Protective effects of Stephania pierrei tuber-derived oxocrebanine against LPS-induced acute lung injury in mice.

Wanatsanan Chulrik, Chutima Jansakun, Waraluck Chaichompoo, Nassareen Supaweera, Aman Tedasen, Chuchard Punsawad, Rungruedi Kimseng, Kanok-On Rayanil, Apichart Suksamrarn, Warangkana Chunglok
Author Information
  1. Wanatsanan Chulrik: Health Sciences (International Program), College of Graduate Studies, Walailak University, Nakhon Si Thammarat, 80160, Thailand. ORCID
  2. Chutima Jansakun: School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, 80160, Thailand. ORCID
  3. Waraluck Chaichompoo: Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand. ORCID
  4. Nassareen Supaweera: Health Sciences (International Program), College of Graduate Studies, Walailak University, Nakhon Si Thammarat, 80160, Thailand. ORCID
  5. Aman Tedasen: School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, 80160, Thailand. ORCID
  6. Chuchard Punsawad: School of Medicine, Walailak University, Nakhon Si Thammarat, 80160, Thailand. ORCID
  7. Rungruedi Kimseng: Research and Innovation Institute of Excellence, Walailak University, Nakhon Si Thammarat, 80160, Thailand. ORCID
  8. Kanok-On Rayanil: Department of Chemistry, Faculty of Science, Silpakorn University, Nakorn Pathom, 73000, Thailand. ORCID
  9. Apichart Suksamrarn: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, 10240, Thailand. ORCID
  10. Warangkana Chunglok: School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, 80160, Thailand. cwarang@wu.ac.th. ORCID

Abstract

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) have high mortality rates. Though corticosteroids are commonly used for the treatment of these conditions, their efficacy has not been conclusively demonstrated and their use can induce various adverse reactions. Hence, the application of corticosteroids as therapeutic modalities for ALI/ARDS is limited. Meanwhile, the aporphine alkaloid oxocrebanine isolated from Stephania pierrei tubers has demonstrated anti-inflammatory efficacy in murine/human macrophage cell lines stimulated by lipopolysaccharide (LPS). Accordingly, the primary objectives of the present study are to investigate the anti-inflammatory effects of oxocrebanine on LPS-induced murine alveolar epithelial (MLE-12) cells and its efficacy against LPS-induced murine ALI. Results show that oxocrebanine downregulates the abundance of interleukin (IL)-1beta, IL-6, and inducible nitric oxide synthase, as well as the phosphorylation of nuclear factor-kappaB (NF-κB), stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), p38, protein kinase B (Akt), and glycogen synthase kinase-3beta signalling proteins in LPS-induced MLE-12 cells. Moreover, in a murine ALI model, oxocrebanine lowers lung injury scores and lung wet/dry weight ratios while reducing inflammatory cell infiltration. It also suppresses LPS-induced tumour necrosis factor-alpha and IL-6 in the bronchoalveolar lavage fluid and plasma. Moreover, oxocrebanine downregulates NF-κB, SAPK/JNK, p38, and Akt phosphorylation in the lung tissues of LPS-treated mice. Taken together, the foregoing results show that oxocrebanine provides significant protection against LPS-induced ALI in mice primarily by suppressing various inflammatory signalling pathways in alveolar epithelial cells and lung tissues. Hence, oxocrebanine might prove effective as an anti-inflammatory agent for the treatment of lung inflammation.

Keywords

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Grants

  1. WUBG-018/2565/The Royal Patronage of Her Royal Highness Princess Maha Chakri Sirindhorn
  2. CGS-RF-2021/05/The Walailak University Graduate Research Fund
  3. 04/2020/The Walailak University Ph.D. Excellence Scholarship

MeSH Term

Humans
Mice
Animals
NF-kappa B
Proto-Oncogene Proteins c-akt
Lipopolysaccharides
Interleukin-6
Stephania
Acute Lung Injury
Lung
Aporphines
Anti-Inflammatory Agents
Respiratory Distress Syndrome

Chemicals

NF-kappa B
Proto-Oncogene Proteins c-akt
Lipopolysaccharides
oxocrebanine
Interleukin-6
Aporphines
Anti-Inflammatory Agents

Word Cloud

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