How an Herbal Remedy Calms Gut Inflammation at the Molecular Level

For people managing ulcerative colitis, a form of inflammatory bowel disease that flares in unpredictable cycles of abdominal pain, diarrhea, and rectal bleeding, the search for something that helps without harsh side effects never really stops. A new mechanistic study out of researchers at Tongji University and Shanghai Tenth People's Hospital gives a long-used Chinese herbal remedy a concrete molecular explanation for why it might calm that inflammation. The team traced the anti-inflammatory effect of Hudi enteric-coated capsule (HDEC), and its main active ingredient polydatin, down to a single protein switch inside gut immune cells, then confirmed that same switch flips in tissue taken from actual ulcerative colitis patients.

Key takeaways

• Polydatin, the main active compound in a Chinese herbal remedy called Hudi enteric-coated capsule, calmed gut inflammation in mice by binding a protein called KEAP1 and switching on the body's own antioxidant defenses.
• The same molecular switch activated in immune cells and short-term intestinal tissue samples taken from real ulcerative colitis patients, not just mice.
• Blocking that switch with a lab compound called ML385 wiped out polydatin's protective effect, showing the mechanism is required, not incidental.
• This is a mechanistic study, not a clinical trial, so it does not show that the herbal capsule or polydatin is a proven treatment for ulcerative colitis in people.

Polydatin Binds KEAP1 to Switch On the Gut's Antioxidant Defenses

Polydatin, the main bioactive compound in HDEC, directly binds a protein called KEAP1 (a cellular gatekeeper that normally traps a second protein and marks it for disposal), freeing that second protein, NFE2L2 (also called Nrf2), to move into the cell's nucleus and switch on a set of genes that neutralize cell-damaging molecules called reactive oxygen species, or ROS. Researchers first screened nine chemical components found in HDEC, including emodin, gallic acid, quercetin, and kaempferol, and found polydatin was by far the most effective at reining in the inflammatory immune cells driving the disease.

To confirm polydatin physically touches KEAP1 rather than just correlating with the effect, the team ran surface plasmon resonance testing and found the two bind in a dose-dependent way, meaning more polydatin means more binding. Molecular docking simulations mapped exactly where the two molecules connect, with polydatin's ring structure locking against specific amino acids on KEAP1, and a follow-up molecular dynamics simulation showed that connection stays structurally stable over time rather than falling apart. Genetically silencing NFE2L2 in cultured immune cells, and separately blocking it with the drug ML385, both erased polydatin's calming effect on inflammation, confirming this single pathway is doing the work rather than some side effect of the compound.

Why People With Ulcerative Colitis Should Care About Th17 and Treg Cells

Ulcerative colitis is driven in large part by an imbalance among subtypes of a white blood cell called a CD4+ T cell. Two aggressive subtypes, Th1 and Th17 cells (helper T cells that pump out the inflammatory signals IFN-gamma and IL-17A), become overactive in the inflamed gut, while a calming subtype called regulatory T cells, or Tregs, become scarce. That imbalance is a big part of why the lining of the colon stays chronically inflamed and damaged in UC. In this study, polydatin treatment cut the proportion of IFN-gamma and IL-17A producing T cells in mouse colon tissue while boosting the population of Foxp3-positive Treg cells, the combination researchers were specifically trying to restore. The effect held up when the team switched to human cells taken from the blood of 11 healthy volunteers and 10 people with active ulcerative colitis, and again in a short experiment using intestinal tissue removed from UC patients, where polydatin increased the same NFE2L2 activation researchers had seen in mice.

A Chronic Mouse Model Built to Mirror Real Ulcerative Colitis

Most colitis experiments in mice use a chemical irritant to trigger a short, sharp bout of inflammation that clears up on its own, which does not resemble the chronic, relapsing course UC patients actually live with. Here, researchers instead transferred a specific, disease-causing subset of T cells into mice that lack a functioning immune system of their own, producing colitis that builds and persists over roughly two months, a much closer stand-in for human UC. Mice given HDEC (at a dose of 0.984 grams per kilogram of body weight) were dosed daily by mouth starting four weeks after the T cell transfer and continuing through week eight; a separate group of mice received polydatin alone over a comparable multi-week course. Both treatments reduced weight loss, preserved colon length, and lowered pathological damage scores compared with untreated mice. A separate dose-finding experiment tested polydatin at three doses and found the middle dose, 45 milligrams per kilogram, worked about as well as a dose twice that size, so researchers used it for the rest of the study. Blood tests for liver enzymes stayed normal across every dose tested, an early signal against liver toxicity at these amounts in mice.

