Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Esophageal cancer(ESC)is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract.Although the exact pathogenesis of ESC has not been fully elucidated,excessive oxidative stress is an important characteristic that leads to the development of many cancers.Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs,which alters the growth and proliferation of ESCs and promotes their metastasis.Natural compounds,including alkaloids,terpenes,polyphenols,and xanthine compounds,can inhibit reactive oxygen species production in ESCs.These compounds reduce oxidative stress levels and subsequently inhibit the oc-currence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10,superoxide dismutase,the NF-+ACY-kappa+ADs-B/MAPK pathway,and the mammalian Nrf2/ARE target pathway.Thus,targeting tumor oxidative stress has become a key focus in anti-ESC therapy.This review discusses the potential of Natural products(NPs)for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment.The findings of this review provide a reference for drug development targeting ESCs.Nonetheless,further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Coordinated regulation for nature products discovery and overproduction in Streptomyces

Streptomyces is an important treasure trove for natural products discovery.In recent years,many scientists focused on the genetic modification and metabolic regulation of Streptomyces to obtain diverse bioactive compounds with high yields.This review summarized the commonly used regulatory strategies for natural products discovery and overproduction in Streptomyces from three main aspects,including regulator-related strategies,promoter engineering,as well as other strategies employing transposons,signal factors,or feedback regulations.It is expected that the metabolic regulation network of Streptomyces will be elucidated more comprehensively to shed light on natural products research in the future.

Role of natural products and intestinal flora on type 2 diabetes mellitus treatment

Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant factors in the development of type 2 DM(T2DM).The association between changes in intestinal flora and numerous disorders,including obesity,diabetes,and cardiovascular diseases,has been studied in recent years.The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients’intestinal flora,as well as their therapeutic choices.Also included is a summary of the antidiabetic benefits of natural compounds demonstrated by studies.The short-chain fatty acids theory,the bile acid theory,and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM.Due to an intestinal flora imbalance,abnormalities in shortchain fatty acids and secondary bile acids have been found in diabetic patients.Additionally,metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation.The agenda for diabetes treatment includes the use of short-chain fatty acids,probiotics,prebiotics in the diet,fecal bacteria transplantation,and antibiotics.Animal studies have proven the antidiabetic benefits of numerous bioactive substances,including Flavonoids,Alkaloids,Saponin,and Allicin.However,further research is required to contribute to the treatment of diabetes.

Mechanisms of action of natural products on type 2 diabetes

Over the past several decades,type 2 diabetes mellitus(T2DM)has been considered a global public health concern.Currently,various therapeutic modalities are available for T2DM management,including dietary modifications,moderate exercise,and use of hypoglycemic agents and lipid-lowering medications.Although the curative effect of most drugs on T2DM is significant,they also exert some adverse side effects.Biologically active substances found in natural medicines are important for T2DM treatment.Several recent studies have reported that active ingredients derived from traditional medicines or foods exert a therapeutic effect on T2DM.This review compiled important articles regarding the therapeutic effects of natural products and their active ingredients on isletβcell function,adipose tissue inflammation,and insulin resistance.Additionally,this review provided an in-depth understanding of the multiple regulatory effects on different targets and signaling pathways of natural medicines in the treatment of T2DM as well as a theoretical basis for clinical effective application.

Current therapeutic modalities and chemopreventive role of natural products in liver cancer:Progress and promise

Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.

Natural products and extracts from plants as natural UV filters for sunscreens:A review

Although solar exposure is necessary for human health,phototoxicology induced by excessive UVB and UVA radiation,which involves sunburns,skin aging and even tu-morigenesis,has been widely researched.Sunscreen is one of the most important ways to protect skin from UV phototoxic damage.As well as inorganic and organic UV filters,some natural products or plant extracts with aromatic rings in their structures,such as flavonoids or polyphenols,can absorb UV to reduce sunburn,acting as a natu-ral UV filter;they also show antioxidant or/and anti-inflammatory activity.This could explain why,although there are no officially approval natural commercial sun-filters,more and more commercial sunscreen products containing plant extracts are avail-able on the market.Here we summarize articles focusing on natural UV filters from plant published in the last 6 years,selecting the most significant data in order to better understand the photoprotective activity of natural products and extracts from plants,including their major constituents and main biological effects,methods for evaluating UV radiation resistance,anti-UV radiation experimental models and anti-UV radiation mechanisms.

