Phytochemical analysis of water and ethanol liquid extracts prepared using freshly harvested leaves of Mitragyna speciosa (Korth.).

Mitragyna speciosa, also known as kratom, has been reported to have a broad range of pharmacological properties. Freshly harvested leaves and their water extracts are consumed in Southeast Asia while preparations made from dried leaf material are consumed in Western countries. Our study evaluated the phytochemical composition of freshly harvested kratom leaves using LCMS/MS analysis of water and ethanol liquid extracts. Mitragynine and its congeners, including 7-hydroxymitragynine, speciocilliatine, speciogynine, paynantheine, as well as bioactive phenolics including chlorogenic acid, o-coumaric acid, quercitrin, and rutin were identified. However, 7-hydroxymitragynine was detected solely in the water-liquid extract. Currently, unknown compounds were also present in the chromatograms and mass spectra. The study results support that 7-hydroxymitragynine is a post-harvest oxidative derivative or metabolite of mitragynine. Further rigorous and comprehensive evaluations of the phytochemical composition of freshly harvested kratom leaves utilising advanced spectrometric methods are needed to establish the full spectrum of phytochemicals within the plant.

Fine-tuning of mononuclear phagocytes for improved inflammatory responses: role of soybean-derived immunomodulatory compounds.

The concept of inflammation encompasses beneficial and detrimental aspects, which are referred to as infectious and sterile inflammations, respectively. Infectious inflammation plays a crucial role in host defense, whereas sterile inflammation encompasses allergic, autoimmune, and lifestyle-related diseases, leading to detrimental effects. Dendritic cells and macrophages, both of which are representative mononuclear phagocytes (MNPs), are essential for initiating immune responses, suggesting that the regulation of MNPs limits excessive inflammation. In this context, dietary components with immunomodulatory properties have been identified. Among them, soybean-derived compounds, including isoflavones, saponins, flavonoids, and bioactive peptides, act directly on MNPs to fine-tune immune responses. Notably, some soybean-derived compounds have demonstrated the ability to alleviate the symptom of allergy and autoimmunity in mouse models. In this review, we introduce and summarize the roles of soybean-derived compounds on MNP-mediated inflammatory responses. Understanding the mechanism by which soybean-derived molecules regulate MNPs could provide valuable insights for designing safe immunomodulators.

3,3'-Diindolylmethane inhibits the proliferation of esophageal squamous cell carcinoma cells via downregulation of STIM1.

3,3'-Diindolylmethane (DIM) is a natural phytochemical derived from cruciferous plants that has inhibitory effects on a wide range of tumor cells; however, its relevant effects on esophageal cancer cells have been poorly studied. Therefore, in the present study, a pharmacology network approach was used to predict the possible core targets of DIM acting on esophageal cancer. Subsequently, using in vitro experiments, TE-1 human esophageal cancer cells were treated with different concentrations of DIM (0, 40, 60 and 80 µM) for 24 h. Changes in cell activity were detected by Cell Counting Kit-8 assay, and changes in the expression levels of stromal interaction molecule 1 (STIM1) and apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2) and Bax, were assessed by western blotting, followed by the upregulation of STIM1 by thapsigargin (Tg). Network pharmacology analysis showed that there were 39 potential core targets of DIM in esophageal cancer. The results of the in vitro experiments showed that DIM could inhibit the viability of esophageal cancer cells, downregulate the expression of STIM1 and Bcl-2 proteins and upregulate the expression of Bax protein, all in a concentration-dependent manner. The results also demonstrated that toxic carotenoids were agonist against STIM1 protein and upregulated STIM1 and Bax protein expression. After agonizing STIM1 protein expression using Tg, DIM was able to counteract the expression trend of STIM1, Bcl-2 and Bax protein in TE-1 cells. In summary, DIM induced apoptosis and inhibited the viability of esophageal cancer cells by downregulating the expression of STIM1 protein; therefore, the natural phytochemical, DIM, may be a potential substance for the early prevention and treatment of esophageal cancer cells.

Phytotherapeutic options for the treatment of epilepsy: pharmacology, targets, and mechanism of action.

