Glioblastoma Multiforme miRNA based Comprehensive Study to Validate Phytochemicals for Effective Treatment against Deadly Tumour through In Silico Evaluation.

BACKGROUND: Glioblastoma Multiforme (GBM) is a prevalent and deadly type of primary astrocytoma, constituting over 60% of adult brain tumors, and has a poor prognosis, with a high relapse rate within 7 months of diagnosis. Despite surgical, radiotherapy, and chemotherapy treatments, GBM remains challenging due to resistance. MicroRNA (miRNAs) control gene expression at transcriptional and post-transcriptional levels by targeting their messenger RNA (mRNA), and also contribute to the development of various neoplasms, including GBM. METHODS: The present study focuses on exploring the miRNAs-based pathogenesis of GBM and evaluating most potential plant-based therapeutic agents with in silico analysis. Gene chips were retrieved from the Gene Expression Omnibus (GEO) database, followed by the Robust- RankAggereg algorithm to determine the Differentially Expressed miRNAs (DEMs). The predicted targets were intersected with the GBM-associated genes, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the overlapping genes was performed. At the same time, five phytochemicals were selected for the Connectivity map (CMap), and the most efficient ones were those that had undergone molecular docking analysis to obtain the potential therapeutic agents. RESULTS: The hsa-miR-10b, hsa-miR-21, and hsa-miR-15b were obtained, and eight genes were found to be associated with glioma pathways; VSIG4, PROCR, PLAT, and ITGB2 were upregulated while, CAMK2B, PDE1A, GABRA1, and KCNJ6 were downregulated. The drugs Resveratrol and Quercetin were identified as the most prominent drugs. CONCLUSION: These miRNAs-based drugs can be used as a curative agent for the treatment of GBM. However, in vivo, experimental data, and clinical trials are necessary to provide an alternative to conventional GBM cancer chemotherapy.

Phytochemicals targeting ferroptosis in cardiovascular diseases: Recent advances and therapeutic perspectives.

Ferroptosis is a form of iron-dependent regulatory cell death that is related to the pathogenesis and progression of various cardiovascular diseases, such as arrhythmia, diabetic cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure. This makes it a promising therapeutic target for cardiovascular diseases. It is interesting that a significant number of cardiovascular disease treatment drugs derived from phytochemicals have been shown to target ferroptosis, thus producing cardioprotective effects. This study offers a concise overview of the initiation and control mechanisms of ferroptosis. It discusses the core regulatory factors of ferroptosis as potential new therapeutic targets for various cardiovascular diseases, elucidating how ferroptosis influences the progression of cardiovascular diseases. In addition, this review systematically summarizes the regulatory effects of phytochemicals on ferroptosis, emphasizing their potential mechanisms and clinical applications in treating cardiovascular diseases. This study provides a reference for further elucidating the molecular mechanisms of phytochemicals in treating cardiovascular diseases. This may accelerate their application in the treatment of cardiovascular diseases and is worth further research in this field.

Biochemical Perspectives on Natural Products in Wound Healing: Exploring Phytochemicals in Tissue Repair and Scar Prevention.

Wound healing is a critical process in tissue repair following injury, and traditional herbal therapies have long been utilized to facilitate this process. This review delves into the mechanistic understanding of the significant contribution of pharmacologically demonstrated natural products in wound healing. Natural products, often perceived as complex yet safely consumed compared to synthetic chemicals, play a crucial role in enhancing the wound-healing process. Drawing upon a comprehensive search strategy utilizing databases such as PubMed, Scopus, Web of Science, and Google Scholar, this review synthesizes evidence on the role of natural products in wound healing. While the exact pharmacological mechanisms of secondary metabolites in wound healing remain to be fully elucidated, compounds from alkaloids, phenols, terpenes, and other sources are explored here to delineate their specific roles in wound repair. Each phytochemical group exerts distinct actions in tissue repair, with some displaying multifaceted roles in various pathways, potentially enhancing their therapeutic value, supported by reported safety profiles. Additionally, these compounds exhibit promise in the prevention of keloids and scars. Their potential alongside economic feasibility may propel them towards pharmaceutical product development. Several isolated compounds, from natural sources, are undergoing investigation in clinical trials, with many reaching advanced stages.

