Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury

Hong, Mu-Keng; Liu, Haihua; Chen, Guihong; Zhu, Ji-Xiao; Zheng, Songyuan; Zhao, Di; Diao, Jianxing; Jia, Hui; Zhang, Dingding; Chen, Shixian; Gao, Lei; Li, Juan

doi:10.1155/2021/3259238

Cited by 13 publications

(7 citation statements)

References 35 publications

(41 reference statements)

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“…We successfully established cataract lens epithelial cell model in HLE-B3 cells by using H 2 O 2 (Hong et al, 2021). Through a series of in vitro experiments, such as cell counting kit-8 (CCK-8) assay, flow cytometry, Western blot analysis, and enzyme-linked-immunosorbent serologic assay (ELISA), we revealed that ORI promoted the viability of H 2 O 2 -induced HLE-B3 cells, and suppressed apoptosis and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress

Chen

Zeng

Xiao

et al. 2023

Qual. Assur. Saf. Crops Foods

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Cataract is the clouding of eye lens, and is the leading cause of visual impairment and blindness worldwide. There is an urgent need to develop new drugs to combat this disease. Oridonin (ORI), isolated from Rabdosia rubescens, is a natural substance that has been studied as an activator of nuclear factor erythroid 2-related factor 2 (Nrf2) and covalent inhibitor of NLR family pyrin domain containing 3 (NLRP3). Whether ORI has a therapeutic effect on human lens’ epithelial cell injury needs further study. In this study, we used cataract lens epithelial cell lines HLE-B3 and SRA01/04. We found using the MTT assay that ORI treatment increased cell viability induced by hydrogen peroxide (H2O2). In addition, ORI suppressed the apoptosis of H2O2-induced HLE-B3 and SRA01/04 cells detected by flow cytometry and Western blot analysis. Our data further revealed that ORI regulated nuclear factor, erythroid 2 (NFE2) like bZIP transcription factor 2 (Nrf2)-mediated oxidative stress by enzyme-linked-immunosorbent serologic assay. We further found that ORI inhibited NLRP3/nuclear factor-κb (NF-κB) pathway in H2O2-induced HLE-B3 and SRA01/04 cells by Western blot analysis. Therefore, these results suggested that ORI could have the potential to serve as a promising drug to treat cataract.

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Section: Discussionmentioning

confidence: 99%

Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress

Chen

Zeng

Xiao

et al. 2023

Qual. Assur. Saf. Crops Foods

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“…The functional analysis of the KEGG microbial metabolic pathway observed that the HFHF + millet group positively regulated the pathways related to the urea cycle, amino acid biosynthesis (L-lysine, L-threonine, L-methionine, L-phenylalanine, and L-tyrosine) and degradation of sucrose and glycerol, which demonstrates that the germinated millet flour was able to modulate essential metabolic pathways. After amino acid metabolism, the activation of the urea cycle, which is a vital process, converts ammonia as a toxic byproduct into urea, thus allowing unwanted hydrogen to be eliminated from the body [ 42 , 43 ]. The degradation of sucrose and glycerol is also essential to generate energy and maintain homeostasis, in addition to amino acid biosynthesis, which still plays a key role in the immune response and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Germinated Millet (Pennisetum glaucum (L.) R. Br.) Flour Improved the Gut Function and Its Microbiota Composition in Rats Fed with High-Fat High-Fructose Diet

Theodoro

Grancieri

Gomes

et al. 2022

IJERPH

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Germinated millet (Pennisetum glaucum (L.) R. Br.) is a source of phenolic compounds that has potential prebiotic action. This study aims at evaluating the action of germinated pearl millet on gut function and its microbiota composition in Wistar rats fed with a high-fat high-fructose (HFHF) diet. In the first stage, lasting eight weeks, the experiment consisted of two groups: AIN-93M (n = 10) and HFHF group (n = 20). In the second stage, which lasted ten weeks, the animals of the AIN-93M group (n = 10) were kept, while the HFHF group was dismembered into HFHF (HFHF diet, n = 10) and HFHF + millet (HFHF added 28.6% of germinated millet flour, n = 10) groups. After the 18th week, the urine of the animals was collected for the analysis of lactulose and mannitol intestinal permeability by urinary excretion. The histomorphometry was analyzed on the proximal colon and the fecal pH, concentration of short-chain fatty acids (SCFA), and sequencing of microbiota were performed in cecum content. The Mothur v.1.44.3 software was used for data analysis of sequencing. Alpha diversity was estimated by Chao1, Shannon, and Simpson indexes. Beta diversity was assessed by PCoA (Principal Coordinate Analysis). The functional predictive analysis was performed with PICRUSt2 software (version 2.1.2−b). Functional traits attributed to normalized OTU abundance were determined by the Kyoto Encyclopedia of Genes and Genomes (KEGG). In the results, germinated millet flour reduced Oscillibacter genus and Desulfobacterota phylum, while increasing the Eggerthellaceae family. Furthermore, germinated millet flour: increased beta diversity, cecum weight, and cecum/body weight ratio; improved gut histological parameters by increasing the depth and thickness of the crypt and the goblet cell count (p < 0.05); reduced (p < 0.05) the fecal pH and mannitol urinary excretion; increased (p < 0.05) the propionate short-chain fatty acid concentration. Thus, germinated millet has the potential to improve the composition of gut microbiota and the intestinal function of rats fed with an HFHF diet.

