Bioactive Constituents Research Articles

Double-crosslinked hydrogels and hydrogel beads formed by garlic protein hydrolysates for bioactive encapsulation and gastrointestinal delivery.

Garlic protein is one of the main components of garlic. It has several beneficial characteristics. This study aimed to characterize a double crosslinked hydrogel formed with alginate, calcium ions (Ca2+), and garlic protein hydrolysates (GPH), and to develop hydrogel beads for targeted delivery of bioactive constituents to the gastrointestinal tract. The results indicated that the degree of GPH hydrolysis was approximately 3% following trypsin treatment. The inner structure of the double crosslinked hydrogel showed a honeycomb pattern, with solid-like gel rheology and improved texture properties at a 4% (w/v) GPH concentration. The GPH-based hydrogel beads demonstrated pH sensitivity, swelling in near-neutral and alkaline environments, and the encapsulated paclitaxel (PTX) exhibited an amorphous phase with preferential release in intestinal conditions. The GPH group also achieved greater drug encapsulation efficiency than a soy protein hydrolysate (SPH) group, and proteomic analysis suggested that lower molecular weight and peptide charge favored the formation of peptide-integrated double crosslinking hydrogels. This work indicated that GPH was helpful and could inspire the development of drug delivery systems involving GPH with the required mechanical strength and target-release properties. © 2024 Society of Chemical Industry.

Triterpenoids from Ganoderma lucidum inhibit cytochrome P450 enzymes interfering with the metabolic process of specific clinical drugs

BackgroundGanoderma lucidum (G. lucidum), which possesses various biological effects, has been widely used as traditional medicine and functional food in Asian countries, especially China. In consideration of its various biological effects on human healthcare, G. lucidum was usually used in combination with other drugs. However, the potential drug-drug interaction induced by G. lucidum through cytochrome P450 enzymes (CYPs) remain unknown.MethodsUsing the in vivo activity assay of CYPs, the inhibitory effects of G. lucidum and its constituents could be evaluated. The interference of G. lucidum on the metabolic processes of clinical drugs could be investigated. The chemical constituents of G. lucidum could be identified using LC-MS. The interaction between bioactive compounds and CYPs could be proposed through in silico docking analysis and molecular dynamics.ResultsThe dichloromethane extract of G. lucidum could inhibit various CYP450 subtypes in vitro and interfere with the pharmacokinetics of four drugs in rats. Triterpenoids were identified as the main constituents of the dichloromethane extract by Q-TOF-MSn in preliminary analyses. Then, a triterpenoid library containing 66 compounds was established to evaluate their inhibitory effects against CYP 1A2, 2D6, 3A4, 2A6, 2B6, 2C9, and 2C19. CYP 1A2 was inhibited by most lanostane triterpenoids, indicating a strong affinity for these compounds. Among triterpenoids, compound 25 displayed a broad inhibitory effect against CYPs, except for CYP 3A4, 2D6, 2C9, and 2C19. Finally, compounds 6 and 25 exhibited interference with the metabolism of 16 drugs through the inhibition of CYPs in vitro. In silico molecular docking analyses for assaying the interaction between compound 25 and CYPs indicated that the hydrogen bonds formed between the hydroxyl groups and amino acid residues.ConclusionG. lucidum displayed broad inhibitory effects on CYPs, with triterpenoids as the main bioactive constituents, which may induce potential drug-drug interaction. This information should be helpful for the rational use of G. lucidum in promoting human health.

The bioactive constituents from the fruits of Elaeagnus angustifolia L.