Epilepsy is one of the most common, severe, chronic, potentially life-shortening neurological disorders, characterized by a persisting predisposition to generate seizures. It affects more than 60 million individuals globally, which is one of the major burdens in seizure-related mortality, comorbidities, disabilities, and cost. Different treatment options have been used for the management of epilepsy. More than 30 drugs have been approved by the US FDA against epilepsy. However, one-quarter of epileptic individuals still show resistance to the current medications. About 90% of individuals in low and middle-income countries do not have access to the current medication. In these countries, plant extracts have been used to treat various diseases, including epilepsy. These medicinal plants have high therapeutic value and contain valuable phytochemicals with diverse biomedical applications. Epilepsy is a multifactorial disease, and therefore, multitarget approaches such as plant extracts or extracted phytochemicals are needed, which can target multiple pathways. Numerous plant extracts and phytochemicals have been shown to treat epilepsy in various animal models by targeting various receptors, enzymes, and metabolic pathways. These extracts and phytochemicals could be used for the treatment of epilepsy in humans in the future; however, further research is needed to study the exact mechanism of action, toxicity, and dosage to reduce their side effects. In this narrative review, we comprehensively summarized the extracts of various plant species and purified phytochemicals isolated from plants, their targets and mechanism of action, and dosage used in various animal models against epilepsy.

Xenohormetic Phytochemicals Inhibit Neovascularization in Microphysiological Models of Vasculogenesis and Tumor Angiogenesis.

Xenohormesis proposes that phytochemicals produced to combat stressors in the host plant exert biochemical effects in animal cells lacking cognate receptors. Xenohormetic phytochemicals such as flavonoids and phytoalexins modulate a range of human cell signaling mechanisms but functional correlations with human pathophysiology are lacking. Here, potent inhibitory effects of grapefruit-derived Naringenin (Nar) and soybean-derived Glyceollins (Gly) in human microphysiological models of bulk tissue vasculogenesis and tumor angiogenesis are reported. Despite this interference of vascular morphogenesis, Nar and Gly are not cytotoxic to endothelial cells and do not prevent cell cycle entry. The anti-vasculogenic effects of Glyceollin are significantly more potent in sex-matched female (XX) models. Nar and Gly do not decrease viability or expression of proangiogenic genes in triple negative breast cancer (TNBC) cell spheroids, suggesting that inhibition of sprouting angiogenesis by Nar and Gly in a MPS model of the (TNBC) microenvironment are mediated via direct effects in endothelial cells. The study supports further research of Naringenin and Glyceollin as health-promoting agents with special attention to mechanisms of action in vascular endothelial cells and the role of biological sex, which can improve the understanding of dietary nutrition and the pharmacology of phytochemical preparations.

Ethnobotanical survey and phytochemistry of medicinal plants used in the management of HIV/AIDS in Eastern Uganda.

Currently, highly active antiretroviral therapy is unable to cure HIV/AIDS because of HIV latency. This study aimed at documenting medicinal plants used in the management of HIV/AIDS in Eastern Uganda so as to identify phytochemicals with HIV latency reversing potential. An ethnobotanical survey was conducted across eight districts in Eastern Uganda. Traditional medicine practitioners were interviewed using semi-structured questionnaires. Qualitative and quantitative phytochemical tests were respectively, performed to determine the presence and quantity of phytochemicals in frequently mentioned plant species. Data were analysed and presented using descriptive statistics and Informant Consensus Factor (ICF). Twenty-one plant species from fourteen plant families were reported to be used in the management of HIV/AIDS. Six plant species with the highest frequency of mention were: Zanthoxylum chalybeum, Gymnosporia senegalensis, Warbugia ugandensis, Leonatis nepetifolia, Croton macrostachyus and Rhoicissus tridentata. Qualitative phytochemical analysis of all the six most frequently mentioned plant species revealed the presence of flavonoids, tannins, terpenoids, alkaloids and phenolics. Quantitative analysis revealed the highest content of flavonoids in L. nepetifolia (20.4 mg/g of dry extract) while the lowest content was determined in C. macrostachyus (7.1 mg/g of dry extract). On the other hand, the highest content of tannins was observed in L. nepetifolia. (199.9 mg/g of dry extract) while the lowest content was found in R. tridentata. (42.6 mg/g of dry extract). Medicinal plants used by traditional medicine practitioners in Eastern Uganda to manage HIV/AIDS are rich in phytochemicals including flavonoids and tannins. Further studies to evaluate the HIV-1 latency reversing ability of these phytochemicals are recommended to discover novel molecules against HIV/AIDS.

