Isosteviol Sodium Ameliorates Dextran Sodium Sulfate-Induced Chronic Colitis through the Regulation of Metabolic Profiling, Macrophage Polarization, and NF-κB Pathway

Abstract

Inflammatory bowel diseases (IBDs) constitute a group of chronic intestinal conditions prominently featuring deranged metabolism. Effective pharmacological treatments for IBDs are lacking. Isosteviol sodium (STV-Na) exhibits anti-inflammatory activity and may offer therapeutic benefits in chronic colitis. However, the associated mechanism remains unclear. This study is aimed at exploring the therapeutic effects of STV-Na against chronic colitis in terms of metabolic reprogramming and macrophage polarization. Results show that STV-Na attenuated weight loss and colonic pathological damage and restored the hematological and biochemical parameters in chronic colitis mice models. STV-Na also restored intestinal permeability by increasing the goblet cell numbers, which was accompanied by lowered plasma lipopolysaccharide and diamine oxidase levels. Metabolomic analysis highlighted 102 candidate biomarkers and 5 vital pathways that may be crucial in the potential pharmacological mechanism of STV-Na in regulating intestinal inflammation and oxidative stress. These pathways were glycerophospholipid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, the pentose phosphate pathway, and phosphonate and phosphinate metabolism. Furthermore, STV-Na significantly decreased M1 macrophage polarization in the spleen and colon. The mRNA and protein levels of IL-1β, TNF-α, and NF-κB/p65 in colonic tissue from the colitis mice were decreased after the STV-Na treatment. Overall, STV-Na could alleviate chronic colitis by suppressing oxidative stress and inflammation levels, reprogramming the metabolic profile, inhibiting macrophage polarization, and suppressing the NF-κB/p65 signaling pathway. STV-Na remains a promising candidate drug for treating IBDs.

STV‐Na attenuates lipopolysaccharide‐induced lung injury in mice via the TLR4/NF‐kB pathway

“…[16][17][18] Prior research have confirmed that STV-Na can reduce the activity of NF-κB/p65. 18 We therefore utilized a LPS-induced acute lung injury model and explored whether STV-Na has a potential therapeutic impact on lung injury and the intrinsic mechanisms associated with it. These documents demonstrate a potential basis for STV-Na treatment of ALI.…”

“…Despite this, there are not many studies on the potentiality of STV‐Na therapeutic effects for ALI 16–18 . Prior research have confirmed that STV‐Na can reduce the activity of NF‐ κB/p65 18 . We therefore utilized a LPS‐induced acute lung injury model and explored whether STV‐Na has a potential therapeutic impact on lung injury and the intrinsic mechanisms associated with it.…”

“…it was found that STV‐Na inhibited macrophage polarization to reduce inflammatory cytokine production and attenuated LPS‐induced multiorgan damage. Despite this, there are not many studies on the potentiality of STV‐Na therapeutic effects for ALI 16–18 . Prior research have confirmed that STV‐Na can reduce the activity of NF‐ κB/p65 18 .…”

Protective effect of Schistosoma japonicum eggs on TNBS-induced colitis is associated with regulating Treg/Th17 balance and reprogramming glycolipid metabolism in mice

“…Recently, increasing studies indicate that metabolic disorders modulate the pathogenesis of IBDs by regulating immune responses ( Aden et al., 2019 ; Lamb et al., 2022 ; Wang et al., 2022 ). Furthermore, glucose and lipid metabolism play important roles in T cells’ development and functions, even controlling the balance between Th17/Treg ( Qin et al., 2022 ).…”

Induction of cellulase production in Trichoderma reesei by a glucose–sophorose mixture as an inducer prepared using stevioside

“…25 The different conjugated forms of isosteviol show anticancer activities and can thus be used for the synthesis of inexpensive chemotherapeutic agents. 26,27 Moreover, research on isosteviol has revealed that it shows peculiar DNA polymerase, DNA topoisomerase inhibition and acetylcholine inhibition abilities and antidiarrheal and antibacterial activities. [28][29][30] Another hydrolysate, sophorose, has not been directly applied for cellulase production by T. reesei to the best of our knowledge.…”