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Ulcerative colitis (UC) is a chronic inflammatory bowel disease impacting patients’ quality of life and imposing heavy societal and economic burdens. Apoptosis of intestinal epithelial cells (IECs) has been considered an early event during the onset of UC and plays a crucial role in disease development. Thus, effectively inhibiting apoptosis of IEC...
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Context 1
... meticulous review was performed, and the quality of all the included studies was assessed in accordance with the Best practice in research-Overcoming common challenges in phytopharmacological research ( Heinrich et al., 2020). The detailed information of natural products and their potential effects with mechanisms on modulating apoptosis in UC is illustrated in Tables 1, 2, and the chemical structures of isolated metabolites are summarized in Table 3. ...Citations
... STAT3 is involved in cellular physiological events in vivo, including apoptosis, cell proliferation, and cell cycle regulation, and is usually activated by IL-6 [41]. In general, STAT3 is often thought to be associated with cancer as well as immune responses; however, recent studies have shown that STAT3 appears to modulate downstream signaling to stimulate inflammatory bowel disease, such as PI3K/AKT [42]. ...
Dampness-heat syndrome diarrhea (DHSD) is a common clinical disease with a high prevalence but still has no satisfactory therapeutic medicine, so the search for a safe and effective drug candidate is ongoing. This study aims to explore the efficacy and mechanisms of Lianweng granules (LWG) in the treatment of DHSD and to identify the blood transport components of LWG. We assessed the efficacy of LWG in DHSD by various in vivo metrics such as body weight, disease activity index (DAI), histopathologic examination, intestinal barrier function, levels of inflammatory, apoptotic biomarkers, and oxidative stress. We identified the blood components of LWG using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS), and the resolved key components were used to explore the relevant targets. We next predicted the potential mechanisms of LWG in treating DHSD using network pharmacology and molecular docking based on the relevant targets. Finally, the mechanisms were validated in vivo using RT-qPCR, Western blotting, ELISA, and immunofluorescence and evaluated in vitro using Cell Counting Kit-8 (CCK-8), small interfering RNA, cellular enthusiasm transfer assay (CETSA), and drug affinity response target stability (DARTS). Ninety-one pharmacodynamic components of LWG enter the bloodstream and exert possible therapeutic effects. In vivo, LWG treatment improved body weight, reduced colonic injury and DAI scores, lowered inflammation, oxidative stress, and apoptosis markers, and partially restored intestinal barrier function in DHSD mice. Guided by network pharmacology and molecular docking, it is suggested that LWG may exert therapeutic effects by inhibiting IL-6/STAT3/PI3K/AKT signaling. LWG significantly decreased the expression of IL-6, p-STAT3, p-PI3K, p-AKT, and other proteins. These findings were supported by in vitro experiments, where CETSA, DARTS, and siRNA evidenced LWG’s targeting of STAT3. LWG targeted STAT3 to inhibit inflammation, oxidative stress, and apoptosis in the colon, thereby restoring the intestinal barrier function to some extent and exerting a therapeutic effect on DHSD.
... In contrast, the non-classical pathway, driven by Caspase-11 and primarily activated by LPS, also promotes inflammatory responses (34). It's important to note that improper activation of the NLRP3 inflammasome is linked to various conditions, ranging from Inflammatory Bowel Disease (IBD) (35) to acute myocardial infarctions (36). In the face of LPS aggression, the precise modulation of NLRP3 inflammasome activity becomes paramount to maintaining intestinal integrity. ...
Introduction
Cecropin AD (CAD), a renowned antimicrobial peptide, has shown promising potential in treating various bacterial infections. This study investigates the protective effects of CAD against lipopolysaccharide (LPS)-induced intestinal adversities in chickens.
Methods
Sixty SPF-grade chicks were divided into groups and exposed to different dosages of CAD, followed by LPS administration. The study assessed the impact of CAD on intestinal mucosal injury markers, oxidative stress, and inflammation.
Results
LPS significantly increased Diamine oxidase (DAO) and D-lactate (D-LA) levels, both indicators of intestinal mucosal injury. CAD treatment substantially attenuated these elevations, particularly at higher dosages. Additionally, CAD markedly reduced oxidative stress in intestinal tissues, as shown by normalized antioxidant levels and decreased reactive oxygen species. Histological analysis supported these findings, showing better-preserved villi structures in CAD-treated groups. Furthermore, CAD significantly reduced IL-6 and IL-8 expression post-LPS stimulation and effectively regulated the NLRP3 inflammasome pathway, decreasing associated factors like NLRP3, Caspase-1, IL-1b, and IL-18.
