Shenling Baizhu powder (参苓白术散) reduced the oxidative stress and mitochondrial damage during ulcerative colitis via the Kelch-like ECH-associated protein 1-NF-E2-related factor 2/nuclear factor kappa B pathway

doi:10.19852/j.cnki.jtcm.20260304.002

Abstract

Abstract:

OBJECTIVE: To explore the effects and relative mechanisms of Shenling Baizhu powder (参苓白术散, SBP) on ulcerative colitis (UC).

METHODS: This study investigates the potential of SBP, a traditional Chinese herbal formula, in attenuating inflammation and oxidative stress in UC. Applying both in vivo(rat) and in vitro (human colonic epithelial cells) models, we explored the anti-inflammation and oxidative stress effect of SBP, focusing on the Kelch-like ECH-associated protein 1-NF-E2-related factor 2/nuclear factor kappa B (KEAP1-NRF2/NF-κB) pathway and mitochondrial homeostasis.

RESULTS: Results demonstrated that SBP administration significantly improved the health status of rats, with less intestinal injury, and reduced inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) and oxidative stress (myeloperoxidase, malondialdehyde, and reactive oxygen species) both in vivo and in vitro. Moreover, SBP restored the inhibited KEAP1-NRF2/NF-κB signaling during inflammatory responses induced by dextran sulfate sodium or lipopolysaccharide, and decreased the expression level of the inflammatory molecule: NF-κB. Besides, SBP also helped to restore the mitochondrial dynamics, as evidenced by the recovery of mitochondrial membrane potential and mitofusin-2 levels.

CONCLUSION: These findings suggest that SBP may offer a promising alternative therapy for managing UC, providing anti-inflammatory and antioxidant benefits as key molecular mechanisms.

Key words: colitis, ulcerative, inflammation, oxidative stress, Kelch-like ECH-associated protein 1, NF-E2-related factor 2, NF-kappa B, Shenling Baizhu powder

ZHANG Quanhui, ZENG Jinlan, SU Liang, WANG Yi, DENG Yongwen, ZHANG Xiuchai. Shenling Baizhu powder (参苓白术散) reduced the oxidative stress and mitochondrial damage during ulcerative colitis via the Kelch-like ECH-associated protein 1-NF-E2-related factor 2/nuclear factor kappa B pathway[J]. Journal of Traditional Chinese Medicine, 2026, 46(3): 584-593.

Figures/Tables 2

Figure 1 SBP treatment improved the disease status associated with intestinal injury in rats A: DAI was recorded based on observations of weight; B: after sacrifice, intestinal and spleen tissues were collected and the length measured; B1: NC group; B2: model group; B3: MES treated group; B4: SBP low dose group; B5: SBP medium dose group; B6: SBP high dose group; B7: the colon length of rats; B8: the spleen index of rats; C: intestinal tissues were fixed in 10% formalin for FFPE sections and stained with HE; C1: NC group; C2: model group; C3: MES treated group; C4: SBP low dose group; C5: SBP medium dose group; C6: SBP high dose group; C7: quantification of the DAI; C8: quantification of the TDI. NC group: normal control; model group: 5% DSS treatment; MES-treated group: DSS + MES, 0.42 g/kg; SBP low dose group: DSS + SBP 0.54 g/kg; SBP medium dose group: DSS + SBP 1.08 g/kg; SBP high dose group: DSS + SBP 2.16 g/kg. SBP: Shenling Baizhu powder; DSS: dextran sulfate sodium; MES: mesalazine; DAI: disease activity index; FFPE: formalin-fixed paraffin-embedded; HE: hematoxylin and eosin; TDI: tissue damage index. All the significant difference was calculated by one-way analysis of variance with Tukey post hoc comparison. Data are presented as mean ± standard deviation (n = 5). Compared with the NC group, aP < 0.01; compared with the model group, bP < 0.001, cP < 0.05.

Figure 2 SBP inhibited the initial inflammatory response via the KEAP1-NRF2/NF-κB axis A: the mRNA levels of target genes in the intestinal tissues measured by qRT-PCR; A1: the mRNA levels of KEAP1; A2: the mRNA levels of NRF2; A3: the mRNA levels of NF-κB; A4: the mRNA levels of MFN2; B: the expression of target proteins were measured by Western blot; B1: the representative blots; B2: the expression levels of KEAP1; B3: the expression levels of NRF2; B4: the expression levels of NF-κB; B5: the expression levels of MFN2. β-actin was used as the endogenous control for normalization. NC group: normal control; model group: 5% DSS treatment; MES treated group: DSS + MES, 0.42 g/kg; SBP low dose group: DSS + SBP 0.54 g/kg; SBP medium dose group: DSS + SPB 1.08 g/kg; SBP high dose group: DSS + SPB 2.16 g/kg. SBP: Shenling Baizhu powder; KEAP1: Kelch-like ECH-associated protein 1; NRF2: NF-E2-related factor 2; NF-κB: nuclear factor kappa B; DSS: dextran sulfate sodium; qRT-PCR: quantitative reverse transcription-polymerase chain reaction; MFN2: mitofusin-2; MES: mesalazine. All the significant difference was calculated by one-way analysis of variance with Tukey post hoc comparison. Data are presented as mean ± standard deviation (n = 5). Compared with the NC group, aP < 0.01; compared with the model group, bP < 0.001, cP < 0.05.

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