The aqueous extracts of Ageratum conyzoides inhibit inflammation by suppressing NLRP3 inflammasome activation

Inflammasomes are cytosolic multiprotein complexes characterized by sensor proteins such as AIM2, IFI16, and various NOD-like receptor (NLR) subsets (Paerewijck and Lamkanfi, 2022). Upon activation, the sensor proteins oligomerize and then recruit the adaptor proteins ASC and caspase-1 to form inflammasomes, thereby cleaving pro-IL-1β and pro-IL-18 into their active forms, which are essential mediators of inflammation (Paerewijck and Lamkanfi, 2022). Of these inflammasomes, the NLRP3 inflammasome is the most extensively studied. Unlike other inflammasomes, NLRP3 can be sensed by various stimuli, including damage-associated molecular patterns and pathogen-associated molecular patterns (Huang et al., 2021). This system has developed to offer significant and advantageous defence against invasive infections and tissue injury, but it can also be harmful when activated inadvertently. In addition, NLRP3 is expressed in a variety of cell types, including lymphocytes, neutrophils, and monocytes, all of which are known to drive inflammation (Huang et al., 2021). Hence, inappropriately activated NLRP3 inflammasomes can lead to many highly diverse inflammatory diseases, including asthma, enteritis, hepatitis, rheumatoid arthritis, sepsis, Alzheimer's disease, and Parkinson's disease (Li et al., 2021). Therefore, as a key player in the body's immune response and inflammatory diseases, the NLRP3 inflammasome may provide a new target for the treatment of various inflammatory diseases (Leung and Lowery, 2020).

Traditional Chinese medicine (TCM) has long utilized medicinal herbs and their extracts because they have potential pharmacological effects on a variety of diseases, particularly metabolic and chronic inflammatory diseases (Bahtiar et al., 2017). Compared with the single-component and single-target mode of action of chemical drugs, TCM has the characteristics of a multi-component and multi-target mode of action, and the mode of action is more complex, so it shows significant advantages in the treatment of many complex diseases (Wang et al., 2022b). In addition, TCM resources are abundant, easy to grow, harvest, and use, and their side effects are relatively small (Yuan et al., 2022). However, their potential clinical utility is limited by the lack of identification of the active components and their corresponding mechanisms. Ageratum conyzoides L. (Asteraceae) is a traditional tropical medicinal herb that is widely distributed in tropical and subtropical regions of the world (Yadav et al., 2019). In southern China, this traditional medicine has been used to treat various inflammatory diseases, including fever, sore throat, sore eczema, traumatic bleeding, burns, itching, rheumatism, toothache, and conjunctivitis (Lin et al., 2020). In Africa, it has been widely used in the treatment of Crohn's disease, trauma, burns, pneumonia, asthma, dysentery, and other diseases (Ojewale et al., 2020). Pharmacological studies of this medicinal herb have shown it to have analgesic, antiarthritis, anticonvulsant, antispasmodic, and anti-inflammatory properties, as well as antibacterial, antiviral, anticancer, and antioxidant activities (Vigil de Mello et al., 2016). Previous phytochemical analyses of A. conyzoides identified a variety of types of compounds, including coumarins, flavonoids, sterols, chromenes, and pyrrolizidine alkaloids (Yadav et al., 2019). However, little is known about the anti-inflammatory mechanism that results from blocking NLRP3 inflammasome activation. Hence, this work aimed to shed light on the underlying mechanisms of an aqueous extract of A. conyzoides leaf (EAC) in mediating NLRP3 inflammasome activity.

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