Multiple spectroscopic, chromatographic, and chemical reaction methods were combined to investigate the chemical components in the fruits of Elaeagnus angustifolia L. As results, thirty-two compounds were obtained from it as natural products. Six of them, elangphenosides A (1), B (2), C (3) and D (4), elangmegastigmanoside A (5), and elangorganic acid A1 (6) were retrieved by Scifinder as previously undescribed ones. Additionally, a previously undescribed artificial product, elangorganic acid A2, as well as a known artificial one, (3R) 5-ethoxy-3-(ethoxycarbonyl)-3-hydroxy-5-oxopentanoic acid, were yielded. Following the phytochemical investigation, LC-MS analysis was employed to conduct a systematical characterization of the constituents from E. angustifolia fruits. Ultimately, fifty-six compounds, including seventeen phenols, one ionone, twenty-four triterpenes, and fourteen other ones, were unambiguously detected and identified. Moreover, in vitro anti-inflammatory activity screening of forty-four natural compounds presented in E. angustifolia fruits was performed by using the LPS-induced RAW264.7 cell model. Twenty-six compounds, including phenols, organic acids, and other compounds, showed assignable activity. Furthermore, their structure-activity relationships were summarized. Combined with the previous research work in our lab, triterpenes, phenols, and organic acids were speculated to be key components during the E. angustifolia fruits exerting anti-inflammatory activity. In summary, this article fully explored the chemical composition of E. angustifolia fruits, assayed their in vitro NO production inhibitory effects, greatly expanding its material foundation and laying a solid foundation for further research and development.

Phenolic Components And Biological Activity Of Pomegranate.

Pomegranate (Punica granatum L.) have been subject of extensive studies for its abundance of phytochemicals and numerous biological and medicinal properties. It is a fruit-bearing tree, which is widely consumed as a nutraceutical source as well as functional food for putative health benefits. The phenolic components are the characteristic bioactive constitutes of pomegranate, including hydrolysable tannins, flavonoids, and phenolic acids. The whole plant of this tree has many medicinal folkloric uses and good therapeutic effect, such as anticancer, antioxidant, antibacterial, antiviral, hypoglycemic, lipid-lowering, cardioprotection and digestive system protection. Through comprehensive search of available literature, this narrative review can provide an up-to-date overview of the current knowledge of characteristic bioactive constituents's structure and potential health benefits of Pomegranate, which can be used as reference for the future clinical and basic research, and also helpful for the development of pomegranate into functional food and nutraceuticals.

Mushrooms and Colorectal Cancer: Unveiling Mechanistic Insights and Therapeutic Innovations.

Nature has bestowed us with an abundant reservoir of resources that besides having nutritional value, are prolific mines of bioactive constituents with a plethora of medicinal activities. Mushrooms have been used since centuries in traditional system of medicine for their purported health benefits including anticancer activities. Thorough research, spanning over centuries in Japan, China, Korea, and the USA, has established the unique properties of mushrooms and their extractives in the prevention and treatment of various types cancer. The aim of the review article is to provide a comprehensive overview of the existing literature highlighting the potential relationship between mushrooms and colorectal cancer. Different databases such as PubMed, Web of Science, Google Scholar, and ScienceDirect were searched and a total of 62 articles and two book chapters were reviewed, and data were extracted. Multiple studies have demonstrated that mushrooms exhibit anticancer activities, effectively reducing adverse side effects such as nausea, myelosuppression, anemia, and sleeplessness. Furthermore, they have been shown to mitigate drug resistance following chemotherapy and radiation therapy. Certain species such as Antrodia, Pleurotus, Ganoderma, Lentinula, Hericium, Cantharellus, Clitocybe, Coprinopsis, Trametes, Sparassis, Lactarius, and so on manifest anticancer activity in colon. The article can help improve the scientific understanding of the co-relationship between mushrooms and colorectal cancer. This may help in advancing the research directions and integrating the mushroom-based strategies into current treatment protocols of colorectal cancer.

Combining the Strengths of MS and NMR in Biochemometrics: A Case Study on Buddleja officinalis.

