Effects of Chrysomycin A on Lipopolysaccharide-Induced Acute Renal Inflammation in Mice and Its Possible Mechanism
LIU Man, ZHANG Shan-shan, LIU Dong-ni, SHANG Yu-fu, WANG Yue-hua*, DU Guan-hua*
Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
Abstract：OBJECTIVE To investigate the effects and possible mechanisms of chrysomycin A(Chr-A) on lipopolysaccharide (LPS)-induced acute renal inflammation in mice. METHODS BALB/c mice were randomly divided into control group, LPS model group and Chr-A 3, 10 mg·kg-1 treatment groups. After 7 d of Chr-A administration, the mice in LPS model group and Chr-A treatment groups were injected with 5 mg·kg-1 LPS intraperitoneally and renal tissues were obtained for the following detection after 6h of LPS injection on the 7th day. The levels of BUN (urea nitrogen) in the serum was detected to assess the kidney function; the levels of IL-1β, IL-6, TNF-α and MCP-1 in renal tissues were measured by ELISA; the expression of inflammatory protein, including COX2, NLRP3 and P2X7 were detected by Western blot. RESULTS Chr-A dose dependently decreased the level of serum urea nitrogen increased by LPS stimulation. In addition, Chr-A dose dependently decreased the inflammatory factors including IL-1β, IL-6,TNF-α, MCP-1 and COX2 in the renal tissues stimulated by LPS. Further studies found that Chr-A significantly down-regulated the expression of inflammatory pathway related proteins P2X7 and NLRP3. CONCLUSION Chr-A has acute renal inflammatory response, and the mechanism may be related to the down regulation of inflammatory proteins P2X7 and NLRP3.
刘漫, 张姗姗, 刘冬妮, 尚宇夫, 王月华, 杜冠华. 金黄霉素A对脂多糖诱导小鼠急性肾脏炎症的作用及其可能机制[J]. 中国药学杂志, 2022, 57(8): 623-627.
LIU Man, ZHANG Shan-shan, LIU Dong-ni, SHANG Yu-fu, WANG Yue-hua, DU Guan-hua. Effects of Chrysomycin A on Lipopolysaccharide-Induced Acute Renal Inflammation in Mice and Its Possible Mechanism. Chinese Pharmaceutical Journal, 2022, 57(8): 623-627.
BELLOMO R, KELLUM J A, RONCO C. Acute kidney injury[J]. Lancet, 2012, 380(9843): 756-766.
[2]
SKUBE S J, KATZ S A, CHIPMAN J G, et al. Acute kidney injury and aepsis[J]. Surg Infect (Larchmt), 2018,19(2):216-224.
[3]
PEERAPORNRATANA S, MANRIQUE-CABALLERO C L, GOMEZ H, et al. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment [J]. Kidney Int, 2019, 96(5):1083-1099.
[4]
XU L, HU G, XING P, et al. Paclitaxel alleviates the sepsis-induced acute kidney injury via lnc-MALAT1/miR-370-3p/HMGB1 axis [J]. Life Sci, 2020, 1(262):118505. Doi:10.1016/j.lfs.2020.118505.
[5]
KIYONAGA N, MORIYAMA T, KANMURA Y. Effects of dexmedetomidine on lipopolysaccharide-induced acute kidney injury in rats and mitochondrial function in cell culture [J]. Biomed Pharmacother, 2020, 125:109912. Doi: 10.1016/j.biopha.2020.109912.
[6]
LIU X, LU J, LIAO Y, et al. Dihydroartemisinin attenuates lipopolysaccharide-induced acute kidney injury by inhibiting inflammation and oxidative stress [J]. Biomed Pharmacother, 2019, 117:109070. Doi: 10.1016/j.biopha.2019.109070.
[7]
HABIB R. Multifaceted roles of Toll-like receptors in acute kidney injury [J]. Heliyon, 2021, 7(3):e06441. Doi: 10.1016/j.heliyon.2021.e06441.
[8]
LEVEY A S, JAMES M T. Acute kidney injury[J]. Ann Intern Med, 2017, 167(9):ITC66-ITC80.
[9]
PATEL NS, CUZZOCREA S, COLLINO M, et al. The role of cycloxygenase-2 in the rodent kidney following ischaemia/reperfusion injury in vivo [J]. Eur J Pharmacol, 2007, 562(1-2):148-154.
[10]
RANGANATHAN PV, JAYAKUMAR C, MOHAMED R, et al. Netrin-1 regulates the inflammatory response of neutrophils and macrophages, and suppresses ischemic acute kidney injury by inhibiting COX-2-mediated PGE2 production [J]. Kidney Int, 2013, 83(6):1087-1098.
[11]
KOMADA T, USUI F, KAWASHIMA A, et al. Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury [J]. Sci Rep, 2015, 5:10901. Doi: 10.1038/srep10901.
[12]
MARTINEZ-GARCIA J J, MARTINEZ-BANACLOCHA H, ANOGOSTO-BAZARRA D, et al. P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis [J]. Nat Commun, 2019, 10(1):2711. Doi: 10.1038/s41467-019-10626-x.
[13]
WANG W, HU D, FENG Y, et al. Paxillin mediates ATP-induced activation of P2X7 receptor and NLRP3 inflammasome [J]. BMC Biol, 2020, 18(1):182. Doi: 10.1186/s12915-020-00918-w.
