Molecular mechanisms of flavonoids in myocardial ischemia reperfusion injury: Evidence from in-vitro and in-vivo studies.

OBJECTIVES: Flavonoids are polyphenolic compounds found in a wide range of foods, including fruits, vegetables, tea plants, and other natural products. They have been mainly classified as flavanols, flavonols, flavones, isoflavones, flavanones, and flavanonols. In this comprehensive review, we will discuss preclinical pieces of evidence on the potential of flavonoids for the prevention/treatment of myocardial ischemia-reperfusion (IR) injury. KEY FINDINGS: In-vitro and in-vivo studies have shown that flavonoids play an important role in preventing ischemic heart disease (IHD). They possess strong anti-oxidant, anti-inflammatory, anti-bacterial, anti-thrombotic, anti-apoptotic, and anti-carcinogenic activities. In addition, at a molecular level, flavonoids also modulate various pathways like MAPK, NFκB etc. to confer beneficial effects. SUMMARY: The current review of flavonoids in myocardial ischemia-reperfusion injury furnishes updated information that could drive future research. The in-vitro and in-vivo experiments have demonstrated various favourable pharmacological properties of flavonoids. This review provides valuable information to conduct clinical studies, validating the safety aspects of flavonoids in the clinical domain.

Natural-derived acetophenones: chemistry and pharmacological activities.

Acetophenones are naturally occurring phenolic compounds which have found in over 24 plant families and also fungi strains. They are exist in both free or glycosides form in nature. The biological activities of these compounds have been assayed and reported including cytotoxicity, antimicrobial, antimalarial, antioxidant and antityrosinase activities. Herein, we review the chemistry and biological activity of natural acetophenone derivatives that have been isolated and identified until January 2024. Taken together, it was reported 252 acetophenone derivatives in which the genera Melicope (69) and Acronychia (44) were the principal species as producers of acetophenones.

Phytochemical Modulation of Ion Channels in Oncologic Symptomatology and Treatment.

Modern chemotherapies offer a broad approach to cancer treatment but eliminate both cancer and non-cancer cells indiscriminately and, thus, are associated with a host of side effects. Advances in precision oncology have brought about new targeted therapeutics, albeit mostly limited to a subset of patients with an actionable mutation. They too come with side effects and, ultimately, 'self-resistance' to the treatment. There is recent interest in the modulation of ion channels, transmembrane proteins that regulate the flow of electrically charged molecules in and out of cells, as an approach to aid treatment of cancer. Phytochemicals have been shown to act on ion channels with high specificity regardless of the tumor's genetic profile. This paper explores the use of phytochemicals in cancer symptom management and treatment.

Influence of molecular descriptors of plant volatilomics on fumigant action against the three major stored product beetle pests.

Plant volatilomics such as essential oils (EOs) and volatile phytochemicals (PCs) are known as potential natural sources for the development of biofumigants as an alternative to conventional fumigant pesticides. This present work was aimed to evaluate the fumigant toxic effect of five selected EOs (cinnamon, garlic, lemon, orange, and peppermint) and PCs (citronellol, limonene, linalool, piperitone, and terpineol) against the Callosobruchus maculatus, Sitophilus oryzae, and Tribolium castaneum adults. Furthermore, for the estimation of the relationship between molecular descriptors and fumigant toxicity of plant volatiles, quantitative structural activity relationship (QSAR) models were developed using principal component analysis and multiple linear regression. Amongst the tested EOs, garlic EO was found to be the most toxic fumigant. The PCs toxicity analysis revealed that terpineol, limonene, linalool, and piperitone as potential fumigants to C. maculatus (< 20 µL/L air of LC50), limonene and piperitone as potential fumigants to T. castaneum (14.35 and 154.11 µL/L air of LC50, respectively), and linalool and piperitone as potential fumigants to S. oryzae (192.27 and 69.10 µL/L air of LC50, respectively). QSAR analysis demonstrated the role of various molecular descriptors of EOs and PCs on the fumigant toxicity in insect pest species. In specific, dipole and Randic index influence the toxicity in C. maculatus, molecular weight and maximal projection area influence the toxicity in S. oryzae, and boiling point and Dreiding energy influence the toxicity in T. castaneum. The present findings may provide insight of a new strategy to select effective EOs and/or PCs against stored product insect pests.

Phytochemical profile and diverse pharmacology of Garcinia celebica L.