Phytochemicals, antioxidant ability and in vitro anthelmintic activity of crude extracts from Vitexnegundo leaves against Haemonchus contortus.

The aim of this study was to evaluate the in vitro anthelmintic effect of crude aqueous, methanol, ethanol, hydro alcohol and acetone extracts of Vitex negundo leaves against Haemonchus contortus eggs and larvae. Phytochemical analysis to identify the number of compounds in extracts was done by chemical tests and gas chromatography coupled to a mass spectrophotometer detector (GC-MS). First off all the effectiveness of dried plant materials was evaluated on larval development by mixing powdered material (no nano particles) to faecal cultures from donor sheep. Adding powder to the faecal culture resulted into 100% inhibition in larval development at 200 and 300 mg/g of faeces. The anthelmintic activity was assessed using the egg hatch assay (EHA) and the larval mortality assay (LMA). Comparison of mean inhibition percentage of egg embryonation, mean inhibition percentage of egg hatching and mean percentage of larval mortality at different concentrations with control was performed by one-way ANOVA. The means were compared for statistical significance using DMRT at P < 0.05. For both the assays, 50% inhibitory concentration (IC50) and lethal concentration (LC50) were calculated by probit analysis. Chemical test revealed presence of high concentration of saponin and flavoinoids and moderate concentration of total phenols in leaves. The antioxidant activity (radical scavenging activity, RSA %) measured was 35.47%. On GC-MS, the methanolic leaves extract revealed 30 phyto-compounds. On EHA, there was marked effect on inhibition of egg hatching by aqueous, hydro alcohol and acetone extracts. On LMA all the five extracts showed excellent larvicidal activity. V. negundo leaves methanol extract mediated silver nanoparticles were found very effective at much lower concentrations as compared to crude methanol extract. The results indicated that the V. negundo leaves crude extracts possessed excellent in vitro ovicidal and larvicidal properties against H. contortus which needs more investigation, especially in vivo trials for the control of parasite.

Role of CETP, PCSK-9, and CYP7-alpha in cholesterol metabolism: Potential targets for natural products in managing hypercholesterolemia.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, primarily affecting the heart and blood vessels, with atherosclerosis being a major contributing factor to their onset. Epidemiological and clinical studies have linked high levels of low-density lipoprotein (LDL) emanating from distorted cholesterol homeostasis as its major predisposing factor. Cholesterol homeostasis, which involves maintaining the balance in body cholesterol level, is mediated by several proteins or receptors, transcription factors, and even genes, regulating cholesterol influx (through dietary intake or de novo synthesis) and efflux (by their conversion to bile acids). Previous knowledge about CVDs management has evolved around modulating these receptors' activities through synthetic small molecules/antibodies, with limited interest in natural products. The central roles of the cholesteryl ester transfer protein (CETP), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cytochrome P450 family 7 subfamily A member 1 (CYP7A1), among other proteins or receptors, have fostered growing scientific interests in understanding more on their regulatory activities and potential as drug targets. We present up-to-date knowledge on the contributions of CETP, PCSK9, and CYP7A1 toward CVDs, highlighting the clinical successes and failures of small molecules/antibodies to modulate their activities. In recommendation for a new direction to improve cardiovascular health, we have presented recent findings on natural products (including functional food, plant extracts, phytochemicals, bioactive peptides, and therapeutic carbohydrates) that also modulate the activities of CETP, PCSK-9, and CYP7A1, and emphasized the need for more research efforts redirected toward unraveling more on natural products potentials even at clinical trial level for CVD management.

Pharmacophore modelling based virtual screening and molecular dynamics identified the novel inhibitors and drug targets against Waddlia chondrophila.