[14]
WEISS U, YOSHIHIRA K, HIGHET R J, et al. The chemistry of the antibiotics chrysomycin A and B. Antitumor activity of chrysomycin A [J]. J Antibiot (Tokyo), 1982, 35(9):1194-1201.
[15]
WU F, ZHANG J, SONG F, et al. Chrysomycin A derivatives for the treatment of multi-drug-resistant tuberculosis [J]. ACS Cent Sci, 2020, 6(6):928-938.
[16]
LIU M, ZHANG S S, LIU D N, et al. Chrysomycin A attenuates neuroinflammation by down-regulating NLRP3/Cleaved Caspase-1 signaling pathway in LPS-Stimulated mice and BV2 cells [J]. Int J Mol Sci, 2021, 22(13):6799. Doi: 10.3390/ijms22136799.
[17]
CHENG X, YANG Y L, LI W H, et al. Effect and possible mechanism of kaempferol on acute kidney injury on LPS-stimulated mice [J]. Chin Pharm J(中国药学杂志), 2020, 55(17):1439-1443.
[18]
CHENG X, YANG Y L, LI W H, et al. Esculin alleviates acute kidney injury and inflammation induced by LPS in mice and its possible mechanism [J]. J Chin Pharm Sci(中国药学 英文版), 2020, 29(5):322-332.
[19]
BASILE D P, ANDERSON M D, SUTTON T A. Pathophysiology of acute kidney injury [J]. Compr Physiol, 2012, 2(2):1303-1353.
[20]
NIU X, YAO Q, LI W, et al. Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-κB/NLRP3 inflammasome signalling pathway in mice [J]. Eur J Pharmacol, 2019, 849:160-169.
[21]
GORIN Y. The kidney: an organ in the front line of oxidative stress-associated pathologies [J]. Antioxid Redox Signal, 2016, 25(12):639-641.
[22]
LAWRENCE T. The nuclear factor NF-kappaB pathway in inflammation[J]. Cold Spring Harb Perspect Biol,2009, 1(6):a001651. Doi: 10.1101/cshperspect.a001651.
[23]
YOO J Y, CHA D R, KIM B, et al. LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1 [J]. Cell Rep, 2020, 33(3):108245. Doi: 10.1016/j.celrep.2020.108245.
[24]
ZHANG H, CHEN M K, LI K, et al. Eupafolin nanoparticle improves acute renal injury induced by LPS through inhibiting ROS and inflammation [J]. Biomed Pharmacother, 2017, 85:704-711.
[25]
KHAJEVAND-KHAZAEI M R, MOHSENI-MOGHADDAM P, HOSSEINI M, et al. Rutin, a quercetin glycoside, alleviates acute endotoxemic kidney injury in C57BL/6 mice via suppression of inflammation and up-regulation of antioxidants and SIRT1 [J]. Eur J Pharmacol, 2018, 833:307-313.
[26]
AMIRSHAHROKHI K. Thalidomide reduces glycerol-induced acute kidney injury by inhibition of NF-κB, NLRP3 inflammasome, COX-2 and inflammatory cytokines [J]. Cytokine, 2021, 144:155574. Doi: 10.1016/j.cyto.2021.155574.
[27]
SCHRODER K, TSCHOPP J. The inflammasomes [J]. Cell, 2010, 140(6):821-832.
[28]
ANDERS H J, MURUVE D A. The inflammasomes in kidney disease [J]. J Am Soc Nephrol, 2011, 22(6):1007-1018.
[29]
KOMADA T, USUI F, KAWASHIMA A, et al. Role of NLRP3 inflammasomes for rhabdomyolysis-induced acute kidney injury [J]. Sci Rep, 2015, 5:10901. Doi: 10.1038/srep10901.
[30]
LAU A, CHUNG H, KOMADA T, et al. Renal immune surveillance and dipeptidase-1 contribute to contrast-induced acute kidney injury [J]. J Clin Invest, 2018, 128(7):2894-2913.
[31]
CAO J Y, ZHOU L T, LI Z L, et al. Dopamine D1 receptor agonist A68930 attenuates acute kidney injury by inhibiting NLRP3 inflammasome activation [J]. J Pharmacol Sci, 2020, 143(3):226-233.
[32]
ZHU X, LI S, LIN Q, et al. αKlotho protein has therapeutic activity in contrast-induced acute kidney injury by limiting NLRP3 inflammasome-mediated pyroptosis and promoting autophagy [J]. Pharmacol Res, 2021, 167:105531. Doi: 10.1016/j.phrs.2021.105531.
[33]
MARIATHASAN S, WEISS D S, NEWTON K, et al. Cryopyrin activates the inflammasome in response to toxins and ATP [J]. Nature, 2006, 440(7081):228-232.
[34]
MENZIES R I, HOWARTH A R, UNWIN R J, et al. Inhibition of the purinergic P2X7 receptor improves renal perfusion in angiotensin-II-infused rats [J]. Kidney Int, 2015, 88(5):1079-1087.
[35]
NASCIMENTO M, PUNARO G R, SERRALHA R S, et al. Inhibition of the P2X7 receptor improves renal function via renin-angiotensin system and nitric oxide on diabetic nephropathy in rats [J]. Life Sci, 2020, 251:117640. Doi: 10.1016/j.lfs.2020.117640.
2022, Vol. 57 