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“…Recently, many studies have demonstrated the great potential of such drugs in this field, which is inseparable from their targeted regulation of gut microbiota, as shown in Table 1 . Oridonin, a liver protective agent derived from Rabdosia rubescens , is believed to reduce APAP-induced hepatotoxicity and ALI by regulating the Bacteroides vulgatus -urea cycle-Nrf2 axis ( 21 ). A study on the extract of Ampelopsis grossedentata (VTE) indicated that it could alleviate CCl 4 -induced hepatotoxicity and ALI by restoring gut microbiota dysbiosis in mice.…”

Section: Targeting Gut Microbiota For Acute Liver Injurymentioning

confidence: 99%

“…More delicately, prior studies have found that the therapeutic effects of TCMs and NPs on liver disease are closely related to their regulation of gut microbes. For example, the active ingredient Poria cocos polysaccharides (PCP) downregulates the nuclear factor kappa-B (NF-Kb)/CCL3/CCR1 axis by regulating gut microbes to prevent nonalcoholic steatohepatitis (NASH) ( 18 ); Si Miao Formula ( 19 ) and Ophiopogon polysaccharide MDG-1 can alleviate NAFLD by inhibiting the gut microbiota and gut-liver axis ( 20 ); and oridonin has also been proven to reduce liver injury by altering gut microbiota and promoting the hepatic urea cycle ( 21 ). The combination of these studies highlights the great potential of TCMs and NPs in targeting gut microbiota for the treatment of liver diseases.…”

Section: Introductionmentioning

confidence: 99%

Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy

Zhu

Zheng

et al. 2023

Front. Immunol.

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The gut microbiota not only constitutes intestinal microenvironment homeostasis and human health but also exerts indispensable roles in the occurrence and progression of multiple liver diseases, including alcohol-related liver disease, nonalcoholic fatty liver disease, autoimmune liver disease and liver cancer. Given the therapeutic status of these diseases, their prevention and early therapy are crucial, and the detailed mechanism of gut microbiota in liver disease urgently needs to be explored. Meanwhile, multiple studies have shown that various traditional Chinese medicines, such as Si Miao Formula, Jiangzhi Granules, Liushen Capsules, Chaihu-Shugan Power, Cassiae Semen and Gynostemma, as well as some natural products, including Costunolide, Coprinus comatus polysaccharide, Antarctic krill oil, Oridonin and Berberine, can repair liver injury, improve fatty liver, regulate liver immunity, and even inhibit liver cancer through multiple targets, links, and pathways. Intriguingly, the aforementioned effects demonstrated by these traditional Chinese medicines and natural products have been shown to be closely related to the gut microbiota, directly driving the strategy of traditional Chinese medicines and natural products to regulate the gut microbiota as one of the breakthroughs in the treatment of liver diseases. Based on this, this review comprehensively summarizes and discusses the characteristics, functions and potential mechanisms of these medicines targeting gut microbiota during liver disease treatment. Research on the potential effects on gut microbiota and the regulatory mechanisms of traditional Chinese medicine and natural products provides novel insights and significant references for developing liver disease treatment strategies. In parallel, such explorations will enhance the comprehension of traditional Chinese medicine and natural products modulating gut microbiota during disease treatment, thus facilitating their clinical investigation and application.

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Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury

Cited by 13 publications

References 35 publications

Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress

Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress

Germinated Millet (Pennisetum glaucum (L.) R. Br.) Flour Improved the Gut Function and Its Microbiota Composition in Rats Fed with High-Fat High-Fructose Diet

Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy

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