Mechanism Assay of Honeysuckle for Heat-Clearing Based on Metabolites and Metabolomics

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as cyclooxygenase (Cox)-1/2 inhibitor, have emerged as potent antipyretics and analgesics. However, few herbs with Cox-1/2 inhibitory activity are commonly used for heat-clearing in China. Although these are known to have antipyretic activity, there is a lack of molecular data supporting their activity. Using the traditional Chinese medicine herb honeysuckle (Hon) as an example, we explored key antipyretic active compounds and their mechanisms of action by assessing their metabolites and metabolomics. Mitogen-activated protein kinase (MAPK) 3 and protein kinase B (AKT) 1 were suggested as key targets regulated primarily by chlorogenic acid (CA) and swertiamarin (SWE). CA and SWE synergistically inhibited the production of interleukin (IL)-1 and IL-6, alleviated generation of prostaglandin E2, and played an antipyretic role equivalent to honeysuckle extract at the same dose contents within 3 h. Collectively, these findings indicated that lipopolysaccharide-induced fever can be countered by CA with SWE synergistically, allowing the substitution of a crude extract of complex composition with active compounds. Our findings demonstrated that, unlike the traditional NSAIDs, the Hon extract showed a remote and indirect mechanism for alleviating fever that depended on the phosphatidylinositol-3-kinase–AKT and MAPK pathways by regulating the principal mediator of inflammation.

Network pharmacology integrated with experimental verification reveals the antipyretic characteristics and mechanism of Zi Xue powder

“… 2003 ; Blomqvist and Engblom 2018 ; Wang et al. 2022 ). Furthermore, we validated the predicted results of the network pharmacology by conducting an in vivo experiment, which showed that ZXP interfered with LPS-induced fever via inhibition of the MAPK signaling pathway.…”

Swertia L.: A comprehensive review of its genetic relationship, chemical compositions, pharmacological effects, toxicities, and applications

“…Additionally, treatment with an Sirtuin 1 (SIRT1) inhibitor (EX-527) partially abolished the inhibitory effect of gentiopicroside (40, 80 mg/kg) on ovalbumininduced airway inflammation, suggesting that the anti-inflammatory effect of gentiopicroside might be achieved by regulation of the SIRT1/NF-κB p65 signaling pathway (Zou et al, 2021). Wang, Quan, et al, 2022, Wang, Tian, et al, 2022 kg, ip) can increase the expression of SIRT1, and its protective effects on LPS-induced acute liver injury (ALI) can be reversed by the SIRT1 inhibitor EX-527 (Wang et al, 2021). Zhang et al demonstrated that the potent anti-inflammatory effect of sweroside (10 μg/mL for Rat chondrocytes) is mediated in part by suppression of the NF-κB and mammalian target of rapamycin (mTOR) C1 signaling pathways (Zhang, Gao, et al, 2019;Zhang, Wang, et al, 2019).…”

“…Additional studies are needed to elucidate the detailed molecular mechanism and its potential in treating gastritis (Chang et al, 2021). Additionally, their anticonvulsant agent (Vaijanathappa et al, 2020), lung protection (Wang et al, 2021; Yao et al, 2016), antinociception (Jaishree et al, 2009), and antipyretic activity (Wang, Quan, et al, 2022; Wang, Tian, et al, 2022) have also been demonstrated. In a conclusion, based on the diverse pharmacological activities of Swertia L., the incidental action and molecular mechanisms should be primarily ascertained and succedent further illuminated.…”

Chlorogenic acid: a review on its mechanisms of anti-inflammation, disease treatment, and related delivery systems

“…et al, 2017a ). Empirical research has underscored the efficacy of chlorogenic acid in ameliorating inflammatory ailments, attributing this to its multifaceted targeting of inflammatory pathways and its diminished propensity for drug resistance ( Wang et al, 2022a ; Fumiere et al, 2022 ; Feng et al, 2023 ). Specifically, chlorogenic acid can attenuate cardiac and cerebral afflictions triggered by inflammation and oxidative stress, conferring cardiovascular and cerebrovascular protective effects ( Wang et al, 2020a ; Liu et al, 2022 ; Zheng et al, 2022 ).…”