Plant-derived bioactive compounds -
Plants produce a vast number of bioactive compounds with different chemical scaffolds, which modulate a diverse range of molecular targets and are used as drugs for treating numerous diseases.
Most present-day medicines are derived either from plant compounds or their derivatives, and plant compounds continue to offer limitless reserves for the discovery of new medicines. While different classes of plant compounds, like phenolics, flavonoids, saponins and alkaloids, and their potential pharmacological applications are currently being explored, their curative mechanisms are yet to be understood in detail.
Given their scope, these books are valuable resources for members of the scientific community wishing to further explore various medicinal plants and the therapeutic applications of their bioactive compounds. They appeal to scholars, teachers and scientists involved in plant product research, and facilitate the development of innovative new drugs.
Mallappa Kumara Swamy. Mallappa Kumara Swamy is a Professor at the Department of Biotechnology at East West First Grade College Affiliated to Bangalore University , Bengaluru, India.
He pursued his postdoctoral research at the Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia UPM , Serdang, Malaysia from to Before that, he worked as an Associate Professor and Head of the Department of Biotechnology at Padmashree Institute of Management and Sciences, Bangalore University, Bengaluru, India.
He obtained his PhD Biotechnology from Acharya Nagarjuna University, Guntur, India, in He has more than 16 years of teaching and research experience in the fields of plant biotechnology, secondary metabolites production, phytochemistry and bioactive studies, and he has published more than research papers in peer-reviewed journals and 25 book chapters.
He has edited 10 books with Springer Nature Singapore Pte Ltd. He is also an editorial board member and reviewer for various high-impact international journals. He currently works in the area of natural product research, plant cell and tissue culture technology for bioactive compounds production and evaluation of their bioactivities.
His research also focuses on nanobiotechnology for medical applications. Book Title : Plant-derived Bioactives. Book Subtitle : Production, Properties and Therapeutic Applications. Editors : Mallappa Kumara Swamy. Publisher : Springer Singapore. eBook Packages : Biomedical and Life Sciences , Biomedical and Life Sciences R0.
Copyright Information : Springer Nature Singapore Pte Ltd. Hardcover ISBN : Published: 12 May Softcover ISBN : Published: 12 May eBook ISBN : Published: 11 May Edition Number : 1. Number of Pages : XV, Policies and ethics. Skip to main content. Editors: Mallappa Kumara Swamy 0. Mallappa Kumara Swamy Department of Biotechnology, East West First Grade College, Bengaluru, India View editor publications.
Describes major phytocompounds, their chemistry, pharmacology and mode of action A comprehensive account of phytocompounds and their industry applications Presents scientific evidence for the use of bioactives in the treatment of diseases Explores the utility of bioactives as alternative medications to reduce health risks.
Sections Table of contents About this book Keywords Editors and Affiliations About the editor Bibliographic Information Publish with us. Buy it now Buying options eBook EUR Price includes VAT Germany. Softcover Book EUR Hardcover Book EUR Tax calculation will be finalised at checkout.
Licence this eBook for your library. Learn about institutional subscriptions. Table of contents 25 chapters Search within book Search. Page 1 Navigate to page number of 2. Front Matter Pages i-xv. Molecular Approaches to Screen Bioactive Compounds from Medicinal Plants Geeta Swargiary, Mahima Rawal, Manisha Singh, Shalini Mani Pages Essential Oils: An Update on Their Biosynthesis and Genetic Strategies to Overcome the Production Challenges Kartik Singh, Deeksha Kaloni, Kritika Sehgal, Sharadwata Pan, Indira P.
Bioactive compounds have not been adequately defined for the extent of their bioactivity in humans, indicating that their role in disease prevention and maintenance remains unknown. As of , there are no dietary recommendations in North America or Europe for bioactives, except for fiber.
However, there are ongoing discussions whether further bioactives should be included in future dietary guidelines. Contents move to sidebar hide. Article Talk. Read Edit View history. Tools Tools. What links here Related changes Upload file Special pages Permanent link Page information Cite this page Get shortened URL Download QR code Wikidata item.
