Interplay of precision therapeutics and MD study: Calocybe indica's potentials against cervical cancer and its interaction with VEGF via octadecanoic acid.

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision-driven approaches. Embracing this paradigm, our research probes the therapeutic efficacy of the aqueous crude extract (ACE) of Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis and showcasing prebiotic attributes. Characterization of ACE have identified several phytochemicals including significant presence of octadeconoic acid. Simultaneously, utilizing advanced Molecular Dynamics (MD) simulations, we deciphered the intricate molecular interactions between Vascular Endothelial Growth Factor (VEGF) and Octadecanoic acid to establish C.indica's role as an anticancer agent. Our study delineates Octadecanoic acid's potential as a robust binding partner for VEGF, with comprehensive analyses from RMSD and RMSF profiles highlighting the stability and adaptability of the protein-ligand interactions. Further in-depth thermodynamic explorations via MM-GBSA calculations reveal the binding landscape of the VEGF-Octadecanoic acid complex. Emerging therapeutic innovations, encompassing proteolysis-targeting chimeras (PROTACs) and avant-garde nanocarriers, are discussed in the context of their synergy with compounds like Calocybe indica P&C. This convergence underscores the profound therapeutic potential awaiting clinical exploration. This study offers a holistic perspective on the promising therapeutic avenues facilitated by C. indica against cervical cancer, intricately woven with advanced molecular interactions and the prospective integration of precision therapeutics in modern oncology.

Fatty acids characterisation by GC-MS, antiglycation effect at multiple stages and protection of erythrocytes cells from oxidative damage induced by glycation of albumin of Opuntia ficus-indica (L.) Mill seed oil cultivated in Eastern Morocco: Experimental and computational approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia ficus-indica (L.) Mill is frequently observed in the Moroccan traditional medicinal system, where these approaches are employed to mitigate the onset of diabetes and the subsequent complications it may entail. AIM OF THE STUDY: The aim of this research was to examine the effectiveness of Opuntia ficus-indica seed oil in preventing diabetic complications. Specifically, the study assessed its ability to counteract glycation at various stages, protected red blood cells from the harmful effects of glycated albumin, and inhibited pancreatic lipase digestive enzymes to understand its potential antihyperglycemic properties. Additionally, the study aimed to identify the chemical components responsible for these effects, evaluate antioxidant and anti-inflammatory properties, and conduct computational investigations such as molecular docking. MATERIALS AND METHODS: The assessement of Opuntia ficus-indica seed oil antiglycation properties involved co-incubating the extract oil with a bovine serum albumin-glucose glycation model. The study investigated various stages of glycation, incorporating fructosamine (inceptive stage), protein carbonyls (intermediate stage), and AGEs (late stage). Additionally, measurement of ß-amyloid aggregation of albumin was performed using Congo red, which is specific to amyloid structures. Additionally, the evaluation of oil's safeguarding effect on erythrocytes against toxicity induced by glycated albumin included the measurement of erythrocyte hemolysis, lipid peroxidation, reduced glutathione. The fatty acid of Opuntia ficus-indica seed oil were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). The in vitro evaluation of antihyperglycemic activity involved the use of pancreatic lipase enzyme, while the assessement of antioxidant capability was carried out through the utilization of the ABTS and FRAP methods. The in vitro assessement of the denaturation of albumin activity was also conducted. In conjunction with the experimental outcomes, computational investigations were undertaken, specifically employing ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. Furthermore, molecular docking was utilized to predict antioxidant and antiglycation mechanisms based on protein targets. RESULTS: In vitro glycation assays, Opuntia ficus-indica seed oil displayed targeted inhibitory effects at multiple distinct stages. Within erythrocytes, in addition to mitigating hemolysis and lipid peroxidation induced by glycated albumin. GC-MS investigation revealed a richness of fatty acids and the most abundant compounds are Linoleic acid (36.59%), Palmitic acid (20.84%) and Oleic acid (19.33%) respectively. The findings of antioxidant ability showed a remarkable activity on FRAP and ABTS radicals. This oil showed a pronounced inhibitory impact (p < 0.001) on pancreatic lipase enzyme. It also exerted a notibale inhibition of albumin denaturation, in vitro. CONCLUSION: The identified results were supported by the abundant compounds of fatty acids unveiled through GC-MS analysis, along with the computational investigation and molecular docking.

Identification and characterization of silver nanoparticles from Erythrina indica and its antioxidant and Uropathogenic antimicrobial properties.