Biochemometrics has emerged as promising strategy for the targeted identification of bioactive constituents from natural sources. It is based on the correlation of bioactivity data with chemical data to reveal constituents contributing to activity. Providing complementary data and structural information, MS- and NMR-based biochemometric approaches have both been separately applied in the past. The herein presented study is dedicated to the evaluation of a combined MS- and NMR-based biochemometric workflow for the unambiguous identification of bioactives. As an example, a flower extract of Buddleja officinalis Maxim. was selected to unravel bioactive constituents in the context of dry eye disease pathology. While NMR-based biochemometrics relies on heterocovariance analysis (HetCA) of 1H NMR spectra using the previously established ELINA approach, a biochemometric molecular network was generated for the MS-based approach. Both analyses were performed in parallel and were ultimately combined to increase their power to identify the bioactive constituents from the complex mixture. As a result, phenylethanoid glycosides and triterpene saponins were discovered as main contributors for the antioxidant and cytotoxic effects of the extract. This article illustrates the advantages, opportunities, and limitations of MS and NMR in the context of biochemometrics.

Optimization of green extraction technologies for recovering bioactive compounds from Ixora coccinea waste flower biomass: A comparative response surface methodology and artificial neural network modeling

Red pigment from Ixora coccinea waste flower biomass was extracted using water as a cost-effective solvent for a sustainable source of organic color. The significant effect of selected variables on the method of extraction was studied for the green-extraction techniques, i.e., microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE), and conventional technique, i.e., heat-assisted extraction (HAE). Optimization of the pigment extraction was examined using response surface methodology (RSM) for each extraction technique. The parameters considered for MAE were power (W), time (s), pH, and solvent-to-sample ratio (mL/g) while temperature (°C), time (min), pH, and solvent-to-sample ratio (mL/g) were studied for both UAE and HAE. A training set for an artificial neural network (ANN) was created using the same design obtained from RSM. The modeling techniques (ANN and RSM) were then statistically differentiated by the coefficient of determination (R2), root mean square error (RMSE), and mean square error (MSE) which revealed the superiority of the RSM regression design over the ANN model. It was found that the energy consumption of pigment extraction was minimal for MAE. The obtained pigment was further characterized using Fourier transform infrared (FTIR) spectroscopy to reveal functional groups and a gas chromatography-mass spectrometry (GC-MS) to define its bioactive constituents.

VARIATIONS IN VOLATILE OIL CONSTITUENTS OF ECHINOPS SPECIES GROWING IN THE MIDDLE EAST AND THE MEDITERRANEAN REGIONS: MINI REVIEW

The genus Echinops of the family Asteraceae has commonly been a subject of interest because its members have various chemical constituents and crucial pharmacological activities of great medicinal importance over the last decade (2010-2023). Therefore, this genus has attracted serious research in pharmacognosy and herbal medicine. Detailed studies revealed that Echinops species contain numerous bioactive compounds, such as sesquiterpene lactones, essential oils, flavonoids, and polyacetylenic aliphatic acids, largely in plant parts that are important for therapeutic use. These bioactive constituents have been associated with a wide diversity of pharmacological activities such as anti-inflammatory, antimicrobial, and cytotoxic underlined while proceeding to show some antioxidant activity and even hepatoprotective action of the genus, hence encouraging the further development of novel therapeutic agents. Most of these activities have been studied both in vitro and in vivo to establish their underlying effects. This will help us evaluate pharmacological properties attributed to the genus Echinops and pave the way for future studies to validate traditional uses and optimize extraction methods and their clinical applications. This work highlighted the position of Echinops species in Mediterranean areas, especially essential oils as a source of bioactive compounds useful in the well-being of humans and its variation concerning several factors. It has reaffirmed the place of natural products in drug discovery and development.

Bioassay-guided isolation and identification of antimutagenic compounds from Morina coulteriana and evaluation of its therapeutic potential.