Dietary acid load as well as dietary phytochemical index, and association with multiple sclerosis: results from a case-control study.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions. Although the etiology and pathogenesis of MS remains unclear, nutrition is among the environmental factors that may be involved in developing MS. Currently, no specific diet has been associated with MS. This study aimed to investigate the relationship between the dietary phytochemical index (DPI), dietary acid load (DAL), and the risk of developing MS. METHODS: This case‒control study was conducted on 174 patients with MS and 171 healthy individuals in Mashhad, Iran. Data were collected using a 160-item semiquantitative food frequency questionnaire (FFQ). The study investigated the association between DPI, DAL, and MS, considering anthropometric measures, dietary intake, smoking habits, and sex. DPI, potential renal acid load (PRAL), and net endogenous acid production (NEAP), as indicators of DAL, were calculated based on the FFQ. RESULTS: The study analyzed 345 participants, comprising 174 (50.4%) MS patients and 171 (49.6%) healthy individuals. The mean age of the participants was 32.45 ± 8.66 years. The DPI score was significantly lower among MS patients, while the NEAP and PRAL scores were significantly higher among MS patients compared to the healthy group. There was no relationship between NEAP (OR 1.001; 95% CI 0.959-1.044; P = 0.974) and PRAL (OR 1.019; 95% CI 0.979-1.061; P = 0.356) and MS incidence. CONCLUSIONS: The study found higher smoking and obesity rates in MS patients, with a reduced DPI score and increased DAL. Further studies are needed before recommending plant-based foods and dietary acid-base balance evaluation as therapeutic approach.

Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics.

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

Gastroprotective mechanism of Talinum triangulare on ethanol-induced gastric ulcer in Wistar rats via inflammatory, antioxidant, and H+/K+-ATPase inhibition-mediated pathways.

The increase in the incidence of gastric ulcer (GU) has posed major threat on public health. This research aimed to evaluate gastroprotective properties of the aqueous leaf extract of Talium triangulare (AETT) in ethanol-induced gastric ulceration. GU was induced via oral administration of single dose of 5 mLkg-1 of 90% ethanol in rats and protection of 200 mgkg-1 bw of AETT and 20 mgkg-1 bw of omeprazole was investigated for 14 d via oral treatment. Influence of AETT on anti-inflammatory, redox assays, ulcer index (UI), and gastric mucosa histological alterations were evaluated. Significant increase in myeloperoxidase (MPO) and tumor necrosis factor-alpha levels compared to untreated group established gastric inflammation in rats induced by ethanol. Gastric ulcerated group exhibited heightened oxidative stress with concurrent decline in activities of antioxidant enzymes. Ethanol exposure to rats resulted in induction of lipid peroxidation, prominently elevating gastric malondialdehyde (MDA) concentration. Nevertheless, treatment with AETT or omeprazole exhibited substantial anti-inflammatory effects within gastric mucosa by attenuating expression of markers associated with inflammation. AETT demonstrated reduction in concentrations of MDA and H2O2, thereby alleviating progression of lipid peroxidation cascades. Also, AETT exhibited mitigating effect on ethanol-induced oxidative harm by enhancing the functionality of protective enzymes and elevating glutathione (GSH) concentration. Overall, AETT exhibited enhancements in activities of cytoprotective antioxidant enzymes, mitigated impact of oxidative stress and inflammation, inhibited lipid peroxidation, and decreased UI score. These beneficial effects could be attributed to phytochemicals present in AETT including 6,10,14-trimethyl-2-pentadecanone and Phytol. Outcome of this study established the traditional herbal claims of AETT.

Mangaba (hancornia speciosa): exploring potent antifungal and antioxidant properties in lyophilised fruit pulp extract through in vitro analysis.

Mangaba is a fruit native to Brazil, rich in bioactive compounds. To evaluate physicochemical composition, bioactive compounds, antioxidant and antifungal activity of mangaba fruit pulp. Moisture, ash, protein, lipid, energy values and phenolic compounds were determined. Antioxidant activity was determined by capture of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Evaluation of antifungal activity was performed by Minimum Inhibitory Concentration, according to protocols M07-A9 and M27-S3, and minimum fungicidal concentration. Freeze-dried mangaba pulp presented high levels of carbohydrates, low levels of lipids, and high energy density. Phenolic analysis demonstrated that chlorogenic acid was found in the highest concentration, followed by p-coumaric acid and ferulic acid. Mangaba extract showed antioxidant activity like BHT. Mangaba extract inhibited the growth of Candida albicans (ATCC 90028), Cryptococcus gattii (AFLP4), Candida guilliermondii (ATCC 6260) and Candida albicans (MYA 2876). Freeze-dried mangaba inhibited fungal activity associated with antioxidant effect due to presence of phenolic compounds.