The plant Erythrina indica comes under Fabaceae family, mainly used for used in traditional medicine as nervine sedative, antiepileptic, antiasthmatic, collyrium in opthalmia, antiseptic. Current study focused synthesize of silver nanoparticles (AgNPs) by E. indica leaf ethanol extract. The green-synthesized AgNPs underwent characterization using multiple analytical techniques, including UV-visible, FTIR, DLS, SEM, TEM, XRD, and EDX, and estimation of their antioxidant activity and antimicrobial activity. Phytochemical analysis identified alkaloids, tannins, saponins, flavonoids, and phenols as secondary metabolites. The Total Phenol Content (TPC) was determined to be 237.35 ± 2.02 mg GAE-1, indicating a substantial presence of phenolic compounds. The presence of AgNPs was verified through UV-Visible analysis at 420 nm, and FT-IR revealed characteristic phenolic functional groups. DLS analysis indicated a narrow size distribution (polydispersity index - PDI: 3.47%), with SEM revealing spherical AgNPs of approximately 20 nm. TEM showed homogeneous, highly polycrystalline AgNPs with lattice spacing at 0.297. XRD analysis demonstrated crystallinity and purity, with distinct reflection peaks corresponding to miller indices of JCPDS card no. 01 087 1473. In vitro, AgNPs exhibited robust antioxidant activity like; DPPH, ABTS, and H2O2, surpassing E. indica-assisted synthesis. ABTS assay indicated higher antioxidant activity (81.94 ± 0.05%) for AgNPs at 734 nm, while E. indica extraction showed 39.67 ± 0.07%. At 532 nm, both E. indica extraction (57.71 ± 0.11%) and AgNPs (37.41 ± 0.17%) exhibited H2O2 scavenging. Furthermore, AgNPs displayed significant antimicrobial properties, inhibiting Staphylococcus aureus (15.7 ± 0.12 mm) and Candida albicans (10.7 ± 0.17 mm) byfor the concentration of 80 µg/mL. Through the characterizations underscore of the potential of Erythrina indica-synthesized AgNPs, rich in polyphenolic compounds, for pharmacological, medical, biological applications and antipyretic properties.

Nimbolide: promising agent for prevention and treatment of chronic diseases (recent update).

Background: Nimbolide, a bioactive compound derived from the neem tree, has garnered attention as a potential breakthrough in the prevention and treatment of chronic diseases. Recent updates in research highlight its multifaceted pharmacological properties, demonstrating anti-inflammatory, antioxidant, and anticancer effects. With a rich history in traditional medicine, nimbolide efficacy in addressing the molecular complexities of conditions such as cardiovascular diseases, diabetes, and cancer positions it as a promising candidate for further exploration. As studies progress, the recent update underscores the growing optimism surrounding nimbolide as a valuable tool in the ongoing pursuit of innovative therapeutic strategies for chronic diseases. Methods: The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus and Web of Knowledge databases. Results: Most studies have shown the Nimbolide is one of the most potent limonoids derived from the flowers and leaves of neem (Azadirachta indica), which is widely used to treat a variety of human diseases. In chronic diseases, nimbolide reported to modulate the key signaling pathways, such as Mitogen-activated protein kinases (MAPKs), Wingless-related integration site-ß (Wnt-ß)/catenin, NF-κB, PI3K/AKT, and signaling molecules, such as transforming growth factor (TGF-ß), Matrix metalloproteinases (MMPs), Vascular Endothelial Growth Factor (VEGF), inflammatory cytokines, and epithelial-mesenchymal transition (EMT) proteins. Nimbolide has anti-inflammatory, anti-microbial, and anti-cancer properties, which make it an intriguing compound for research. Nimbolide demonstrated therapeutic potential for osteoarthritis, rheumatoid arthritis, cardiovascular, inflammation and cancer. Conclusion: The current review mainly focused on understanding the molecular mechanisms underlying the therapecutic effects of nimbolide in chronic diseases.