BackgroundIn the expanding field of cancer research, antimutagenic studies hold a promising ground. In recent times these studies have shown a shift towards the diverse flora of nature and its potential to treat cancer. Genus Morina has been extensively used in Chinese, Tibetan, and Indian traditional medicine to cure numerous diseases. The plant Morina coulteriana has been traditionally used to cure eye diseases. Nevertheless, it has been explored for the first time for its antimutagenic/antigenotoxic potential and phytochemical profile. PurposeThe present study aimed to determine the antimutagenic/antigenotoxic potential of Morina coulteriana and the bioassay-guided identification of its bioactive constituents. MethodsThe methanol crude extract and its subsequent fractions were tested for antimutagenic/antigenotoxic activity in vitro (Ames assay) and in vivo (Chromosomal aberration assay in Balb/c mice). The active (ethyl acetate) fraction was further investigated to isolate and identify its bioactive compounds utilizing chromatographic purification and detailed spectroscopic techniques respectively. ResultsThe results revealed that the plant and its fractions were neither mutagenic nor toxic. The ethyl acetate fraction showed significant antimutagenic/antigenotoxic activity (66.13%) in vitro and (88.15%) in vivo. Further, four identified major compounds which were also tested in vitro. Our results revealed that the plant is a potent antimutagen. It worked in a dose-dependent manner and its administration decreased the mutagenic load on the cells both in vitro and in vivo experiments. The 2 isolated compounds viz.; 4hydroxyacetophenone, a phenol and picein, a phenolic glycoside were reported for the first time from the genus Morina. ConclusionThe findings of the present investigation clearly show that the plant M. coulteriana Royle has a strong antimutagenic potential. Its administration decreased the mutagenic load on the cells both in vitro and in vivo experiments Thus the present study provides a platform for the exploration of new plants with potential antimutagenic properties.

Gene-Directed In Vitro Mining Uncovers the Insect-Repellent Constituent from Mugwort (Artemisia argyi).

Plants contain a vast array of natural products yet to be discovered, particularly those minor bioactive constituents. Identification of these constituents requires a significant amount of plant material, presenting considerable technical challenges. Mugwort (Artemisia argyi) is a widely recognized insect repellent herb, particularly renowned for its extensive usage during the Dragon Boat Festival in China, but the specific constituent responsible for its repellent activity remains unknown. Here, we employed a gene-directed in vitro mining approach to characterize mugwort terpene synthases (TPSs) systematically in a yeast expression system. Based on the establishment of "Terpene synthase-standard library", we have successfully identified 54 terpene products, including a novel compound designated as cyclosantalol. Through activity screening, we have identified that (+)-intermedeol, which presents in trace amount in plants, exhibits significant repellent activity against mosquitoes and ticks. After establishing its safety and efficacy, we then achieved its biosynthetic production in a yeast chassis, with an initial yield of 2.34 g/L. The methodology employed in this study not only identified a highly effective, safe, and commercially viable insect repellent derived from mugwort but also holds promise for uncovering and producing other valuable plant natural products in future research endeavors.

UNDERSTANDING THE BENEFITS OF STEVIA REBAUDIANA BERTONI FOR DIABETES: A COMPREHENSIVE REVIEW

Diabetes Mellitus (DM) is a complicated metabolic condition defined by long-term elevated blood glucose levels. This chronic hyperglycemia induces metabolic dysfunctions that cause structural and functional disruptions in the vasculature, leading to macrovascular and microvascular complications. Stevia rebaudiana Bertoni, commonly known as Stevia, is a perennial shrub that contains various bioactive constituents responsible for its sweetness and several other activities. Many studies on Stevia have shown that it possesses various beneficial effects on health, including being zero-calorie, anti-obesity, anti-diabetic, anti-hypertensive, antioxidant, antimicrobial and anti-tumor. Several studies have found that neither gastric juice nor digestive enzymes decompose stevioside. The presence of bioactive phenolic and flavonoid compounds supports Stevia's medicinal properties and its potential use in both the food/nutraceutical and pharmaceutical industries. A significant antioxidant capacity of Stevia has been identified recently. It can also help limit essential nutrient supply to tumor cells. Research on Stevia's effects on the human body has largely found no negative side effects. The growing body of evidence underscores Stevia's potential role in managing various health conditions, particularly for diabetic patients, due to its minimal impact on blood sugar levels. However, to fully harness its benefits and meet the increasing global demand, further scientific research is essential to optimize its cultivation, enhance its chemical constituents and ensure its safety. Overall, Stevia stands out as a promising natural sweetener with significant health benefits for diabetic patients. In this review article, we explore different aspects of Stevia and its beneficial effects on diabetic patients.

