Objective To investigate the therapeutic effect of Houttuynia cordata extract on endotoxin induced uveitis (EIU) in rats and analyze its anti-inflammatory molecular mechanism.
Methods In the animal experiment, Lewis rats were randomly divided into 5 groups: normal control group, EIU model group, EIU model+normal saline group, EIU model+Houttuynia cordata extract group and EIU model+dexamethasone group. At 24 hours after modeling, ocular inflammation in five groups of rats was observed and scored, the concentrations of infiltrating cells and proteins in aqueous humor were detected, and HE staining was performed to observe the histopathological changes of ocular tissues. In the cell experiment, rat retinal cells were cultured, and the cells were randomly divided into 4 groups: the normal control group, the LPS group, the LPS+ normal saline group, and the LPS+Houttuynia cordata group. After 24 hours, the survival ability of the four groups of cells, TNF-α, IL-6, and the protein expression levels of inflammation-related pathways were detected.
Results Compared with the EIU model group, the clinical inflammation score, the number of infiltrating cells, pathological grade and the protein concentration in the EIU model+Houttuynia cordata extract group were significantly decreased (P<0.05). Compared with the LPS group and LPS+normal saline group, the survival rate of retinal cells in the LPS+ Houttuynia cordata group of rats was significantly increased. However, the expression levels of TNF-α, IL-6 mRNA and protein, as well as the protein expression levels of factors related to the PI3K/AKT/mTOR, Wnt/β-catenin, NF-κB/MAPK signaling pathways were significantly decreased (P<0.05).
Conclusion Houttuynia cordata extract can effectively treat EIU rats and alleviate LPS induced retinal cell inflammation in rats. Its mechanism may be related to inhibition of the activity of PI3K/AKT/mTOR, Wnt/β- Catenin and NF- κB/MAPK signaling pathways.
1.熊慧, 杨明明, 于旭辉. 补体系统在葡萄膜炎发病机制中的作用[J]. 国际眼科杂志, 2022, 22(8): 1293-1297. [Xiong H, Yang MM, Yu XH. Role of complement system in the pathogenesis of uveitis[J]. International Eye Science, 2022, 22(8): 1293-1297.] DOI: 10.3980/j.issn.1672-5123.2022.8.11.
2.王洪亚, 郑文, 戴永刚, 等. HLA-B27阳性与阴性葡萄膜炎患者外周血中炎症因子表达研究[J]. 国际眼科杂志, 2022, 22(9): 1559-1563. [Wang HY, Zheng W, Dai YG, et al. Expression of inflammatory factors in peripheral blood of patients with HLA-B27 positive and negative uveitis[J]. International Eye Science, 2022, 22(9): 1559-1563.] DOI: 10.3980/j.issn.1672-5123.2022.9.28.
3.荆锋, 宋志红. NLRP3炎症小体与葡萄膜炎的关系[J]. 检验医学与临床, 2021, 18(5): 690-693. [Jing F, Song ZH. The relationship between NLRP3 inflammasome and uveitis[J]. Laboratory Medicine and Clinic, 2021, 18(5): 690-693.] DOI: 10.3969/j.issn.1672-9455.2021.05.035.
4.Gamalero L, Simonini G, Ferrara G, et al. Evidence-based treatment for uveitis[J]. Isr Med Assoc J, 2019, 21(7): 475-479. https://pubmed.ncbi.nlm.nih.gov/31507124/.
5.Wu Z, Deng X, Hu Q, et al. Houttuynia cordata Thunb: an ethnopharmacological review[J]. Front Pharmacol, 2021, 12: 714694. DOI: 10.3389/fphar.2021.714694.
6.Rafiq S, Hao H, Ijaz M, et al. Pharmacological effects of Houttuynia cordata Thunb (H. cordata): a comprehensive review[J]. Pharmaceuticals (Basel), 2022, 15(9): 1079. DOI: 10.3390/ph15091079.
7.Laldinsangi C. The therapeutic potential of Houttuynia cordata: a current review[J]. Heliyon, 2022, 8(8): e10386. DOI: 10.1016/j.heliyon.2022.e10386.
8.Fang H, Yang Z, Yang L. Protective effect of Houttuynia cordata extract on propofol-induced injury of rat hippocampal neurons by regulating PI3K/Akt and Toll-like receptor 4/NF-κB signaling pathway[J]. Neuroreport, 2021, 32(7): 577-582. DOI: 10.1097/WNR.0000000000001627.
