Targeting inflammasome in digestive diseases: A dual approach of Western and Chinese medicine

Table 1 Traditional Chinese medicine syndrome-based classification, indications, and contraindications of herbal interventions for NOD-like receptor family pyrin domain-containing 3-mediated digestive diseases

TCM intervention	TCM syndrome type	Core therapeutic principle	Typical digestive indications	Clinical contraindications/cautions
Saikosaponin-d (from Bupleurum Chinense)	Liver depression and spleen deficiency	Soothing liver, harmonizing stomach, tonifying spleen	Chronic hepatitis, MASLD with qi stagnation	Avoid in yin deficiency with fire
Ursolic acid (from Crataegus/Ligustrum)	Damp-heat in the intestines	Clearing heat, resolving dampness, relieving toxicity	UC (active phase)	Caution in spleen deficiency with cold
Emodin (from Rheum palmatum)	Heat toxin and blood stasis	Purging heat, removing stasis, unblocking fu organs	AP, severe constipation	Contraindicated in pregnancy and spleen-stomach deficiency
Curcumin (from Curcuma longa)	Damp-heat jaundice	Clearing damp-heat, promoting gallbladder function, protecting liver	Viral hepatitis, cholestasis	Use with caution in blood deficiency
Buzhong Yiqi decoction	Spleen qi sinking	Tonifying middle-qi, lifting yang, replenishing qi	IBD in remission, chronic diarrhea with fatigue	Contraindicated in Damp-Heat syndrome (e.g., active UC with bloody diarrhea, fever, greasy tongue coating) – may “block the pathogen” and worsen inflammation
Shaoyao decoction	Damp-heat dysentery	Clearing heat, drying dampness, regulating qi and blood	Active UC, bacterial dysentery	Avoid in spleen deficiency with cold diarrhea
Qingyi decoction	Excessive heat in fu organs	Clearing heat, detoxifying, purging fu organs, reducing turbidity	AP (early stage)	Contraindicated in chronic deficiency patterns

AP: Acute pancreatitis; TCM: Traditional Chinese medicine; MASLD: Metabolic dysfunction-associated steatotic liver disease; IBD: Inflammatory bowel disease; UC: Ulcerative colitis.

Table 2 Summary of Western medicine and traditional Chinese medicine agents targeting the NOD-like receptor family pyrin domain-containing 3 inflammasome for digestive system diseases

Category	Name	Target pathway	Disease model	Key efficacy indicators	Ref.
Western medicine inhibitor	MCC950	NLRP3 ATPase/NEK7 interaction	MASLD, AP, UC	Reduced IL-1β, reduced IL-18, ameliorated hepatic steatosis, reduced pancreatic necrosis, improved colitis	Coll et al[89], Perera et al[90], Zheng et al[91]
Western medicine inhibitor	CY-09	NLRP3 ATPase (direct binding)	MASLD, gouty arthritis	Reduced caspase-1, reduced IL-1β, blocked NLRP3 oligomerization	Wang et al[1], Li et al[2]
Western medicine inhibitor	OLT1177	NLRP3 (allosteric inhibition)	MASH, AP	Reduced IL-1β, reduced IL-18, safe in humans (phase II)	Yao et al[3], Xu and Núñez[4]
Western medicine pathway modulator	Pyrrolidine dithiocarbamate	NF-κB	IBD, colitis	Downregulated NLRP3 expression, inhibited cytokine release	Blevins et al[95], Zhai et al[96], Bae and Park[97]
TCM single component	Saikosaponin-d (already present, but enriched mechanism)	NF-κB/NLRP3 ubiquitination	MASLD, liver fibrosis	Reduced NLRP3 inflammasome activation, reduced hepatic inflammation, increased NLRP3 degradation	Islamuddin and Qin[5], Fan et al[104], Lai et al[105], Lim et al[106]
TCM single component	Ursolic acid	ROS scavenging/TXNIP-NLRP3 axis	UC, colitis-associated cancer	Reduced ROS, reduced NLRP3 oligomerization, protected intestinal barrier	Liu et al[6], Swanson et al[7]
TCM single component	Emodin	Autophagy/NLRP3 assembly	AP, colitis	Increased autophagic flux, reduced caspase-1, reduced IL-1β, reduced pancreatic injury	Wang and Ma[8], Zhen and Zhang[9]
TCM single component	Curcumin	ROS/NF-κB/NLRP3	Viral hepatitis, MASLD	Reduced ROS, reduced NF-κB nuclear translocation, reduced NLRP3, reduced IL-1β	Wang et al[10], Man[11]
TCM classic formula	Buzhong Yiqi decoction	Gut microbiota/TLR4/NF-κB	UC, IBD	Improved intestinal barrier, reduced NLRP3, reduced IL-1β, restored tight junctions	Martinon et al[12], Agostini et al[13]
TCM classic formula	Shaoyao decoction	MKP1/NF-κB/NLRP3	DSS-induced colitis	Reduced NLRP3, reduced caspase-1, reduced IL-1β, reduced macrophage infiltration	Mariathasan et al[14], Schroder and Tschopp[15]
TCM classic formula	Qingyi decoction	NLRP3/caspase-1	AP	Reduced serum amylase/lipase, mitigated pancreatic injury	Jiang et al[122], Su et al[123], Fu et al[124]