Phytochemical-mediated modulation of autophagy and endoplasmic reticulum stress as a cancer therapeutic approach.

Autophagy and endoplasmic reticulum (ER) stress are conserved processes that generally promote survival, but can induce cell death when physiological thresholds are crossed. The pro-survival aspects of these processes are exploited by cancer cells for tumor development and progression. Therefore, anticancer drugs targeting autophagy or ER stress to induce cell death and/or block the pro-survival aspects are being investigated extensively. Consistently, several phytochemicals have been reported to exert their anticancer effects by modulating autophagy and/or ER stress. Various phytochemicals (e.g., celastrol, curcumin, emodin, resveratrol, among others) activate the unfolded protein response to induce ER stress-mediated apoptosis through different pathways. Similarly, various phytochemicals induce autophagy through different mechanisms (namely mechanistic target of Rapamycin [mTOR] inhibition). However, phytochemical-induced autophagy can function either as a cytoprotective mechanism or as programmed cell death type II. Interestingly, at times, the same phytochemical (e.g., 6-gingerol, emodin, shikonin, among others) can induce cytoprotective autophagy or programmed cell death type II depending on cellular contexts, such as cancer type. Although there is well-documented mechanistic interplay between autophagy and ER stress, only a one-way modulation was noted with some phytochemicals (carnosol, capsaicin, cryptotanshinone, guangsangon E, kaempferol, and δ-tocotrienol): ER stress-dependent autophagy. Plant extracts are sources of potent phytochemicals and while numerous phytochemicals have been investigated in preclinical and clinical studies, the search for novel phytochemicals with anticancer effects is ongoing from plant extracts used in traditional medicine (e.g., Origanum majorana). Nonetheless, the clinical translation of phytochemicals, a promising avenue for cancer therapeutics, is hindered by several limitations that need to be addressed in future studies.

A critical appraisal on the involvement of plant-based extracts as neuroprotective agents (2012-2022): an effort to ease out decision-making process for researchers.

The purpose of this review study is to provide a condensed compilation of 164 medicinal plants that have been investigated for their neuroprotective aspects by researchers between the years 2012 and 2022 which also includes a recent update of 2023-2024. After using certain keywords to retrieve the data from SCOPUS, it was manually sorted to eliminate any instances of duplication. The article is streamlined into three major segments. The first segment takes a dig into the current global trend and attempts to decrypt vital information related to plant names, families, plant parts used, and neurological disorders investigated. The second segment of the article makes an attempt to present a comprehensive insight into the various mechanistic pathways through which phytochemicals can intervene to exert neuroprotection. The final segment of the manuscript is a bibliometric appraisal of all researches conducted. The study is based on 256 handpicked articles based on decided inclusion criteria. Illustrative compilation of various pathways citing their activation and deactivation channels are also presented with possible hitting points of various phytochemicals. The present study employed Microsoft Excel 2019 and VOS viewer as data visualisation tools.

Phytochemical-mediated regulation of aflatoxigenic fungi contamination in a shifting climate and environment.

Mycotoxin contamination poses a significant problem in developing countries, particularly in northern Pakistan's fluctuating climate. This study aimed to assess aflatoxin contamination in medicinal and condiment plants in Upper Dir (dry-temperate) and Upper Swat (moist-temperate) districts. Plant samples were collected and screened for mycotoxins (Aflatoxin-B1 and Aflatoxin-B-2). Results showed high levels of AFB-1 (11,505.42 ± 188.82) as compared to AFB-2 (846 ± 241.56). The maximum contamination of AFB-1 in Coriandrum sativum (1154.5 ± 13.43 ng to 3328 ± 9.9 ng) followed by F. vulgare (883 ± 9.89 ng to 2483 ± 8.4 ng), T. ammi (815 ± 11.31 ng to 2316 ± 7.1 ng), and C. longa (935.5 ± 2.12 ng to 2009 ± 4.2 ng) while the minimum was reported in C. cyminum (671 ± 9.91 ng to 1995 ± 5.7 ng). Antifungal tests indicated potential resistance in certain plant species (C. cyminum) while A. flavus as the most toxins contributing species due to high resistance below 80% (54.2 ± 0.55 to 79.5 ± 2.02). HPLC analysis revealed hydroxyl benzoic acid (5136 amu) as the dominant average phytochemical followed by phloroglucinol (4144.31 amu) with individual contribution of 8542.08 amu and 12,181.5 amu from C. cyaminum. The comparison of average phytochemicals revealed the maximum concentration in C. cyminum (2885.95) followed by C. longa (1892.73). The findings revealed a statistically significant and robust negative correlation (y = - 2.7239 × + 5141.9; r = - 0.8136; p < 0.05) between average mycotoxins and phytochemical concentrations. Temperature positively correlated with aflatoxin levels (p < 0.01), while humidity had a weaker correlation. Elevation showed a negative correlation (p < 0.05), while geographical factors (latitude and longitude) had mixed correlations (p < 0.05). Specific regions exhibited increasing aflatoxin trends due to climatic and geographic factors.