Anthelmintic screening of Bangladeshi medicinal plants and related phytochemicals using in vitro and in silico methods: An ethnobotanical perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Infections caused by parasitic worms or helminth continue to pose a great burden on human and animal health, particularly in underdeveloped tropical and subtropical countries where they are endemic. Current anthelmintic drugs present serious limitations and the emergence of drug resistance has made it increasingly challenging to combat such infections (helminthiases). In Bangladesh, medicinal plants are often used by indigenous communities for the treatment of helminthiases. Knowledge on such plants along with screening for their anthelmintic activity has the potential to lead to the discovery of phytochemicals that could serve as novel molecular scaffolds for the development of new anthelminthic drugs. AIM OF THE STUDY: The purpose of this study was i) to conduct an ethnobotanical survey to gather data on Bangladeshi medicinal plants used in the treatment of helminthiases, ii) to test plants with the highest use values for their in vitro anthelmintic activity, and iii) to carry out in silico screening on phytochemicals present in the most active plant extract to investigate their ability to disrupt ß-tubulin function in helminths. METHODS: The ethnobotanical survey was conducted across three sub-districts of Bangladesh, namely Mathbaria, Phultala and Khan Jahan Ali. The in vitro screening for anthelmintic activity was performed in a motility test using adult Haemonchus contortus worms. Virtual screening using PyRx was performed on the phytochemicals reported from the most active plant, exploring their interactions with the colchicine binding site of the ß-tubulin protein target (PDB ID: 1SA0). RESULTS: The survey respondents reported a total of 32 plants for treating helminthiases. Based on their use values, the most popular choices were Ananas comosus (L.) Merr., Azadirachta indica A.Juss., Carica papaya L., Citrus maxima (Burm.) Merr., Curcuma longa L., Momordica charantia L., Nigella sativa L. and Syzygium cumini (L.) Skeels. In vitro anthelmintic testing revealed that A. indica leaves and bark had the highest activity with LC50 values of 16 mg/mL in both cases. Other plant extracts also exhibited good anthelmintic activity with LC50 values ranging from 16 to 52 mg/mL, while the value for albendazole (positive control) was 8.39 mg/mL. The limonoids nimbolide and 28-deoxonimbolide showed a binding affinity of -8.9 kcal/mol, and satisfied all drug-likeness parameters. The control ligand N-deacetyl-N-(2-mercaptoacetyl)colchicine had a binding affinity of -6.9 kcal/mol. CONCLUSION: Further in silico and in vitro studies are warranted on the identified limonoids to confirm the potential of these derivatives as novel drug templates for helminthiases. The current study supports the need for an ethnobotanical survey-based approach to discover novel drug templates for helminthiases.

Acalypha indica induced acute oxidative haemolysis and methaemoglobinaemia: two case reports.

BACKGROUND: Herbal products and traditional remedies are commonly used by individuals worldwide for the management of common ailments, even though most are not without risks. Acalypha indica is a popular medicinal plant consumed in some Asian countries. CASE PRESENTATION: This case report presents a 40-year-old previously unevaluated Sri Lankan female and her 8-year-old son who presented with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency related acute intravascular oxidative haemolysis and methaemoglobinaemia precipitated by Acalypha indica consumption, successfully managed with supportive care and blood transfusion. CONCLUSIONS: This case highlights the potential hemolytic and methaemoglobinaemic effects of ingesting oxidant herbal products and the importance of considering such exposures in patients presenting with hemolysis and multiorgan involvement, particularly in communities where herbal product intake is popular. Healthcare providers should be aware of the risks associated with traditional remedies and maintain a high index of suspicion to ensure prompt recognition and appropriate management.

Genomic and transcriptomic studies on flavonoid biosynthesis in Lagerstroemia indica.

BACKGROUND: Lagerstroemia indica is a widely cultivated ornamental woody shrub/tree of the family Lythraceae that is used as a traditional medicinal plant in East Asia and Egypt. However, unlike other ornamental woody plants, its genome is not well-investigated, which hindered the discovery of the key genes that regulate important traits and the synthesis of bioactive compounds. RESULTS: In this study, the genomic sequences of L. indica were determined using several next-generation sequencing technologies. Altogether, 324.01 Mb sequences were assembled and 98.21% (318.21 Mb) of them were placed in 24 pseudo-chromosomes. The heterozygosity, repeated sequences, and GC residues occupied 1.65%, 29.17%, and 38.64% of the genome, respectively. In addition, 28,811 protein-coding gene models, 327 miRNAs, 552 tRNAs, 214 rRNAs, and 607 snRNAs were identified. The intra- and interspecies synteny and Ks analysis revealed that L. indica exhibits a hexaploidy. The co-expression profiles of the genes involved in the phenylpropanoid (PA) and flavonoid/anthocyanin (ABGs) pathways with the R2R3 MYB genes (137 members) showed that ten R2R3 MYB genes positively regulate flavonoid/anthocyanin biosynthesis. The colors of flowers with white, purple (PB), and deep purplish pink (DPB) petals were found to be determined by the levels of delphinidin-based (Dp) derivatives. However, the substrate specificities of LiDFR and LiOMT probably resulted in the different compositions of flavonoid/anthocyanin. In L. indica, two LiTTG1s (LiTTG1-1 and LiTTG1-2) were found to be the homologs of AtTTG1 (WD40). LiTTG1-1 was found to repress anthocyanin biosynthesis using the tobacco transient transfection assay. CONCLUSIONS: This study showed that the ancestor L. indica experienced genome triplication approximately 38.5 million years ago and that LiTTG1-1 represses anthocyanin biosynthesis. Furthermore, several genes such as LiDFR, LiOMTs, and R2R3 LiMYBs are related to anthocyanin biosynthesis. Further studies are required to clarify the mechanisms and alleles responsible for flower color development.