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Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Bioactive compound" — news · newspapers · books · scholar · JSTOR May April European Journal of Nutrition.
doi : PMC PMID Micronutrient Information Center, Linus Pauling Institute, Oregon State University. Retrieved 15 May June Nutrition Reviews. January
Plant secondary metabolites are rich sources of bioactive Plant-deried eliciting Plant-derievd beneficial health Plant-derived bioactive compounds in man biiactive animals. Plant-based foods, including Plant-derived bioactive compounds, fruits, bioactove, Plant-derived bioactive compounds, nuts, and legumes, may contain hundreds of coompounds phytochemicals. Plannt-derived, research on phytochemicals suggests their possibility as an Plant-edrived source of therapeutic and bioactkve agents against diseases. Improving gut health types of foods containing these bioactive components are those functional foods that can provide desirable health benefits beyond their natural properties when consumed in a regular and consistent manner through diet. Alternatively, dietary supplements can be supplied to consumers in a concentrated form to deliver a specific bioactive phytochemical or a group of phytochemicals. Usually, these nutraceutical ingredients are administered with higher doses than in normal food or in a medicinal form with the purpose of improving human health. This chapter highlights the four most common groups of plant-derived bioactive components, polyphenols, alkaloids, terpenes, and saponins, mainly focusing on their chemistry, sources, and biological functions.Plant-derived bioactive compounds -
This research topic aims to elucidate the potential of plant-derived bioactive compounds as nutritional supplements for the alleviation of chronic inflammation by exploring precise molecular pathways, evaluating in vivo outcomes, and embracing a multidisciplinary approach, to provide insights into evidence-based dietary recommendations for natural anti-inflammatory solutions.
The impact of processing methods on the effectiveness of anti-inflammatory properties will also be explored. Assess outcomes such as changes in inflammatory biomarkers, symptom relief, and disease progression. Investigate how processing methods can influence the anti-inflammatory potential.
Explore methods to enhance the overall anti-inflammatory properties through processing strategies. Keywords : plant-derived bioactive compounds, natural products, health-promoting, inflammation, nutritional intervention.
Important Note : All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
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Find out more on how to host your own Frontiers Research Topic or contribute to one as an author. Overview Articles Authors Impact. Activation of the NLRP3 inflammasome involves initiation and activation steps.
The initiation step Signal 1 is provided by an inflammatory stimulant that stimulates the toll-like receptor TLR and then induces nuclear factor kappa-B NF-κB activation. NF-κB further promotes the expression of NLRP3, pro-IL-1β, and pro-IL Activation of the NLRP3 inflammasome can lead to recruitment of ASC and caspase-1, promotion of self-oligomerization, self-shearing and activation of caspase-1, and lysis of pro-IL-1β and pro-IL to form mature IL-1β and IL and exert inflammatory effects Shao et al.
In a liver sample from 77 full-spectrum NAFLD patients, mRNA and protein levels of NLRP3 and IL were significantly higher than those in non-NASH patients, and IL-1β mRNA expression was associated with collagen-1A1, a pro-fibrosis gene expressed by activated hepatic stellate cells HSCs Wree et al.
In another study, NLRP3 inflammasome-associated genes ASC, caspase-1, and NLRP3 were significantly upregulated in patients with NASH Csak et al.
In animal studies, hepatic NLRP3, ASC, procaspase-1, and pro-IL-1β mRNA expression increased in methionine-choline deficient diet MCD -fed mice Csak et al. In in vitro experiments, MCC reduced IL-1β release by KCs and bone marrow-derived macrophages BMDMs and eliminated associated neutrophil migration Mridha et al.
NLRP3 deletion inhibited the upregulation of NLRP3, ASC, and caspase-1 mRNA and protein expression levels in palmitic acid PA -treated KCs Csak et al.
Similarly, in HepG2 and L02 cells, inhibition of NLRP3 activity reduced uric acid-induced lipid accumulation Wan et al. These clinical and basic studies suggest that activation of the NLRP3 inflammasome may promote the pathological progression of NAFLD.