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.

Harvesting Health: Phytochemicals in Cognitive Impairment Therapy.

Mild Cognitive Impairment (MCI) is swiftly emerging as a prevalent clinical concern within the elderly demographic. Willoughby spearheaded the pioneering investigation into the evolution of memory decline spanning from the age of 20 to 70. Employing a computerized substitution examination, he pinpointed a zenith in memory prowess at the age of 22, signifying the shift from infancy, succeeded by a gradual decline in later years in 1929. Cognitive impairment impacts various facets, encompassing cognition, memory, perceptual acuity, and linguistic proficiency. Compelling evidence indicates that genetic, dietary, and metabolic factors influence the trajectory of cognitive decline in this patient cohort. In addition to the widely recognized influence of the Mediterranean diet on cognitive function, numerous studies have delved into the potential impact of diverse phytochemicals on cognitive deterioration. Many of these compounds are renowned for their inflammation reducer or free-radical scavenger properties, coupled with their commendable acceptability and defense profiles. Phytochemicals sourced from medicinal plants play an essential role in upholding the intricate chemical equilibrium of the brain by modulating receptors linked to crucial inhibitory neurotransmitters. Across the annals of historical medicinal traditions, a multitude of plants have been cataloged for their efficacy in mitigating cognitive disorders. This study presents a concise examination of distinct medicinal herbs, highlighting their neuroprotective phytochemical components such as fatty acids, phenols, alkaloids, flavonoids, saponins, terpenes, and beyond. The principal objective of this inquiry is to meticulously inspect and provide discernment into the extant evidence concerning phytochemicals exhibiting clinically demonstrable effects on cognitive decline.

Antimicrobial Activity of Crude Metabolites of Vitis vinifera using Methanol Extract against the Clinical Pathogens.

Background: The Vitis vinifera, also known as grapevine, is one of the most widely grown fruit crops in the world and is renowned for producing wine and grapes. Other than their importance in gastronomy and ecology, certain sections of the V. vinifera plant have shown promising bioactive qualities. The numerous phytochemicals in this plant, including flavonoids, stilbenes, and phenolic acids, are what gives its antibacterial and antifungal properties though the antimicrobial properties of seed extract have to be studied, however in this present study we focus on screening and its biological compatibility of seed extracts of V. vinifera. Methods: The commercial power of seed (V. vinifera) obtained from local market near Poonamallee, Chennai, India. and the extraction of crude metabolites was done by direction extraction method, the antimicrobial activity was done by well diffusion method, and Minimum Inhibitory concentration was done by CLSI guideline. To check the biocompatibility of crude metabolites was done by hemolytic assay. Results: Studies have demonstrated that grapevine extracts and their separated components have potent antibacterial and antifungal effects against a variety of pathogenic microorganisms, including bacterial strains that are resistant to antibiotics. The Minimum Inhibitory Concentration of the plant's extracts have demonstrated potential 128 µg/mL for S. aureus, and 256 µg/mL E. faecalis and C. albicans as the best inhibitory concentration. The biological compatibility of crude metabolites shows 3 % of lysis at 512 µg/mL. Conclusion: V. vinifera is a prospective source for the creation of novel antimicrobial drugs because of its antibacterial capabilities. To completely understand the chemicals' mode of action and to create efficient treatments for microbial illnesses, more research is necessary.

