Plant-derived Bioactive Compounds Research Articles

Biodegradation of the methylenedioxyphenyl group in piperine and its derivatives: discovery of a novel methylenetransferase in an actinomycete.

Pepper is a spice that has been used worldwide since the Age of Discovery. The substance that is responsible for the spiciness in pepper is piperine, a type of alkaloid. It has never been reported how piperine is degraded by microorganisms. In this study, we discovered a bacterium in the soil that is capable of catabolizing piperine as its sole nitrogen source. Furthermore, we discovered the enzyme involved in piperine metabolism. This enzyme decomposed the methylenedioxyphenyl group, which is the common structure in various plant-derived bioactive compounds such as sesamin, piperonal, safrole, and berberin. By utilizing this enzyme, piperine can be converted into a useful antioxidant compound. The findings about previously unknown metabolic pathways in nature can lead to the discovery of new enzymes and provide methods for the enzymatic synthesis of useful compounds.

Oleanolic Acid Complexation with Cyclodextrins Improves Its Cell Bio-Availability and Biological Activities for Cell Migration.

Wound healing is a complex process to restore skin. Plant-derived bioactive compounds might be a source of substances for the treatment of wounds stalled in a non-resolving stage of wound healing. Oleanolic acid (OA), a pentacyclic triterpene, has shown favorable wound healing properties both in vitro and in vivo. Unfortunately, OA cannot be solubilized in aqueous media, and it needs to be helped by the use of dimethyl sulfoxide (DMSO). In this paper, we have shown that cyclodextrins (CDs) are a good alternative to DMSO as agents to deliver OA to cells, providing better features than DMSO. Cyclodextrins are natural macromolecules that show a unique tridimensional structure that can encapsulate a wide variety of hydrophobic compounds. We have studied the cyclodextrin-encapsulated form of OA with OA/DMSO, comparing their stability, biological properties for cell migration, and cell viability. In addition, detailed parameters related to cell migration and cytoskeletal reorganization have been measured and compared. Our results show that OA-encapsulateds compound exhibit several advantages when compared to non-encapsulated OA in terms of chemical stability, migration enhancement, and preservation of cell viability.

The efficacy of natural bioactive compounds against prostate cancer: Molecular targets and synergistic activities.

Globally, prostate cancer (PCa) is regarded as a challenging health issue, and the number of PCa patients continues to rise despite the availability of effective treatments in recent decades. The current therapy with chemotherapeutic drugs has been largely ineffective due to multidrug resistance and the conventional treatment has restricted drug accessibility to malignant tissues, necessitating a higher dosage resulting in increased cytotoxicity. Plant-derived bioactive compounds have recently attracted a great deal of attention in the field of PCa treatment due to their potent effects on several molecular targets and synergistic effects with anti-PCa drugs. This review emphasizes the molecular mechanism of phytochemicals on PCa cells, the synergistic effects of compound-drug interactions, and stem cell targeting for PCa treatment. Some potential compounds, such as curcumin, phenethyl-isothiocyanate, fisetin, baicalein, berberine, lutein, and many others, exert an anti-PCa effect via inhibiting proliferation, metastasis, cell cycle progression, and normal apoptosis pathways. In addition, multiple studies have demonstrated that the isolated natural compounds: d-limonene, paeonol, lanreotide, artesunate, and bicalutamide have potential synergistic effects. Further, a significant number of natural compounds effectively target PCa stem cells. However, further high-quality studies are needed to firmly establish the clinical efficacy of these phytochemicals against PCa.

Suppression of sweet taste-related responses by plant-derived bioactive compounds and eating. Part II: A systematic review in animals

This article, the second in a two-part series, continues the discussion on the nature of the relationship between the level of sweet taste suppression and eating behaviour, but in animal rather human subjects. In particular, the aim was to review the scientific literature on the impact that bioactive compounds that decrease oral sweet sensations have on intake, preference and physiological status in preclinical studies. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 28 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. We identified three plant species, Gymnema sylvestre, Hovenia dulcis, and Ziziphus jujuba, that possess acute sweetness-inhibitory properties. When administered orally, these plants reduced neural responses to sweet stimuli and decreased consumption. However, studies on the longer-term effects of antisweet activity remain to be conducted. Translating the valuable insights into the mechanisms underlying the relationship between sweet taste impairment and eating behaviour into practical clinical applications are discussed.