Activated NLRP3 inflammasome releases inflammatory particles and induces pyroptosis, which is significantly associated with NAFLD.
Studies have shown that activated NLRP3 inflammasomes result in caspase-1 activation Qiu et al. Activated caspase-1 performs two important functions. First, it promotes the conversion of pro-IL-1β and pro-IL to IL-1β and IL The persistence of this process leads to the secretion of large amounts of IL-1β and IL and the initiation of pyroptosis, all of which are major contributors to the progress of inflammatory diseases.
These processes spread the inflammatory process to the outside of the cell and release a large number of inflammasome particles, which aggravate the inflammatory response of the liver and promote the occurrence of NAFLD Henao-Mejia et al.
Second, pyroptosis depends on the inflammasome-mediated activation of caspase Membrane insertion of the pyroptosis medium Gasdermin D GSDMD leads to the formation of plasma membrane pores, causing intracellular protein release, ion decompensation, water influx, and cell swelling.
Active caspase-1 promotes the cleavage of GSDMD, then GSDMD binds to phosphatidylserine and phosphatidylinositol on the cell membrane and forms membrane pores that signal the beginning of cell death. These pores allow the introduction of a large number of active inflammatory cytokines and DAMPs into the extracellular environment, where they are recognized by inflammatory cells and lead to pyroptosis Swanson et al.
This suggests a correlation between the expression of the NLRP3 inflammasome-GSDMD-pyroptosis triplet and the development of NASH. Hepatocyte pyroptosis and the continuous release of inflammatory factors induce the formation of an inflammatory fibrotic microenvironment in the liver, which promotes the development of NAFLD Gaul et al.
FIGURE 1. Activation of NLRP3 inflammasome mediates the development of NAFLD. The activation of NLRP3 inflammasome includes initiation and activation steps. During the initiation step, TLR is stimulated by extracellular signalling molecules, leading to NF-κB activation, which activates NLRP3 and promotes the expression of pro-IL-1β and pro-IL Signal 1.
After NLRP3 inflammasome activation, activated caspase-1 converts pro-IL-1β and pro-IL into mature IL-1β and IL, leading to the release of inflammatory cytokines. Activated caspase-1 dissociates GSDMD, releases its N-terminal, and forms pores in the plasma membrane, stimulating the occurrence of pyroptosis.
The interaction between inflammatory factors and pyroptosis induces the inflammatory fibrosis microenvironment in the liver and promotes the occurrence and development of NAFLD. Here, we described plant-derived active ingredients that improve NAFLD by inhibiting the NLRP3 inflammasome in a variety of cell and animal models and the mechanisms underlying these inhibitory effects.
These active ingredients are mainly isolated or derived from plants or traditional Chinese herbs and can be roughly classified as terpenoids, flavonoids, alkaloids, and phenols Table 1.
TABLE 1. Plant-derived bioactive compounds treat NAFLD by regulating NLRP3 inflammasome. Terpenoids are natural products with a wide distribution, diverse structures, and various biological activities.
They are composed of isoprene and play important roles in the metabolism of all organisms Bouvier et al. Terpenoids have been proven to have antioxidant and anti-inflammatory effects and can be used as therapeutic drugs for many inflammatory diseases Grassmann ; Kim et al.
Many plant-derived terpenoids exert anti-NASH effects by inhibiting NLRP3 inflammasome activation. Antcin A, a terpenoid isolated from Antrodia camphorata , is a classical, traditional Chinese medicine used for NAFLD therapy.
Antcin A has strong anti-inflammatory and hepatoprotective effects Xu G. In vivo and in vitro studies have shown that antcin A could ameliorate liver lipid deposition, reduce ALT and AST levels, and inhibit the expression levels of NLRP3 inflammasome including NLRP3, ASC, and caspase-1 and pyroptosis-associated proteins GSDMD-FL and GSDMD-NT.