9.Li W, Yang F, Zhan H, et al. Houttuynia cordata extract ameliorates bladder damage and improves bladder symptoms via anti-inflammatory effect in rats with interstitial cystitis[J]. Evid Based Complement Alternat Med, 2020, 2020: 9026901. DOI: 10.1155/2020/9026901.
10.Han EH, Park JH, Kim JY, et al. Houttuynia cordata water extract suppresses anaphylactic reaction and IgE-mediated allergic response by inhibiting multiple steps of FcepsilonRI signaling in mast cells[J]. Food Chem Toxicol, 2009, 47(7): 1659-1666. DOI: 10.1016/j.fct.2009.04.025.
11.Du L, Yip YWY, Ng HK, et al. Ruxolitinib alleviates uveitis caused by salmonella typhimurium endotoxin[J]. Microorganisms, 2021, 9(7): 1481. DOI: 10.3390/microorganisms9071481.
12.Zhang D, Wang C, Cao S, et al. High-salt enhances the inflammatory response by retina pigment epithelium cells following lipopolysaccharide stimulation[J]. Mediators Inflamm, 2015, 2015: 197521. DOI: 10.1155/2015/197521.
13.Chen CL, Chen JT, Liang CM, et al. Silibinin treatment prevents endotoxin-induced uveitis in rats in vivo and in vitro[J]. PLoS One, 2017, 12(4): e0174971. DOI: 10.1371/journal.pone.0174971.
14.Cheng D, Sun L, Zou S, et al. Antiviral effects of Houttuynia cordata polysaccharide extract on murine norovirus-1 (MNV-1)-A human norovirus surrogate[J]. Molecules, 2019, 24(9): 1835. DOI: 10.3390/molecules24091835.
15.Agarwal A, Aggarwal K, Gupta V. Infectious uveitis: an Asian perspective[J]. Eye (Lond), 2019, 33(1): 50-65. DOI: 10.1038/s41433-018-0224-y.
16.张明新, 彭晓燕, 呼风, 等. 宏基因组测序技术检测感染性葡萄膜炎病原体的初步研究[J]. 中华眼科杂志, 2020, 56(7): 519-523. [Zhang MX, Peng XY, Hu F, et al. Identification of pathogens in the vitreous of patients with infectious uveitis by metagenomic sequencing[J]. Chinese Journal of Ophthalmology, 2020, 56(7): 519-523.] DOI: 10.3760/cma.j.cn112142-20190711-00371.
17.殷学伟, 郭励劼, 周梦贤, 等. 龙胆泻肝汤对实验性自身免疫性葡萄膜炎大鼠M1/M2巨噬细胞极化平衡的调控作用[J]. 眼科新进展, 2021, 41(5): 408-412. [Yin XW, Guo LJ, Zhou MX, et al. Regulatory role of Longdan Xiegan decoction in polarization balance of M1/M2 macrophages in rats with experimental autoimmune uveitis[J]. Recent Advances in Ophthalmology, 2021, 41(5): 408-412.] DOI: 10.13389/j.cnki.rao.2021.0085.
18.周梦贤, 殷学伟, 郭励劼, 等. 龙胆泻肝汤抑制Notch信号通路活化对实验性自身免疫性葡萄膜炎大鼠Th1、Th2细胞分化的影响 [J]. 眼科新进展, 2021, 41(6): 506-510. [Zhou MX, Yin XW, Guo LJ, et al. Effects of Longdan Xiegan decoction on Th1 and Th2 cell differentiation by inhibiting Notch pathway activation in experimental autoimmune uveitis rats[J]. Recent Advances in Ophthalmology, 2021, 41(6): 506-510.] DOI: 10.13389/j.cnki.rao.2021.0105.
19.袁立飞, 刘静娜, 张越, 等. 清热明目颗粒对实验性自身免疫性葡萄膜炎大鼠的治疗作用及抗炎机制研究[J]. 中国中医眼科杂志, 2021, 31(11): 770-775, 782. [Yuan LF, Liu JN, Zhang Y, et al. Therapeutic effect of Qingremingmu granule on experimental autoimmune uveitis rats and its anti-inflammatory mechanism[J]. Chinese Journal of Chinese Ophthalmology, 2021, 31(11): 770-775, 782.] DOI: 10.13444/j.cnki.zgzyykzz.2021.11.002.