Garcinia celebica L. syn. Garcinia hombroniana Pierre belongs to the family Clusiaceae, is indigenous to Southeast Asian countries. This review aims to provide updated, comprehensive and categorized information on the phytoconstituents and pharmacological effects of this species. The data collection mainly involved searches through databases named Scopus, Google Scholar, Pubmed and Springer Link. Approximately 100 phytochemicals were recorded in this review, with various classes of compounds such as triterpenoids, flavonoids, benzophenones, xanthones, depsidones and sterols identified. The most abundant compounds isolated belong to two chemical classes: triterpenoids and xanthones. Their extracts and pure compounds have been reported for their antibacterial, antiparasitic, hepatoprotective, antioxidant, antidiabetic, antituberculosis, antiplatelet aggregation, anti-neuraminidase and cholinesterase inhibitory activities. This review will provide a comprehensive understanding between the phytochemical components and its medicinal uses that may serve as a valuable resource for future drug development.

Drying enhances the antioxidant activity of Allium mongolicum Regel through the phenylpropane and AA-MA pathway as shown by metabolomics.

Fresh Allium mongolicum Regel (FA) and dried A. mongolicum Regel (DA) are significantly different in antioxidant activity. However, the relevant mechanisms have not yet been explored. We evaluated the antioxidant activities of two varieties of FA and DA and characterized their metabolites using targeted metabolomics. The effect of different metabolites on the antioxidant activity of A. mongolicum Regel was investigated by multivariate analysis. A total of 713 metabolites were detected in all samples. Pearson correlation analysis demonstrated that the key primary metabolites were directly and significantly correlated with the total phenolic content (TPC) and total flavonoid content (TFC), while the secondary metabolites were directly correlated with antioxidant activity. The higher antioxidant activity of DA may be mainly attributed to the higher TPC and TFC. This study revealed the potential mechanism by which drying enhances the antioxidant activity of A. mongolicum Regel.

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

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

The artificial neural network selects saccharides from natural sources a promise for potential FimH inhibitor to prevent UTI infections.

The major challenge in the development of affordable medicines from natural sources is the unavailability of logical protocols to explain their mechanism of action in biological targets. FimH (Type 1 fimbrin with D-mannose specific adhesion property), a lectin on E. coli cell surface is a promising target to combat the urinary tract infection (UTI). The present study aimed at predicting the inhibitory capacity of saccharides on FimH. As mannosides are considered FimH inhibitors, the readily accessible saccharides from the PubChem collection were utilized. The artificial neural networks (ANN)-based machine learning algorithm Self-organizing map (SOM) has been successfully employed in predicting active molecules as they could discover relationships through self-organization for the ligand-based virtual screening. Docking was used for the structure-based virtual screening and molecular dynamic simulation for validation. The result revealed that the predicted molecules malonyl hexose and mannosyl glucosyl glycerate exhibit exactly similar binding interactions and better docking scores as that of the reference bioassay active, heptyl mannose. The pharmacokinetic profile matches that of the selected bioflavonoids (quercetin malonyl hexose, kaempferol malonyl hexose) and has better values than the control drug bioflavonoid, monoxerutin. Thus, these two molecules can effectively inhibit type 1 fimbrial adhesin, as antibiotics against E. coli and can be explored as a prophylactic against UTIs. Moreover, this investigation can pave the way to the exploration of the potential benefits of plant-based treatments. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00212-5.

Ultrasound assisted extraction of phytochemicals from Piper betel L.

Piper betel contains phytochemicals with diverse pharmacological effects. The objective of this study was to enhance the extraction efficiency of phytochemicals and the chlorophyll content using ultrasonication. The Box-Behnken design was employed to optimize the time (10, 20, 30 min), temperature (20, 30, and 40 °C), and solid-solvent ratio (1:10, 1:20, 1:30) by utilizing response surface methods with three independent variables. Multiple parameters, including extract yield, total phenol, total flavonoid, antioxidant activity, and chlorophyll content were used to optimize the conditions. The linear relationship between power intensity and responses was determined to be statistically significant, with a p-value less than 0.01. The interaction effect of temperature, time, and ratio of solid solvent was shown to be statistically significant (p < 0.05) for all the obtained results. The optimal parameters for achieving the highest extract yield were as follows: a temperature of 40 °C, a sonication time of 30 min, and a solid solvent ratio of 1:10. These conditions result in an extract yield of 21.99 %, a total flavonoid content of 44.97 mg/GAE, a total phenolic content of 185.05 mg/GAE, a DPPH scavenging activity of 99.1 %, and a chlorophyll content of 49.95 mg/ml. This study highlights the significance of customized extraction methodologies for optimizing the bioactive capacity of phytochemicals derived from betel leaves. The elucidation of extraction parameters and the resultant phytochemical profiles serves as a fundamental framework for the advancement of innovative pharmaceuticals and nutraceuticals, capitalizing on the therapeutic attributes of this traditional medicinal botanical.