Untargeted metabolomics-based identification of bioactive compounds from Mangifera indica L. seed extracts in drug discovery through molecular docking and assessment of their anticancer potential.

BACKGROUND: Mangifera indica L. (mango), a medicinal plant rich in biologically active compounds, has potential to be used in disease-preventing and health-promoting products. The present investigation reveals and uncovers bioactive metabolites with remarkable therapeutic efficiency from mango (family: Anacardiaceae) seeds. RESULTS: Biological activity was determined by antimicrobial, antioxidant and anticancer assays, and metabolite profiling was performed on gas chromatography coupled to quadrupole time-of-flight mass spectrometry (GC-QTOF-MS) and liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) platforms. Validation of active metabolites was carried out by in silico molecular docking (Molinspiration Cheminformatics Server and PASS). Extracted and identified metabolites were screened; 54 compounds associated with various groups were selected for the in silico interaction study. CONCLUSIONS: Molecular docking revealed lead molecules with a potential binding energy score, efficacy and stable modulation with a selected protein domain. Investigation, directed by in vitro and in silico analysis, confirms mango seeds as an excellent source of potential metabolites as a therapeutic agent. © 2024 Society of Chemical Industry.

Alternative first-line malaria treatment.

Malaria is a disease affecting millions of people, especially in Africa, Asia, and South America, and has become a substantial economic burden. Because malaria is contracted through the bite of a mosquito vector, it is very challenging to prevent. Bed nets and insect repellents are used in some homes; others do not have or use them even when available. Thus, treatment measures are crucial to controlling this disease. Artemisinin-based combination therapy (ACT) is currently the first-line treatment for malaria. ACT has been used for decades, but recently, there has been evidence of potential resistance. This threat of resistance has led to the search for possible alternatives to ACT. In sub-Saharan Africa, Azadirachta indica, or simply neem, is a plant used to treat a variety of ailments, including malaria. Neem is effective against one of the more deadly malaria parasites Plasmodium falciparum. Reports show that neem inhibits microgametogenesis of P. falciparum and interferes with the parasite's ookinete development. Although there is substantial in vitro research on the biological activity of A. indica (neem), there is limited in vivo research. Herein, we discuss the in vivo effects of neem on malaria parasites. With A. indica, the future of malaria treatment is promising, especially for high-risk patients, but further research and clinical trials are required to confirm its biological activity.

Résumé Le paludisme est une maladie qui touche des millions de personnes, notamment en Afrique, en Asie et en Amérique du Sud, et est devenu un problème économique majeur fardeau. Le paludisme étant contracté par la piqûre d'un moustique vecteur, il est très difficile à prévenir. Moustiquaires et insectifuges sont utilisés dans certaines maisons ; d'autres ne les possèdent pas ou ne les utilisent pas même lorsqu'ils sont disponibles. Les mesures thérapeutiques sont donc cruciales pour contrôler cette maladie. La thérapie combinée à base d'artémisinine (ACT) constitue actuellement le traitement de première intention contre le paludisme. L'ACT est utilisé depuis des décennies, mais récemment, il y a eu des preuves d'une résistance potentielle. Cette menace de résistance a conduit à la recherche d'alternatives possibles à l'ACT. En Afrique subsaharienne, Azadirachta indica, ou simplement neem, est une plante utilisée pour traiter diverses maladies, dont le paludisme. Le Neem est efficace contre l'un des des parasites du paludisme plus mortels, Plasmodium falciparum. Des rapports montrent que le neem inhibe la microgamétogenèse de P. falciparum et interfere avec le développement de l'ookinète du parasite. Bien qu'il existe d'importantes recherches in vitro sur l'activité biologique d'A. indica (neem), il existe la recherche in vivo est limitée. Nous discutons ici des effets in vivo du neem sur les parasites du paludisme. Avec A. indica, l'avenir du traitement du paludisme est prometteur, en particulier pour les patients à haut risque, mais des recherches et des essais cliniques supplémentaires sont nécessaires pour confirmer son activité biologique. Mots-clés: Azadirachta indica, paludisme, neem, Plasmodium falciparum.