20.Choi Y, Jung K, Kim HJ, et al. Attenuation of experimental autoimmune uveitis in lewis rats by betaine[J]. Exp Neurobiol, 2021, 30(4): 308-317. DOI: 10.5607/en21011.
21.ParkJ, KimJT, Lee SJ, et al. The anti-inflammatoryeffects of angiogenininanendotoxininduceduveitis inrats[J]. Int J Mol Sci, 2020, 2(2): 413. DOI: 10.3390/ijms21020413.
22.Shi X, Zhu S, Jin H, et al. The anti-inflammatory effect of KS23, a novel peptide derived from globular adiponectin, on endotoxin-induced uveitis in rats[J]. Front Pharmacol, 2021, 11: 585446. DOI: 10.3389/fphar.2020.585446.
23.罗秋莲. 鱼腥草多糖的理化性质及抗氧化活性研究[J]. 安徽农业科学, 2022, 50(22): 164-166, 214. [Luo QL. Study on physic-chemical properties and antioxidant activity of polysaccharide from Houttuynia cordata[J]. Journal of Anhui Agricultural Sciences, 2022, 50(22): 164-166, 214.] DOI: 10.3969/j.issn.0517-6611. 2022.22.040.
24.张俊, 柴琳, 刘荣均, 等. 鱼腥草提取物对支原体肺炎小鼠TLR-2/MyD88/NF-κB信号通路的影响[J]. 中药材, 2021, 44(9): 2189-2193. [Zhang J, Chai L, Liu RJ, et al. The effect of Houttuynia cordata extract on the TLR-2/MyD88/NF-κB signaling pathway in mice with mycoplasma pneumonia[J]. Journal of Chinese Medicinal Materials, 2021, 44(9): 2189-2193.] DOI: 10.13863/j. issn1001-4454.2021.09.033.
25.王莹巍, 石立慧, 王颖, 等. 鱼腥草素钠通过抑制STAT3/NF-κB信号通路减轻哮喘幼鼠的肺内炎症反应[J]. 解剖科学进展, 2022, 28(3): 311-314. [Wang YW, Shi LH, Wang Y, et al. Sodium houttuynia reduced lung inflammation in asthmatic young mice by inhibiting STAT3/ NF-κB signaling pathway[J]. Progress of Anatomical Sciences, 2022, 28(3): 311-314.] DOI: 10.16695/j.cnki.1006-2947.2022.03.018.
26.张娅琴, 李小明, 吴守业. 复方鱼腥草软胶囊联合头孢硫脒治疗儿童急性扁桃体炎的临床研究[J]. 药物评价研究, 2020, 43(2): 269-272. [Zhang YQ, Li XM, Wu SY. Clinical study on compound Yuxingcao soft capsules combined with cefathiamidine in treatment of acute tonsillitis in children[J]. Drug Evaluation Research, 2020, 43(2): 269-272.] DOI: 10.7501/j.issn.1674-6376.2020.02.017.
27.Cen L, Yi T, Hao Y, et al. Houttuynia cordata polysaccharides alleviate ulcerative colitis by restoring intestinal homeostasis[J]. Chin J Nat Med, 2022, 20(12): 914-924. DOI: 10.1016/S1875-5364(22)60220-6.
28.Yang L, Qiu Y, Liu J, et al. Retinal transcriptome analysis in the treatment of endotoxin-induced uveitis with tetramethylpyrazine eye drops[J]. J Ocul Pharmacol Ther, 2019, 35(4): 235-244. DOI: 10.1089/jop.2018.0105.
29.Li W, Liu L, Zhang Z, et al. Morroniside ameliorates endotoxin-induced uveitis by regulating the M1/M2 polarization balance of macrophages[J]. J Immunol Res, 2023, 2023: 1252873. DOI: 10.1155/2023/1252873.
30.Chen H, Feng X, Gao L, et al. Inhibiting the PI3K/AKT/mTOR signalling pathway with copper oxide nanoparticles from Houttuynia cordata plant: attenuating the proliferation of cervical cancer cells[J]. Artif Cells Nanomed Biotechnol, 2021, 49(1): 240-249. DOI: 10.1080/21691401.2021.1890101.