Pachymic acid inhibits inflammation and cell apoptosis in lipopolysaccharide (LPS)-induced rat model with pneumonia by regulating NF-κB and MAPK pathways

Main Article Content

Yanjun Gui
Lijuan Sun
Rui Liu
Jinzhu Luo

Keywords

apoptosis, inflammation, MAPK, NF-κB, pachymic acid (PA), pneumonia

Abstract

Pneumonia is a common infectious disease with high morbidity and mortality. It is caused by a variety of pathogenic microorganisms that infect the lung parenchyma. Anti-infective drugs are one of the preferred choices for the treatment of pneumonia. Pachymic acid (PA) is a lanolin triterpene compound from Poria cocos, which has antiemetic, anti-inflammatory, and anticancer properties. Although PA inhibits inflammatory response in a variety of diseases, its role in pneumonia is not clear. In this study, we established that PA improved histopathological changes in the lungs of rats with pneumonia. PA inhibited the expression of inflammatory cytokines in the serum of rats having pneumonia. In addition, PA inhibited the apoptosis of cells from rat lung tissues. Mechanically, PA inhibited inflammation and cell apoptosis via NF-κB and MAPK pathways. Therefore, PA could serve as a promising drug for treating pneumonia.

Abstract 172 | PDF Downloads 76 XML Downloads 17 HTML Downloads 8

References

1. Hur I, Ozkan S, Halici A, Abatay K, Usul E, Cetin E, et al. Role of plasma presepsin, procalcitonin and C-reactive protein levels in determining the severity and mortality of community-acquired pneumonia in the emergency department. Signa Vitae. 2020;1:8. https://doi.org/10.22514/sv.2020.16.0034
2. Schnickel GT, Greenstein S, Berumen JA, Elias N, Sudan DL, Conzen KD, et al. Understanding the impact of pneumonia and other complications in elderly liver transplant recipients: An analysis of NSQIP transplant. Transplant Direct. 2021;7(5):e692. https://doi.org/10.1097/TXD.0000000000001151
3. Kiboshi T, Kotani T, Konma J, Makino H, Matsuda S, Suzuka T, et al. Comparison of therapeutic effects of combination therapy with prednisolone and tacrolimus or azathioprine on progressive interstitial pneumonia with systemic sclerosis. Modern Rheumatol. 2021:1–17. https://doi.org/10.1080/14397595.2021.1918864
4. Guo JG, Kong Q, Liu C, Kang TS, Qin C. Evaluating the Health Risks of pneumonia from airborne bacterial communities using 16S rDNA sequences of pneumonia-related pathogens. Biomed Environ Sci (BES). 2021;34(4):265–71. https://doi.org/10.3967/bes2021.035
5. Gao HM, Ambroggio L, Shah SS, Ruddy RM, Florin TA. Predictive value of clinician “Gestalt” in pediatric community-acquired pneumonia. Pediatrics. 2021; 147(5) e2020041582. https://doi.org/10.1542/peds.2020-041582
6. Cai H, Cheng Y, Zhu Q, Kong D, Chen X, Tamai I, et al. Identification of triterpene acids in poria cocos extract as bile acid uptake transporter inhibitors. Drug metabolism and disposition. 2021;49(5):353–60. https://doi.org/10.1124/dmd.120.000308
7. Akihisa T, Uchiyama E, Kikuchi T, Tokuda H, Suzuki T, Kimura Y. Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos. J Natural Prod. 2009;72(10):1786–92. https://doi.org/10.1021/np9003239
8. Akihisa T, Mizushina Y, Ukiya M, Oshikubo M, Kondo S, Kimura Y, et al. Dehydrotrametenonic acid and dehydroeburiconic acid from Poria cocos and their inhibitory effects on eukaryotic DNA polymerase alpha and beta. Biosci, Biotechnol Biochem. 2004;68(2):448–50. https://doi.org/10.1271/bbb.68.448
9. Yasukawa K, Kaminaga T, Kitanaka S, Tai T, Nunoura Y, Natori S, et al. 3 beta-p-hydroxybenzoyldehydrotumulosic acid from Poria cocos, and its anti-inflammatory effect. Phytochemistry. 1998;48(8):1357–60. https://doi.org/10.1016/S0031-9422(97)01063-7
10. Xu H, Wang Y, Jurutka PW, Wu S, Chen Y, Cao C, et al. 16Alpha-hydroxytrametenolic acid from poria cocos improves intestinal barrier function through the glucocorticoid receptor-mediated PI3K/Akt/NF-kappa B pathway. J Agr Food Chem. 2019;67(39):10871–9. https://doi.org/10.1021/acs.jafc.9b04613
