and dynamics explored PS interactions with S5αR2’s active site. The in vitro tests indicated significantly higher IC50 values (β-sitosterol, 3.24 ± 0.32 µM; stigmasterol, 31.89 ± 4.26 µM; and campesterol, 15.75 ± 5.56 µM) for PSs compared to dutasteride (4.88 × 10−3 ± 0.33 µM), suggesting a lower efficiency in inhibiting S5αR2. The in silico studies confirmed these observations, explained by the lower binding affinity identified for PSs to the enzyme’s active site in the molecular docking studies and the reduced stability of the interactions with the active site of the enzyme during the molecular dynamics simulations compared to dutasteride. The results suggest that PSs exhibit low-to-negligible inhibitory activity against S5αR2 (µM range) compared to the synthetic inhibitor dutasteride (nM range). Among the three PSs studied, β-sitosterol showed the highest inhibitory activity and the best stability in its interaction with S5αR2, when compared with stigmasterol and campesterol.

Modulation of the Respiratory Epithelium Physiology by Flavonoids—Insights from 16HBEσcell Model

Extensive evidence indicates that the compromise of airway epithelial barrier function is closely linked to the development of various diseases, posing a significant concern for global mortality and morbidity. Flavonoids, natural bioactive compounds, renowned for their antioxidant and anti-inflammatory properties, have been used for centuries to prevent and treat numerous ailments. Lately, a growing body of evidence suggests that flavonoids can enhance the integrity of the airway epithelial barrier. The objective of this study was to investigate the impact of selected flavonoids representing different subclasses, such as kaempferol (flavonol), luteolin (flavone), and naringenin (flavanone), on transepithelial electrical resistance (TEER), ionic currents, cells migration, and proliferation of a human bronchial epithelial cell line (16HBE14σ). To investigate the effect of selected flavonoids, MTT assay, trypan blue staining, and wound healing were assessed. Additionally, transepithelial resistance and Ussing chamber measurements were applied to investigate the impact of the flavonoids on the electrical properties of the epithelial barrier. This study showed that kaempferol, luteolin, and naringenin at micromolar concentrations were not cytotoxic to 16HBE14σ cells. Indeed, in MTT tests, a statistically significant change in cell metabolic activity for luteolin and naringenin was observed. However, our experiments showed that naringenin did not affect the proliferation of 16HBE14σ cells, while the effect of kaempferol and luteolin was inhibitory. Moreover, transepithelial electrical resistance measurements have shown that all of the flavonoids used in this study improved the epithelial integrity with the slightest effect of kaempferol and the significant impact of naringenin and luteolin. Finally, our observations suggest that luteolin increases the Cl- transport through cystic fibrosis transmembrane conductance regulator (CFTR) channel. Our findings reveal that flavonoids representing different subclasses exert distinct effects in the employed cellular model despite their similar chemical structures. In summary, our study sheds new light on the diverse effects of selected flavonoids on airway epithelial barrier function, underscoring the importance of further exploration into their potential therapeutic applications in respiratory health.

The Cognitive Restoration Effects of Resveratrol: Insight Molecular through Behavioral Studies in Various Cognitive Impairment Models.

Cognition is essential for daily activities and progressively deteriorates with age due to various factors leading to cognitive decline. This decline often begins with memory impairment and advances to broader cognitive dysfunctions. Resveratrol (RES), a natural phenolic compound found in red wine, has garnered significant attention for its potential to prevent cognitive decline. This review aims to synthesize the latest preclinical data on the cognitive restorative effects of RES. We highlight RES activities from cellular mechanisms to behavioral outcomes. Evidence from various cognitive impairment models demonstrates that RES exerts neuroprotective effects through multiple mechanisms, including anti-inflammatory, antioxidative, anti-apoptotic, and neurotrophic actions, all of which contribute to cognitive enhancement in behavioral studies. Despite the established role of RES in mitigating memory decline, our review identifies a critical gap in behavioral studies regarding cognitive flexibility. Further research in this domain is recommended. Additionally, species-specific pharmacokinetic differences may account for the inconsistencies between preclinical and clinical outcomes, particularly in rats and humans. We propose that formulations designed to delay gut metabolism through enterohepatic circulation could enhance the translational potential of RES. Furthermore, long-term studies are needed to determine the optimal dose capable of maximizing health benefits without raising toxicity during chronic use.