A Review on Picrosides Targeting NFκB and its Proteins for Treatment of Breast Cancer.

Breast cancer is the most frequently diagnosed disease causing most deaths in women worldwide. Chemotherapy and neo-adjuvant therapy are the standard method of treatment in early stages of breast cancer. However drug resistance in breast cancer limit the use of these methods for treatment. Research focus is now shifted towards identifying natural phytochemicals with lower toxicity. This review illustrates the NF κB interaction with different signaling pathways in normal condition, breast cancer and other cancer and thus represent a potential target for treatment. No reports are available on the action of picrosides on NFκB and its associated proteins for anticancer activity. In the present review, potential interaction of picrosides with NF-κB and its associated proteins is reviewed for anticancer action. Further, an important facet of this review entails the ADMET analysis of Picroside, elucidating key ADMET properties which serves to underscore the crucial characteristics of Picroside as a potential drug for treating breast cancer. Furthermore, in silico analysis of Picrosides was executed in order to get potential binding modes between ligand (Picrosides II) and NFκB.

Wild edible Ficus fruits of Uttarakhand, India: a natural remedy towards malnutrition and human health enrichment.

Wild fruits play a vital role in the diets and economic well-being of tribal communities of Uttarakhand, India. Despite their significance, there is limited information on some of the wild Ficus species such as Ficus drupacea, Ficus rumphii, Ficus semicordata, Ficus subincisa and Ficus hispida. This research aimed to analyse the nutritional potential, anti-nutritional compositions, mineral composition, antioxidant and finally the phytochemical properties of Ficus fruits to ascertain their medicinal and nutritional significance. The proximate analysis results of all the five wild Ficus species displayed varying percentages of protein, moisture, fat, ash, crude fibre, carbohydrates. Ficus species exhibited superior nutritional and mineral parameters along with a significant amount of vitamin C. Additionally, these fruits significantly showed lower levels of anti-nutritional and good amount of antioxidant parameters. Thus, adequate consumption of these wild Ficus fruits could potentially contribute to human nutritional needs and may serve as sources for dietary enhancements.

"Exploring the Biochemical and Nutra-pharmaceutical Prospects of Some Thymus Species- A Review.

The Thymus genus includes various medicinal and aromatic species, cultivated worldwide for their unique medicinal and economic value. Besides, their conventional use as a culinary flavoring agent, Thymus species are well-known for their diverse biological effects, such as antioxidant, anti-fungal, anti-bacterial, anti-viral, anti-tumor, anti-inflammatory, anti-cancer, and anti-hypertensive properties. Hence, they are used in the treatment of fever, colds, and digestive and cardiovascular diseases. The pharmaceutical significance of Thymus plants is due to their high levels of bioactive components such as natural terpenoid phenol derivatives (p-cymene, carvacrol,  thymol, geraniol), flavonoids, alkaloids, and phenolic acids. This review examines the phytochemicals, biological properties, functional food and nutraceutical attributes of some important Thymus species, with a specific focus on their potential uses in the nutra-pharmaceutical industries. Furthermore, the review provides an insight into the mechanisms of biological activities of key phytochemicals of Thymus species exploring their potential for the development of novel natural drugs.

Environmentally friendly swift and perfect extraction procedures for analysing the phytochemistry and proximate nutritional biochemistry of biomaterial processed from Avicennia marina leaves.

