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.

Holistic and dynamic metabolic alterations of traditional Chinese medicine syndrome in a toxic heat and blood stasis syndrome rat model

“…25 In this study, the inhibition of nicotinate and nicotinamide metabolism in model rats at 2 h, 8 h and 24 h may lead to the inhibition of SIRT1, resulting in the activation of NF-kB and the elevation of inammatory cytokines as an inammatory response. Besides, the extent of inhibition of nicotinate and nicotinamide metabolism was reduced at 24 h, suggesting that the inammatory response decreased, which was consistent with the decreasing levels of IL-6, TNFa and IL-1b over time.…”

“…Then 6 mL blood obtained with the heart puncture technique was collected into one 2 mL sodium citrate vacuum blood collection tube (SCVBCT) and two 2 mL EDTA vacuum blood collection tubes (EVBCTs). The blood sample in one of the EVBCTs stood at room temperature (22)(23)(24)(25) C) for 30 min. The blood samples in the SCVBCT and the other EVBCT were centrifuged at 3000 rpm for 10 min to get the plasma and stored at À80 C until the biochemical analysis.…”

“…Prior to UPLC-MS analysis, the urine samples were thawed at room temperature (22)(23)(24)(25) C), diluted at a ratio of 2 : 1 (v/v) using ultra high purity water, vortex mixed and centrifuged at 14 000 rpm for 10 min at 4 C.…”

Radix Bupleuri: A Review of Traditional Uses, Botany, Phytochemistry, Pharmacology, and Toxicology

“…Chun et al reported that saikosaponins from Radix Bupleuri exhibited anti-inflammatory activity on inflammatory processes including inhibition of inflammatory exudation, capillary permeability, inflammatory mediators release, migration of white cells, connective tissue hyperplasia, and a variety of allergic inflammation [67]. Ma et al was the first to show that saikosaponins exerted anti-inflammatory activity on paw edema mainly via regulating the nicotinate and nicotinamide metabolism and arachidonic acid metabolism [5]. Zhu et al found that saikosaponin a (SSa) exhibited an inhibitory effect on proinflammatory cytokines in LPS-stimulated macrophages.…”

“…According to ancient Chinese medical literatures, Radix Bupleuri is capable of regulating the exterior and interior metabolisms, dispersing evil heat from the superficies, soothing the liver, and promoting yang and qi (representing "life energy" or "life force" in TCM theories). In recent decades, investigations of Radix Bupleuri have focused on its biological activities, including its anti-inflammatory [4,5], anticancer [6,7], antipyretic [8], antimicrobial [9], antiviral [10], hepatoprotective [11], and immunomodulatory effects [12]. In addition, Radix Bupleuri also exhibited significant effects on membrane fluidity [13].…”