Acute kidney injury:microRNAs and new therapeutic opportunities for natural products

In the past few decades,acute kidney injury(AKI),characterized by an abrupt decrease in kidney filtration rate,has become a public health issue affecting between 1%and 15%of the population,which causes high morbidity and death.There is mounting evidence that miRNAs are noncoding single-stranded RNAs with a short length of about 20 nucleotides and have been highly conserved through evolution.Through targeting mRNAs,miRNA may mediate intercellular communication during AKI’s physiological and pathological processes.It is interesting to note that natural products can improve AKI by regulating miRNA expression,which might represent a potentially innovative therapeutic strategy.This review aims at providing an overview of the new data obtained on miRNAs in the treatment and diagnosis of AKI,summarizing studies on natural products improving AKI through regulating miRNAs’expression;in the same time,it will shed new light on AKI risk biomarkers and therapeutic intervention as well.We summarized the roles of miRNAs involved in AKI progression or protection against renal injury in 32 articles;we found five natural products can improve AKI by regulating miRNA expression,which will potentially provide a reference for clinical treatment.Natural products might represent a potentially innovative therapeutic strategy;in the same time,miRNAs will shed new light on AKI risk biomarkers and therapeutic intervention.

Research progress of natural products in treating polycystic ovary syndrome

Polycystic ovary syndrome(PCOS)is a common metabolic disorder reproductive endocrine disease in puberty and women of childbearing age.At present,metformin is mainly used in clinical to treat PCOS.From recent researches,many natural products,such as flavonoids,alkaloids,cumarins,etc,showed curing effects on PCOS.These have been attracting more and more attention.By searching the researches from database of CNKI,PubMed etc,this paper aims at providing a reference for PCOS drug research and development.

Recent advance in natural plant products for treatment of dry eye disease

Dry eye disease(DED),a chronic multifactorial illness of the ocular surface with itching,burning,irritation,eye fatigue and ocular inflammation,may result in potential damage,such as cornea and conjunctiva,and even decreased vision.With the global prevalence of DED on the rise,it is crucial to find treatment options with minimal side effects.Natural plant products have shown promise in alleviating DED symptoms and may serve as a potential approach for its treatment.However,their application as instilled drugs is limited by solubility,stability and biological barriers.This review summarizes recent studies(published in the last 5 years)on natural plant products and their derivatives for the treatment of DED,focusing on efficacy,mechanism,drug delivery systems.Meanwhile,their shortcomings are also discussed.By exploring these aspects,we find polyphenol,flavonoid and others natural plant products can effectively improve or treat DED by different mechanisms,and suitable delivery system and structural modification can enhance their therapeutic effect,suggesting they are likely to become candidates for the treatment of DED.

A Review of Textile Fabrication Using Bioactive Compounds Derived from Natural Products

Antimicrobial-treated textiles should exhibit efficacy against a broad spectrum of bacterial and fungal species,all while maintaining user safety with a non-toxic profile.Natural antimicrobial compounds play a vital role in textile finishing processes.The proliferation of synthetic antimicrobial agents introduces environmental and consumer safety concerns.Given these potential hazards associated with synthetic agents,the utilization of natural antimicrobial agents is gaining traction,as they tend to have fewer adverse effects on users and are more environmentally sustainable.Numerous natural antimicrobial compounds,sourced from plants such as neem,basil,turmeric,aloe vera,and clove oil,have been developed,showcasing inherent antimicrobial properties.This review article highlights the importance of incorporating bioactive components in the creation of antibacterial textile fabrics.

