In silico and in vivo study: chamazulene and/or cinnamic acid modulate IRS2/GLUT4, HNF4α, GLUT2, redox system, DNA damage, and lipid profile signifying their potential antidiabetic effect

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Glycogen synthase kinase 3β (GSK-3β) plays a pivotal role in AD pathogenesis, particularly in tau protein hyperphosphorylation. Natural bioactive compounds have a wide range of sources, and medicinally valuable active compound can be extracted from plants, animals, and microorganisms. Currently, studies have found that various natural bioactive compounds from plants have the potential to improve AD symptoms, such as resveratrol and berberine. Therefore, this review examines the potential of natural bioactive compounds to modulate GSK-3β activity and inhibit the hyperphosphorylation of tau, offering a promising therapeutic strategy for AD. We summarize the current understanding of alkaloids, phenols, flavonoids, terpenoids and other natural compounds, highlighting their mechanisms of action and preclinical efficacy.

Stroke represents one of the main causes of disability and death worldwide. The pathological subtypes of stroke are ischemic stroke, the most frequent, and hemorrhagic stroke. Nrf2 is a transcription factor that regulates redox homeostasis. In stress conditions, Nrf2 translocates inside the nucleus and induces the transcription of enzymes involved in counteracting oxidative stress, endobiotic and xenobiotic metabolism, regulators of inflammation, and others. Different natural compounds, including food and plant-derived components, were shown to be able to activate Nrf2, mediating an antioxidant response. Some of these compounds were tested in stroke experimental models showing several beneficial actions. In this review, we focused on the studies that evidenced the positive effects of natural bioactive compounds in stroke experimental models through the activation of Nrf2 pathway. Interestingly, different natural compounds can activate Nrf2 through multiple pathways, inducing a strong antioxidant response associated with the beneficial effects against stroke. According to several studies, the combination of different bioactive compounds can lead to a better neuroprotection. In conclusion, natural bioactive compounds may represent new therapeutic strategies against stroke.

Several epidemiologic studies have shown that chronic inflammation predisposes individuals to various types of cancer. Many cancers arise from sites of infection, chronic irritation, and inflammation. Conversely, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumors. Natural bioactive compounds in dietary plant products including fruits, vegetables, grains, legumes, tea, and wine are claimed to help prevent cancer, degenerative diseases, and chronic and acute inflammation. Modern methods in cell and molecular biology allow us to understand the interactions of different natural bioactive compounds with basic mechanisms of inflammatory response. The molecular pathways of this cancer-related inflammation are now unraveled. Natural bioactive compounds exert anti-inflammatory activity by modulating pro-inflammatory gene expressions have shown promising chemopreventive activity. This review summarizes current knowledge on natural bioactive compounds that act through the signaling pathways and modulate inflammatory gene expressions, thus providing evidence for these substances in cancer chemopreventive action.

The use of natural food ingredients has been increased in recent years due to the negative health implications of synthetic ingredients. Natural bioactive compounds are important for the development of health-oriented functional food products with better quality attributes. The natural bioactive compounds possess different types of bioactivities, e.g., antioxidative, antimicrobial, antihypertensive, and antiobesity activities. The most common method for the development of functional food is the fortification of these bioactive compounds during food product manufacturing. However, many of these natural bioactive compounds are heat-labile and less stable. Therefore, the industry and researchers proposed the microencapsulation of natural bioactive compounds, which may improve the stability of these compounds during processing and storage conditions. It may also help in controlling and sustaining the release of natural compounds in the food product matrices, thus, providing bioactivity for a longer duration. In this regard, several advanced techniques have been explored in recent years for microencapsulation of bioactive compounds, e.g., essential oils, healthy oils, phenolic compounds, flavonoids, flavoring compounds, enzymes, and vitamins. The efficiency of microencapsulation depends on various factors which are related to natural compounds, encapsulating materials, and encapsulation process. This review provides an in-depth discussion on recent advances in microencapsulation processes as well as their application in food systems.