Screening and Analysis of Skin Cancer Treatment Using Biocomponents of Plants Using Backpropagation Neural Networks: A Comprehensive Review

: In recent years, the use of natural compounds derived from plants for the treatment of skin cancer has gained significant attention due to their potential therapeutic effects and minimal side effects. This review focuses on the innovative approach of utilizing biocomponents sourced from plants in combination with backpropagation neural networks (BPNN) for the screening and analysis of skin cancer treatments. The integration of plant-derived compounds and AI-driven algorithms holds promise for enhancing the precision and effectiveness of skin cancer therapies. The review begins by highlighting the escalating global burden of skin cancer and the limitations of conventional treatment approaches. With the rise in concerns about the adverse effects of synthetic drugs, researchers have turned their attention towards exploring the therapeutic potential of plant-derived biocomponents. These natural compounds are known for their rich bioactive constituents that exhibit anti-cancer properties, making them suitable candidates for skin cancer treatment. One of the key challenges in harnessing the potential of plant-derived compounds is the need for accurate screening and analysis of their effects. This is where backpropagation neural networks, a type of artificial neural network, comes into play. These networks can process complex data and recognize intricate patterns, enabling them to predict the efficacy of various biocomponents in combating skin cancer. The review delves into the functioning of BPNN and its applications in drug discovery and treatment evaluation. Furthermore, the review explores several case studies that demonstrate the successful integration of plant-derived compounds with BPNN in the context of skin cancer treatment. These studies provide evidence of how this synergistic approach can lead to improved treatment outcomes by minimizing adverse effects and maximizing therapeutic benefits. The methodology section discusses the steps involved in training the neural network using relevant datasets and optimizing its performance for accurate predictions. While the integration of plant-derived compounds and BPNN shows great promise, the review also addresses the existing challenges and limitations. These include the need for comprehensive and standardized datasets, potential biases in training data, and the complexity of neural network architectures. The regulatory considerations surrounding plant-based therapies are also discussed, highlighting the importance of rigorous testing and validation.

Xylopia parviflora (A. rich.) benth. Mitigates anxiety behavior and chronic mild stress-induced depression-like behavior in mice: The involvement of biogenic amine neurotransmitters, cyclooxygenase-2 and stress biomarkers in its antidepressant activity

BackgroundXylopia parviflora is a novel botanical in Modern Chinese Medicine that contains bioactive constituents including alkaloids, flavonoids, and terpenoids, which are the pharmacologically active components in various Chinese herbal formulations such as Coptis chinensis (alkaloid-rich herbs), Ginkgo biloba (flavonoid-rich herbs) and Artemisia annua (terpenoid-rich herbs). ObjectiveThis investigation sought to evaluate the anxiolytic and antidepressant-like effects of the hydroethanol leaf extract of Xylopia parviflora using mouse models. We elucidated the roles of noradrenaline, serotonin, cyclooxygenase-2, and reactive oxidative species in mediating its antidepressant effects, providing a fresh perspective on the pharmacological activity of Xylopia parviflora. MethodsThe acute toxicity of XPE was assessed following OECD guideline 420. Established behavioral tests were used to evaluate the anxiolytic (including the hole-board, open field, elevated plus maze, and light/dark exploration assessments) and antidepressant (encompassing the forced swim and tail suspension tests) effects of the extract. Mice received treatments of distilled water (10 mL/kg, serving as the negative control), fluoxetine (20 mg/kg, acting as the reference medication), and XPE (at doses of 50, 100, and 200 mg/kg). The concentrations of noradrenaline, serotonin, and COX-2 within the brain tissue were quantified using ELISA kits. The levels of antioxidant biomarkers were evaluated using standardized commercial assay kits. ResultsThe oral/intraperitoneal LD50 for the extract was established at 2000 mg/kg. In the behavioral assessments designed to measure anxiolytic effects, XPE significantly mitigated anxiety levels in mice, as evidenced by an increase in exploratory behaviors (including head dips, sectional crossings, general square crossings, rearing, and assisted rearing) and an increased time spent in the brightly illuminated compartments. Concerning the antidepressant evaluations, XPE significantly reduced depression-like behaviors in mice, which was indicated by an increased latency to immobility and a decrease in the duration of immobility. XPE was found to modulate noradrenaline and serotonin transmissions, attenuate oxidative species, and inhibit COX-2 activity. ConclusionThe findings above demonstrate that Xylopia parviflora possesses anxiolytic and antidepressant-like activities. The antidepressant property of XPE, as revealed in this study, may be attributable to the enhancement of biogenic amines (specifically noradrenaline and serotonin), the suppression of oxidative species, and the inhibition of COX-2 activity.