Waddlia chondrophila is a possible cause of fetal death in humans. This Chlamydia-related bacterium is an emergent pathogen that causes human miscarriages and ruminant abortions, which results in financial losses. Despite the years of efforts, the underlying mechanism behind the pathogenesis of W. chondrophila is little known which hindered the development of novel treatment options. In the framework of current study, computational approaches were used to identify novel inhibitors (phytocompounds) and drug targets against W. chondrophila. At first, RNA polymerase sigma factor SigA and 3-deoxy-D-manno-octulosonic acid transferase were identified through subtractive proteomics pipeline. Afterwards, extensive docking and simulation analyses were conducted to optimize potentially novel phytocompounds by assessing their binding affinity to target proteins. A 100ns molecular dynamics simulation well complimented the compound's binding affinity and indicated strong stability of predicted compounds at the docked site. The calculation of binding free energies with MMGBSA corroborated the significant binding affinity between phytocompounds and target protein binding sites. The proposed phytocompounds may be a viable treatment option for patients infected with W. chondrophila; however, further research is required to ensure their safety.

Fustin suppressed melanoma cell growth via cAMP/PKA-dependent mechanism.

Melanoma, a cancer arising from melanocytes, requires a novel treatment strategy because of the ineffectiveness of conventional therapies in certain patients. Fustin is a flavanonol found in young fustic (Cotinus coggygria). However, little is known about its antimelanoma effects. Our study demonstrates that fustin suppresses the growth of B16 melanoma cells. Phalloidin staining of cytoskeletal actin revealed that fustin induced a conformational change in the actin structure of melanoma cells, accompanied by suppressed phosphorylation of myosin regulatory light chain 2 (MLC2), a regulator of actin structure. Furthermore, the protein kinase A (cAMP-dependent protein kinase) inhibitor H89 completely attenuated fustin-induced downregulation of phosphorylated myosin phosphatase targeting subunit 1 (MYPT1), which is involved in dephosphorylation of MLC2. In a mouse model, administration of fustin suppressed tumor growth in B16 melanoma cells without adverse effects. In conclusion, our findings suggest that fustin effectively suppresses melanoma cell growth both in vitro and in vivo.

Plant Flavonoids with Antimicrobial Activity against Methicillin-Resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious threat to human public health and global economic development, and there is an urgent need to develop new antimicrobial agents. Flavonoids are the largest group of plant secondary metabolites, and the anti-S. aureus and anti-MRSA activities of flavonoids have now been widely reported. The aim of this Review is to describe plant-derived flavonoid active ingredients and their effects and mechanisms of inhibitory activity against MRSA in order to provide insights for screening novel antimicrobial agents. Here, 85 plant-derived flavonoids (14 flavones, 21 flavonols, 26 flavanones, 9 isoflavones, 12 chalcones, and 3 other classes) with anti-MRSA activity are reviewed. Among these flavonoids, flavones and isoflavones generally showed the most significant anti-MRSA activity (MICs: 1-8 µg/mL). The results of the present Review display that most of the flavonoids with excellent anti-MRSA activity were derived from Morus alba L. and Paulownia tomentosa (Thunb.) Steud. The antibacterial mechanism of flavonoids against MRSA is mainly achieved by disruption of membrane structures, inhibition of efflux pumps, and inhibition of ß-lactamases and bacterial virulence factors. We hope this Review can provide insights into the development of novel antimicrobials based on natural products for treating MRSA infections.

Mechanism of antibacterial activity of diallyl sulfide against Bacillus cereus.

World health organization (WHO) recognizes antimicrobial resistance as a silent pandemic. It is estimated that 10 million deaths will occur annually due to antimicrobial resistant infections by 2050. Phytochemicals exhibit activity against drug resistant bacteria, offering potential for developing novel antibacterial agents. Garlic organosulphur compounds exhibit potent activity against a variety of drug-resistant bacteria. Identifying their mechanism of action is critical to assess their potential to be developed as novel antibacterial agents. Diallyl sulfide (DAS) is a component of garlic essential oil with antibacterial activity. In this study antibacterial activity of DAS was investigated against Bacillus cereus, a common foodborne pathogen. DAS exhibited activity against B. cereus with a minimum inhibitory concentration (MIC) of 54.75 mM. The presence of DAS significantly reduced the growth of B. cereus. The study also investigated the mechanism of antibacterial activity of DAS against B. cereus. Treating B. cereus with sub-MIC and MIC concentration of DAS resulted in a dose and time-dependent leakage of intracellular proteins. The protein leakage was enhanced at acidic pH. Scanning electron microscopy (SEM) of B. cereus treated with DAS showed deformation in the cell membrane. Thus, the data indicate that DAS exerts its antibacterial activity by compromising the membrane integrity of B. cereus. The study demonstrates DAS could be used to control B. cereus infections. The findings indicate that DAS has a membrane altering activity, suggesting that development of resistance to this mechanism is less likely and the compound could be novel antibacterial or a good adjuvant for antibiotics.