Suppression of sweet taste-related responses by plant-derived bioactive compounds and eating. Part I: A systematic review in humans

The taste of food plays a crucial role in determining what and how much we eat. Thus, interventions that temporarily block sweet taste receptors offer a promising approach to addressing unhealthy behaviours associated with sugary foods. However, the relationship between reduced sweet taste response and food consumption remains unclear, with contradictory findings. Certain studies suggest that a diminished perception of sweetness leads to a sense of fullness and results in reduced food intake, while others suggest the opposite effect. To shed some light, our systematic review looked into the relationship between diminished sweet taste response and food consumption by examining the effects of bioactive compounds that experimentally inhibit sweetness in healthy individuals. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network, and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 33 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. The current literature predominantly focuses on the immediate impact of oral gymnemic acids, failing to provide preliminary evidence in support of the specific threshold hypothesis, above which food consumption decreases and below which the opposite effect occurs. Additionally, there was inconsistency in the findings regarding the short-term desire to eat following sweetness inhibition. Considering the downstream effects on energy intake and their clinical applications, further research is needed to clarify both the acute within-session effects (i.e., not wanting any more now) and the longer-term effects (i.e., deciding not to start eating) linked to oral sweet-taste-suppressing compounds.

Technological strategies for the use of plant-derived compounds in the preservation of fish products.

New approaches to reducing synthetic preservatives in the preservation of foods draw the attention of plant-derived bioactive compounds, especially for application in foods highly susceptible to spoilage, such as fish products. The review presents relevant data from procurement, application, and methodological research trends to investigate the potential effects of plant-derived bioactive compounds on shelf life extension in fish products. The systematization of data allowed observation that the different methods of extraction and application of bioactive plant compounds result in different effects, such as the reduction of lipid oxidation, antimicrobial effects, and maintenance of sensory characteristics, benefiting the extension of shelf life. In general, plant-derived bioactive compounds are an alternative for the preservation of fish products; however, approaches to the composition of the compounds can contribute to the optimization and efficiency of the process from a technical point of view and industrial viability.

Multi-Anticancer Activities of Phytoestrogens in Human Osteosarcoma.

Phytoestrogens are plant-derived bioactive compounds with estrogen-like properties. Their potential health benefits, especially in cancer prevention and treatment, have been a subject of considerable research in the past decade. Phytoestrogens exert their effects, at least in part, through interactions with estrogen receptors (ERs), mimicking or inhibiting the actions of natural estrogens. Recently, there has been growing interest in exploring the impact of phytoestrogens on osteosarcoma (OS), a type of bone malignancy that primarily affects children and young adults and is currently presenting limited treatment options. Considering the critical role of the estrogen/ERs axis in bone development and growth, the modulation of ERs has emerged as a highly promising approach in the treatment of OS. This review provides an extensive overview of current literature on the effects of phytoestrogens on human OS models. It delves into the multiple mechanisms through which these molecules regulate the cell cycle, apoptosis, and key pathways implicated in the growth and progression of OS, including ER signaling. Moreover, potential interactions between phytoestrogens and conventional chemotherapy agents commonly used in OS treatment will be examined. Understanding the impact of these compounds in OS holds great promise for developing novel therapeutic approaches that can augment current OS treatment modalities.

