The number of people diagnosed with type 2 diabetes is on the increase worldwide. Of growing concern, the prevalence of type 2 diabetes in children and youths is increasing rapidly and mirrors the increasing burden of childhood obesity. There are many risk factors associated with the condition; some are due to lifestyle, but many are beyond our control, such as genetics. There is an urgent need to develop better therapeutics for the prevention and management of this complex condition since current medications often cause unwanted side effects, and poorly managed diabetes can result in the onset of related comorbidities. Naturally derived compounds have gained momentum for preventing and managing several complex conditions, including type 2 diabetes. Here, we provide an update on the benefits and limitations of fenugreek and its components as a therapeutic for type 2 diabetes, including its bioavailability and interaction with the microbiome.

Proteases are implicated in every hallmark of cancer and have complicated functions. For cancer cells to survive and thrive, the process of controlling intracellular proteins to keep the balance of the cell proteome is essential. Numerous natural compounds have been used as ligands/ small molecules to target various proteases that are found in the lysosomes, mitochondria, cytoplasm, and extracellular matrix, as possible anticancer therapeutics. Promising protease modulators have been developed for new drug discovery technology through recent breakthroughs in structural and chemical biology. The protein structure, function of significant tumor-related proteases, and their natural compound inhibitors have been briefly included in this study. This review highlights the most current frontiers and future perspectives for novel therapeutic approaches associated with the list of anticancer natural compounds targeting protease and the mode and mechanism of proteinase-mediated molecular pathways in cancer.

Immunogenic cell death (ICD) can activate adaptive immune response in the host with normal immune system. Some synthetic chemotherapeutic drugs and natural compounds have shown promising results in cancer treatment by triggering the release of damage-associated molecules (DAMPs) to trigger ICD. However, most chemotherapeutic drugs exhibit non-selective cytotoxicity and may also induce and promote metastasis, thereby significantly reducing their clinical efficacy. Among the natural compounds that can induce ICD, plant-derived compounds account for the largest proportion, which are of increasing value in the treatment of cancer. Understanding which plant-derived natural compounds can induce ICD and how they induce ICD is crucial for developing strategies to improve chemotherapy outcomes. In this review, we focus on the recent findings regarding plant-derived natural compounds that induce ICD according to the classification of flavonoids, alkaloids, glycosides, terpenoids and discuss the potential mechanisms including endoplasmic reticulum (ER) stress, DNA damage, apoptosis, necroptosis autophagy, ferroptosis. In addition, plant-derived natural compounds that can enhance the ICD induction ability of conventional therapies for cancer treatment is also elaborated. The rational use of plant-derived natural compounds to induce ICD is helpful for the development of new cancer treatment methods.

The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer\'s disease (AD) progression. Once it enters the brain, the SARS-CoV-2 virus stimulates accumulation of amyloids in the brain that are highly toxic to neural cells. These amyloids may trigger neurological symptoms in COVID-19. The meningeal lymphatic vessels (MLVs) play an important role in removal of toxins and mediate viral drainage from the brain. MLVs are considered a promising target to prevent COVID-19-exacerbated dementia. However, there are limited methods for augmentation of MLV function. This review highlights new discoveries in the field of COVID-19-mediated amyloid accumulation in the brain associated with the neurological symptoms and the development of promising strategies to stimulate clearance of amyloids from the brain through lymphatic and other pathways. These strategies are based on innovative methods of treating brain dysfunction induced by COVID-19 infection, including the use of photobiomodulation, plasmalogens, and medicinal herbs, which offer hope for addressing the challenges posed by the SARS-CoV-2 virus.

The aim of this review is to present the potential application of camphor-a bicyclic monoterpene ketone-in the prevention of skin infections. Skin diseases represent a heterogeneous group of disorders characterized by prolonged symptoms that significantly diminish the quality of life. They affect the dermis, the epidermis, and even subcutaneous tissue. They very often have a bacterial or fungal background. Therapy for dermatological skin disorders is difficult and long-term. Therefore, it is important to find a compound, preferably of natural origin, that (i) prevents the initiation of this infection and (ii) supports the skin\'s repair process. Based on its documented anti-inflammatory, antibacterial, antifungal, anti-acne, anesthetic, strengthening, and warming properties, camphor can be used as a preventative measure in dermatological infectious diseases and as a component in medical and cosmetic products. This work discusses the structure and physicochemical properties of camphor, its occurrence, and methods of obtaining it from natural sources as well as through chemical synthesis. The use of camphor in industrial preparations is also presented. Additionally, after a detailed review of the literature, the metabolism of camphor, its interactions with other medicinal substances, and its antimicrobial properties against bacteria and fungi involved in skin diseases are discussed with regard to their resistance.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter regulating numerous physiological functions, and its dysregulation is a crucial component of the pathological processes of schizophrenia, depression, migraines, and obesity. 5-HT interacts with 14 different receptors, of which 5-HT1A-1FRs, 5-HT2A-CRs, and 5-HT4-7Rs are G protein-coupled receptors (GPCRs), while 5-HT3R is a ligand-gated ion channel. Over the years, selective orthosteric ligands have been identified for almost all serotonin receptors, yielding several clinically relevant drugs. However, the high degree of homology between 5-HTRs and other GPCRs means that orthosteric ligands can have severe side effects. Thus, there has recently been increased interest in developing safer ligands of GPCRs, which bind to less conserved, more specific sites, distinct from that of the receptor\'s natural ligand. The present review describes the identification of allosteric ligands of serotonin receptors, which are largely natural compounds (oleamide, cannabidiol, THC, and aporphine alkaloids), complemented by synthetic modulators developed in large part for the 5-HT2C receptor. The latter are positive allosteric modulators sought after for their potential as drugs preferable over the orthosteric agonists as antiobesity agents for their potentially safer profile. When available, details on the interactions between the ligand and allosteric binding site will be provided. An outlook on future research in the field will also be provided.