Conventional extraction methods have mislaid their best possible performance because of the slow extraction process using demand in inexperienced and innovative technologies. Concerning this view, several eco-friendly novel techniques alienate to develop by us for the entire extraction of nutrients and phytocompounds from plant sources. The specific organic, inorganic chemical compounds have been explored using ultra sonication and GC-MS assisted techniques. The results are evident to facilitate the ultrasonic and GC-MS supported extraction descent that is less solvent consumed, green analytical methods suitable for complete speedy bioactive compounds drawing out. This study has revealed the occurrence of nutrients, phytochemicals, with biological value, and also the GC-MS analysis exposed 20 peaks through 20 individual chemical compounds, and all the compounds are deliberated as energetic medicinal bioactive compounds. Likewise the FE-SEM is used to find out the topographical characteristics of biomaterial and the FTIR analysis.

A comprehensive review on ethnomedicinal, phytochemical and pharmacological properties of genus Bistorta (L.) scop.

The genus Bistorta comprises about 43 accepted species that are widely used by local people and medicinal practitioners for the treatment of rheumatism, tuberculosis, inflammation, respiratory infection, and other diseases. The objective of this review is to present up-to-date information from the scientific literature about the phytochemistry, pharmacology, and toxicology of Bistorta. At present, there is a lack of a comprehensive review that consolidates the various scientific studies conducted on the genus Bistorta. To address this knowledge gap, a global review has been compiled on the genus Bistorta, which emphasizes ethnomedicinal uses, phytochemistry, and pharmacology. To gather information about Bistorta, relevant keywords were used to search internet databases including Google scholar, PubMed, ResearchGate, Web of Science, Europe PMC, CNKI, and Wiley Online Library. Additionally, published books that provided an overview of existing literature studies were consulted for reference purposes. Chemical structures and formulas of compounds were verified using the PubChem database and drawn using Chem Draw Ultra 6.0. The scientific nomenclature utilized in this review follows The World Flora Online and The Plant of the World Online (PoWo). A comprehensive evaluation of literature sources revealed that the genus Bistorta has been recognized for its ethnomedical properties and has been used in traditional healthcare for several millennia. Chemical analysis has identified various compounds such as phenolics, flavonoids saponins, terpenes, sterols, and coumarins which have been shown to have significant pharmacological effects such as anti-tumor, anti-inflammatory, anti-oxidant anti-rheumatic and anti-microbial properties. The pharmacological research has only partially validated the traditional and local uses of Bistorta species. Further research is required to investigate the mechanisms of the plant's active compounds, as well as its potential therapeutic applications in treating conditions like diabetes and neurodegenerative diseases. Additionally, there is no clinical evidence to provide the health benefits of these plants. To confirm the pharmacological activities, clinical efficacy, and non-toxicity of Bistorta species, more comprehensive and systematic preclinical studies, and clinical trials are needed.

Phytochemical screening, FTIR and GCMS analysis of Cucurbita pepo seeds cultivated in Kiambu county, Kenya.

Bioactive compounds and other constituents of plants have been shown to vary by cultivation region, species, environmental conditions and method of extraction among others. Phytochemical analysis of Cucurbita pepos farmed in Kiambu County, Kenya, or their seeds has not been documented. The present research aimed to bridge this knowledge gap by screening phytochemicals and characterizing the seed extracts of Cucurbita pepo cultivated in Kiambu County, Kenya. Cucurbita pepo seeds extracted using organic solvent extraction method employing methanol and preconcentrated in a vacuum rotatory evaporator. The extracts were characterized by GCMS and Fourier transform infrared (FTIR) techniques. Phytochemical analysis of the seeds revealed the presence of flavonoids, alkaloids, saponins, cardiac glycosides, and steroids. FT-IR analysis showed significant peaks for C-N, N-H, C-O, C-H, and CH3 functional groups. The GCMS studies revealed a significant number of fatty acids and their derivatives with 12-cis-octadecadienoate being the most abundant in the oil (53.93 %). A significant amount of the macrocyclic lactone 7,9-ditert-butyl-1-oxaspiro [4.5] deca-6,9-diene-2,8-dione (0.58 %) in the seeds was reported. Macrocyclic lactones are generally a class of anthelminthic drugs. These reported biologically active compounds have a wide range of medicinal and nutritional value. One interesting compound from the GCMS analysis of the seed extracts analyzed was the macrocyclic lactone providing a basis for further research on the anthelminthic actions of the seeds.

The promising antioxidant effects of lignans: Nrf2 activation comes into view.

