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Acupuncture enhances warm kidney and spleen granules efficacy in diabetic diarrhea through synergistic p300/CBP inhibition and Nrf2/HO-1 pathway activation.

Molecular immunology·May 2026·Zitong Wang, Xiaochuan Li, Yuanfei Tan et al.
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Key Finding

Combined acupuncture and Warm Kidney and Spleen Granules synergistically ameliorate diabetic diarrhea through p300/CBP inhibition, activating Nrf2/HO-1 antioxidant pathways while suppressing NF-κB-mediated inflammation more effectively than either monotherapy.

What This Means For You

Researchers investigated whether combining acupuncture with a traditional Chinese herbal formula could help diabetic patients suffering from chronic diarrhea, a condition affecting approximately 20% of people with diabetes. The study used diabetic rats that developed diarrhea after receiving a high-fat diet and chemical induction. Animals received either an herbal treatment called Warm Kidney and Spleen Granules (WKSG), acupuncture at seven specific points, or both therapies together over 35 days.

The results showed that WKSG worked by inhibiting proteins called p300 and CBP in intestinal tissue, which triggered a cascade of beneficial effects: reduced oxidative stress and inflammation, strengthened intestinal barrier function, and activated protective antioxidant pathways. When researchers combined acupuncture with the herbal formula, the therapeutic effects were significantly stronger than either treatment alone. The combination therapy better controlled blood sugar, reduced diarrhea frequency and stool moisture, improved intestinal permeability, and decreased cell death in the intestinal lining.

The study identified specific biological mechanisms explaining how these therapies work together. The herbal formula suppressed harmful inflammatory signals while activating the body's natural antioxidant defenses through the Nrf2/HO-1 pathway. Acupuncture amplified these effects synergistically. For diabetic patients struggling with chronic diarrhea—a condition with limited conventional treatment options—this research suggests that integrated acupuncture and herbal therapy may offer meaningful relief by addressing multiple underlying mechanisms simultaneously. If you're considering this approach for diabetic diarrhea, consult a licensed acupuncturist trained in traditional Chinese medicine who can create an individualized treatment protocol.

Clinical Notes for Practitioners

This study examined Warm Kidney and Spleen Granules (WKSG) combined with acupuncture for diabetic diarrhea in HFD/STZ-induced male Wistar rats. WKSG (1g/day, 14 days) and acupuncture (daily, 4 weeks at seven acupoints) were administered as monotherapies or combined over 35 days. Mechanistic validation used p300 overexpression/silencing in vivo and in high-glucose-stimulated Caco-2 cells. WKSG suppressed colonic p300/CBP-HAT activity and H3K27ac acetylation, reducing oxidative stress (ROS/MDA) while restoring antioxidants (SOD/GSH). This activated Nrf2/HO-1 antioxidant pathways and inhibited NF-κB-mediated inflammation (TNF-α/IL-6), improving tight junction proteins (ZO-1/occludin), TEER, and reducing FITC-dextran permeability. Combined therapy demonstrated synergistic enhancement across all parameters including reduced epithelial apoptosis. Clinical outcomes improved: body weight stabilization, reduced fasting glucose, decreased defecation frequency and fecal moisture. The p300/CBP-H3K27ac pathway represents a novel therapeutic target for DD management through integrated acupuncture-herbal protocols.

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