Sweet-inhibiting effects of gurmarin on intake during repeated acute and long-term sugar exposure: A behavioural analysis using an animal model

Excessive consumption of added sugars is linked to chronic diseases, such as obesity, diabetes, dyslipidaemia or cardiovascular disease; and public health is searching for new strategies to reduce it. Although plant-derived bioactive compounds with inhibitory properties of sweet taste like Gymnema sylvestre show the potential to reduce sugar intake acutely, their impact after repeated administration is unknown. Therefore, we examined the changes of single and repeated exposures of a Gymnema sylvestre constituent, gurmarin, in sweet beverage consumption and preference in a preclinical model. 24 Wistar rats (50 % females) were divided into experimental (gurmarin) and two control groups (gymnemic acids or phosphate buffer solutions) according to the substances orally applied. Then acceptance and preference tests with sugar were performed within (Experiment 1) and between sessions (Experiment 2). We found that administering gurmarin decreased sucrose intake significantly, even after multiple treatments, without rebound effects. These findings suggest that sweet taste suppressors could be an effective tool for reducing long-term sugar consumption when repeatedly administrated.

Menthol causes mitochondrial Ca2+-influx, affects structure-function relationship and cools mitochondria

Menthol is a small bioactive compound able to cause several physiological changes and has multiple molecular targets. Therefore, cellular response against menthol is complex, and still poorly understood. In this work, we used a human osteosarcoma cell line (Saos-2) and analysed the effect of menthol, especially in terms of cellular, subcellular and molecular aspects. We demonstrate that menthol causes increased mitochondrial Ca2+ in a complex manner, which is mainly contributed by intracellular sources, including ER. Menthol also changes the Ca2+-load of individual mitochondrial particles in different conditions. Menthol increases ER-mito contact points, causes mitochondrial morphological changes, and increases mitochondrial ATP, cardiolipin, mitochondrial ROS and reduces mitochondrial membrane potential (ΔΨm). Menthol also prevents the mitochondrial quality damaged by sub-lethal and lethal doses of CCCP. In addition, menthol lowers the mitochondrial temperature within cell and also serves as a cooling agent for the isolated mitochondria in a cell free system too. Notably, menthol-induced reduction of mitochondrial temperature is observed in diverse types of cells, including neuronal, immune and cancer cells. As the higher mitochondrial temperature is a hallmark of several inflammatory, metabolic, disease and age-related disorders, we propose that menthol can serve as an active anti-aging compound against all these disorders. These findings may have relevance in case of several pharmacological and clinical applications of menthol. Significance statementMenthol is a plant-derived bioactive compound that is widely used for several physiological, behavioural, addictive, and medicinal purposes. It is a well-established “cooling and analgesic agent”. However, the exact cellular and sub-cellular responses of menthol is poorly understood. In this work, we have characterized the effects of menthol on mitochondrial metabolism. Menthol regulates mitochondrial Ca2+, ATP, superoxides, cardiolipin, membrane-potential, and ER-mito contact sites. Moreover, the cooling agent menthol also cools down mitochondria and protects mitochondrial damage by certain toxins. These findings may promote use of menthol as a useful supplementary agent for anti-aging, anti-cancer, anti-inflammatory purposes where higher mitochondrial temperature is prevalent.

New Insights into the Latest Advancement in α-Amylase Inhibitors of Plant Origin with Anti-Diabetic Effects.

The rising predominance of type 2 diabetes, combined with the poor medical effects seen with commercially available anti-diabetic medications, has motivated the development of innovative treatment approaches for regulating postprandial glucose levels. Natural carbohydrate digestion enzyme inhibitors might be a viable option for blocking dietary carbohydrate absorption with fewer side effects than manufactured medicines. Alpha-amylase is a metalloenzyme that facilitates digestion by breaking down polysaccharides into smaller molecules such as maltose and maltotriose. It also contributes to elevated blood glucose levels and postprandial hyperglycemia. As a result, scientists are being urged to target α-amylase and create inhibitors that can slow down the release of glucose from carbohydrate chains and prolong its absorption, thereby resulting in lower postprandial plasma glucose levels. Natural α-amylase inhibitors derived from plants have gained popularity as safe and cost-effective alternatives. The bioactive components responsible for the inhibitory actions of various plant extracts have been identified through phytochemical research, paving the way for further development and application. The majority of the findings, however, are based on in vitro investigations. Only a few animal experiments and very few human investigations have confirmed these findings. Despite some promising results, additional investigation is needed to develop feasible anti-diabetic drugs based on plant-derived pancreatic α-amylase inhibitors. This review summarizes the most recent findings from research on plant-derived pancreatic α-amylase inhibitors, including plant extracts and plant-derived bioactive compounds. Furthermore, it offers insights into the structural aspects of the crucial therapeutic target, α-amylases, in addition to their interactions with inhibitors.