Eco-friendly Synthesis of Azadirachta indica-based Metallic Nanoparticles for Biomedical Application & Future Prospective.

The process of producing the metallic nanoparticles (MNPs) in a sustainable and environment- friendly process is very desirable due to environmental hazards posed by climatic changes. Biomedical one of the fields classified under nanoscience, nanoparticles have a potential synthetic application, which makes it a vast area of research. These particles can be prepared using chemical, physical, and biological methods. One of the methods of synthesis of nanoparticles is by the use of plant extracts, known as green synthesis. Because of its low cost and nontoxicity, it has gained attention in recent times. This review was conducted to find the possible outcomes and uses of metallic nanoparticles synthesized using different parts like gum, root, stem, leaf, fruits, etc. of Azadirachta indica (AI). AI, a popular medicinal plant commonly known as neem, has been studied for the green synthesis of NPs by using the capping and reducing agents secreted by the plant. Various phytochemicals identified in neem are capable of metal ion reduction. Green synthesis of NPs from neem is an eco-friendly and low-cost method. These NPs are reported to exhibit good antimicrobial activity. The review covers the preparation, characterization, and mechanism associated with the antibacterial, anticancer, and neurological diseases of the MNPs. Furthermore, the limitations associated with the existing NPs and the prospects of these NPs are also examined.

Mango Peels as an Industrial By-Product: A Sustainable Source of Compounds with Antioxidant, Enzymatic, and Antimicrobial Activity.

Plant waste materials are important sources of bioactive compounds with remarkable health-promoting benefits. In particular, industrial by-products such as mango peels are sustainable sources of bioactive substances, with antioxidant, enzymatic, and antimicrobial activity. Appropriate processing is essential to obtain highly bioactive compounds for further use in generating value-added products for the food industry. The objective of the study was to investigate and compare the biological activity of compounds from fresh and dried mango peels obtained by different conventional methods and unconventional extraction methods using supercritical fluids (SFE). The highest total phenolic content (25.0 mg GAE/g DW) and the total content of eight phenolic compounds (829.92 µg/g DW) determined by LC-MS/MS were detected in dried mango peel extract obtained by the Soxhlet process (SE). SFE gave the highest content of proanthocyanidins (0.4 mg PAC/g DW). The ethanolic ultrasonic process (UAE) provided the highest antioxidant activity of the product (82.4%) using DPPH radical scavenging activity and total protein content (2.95 mg protein/g DW). Overall, the dried mango peels were richer in bioactive compounds (caffeic acid, chlorogenic acid, gallic acid, catechin, and hesperidin/neohesperidin), indicating successful preservation during air drying. Furthermore, outstanding polyphenol oxidase, superoxide dismutase (SOD), and lipase activities were detected in mango peel extracts. This is the first study in which remarkable antibacterial activities against the growth of Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) were evaluated by determining the microbial growth inhibition rate after 12 and 24 h incubation periods for mango peel extracts obtained by different methods. Ethanolic SE and UAE extracts from dried mango peels resulted in the lowest minimum inhibitory concentrations (MIC90) for all bacterial species tested. Mango peels are remarkable waste products that could contribute to the sustainable development of exceptional products with high-added value for various applications, especially as dietary supplements.

Azadirachta indica (AI)leaf extract coated ZnO-AInanocore-shell particles for enhanced antibacterial activity against methicillin-resistantStaphylococcus aureus(MRSA).

With the rise in microbial resistance to traditional antibiotics and disinfectants, there is a pressing need for the development of novel and effective antibacterial agents. Two major approaches being adopted worldwide to overcome antimicrobial resistance are the use of plant leaf extracts and metallic nanoparticles (NPs). However, there are no reports on the antibacterial potential of NPs coated with plant extracts, which may lead to novel ways of treating infections. This study presents an innovative approach to engineer antibacterial NPs by leveraging the inherent antibacterial properties of zinc oxide NPs (ZnO NPs) in combination withAzadirachta indica(AI) leaf extract, resulting in enhanced antibacterial efficacy. ZnO NPs were synthesised by the precipitation method and subsequently coated withAIleaf extract to produce ZnO-AInanocore-shell structures. The structural and morphological characteristics of the bare and leaf extract coated ZnO NPs were analysed by x-ray diffraction and field emission scanning electron microscopy, respectively. The presence of anAIleaf extract coating on ZnO NPs and subsequent formation of ZnO-AInanocore-shell structures was verified through Fourier transform infrared spectroscopy and photoluminescence techniques. The antibacterial efficacy of both ZnO NPs and ZnO-AInanocore-shell particles was evaluated against methicillin-resistantStaphylococcus aureususing a zone of inhibition assay. The results showed an NP concentration-dependent increase in the diameter of the inhibition zone, with ZnO-AInanocore-shell particles exhibiting superior antibacterial properties, owing to the combined effect of ZnO NPs and the poly phenols present inAIleaf extract. These findings suggest that ZnO-AInanocore-shell structures hold promise for the development of novel antibacterial creams and hydrogels for various biomedical applications.