Investigation of Potent Antifungal Metabolites from Marine Streptomyces bacillaris STR2 (MK045300) from Western Algeria

Fungal infections significantly threaten public health, and many strains are resistant to antifungal drugs. Marine Actinobacteria have been identified as the generators of powerful bioactive compounds with antifungal activity and can be used to address this issue. In this context, strains of Actinomycetes were isolated from the marine area of Rachgoun Island, located in western Algeria. The isolates were phenotypically and genetically characterized. The most potent antifungal isolate was selected, and its crude extract was purified and characterized by the GC/MS method. The results revealed that the STR2 strain showed the strongest activity against at least one target fungal species tested on a panel of fungal pathogens, including Candida albicans, Aspergillus fumigatus, Aspergillus niger, and Fusarium oxysporum. The molecular assignment of the STR2 strain based on the 16S rRNA gene positioned this isolate as a Streptomyces bacillaris species. The presence of safranal (2,3-dihydro-2,2,6-trimethylbenzaldehyde) in the crude chloroform extract of Streptomyces bacillaris STR2 strain was discovered for the first time in bacteria using chromatographic analysis of its TLC fractions. Moreover, certain molecules of biotechnological interest, such as phenols, 1,3-dioxolane, and phthalate derivatives, were also identified. This study highlights the potential of marine actinomycetes to produce structurally unique natural compounds with antifungal activity.

Inhibitory Potency of Chlorogenic Acid from Apple Cider Vinegar Against Alzheimer’s Disease: Molecular Docking and Dynamics Validation

Objective The primary cause of memory loss is Alzheimer’s disease (AD). Recent studies have shown that natural compounds like apple cider vinegar (ACV) have anti-Alzheimer’s capabilities. Essential components of ACV, such as gallic acid and chlorogenic acid, may be in charge of the drug’s pharmacological effects. Methods Using molecular docking and dynamics (MD), the current work looks at the aspect of ACV that protects against AD. To study the conformational relationships and interaction mechanisms between two biological molecules (such as interactions between proteins and drugs or between proteins), MD simulation is frequently used. MD can help understand molecular structural differences between proteins and small compounds. We used acetylcholinesterase (AChE, PDB ID: 1UT6) to MD chlorogenic and gallic acids, as well as the currently prescribed medication rivastigmine (Standard medication). Furthermore, we determine the binding affinity, which may be responsible for AChE inhibition. MD simulations were performed on docked complexes of chlorogenic acid, gallic acid, and rivastigmine with receptor 1UT6 for a 300 ns trajectory to ensure the stability of docked ligand-protein complexes. Results The results showed that chlorogenic acid has the highest binding affinity and stability for AChE inhibition. In the docking and dynamics analysis, both techniques have predicted chlorogenic acid to be a potential constituent of ACV which shows a similar activity when compared to rivastigmine by virtue of binding affinity. Conclusion These findings identify chlorogenic acid as the key component of ACV that protects against AD-related cognitive and behavioral impairments. This finding will be critical in the development of ACV-based drugs for Alzheimer’s disease treatment.

Structural Metamorphosis: Rearranging Camphor-based Systems

Natural compounds are pivotal sources for synthesizing a vast array of biologically active substances in chemistry. Camphor is one of these substances, and both enantiomers are readily obtainable and play significant roles in various synthetic and therapeutic applications. This mini-review provides information on a few synthetic routes for camphor production that have been documented over time. It presents several rearrangements that this chemical and its derivatives can undergo to showcase possible starting points for new compounds that may have biological activity.

Rutin and luteolin purified from Gerbera jamesonii and Chrysanthemum ‘dante purple’ flowers exert remarkable protection against the enteropathogen, E. coli O78, in poultry

Recently, the world directed to the use of natural products as antibiotic alternatives to substitute antibiotics, particularly in livestock animals and poultry to avoid antibiotic resistance and antibiotic residues in all products used for human consumption. Therefore, this study aimed to evaluate in vitro and in vivo antibacterial activities of Gerbera jamesonii and Chrysanthemum “dante purple” flowers extracts as well as rutin and luteolin previously isolated from Gerbera jamesonii and Chrysanthemum “dante purple”, respectively, against the enteropathogen Escherichia coli (E. coli O78) as well as, the detection of their effects on the blood parameters and the clinical signs of the treated birds. Firstly, in vitro antimicrobial activity of the total methanolic extracts, and fractions (petroleum ether or hexane, ethyl acetate and butanol) of Gerbera jamesonii and Chrysanthemum “dante purple” flowers as well as the pure isolated compounds; rutin and luteolin were tested against different pathogens. Further in vivo antimicrobial activity of the pure compounds, rutin and luteolin against E. coli was evaluated. The two pure compounds remarkably protected against the infection induced by the enteropathogen, E. coli O78, in infected chicks. This could prove the efficacy of using the two natural compounds, rutin and luteolin, as protective supplements in poultry.

