Ancient Chinese Herbal Formula Shows Promise Against Disc Degeneration

Chronic low back pain driven by intervertebral disc degeneration afflicts hundreds of millions of people worldwide, and current treatments—painkillers, rehabilitation, and eventually surgery—manage symptoms without halting the underlying disease. Now, a team of researchers at West China Hospital of Sichuan University reports that a classical Chinese herbal formula with a documented clinical history stretching back nearly three centuries may offer something closer to true disease modification. In a study published in Immunity, Inflammation and Disease, the formula Juanbi Tang, first recorded in 1732 in the Qing dynasty text Yi Xue Xin Wu, significantly preserved disc structure in a rat model of degeneration while reshaping the inflammatory immune environment that drives the condition.

The research team, led by Ye-Hui Wang and Yang Yu, approached the problem through the lens of immunopathology. Degenerating discs are not merely worn-out cushions; they become hubs of chronic inflammation in which nucleus pulposus cells—the disc’s load-bearing cells—die off, the extracellular matrix is chewed apart by catabolic enzymes, and macrophages flood the tissue in a pro-inflammatory M1 state, secreting tumor necrosis factor-alpha, interleukin-1 beta, and matrix metalloproteinase-13. Macrophages that instead adopt the M2 phenotype produce interleukin-10 and transforming growth factor-beta, supporting tissue homeostasis and cell survival. Pharmacologically steering this M1-to-M2 transition has therefore become a leading therapeutic strategy, and the new study positions Juanbi Tang as a surprisingly sophisticated tool for exactly that purpose.

The formula itself is a study in polypharmacology. It contains eleven herbs organized according to the traditional jun-chen-zuo-shi hierarchy, in which sovereign, minister, assistant, and courier herbs play defined roles. Notopterygium incisum and Angelica pubescens serve as sovereign herbs with primary anti-inflammatory activity; cinnamon, large-leaved gentian, chuanxiong, and angelica root augment circulation and curb matrix breakdown; kadsura pepper, mulberry twig, costus root, and frankincense reinforce the anti-inflammatory effect; and licorice harmonizes the whole. Notably, boswellic acids from the frankincense component are established inhibitors of the transcription factor NF-κB, while osthole from Angelica pubescens has documented activity against the p38 mitogen-activated protein kinase pathway—two of the very molecular targets the study ultimately confirmed.

Before any biological testing, the researchers subjected their preparation to rigorous chemical quality control. Using high-performance liquid chromatography with osthole as the quantitative reference standard, they confirmed a linear standard curve across 20 to 160 micrograms per milliliter and demonstrated an inter-batch relative standard deviation of just 2.3 percent across three independent preparations, well below the 5 percent acceptance threshold. A multi-component fingerprint analysis resolving sixteen common peaks between the raw decoction and the vacuum-concentrated preparation yielded similarity values of 0.9994 and 0.9989 by the cosine angle and correlation coefficient methods respectively, confirming that the full chemical complexity of the formula survives processing and is reproducible batch to batch.

The in vivo work used a rat caudal annular puncture model, in which full-thickness needle puncture of the outer annulus at two tail disc levels reliably induces degeneration. One hundred and five Sprague-Dawley rats were randomized into five groups: a sham surgery control, untreated degeneration, degeneration treated with oral Juanbi Tang at a dose converted from the clinical human prescription, degeneration treated with the autophagy inhibitor 3-methyladenine alone, and degeneration treated with both. After four weeks of twice-daily gavage, the treated animals were assessed across five complementary dimensions: magnetic resonance imaging for disc water content, computed tomography for disc height, and three histological stains capturing cellular architecture, proteoglycan content, and collagen fiber organization.

The results were strikingly consistent. The disc height index, which fell from 1.0 in sham animals to 0.6 in degenerated controls, was preserved at 0.9 with Juanbi Tang treatment. Pfirrmann MRI grading, which worsened from 1.4 to 3.8 with degeneration, improved to 2.6 under treatment, while Thompson histological grading fell from 3.8 to 2.4. Proteoglycan content, reduced to a quarter of sham levels by degeneration, recovered to three-quarters, and Masson trichrome staining showed collagen content rising from 21.5 percent of disc area in degenerated animals to 56.8 percent with treatment—approaching the sham value of 67.3 percent. At the molecular level, type II collagen was substantially restored and matrix metalloproteinase-13 sharply suppressed, and these structural and molecular benefits were consistently but partially reversed when the autophagy inhibitor 3-methyladenine was co-administered, pointing to autophagy as a necessary component of the formula’s protective activity.