Study of the mechanism underlying the anti-inflammatory effect of Miao medicine comprising raw and processed Radix Wikstroemia indica using the "sweat soaking method".

ETHNOPHARMACOLOGICAL RELEVANCE: To explore the differences in the anti-inflammatory efficacy and mechanisms of the Miao medicine, both raw and after processing, using the "sweat soaking method" of Radix Wikstroemia indica (RWI). AIM OF THE STUDY: The purpose of this study was to explore the differences in the anti-inflammatory efficacy and mechanism of action before and after the processing of the Miao medicine (RWI) using the "sweat soaking method." MATERIALS AND METHODS: Network pharmacology technology was used to construct the "drug-component target-pathway-disease" network, and the main anti-inflammatory pathways of RWI were identified. Rat models of collagen-induced arthritis were established. The changes in body weight, swelling rate of the foot pad and ankle joint, arthritis index, thymus index, spleen index, pathological changes of the ankle joint, and the content of inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-10, TNF-α, and NO) were used as indices to evaluate the effect of RWI on rats with collagen-induced arthritis before and after its processing. Plasma and urine samples were collected from the rats, and the potential biomarkers of, and metabolic pathways underlying the anti-inflammatory effects of RWI before and after processing were identified using 1H-Nuclear magnetic resonance metabolomics combined with a multivariate statistical analysis. RESULTS: Eleven key anti-inflammatory targets of IL6, IL-1ß, TNF, ALB, AKT1, IFNG, INS, STAT3, EGFR, TP53, and SRC were identified by network pharmacology. The PI3K-Akt signaling pathway, steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, tryptophan metabolism, and other pathways were mainly involved in these effects. Pharmacodynamic studies found that both raw and processed RWI products downregulated inflammatory factors in rats with collagen-induced arthritis and alleviated the pathological changes. A total of 41 potential pathways for the anti-inflammatory effects of raw RWI products and 36 potential pathways for the anti-inflammatory effects of processed RWI products were identified by plasma and urine metabolomics. The common pathways of network pharmacology and metabolomics were steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. CONCLUSIONS: The anti-inflammatory effect of RWI was mainly related to the regulation of steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. Finally, the "sweat soaking method" enhanced the anti-inflammatory effect of RWI.

Optimizing the ultrasonic extraction of polyphenols from mango peel and investigating the characteristics, antioxidant activity and storage stability of extract nanocapsules in maltodextrin/whey protein isolate.

In this study, the extraction and nanoencapsulation of mango peel extract (MPE) were investigated to enhance its stability and preserve its antioxidant properties. Initially, using the central composite design (CCD)-response surface methodology (RSM), optimal conditions for the extraction of MPE via an ultrasonic system were determined to be a temperature of 10.53 °C, a time of 34.35 min, and an ethanol concentration of 26.62 %. Subsequently, the extracted extract was spray-dried and nanoencapsulated using three types of coatings: maltodextrin, whey protein isolate (WPI), and their combination. The results showed that nanoencapsulation led to a significant improvement in the stability of phenolic compounds in the extract during storage compared to free extract. Furthermore, capsules prepared with the combined coating exhibited the highest levels of phenolic compounds and antioxidant activity. Therefore, it can be concluded that nanoencapsulation can serve as an effective method for preserving the bioactive properties of MPE.

Elucidating the structural, catalytic, and antibacterial traits of Ficus carica and Azadirachta indica leaf extract-mediated synthesis of the Ag/CuO/rGO nanocomposite.