Modulating the anti-inflammatory and barrier protective effects on intestinal epithelial cells utilizing an aqueous Aspalathus linearis extract in vitro

BackgroundRooibos is a natural herbal plant containing numerous unique polyphenols which have been associated with certain health benefits. Several of these bioactive constituents have been linked to promoting gut health through its beneficial actions such as anti-inflammatory and anti-spasmodic characteristics. PurposeThe study aims to compare the anti-inflammatory and barrier protective effects of an unfermented and fermented rooibos aqueous extract on intestinal porcine epithelial cells (IPEC-J2). MethodsAqueous extracts of unfermented and fermented rooibos were prepared, and chemical and antioxidant analysis were performed of each extract. Intestinal porcine epithelial cells (IPEC-J2) were pre-treated with either unfermented or fermented aqueous rooibos extracts (0.1 and 0.05 mg/ml) then exposed to 10 µg/ml of Escherichia coli lipopolysaccharide (LPS). Cell viability, protein and gene expression of pro-inflammatory cytokines were investigated to determine the anti-inflammatory effect of both extracts. Barrier integrity of IPEC-J2 was investigated by measuring the Transepithelial electrical resistance (TEER) and quantifying tight junction gene expression. ResultsBoth the unfermented and fermented rooibos extracts have significant anti-inflammatory properties by reducing pro-inflammatory cytokine production. Interestingly for certain genes (IL-8, IL-6, IL-1B and CCL20) the fermented extracts, specifically at 0.1 mg/ml, exhibited greater effectiveness by decreasing the expression after LPS-induced inflammation whilst for another gene (TNF-α) the unfermented extract at both concentrations was more efficient in decreasing expression and ultimately protecting the IPEC-J2 cells from inflammation. When evaluating the barrier integrity, 0.1 mg/ml of the unfermented rooibos extract showed the most significant barrier protective effects through upregulation of tight junction proteins, ZO-1, Occludin as well as Claudin-4. ConclusionHigher concentration of the fermented rooibos extract prevented the inflammatory response significantly whilst the higher concentration of the unfermented rooibos extract enhanced tight junction expression and protected barrier integrity in LPS-induced inflamed intestinal cells. This is attributed to the differences in the polyphenol content of each extract and demonstrating the unique activity mechanisms of different rooibos extracts to reduce onset of early inflammation.

Ethnobotany, Phytochemistry, and Pharmacological Activity of Dioscorea bulbifera: A Comprehensive Review.