Garden cress seeds: a review on nutritional composition, therapeutic potential, and industrial utilization.

The growing preference for natural remedies has resulted in increased use of medicinal plants. One of the most significant and varied plants is garden cress (Lepidium sativum), which has large concentrations of proteins, fatty acids, minerals, and vitamins. It also contains a wide range of bioactive components, including kaempferol glucuronide, gallic acid, protocatechuic acid, coumaric acid, caffeic acid, terpenes, glucosinolates, and many more. These substances, which include antioxidant, thermogenic, depurative, ophthalmic, antiscorbutic, antianemic, diuretic, tonic, laxative, galactogogue, aphrodisiac, rubefacient, and emmengogue qualities, add to the medicinal and functional potential of garden cress. An extensive summary of the phytochemical profile and biological activity of garden cress seeds is the main goal of this review. Research showed that garden cress is one of the world's most underutilized crops, even with its nutritional and functional profile. Consequently, the goal of this review is to highlight the chemical and nutritional makeup of Lepidium sativum while paying particular attention to its bioactive profile, various health claims, therapeutic benefits, and industrial applications.

Amelioration of phytotoxic impact of biosynthesized zinc oxide nanoparticles: Plant growth promoting rhizobacteria facilitates the growth and biochemical responses of Eggplant (Solanum melongena) under nanoparticles stress.

The consistently increasing use of zinc oxide nanoparticles (ZnONPs) in crop optimization practices and their persistence in agro-environment necessitate expounding their influence on sustainable agro-environment. Attempts have been made to understand nanoparticle-plant beneficial bacteria (PBB)- plant interactions; the knowledge of toxic impact of nanomaterials on soil-PBB-vegetable systems and alleviating nanotoxicity using PBB is scarce and inconsistent. This study aims at bio-fabrication of ZnONPs from Rosa indica petal extracts and investigates the impact of PBB on growth and biochemical responses of biofertilized eggplants exposed to phyto-synthesized nano-ZnO. Microscopic and spectroscopic techniques revealed nanostructure, triangular shape, size 32.5 nm, and different functional groups of ZnONPs and petal extracts. Inoculation of Pseudomonas fluorescens and Azotobacter chroococcum improved germination efficiency by 22% and 18% and vegetative growth of eggplants by 14% and 15% under NPs stress. Bio-inoculation enhanced total chlorophyll content by 36% and 14 %, increasing further with higher ZnONP concentrations. Superoxide dismutase and catalase activity in nano-ZnO and P. fluorescens inoculated eggplant shoots reduced by 15-23% and 9-11%. Moreover, in situ experiment unveiled distortion and accumulation of NPs in roots revealed by scanning electron microscope and confocal laser microscope. The present study highlights the phytotoxicity of biosynthesized ZnONPs to eggplants and demonstrates that PBB improved agronomic traits of eggplants while declining phytochemicals and antioxidant levels. These findings suggest that P. fluorescens and A. chroococcum, with NPs ameliorative activity, can be cost-effective and environment-friendly strategy for alleviating NPs toxicity and promoting eggplant production under abiotic stress, fulfilling vegetable demands.

A review on the biological and bioactive components of Cyperus esculentus L.: insight on food, health and nutrition.