Future scope of plant-derived bioactive compounds in the management of methicillin-resistant Staphylococcus aureus: In vitro antimicrobial and antivirulence prospects to combat MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) is a foremost human and animal pathogen with public health and veterinary significance causing hospital and community infections and contagious bovine mastitis. Due to its ability to develop multidrug resistance (MDR) and its pathogenicity, MRSA infection control is becoming a global concern. Natural antibacterial options are needed to combat MDR development and infectious dissemination. This study investigated the antimicrobial resistance and virulence genes profiling of MRSA isolates and explored the antivirulence efficacy of trans-cinnamaldehyde, thymol, and carvacrol essential oils (EOs) against multivirulent and MDR-MRSA isolates. Thirty six S. aureus isolates (25%) were retrieved, of which 34 (94.4%) were MRSA. A high prevalence of MDR (66.7%) was monitored and all 53 molecularly verified isolates possessed icaA and cna virulence genes. Moreover, 94.1% of these isolates were multivirulent with 23.5% of them carrying icaA, cna, eta, tst, and sea virulence genes. Our data proved superior in vitro antimicrobial and antivirulence activities of trans-cinnamaldehyde, thymol, and carvacrol. They inhibited the growth of multi-virulent and MDR-MRSA isolates and downregulated the transcription of examined virulence genes. Our study suggests using EOs as prospective antimicrobials with excellent antivirulence activities against MRSA isolates. We provided data regarding the eventual role of phytogenics in prevention and control of MRSA infection.

Mechanistic insights into Corona viruses and Covid-19: unravelling the possible treatment strategies with emphasis on plant-derived bioactive compounds

Mechanistic insights into Corona viruses and Covid-19: unravelling the possible treatment strategies with emphasis on plant-derived bioactive compounds

Physalin A Enhances Autophagy and Suppresses Oxidative Stress Injury and Extracellular Matrix Deposition in Diabetic Nephropathy

Diabetic nephropathy is the major cause of chronic kidney disease worldwide. Persistent hyperglycemia plays a causative role in diabetic nephropathy. Physalin A, a steroidal plant-derived bioactive compound known to exhibit anti-inflammatory, anti-tumor, anti-fungal, and analgesic activities, has been widely used in traditional Chinese medicine practice. The present study examined the effect of Physalin A on high-glucose-treated HBZY-1 cells, a cell culture model of diabetic nephropathy. The results show that Physalin A alleviated cell proliferation, oxidative stress, extracellular matrix protein deposition, and insufficient autophagy induced by high glucose through inhibiting the mitogen-activated protein kinase pathway.

The effect of Sinensetin and Imperatorin on A-549 lung cancer cell viability in vitro

Introduction: Lung cancer remains the leading cause of cancer death worldwide, so research is ongoing to discover new therapeutics, such as plant-derived bioactive compounds. For example, Sinensetin, a plant-derived polymethoxylated flavonoid, and Imperatorin, a natural furanocoumarin, have anti-cancer properties. This study assessed the effects of sinensetin and imperatorin separately and in combination on A-549 lung cancer cell viability. Method: The A-549 lung cancer cell line was treated with sinensetin (60 μM), imperatorin (30 M), or a combination of both compounds (Sin:Imp 30:30 μM; 50:50 μM and 60:30 μM) for 48 hours. Cell viability was then assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and apoptosis was determined using fluorescein isothiocyanate (FITC) Annexin-V/Propidium iodide staining. Results: The combination treatment of Sin:Imp 50:50 and Sin:Imp 60:30 μM reduced cell viability more than the individual treatment of sinensetin and imperatorin, with the lowest cell viability observed for the combination treatment of Sin:Imp 50:50 μM. Likewise, the combination treatment of Sin:Imp 50:50 μM induced the most apoptosis compared to individual treatment. Conclusion: Sinensetin and imperatorin can decrease A-549 lung cancer cell viability and are potent apoptotic inducers, especially when they are used in combination, therefore they are potential lung cancer therapeutics.