Discussion
The study demonstrates CAD's therapeutic potential in alleviating LPS-induced intestinal injuries. The protective effects are primarily attributed to its anti-inflammatory and antioxidative actions and modulation of the NLRP3 inflammasome pathway.
... Mitochondria are a major contributor to apoptosis signaling during oxidative stress (Baregamian et al., 2011). Excessive ROS production or impaired antioxidant defense can reduce MMP and trigger the release of pro-apoptotic proteins, resulting in mitochondrial-dependent apoptosis activation (Kim et al., 2012;Liu et al., 2022). Under physiological conditions, anti-apoptotic proteins (Bcl-2 and Bcl-xL) sequester pro-apoptotic proteins (Bax, Bad, Bak, Bim, and Bid) to maintain the integrity of the mitochondrial membrane, thereby preventing cell death (Jeong and Seol, 2008;Xiong et al., 2014). ...
... Activated caspase-9 initiates pro-caspase-3 and pro-caspase-7, which in turn activate caspase-9, forming a positive feedback loop. At this point, activated caspase cleaves downstream substrates, resulting in DNA fragmentation and the formation of apoptotic bodies (Liu et al., 2022). ...
Post-weaning diarrhea (PWD) in piglets poses a significant challenge and presents a grave threat to the global swine industry, resulting in considerable financial losses and compromising the welfare of animals. PWD is commonly associated with gut homeostatic imbalance, including oxidative stress, excessive inflammation, and microbiota dysbiosis. Antibiotic use has historically been a common initiative to combat PWD, but concerns about the development of antibiotic resistance have led to increased interest in alternative strategies. Mitochondria are key players in maintaining cellular homeostasis, and their dysfunction is intricately linked to the onset and progression of PWD. Accumulating evidence suggests that targeting mitochondrial function using antioxidant nutrients, such as vitamins, minerals and polyphenolic compounds, may represent a promising approach for preventing and treating PWD. Moreover, nutrients based on antioxidant strategies have been shown to improve mitochondrial function , restore intestinal redox balance, and reduce oxidative damage, which is a key driver of PWD. The present review begins with an overview of the potential interplay between mitochondria and gut ho-meostasis in the pathogenesis of PWD in piglets. Subsequently, alternative strategies to prevent and treat PWD using antioxidant nutrients to target mitochondria are described and discussed. Ultimately, we delve into potential limitations and suggest future research directions in this field for further advancement. Overall, targeting mitochondria using antioxidant nutrients may be a promising approach to combat PWD and provides a potential nutrition intervention strategy for regulating gut homeostasis of weaned piglets.
... Primary clinical features of UC are diarrhea, abdominal pain, and bloody mucus, which constantly fluctuate with alternating phases of exacerbation and remission, thus reducing health-related quality of life [1,2]. Long-term uncontrolled inflammation occurring in the colons of chronic UC patients could lead to irreversible intestinal damage, increased risk of colorectal cancer, and even death [2,3]. Despite the uncertain pathogenesis of UC, the interaction of multiple factors including genetic susceptibility, intestinal barrier dysfunction, immune imbalance, dietary, and environmental factors, etc., has been considered to be involved in its development and progression [2,4]. ...
... To explore the effect of Eckol treatment on DC infiltration in the colon tissues of The Bcl-2 protein family, including pro-apoptotic Bax and anti-apoptotic Bcl-2, play vital roles in the mitochondrial-dependent apoptotic pathway, and the Bcl-2/Bax ratio is commonly employed to evaluate the colonic apoptosis during chronic UC [30]. Caspase-3 is a key enzyme that can cleave other protein substrates, thus activating various apoptosis stimulators, and activation of the Caspase-3 apoptotic cascade is involved in pathogenicity of chronic UC [3]. In this study, we demonstrated that Eckol, especially at a high dose, could significantly inhibit colonic cell apoptosis in chronic UC mice. ...