Future Roadmaps for the Treatment of Guinea Worm Disease: Progress in Synthetic and Green Approaches.

For decades, guinea worm disease, caused by the parasitic worm Dracunculus medinensis, has been a major public health concern, impacting vulnerable populations in Africa and Asia. This review gives an in-depth examination of the various therapeutic approaches used to combat guinea worm disease. This study seeks to provide a current and evidence-based summary of available treatment techniques by conducting an exhaustive examination of peer-reviewed literature, medical databases, and official health organisation publications. The current review intends to contribute to the knowledge base and influence plans for guinea worm disease control and eradication by critically evaluating the success and obstacles associated with various treatment approaches through standard heterocyclic medications, herbal sources, phytochemicals, and nanomedicines. The importance of integrating community engagement and collaboration among national and international stakeholders is emphasised to foster sustainable solutions and ensure a collective effort towards a guinea worm-free world.

The Evaluation of the Phytochemical Profiles and Antioxidant and α-Glucosidase Inhibitory Activities of Four Herbal Teas Originating from China: A Comparative Analysis of Aqueous and Ethanol Infusions.

Recent research has demonstrated the positive impact of herbal tea consumption on postprandial blood glucose regulation. This study conducts a comparative analysis of aqueous and ethanol extractions on four herbal teas (Mallotus, Cyclocarya, Rubus, and Vine) to assess their phytochemical profiles and functional attributes. Phytochemical contents, antioxidant activities, α-glucosidase inhibitory activities, and chemical compositions are investigated via colorimetric analyses and UPLC-Q-Orbitrap HRMS/MS, respectively. Results indicate that Vine, among the teas studied, exhibits the most pronounced glucose-regulating effects under both extraction methods. While ethanol extractions yield higher phytochemical content overall, the compositions vary. Conversely, aqueous extracts demonstrate unexpectedly potent antioxidant activities and comparable α-glucosidase inhibitory activities to ethanol extracts. Phytochemical contents correlate positively with antioxidant activities and α-glucosidase inhibitory activities. However, antioxidant activities exhibit a weak positive correlation with α-glucosidase inhibitory activities. These findings provide evidence that aqueous extracts from herbal teas contain valuable phytochemical compositions beneficial for antioxidants and individuals with hyperglycemia, suggesting their potential as functional ingredients to enhance the nutritional value of herbal food products.

Analysis of Quantitative Phytochemical Content and Antioxidant Activity of Leaf, Stem, and Bark of Gymnosporia senegalensis (Lam.) Loes.

To the best of our knowledge, there was no prior report providing valuable preliminary data through a demonstration of the quantitative phytochemical and antioxidant activity of Gymnosporia senegalensis. The total contents of phenols, flavonoid, flavanol, tannin, and saponin were evaluated from different fractions extracted from the leaf, stem, and bark of G. senegalensis by using standards such as gallic acid, quercetin, rutin, tannic acid, and saponin quillaja. The antioxidant potential was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide scavenging (H2O2), superoxide anion radical scavenging, metal chelating ferrous ion, ferric reducing antioxidant power (FRAP), and total antioxidant capacity (TAC). Data were subjected to half-inhibitory concentration (IC50) and one-way analysis of variance (ANOVA) at p < 0.05 as a significant value. The total phenol content was found to be highest in the chloroform extract of stem at 97.7 ± 0.02 mg GAE/g. The total flavonoid and flavonol contents in the aqueous extract were 97.1 ± 0.03 mg QE/g and 96.7 ± 0.07 mg RE/g, respectively. The total tannin content in the ethyl acetate extract of leaf was 97.5 ± 0.01 mg TAE/g, and the total saponin content in the methanol extract of stem was 79.1 ± 0.06 mg SQE/g. The antioxidant analysis indicated that IC50 and percentage (%) inhibition were dose-dependent and showed the highest antioxidant activity (40.9 ± 0.9 µg/mL) in methanol extract of leaf for DPPH, (88.8 ± 1.12 µg/mL) in the chloroform extract of stem for H2O2, (43.9 ± 0.15 µg/mL) in the aqueous extract of bark for superoxide anion radical scavenging activity, (26.9 ± 0.11 µg/mL) in the chloroform extract of leaf for the metal chelating ferrous ion activity, (7.55 ± 0.10 mg/mL) in the benzene extract of leaf for FRAP, and (2.97 ± 0.01 mg/mL) in the methanol extract of bark for TAC. These results show that G. senegalensis has great potential in antioxidant activities. The isolation and characterization of specific bioactive compounds and the in vivo applicability of such activity await further extensive studies for drug discovery and development.