Systemic cytokine measurements reinforced the immunological story. Serum tumor necrosis factor-alpha, which surged from 37.6 to 304.6 picograms per milliliter after disc injury, fell to 99.2 picograms per milliliter with treatment, while the anti-inflammatory cytokine interleukin-10, depleted from 183.2 to 44.2 picograms per milliliter, was restored to 160.1 picograms per milliliter. Western blotting of disc tissue confirmed that the formula selectively suppressed the phosphorylated, active forms of both p38MAPK and the NF-κB subunit p65, the signaling hub through which mechanical stress, danger signals, and inflammatory cytokines converge to drive catabolic gene transcription in the disc.

In cell culture, the picture sharpened. When primary rat nucleus pulposus cells were injured with lipopolysaccharide, Juanbi Tang cut total apoptosis from 29.1 percent to 14.5 percent, restored mitochondrial membrane potential as measured by JC-1 fluorescence, and reduced reactive oxygen species accumulation. The Bax-to-Bcl-2 ratio, a key determinant of the intrinsic apoptotic pathway, was rebalanced, and LC3 puncta—hallmarks of autophagosome formation—dotted the cytoplasm of treated cells. In RAW264.7 macrophages, flow cytometry revealed that the formula shifted the polarization balance dramatically: the M1 fraction fell from 52.4 percent to 18.9 percent, the M2 fraction rose from 28.1 percent to 49.7 percent, and the M1-to-M2 ratio dropped from 1.9 to 0.4, accompanied by reduced tumor necrosis factor-alpha and increased interleukin-10 secretion.

The mechanistic centerpiece came from genetic manipulation of Atg5, a protein essential for autophagosome formation. When Atg5 was overexpressed, the formula’s suppression of p62/SQSTM1—a scaffold protein that sustains NF-κB activation—deepened, and pathway inhibition was nearly complete. When Atg5 was knocked down, autophagic flux collapsed, p62 remained elevated, and the formula’s suppression of p-p38MAPK and p-NF-κB p65 fell from roughly 90 percent to about 45 percent. These bidirectional data support a regulatory module in which the formula suppresses p38MAPK/NF-κB signaling while simultaneously activating Atg5-dependent autophagy; the resulting autophagic clearance of p62 then consolidates NF-κB inhibition, lowering the threshold for M2 polarization. The authors are careful to frame this as a mechanistic model rather than a fully resolved linear causal chain, noting that whether p38 inhibition lies upstream of autophagy activation remains an open question for ongoing work with selective p38 inhibitors and ATG5 phosphorylation assays.

The study has honest limitations, which the authors state plainly. There was no clinical positive control such as celecoxib or rapamycin to benchmark effect size; the macrophage work used a murine cell line while the animal model was rat, constraining cross-species inference; and direct co-culture experiments linking M2-polarized macrophages to nucleus pulposus cell protection are planned. Head-to-head comparisons against established anti-inflammatory and autophagy-inducing agents, more selective autophagy inhibitors, and UPLC-MS/MS quantification of multiple constituents are defined next steps. Even so, the convergence of evidence—five structural endpoints in vivo, coordinated molecular and cytokine changes, and a genetically dissected autophagy-dependent mechanism—offers a rare degree of mechanistic rigor for a traditional formula. If subsequent work confirms these findings in primary macrophages and establishes the paracrine link between macrophage reprogramming and disc cell survival, an eighteen-hundred-year-old prescription for painful obstruction may yet find a place in the modern pharmacology of back pain.

Subject of Research: The immunomodulatory mechanisms by which the traditional Chinese medicine formula Juanbi Tang attenuates intervertebral disc degeneration through p38MAPK/NF-κB suppression, Atg5-dependent autophagy, and macrophage M2 polarization.

Article Title: Juanbi Tang Attenuates Intervertebral Disc Degeneration by Suppressing p38MAPK/NF‐κB Signaling and Activating Atg5‐Dependent Autophagy to Promote Macrophage M2 Polarization: In Vivo and In Vitro Evidence

Article References: Wang, Y.-H., Hou, W., Tang, G.-S., Deng, X.-G., Song, S.-M., Cui, W., Ye, Y., & Yu, Y. (2026). Juanbi Tang Attenuates Intervertebral Disc Degeneration by Suppressing p38MAPK/NF‐κB Signaling and Activating Atg5‐Dependent Autophagy to Promote Macrophage M2 Polarization: In Vivo and In Vitro Evidence. Immunity, Inflammation and Disease, 14(9), Article e70498. https://doi.org/10.1002/iid3.70498

Image Credits: AI Generated

DOI: 10.1002/iid3.70498

Keywords: intervertebral disc degeneration, Juanbi Tang, traditional Chinese medicine, macrophage polarization, autophagy, Atg5, p38MAPK, NF-κB, p62/SQSTM1, nucleus pulposus cells, M2 macrophages, low back pain