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							| Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007



	

				
						
 
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																Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007
										

				


				
				
					
					
						
																					
				
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					Vol. 12 No. 2 (2022): February 2022
				
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									Research Articles
							
		



	
		  	 

		
	
		Hepatoprotective and anti-inflammatory profile of sokeikakketsuto and makyoyokukanto in primary cultured rat hepatocytes
	


	
	
		

							
					Authors

						
							
								Tatsuma Sakaguchi
							
															
									Kansai Medical University, Department of Surgery
																	
																																		
	
							
								Tetsuya Okuyama
							
															
									Kansai Medical University, Department of Surgery
																	
																																		
	
							
								Masaya Kotsuka
							
															
									Kansai Medical University, Department of Surgery
																	
																																		
	
							
								Terufumi Yoshida
							
															
									Kansai Medical University, Department of Surgery
																	
																																		
	
							
								Tadayoshi Okumura
							
															
									Kansai Medical University, Department of Surgery, Research Organization of Science and Technology, Ritsumeikan University
																	
																																		
	
							
								Mikio Nishizawa
							
															
									Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu, Japan
																	
																																		
	
							
								Masaki Kaibori
							
															
									Kansai Medical University, Department of Surgery
																	
																																		
	
							
								Mitsugu Sekimoto
							
															
									Kansai Medical University, Department of Surgery
																	
																																		


				
			
																	
					
												DOI:
					

					
						
							https://doi.org/10.31989/ffhd.v12i2.887
						
					
				
			

						
										
					Abstract

					Background: Sokeikakketsuto (SOK) is a Kampo medicine that can mitigate several types of pain, including arthralgia, neuralgia, low back pain, and myalgia, which may be introduced for the treatment of neuropathic pain in anti-cancer therapy. Considering that several Kampo medicines are known to have hepatoprotective and anti-inflammatory effects, we investigated the pharmacological mechanism of SOK in hepatocytes. Additionally, we examined another Kampo medicine, makyoyokukanto (MAK), as a reference as it has been reported to have similar efficacy for neuropathic pain.
Methods: SOK or MAK was incubated with rat primary cultured hepatocytes treated with interleukin (IL)-1β. The induction of inducible nitric oxide synthase (iNOS), nitric oxide (NO) production, iNOS signaling pathways, and the expression of other inflammatory mediators was investigated.
Results: IL-1β activated iNOS induction, followed by NO production. SOK and MAK reduced the expression of iNOS mRNA and its protein and decreased NO production. SOK and MAK also decreased the levels of tumor necrosis factor (TNF)-α and increased the levels of IL-6 and IL-1β. Transfection experiments with iNOS promoter-luciferase constructs revealed that MAK reduced iNOS mRNA synthesis and stability; however, SOK only reduced mRNA synthesis. Both medicines suppressed the activation of nuclear factor (NF)-κB but did not block the upregulation of type I IL-1 receptor in two essential signaling pathways.
Conclusions: SOK and MAK could prevent NO production by inhibiting iNOS gene expression, partly through NF-κB activation, in inflamed hepatocytes. However, both medicines may have different mechanisms of action in the treatment of injured organs.

Keywords: Kampo medicine, sokeikakketsuto, makyoyokukanto, inducible nitric oxide synthase, cultured hepatocytes

				
			
			

						
																																																																				
						
		


		

										
					
																				
											

				

			
										
					
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																			2022-02-15
																	

				
							

			
						
										

											
							
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									Vol. 12 No. 2 (2022): February 2022
								
							

						
					
											
							
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								Research Articles
							

						
					
									

			
						
										
					
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