Lactation Performance and Rumen Fermentation in Dairy Cows Fed a Diet Supplemented with Monensin or Gum Arabic-Nano Montmorillonite Compost.

The exploration of natural alternatives to antibiotics for enhancing productivity and performance in dairy cows is a crucial objective in farm animal management. This is the first study aimed at developing and evaluating the physicochemical properties and effects of Arabic gum-nano montmorillonite (AGNM) compost compared to ionophore monensin as feed additives on rumen fermentation, blood metabolites, and milk production of Holstein dairy cows. In a replicated 4 × 4 Latin square design, four multiparous mid-lactation Holstein dairy cows with an average body weight of 520 ± 15 kg were enrolled. The dietary treatments included a control diet (basal diet without feed additives), monensin diet [a basal diet supplemented with 35 mg/kg dry matter (DM) monensin], and AGNM diets comprising basal diet supplemented with two levels: low (L-AGNM) at 1.5 g/kg DM, and high (H-AGNM) at 3 g/kg DM. AGNM as a feed additive demonstrated promising physiochemical parameters, including containing highly bioactive components (α-amyrin and lupeol), functional groups (OH and Si-O), and essential mineral contents (Mg2+). Supplementations with H-AGNM significantly improved ruminal (p = 0.031) concentrations of total volatile fatty acids (VFAs), acetic (p = 0.05) and butyric (p = 0.05), enhanced (p < 0.05) digestibility of fiber and organic matter, while decreased (p = 0.013) estimated methane production. However, an increase (p = 0.04) in blood high-density lipoprotein levels and decrease (p < 0.05) in concentrations of creatinine (CREA), bilirubin (BILT), cholesterol (CHOL), and sodium (Na) were observed with H-AGNM supplementation. Both monensin and H-AGNM improved (p = 0.008) feed efficiency compared to L-AGNM; however, neither AGNM nor monensin affected the milk composition or energy status indicators of the dairy cows. The findings of this study highlight the potential of AGNM as a natural candidate to replace monensin in enhancing ruminal VFA production, nutrient digestibility, feed efficiency, blood metabolites, and milk yield in dairy cows.

Hoslundia opposita vahl; a potential source of bioactive compounds with antioxidant and antibiofilm activity for wound healing.

BACKGROUND: Biofilms and oxidative stress retard wound healing. The resistance of biofilms to antibiotics has led to a search for alternative approaches in biofilm elimination. Antioxidants work synergistically with antibacterial agents against biofilms. Hence recent research has suggested plants as candidates in the development of new alternatives in biofilm treatments and as antioxidants due to the presence of phytocompounds which are responsible for their bioactivities. Hoslundia opposita Vahl is one of the plants used by traditional healers to treat wounds and other infections, this makes it a potential candidate for drug discovery hence, in this study, we investigate the antibiofilm and antioxidant activity of methanolic extract of hoslundia opposita Vahl from Uganda. We also identify phytochemicals responsible for its bioactivity. METHOD: the plant was extracted by maceration using methanol, and the extract was investigated for antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay. The antibiofilm activity using microtiter plate assay (MTP) assay where the Minimum biofilm inhibitory concentration required to inhibit 50% or 90% of the biofilm (MBIC50 and MBIC90) and Minimum biofilm eradication concentration required to remove 50% or 90% of the biofilm (MBEC50 and MBEC90) were measured. It was further analysed for its phytochemical composition using quantitative screening, as well as Gas chromatography-mass spectrometry (GC-MS) and Liquid chromatography mass-spectrometry (LC-MS). RESULTS: H. Opposita Vahl extract showed good antioxidant activity with of 249.6 mg/mL. It inhibited the growth of P. aeruginosa and S. aureus biofilms with MBIC50 of 28.37 mg/mL and 10 mg/mL, respectively. It showed the ability to eradicate P. aeruginosa and S. aureus biofilms with MBEC50 of 23.85 and 39.01 mg/mL respectively. Phytochemical analysis revealed the presence of alkaloids, tannins, flavonoids, and phenols. GC-MS analysis revealed 122 compounds in the extract of which, 23 have evidence of antioxidant or antibiofilm activity in literature. The most abundant compounds were; 1,4- Citric acid, Tetracontane-1,40-diol (43.43.3%, 1, Olean-12-en-28-oic acid, 3-hydroxy-, methyl ester, (3.beta) (15.36%) 9-Octadecenamide (12.50%), Squalene (11.85%) Palmitic Acid 4TMS (11.28%), and alpha Amyrin (11.27%). The LC-MS identified 115 and 57 compounds in multiple reaction mode (MRM) and scan modes respectively. CONCLUSION: H. opposita Vahl showed antibiofilm and antioxidant activity due to bioactive compounds identified, hence the study justifies its use for wound healing. It can be utilised in further development of new drugs as antibiofilm and antioxidants.

