Food & Function
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2018
·Vol. 9
·期 3
·1701-1712
·
IF 3.289
Shangkun Tang,Qian Tang,Jialei Jin,Gang Zheng,Jianchen Xu,Wu Huang,Xiaobin Li,Ping Shang,Haixiao Liu
Osteoarthritis (OA), which is characterized by progressive degradation of the articular cartilage, is the most prevalent form of human arthritis. Accumulating evidence has shown that polydatin (PD) exerts special biological functions in a variety of diseases. However, whether it protects against OA development has remained unknown. Here, we investigated the anti-inflammatory and chondroprotective effects of PD on interleukin (IL)-1β-induced human osteoarthritic chondrocytes and in the surgical destabilization of medial meniscus mouse (DMM) OA models. In vitro, PD treatment completely suppressed the over-production of pro-inflammatory mediators, including prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), nitric oxide (NO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6 in IL-1β-induced human OA chondrocytes. Moreover, PD exerted a suppressive effect on the expression of matrix-degrading proteases, including matrix metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS-5), which leads to the degradation of the extracellular matrix (ECM). Meanwhile, specific inhibition of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) level by short-interfering RNA (siRNA) strongly reversed the anti-inflammatory and chondroprotective effects of PD in human OA chondrocytes. The protective effects of PD were also observed in vivo. In conclusion, our studies demonstrate that PD holds novel therapeutic potential for the development of OA.
研究领域:
风湿病学
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药理学
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炎症
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骨科
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分子生物学
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JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING
·
2026
·
IF 2
Jing Zhu,Mengmeng Gao,Hao Ling,Phar Ku Ngwe,Chengxiang Guo,Yinan Hu,Jicang Wang
This study investigated the protective effects of naringenin (Nar) against lead (Pb)-induced testicular injury in rats, focusing on the Nrf2/Keap1 antioxidant pathway and PINK1/Parkin-mediated mitophagy. To this end, male SD rats were exposed to Pb (60 mg/kg) and co-treated with Nar (50 mg/kg) for 8 consecutive weeks, followed by assessments via biochemical detection, oxidative stress (OS) evaluation, hematological examination, histopathological observation, qPCR, WB, and IHC analyses. Pb exposure caused hematological disturbances, reduced serum LH and T levels, and OS imbalance (lower GSH, SOD, CAT; higher MDA), aggravating testicular damage. Meanwhile, it suppressed the Nrf2/NQO1 pathway, elevated Keap1, impaired autophagy (elevated p62, declined LC3‑II/LC3‑I ratio), and induced aberrant accumulation of PINK1/Parkin. Co-treatment with Nar mitigated these alterations, ameliorating testicular injury, restoring redox homeostasis and serum reproductive hormone levels, and normalizing key molecular expressions in both pathways. In conclusion, Nar alleviates Pb-induced rat testicular damage by reactivating the Nrf2/Keap1 axis to suppress OS, and by restoring autophagic flux to facilitate PINK1/Parkin-mediated clearance of damaged mitochondria.
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SOUTH AFRICAN JOURNAL OF BOTANY
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2026
·
IF 3.1
Xian Dong Lv,Meiherinisa Maitituersun,Fei Li
This study established HPLC fingerprints of PCAE 70% and RLQ, supported by the 2020 edition of the Chinese Pharmacopeia and relevant literature, and performed network pharmacology prediction for the common constituents. • Multi-index regression analysis of uniform design data was conducted by partial least squares, by which seven active components were optimized and determined as six important active components, and their rationality was experimentally validated. • The entropy weight method was employed to unify heterogeneous data from in vitro and in vivo experiments, and the integrated important active component combination was subjected to in vivo activity validation through a mouse urinary tract infection model. • This study suggests that the active components centered on gallic acid, myricitrin, and quercitrin may constitute the major pharmacodynamic material basis of Polygonum capitatum against UTI, and preliminarily explored the underlying mechanism. Ethnopharmacological relevance As a cornerstone herb in the traditional medicine of the Miao ethnic group in Guizhou Province, Polygonum capitatum has long been used to treat diseases of the urinary system. Documented in Miao medical theory as cold in nature and bitter-pungent in