The use of functional foods and their bioactive components is receiving increasing attention as a complementary and alternative therapy for chronic ulcerative colitis (UC). This study explored the protective effect and mechanisms of Eckol, a seaweed-derived bioactive phlorotannin, on the dextran sodium sulfate (DSS)-induced chronic UC in mice. Eckol (0.5–1.0 mg/kg) reduced DSS-enhanced disease activity indexes, and alleviated the shortening of colon length and colonic tissue damage in chronic UC mice. The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were significantly decreased, and the level of anti-inflammatory IL-10 was enhanced in the serum and colonic tissues collected from Eckol-treated mice compared with the DSS controls. Eckol administration significantly reduced the number of apoptotic cells and the expression of cleaved Caspase-3, and increased the B-cell lymphoma-2 (Bcl-2)/B-cell lymphoma-2- associated X (Bax) ratio in DSS-challenged colons. There were more cluster of differentiation (CD)11c+ dendritic cells and CD8+ T cells, and less CD4+ T cells infiltrated to inflamed colonic tissues in the Eckol-treated groups. Expression of colonic Toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB) p65, phosphorylated-signal transducer and activator of transcription (pSTAT)3 was significantly down-regulated by Eckol compared with the DSS-challenged group. In conclusion, our data suggest that Eckol appeared to be a potential functional food ingredient for protection against chronic UC. The anti-colitis mechanisms of Eckol might be attributed to the down-regulation of the TLR4/NF-κB/STAT3 pathway, inhibition of inflammation and apoptosis, as well as its immunoregulatory activity.
... In recent years, natural products (NPs) have become a research hotspot in cancer treatment Atanasov et al., 2021;Kim et al., 2021;Anjum et al., 2022;Liu et al., 2022;Huang et al., 2023;Yuan et al., 2023). NPs refer to components, isolated metabolites, and extracts from natural plants and be of multiple bioactivities, such as regulating oxidative stress, inflammatory response, and cellular apoptosis. ...
Endometrial cancer (EC) is a prevalent epithelial malignancy in the uterine corpus's endometrium and myometrium. Regulating apoptosis of endometrial cancer cells has been a promising approach for treating EC. Recent in-vitro and in-vivo studies show that numerous extracts and monomers from natural products have pro-apoptotic properties in EC. Therefore, we have reviewed the current studies regarding natural products in modulating the apoptosis of EC cells and summarized their potential mechanisms. The potential signaling pathways include the mitochondria-dependent apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, the mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, NF-κB-mediated apoptotic pathway, PI3K/AKT/mTOR mediated apoptotic pathway, the p21-mediated apoptotic pathway, and other reported pathways. This review focuses on the importance of natural products in treating EC and provides a foundation for developing natural products-based anti-EC agents.
... Relative to refractoriness to treatment, most current anti-cancer therapies, including chemotherapy as well as radio-and immunotherapies, primarily act by activating cell death pathways, including apoptosis, in cancer cells. Examples of targeting both the intrinsic (inhibitors of BCL2, MCL, and IAP/survivin) and extrinsic pathways (death receptor agonists) that regulate apoptosis have been published, and natural products that modulate apoptosis have recently been reviewed [67,68]. A specific paradigm-shifting example is the use of venetaclax, a small molecule BH3 mimetic, as a sole therapy for the treatment of chronic lymphocytic leukemia or in combination with a small-molecule inhibitor of Bruton's kinase, ibrutinib or acalabrtinib, which have rendered conventional chemotherapeutic and immunotherapeutic approaches to being second tier approaches [69]. ...
While diet and nutrition are modifiable risk factors for many chronic and infectious diseases, their role in cancer prevention and control remains under investigation. The lack of clarity of some diet–cancer relationships reflects the ongoing debate about the relative contribution of genetic factors, environmental exposures, and replicative errors in stem cell division as determinate drivers of cancer risk. In addition, dietary guidance has often been based upon research assuming that the effects of diet and nutrition on carcinogenesis would be uniform across populations and for various tumor types arising in a specific organ, i.e., that one size fits all. Herein, we present a paradigm for investigating precision dietary patterns that leverages the approaches that led to successful small-molecule inhibitors in cancer treatment, namely understanding the pharmacokinetics and pharmacodynamics of small molecules for targeting carcinogenic mechanisms. We challenge the scientific community to refine the paradigm presented and to conduct proof-in-concept experiments that integrate existing knowledge (drug development, natural products, and the food metabolome) with developments in artificial intelligence to design and then test dietary patterns predicted to elicit drug-like effects on target tissues for cancer prevention and control. We refer to this precision approach as dietary oncopharmacognosy and envision it as the crosswalk between the currently defined fields of precision oncology and precision nutrition with the goal of reducing cancer deaths.
... Balancing their regulation in transformed cells presents a physiological yet effective way to eliminate proliferative potential and reduce the progression of cancer. Natural products that modulate apoptosis have recently been reviewed [74]. ...