Lignans are biologically active compounds widely distributed, recognized, and identified in seeds, fruits, and vegetables. Lignans have several intriguing bioactivities, including anti-inflammatory, antioxidant, and anticancer activities. Nrf2 controls the expression of many cytoprotective genes. Activation of Nrf2 is a promising therapeutic approach for treating and preventing diseases resulting from oxidative injury and inflammation. Lignans have been demonstrated to stimulate Nrf2 signaling in a variety of in vitro and experimental animal models. The review summarizes the findings of fourteen lignans (Schisandrin A, Schisandrin B, Schisandrian C, Magnolol, Honokiol, Sesamin, Sesamol, Sauchinone, Pinoresinol, Phyllanthin, Nectandrin B, Isoeucommin A, Arctigenin, Lariciresinol) as antioxidative and anti-inflammatory agents, affirming how Nrf2 activation affects their pharmacological effects. Therefore, lignans may offer therapeutic candidates for the treatment and prevention of various diseases and may contribute to the development of effective Nrf2 modulators.

A comprehensive review on phytochemicals in the treatment and prevention of pancreatic cancer: Focusing on their mechanism of action.

Background and Aims: Pancreatic cancer develops in the normal tissues of the pancreas from malignant cells. The chance of recovery is not good, and the chance of survival 5 years following diagnosis is quite low. Pancreatic cancer treatment strategies such as radiotherapy and chemotherapy had relatively low success rates. Therefore, the present study aims to explore new therapies for treating pancreatic cancer. Methods: The present study searched for information about pancreatic cancer pathophysiology, available treatment options; and their comparative benefits and challenges. Aiming to identify potential alternative therapeutics, this comprehensive review analyzed information from renowned databases such as Scopus, PubMed, and Google Scholar. Results: In recent years, there has been a rise in interest in the possibility that natural compounds could be used as treatments for cancer. Cannabinoids, curcumin, quercetin, resveratrol, and triptolide are some of the anticancer phytochemicals now used to manage pancreatic cancer. The above compounds are utilized by inhibiting or stimulating biological pathways such as apoptosis, autophagy, cell growth inhibition or reduction, oxidative stress, epithelial-mesenchymal transformation, and increased resistance to chemotherapeutic drugs in the management of pancreatic cancer. Conclusion: Right now, surgery is the only therapeutic option for patients with pancreatic cancer. However, most people who get sick have been diagnosed too late to benefit from potentially effective surgery. Alternative medications, like natural compounds and herbal medicines, are promising complementary therapies for pancreatic cancer. Therefore, we recommend large-scale standardized clinical research for the investigation of natural compounds to ensure their consistency and comparability in pancreatic cancer treatment.

Phytochemicals: Promising Inhibitors of Human Rhinovirus Type 14 3C Protease as a Strategy to Fight the Common Cold.

BACKGROUND: Human rhinovirus 3C protease (HRV-3Cpro) plays a crucial role in viral proliferation, establishing it as a prime target for antiviral therapy. However, research on identifying HRV-3Cpro inhibitors is still limited. OBJECTIVE: This study had two primary objectives: first, to validate the efficacy of an end-point colorimetric assay, previously developed by our team, for identifying potential inhibitors of HRV-3Cpro; and second, to discover phytochemicals in medicinal plants that inhibit the enzyme's activity. METHODS: Rupintrivir, a well-known inhibitor of HRV-3Cpro, was used to validate the colorimetric assay. Following this, we conducted a two-step in silico screening of 2532 phytochemicals, which led to the identification of eight active compounds: apigenin, carnosol, chlorogenic acid, kaempferol, luteolin, quercetin, rosmarinic acid, and rutin. We subsequently evaluated these candidates in vitro. To further investigate the inhibitory potential of the most promising candidates, namely, carnosol and rosmarinic acid, molecular docking studies were performed to analyze their binding interactions with HRV-3Cpro. RESULTS: The colorimetric assay we previously developed is effective in identifying compounds that selectively inhibit HRV-3Cpro. Carnosol and rosmarinic acid emerged as potent inhibitors, inhibiting HRV-3Cpro activity in vitro by over 55%. Our analysis indicated that carnosol and rosmarinic acid exert their inhibitory effects through a competitive mechanism. Molecular docking confirmed their competitive binding to the enzyme's active site. CONCLUSION: Carnosol and rosmarinic acid warrant additional investigation for their potential in the development of cold treatment. By highlighting these compounds as effective HRV-3Cpro inhibitors, our study presents a promising approach for discovering phytochemical inhibitors against proteases from similar pathogens.