Natural autophagy activators: A promising strategy for combating photoaging.

BACKGROUND: Photodamage to the skin stands out as one of the most widespread epidermal challenges globally. Prolonged exposure to sunlight containing ultraviolet radiation (UVR) instigates stress, thereby compromising the skin's functionality and culminating in photoaging. Recent investigations have shed light on the importance of autophagy in shielding the skin from photodamage. Despite the acknowledgment of numerous phytochemicals possessing photoprotective attributes, their potential to induce autophagy remains relatively unexplored. PURPOSE: Diminished autophagy activity in photoaged skin underscores the potential benefits of restoring autophagy through natural compounds to enhance photoprotection. Consequently, this study aims to highlight the role of natural compounds in safeguarding against photodamage and to assess their potential to induce autophagy via an in-silico approach. METHODS: A thorough search of the literature was done using several databases, including PUBMED, Science Direct, and Google Scholar, to gather relevant studies. Several keywords such as Phytochemical, Photoprotection, mTOR, Ultraviolet Radiation, Reactive oxygen species, Photoaging, and Autophagy were utilized to ensure thorough exploration. To assess the autophagy potential of phytochemicals through virtual screening, computational methodologies such as molecular docking were employed, utilizing tools like AutoDock Vina. Receptor preparation for docking was facilitated using MGLTools. RESULTS: The initiation of structural and functional deterioration in the skin due to ultraviolet radiation (UVR) or sunlight-induced reactive oxygen species/reactive nitrogen species (ROS/RNS) involves the modulation of various pathways. Natural compounds like phenolics, flavonoids, flavones, and anthocyanins, among others, possess chromophores capable of absorbing light, thereby offering photoprotection by modulating these pathways. In our molecular docking study, these phytochemicals have shown binding affinity with mTOR, a negative regulator of autophagy, indicating their potential as autophagy modulators. CONCLUSION: This integrated review underscores the photoprotective characteristics of natural compounds, while the in-silico analysis reveals their potential to modulate autophagy, which could significantly contribute to their anti-photoaging properties. The findings of this study hold promise for the advancement of cosmeceuticals and therapeutics containing natural compounds aimed at addressing photoaging and various skin-related diseases. By leveraging their dual benefits of photoprotection and autophagy modulation, these natural compounds offer a multifaceted approach to combatting skin aging and related conditions.

Joint effects about antibiotics combined using with antibiotics or phytochemicals on Aeromonas hydrophila.

Aeromonas hydrophila is highly prevalent in aquaculture animals and aquaculture environment. Due to the abuse of antibiotics, A. hydrophila can change the antibiotic resistance spectrum directly and affect human health indirectly. The use of combined drugs replacement therapy and the long-term coexistence with drug-resistant bacteria are the reality that human beings have to face in dealing with the problem of antibiotic resistance in the future. This study showed the characteristics and trends through abundant results of combined effects related with the combinations of antibiotic and the combinations of antibiotic and phytochemical on A. hydrophila, and revealed the antagonism probability of combinations of antibiotic and phytochemical is significantly higher than that of the combinations of antibiotic. Meanwhile, the combinations of antibiotic and phytochemical could protect the host cells which also achieved the same effectiveness as combination of antibiotics, and the enrichment pathway was proved to be relatively discrete. In addition, the possible mechanism about the reverse "U" shape of the combined effect curve on wild/antibiotic-resistant bacteria was clarified, and it was confirmed that the antagonism for the combinations of antibiotic and phytochemical might has the significance in inhibiting the evolution of bacterial resistance mutations. This study was aims to provide theoretical basis and some clues for the antibiotic resistance control associated with A. hydrophila.