The cell membrane pore permeability and the number of pyroptotic cells significantly decreased after treatment with Antcin A. It worked by binding to NLRP3 and inhibiting the assembly and activation of the NLRP3 inflammasome, further mediating the inflammatory response and pyroptosis and thereby improving NASH Ruan et al.
Ginseng saponins can be divided into Rg1, Re, Rg2, Rh1, Rf, Rb1, Rb2, Rd, Rg3, Rh2, and Ro. Substantial evidence suggests that ginseng saponins have antioxidant, anti-inflammatory, and anti-pyroptosis properties Wong et al. In vitro experiments have shown the exertion of anti-NASH effects by maintaining mitochondrial homeostasis and inhibiting NLRP3 inflammasome activation Wang et al.
Another study showed that ginsenoside Rg1 also alleviated this phenotype and reduced NLRP3, IL-1β, and cleaved IL-1β expression in NASH model mice by inhibiting inflammasome activation Xu B. Andro, a natural terpenoid from Andrographis paniculata , possesses a wide range of bioactive compounds, including anti-inflammatory, antitumor, anti-diabetic, anti-bacterial, anti-malarial, and hepatoprotective properties Lim et al.
In vivo experiments have shown that it could reduce liver fat content, alleviate the expression of liver fibrosis indicators and autophagy, and inhibit the expression of NLRP3, ASC, caspase-1, and IL-1β. In vitro studies also have detailed good anti-inflammatory and anti-fibrosis effects of Andro and its anti-NASH effects were mainly regulated by NF-κB-dependent NLRP3 inflammasome Cabrera et al.
One study found that the oral bioavailability of Deoxy, Didehydroandrographolid, a derivative of Andro was higher than Andro Guan et al. It could lower ALT and hepatic total cholesterol TC levels and reduce the expression of NLRP3 and related inflammatory factors by increasing antioxidant and anti-inflammatory activities in NAFLD mice Liu Y.
β-PAE, a natural terpenoid of Pogostemonis herba , has anti-inflammatory, antioxidant, and hepatoprotective effects Wu et al. Studies have shown that β-PAE ameliorates serum lipid and liver transaminase in a high-fat diet HFD -induced NASH model.
In addition, β-PAE reduced the expression of thioredoxin interaction protein TXNIP , NLRP3, ASC, and cleaved-caspase-1 and inhibited the release of IL-Iβ. TXNIP is a key modulator of the redox system that inhibits TXN thioredoxin to cause cellular oxidative stress Zhou et al.
β-PAE reduced the levels of ROS and TXNIP, futher inhibited NLRP3 inflammasome activation Luo et al. Sweroside, a plant-derived terpenoid, can effectively alleviate liver fibrosis and liver injury-related diseases Yang Q.
This was accompanied by inhibitory effects on the hepatic NLRP3 inflammasome. Additionally, it has been shown to inhibit inflammasome activation as NLRP3, ASC, procaspase-1, caspase-1, and IL-1β reduced in the BMDMs inflammatory model induced by lipopolysaccharide LPS , adenosine triphosphate ATP , and nigericin Yang et al.
These results indicated that targeting the NLRP3 inflammasome with sweroside could be beneficial for improving NASH symptoms. CA is a natural terpenoid isolated from rosemary and common sages.
It has been shown that CA can reduce TC, triglyceride TG , ALT, AST, and insulin resistance, inhibit the expression of pro-inflammatory factors and adipogenic genes, and improve the expression of myristoylated alanine-rich protein kinase C substrate MARCKS.
MARCKS is a major protein kinase C PKC substrate in many different cell types, which has been investigated in LPS-induced disease from inflammation-related signaling pathways Yin et al.
The protein expression of NLRP3 and caspase-1 were upregulated in the MARCKS-deficient mice. MARCKS deficiency induced pro-inflammatory cytokine secretion, including IL-1β, IL, and tumor necrosis factor TNF -α, and induced NLRP3 inflammasome activation in vivo.
This study suggested that the mechanism of CA treatment for NASH is to inhibit the activation of the NLRP3 inflammasome signaling pathway by increasing the expression of MARCKS Song et al.