Tiger nut (Cyperus esculentus L.) is a small, tuberous root vegetable that has gained increasing attention in recent years due to its potential health benefits. This review article provides an elaborate overview of tiger nut, including its botany, historical uses, nutritional composition, potential health benefits and traditional medicinal uses. This review article comprehensively discusses the nutritional profile of tiger nut, providing a detailed understanding of its nutrient content. Furthermore, the potential health benefits of tiger nut are thoroughly reviewed, including its effects on digestive health, cardiovascular health, blood sugar control, immune function and other potential therapeutic uses. Scientific articles used for this review were retrieved from ScienceDirect, Google Scholar, PubMed and SciELO databases. Only articles published between 1997 and 2022 were used for research. This review contributes to a better understanding of tiger nut and its prospective uses in functional foods and medicine by combining the available scientific material. © 2024 Society of Chemical Industry.

Momordica charantia Bioactive Components: Hypoglycemic and Hypolipidemic Benefits Through Gut Health Modulation.

Momordica charantia (MC), a member of the Cucurbitaceae family, is well known for its pharmacological activities that exhibit hypoglycemic and hypolipidemic properties. These properties are largely because of its abundant bioactive compounds and phytochemicals. Over the years, numerous studies have confirmed the regulatory effects of MC extract on glycolipid metabolism. However, there is a lack of comprehensive reviews on newly discovered MC-related components, such as insulin receptor-binding protein-19, adMc1, and MC protein-30 and triterpenoids 3ß,7ß,25-trihydroxycucurbita-5,23(E)-dien-19-al, and the role of MC in gut microbiota and bitter taste receptors. This review offers an up-to-date overview of the recently reported chemical compositions of MC, including polysaccharides, saponins, polyphenolics, peptides, and their beneficial effects. It also provides the latest updates on the role of MC in the regulation of gut microbiota and bitter taste receptor signaling pathways. As a result, this review will serve as a theoretical basis for potential applications in the creation or modification of MC-based nutrient supplements.

Investigating the Antiviral Properties of Nyctanthes arbor-tristis Linn against the Ebola, SARS-CoV-2, Nipah, and Chikungunya Viruses: A Computational Simulation Study.

Background: The hunt for naturally occurring antiviral compounds to combat viral infection was expedited when COVID-19 and Ebola spread rapidly. Phytochemicals from Nyctanthes arbor-tristis Linn were evaluated as significant inhibitors of these viruses. Methods: Computational tools and techniques were used to assess the binding pattern of phytochemicals from Nyctanthes arbor-tristis Linn to Ebola virus VP35, SARS-CoV-2 protease, Nipah virus glycoprotein, and chikungunya virus. Results: Virtual screening and AutoDock analysis revealed that arborside-C, beta amyrin, and beta-sitosterol exhibited a substantial binding affinity for specific viral targets. The arborside-C and beta-sitosterol molecules were shown to have binding energies of -8.65 and -9.11 kcal/mol, respectively, when interacting with the major protease. Simultaneously, the medication remdesivir exhibited a control value of -6.18 kcal/mol. The measured affinity of phytochemicals for the other investigated targets was -7.52 for beta-amyrin against Ebola and -6.33 kcal/mol for nicotiflorin against Nipah virus targets. Additional molecular dynamics simulation (MDS) conducted on the molecules with significant antiviral potential, specifically the beta-amyrin-VP35 complex showing a stable RMSD pattern, yielded encouraging outcomes. Conclusions: Arborside-C, beta-sitosterol, beta-amyrin, and nicotiflorin could be established as excellent natural antiviral compounds derived from Nyctanthes arbor-tristis Linn. The virus-suppressing phytochemicals in this plant make it a compelling target for both in vitro and in vivo research in the future.

Exploring Synergistic Interactions between Natural Compounds and Conventional Chemotherapeutic Drugs in Preclinical Models of Lung Cancer.