Dioscorea bulbifera (Family: Dioscoreaceae) also referred to as 'Air potato,' carries significant importance in the traditional medicine of China, West Africa and India. It is a common ingredient in numerous herbals and Ayurvedic formulations used to treat a variety of ailments. The literature review extensively examined the historical usage, phytoconstituents, characterisation of phytoconstituents, and medicinal uses of tubers, leaves, rhizomes and bulbils, with a particular focus on comparing research findings. Among the bioactive constituents, aglycone forms of steroidal saponins such as dioscorine, dioscin, diosbulbins, and diosgenin exhibit significant biological activities. Extracts from different parts of the plant exhibited pharmacological activities like anti-viral, anti-malarial, analgesic, antidiabetic, and anticancer. It is necessary to conduct an in-depth investigation to bridge between traditional knowledge and scientific evidence. This comprehensive review aims to provide a detailed understanding of the ethnobotany, phytoconstituent, chemical characterization and pharmacological potential of D. bulbifera, highlighting its prospects and challenges for future research and medicinal application.

Roseoside Is a Bioactive Compound in Kirengeshoma koreana Nakai Extract with Potent In Vitro Antiviral Activity Against Hepatitis C Virus.

Hepatitis C virus (HCV) is a pathogen that causes cirrhosis and hepatocellular carcinoma through chronic hepatitis C. This study focused on the anti-HCV activity of a 70% ethanol extract of Kirengeshoma koreana Nakai (KKE) and its bioactive chemical constituent(s). The KKE and its n-butanol (n-BuOH) fraction induced a significant reduction in HCV RNA levels without inducing cytotoxicity. A high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis revealed the presence of roseoside in the n-butanol fraction of the KKE, which inhibited HCV RNA replication in a concentration- and time-dependent manner without exerting cytotoxicity. Consistent with in silico molecular docking analysis data, roseoside targets and inhibits HCV NS5A/B replicase. Collectively, our findings demonstrate that roseoside is a chemical constituent in KKE that interferes with HCV replication by targeting NS5A/B replicase.

Mechanistic exploration of bioactive constituents in Gnetum gnemon for GPCR-related cancer treatment through network pharmacology and molecular docking

G Protein-Coupled Receptors (GPCRs) are integral membrane proteins that have gained considerable attention as drug targets, particularly in cancer treatment. In this study, we explored the capacity of bioactive compounds derived from Gnetum gnemon (GG) for the development of of pharmaceuticals targeting GPCRs within the context of cancer therapy. Integrated approach combined network pharmacology and molecular docking to identify and validate the underlying pharmacological mechanisms. We retrieved targets for GG-derived compounds and GPCRs-related cancer from databases. Subsequently, we established a protein-protein interaction (PPI) network by mapping the shared targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to predict the mechanism of action of these targets. Molecular docking was conducted to validate our findings. We identified a total of 265 targets associated with GG-derived bioactive compounds for the treatment of GPCRs-related cancer. Functional enrichment analysis revealed the promising therapeutic effects of these targets on GPCRs-related cancer pathways. The PPI network analysis identified hub targets, including MAPK3, SRC, EGFR, STAT3, ESR1, MTOR, CCND1, and PPARG, which demonstrate as treatment targets for GPCRs-related cancer using GG-derived compounds. Additionally, molecular docking experiments demonstrated the strong binding affinity of gnetin A, gnetin C, (-)-viniferin, and resveratrol dimer, thus inhibiting MAPK3, SRC, EGFR, and MTOR. Survival analysis established the clinical prognostic relevance of identified hub genes in cancer. This study presents a novel approach for comprehending the therapeutic mechanisms of GG-derived active compounds and thereby paving the way for their prospective clinical applications in the field of cancer treatment.