Promising Role of the Scutellaria baicalensis Root Hydroxyflavone–Baicalein in the Prevention and Treatment of Human Diseases

Plant roots, due to a high content of natural antioxidants for many years, have been used in herbal medicine. It has been documented that the extract of Baikal skullcap (Scutellaria baicalensis) has hepatoprotective, calming, antiallergic, and anti-inflammatory properties. Flavonoid compounds found in the extract, including baicalein, have strong antiradical activity, which improves overall health and increases feelings of well-being. Plant-derived bioactive compounds with antioxidant activity have for a long time been used as an alternative source of medicines to treat oxidative stress-related diseases. In this review, we summarized the latest reports on one of the most important aglycones with respect to the pharmacological activity and high content in Baikal skullcap, which is 5,6,7-trihydroxyflavone (baicalein).

Plant-Derived Bioactive Compounds in the Management of Neurodegenerative Disorders: Challenges, Future Directions and Molecular Mechanisms Involved in Neuroprotection.

Neurodegenerative disorders encompass a wide range of pathological conditions caused by progressive damage to the neuronal cells and nervous-system connections, which primarily target neuronal dysfunction and result in problems with mobility, cognition, coordination, sensation, and strength. Molecular insights have revealed that stress-related biochemical alterations such as abnormal protein aggregation, extensive generation of reactive oxygen and nitrogen species, mitochondrial dysfunction, and neuroinflammation may lead to damage to neuronal cells. Currently, no neurodegenerative disease is curable, and the available standard therapies can only provide symptomatic treatment and delay the progression of the disease. Interestingly, plant-derived bioactive compounds have drawn considerable attention due to their well-established medicinal properties, including anti-apoptotic, antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as neuroprotective, hepatoprotective, cardioprotective, and other health benefits. Plant-derived bioactive compounds have received far more attention in recent decades than synthetic bioactive compounds in the treatment of many diseases, including neurodegeneration. By selecting suitable plant-derived bioactive compounds and/or plant formulations, we can fine tune the standard therapies because the therapeutic efficacy of the drugs is greatly enhanced by combinations. A plethora of in vitro and in vivo studies have demonstrated plant-derived bioactive compounds' immense potential, as proven by their capacity to influence the expression and activity of numerous proteins implicated in oxidative stress, neuroinflammation, apoptosis, and aggregation. Thus, this review mostly focuses on the antioxidant, anti-inflammatory, anti-aggregation, anti-cholinesterase, and anti-apoptotic properties of several plant formulations and plant-derived bioactive compounds and their molecular mechanisms against neurodegenerative disorders.

Plant-derived Bioactive Compounds Targeting MMP-9 for Treatment of Endometrial Carcinoma: An In silico Study

Endometrial cancer, also called uterine cancer, is the second most common and fourth leading cause of death among gynecological problems in the world. Matrix metalloproteinase-9 (MMP-9) has been found to play an important role in the formation and metastases of endometrial cancer. Thus, this study investigates the naturally anti-inflammatory compounds available from plant sources that can target the MMP-9 by various in silico approaches. The target 1L6J (Crystal structure of human matrix metalloproteinase-9) structure was retrieved from the PDB database. Five plant compounds were selected based on Lipinski’s rule of five using the PubChem database. The pharmacokinetics, ADMET properties, and biological activity of these compounds were predicted computationally using databases such as SWISS-ADME, pkCSM, and PASS. Comparative analysis of the bioactive compounds with the target was performed by AutoDock 4.2.6. The target residues interacting with the compounds were visualized in a 2D manner using LigPlot v.2.2. Based on the docking results, the compounds namely lupeol, ß amyrin, ursolic acid, kaempferol, and quercetin exhibited binding energy value of -10.68 kcal/mol, -9.4 kcal/mol, -9.02 kcal/mol, -8.72 kcal/mol and -8.45 kcal/mol respectively; whereas the control drug, Megestrol acetate showed -8.84 kcal/mol kcal thus, indicating that few of the selected compounds were seen to have better binding energy comparative to the control drug. We conclude that lupeol, ß amyrin, and ursolic acid can be potent inhibitors of target MMP-9 with the least side effects. Therefore, by in vitro and in vivo studies, these compounds can be effectively explored to evaluate the level of toxicity and efficacy to develop more effective treatments for endometrial carcinoma.

