title: Anti-Inflammation Effects and Potential Mechanism of Saikosaponins by Regulating Nicotinate and Nicotinamide Metabolism and Arachidonic Acid Metabolism.
abstract: Inflammation is an important immune response; however, excessive inflammation causes severe tissue damages and secondary inflammatory injuries. The long-term and ongoing uses of routinely used drugs such as non-steroidal anti-inflammatory drugs (NSAIDS) are associated with serious adverse reactions, and not all patients have a well response to them. Consequently, therapeutic products with more safer and less adverse reaction are constantly being sought. Radix Bupleuri, a well-known traditional Chinese medicine (TCM), has been reported to have anti-inflammatory effects. However, saikosaponins (SS) as the main pharmacodynamic active ingredient, their pharmacological effects and action mechanism in anti-inflammation have not been reported frequently. This study aimed to explore the anti-inflammatory activity of SS and clarify the potential mechanism in acute inflammatory mice induced by subcutaneous injection of formalin in hind paws. Paw edema was detected as an index to evaluate the anti-inflammatory efficacy of SS. Then, a metabolomic method was used to investigate the changed metabolites and potential mechanism of SS. Metabolite profiling was performed by high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). The detection and identification of the changed metabolites were systematically analyzed by multivariate data and pathway analysis. As a result, 12 different potential biomarkers associated with SS in anti-inflammation were identified, including nicotinate, niacinamide, arachidonic acid (AA), and 20-carboxy-leukotriene B4, which are associated with nicotinate and nicotinamide metabolism and arachidonic acid metabolism. The expression levels of biomarkers were effectively modulated towards the normal range by SS. It indicated that SS show their effective anti-inflammatory effects through regulating nicotinate and nicotinamide metabolism and arachidonic acid metabolism.
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, No.18 of DD5 Street, Dalian, Liaoning Province, 116600, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, No.18 of DD5 Street, Dalian, Liaoning Province, 116600, China.|Component Medicine Engineering Research Center of Liaoning Province, Dalian, 116600, China.|Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, 116600, China.
authors.forename: Yongrui
authors.initials: Y
authors.lastname: Bao
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, No.18 of DD5 Street, Dalian, Liaoning Province, 116600, China.|Component Medicine Engineering Research Center of Liaoning Province, Dalian, 116600, China.|Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, 116600, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, No.18 of DD5 Street, Dalian, Liaoning Province, 116600, China.|Component Medicine Engineering Research Center of Liaoning Province, Dalian, 116600, China.|Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, 116600, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Li
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, No.18 of DD5 Street, Dalian, Liaoning Province, 116600, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chang
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, No.18 of DD5 Street, Dalian, Liaoning Province, 116600, China.
authors.forename: Guanlin
authors.initials: G
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, No.18 of DD5 Street, Dalian, Liaoning Province, 116600, China. mxsvvv@163.com.|Component Medicine Engineering Research Center of Liaoning Province, Dalian, 116600, China. mxsvvv@163.com.|Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, 116600, China. mxsvvv@163.com.
authors.forename: Xiansheng
authors.initials: X
authors.lastname: Meng
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D015415:Biomarkers; D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D008660:Metabolism / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D009525:Niacin / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism; D009828:Oleanolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D012503:Saponins / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D012503:Saponins; D009536:Niacinamide; D009525:Niacin; D016718:Arachidonic Acid; D009828:Oleanolic Acid; C025759:saikosaponin D
keywords: arachidonic acid metabolism; effects; inflammation; mechanism; nicotinate and nicotinamide metabolism; saikosaponin