Gardenoside is the most effective bioactive molecule of the medicinal plant Gardenia jasminoides Ellis and has been shown to inhibit inflammatory cytokines and hepatocyte steatosis induced by free fatty acids FFA , which play an important role in NAFLD Liang et al.
Gardenoside can ameliorate lipid deposition and liver fibrosis, and has been shown to decrease the expression levels of dipeptidyl peptidase-4 DPP4 , CCCTC-binding factor CTCF , NLRP3, ASC, caspase-1 p20, GSDMD-N, and IL-1β in vitro and in vivo NAFLD models.
DPP4, an aminopeptidase, regulates the activity of a variety of biological peptides and participates in a variety of pathological and physiological processes Lambeir et al. CTCF is a gene known for its chromatin-organizing and transcription factor properties Braccioli and de Wit Importantly, CTCF or DPP4 silencing showed effects similar to those of Gardenoside treatment, whereas CTCF overexpression offset this trend.
Compared with the NAFLD model group, the number of apoptotic cells decreased and the cell membrane integrity of hepatocytes improved significantly in the gardenoside group. GL, derived from the traditional Chinese medicine licorice, is widely used for treating liver disease Wang H.
In an MCD-induced NAFLD model study, GL reduced the lipid levels in the liver and serum, reduced the expression of apoptosis marker genes, regulated FFA synthesis, and inhibited liver fibrosis.
The expression levels of TLR, NLRP3, ASC, caspase-1, and IL-1β were reduced after treatment with GL. Flavonoids are naturally existing and broadly distributed secondary metabolites of plants with a variety of biological functions, including antibacterial, antioxidant, anti-inflammatory, and anti-fibrosis activities.
Flavonoids can inhibit the production of inflammatory mediators such as IL-1β, IL, TNF-α, and IL-6 Yi, An increasing number of flavonoids have been reported to show anti-inflammatory and anti-fibrotic activities through the inhibition of NLRP3 inflammasome activation. Naringenin is mainly found in plants, especially citrus fruits such as grapefruit Orhan, Nabavi et al.
Meanwhile, similar results have been obtained in vitro. API, a naturally existing bioflavonoid, is commonly found in fruits, herbs, and vegetables Miean and Mohamed API has distinct pharmacological activities, such as antioxidant, anti-inflammatory activity Lee et al.
Many studies have indicated that API has anti-obesity and anti-diabetic activity Ono and Fujimori ; Kim et al. The potential mechanism of these therapeutic effects was attributed to the regulation of xanthine oxidase XO by API, which further regulated NLRP3 inflammasome activation and the release of inflammatory cytokines IL-1β and IL Echi, a bioactive flavonoid of Glycyrrhiza plants licorice , has antioxidant and anti-inflammatory activities Fu et al.
Echi ameliorated lipid deposition, fibrosis, and inflammation in an MCD-induced NASH mouse model. This study showed that Echi treatment had a beneficial effect on the level of ALT, AST, caspase-1, IL-1β, TNF-α, and lipid steatosis and fibrosis in the liver in MCD-induced NASH, which is similar to NLRP3 inhibitors, MCC These findings suggested that Echi could alleviate liver inflammation and the NASH pathology via inhibition of NLRP3 inflammasome.
Licochalcone E, a flavonoid isolated from licorice, possesses various biological activities, especially anti-diabetic effects Park et al. Licochalcone E significantly raised the consumption of glucose and reduced the concentrations of TC and TG in PA-treated HepG2 cells.
Further, licochalcone E depressed the expression of NLRP3, caspase-1, and IL-1β. Meanwhile, molecular simulations exhibited that licochalcone E has a high binding affinity for the NLPR3 inflammasome and inhibits the NLPR3 signalling pathway Cao et al. Silybin, a natural flavonoid from milk thistle silybum marianum , has been shown to have significant anticancer, anti-diabetic, and beneficial liver effects Ferenci et al.