Resveratrol, Epigallocatechin Gallate and Curcumin for Cancer Therapy: Challenges from Their Pro-Apoptotic Properties

Plant-derived bioactive compounds are gaining wide attention for their multiple health-promoting activities and in particular for their anti-cancer properties. Several studies have highlighted how they can prevent cancer initiation and progression, improve the effectiveness of chemotherapy, and, in some cases, limit some of the side effects of chemotherapy agents. In this paper, we provide an update of the literature on the anti-cancer effects of three extensively studied plant-derived compounds, namely resveratrol, epigallocatechin gallate, and curcumin, with a special focus on the anti-cancer molecular mechanisms inducing apoptosis in the major types of cancers globally.

Myrtaceae family: an update on plant-derived bioactive compounds against bacteria that affect the respiratory system

Abstract Respiratory bacterial infections are a cause of morbidity and mortality worldwide; most of these infections respond well to antibiotic therapies, although several factors cause bacteria to become increasingly resistant, leading to a concerning public health problem. Hence, researchers have sought new antibiotics that can replace or enhance the effectiveness of existing drugs. Given this scenario, this review is based on original articles from the PubMed and Science Direct databases published from May 2015 to February 2022 that reported the potential of essential oils, extracts, and formulations containing Myrtaceae and nanoparticles against bacteria that affect the respiratory system.

Strategies for the discovery of potential anticancer agents from plants collected from Southeast Asian tropical rainforests as a case study.

Covering up to early 2023The present review summarizes recent accomplishments made as part of a multidisciplinary, multi-institutional anticancer drug discovery project, wherein samples comprising higher plants were collected primarily from Southeast Asia, and also from Central America, and the West Indies. In the introductory paragraphs, a short perspective is provided on the current importance of plants in the discovery of cancer therapeutic agents, and the contributions of other groups working towards this objective are mentioned. For our own investigations, following their collection, tropical plants have been subjected to solvent extraction and biological evaluation for their antitumor potential. Several examples of purified plant lead bioactive compounds were obtained and characterized, and found to exhibit diverse structures, including those of the alkaloid, cardiac glycoside, coumarin, cucurbitacin, cyclobenzofuran (rocaglate), flavonoid, lignan, and terpenoid types. In order to maximize the efficiency of work on drug discovery from tropical plant species, strategies to optimize various research components have been developed, including those for the plant collections and taxonomic identification, in accordance with the requirements of contemporary international treaties and with a focus on species conservation. A major component of this aspect of the work is the development of collaborative research agreements with representatives of the source countries of tropical rainforest plants. The phytochemical aspects have included the preparation of plant extracts for initial screening and the selection of promising extracts for activity-guided fractionation. In an attempt to facilitate this process, a TOCSY-based NMR procedure has been applied for the determination of bioactive rocaglate derivatives in samples of Aglaia species (Meliaceae) collected for the project. Preliminary in vitro and in vivo mechanistic studies carried out by the authors are described for two tropical plant-derived bioactive lead compounds, corchorusoside C and (+)-betulin, including work conducted with a zebrafish (Danio rerio) model. In the concluding remarks, a number of lessons are summarized that our group has learned as a result of working on anticancer drug discovery using tropical plants, which we hope will be of interest to future workers.