Cancer is a dreadful disease, and it is considered as one of the biggest health problems for the human populations and demands an intense strategy to cure. Cancer causes around 70% death in lower- and middle-income countries. Recent studies have reported that natural bioactive compounds (obtained from medicinal plants) in combination with anticancer drugs have great potential to destroy cancerous cells while not affecting normal cells. Natural bioactive compounds are considered suitable candidates for anticancer drug development with the great success opportunity due to their excellent properties for modulating multiple cellular and molecular targets of oncogenesis directly or indirectly and have shown great progress past several decades. The chief anticancerous properties include the inhibition of tumor cell growth, the induction of apoptosis, DNA damage, the inhibition of topoisomerases I and II, and others. Nowadays, many researchers are on the way to develop potential drugs that can inhibit or delay the growth of tumor cells without any type of side effects from natural bioactive compounds. The chief plant-based bioactive compounds with potential cancer therapeutic potential include curcumin, camptothecin, diosgenin, epigallocatechin-3-gallate, homoharringtonine, piperine, podophyllotoxin, resveratrol, vinca alkaloids, etc.This chapter provides a comprehensive report on the recent advancements and breakthrough accomplished in cancer treatments using natural bioactive compounds alone or in combination with other known therapies along with their possible mechanism of action on nuclear and cellular factors.KeywordsBioactive compoundsAnticancer therapeuticsApoptosisTopoisomerase inhibition

Gut microbiota composition has caused perplexity in developing precision therapy to cure metabolic disorders. However, recent research has focused on using daily diet and natural bioactive compounds to correct gut microbiota dysbiosis and regulate host metabolism. Complex interactions between the gut microbiota and dietary compounds disrupt or integrate the gut barrier and lipid metabolism. In this review, we investigate the role of diet and bioactive natural compounds in gut microbiota dysbiosis and also the modulation of lipid metabolism by their metabolites. Recent studies have revealed that diet, natural compounds and phytochemicals impact significantly on lipid metabolism in animals and humans. These findings suggest that dietary components or natural bioactive compounds have a significant impact on microbial dysbiosis linked to metabolic diseases. The interaction between dietary components or natural bioactive compounds and gut microbiota metabolites can regulate lipid metabolism. Additionally, natural products can shape the gut microbiota and improve barrier integrity by interacting with gut metabolites and their precursors, even in unfavourable conditions, potentially contributing to the alignment of host physiology.

Although synthetic bioactive compounds are approved in many countries for food applications, they are becoming less and less welcome by consumers. Therefore, there has been an increasing interest in replacing these synthetic compounds by natural bioactive compounds. These natural compounds can be used as food additives to maintain the food quality, food safety and appeal, and as food supplements or nutraceuticals to correct nutritional deficiencies, maintain a suitable intake of nutrients, or to support physiological functions, respectively. Recent studies reveal that numerous food wastes, particularly fruit and vegetables byproducts, are a good source of bioactive compounds that can be extracted and reintroduced into the food chain as natural food additives or in food matrices for obtaining nutraceuticals and functional foods. This review addresses general questions concerning the use of fruit and vegetables byproducts as new sources of natural bioactive compounds that are being addressed to foods as natural additives and supplements. Those bioactive compounds must follow the legal requirements and evaluations to assess the risks for human health and their toxicity must be considered before being launched into the market. To overcome the potential health risk while increasing the biological activity, stability and biodistribution of the supplements’ technological alternatives have been studied such as encapsulation of bioactive compounds into micro or nanoparticles or nanoemulsions. This will allow enhancing the stability and release along the gastrointestinal tract in a controlled manner into the specific tissues. This review summarizes the valorization path that a bioactive compound recovered from an agro-food waste can face from the moment their potentialities are exhibited until it reaches the final consumer and the safety and toxicity challenges, they may overcome.