The present study demonstrated that silybin reduced NLRP3, ASC, and the secretion of IL-1β. BA, a primary bioactive flavonoid ingredient that originates from the root of Scutellaria baicalensis Georgi , has anti-inflammatory and antioxidant properties and extenuates cell lipotoxicity Zhang Y.
This study showed that BA inhibited the expression of NLRP3 and decreased the production of IL-1β and IL C3G, one of the most plentiful anthocyanins belonging to the flavonoid family Galvano et al. C3G lessened body weight, liver weight, TG, and lipid droplets in HFD-induced NAFLD. Meanwhile, C3G reduced the expression of NLRP3, caspase-1, IL-1β, and IL The knockdown of hepatic PINK1 canceled the mitophagy-inducing effect of C3G, which blunted the useful effects of C3G on oxidative stress, NLRP3 inflammasome activation, glucose metabolism, and hepatic steatosis Zhu et al.
Man is particularly abundant in the leaves of mangoes and has anti-oxidative, anti-inflammatory, anticancer, and anti-diabetic activities Yon, Teramoto et al. A study indicated that body weight, liver weight, TC, TG, ALT, and AST were reduced after treatment with Man, while NLRP3, caspase-1, IL-1β, and GSDMD expression were downregulated in vivo and in vitro.
These results indicated that the anti-NAFLD activity of Man is mediated by its anti-inflammatory effects via NLRP3 inflammasome inhibition Yong, Ruiqi et al. Nob, a polymethoxylated flavonoid present in citrus peels, has antioxidant, antitumor, and anti-lipotoxic properties Nemoto, Ikeda et al.
Nob decreased the expression of NLRP3, caspase-1, IL-1β, and IL in AML cells. Furthermore, Nob improved PA-induced lipotoxicity by inhibiting NLRP3 inflammasome activation in a SIRT1-dependent manner Peng, Li et al.
Alkaloids are widely distributed in various plants and are a kind of organic secondary metabolites containing nitrogen with various structures, which have a wide variety of bioactive roles, including antioxidant, anti-inflammatory, antitumor, and immunoregulatory activities Liu, Yang et al.
Several studies have shown that the effects of alkaloids on NASH were mediated by the inhibition of NLRP3 inflammasome activation. BBR is an isoquinoline alkaloid that is derived from diverse herbal plants, including Coptis chinensis.
Studies have shown that BBR has anti-lipogenic, anti-inflammatory, anti-fibrotic, and antitumor effects Luo, Tian et al. BBR significantly reduced ALT, AST, TC, and TG levels. BBR works by enhancing the permeability of intestinal mucosa and balancing intestinal innate immune constituents. Research has shown that the expressions of NOD1, NOD2, NLRP3, caspase-1, and the release of IL-1β, IL, and TNF-α were upregulated in NAFLD intestine and reduced after treatment of BBR.
Another study suggested that BBR significantly ameliorated lipid accumulation, lipid peroxides, TNF-α expression, inhibited NLRP3 expression, caspase-1 activity, and GSDMD-N expression with a decrease in ROS levels and TXNIP expression in vivo and in vitro.
DMTHB, an innovative berberine derivative, has a similar structure to dimethyleneberberine DMB , a natural mitochondria-targeting antioxidant that exhibits significant anti-inflammatory and antioxidant pharmacological activities Zhang et al. DMTHB suppressed AST and ALT, hepatic TG and TC, and indicators related to hepatic fibrosis in the MCD-fed model.
In addition, further results have shown that DMTHB inhibited the release of IL-1β by suppressing the expression of NLRP3, ASC, and caspase The anti-NASH mechanism was regarded to involve DMTHB, which could target the NLRP3 inflammasome to suppress NLRP3 inflammasome activation Zhang et al.
Mtr is originally derived from the plant Sophora flavescens and possesses potent hepatoprotective Liu et al. It was verified that Mtr reduced AST, ALT, and collagen-1 and inhibited the expression of hepatic TNF-α and NLRP3 in the MCD-fed model.
The anti-NASH was related to the downregulation of NLRP3 in the NASH model Mahzari et al. Betaine, a naturally occurring compound in common foods, has been used to treat NAFLD Sookoian et al.
