Extracts ofHylotelephiumerythrostictum (miq.) H. Ohba ameliorate intestinal injury by scavenging ROS and inhibiting multiple signaling pathways in Drosophila

Neutralizing ROS: A Shield Against Cellular Damage

• Survival Boost: Flies treated with HEWE (8 mg/ml) or HEBE (1 mg/ml) saw survival rates jump by 55% after DSS exposure. Even with SDS (another irritant), survival improved by 35–51% .
• Reduced Cell Death: 7-AAD staining showed HEWE/HEBE cut intestinal cell death by 76%, preserving the gut barrier .

Table 1: Survival Rates with H. erythrostictum Extracts

Treatment	DSS Survival Increase	SDS Survival Increase
HEWE (8 mg/ml)	55.8%	51.6%
HEBE (1 mg/ml)	54.2%	35.5%

Blocking Pro-Inflammatory Pathways

• JNK Pathway Suppression: HEWE/HEBE reduced p-JNK fluorescence by 76%, preventing stress signals from triggering ISC overgrowth .
• EGFR and JAK-STAT Inhibition: Both extracts lowered Vein-lacZ (EGFR marker) activity and STAT-responsive genes, curbing unnecessary cell division .

Table 2: Pathway Inhibition by HEWE/HEBE

Pathway	Key Effect	Impact on ISCs
JNK	Reduced p-JNK signaling	25–51% fewer dividing cells
EGFR	Lower Vein-lacZ expression	1.5x fewer progenitors
JAK-STAT	Blocked cytokine overproduction	Restored stem cell homeostasis

Restoring Gut Microbiota Balance

16S rDNA sequencing revealed HEWE/HEBE reversed DSS-induced shifts in gut bacteria:

• Proteobacteria (linked to inflammation) decreased.
• Firmicutes and Acidobacteriota (beneficial phyla) rebounded .

Table 3: Gut Microbiota Changes Post-Treatment

Phylum	DSS-Induced Change	HEWE/HEBE Effect
Proteobacteria	Increased	Normalized
Firmicutes	Decreased	Restored
Acidobacteriota	Disrupted	Balanced

The Bioactive Compounds Behind the Magic

Network pharmacology identified 19 active components in HEWE and 14 in HEBE linked to IBD targets. Key candidates include:

• Phenolic compounds (230 mg/g in HEAG extract): Scavenge ROS and reduce cytokines like TNF-α and IL-6 .
• Antibacterial agents: Found in ethyl acetate extracts, these combat pathogens like Ecc15 .

From Flies to Humans: What’s Next?

While Drosophila studies are promising, human trials are needed to:

Confirm safety and efficacy.

Isolate the most potent compounds.

Optimize delivery methods (e.g., supplements or targeted therapies).

Conclusion: A New Hope for IBD Patients

Hylotelephium erythrostictum extracts offer a multi-pronged defense against gut inflammation—scavenging ROS, rebalancing microbiota, and silencing harmful pathways. As research advances, this plant could become a cornerstone of natural IBD therapies, merging ancient wisdom with cutting-edge science.

References
Embedded as notations, citing evidence from provided sources.