Natural product-induced oxidative stress-synergistic anti-tumor effects of chemotherapeutic agents

Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

Sustainable, thermoplastic and hydrophobic coating from natural cellulose and cinnamon to fabricate eco-friendly catering packaging

Non-degradable polymers cause serious environmental pollution problem,such as the widely-used while unrecyclable coatings which significantly affect the overall degradation performance of products.It is imperative and attractive to develop biodegradable functional coatings.Herein,we proposed a novel strategy to successfully prepare biodegradable,thermoplastic and hydrophobic coatings with high transparence and biosafety by weakening the interchain interactions between cellulose chain.The natural cellulose and cinnamic acid were as raw materials.Via reducing the degree of polymerization(DP)of cellulose and regulating the degree of substitution(DS)of cinnamate moiety,the obtained cellulose cinnamate(CC)exhibited not only the thermalflow behavior but also good biodegradability,which solves the conflict between the thermoplasticity and biodegradability in cellulose-based materials.The glass transition temperature(T_(g))and thermalflow temperature(T_(f))of the CC could be adjusted in a range of 150–200℃ and 180–210℃,respectively.The CC with DS<1.2 and DP≤100 degraded more than 60%after an enzyme treatment for 7 days,and degraded more than 80%after a composting treatment for 42 days.Furthermore,CC had no toxicity to human epidermal cells even at a high concentration(0.5 mg mL^(-1)).In addition,CC could be easily fabricated into multifunctional coating with high hydrophobicity,thermal adhesion and high transparence.Therefore,after combining with cellophane and paperboard,CC coating with low DP and DS could be used to prepare fully-biodegradable heat-sealing packaging,art paper,paper cups,paper straws and food packaging boxes.

Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.

Steroids, Tri- and Meroterpenoids with a Quinone Structure—A Review

Terpenoids with quinoid structures are found as natural products. This includes steroidal quinones, quinones with a secosteroid structure and meroterpenoid quinones. Importantly, catechol estrogens as endogenous metabolites of estradiol and estrone are precursors of reactive quinones and semiquinones, which are thought to contribute to estrogen-induced carcinogenesis. On the other hand, a number of quinones that include substituted naphthoquinones and anthraquinones are highly cytotoxic and have been used in cancer treatment. This makes the structures interesting synthetic targets. The following is a review of important natural and synthetic terpenoid and steroid quinone hybrids.

Cytotoxicity, Toxicity and Anticancer Activity of Manuka Honey, Saudi’s Honey and Peganum harmala Plant against Cancer Cells

Cancer occurs when the body’s cells grow beyond the usual control. Normal body cells multiply in a controlled manner and undergo apoptosis when the body no longer needs them. Different types of cancers exist, and the common ones include breast, cervical, prostate, lung, colon, and skin cancers. Several factors have been associated with cancers, and these factors include poor dieting, exposure to harmful chemicals and radiation, weak immune system, and genetics. Cancer presents an enormous health threat in the modern world and thus the need to identify an effective treatment. The conventional treatments used in the management of cancer include chemotherapy and physiotherapy. These forms of cancer treatments usually have enormous side effects on the subjects. In this respect, an alternative form of treatment would be effective in managing cancer patients. A substantial number of natural products have been observed to be effective in the management of cancer. These natural products include plants and other natural substances such as honey. This study focuses on the efficiency of natural products in the treatment of cancer. Also, the anticancer effects of Peganum harmala, Manuka honey, and Saudi honey will be analyzed. Bee honey and Peganum harmala have been traditionally used in the treatment of cancer. The extracts from Peganum harmala plant have also been shown to exhibit divers’ antitumor effects similar to the mode of action of a vast number of anticancer agents. These established hypotheses thus give the rationale for this study. In this experiment, extracts were obtained from Peganum harmala leaves and exposed to cervical, lung, and prostate cancer cells. Similarly, solutions of Manuka honey and Saudi honey were exposed to the cervical, lung, and prostate cancer cells. The experiment duration was 24 hours, which obtained results were recorded and analyzed. Peganum harmala extracts inhibit cancer cell growth at different and achievable concentrations. Manuka honey highly inhibits the growth of HeLa cancer cells while Saudi honey highly inhibits the growth of A549 cells. Peganum harmala can form an effective treatment for managing several types of cancers. Manuka Honey can be applied as an effective treatment for managing cervical cancer while Saudi honey can form an effective treatment for managing lung cancers.