taste, and as acting on the kidney and bladder meridians, it is traditionally used to clear heat, promote diuresis, relieve stranguria, and detoxify, thereby relieving pain. The aqueous extract of this herb is the sole component of Relinqing Granules (RLQ), a clinically widespread formulation. Despite its broad clinical application, the underlying material basis of its pharmacological activity remains to be fully elucidated. Materials and methods The target compounds were identified through literature investigation, and their presence in both the Polygonum capitatum 70% aqueous ethanol extract (PCAE 70%) and RLQ was subsequently verified. The common constituents shared by the two were identified by comparing the fingerprint chromatograms with reference standards, and network pharmacology was employed to predict the potential targets of these components. The constituents were then combined through uniform design to evaluate their antibacterial, anti-inflammatory, and antioxidant activities, optimized via partial least squares regression and the entropy weight method, and ultimately validated in a mouse model of UTI. Results A total of seven common constituents were identified: gallic acid, protocatechuic acid, catechin, myricitrin, quercitrin, quercetin, and kaempferol. Network pharmacology predicted that these constituents might exert anti-UTI effects through modulation of the PI3K-Akt signaling pathway. The optimal ratio combination demonstrated significant antibacterial activity against Escherichia coli and Staphylococcus aureus , while another optimal ratio enhanced catalase activity and modulated the expression of AKT-1/Nrf 2 / HO-1/NF-κB 3 in zebrafish. Following data integration using the entropy weight method, mouse validation results revealed decreased TNF-α/IL-1β levels and increased IL-10 levels, with superior efficacy compared to PCAE 70% and RLQ, without dose-dependent differences. The results implied that gallic acid, myricitrin, and quercitrin represent the potential principal active components of P. capitatum. Conclusion The optimized combination dominated by gallic acid, myricitrin, and quercitrin, identified from P. capitatum , exhibited antibacterial, anti-inflammatory, and antioxidant performance superior or equivalent to existing preparations, holding significant theoretical and practical value. Download: Download high-res image (228KB) Download: Download full-size image Graph A illustrates the experimental procedure for determining the in vitro antibacterial activity of target drugs by the MTT method; Graph B illustrates the experimental procedure for the acute toxicity assay in zebrafish; Graph C illustrates the mechanism diagram of drug administration in the zebrafish oxidative stress model; Graph D illustrates the simplified experimental procedure and mechanism diagram before drug administration in the mouse UTI model.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2026
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IF 5.2
Hongchuang Ma,Nan Shen,Xin Liu,Fangfang Zhou,Chuanming Hao,Qun Luo
Background Acute kidney injury (AKI) remains a major clinical challenge lacking effective pharmacological interventions. Ferroptosis has emerged as a critical mechanism contributing to renal tubular injury. While p -coumaric acid (pCA), a natural phenolic compound, has been reported to exert renoprotective effects, its regulatory role in ferroptosis, particularly under different pathological contexts of AKI, remains incompletely understood. Methods A folic acid (FA, 250 mg/kg)–induced AKI model was established in mice treated with pCA (10 and 50 mg/kg). Renal function, histopathology, inflammatory responses, and ferroptosis-related markers were evaluated. Integrated transcriptomic and metabolomic analyses were performed to identify global regulatory alterations. Mechanistic studies were conducted in erastin-treated HK-2 cells. NRF2 signaling involvement was further assessed using pharmacological inhibition. Results pCA treatment significantly improved renal function, attenuated tubular injury, and suppressed inflammatory responses in FA-induced AKI. Multi-omics integration revealed that pCA markedly reprogrammed metabolic and transcriptional networks associated with ferroptosis and redox homeostasis. Mechanistically, pCA restored antioxidant capacity and normalized the expression of ferroptosis-related proteins. Notably, pCA activated NRF2 signaling, leading to upregulation of downstream targets involved in ferroptosis regulation. Inhibition of NRF2 partially abolished the cytoprotective and anti-ferroptotic effects of pCA in vitro. Conclusion pCA alleviates FA-induced AKI by suppressing ferroptosis through NRF2-dependent regulation of redox and metabolic homeostasis, highlighting NRF2 as a potential therapeutic target for AKI.