Chlorpyrifos (CPF) is a widely used organophosphate insecticide, though its excessive use causes environmental contamination, raising concerns about its adverse effects on human health. In this regard, Urtica dioica stands out as a promising candidate for counteracting chemical \'contaminant\' toxicity thanks to its therapeutic properties. Therefore, our study aimed to investigate the potential of an Urtica dioica ethanolic extract (UDE) to mitigate chlorpyrifos-induced toxicity. Eight compounds in the Urtica dioica ethanolic extract have been identified, most of which present significant potential as antioxidant, anti-inflammatory, and neuroprotective agents. Chlorpyrifos exposure altered hatching rates, increased the incidence of teratogenic effects, and upregulated the expression of brain-derived neurotrophic factor (Bdnf) in zebrafish larvae telencephalon. On the other hand, UDE demonstrated a preventive effect against CPF-induced teratogenicity, which is expressed by a lower morphological deformity rate. Moreover, the UDE showed a rather protective effect, maintaining the physiological condition of the telencephalon. Additionally, CPF altered the locomotor behavior of larvae, which was characterized by irregular swimming and increased activity. This defective behavioral pattern was slightly attenuated by the UDE. Our findings suggest that the UDE possesses significant protective properties against CPF-induced toxicity, probably conferred by its natural antioxidant and anti-inflammatory contents. Still, further research is needed to elucidate the recruited mechanisms and implicated pathways on UDE\'s protective effects.

This review evaluates the therapeutic effects of polysaccharides derived from mushroom species that have medicinal and edible properties. The fungal polysaccharides were recently studied, focusing on their modulation of the gut microbiota and their impact on various diseases. The study covers both clinical and preclinical studies, detailing the results and highlighting the significant influence of these polysaccharides on gut microbiota modulation. It discusses the potential health benefits derived from incorporating these polysaccharides into the diet for managing chronic diseases such as diabetes, neurodegenerative disorders, and cancer. Furthermore, the review emphasizes the interaction between fungal polysaccharides and the gut microbiota, underscoring their role in modulating the gut microbial community. It presents a systematic analysis of the findings, demonstrating the substantial impact of fungal polysaccharides on gut microbiota composition and function, which may contribute to their therapeutic effects in various chronic conditions. We conclude that the modulation of the gut microbiota by these polysaccharides may play a crucial role in mediating their therapeutic effects, offering a promising avenue for further research and potential applications in disease prevention and treatment.

There is a growing shift from the use of conventional pharmaceutical oral care products to the use of herbal extracts and traditional remedies in dental caries prevention. This is attributed to the potential environmental and health implications of contemporary oral products. This comprehensive review aims at the analysis of plant-derived compounds as preventive modalities in dental caries research. It focuses on data collected from 2019 until recently, trying to emphasize current trends in this topic. The research findings suggest that several plant-derived compounds, either aqueous or ethanolic, exhibit notable antibacterial effects against Streptococcus mutans and other bacteria related to dental caries, with some extracts demonstrating an efficacy comparable to that of chlorhexidine. Furthermore, in vivo studies using plant-derived compounds incorporated in food derivatives, such as lollipops, have shown promising results by significantly reducing Streptococcus mutans in high-risk caries children. In vitro studies on plant-derived compounds have revealed bactericidal and bacteriostatic activity against S. mutans, suggesting their potential use as dental caries preventive agents. Medicinal plants, plant-derived phytochemicals, essential oils, and other food compounds have exhibited promising antimicrobial activity against oral pathogens, either by their anti-adhesion activity, the inhibition of extracellular microbial enzymes, or their direct action on microbial species and acid production. However, further research is needed to assess their antimicrobial activity and to evaluate the cytotoxicity and safety profiles of these plant-derived compounds before their widespread clinical use can be recommended.

BACKGROUND: Alzheimer\'s disease (AD) is a complicated neurodegenerative disease with cognitive impairment occurring in the older people, in which extracellular accumulation of β-amyloid and intracellular aggregation of hyperphosphorylated tau are regarded as the prevailing theories. However, the exact AD mechanism has not been determined. Moreover, there is no effective treatment available in phase III trials to eradicate AD, which is imperative to explore novel treatments.
OBJECTIVE: A number of up-to-date pre-clinical studies on cognitive impairment is beneficial to clarify the pathology of AD. This review recapitulates several advances in AD pathobiology and discusses the neuroprotective effects of natural compounds, such as phenolic compounds, natural polysaccharides and oligosaccharides, peptide, and lipids, underscoring the therapeutic potential for AD.
METHODS: Electronic databases involving PubMed, Web of Science, and Google Scholar were searched up to October 2023. Articles were conducted using the keywords like Alzheimer\'s disease, pathogenic mechanisms, natural compounds, and neuroprotection.
RESULTS: This review summarized several AD pathologies and the neuroprotective effects of natural compounds such as natural polysaccharides and oligosaccharides, peptide, and lipids.
CONCLUSIONS: We have discussed the pathogenic mechanisms of AD and the effect natural products on neurodegenerative diseases particularly in treating AD. Specifically, we investigated the molecular pathways and links between natural compounds and Alzheimer\'s disease such as through NF-κB, Nrf2, and mTOR pathway. Further investigation is necessary in exploring the bioactivity and effectiveness of natural compounds in clinical trials, which may provide a promising treatment for AD patients.