Illustration of a person with arthritis finding relief in a Polyphyllin I forest.

Could This Ancient Herb Be the Key to Easing Arthritis?

Soraya Malik in Health & Wellness December 2025 • 4 min read.

"New research highlights the potential of Polyphyllin I in alleviating inflammation and joint damage associated with collagen-induced arthritis."

Rheumatoid arthritis (RA) is a chronic autoimmune condition affecting millions worldwide, marked by persistent joint inflammation that can lead to cartilage and bone damage. Current treatments primarily focus on managing symptoms, often with significant side effects, leading researchers to explore alternative and complementary therapies.

Macrophages, a type of immune cell, play a central role in the development and progression of RA. In RA, an increased number of M1-like macrophages infiltrate the joints, releasing pro-inflammatory cytokines that exacerbate inflammation and tissue damage. Targeting these macrophages and the inflammatory pathways they activate has become a focal point in RA research.

A recent study published in Frontiers in Immunology sheds light on a promising natural compound called Polyphyllin I (PPI). Found in the Rhizoma of Paris polyphyllin plant, traditionally used in Chinese medicine, PPI has demonstrated selective inhibitory effects on various tumor cells. Now, scientists are exploring its potential in managing rheumatoid arthritis by suppressing inflammation in macrophages.

How Does Polyphyllin I Fight Inflammation in Arthritis?

Illustration of a person with arthritis finding relief in a Polyphyllin I forest.

The Frontiers in Immunology study thoroughly investigated the effects of PPI on macrophages, both in vitro (in lab settings) and in vivo (in a collagen-induced arthritis mouse model). Researchers examined how PPI influences the inflammatory response in macrophages stimulated by lipopolysaccharide (LPS) and interferon-gamma (IFN-γ), two substances known to trigger inflammation.

One of the key findings of the study revolves around the NF-κB pathway, a critical signaling cascade that regulates the expression of pro-inflammatory mediators. When activated, the NF-κB pathway leads to the production of cytokines and other molecules that amplify inflammation. The study found that PPI effectively inhibits the NF-κB pathway in macrophages by:

Reducing the production of inflammatory cytokines (IL-1β, IL-6, TNF-α)
Inhibiting the phosphorylation of IKKα/β and p65, key proteins in the NF-κB pathway
Preventing the translocation of p65 into the nucleus, where it activates gene expression

To confirm the significance of the NF-κB pathway, researchers used NF-κB inhibitors, siRNA (small interfering RNA) to silence the p65 gene, and a p65 overexpression plasmid. Blocking or silencing p65 eliminated PPI's anti-inflammatory effects, while overexpressing p65 blunted PPI's ability to suppress inflammation. These experiments underscored that PPI exerts its effects specifically by targeting the NF-κB pathway.

What Does This Mean for Arthritis Sufferers?

This research suggests that Polyphyllin I holds promise as a therapeutic agent for rheumatoid arthritis. By targeting the NF-κB pathway in macrophages, PPI can effectively reduce inflammation and prevent joint damage, potentially slowing the progression of the disease. However, it's important to note that this study was primarily conducted in vitro and in animal models. Further research, including clinical trials in humans, is needed to confirm these findings and determine the optimal dosage and safety of PPI for RA treatment. While more studies are underway, PPI presents a new possible method for treatment of RA.

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Everything You Need To Know

What is rheumatoid arthritis, and what role do macrophages play in it?

Rheumatoid arthritis is an autoimmune disease where the body's immune system mistakenly attacks the joints, leading to inflammation, pain, and potential joint damage. Macrophages, a type of immune cell, play a key role in this process. Specifically, an increased number of M1-like macrophages infiltrate the joints, releasing pro-inflammatory cytokines that exacerbate inflammation and tissue damage.

What is Polyphyllin I (PPI), and where does it come from?

Polyphyllin I (PPI) is a compound found in the *Rhizoma of Paris polyphyllin* plant, a herb traditionally used in Chinese medicine. Research indicates that PPI has selective inhibitory effects on tumor cells and may also have potential in managing rheumatoid arthritis by suppressing inflammation in macrophages.

What is the NF-κB pathway, and how does Polyphyllin I (PPI) affect it?

The NF-κB pathway is a critical signaling cascade that regulates the expression of pro-inflammatory mediators. When activated, it leads to the production of cytokines and other molecules that amplify inflammation. Polyphyllin I (PPI) has been shown to inhibit this pathway in macrophages, reducing inflammation. This occurs by reducing the production of inflammatory cytokines, inhibiting the phosphorylation of IKKα/β and p65 (key proteins in the NF-κB pathway) and preventing the translocation of p65 into the nucleus, where it activates gene expression.

How could Polyphyllin I (PPI) potentially help people with rheumatoid arthritis?

Polyphyllin I (PPI) targets the NF-κB pathway in macrophages to reduce inflammation and potentially prevent joint damage. By inhibiting the NF-κB pathway, PPI reduces the production of inflammatory cytokines (IL-1β, IL-6, TNF-α) and modulates other processes that amplify inflammation. This suggests it could slow the progression of rheumatoid arthritis. However, it is important to know that research is preliminary and has primarily been conducted in vitro and in animal models, so clinical trials in humans are needed.

How was the research about Polyphyllin I (PPI) and its effects on arthritis conducted?

The study used in vitro (lab settings) and in vivo (a collagen-induced arthritis mouse model) experiments to examine how Polyphyllin I (PPI) influences the inflammatory response in macrophages. The researchers investigated the effects of PPI on macrophages stimulated by lipopolysaccharide (LPS) and interferon-gamma (IFN-γ), which are known to trigger inflammation. They confirmed that PPI exerts its effects specifically by targeting the NF-κB pathway by using NF-κB inhibitors, siRNA (small interfering RNA) to silence the p65 gene, and a p65 overexpression plasmid.