Hexavalent chromium [Cr(VI)] has emerged as a prevailing environmental and occupational contaminant over the past few decades. However, the knowledge is sparse regarding Cr(VI)-induced neurological aberrations, and its remediation through natural bioactive compounds has not been fully explored. This study intended to probe the possible invigorative effects of nutraceuticals such as coenzyme Q10 (CoQ10), biochanin A (BCA), and phloretin (PHL) on Cr(VI) intoxicated Swiss albino mice with special emphasis on Nrf2/HO-1/NQO1 gene expressions. Mice received potassium dichromate (75ppm) through drinking water and were simultaneously co-treated intraperitoneally with CoQ10 (10mg/kg), BCA, and PHL (50mg/kg) each for 30-day treatment period. The statistics highlight the elevated levels of lipid peroxidation (LPO) and protein carbonyl content (PCC) with a concomitant reduction in the superoxide dismutase (SOD), glutathione-S-transferase (GST), reduced glutathione (GSH), total thiols (TT), catalase (CAT), and cholinesterase activities in the Cr(VI)-exposed mice. The collateral assessment of DNA fragmentation, DNA breakages, and induced histological alterations was in conformity with the above findings in conjugation with the dysregulation in the Nrf2 and associated downstream HO-1 and NQO1 gene expressions. Co-treatment with the selected natural compounds reversed the above-altered parameters significantly, thereby bringing cellular homeostasis in alleviating the Cr(VI)-induced conciliated impairments. Our study demonstrated that the combination of different bioactive compounds shields the brain better against Cr(VI)-induced neurotoxicity by revoking the oxidative stress-associated manifestations. These compounds may represent a new potential combination therapy due to their ability to modulate the cellular antioxidant responses by upregulating the Nrf2/HO-1/NQO1 signaling pathway against Cr(VI)-exposed population. HIGHLIGHTS: Cr(VI)-associated heavy metal exposure poses a significant threat to the environment, especially to living organisms. Cr(VI) exposure for 30 days resulted in the free radical's generation that caused neurotoxicity in the Swiss albino mice. Natural compounds such as coenzyme Q10, biochanin A, and phloretin counteracted the neurotoxic effect due to Cr(VI) exposure in scavenging of free radicals by enhancing Nrf2/HO-1/NQO1 gene expressions in maintaining the cellular homeostasis.

Whenever we focus our attention towards malignancies caused by cancer, usually our mind gets preoccupied with many conflicting thoughts. When we look at cancer statistics, our heart starts sinking more and more as we drill down to details about incidence rate, mortality rate, trends etc. In spite of tremendous technological advancements over several decades, cancer is second only to cardiovascular disease as a cause of death. When we see so many people dying from cancer, sometimes we wonder if this is a nature’s answer to keep population under control. But when we bring together data from different sources like epidemiological studies, cancer molecular biology, molecular epidemiological studies; we are more than convinced that cancer is a man-made malignancy akin global warming. In fact when we review source of drugs available for cancer treatment, it’s inevitable to miss fact that majority of anticancer drugs are sourced either directly from natural bioactive compounds or after structural optimization of natural compound. We can say that nature holds bounty of medicinal compounds, and onus is on us to discover and explore their possible medicinal applications. Usage of compounds from natural sources especially plant based can be dated back to possibly even before dawn of civilization. Most of the chemotherapeutic drugs are also derived from natural bioactive compounds. Research effort during past several decades has been dedicated on screening of bioactives from natural sources, with more focus on easily available resources like terrestrial fauna and flora. However, big pharmaceutical companies have diverted their focus from natural compound based discovery most probably to avoid possible patent conflicts. ‘

Aim: This documentary review aimed to make a synthesis of bioactive plants or natural compounds on schistosomes. We carried out a review from 2000 to 2022, oriented towards the plants in order to search natural compounds bioactive on schistosomes which can be a great contribution for new drugs discovering.
 Terms such as “schistosomiasis and medicinal plants”, “natural anti-schistosome compounds”, “phytochemical screening”, “bioactive compounds on schistosomes” were used for the online literature search through the following sites: PubMed; Google Scholar; ScienceDirect and Hinari.
 Results: There are many plants already used for the traditional treatment of schistosomiasis. This review found nearly 72 families of plants belonging to 228 botanical species have been listed. Some of these have been studied in vitro / in vivo and preliminary results have shown their schistosomicidal properties. Moreover, the results of qualitative phytochemical screening and toxicity testing of these natural compounds provide hope for new drug discoveries.
 Conclusion: Even if plants efficacy is proven, we need more in-depth investigations to determine their chemical components in order to minimize the undesirable effects and to guarantee their safety by assessing their toxicity.