Striking progress is being made in cancer treatment by using small molecule inhibitors of specific protein kinases that are products of genes recognized as drivers for a specific type of cancer. However, the cost of newly developed drugs is high, and these pharmaceuticals are neither affordable nor accessible in most parts of the world. Accordingly, this narrative review aims to probe how these recent successes in cancer treatment can be reverse-engineered into affordable and accessible approaches for the global community. This challenge is addressed through the lens of cancer chemoprevention, defined as using pharmacological agents of natural or synthetic origin to impede, arrest, or reverse carcinogenesis at any stage in the disease process. In this regard, prevention refers to reducing cancer-related deaths. Recognizing the clinical successes and limitations of protein kinase inhibitor treatment strategies, the disciplines of pharmacognosy and chemotaxonomy are juxtaposed with current efforts to exploit the cancer kinome to describe a conceptual framework for developing a natural product-based approach for precision oncology.
... Apoptosis is a kind of organized cell death, and it represents a crucial process for maintenance of homeostasis [85]. The induction of apoptosis and inhibition of cell proliferation are the main general mechanisms through which several natural compounds exert their anticancer role [86,87], and the main examples in the field of ovarian cancer are reported below. ...
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).
... Numerous studies have proved that NPs can inhibit IEC apoptosis through multiple pathways [188]. The main pathways involved are the death receptor-mediated pathway, mitochondriadependent pathway, endoplasmic reticulum stress-mediated pathway, MAPK-mediated pathway, NF-κB-mediated pathway, and P13K/Akt-mediated pathway [307]. For example, biodegradation products of chitosan can prevent apoptosis in IEC by inhibiting NF-κB activation and decreasing TNF-α and IL-6 production [270]. ...
Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory disease of the intestine that can be classified as ulcerative colitis (UC) and Crohn’s disease (CD). Currently, the incidence of IBD is still increasing in developing countries. However, current treatments for IBD have limitations and do not fully meet the needs of patients. There is a growing demand for new, safe, and highly effective alternative drugs for IBD patients. Natural products (NPs) are used in drug development and disease treatment because of their broad biological activity, low toxicity, and low side effects. Numerous studies have shown that some NPs have strong therapeutic effects on IBD. In this paper, we first reviewed the pathogenesis of IBD as well as current therapeutic approaches and drugs. Further, we summarized the therapeutic effects of 170 different sources of NPs on IBD and generalized their modes of action and therapeutic effects. Finally, we analyzed the potential mechanisms of NPs for the treatment of IBD. The aim of our review is to provide a systematic and credible summary, thus supporting the research on NPs for the treatment of IBD and providing a theoretical basis for the development and application of NPs in drugs and functional foods.
... Besides, excess activation of glutamate receptors induces neuronal necrosis Responsible Editor: Mohamed M. Abdel-Daim due to persistent neuronal depolarization (El Okle et al. 2018). Former studies unveiled that glutamate remarkably decreased the levels of norepinephrine (NE) and dopamine (DA) and suppressed the activity of acetylcholine esterase in different brain areas (Liu et al. 2022, Odenwald and Turner 2017, Pravda 2005). Actually, a high level of circulating glutamate has been linked with the formation of toxic reactive oxygen (ROS) and nitrogen species (RNS) (Bickel 1993, Gaffen andLiu 2004). ...
Monosodium glutamate (MSG) is used as a flavor, and a taste enhancer was reported to evoke marked neuronal impairments. This study investigated the neuroprotective ability of flavonoid apigenin against neural damage in MSG-administered rats. Adult male rats were allocated into four groups: control, apigenin (20 mg/kg b.wt, orally), MSG (4 g/kg b.wt, orally), and apigenin + MSG at the aforementioned doses for 30 days. Regarding the levels of neurotransmitters, our results revealed that apigenin augmented the activity of acetylcholinesterase (AChE) markedly, and levels of brain monoamines (dopamine, norepinephrine, and serotonin) accompanied by lessening the activity of monoamine oxidase (MAO) as compared to MSG treatment. Moreover, apigenin counteracted the MSG-mediated oxidative stress by decreasing the malondialdehyde (MDA) levels together with elevating the glutathione (GSH) levels. In addition, pretreatment with apigenin induced notable increases in the activities of cortical superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Furthermore, apigenin attenuated the cortical inflammatory stress as indicated by lower levels of pro-inflammatory mediators such as interleukin-1 b (IL-1b), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) as well as downregulated inducible nitric oxide synthase (iNOS) expression levels. Histopathological screening validated the abovementioned results and revealed that apigenin restored the distorted cytoarchitecture of the brain cortex. Thus, the present findings collectively suggest that apigenin exerted significant protection against MSG-induced neurotoxicity by enhancing the cellular antioxidant response and attenuating inflammatory machineries in the rat brain cortex.