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Foods
·
2024
·Vol. 13
·期 15
·2440
·
IF 4.7
Jingwen Yu,Xiangwei Xiao,Baiying Chen,Zeyuan Deng,Xuan Chen,Yawei Fan,Hongyan Li
The antioxidant activities of lycopene (LY), lutein (LU), chlorogenic acid (CA), and delphinidin (DP) were tested in vitro on H9c2 cell-based models. Some indicators, such as the generation of reactive oxygen (ROS), the quantification of cell antioxidant activity (CAA), and the expressions of SOD, GSH-Px, and CAT, were calculated to examine their antioxidant interactions. From our results, the phytochemical mixtures (M1: CA-LU: F3/10, M2: DP-CA: F7/10, M3: DP-LY: F5/10) displayed strong synergistic effects based on the generation of ROS and the quantification of CAA. However, great antagonistic bioactivities were seen in the combinations of LY-LU: F5/10 (M4), CA-LU: F9/10 (M5), and DP-LY: F7/10 (M6). Western blotting analysis indicated that the possible mechanism underlying the synergistic antioxidant interactions among phytochemical combinations was to enhance the accumulation of Nrf2 in the nucleus and the expression of its downstream antioxidant enzymes, HO-1 and GCLC. The combinations (M1–M3 groups) showed significant protection against the loss of mitochondrial membrane potential than individual groups to avoid excessive ROS production. The M4–M6 groups exerted antagonistic protective effects compared with the individual groups. In addition, lutein and lycopene absorption was improved more because of the presence of chlorogenic acid and delphinidin in the M1 and M3 groups, respectively. However, delphinidin significantly reduced the cellular uptake of lycopene in the M6 group. It appeared that antioxidant interactions of phytochemical combinations may contribute to the restoration of cellular redox homeostasis and lead to an improvement in diet quality and collocation.
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Scientific Reports
·
2026
·
IF 4.9
Zhang Panpan,Zhang Xun,Ma Siyu,Jiang Mengqiang,Zhao Wenhong
Astaxanthin (ATX), a natural antioxidant whose benefits in age-related liver and kidney damage remain unclear. We established a D-galactose-induced ageing model in rats and observed the daily behaviour of the rats. Using staining methods to detect ROS, apoptosis and histopathological changes in liver and brain tissue. Determination of antioxidant levels of IL-2, IL-6 and AGES in rats. Assessment of cognitive function using the Morris water maze and ChAT. The mRNA and protein expression levels of Nrf2, Bach1, SOD1, SOD2, HO-1 were determined by real-time PCR and Western blotting. To investigate the role of the Nrf2/Bach1-ARE pathway, we used ML385, a specific inhibitor of the Nrf2 pathway, to treat rats in the inhibitor group. Aging rats showed impaired learning and memory, along with decreased levels of neurotransmitters and antioxidant enzymes. ATX and vitamin E (VE) interventions significantly alleviated these symptoms and activated the Nrf2/Bach1-ARE pathway in liver and brain tissues of aged SD rats. Furthermore, the protective effects of ATX were attenuated by the addition of the Nrf2 inhibitor ML385. ATX reduces oxidative stress and ameliorates liver and brain damage in aged rats via activation of the Nrf2/Bach1-ARE pathway.
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FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Wenyue Qiu,Xinting Zhang,Xiaoyue Pang,Jianjia Huang,Shuilian Zhou,Rongmei Wang,Zhaoxin Tang,Rongsheng Su
Asiatic acid (AA), a triterpenoid compound isolated from Centella asiatica , has anti-inflammatory, antioxidant and anticancer biological characteristics . To explore the effect of AA on LPS-induced acute kidney injury (AKI) in broilers, a total of 60 one-day-old broilers were randomly divided into 6 groups, including the normal group, AKI model group, AKI + AA 15 mg/kg group, AKI + AA 30 mg/kg group, AKI + AA 60 mg/kg group and normal + AA 60 mg/kg group. Hematoxylin-eosin staining was used to observe the histopathology in kidney tissue, and the mRNA and protein expressions related to oxidative stress and ferroptosis were tested by qPCR and western blotting respectively. AA mitigated vacuolar degeneration and enlarged glomerular space caused by LPS in kidney tissue. Additionally, AA significantly increased the mRNA levels of Nrf2, HO-1, NQO1, GCLC, GCLM , GPX4 , SLC7A11 and FTH1 , and decreased the mRNA levels of Keap1 and PTGS2 in LPS-induced AKI. Likewise, AA significantly upregulated the protein expressions of Nrf2, HO-1, NQO1, GPX4, SLC7A11 and FTH1, and downregulated the protein expressions of Keap1 and PTGS2 in LPS-induced AKI. These results suggested that AA alleviated LPS-induced AKI by inhibiting oxidative stress and ferroptosis through targeting regulation of the Nrf2 pathway in broilers.