Anemonin is a natural bioactive compound that can regulate tyrosinase-related proteins and mRNA in human melanocytes

Natural bioactive compounds abundantly presented in foods and medicinal plants have recently received a remarkable attention because of their various biological activities and minimal toxicity. In recent years, many natural compounds appear to offer significant effects in the regulation of ferroptosis. Ferroptosis is the forefront of international scientific research which has been exponential growth since the term was coined. This type of regulated cell death is driven by iron-dependent phospholipid peroxidation. Recent studies have shown that numerous organ injuries and pathophysiological processes of many diseases are driven by ferroptosis, such as cancer, arteriosclerosis, neurodegenerative disease, diabetes, ischemia-reperfusion injury and acute renal failure. It is reported that the initiation and inhibition of ferroptosis plays a pivotal role in lipid peroxidation, organ damage, neurodegeneration and cancer growth and progression. Recently, many natural phytochemicals extracted from edible plants have been demonstrated to be novel ferroptosis regulators and have the potential to treat ferroptosis-related diseases. This review provides an updated overview on the role of natural bioactive compounds and the potential signaling pathways in the regulation of ferroptosis.

Triple-negative breast cancer (TNBC) is characterized by the absence of HER2 expression, progesterone receptor (PR), and estrogen receptor (ER). TNBC has a poor prognosis and limited therapy options due to its lack of specific targets and aggressive behavior. This review demonstrates the therapeutic efficacy and mechanisms of natural compounds in targeting key molecular pathways involved in the development and progression of TNBC, investigating their interaction with oncogenic signaling pathways. A thorough literature review was conducted using databases such as PubMed, Scopus, and Web of Science to identify studies assessing the anti-TNBC properties of natural compounds. Natural bioactive compounds like curcumin, resveratrol, quercetin, EGCG, berberine, and thymoquinone have demonstrated promising anticancer properties in TNBC models. These limit metastasis, induce apoptosis, inhibit proliferation, and reverse chemoresistance by altering vital pathways like PI3K/AKT/ mTOR, MAPK/ERK, NF-κB, JAK/STAT, and Wnt/β-catenin. For example, quercetin inhibits NF-κB signalling and increases the cytotoxicity of doxorubicin, but curcumin decreases AKT phosphorylation. Furthermore, natural compounds may enhance immune response in BRCA-mutated TNBC by modifying immunological checkpoints, including PD-L1, when combined with PARP inhibitors. Natural compounds are a promising supplementary method for TNBC therapy due to their ability to target unregulated pathways and overcome therapeutic resistance. Nevertheless, challenges such as pharmacokinetics, limited bioavailability, and a lack of clinical validation persist. Future research should focus on combinatorial regimens, nanocarrier-based delivery technologies, and biomarker-guided clinical trials to develop successful TNBC treatments.

The data here is related to the article, “Curcumin enhances poly (ADP-ribose) polymerase inhibitor sensitivity to chemotherapy in breast cancer cells” (Y.E Choi, and E. Park, 2015) [1]. The article shows that curcumin, as a natural bioactive compound, enhanced DNA damage response and induced cell death in MDA-MB-231 cells [1]. This data includes that breast cancer cells, MDA-MB-231 respond to DNA damage after UV irradiation, post to resveratrol treatment. The data shows that resveratrol treatment results in reduction of S-phase cell cycle and induction of γ-H2AX, which is a hallmark of DNA damage after UV irradiation in breast cancer cells, MDA-MB-231. Moreover, resveratrol sensitizes breast cancer cells to respond to UV treatment as a natural bioactive compound.

Ovarian cancer represents a major health concern for the female population: there is no obvious cause, it is frequently misdiagnosed, and it is characterized by a poor prognosis. Additionally, patients are inclined to recurrences because of metastasis and poor treatment tolerance. Combining innovative therapeutic techniques with established approaches can aid in improving treatment outcomes. Because of their multi-target actions, long application history, and widespread availability, natural compounds have particular advantages in this connection. Thus, effective therapeutic alternatives with improved patient tolerance hopefully can be identified within the world of natural and nature-derived products. Moreover, natural compounds are generally perceived to have more limited adverse effects on healthy cells or tissues, suggesting their potential role as valid treatment alternatives. In general, the anticancer mechanisms of such molecules are connected to the reduction of cell proliferation and metastasis, autophagy stimulation and improved response to chemotherapeutics. This review aims at discussing the mechanistic insights and possible targets of natural compounds against ovarian cancer, from the perspective of medicinal chemists. In addition, an overview of the pharmacology of natural products studied to date for their potential application towards ovarian cancer models is presented. The chemical aspects as well as available bioactivity data are discussed and commented on, with particular attention to the underlying molecular mechanism(s).