Anti-Inflammatory Effects of Calcium Hydroxide Combined with Ellagic Acid as Pulp Capping Material: In Vivo Study.

Pulp capping is a pivotal treatment in dentistry aimed at preserving pulp vitality. While calcium hydroxide has long been considered the gold standard in pulp capping materials, its long-term use can induce chronic inflammation, ultimately leading to pulp necrosis and affecting human health. In this context, ellagic acid, a natural compound with potent anti-inflammatory properties, emerged as a promising adjunct to mitigate inflammation associated with calcium hydroxide application, thereby sustaining pulp vitality. This study aimed to investigate the inflammatory response by alterations in neutrophil, macrophage, lymphocyte, and tumor necrosis factor-α (TNF-α) expression following the treatment with a combination of calcium hydroxide and ellagic acid. Dental pulp perforation was made on 27 male Wistar rats on the upper first molar and then pulp capped with calcium hydroxide and ellagic acid. The pulp of the control positive group was capped with calcium hydroxide, and the control group was not capped. The teeth were then extracted after 1, 3, and 7 days posttreatment. The differences in the number of neutrophils, macrophages, lymphocytes, and TNF-α expression were analyzed using one-way analysis of variance (ANOVA) and Tukey's honestly significant difference (HSD) test. The treatment combination of calcium hydroxide and ellagic acid showed the lowest neutrophil number and TNF-α expression compared with the other groups (p < 0.05), while the macrophage and lymphocyte numbers were the highest compared with the other groups (p < 0.05). The combination of calcium hydroxide and ellagic acid as a pulp capping material exhibited a dual effect on the inflammatory response in dental pulp. These findings suggest that calcium hydroxide and ellagic acid modulate the inflammatory response in a complex manner, promoting a more controlled and potentially beneficial healing process.

ASSESSMENT OF TOTAL PHENOLIC CONTENT (TPC), TOTAL FLAVONOID CONTENT (TFC) AND ANTIDIARRHEAL AND ANTIOXIDANT ACTIVITIES OF DIOSCOREA BULBIFERA TUBER EXTRACT

Objective: This study aims to conduct a comprehensive phytochemical screening of the tuber of Dioscorea bulbifera extract, evaluate its antioxidant capacity, and assess its anti-diarrheal activity. Methods: In this research, we reported the phytochemical screening, antidiarrheal and antioxidant activity of methanol, acetone, and dichloromethane (DCM) extracts. The qualitative phytochemical assessment of the bioactive extracts of the tuber of Dioscorea bulbifera was done. Quantitative analysis of total phenolic contents (TPC) and total flavonoid contents (TFC) were also determined. The scavenging activity of D. bulbifera was determined by DPPH assay. The antidiarrheal activity was experimented by the castor oil-induced diarrhea method. Results: TPC of Acetone, Methanol &amp; DCM extract of D. bulbifera was 537.2, 352.7, and 79.12 μgGAE/ml, respectively, and TFC of those extracts were 2.96, 1.08, and 0.35 mgQE/g, respectively. The Acetone extract of D. bulbifera (IC50 27.99 μg/ml) showed the highest antioxidant activity. Antidiarrheal properties of the three extracts were tested at 150 mg/kg, 300 mg/kg, and 600 mg/kg per body weight (bw) in mice. The methanol and DCM extracts showed an important antidiarrheal activity by curbing 69.56% and 86.95% of diarrheal faces at the doses of 600 and 300 mg/kg/bw, respectively. Conclusion: Since the current study implies that the plant extracts gave significant results for Antidiarrheal, Antioxidant, and Phytochemical analysis, the tuber of D. bulbifera may contain therapeutic potential compounds, such as flavonoids, terpenoids, alkaloids, tannins, and saponins. These results moderate more investigation for the potential discovery of new natural bioactive compounds from this medicinal plant.