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Toxins
·
2022
·Vol. 14
·期 12
·876
·
IF 5.075
Yanan Wang,Jiayu Wu,Lingfeng Wang,Ping Yang,Zuhong Liu,Shahid Ali Rajput,Mubashar Hassan,Desheng Qi
Aflatoxin B1(AFB1) exists widely in feed and food with severe hazards, posing a serious threat to human and animal health. Epigallocatechin gallate (EGCG) and glutathione (GSH) have been reported as having anti-oxidative and other functions. The present study aimed to investigate the detoxification effect of EGCG and GSH alone or in combination on AFB1exposure in ducklings. Fifty one-day-old male ducklings were randomly assigned into five experimental groups (n= 10): 1. Control (CTR); 2. 0.3 mg/kg BW AFB1(AFB1); 3. 0.3 mg/kg BW AFB1+ 100 mg/kg BW EGCG (AFB1+ EGCG); 4. 0.3 mg/kg BW AFB1+ 30 mg/kg BW GSH (AFB1+ GSH); 5. 0.3 mg/kg BW AFB1+ 100 mg/kg BW EGCG + 30 mg/kg BW GSH (AFB1+ EGCG + GSH). The experiment lasted for seven days. Compared with the CTR group, AFB1reduced growth performance, total serum protein and albumin content, increased serum enzyme activity (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase), and caused pathological damage to the ducklings’ livers. AFB1exposure increased malondialdehyde content and decreased superoxide dismutase, total antioxidant capacity, catalase, glutathione peroxidase activities, and glutathione content in the liver. EGCG and GSH alone or in combination mitigated these adverse effects. Meanwhile, EGCG and GSH attenuate apoptosis of hepatocytes, and regulated AFB1-induced changes in the abundance of genes contained in the Keap1/Nrf2 signalling and apoptotic pathways. Collectively, these results suggest that EGCG and GSH alleviate the hepatocyte injury induced by AFB1by inhibiting oxidative stress and attenuating excessive mitochondria-mediated apoptosis.Keywords:aflatoxin B1;duckling;epigallocatechin gallate;glutathione;oxidative stress;Keap1/Nrf2 signalling;apoptosisKey Contribution:EGCG and GSH alleviate AFB1-induced liver injury in ducklings by increasing antioxidant capacity and antagonising apoptosis.
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CHEMISTRY & BIODIVERSITY
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2022
·Vol. 19
·期 8
·e202200471
·
IF 2.745
Qiang-Ming Li,Xiu-Rong Yang,Xue-Qiang Zha,Li-Hua Pan,Dan-Dan Zang,Feng-Yun Zhang,Jian-Ping Luo
Dendrobium huoshanense flowers have been widely used for liver protection in China. This work was aimed to discover the natural products with activity of mitigating alcoholic hepatocyte injury from Dendrobium huoshanense flowers via bioactivity-guided isolation, and to clarify the underlying mechanisms of these natural products. As a result, three flavonoids, 3′- O- methylquercetin-3- O-β -D-galactopyranoside ( 1 ), 3′- O- methylquercetin-3- O-β -D-glucopyranoside ( 2 ) and quercetin-3- O-β -D-glucopyranoside ( 3 ), were firstly isolated from D. huoshanense flowers. Results exhibited that flavonoids 1 – 3 could enhance the cell viability, decrease the expression of ALT and AST, inhibit the cell apoptosis, alleviate the oxidative stress, and mitigate the inflammatory response of alcohol-induced L02 cells. Mechanism study exhibited that flavonoids 1 – 3 could increase the expression of Nrf2 as well as its downstream antioxidation genes of alcohol-induced L02 cells, while ML-385 (Nrf2 inhibitor) could abolish the inhibitory effects of 1 – 3 on alcohol-induced hepatocyte injury. Flavonoids 1 – 3 could also reduce the phosphorylation levels of I κ B α and NF- κ B p65 of alcohol-induced L02 cells, while SC75741 (NF- κ B inhibitor) could not enhance the inhibitory effects of 1 – 3 on alcohol-induced L02 cells injury. The data above indicated that flavonoids 1 – 3 could inhibit alcohol-induced hepatocyte injury, which might be attributed to alleviating oxidative stress and mitigating inflammatory response by activating Nrf2 and inhibiting NF- κ B pathways.