COMPARATIVE STUDY OF BIOACTIVE COMPOUNDS IN MILK THISTLE SEED VARIETIES IN SULAIMANI, IRAQ

This study was conducted using two different varieties of milk thistle, var. marianum, and var. albiflorum. The plant samples were collected from the Sulaimani region to determine silymarin content, bioactive constituents, and antioxidant activity. HPLC analysis showed that var. marianum contains a high amount of silymarin (365.680±3.815 mg/g). Silybin B, Silychristin A, and Silybin A were the major flavonolignans in these varieties—the var. marianum contains silybins B, silychristin A, and silybin A (174.880±6.495, 86.720±2.113, and 54.960±2.483 mg/g) respectively. The hexane extract analysis of milk thistle seeds of the marianum and albiflorum varieties identified 26 (95.229±1.318) and 19 (94.547±6.541) phytochemical compounds, respectively. Both varieties contain a higher amount of oleic acid, which was found to be 14.800±0.481 and 31.940±0.726 in both varieties, respectively. This study evaluates the scavenging effect of milk thistle plants using a DPPH assay. The result indicated that the var. marianum had a maximum scavenging effect of 72.944% compared to the var. albiflorum, (61.846%). The stronger IC50 was obtained by var. marianum with 17.027±0.064 µg/mL.

Bioactive constituents and action mechanism of Xiaoyao San for treatment of non-alcoholic fatty liver disease.

Xiaoyao San (XYS) is a classic Chinese medicine prescription. It is traditionally used to relieve syndrome of "liver stagnation and spleen deficiency", a common syndrome type in traditional Chinese medicine, through soothing liver, tonifying spleen, and nourishing blood. Correspondingly, XYS has long application in the treatment of depression, dyspepsia and liver diseases. Given the rising of cutting-edge researches on XYS, there's a significant need to diligently uncover the bioactive constituents and action mechanisms of XYS for treating non-alcoholic fatty liver disease accordingly.

Mitochondrial resilience and antioxidant defence against HIV-1: unveiling the power of Asparagus racemosus extracts and Shatavarin IV.

Asparagus racemosus (AR), an Ayurvedic botanical, possesses various biological characteristics, yet its impact on HIV-1 replication remains to be elucidated. This study aimed to investigate the inhibitory effects of AR root extracts and its principal bioactive molecule, Shatavarin IV (Shatavarin), on HIV-1 replication and their role in mitigating mitochondrial dysfunction during HIV-1 infection, utilizing both in vitro and in silico methodologies. The cytotoxicity of the extracts was evaluated using MTT and ATPlite assays. In vitro anti-HIV-1 activity was assessed in TZM-bl cells against X4 and R5 subtypes, and confirmed in peripheral blood mononuclear cells using HIV-1 p24 antigen capture ELISA and viral copy number assessment. Mechanistic insights were obtained through enzymatic assays targeting HIV-1 Integrase, Protease and Reverse Transcriptase. Shatavarin's activity was also validated via viral copy number and p24 antigen capture assays, along with molecular interaction studies against key HIV-1 replication enzymes. HIV-1 induced mitochondrial dysfunction was evaluated by detecting mitochondrial reactive oxygen species (ROS), calcium accumulation, mitochondrial potential, and caspase activity within the infected cells. Non-cytotoxic concentrations of both aqueous and hydroalcoholic extracts derived from Asparagus racemosus roots displayed dose-dependent inhibition of HIV-1 replication. Notably, the hydroalcoholic extract exhibited superior Reverse Transcriptase activity, complemented by moderate activity observed in the Protease assay. Molecular interaction studies revealed that Shatavarin IV, the key bioactive constituent of AR, formed hydrogen bonds within the active binding pocket site residues crucial for HIV replication enzyme catalysis, suggesting its potential in attenuating HIV-1 infection. Mitochondrial dysfunction induced by HIV-1 infection, marked by increased oxidative stress, mitochondrial calcium overload, loss of mitochondrial membrane potential, and elevated caspase activity, was effectively mitigated by treatment with AR extracts and Shatavarin IV. These findings underscore the potential of AR extracts and Shatavarin IV as antiviral agents, while enhancing mitochondrial function during HIV-1 infection. In conclusion, Asparagus racemosus extracts, particularly Shatavarin IV, demonstrate promising inhibitory effects against HIV-1 replication while concurrently ameliorating mitochondrial dysfunction induced by the virus. These findings suggest the therapeutic potential of AR extracts and Shatavarin in combating HIV-1 infection and improving mitochondrial health.