NLRP3: NOD-like receptor family pyrin domain-containing 3; NF-κB: Nuclear factor kappa B; MKP1: Mitogen-activated protein kinase phosphatase 1; TXNIP: Thioredoxin-interacting proteins; TCM: Traditional Chinese medicine; MASLD: Metabolic dysfunction-associated steatotic liver disease; UC: Ulcerative colitis; AP: Acute pancreatitis; IL: Interleukin; MASH: Metabolic dysfunction-associated steatohepatitis; IBD: Inflammatory bowel disease; ROS: Reactive oxygen species; TLR4: Toll-like receptor 4.

Table 3 Mapping of traditional Chinese medicine interventions to specific molecular steps of NOD-like receptor family pyrin domain-containing 3 inflammasome activation

TCM intervention	Priming stage (NF-κB)	Activation stage (ROS/TXNIP/oligomerization)	Effector stage (caspase-1/IL-1β)	Negative regulation (autophagy/ubiquitination)
Saikosaponin-d	Reduced NF-κB translocation	Not directly reported	Reduced caspase-1, reduced IL-1β/IL-18	Increased K48-linked ubiquitination → proteasomal degradation
Ursolic acid	Not directly reported	Reduced ROS → disrupts TXNIP-NLRP3 binding → reduced oligomerization	Reduced caspase-1, reduced IL-1β	NR
Emodin	Not directly reported	Not directly reported	Reduced caspase-1, reduced IL-1β	Increased AMPK/mTOR-dependent autophagy → degradation of NLRP3 and ASC
Curcumin	Reduced NF-κB	Reduced ROS; directly binds NLRP3 NACHT domain → blocks ATPase	Reduced caspase-1, reduced IL-1β/IL-18	NR
Buzhong Yiqi decoction	Reduced TLR4/NF-κB (via microbiota)	Reduced ROS (indirect)	Reduced IL-1β, reduced IL-18	NR
Shaoyao decoction	Increased MKP1 → reduced p38/JNK → reduced NF-κB	Not directly reported	Reduced NLRP3 assembly, reduced caspase-1, reduced IL-1β	NR
Qingyi decoction	Not directly reported	Not directly reported	Reduced NLRP3/caspase-1 axis	NR

NLRP3: NOD-like receptor family pyrin domain-containing 3; ASC: Apoptosis-associated speck-like protein containing a CARD; NF-κB: Nuclear factor kappa B; MKP1: Mitogen-activated protein kinase phosphatase 1; TLR4: Toll-like receptor 4; TXNIP: Thioredoxin-interacting proteins; TCM: Traditional Chinese medicine; NR: Not report; IL: Interleukin; ROS: Reactive oxygen species.