The present exploration demonstrates the efficient, sustainable, cost-effective, and environment-friendly green approach for the synthesis of silver (Ag)-doped copper oxide (CuO) embedded with reduced graphene oxide (rGO) nanocomposite using the green one-pot method and the green deposition method. Leaf extracts of Ficus carica and Azadirachta indica were used for both methods as reducing and capping agents. The effect of methodology and plant extract was analyzed through different characterization techniques such as UV-visible spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), x-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM). The lowest band gap of 3.0 eV was observed for the Ag/CuO/rGO prepared by the green one-pot method using F. carica. The reduction of graphene oxide (GO) and the formation of metal oxide was confirmed through functional group detection using FT-IR. Calculation of thermodynamic parameters showed that all reactions involved were nonspontaneous and endothermic which shows the stability of nanocomposites. XRD studies revealed the crystallinity, phase purity and small average crystallite size of 32.67 nm. SEM images disclosed that the morphology of the nanocomposites was spherical with agglomeration and rough texture. The particle size of the nanocomposites calculated through HRTEM was found in agreement with the XRD results. The numerous properties of the synthesized nanocomposites enhanced their potential against the degradation of methylene blue, rhodamine B, and ciprofloxacin. The highest percentage degradation of Ag/CuO/rGO was found to be 97%, synthesized using the green one-pot method with F. carica against ciprofloxacin, which might be due to the lowest band gap, delayed electron-hole pair recombination, and large surface area available. The nanocomposites were also tested against the Gram-positive and Gram-negative bacteria. RESEARCH HIGHLIGHTS: Facile synthesis of Ag/CuO/rGO nanocomposite using a green one-pot method and the green deposition method. The lowest band gap of 3.0 eV was observed for nanocomposite prepared by a green one-pot method using Ficus carica. Least average crystallite size of 32.67 nm was found for nanocomposite prepared by a green one-pot method using F. carica. Highest antibacterial and catalytic activity (97%) was obtained against ciprofloxacin with nanocomposite prepared through green one-pot method using F. carica. A mechanism of green synthesis is proposed.

In Vitro Screening and Lipid-Lowering Effect of Prickly Pear (Opuntia Ficus-Indica L. Mill.) Fruit Extracts in 3T3-L1 Pre-Adipocytes and Mature Adipocytes.

Opuntia ficus-indica fruits have been widely used due to their nutritional composition and beneficial effects on health, particularly against chronic diseases such as diabetes, obesity, cardiovascular diseases and cancer, among others. In recent years, prickly pear peel and pulp extracts have been characterised, and a high number of bioactive compounds have been identified. This study aimed to analyse the triglyceride-lowering effect of prickly pear peel and pulp extracts obtained from fruits of three varieties (Pelota, Sanguinos, and Colorada) in 3T3-L1 maturing and mature adipocytes. At a concentration of 50 µg/mL, peel extracts from Colorada reduced triglyceride accumulation in pre-adipocytes and mature adipocytes. Additionally, at 25 µg/mL, Pelota peel extract decreased triglyceride content in mature adipocytes. Moreover, maturing pre-adipocytes treated with 50 and 25 µg/mL of Sanguinos pulp extract showed a reduction of triglyceride accumulation. In addition, the lipid-lowering effect of the main individual betalain and phenolic compounds standards were assayed. Piscidic acid and isorhamnetin glycoside (IG2), found in Colorada peel extract, were identified as the bioactive compounds that could contribute more notably to the triglyceride-lowering effect of the extract. Thus, the betalain and phenolic-rich extracts from Opuntia ficus indica fruits may serve as an effective tool in obesity management.

Phytochemical Analysis and Antioxidant Activity of Endophytic Fungi Isolated from Dillenia indica Linn.

Endophytic fungi live symbiotically inside plants and are hidden source of natural bioactive molecules. The present study was carried out to investigate the phytochemical analysis and antioxidant activity of endophytic fungi isolated from the ethnomedicinal plant Dillenia indica L. The ethyl acetate crude extracts of the endophytic fungal strains were preliminarily evaluated for their phytochemical analysis, and the results showed the presence of alkaloids, flavonoids, phenolics, terpene, and saponins. The crude extracts of more than 60% of the isolates showed 50-90% antioxidant activity by DPPH and H2O2 assay. The inhibition percentage of ethyl acetate extracts ranges from 34.05 to 91.5%, whereas IC50 values vary from 72.2 to 691.14%. Among all the strains, Fomitopsis meliae crude extract showed a maximum inhibition percentage, i.e., 91.5%, with an IC50 value of 88.27 µg/mL. Chaetomium globosum showed significant activity having an inhibition percentage of 89.88% and an IC50 value of 74.44 µg/mL. The total phenolic and flavonoid content in the crude extract of Chaetomium globosum was 37.4 mg gallic acid equivalent (GAE)/g DW and 31.0 mg quercetin equivalent (GAE)/g DW. GC-MS analysis of crude extract of C. globosum revealed different compounds, such as squalene; butanoic acid, 2-methyl-; hexadecanoic acid; 2-propanone, 1-phenyl-; 5-oxo-pyrrolidine-2-carboxylic acid methyl ester; 9,12-octadecadienoic acid (z)- etc. Many of these belong to phenolics, which are natural antioxidant compounds. The findings suggested that endophytic fungi associated with Dillenia indica L. can be a potential source of novel antioxidant compounds.