In the current work, the synergy between natural compounds and conventional chemotherapeutic drugs is comprehensively reviewed in light of current preclinical research findings. The prognosis for lung cancer patients is poor, with a 5-year survival rate of 18.1%. The use of natural compounds in combination with conventional chemotherapeutic drugs has gained significant attention as a potential novel approach in the treatment of lung cancer. The present work highlights the importance of finding more effective therapies to increase survival rates. Chemotherapy is a primary treatment option for lung cancer but it has limitations such as reduced effectiveness because cancer cells become resistant. Natural compounds isolated from medicinal plants have shown promising anticancer or chemopreventive properties and their synergistic effect has been observed when combined with conventional therapies. The combined use of an anti-cancer drug and a natural compound exhibits synergistic effects, enhancing overall therapeutic actions against cancer cells. In conclusion, this work provides an overview of the latest preclinical research on medicinal plants and plant-derived compounds as alternative or complementary treatment options for lung cancer chemotherapy and discusses the potential of natural compounds in treating lung cancer with minimal side effects.

Network Pharmacology and Experimental Validation to Explore the Potential Mechanism of Nigella sativa for the Treatment of Breast Cancer.

Breast cancer is a prevalent and potentially life-threatening disease that affects women worldwide. Natural products have gained attention as potential anticancer agents due to their fewer side effects, low toxicity, and cost effectiveness compared to traditional chemotherapy drugs. In the current study, the network pharmacology approach was used following a molecular docking study to evaluate the therapeutic potential of N. sativa-derived phytochemicals against breast cancer. Specifically, the study aimed to identify potential anticancer agents targeting key proteins implicated in breast cancer progression. Five proteins (i.e., EGFR, MAPK3, ESR1, MAPK1, and PTGS2) associated with breast cancer were selected as receptor proteins. Fourteen phytochemicals from N. sativa were prioritized based on drug-likeness (DL) and oral bioavailability (OB) parameters (with criteria set at DL > 0.18 and OB > 30%, respectively). Subsequent analysis of gene targets identified 283 overlapping genes primarily related to breast cancer pathogenesis. Ten hub genes were identified through topological analysis based on their significance in the KEGG pathway and GO annotations. Molecular docking revealed strong binding affinities between folic acid, betulinic acid, stigmasterol, and selected receptor proteins. These phytochemicals also demonstrated druggability potential. In vitro experiments in the MDA-MB-231 breast cancer cell line revealed that betulinic acid and stigmasterol significantly reduced cell viability after 24 h of treatment, confirming their anticancer activity. Furthermore, in vivo evaluation using a DMBA-induced rat model showed that betulinic acid and stigmasterol contributed to the significant recovery of cancer markers. This study aimed to explore the mechanisms underlying the anticancer potential of N. sativa phytochemicals against breast cancer, with the ultimate goal of identifying novel therapeutic candidates for future drug development. Overall, these results highlight betulinic acid and stigmasterol as promising candidates to develop novel anticancer agents against breast cancer. The comprehensive approach of this study, which integrates network pharmacology and molecular docking study and its experimental validation, strengthens the evidence supporting the therapeutic benefits of N. sativa-derived phytochemicals in breast cancer treatment, making them promising candidates for the development of novel anticancer agents against breast cancer.

Hypoglycemic Effects of Extracts Obtained from Endemic Betonica bulgarica Degen and Neic.

The increasing prevalence of diabetes mellitus, together with the limited access of many patients to conventional antidiabetic drugs and the side effects resulting from their use, are the reason for the ever-increasing need for new agents. One of the most important strategies used in the therapy of this disease is to reduce the postprandial blood glucose level by inhibiting the carbohydrate-degrading enzymes α-amylase and α-glucosidase. The purpose of the present study was to provide in vitro evidence for the potential hypoglycemic effect of leaf and inflorescence aqueous extracts of Bulgarian endemic species Betonica bulgarica Degen and Neic. Total phenolic and flavonoid contents and antioxidant activities were determined by spectrophotometric methods. Qualitative and quantitative determinations of principal phenolic acids and flavonoids were performed using HPLC with a dual absorbance detector. The plant extracts were able to retard the enzymatic breakdown of starch to glucose with 50% inhibiting concentrations of 1.86 mg/mL and 1.54 mg/mL respectively for leaf and flower extract. Some of the plant constituents are proven inhibitors of α-amylase and/or α-glucosidase, but their adsorption on starch seems to be one additional mechanism for the inhibition of glucose release. Combination index analysis carried out with binary mixtures of acarbose and plant extracts showed a tendency toward synergism with an increase in concentrations and level of inhibition.