What This Means If You're Managing Gut Inflammation

HDEC is not a new or experimental product. It's an existing traditional Chinese medicine already used in China for intestinal complaints like diarrhea, abdominal pain, and tenesmus (a persistent urge to pass stool with little result). What this study adds is a plausible reason it might help with something more specific, ulcerative colitis, and a molecular target, KEAP1, that a drugmaker could aim a more refined compound at. That is meaningfully different from proof that the capsule, or polydatin as a supplement, safely treats UC in people. Nothing here has been tested in a controlled human trial, dosing for people is unknown, and herbal compounds can interact with prescription UC medications like biologics or immunosuppressants. Anyone with UC who is curious about this research should treat it as a reason to ask a gastroenterologist about it, not a reason to start self-dosing with an herbal capsule instead of prescribed treatment.

What the Study Doesn't Yet Answer

The human portion of this work involved cultured cells from 11 healthy donors and 10 UC patients, plus a short-term tissue experiment, which is a small and exploratory sample rather than anything resembling a clinical trial population. The researchers themselves note that basic pharmacology questions, how much polydatin the body actually absorbs when swallowed, how it distributes into intestinal tissue, and how long it stays active, were not measured here. It's also unclear whether the boost in Treg cells is durable or whether those cells could later flip back into inflammatory Th17 cells under continued stress, a kind of plasticity the authors flag as unresolved. And because this is a mouse and cell-culture study, the doses and timelines used cannot be directly translated into a human treatment schedule.

Next Steps Toward Testing This in People

The research team is calling for follow-up work to nail down safe and effective human dosing, run longer safety studies, and ultimately test polydatin, or a KEAP1-targeting drug built on the same binding mechanism, in a real clinical trial for ulcerative colitis. Because KEAP1 is a well-studied target in other diseases, with existing drugs like dimethyl fumarate already working the same molecular switch for a different condition, the path from this mechanistic finding to a testable human therapy is shorter than it would be for a completely novel target.

Common Questions

Is Hudi enteric-coated capsule already available or prescribed? Yes. In China it is an existing traditional Chinese medicine already used for intestinal complaints like diarrhea and abdominal pain, but this study is the first to test it directly in a model built to mimic chronic UC and to explain how it works at the molecular level.

What is polydatin and where does it come from? Polydatin is a natural compound extracted from Polygonum cuspidatum (also known as Japanese knotweed), which researchers identified as HDEC's single most potent anti-inflammatory ingredient after comparing it against eight of the capsule's other chemical components.

Does this mean polydatin cures ulcerative colitis? No. The findings come from mice, cultured human cells, and short-term human tissue samples, not a clinical trial, so nothing here shows polydatin is a safe or effective treatment for UC in people. That would require dedicated human trials the authors say still need to happen.

What is the KEAP1-NFE2L2 pathway in plain terms? KEAP1 is a protein that normally traps NFE2L2 in the cell and marks it for disposal. When a compound like polydatin binds KEAP1, NFE2L2 escapes into the nucleus and switches on genes that clean up cell-damaging molecules, calming down the inflammatory immune response in the process.

References

1. Xiaohan Wu, Lei Shi, Lei Zhu, et al. (2026). Hudi enteric-coated capsule and its active constituent polydatin suppress Th1/Th17-mediated intestinal inflammation by modulating the KEAP1-NFE2L2 signaling pathway. Precision Clinical Medicine. https://doi.org/10.1093/pcmedi/pbag018
2. Wenjun Tu, Hong Wang, Song Li, Qiang Liu, Hong Sha (2019). The Anti-Inflammatory and Anti-Oxidant Mechanisms of the Keap1/Nrf2/ARE Signaling Pathway in Chronic Diseases. Aging and disease. https://doi.org/10.14336/ad.2018.0513
3. Yuyuan Hu, Yuhang Yang, Yan Li, et al. (2025). Th17/Treg imbalance in inflammatory bowel disease: immunological mechanisms and microbiota-driven regulation. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2025.1651063
4. Xudong Tang, Yilin Huang, Ying Zhu, Yin Xu (2025). Immune dysregulation in ulcerative colitis: pathogenic mechanisms and therapeutic strategies of traditional Chinese medicine. Frontiers in Cell and Developmental Biology. https://doi.org/10.3389/fcell.2025.1610435