Antinociceptive Effect of Dillenia indica (Linn.) Mediated by Opioid and Cannabinoid Systems: Pharmacological and Chemical Studies.

Dillenia indica (Linn.) has been reported by several biological activities, including anti-inflammatory, antioxidant, antidiabetic, anti-hyperglycemic, antiproliferative, antimutagenic, anticholinesterase, and antimicrobial. In Brazilian traditional medicine, the fruits of D. indica have been used to treat general topical pain and inflammation, but with no scientific validation. Thus, aiming to study its chemical constitution and antinociceptive properties, the crude extract (CE) and fractions obtained from the fruits of D. indica were submitted to an in vivo pharmacological evaluation and a dereplication study by LC-MS/MS analysis, assisted by the Global Natural Product Social Molecular Networking (GNPS). The oral antinociceptive activity of the fruits of D. indica and the possible participation of the opioid and cannabinoid systems were demonstrated in the formalin-induced nociception model. The chemical dereplication study led us to identify several known chemical constituents, including flavonoids, such as caffeoylmalic acid, naringenin, quercetin, and kaempferol. According to literature data, our results are compatible with significant antinociceptive and anti-inflammatory activities. Therefore, the flavonoid constituents of the fruits of D. indica are probably responsible for its antioxidant, anti-inflammatory, and antinociceptive effects mediated by both opioid and cannabinoid systems, confirming its folk use in the treatment and relief of pain.

Anti-inflammatory and healing effect of the polysaccharidic extract of Opuntia ficus-indica cladodes in cutaneous excisional wounds in rats.

This study aimed to investigate the anti-inflammatory and wound healing effects of the polysaccharide extract from Opuntia ficus-indica cladodes (TPL-Ofi) using a rat cutaneous wound model. After anaesthesia, four 7-mm-diameter dorsal wounds per animal (n = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL-Ofi (0.01-1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF-2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL-Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL-Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL-Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF-2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL-Ofi exhibited anti-inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds.

Phytochemical analysis, GC-MS profile and determination of antibacterial, antifungal, anti-inflammatory, antioxidant activities of peel and seeds extracts (chloroform and ethyl acetate) of Tamarindus indica L.

Tamarindus indica L., is widely used tree in ayurvedic medicine. Here, we aimed to understand the presence of important constituents in seeds and peel of Tamarind fruits and their biological activities. Hence, seeds and peel of Tamarind fruits are used for further extraction process by soxhlet method (chloroform and ethyl acetate solvents). Results suggest that the ethyl acetate extract (seeds) consists of terpenoids (72.29 ± 0.513 mg/g), phenolic content (68.67 ± 2.11 mg/g) and flavonoids (26.36 ± 2.03 mg/g) whereas chloroform extract (seeds) has terpenoids (42.29 ± 0.98 mg/g). Similarly, chloroform extract (peel) has terpenoids (25.96 ± 3.20 mg/g) and flavonoids (46.36 ± 2.03 mg/g) whereas ethyl acetate extract (peel) has terpenoids (62.93 ± 0.987 mg/g). Furthermore, anti-inflammation activity results revealed that the chloroform extract of peel was found to be more effective with IC50 of 226.14 µg/ml by protein denaturation analysis and with IC50 of 245.5 µg/ml on lipoxygenase inhibition activity. Chloroform extract (peel and seeds) shown better antioxidant activity using DPPH than ethyl acetate extract (peel and seeds). Ethyl acetate extract of seeds showed impressive potency by inhibiting the growth of fungus, Candida albicans. Additionally, ethyl acetate extract of seeds showed impressive potency inhibiting the growth of Escherichia coli than Bacillus cereus. GC-MS analysis shown the existence of diverse set of phytochemicals in each extract. Overall, comparative studies highlight the effectiveness of seeds extracts than peel extracts. Moreover, GC-MS results suggest that the seeds and peel extracts (chloroform and ethyl acetate) contains a wide range of compounds (including flavonoids, isovanillic acid, fatty acids and phenolic compounds) which can be utilized for therapeutic purpose.