Effects of plants and plant products on the testis

For centuries, plants and plant-based products have been used as a valuable and safe natural source of medicines for treating various ailments. The therapeutic potential of most of these plants could be ascribed to their anticancer, antidiabetic, hepatoprotective, cardioprotective, antispasmodic, analgesic and various other pharmacological properties. However, several commonly used plants have been reported to adversely affect male reproductive functions in wildlife and humans. The effects observed with most of the plant and plant-based products have been attributed to the antispermatogenic and/or antisteroidogenic properties of one or more active ingredients. This review discusses the detrimental effects of some of the commonly used plants on various target cells in the testis. A deeper insight into the molecular mechanisms of action of these natural compounds could pave the way for developing therapeutic strategies against their toxicity.

Current Perspective in the Discovery of Anti-aging Agents from Natural Products

Aging is a process characterized by accumulating degenerative damages,resulting in the death of an organism ultimately.The main goal of aging research is to develop therapies that delay age-related diseases in human.Since signaling pathways in aging of Caenorhabditis elegans(C.elegans),fruit flies and mice are evolutionarily conserved,compounds extending lifespan of them by intervening pathways of aging may be useful in treating age-related diseases in human.Natural products have special resource advantage and with few side effect.Recently,many compounds or extracts from natural products slowing aging and extending lifespan have been reported.Here we summarized these compounds or extracts and their mechanisms in increasing longevity of C.elegans or other species,and the prospect in developing antiaging medicine from natural products.

Gut microbiota as a target for prevention and treatment of type 2 diabetes:Mechanisms and dietary natural products

Type 2 diabetes mellitus(T2DM)is among the most remarkable public health concerns globally.Accumulating research evidence documents that alteration of gut microbiota has an indispensable role in the onset and progression of obesity and T2DM.A reduced microbial diversity is linked to insulin resistance and energy metabolism,especially for the rise of the Firmicutes/Bacteroidetes ratio.Changes in metabolites followed by the gut dysbacteriosis are linked to the presence of T2DM.Moreover,endotoxin leakage and gut permeability caused by gut dysbacteriosis is more of a trigger for the onset and progression of T2DM.Research documents that natural products are remarkable arsenals of bioactive agents for the discovery of anti-T2DM drugs.Many studies have elucidated that the possible mechanisms of the anti-T2DM effects of natural products are remarkably linked to its regulation on the composition of gut microflora and the successive changes in metabolites directly or indirectly.This review presents a brief overview of the gut microbiota in T2DM and several relevant mechanisms,including short-chain fatty acids,biosynthesis and metabolism of branched-chain fatty acids,trimethylamine N-oxide,bile acid signaling,endotoxin leakage,and gut permeability,and describes how dietary natural products can improve T2DM via the gut microbiota.

Natural Products in Cancer Therapy: Past, Present and Future

Natural products,with remarkable chemical diversity,have been extensively investigated for their anticancer potential for more than a half-century.The collective efforts of the community have achieved the tremendous advancements,bringing natural products to clinical use and discovering new therapeutic opportunities,yet the challenges remain ahead.With remarkable changes in the landscape of cancer therapy and growing role of cutting-edge technologies,we may have come to a crossroads to revisit the strategies to understand nature products and to explore their therapeutic utility.This review summarizes the key advancements in nature product-centered cancer research and calls for the implementation of systematic approaches,new pharmacological models,and exploration of emerging directions to revitalize natural products search in cancer therapy.