11. Gapter L, Wang Z, Glinski J, Ng KY. Induction of apoptosis in prostate cancer cells by pachymic acid from Poria cocos. Biochem Biophy Res Comm. 2005;332(4):1153–61. https://doi.org/10.1016/j.bbrc.2005.05.044
12. Yang J, Deng F, Pan N. [Butein promotes the role of mH2A in MAPK signaling pathway through targeting GRP78 in regulating biological behaviors of melanoma]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. (J Central South Univ Med Sci. 2017;42(10):1129–35. https://doi.org/10.11817/j.issn.1672-7347.2017.10.001
13. Wang Z, Ka SO, Lee Y, Park BH, Bae EJ. Butein induction of HO-1 by p38 MAPK/Nrf2 pathway in adipocytes attenuates high-fat diet induced adipose hypertrophy in mice. Eur J Pharmacol. 2017;799:201–10. https://doi.org/10.1016/j.ejphar.2017.02.021
14. Swiderek E, Kalas W, Wysokinska E, Pawlak A, Rak J, Strzadala L. The interplay between epigenetic silencing, oncogenic KRas and HIF-1 regulatory pathways in control of BNIP3 expression in human colorectal cancer cells. Biochem Biophy Res Comm. 2013;441(4):707–12. https://doi.org/10.1016/j.bbrc.2013.10.098
15. El Gharib K, Masri K, Daoud Z, Sfeir T. Community-acquired Acinetobacter calcoaceticus pneumonia in a patient with a gammaglobulinaemia. New Microbes New Infect. 2021;41:100870. https://doi.org/10.1016/j.nmni.2021.100870
16. Sultana M, Alam NH, Ali N, Faruque ASG, Fuchs GJ, Gyr N, et al. Household economic burden of childhood severe pneumonia in Bangladesh: A cost-of-illness study. Arch Dis Child. 2021; 320834. https://doi.org/10.1136/archdischild-2020-320834
17. Raftery NB, Murphy CF, Donohoe CL, O’Connell B, King S, Ravi N, et al. The complexity of defining postoperative pneumonia following esophageal cancer surgery: A spectrum of lung injury rather than a simple infective complication? Ann Surg. 2021. https://doi.org/10.1097/SLA.0000000000004873
18. Nair R, Gao Y, Vaughan-Sarrazin MS, Perencevich E, Girotra S, Pandey A. Risk-standardized home time as a novel hospital performance metric for pneumonia hospitalization among medicare beneficiaries: A retrospective cohort study. J Gen Intern Med. 2021. https://doi.org/10.1007/s11606-021-06712-w
19. Song Z, Bi K, Luo X, Chan K. The isolation, identification and determination of dehydrotumulosic acid in Poria cocos. Anal Sci Int J Jap Soc Anal Chem. 2002;18(5):529–31. https://doi.org/10.2116/analsci.18.529
20. Wang SC, Dowhan DH, Eriksson NA, Muscat GE. CARM1/PRMT4 is necessary for the glycogen gene expression programme in skeletal muscle cells. Biochem J. 2012;444(2):323–31. https://doi.org/10.1042/BJ20112033
21. Jiang T, Xia Y, Lv J, Li B, Li Y, Wang S, et al. A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling. Mol Cancer. 2021;20(1):66. https://doi.org/10.1186/s12943-021-01358-y
22. Zhang BF, Jiang H, Chen J, Guo X, Hu Q, Yang S. KDM3A inhibition attenuates high concentration insulin induced vascular smooth muscle cell injury by suppressing MAPK/NFkappaB pathways. Int J Mol Med. 2018;41(3):1265–74. https://doi.org/10.3892/ijmm.2017.3351
23. Xia L, Xiao X, Liu WL, Song Y, Liu TJJ, Li YJ, et al. Coactosin-like protein CLP/Cotl1 suppresses breast cancer growth through activation of IL-24/PERP and inhibition of non-canonical TGFbeta signaling. Oncogene. 2018;37(3):323–31. https://doi.org/10.1038/onc.2017.342
24. Szuster-Ciesielska A, Mizerska-Dudka M, Daniluk J, Kandefer-Szerszen M. Butein inhibits ethanol-induced activation of liver stellate cells through TGF-beta, NFkappaB, p38, and JNK signaling pathways and inhibition of oxidative stress. J Gastroenterol. 2013;48(2):222–37. https://doi.org/10.1007/s00535-012-0619-7
25. Hu QP, Huang XY, Peng F, Yang H, Wu C. MS275 reduces seizure-induced brain damage in developing rats by regulating p38 MAPK signaling pathways and epigenetic modification. Brain Res. 2020;1745:146932. https://doi.org/10.1016/j.brainres.2020.146932