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Nutrients
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2022
·Vol. 14
·期 15
·3102
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IF 6.706
Ning Li,Liuding Wen,Tiange Li,Huijie Yang,Mingwu Qiao,Tianlin Wang,Lianjun Song,Xianqing Huang,Mingming Li,Erkigul Bukyei,Fangyu Wang
Many researchers have found that Pb exposure can cause oxidative stress damage to the body’s tissue. Black soybean peptide (BSP) has a variety of physiological functions, especially in terms of oxidative stress. Nevertheless, the mitigation function of BSPs on Pb-induced oxidative stress damage in PC12 cells has not been clearly defined. In this study, cell viability was detected by CCK8. Oxidative stress indicators, such as ROS, GSH/GSSG, MDA, SOD, CAT, GPx, and GR, were tested with biochemical kit. Protein expression of Keap1, Nrf2, and TXNIP was measured by Western blot. Compared with the control group, Pb reduced the cell viability of PC12 cells. However, BSP treatment significantly increased the viability of PC12 cells induced by lead exposure (p< 0.05). Lead can enrich the contents of MDA and ROS, but decrease the amount of CAT, SOD, GR, GPx, and GSH/GSSG in PC12 cells, while BSP can alleviate it (p< 0.05). Lead can enhance the expression of Keap1 and TXNIP proteins, but reduce Nrf2 expression. In contrast, BSPs reversed this phenomenon (p< 0.05). BSPs can alleviate oxidative stress injury induced by lead in PC12 cells through the Keap1/Nrf2/TXNIP signaling pathway.Keywords:black soybean peptide;Pb;PC12 cells;Keap1/Nrf2/TXNIP;oxidative stress
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BIOORGANIC CHEMISTRY
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2021
·
IF 5.275
Lanmei Chen,Jie Wang,Xianhong Cai,Suxiang Chen,Jingjing Zhang,Baojun Li,Weigang Chen,Xinhua Guo,Hui Luo,Jincan Chen
Both ruthenium (Ru) and isoquinoline (IQ) compounds are regarded as potential anticancer drug candidates. Here, we report the synthesis and characterization of three novel cyclometalated Ru(II)-isoquinoline complexes: RuIQ-3 , RuIQ-4 , and RuIQ-5, and evaluation of their in vitro cytotoxicities against a panel of cell lines including A549/DDP, a cisplatin-resistant human lung cancer cell line. A549/DDP 3D multicellular tumor spheroids (MCTSs) were also used to detect the drug resistance reversal effect of Ru(II)-IQ complexes. Our results indicated that the cytotoxic activities against cancer cells of Ru(II)-IQ complexes, especially RuIQ-5 , were superior compared with cisplatin. In addition, RuIQ-5 exhibited low toxicity towards both normal HBE cells in vitro and zebrafish embryos in vivo . Further investigation on cellular mechanism of action indicated that after absorption by A549/DDP cells, RuIQ-5 was mainly distributed in the nucleus, which is different from cisplatin. Besides, RuIQ-5 could induce apoptosis through mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, ROS-mediated DNA damage, and cycle arrest at both S and G2/M phases. Moreover, RuIQ-5 could inhibit the overexpression of Nrf2 through regulation of Akt/GSK-3β/Fyn signaling pathway and hindering the nuclear translocation of Nrf2. Based on these findings, we firmly believe that the studied Ru(II)-IQ complexes hold great promise as anticancer therapeutics with high effectiveness and low toxicity.
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CELL STRESS & CHAPERONES
·
2020
·Vol. 26
·期 2
·367-375
·
IF 2.892
Chen Jun,Li Lihua,Zhou Yun,Zhang Jiahua,Chen Lei
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. Gambogic acid has been reported to have anti-inflammatory effect. However, the effect of GA on inflammatory response of ARPE-19 cells remains unclear. In our study, ARPE-19 cells were stimulated by palmitic acid (PA) induction in the presence of 30 mM glucose and then treated with 0.5, 1, 2, 5, 10, or 20 μM GA. CCK-8 assay showed that cell viability was increased by GA treatment at doses of 0.5, 1, and 2 μM instead of higher doses. ELISA analysis found that GA dose-dependently reduced the production of pro-inflammatory mediators TNF-α and IL-1β. Western blot indicated that GA downregulated the expression of NLRP3 inflammasome components including TXNIP, NLRP3, ASC, cleaved-caspase-1, and cleaved-IL-1β in a dose-dependent manner. In addition, Western blot and immunofluorescence analysis suggested that GA effectively increased the protein level of nuclear factor E2-related factor-2 (Nrf2). RT-qPCR showed that GA significantly increased the mRNA levels of Heme oxygenase-1 (HO-1) and NADPH:quinone oxidoreductase1 (NQO1). Furthermore, Nrf2 siRNA transfection confirmed the above effects of GA. In total, subtoxic doses of GA significantly flattened the inflammatory response induced by HG and PA in ARPE-19 cells via modulating the Nrf2 signaling pathway.
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