Betaine could lower serum lipid, hepatic lipid, and blood glucose and reduce the levels of NLRP3, ASC, caspase-1, and IL-1β. Phenolic compounds are secondary metabolites synthesized in the process of plant growth as important plant components.
They have excellent lipid-lowering and anti-inflammatory properties, improve mitochondrial function, effectively inhibit lipid oxidation, and treat NASH and other inflammatory diseases Lee et al.
CBD, a non-psychoactive compound extracted from Cannabis sativa , possesses a wide range of pharmacological functions, including antioxidant and anti-inflammatory functions, cardiac and neural protection, and anti-epileptic potential Yang et al.
A previous study showed that CBD alleviated hepatic steatosis and oxidative stress and significantly decreased the expression of NF-κB, NLRP3, ASC, procaspase-1, caspase-1 p20, GSDMD, and cleaved GSDMD both in vivo and in vitro.
SalA, a highly efficacious phenolic acid, is a water-soluble compound isolated from Radix Salvia miltiorrhiza. Many studies have shown that SalA exerts various pharmacological properties, such as antioxidant, anti-inflammatory, anti-fibrotic, anti-carcinogenic Zhang et al.
It reduced the levels of hepatic pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 and lipid accumulation TG and TC in the NAFLD model. This study concluded that TXNIP and NLRP3 inflammasome activation is involved in the pathogenesis of NAFLD. DK, a natural phenolic compound found in Laminaria japonica , decreases hepatic steatosis by alleviating hepatic inflammation Byun et al.
The accumulation of TG and histological NAFLD score in the liver were reduced by DK in the HFD-induced NAFLD model. In addition, DK could decrease the expression of NLRP3, ASC, caspase-1, GSDMD, and cleaved-GSDMD to improve NAFLD in vivo. The pyroptotic cell numbers in the liver were increased by HFD and decreased after treatment with DK.
Above all were related to decreased formation of the NLRP3 inflammasome and inhibition of pyroptosis Oh et al. Polydatin downregulated NLRP3, ASC, caspase-1, IL-1β, TG, and TC in the livers of fructose-fed rats. It was verified that the mechanism for NASH involves blocking ROS-driven TXNIP to suppress NLRP3 inflammasome activation Zhao et al.
Resveratrol, a polyphenol present in grapes, mulberries, and red wine, exerts antioxidant and anti-inflammatory effects Szkudelski and Szkudelska Resveratrol significantly reduced serum glucose and TG content.
In addition, resveratrol treatment reduced the levels of pro-inflammatory markers such as IL-1, IL-6, and TNF-α. MG, a major bioactive compound isolated from Magnolia officinalis , has been shown to possess anti-inflammatory, anti-oxidative, and hepatoprotective properties Tian et al.
MG reduced serum TG and TC content, decreased the expression of NLRP3, ASC, and caspase-1, and reduced the production of IL-1β, IL, IL-6, and TNF-α in vivo and in vitro. Another study showed that MG inhibited hepatic steatosis-induced NLRP3 inflammasome activation through the restoration of autophagy to promote Heme Oxygenase-1 HO-1 signalling.
HO-1 is an anti-inflammatory, antioxidant and neuroprotective inducible enzyme Campbell et al. SAL, a phenylpropanoid glycoside compound, is the major active ingredient of Rhodiola rosea. Earlier studies have shown that salidroside has pharmacological properties, including antioxidant and metabolic regulation, and exerts therapeutic effects on type 2 diabetes Zheng et al.
We have summarized the latest research results on the improvement of NAFLD afforded by the regulation of NLRP3 by plant-derived active ingredients. First, we systematically discussed the mechanism of the NLRP3 inflammasome in the development of NAFLD, which mainly participates in the occurrence and development of NAFLD by mediating the inflammatory response and pyroptosis.
We then described in detail the effects of these plant-derived compounds on the phenotype of the NAFLD model in vitro and in vivo. In addition, we summarized their effect on the NLRP3 inflammasome and its related indicators, procaspase-1, active caspase-1, ASC, pro-IL-1β, and IL-1β, and pyroptosis-related indicators, as well as the mechanism by which these compounds inhibit the NLRP3 inflammasome to improve NAFLD.
The NLRP3 inflammasome plays an important role in the development and progression of NAFLD. Excitingly, many plant-derived active ingredients can improve NAFLD by inhibiting NLRP3 inflammasome. Therefore, identifying NLRP3 inhibitors in plant-derived active compounds is of great significance for drug discovery as they are mostly safe, widely distributed, and available.
These compounds included terpenoids, flavonoids, phenols, and alkaloids. Antcin A, a terpenoid, can improve NAFLD by binding to NLRP3 to inhibit both the inflammatory response and pyroptosis.
Gardenoside, mangiferin, berberine, and dieckol can also inhibit inflammatory response and pyroptosis. We suspect that these five compounds may elicit a better anti-NAFLD effect in combination because of synergistic inhibitory effects.
Naringin and antcin A have inhibitory effects on NLRP3 inflammasome assembly, which could provide a reference for the development of inhibitors of NLRP3 assembly. Nrf2 is an essential transcription factor that regulates an array of detoxifying and antioxidant defense gene expression in the liver Beyer and Werner Berberine and ginsenoside have been studied the most.
DMTHB, a derivative of berberine, has a significant effect on improving NAFLD models in vitro and in vivo. The 31 plant-derived compounds mentioned herein exhibit inhibitory effects on NLRP3, serving as a reference for the development of treatments for NAFLD. Nevertheless, much work remains to be done to screen for natural drugs that are effective against NAFLD.
Our analysis found that most of the current studies are limited to descriptive findings, and only a few studies have explored the potential interaction between these compounds and NLRP3, whereas most of the studies lack in-depth mechanistic research.
For example, one included study of using resveratrol in treating NAFLD, only the effects of resveratrol on the expressions of NLRP3, caspase-1 and ASC proteins were observed, but the mechanism was not further explored.
In addition, in a study on mangiferin inhibiting pyroptosis, the authors only showed the effect of mangiferin on cell pyrosis marker GSDMD, but did not observe the pathological manifestation of pyroptosis. Therefore, future studies on these mechanisms in depth and comprehensiveness will contribute to a better understanding of the complex mechanisms of NLRP3 inflammasome activation.
All of the compounds mentioned herein inhibit NLRP3, but further research is needed to reveal whether this relationship is direct. Although the binding site of NLRP3 inflammasome-associated proteins to a natural product has been identified, further studies are needed to uncover the mechanism of action of potential NLRP3 inflammasome inhibitors and to screen for molecules that can selectively antagonize NLRP3 for NAFLD treatment.
The large dose difference of compounds used in different studies may lead to off-target effects and false-positive results. Therefore, standardization of NLRP3 specific inhibitory dose is of great significance for the safety and efficacy of future NAFLD drug studies.
Although many biological effects of these plant-derived active ingredients have been confirmed in cell and animal models in the treatment of NAFLD, insufficient clinical trials have been conducted to confirm the efficacy of these plant-derived substances for NAFLD, and further clinical trials are warranted.
In summary, we have discussed plant-derived active ingredients that can improve NASH by mediating NLRP3 to alleviate the inflammatory response or pyroptosis.
In light of the collected data described herein, we also propose relevant suggestions and improvement measures, which are of significance for the development of NAFLD treatment drugs. QF conceived this study. QH was responsible for organizing the literature and drawing chemical formulas.
QH, XX, QS, ZA, and XG were in charge of consulting the literature. QH wrote the manuscript and drew the figures. QF supervised the study and gave final approval of the version to be published.
All authors critically participated in the discussion and commented on the manuscript. This work was supported by the National Natural Science Foundation of China No.
SHDCCR to QF , the Shanghai Science and Technology Development Funds No. Y to ZA. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Beyer, T. The cytoprotective Nrf2 transcription factor controls insulin receptor signaling in the regenerating liver.
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