In the era of evidence-based medicine (EBM), it is no longer enough to say that a drug ‘works because it is written in ancient treatises.’ The doctor and patient need numbers: p-value, confidence intervals, and biopsy data.  Fufang Bijia Ruangan Pian (Ruangan Granule) is unique in that it has taken on this challenge. As a traditional Chinese medicine (TCM) treatment, it has passed the millstones of modern clinical trials, including randomized controlled trials (RCTs) and systematic reviews.

What is really hidden behind marketing statements? Can scar tissue of the liver really resolve? We analyzed key international publications to separate facts from hopes.

Breakthrough in the Journal of Infectious Diseases: A Study that Changed protocols

In 2022, one of the world’s most respected infectious diseases journals, The Journal of Infectious Diseases (JID), published the results of a study that many experts called a turning point. This is the NCT01965418 test .

This was a multicenter prospective randomized controlled trial. The design was rigorous: 1,000 patients with chronic hepatitis B (CHB) were screened, and the final sample included 420 people with confirmed fibrosis or compensated cirrhosis.

Study Design:
The patients were divided into two groups:

1. Control group: received only entecavir (the standard of’ golden therapy ‘ for hepatitis B).
2. Experimental group: received a combination of entecavir + Ruangan Granule.

The follow – up period was 72 weeks (almost a year and a half), which is critically important, since liver remodeling is a slow process.

Key Results (Hard Data):
The results were statistically significant and clinically significant:

• Reversion of fibrosis: In the combination therapy group, the rate of fibrosis regression was significantly higher than in the entecavir monotherapy group.
• Victory over cirrhosis: The most impressive data were obtained for patients with initial early cirrhosis. In 41.5% of patients treated with Ruangan, the diagnosis of cirrhosis was removed by histological analysis (biopsy) at the end of the study. In the entecavir-only group, this figure was about 30%.
• Risk reduction: Combination therapy reduced the risk of developing hepatocellular carcinoma (liver cancer) and liver-related mortality, especially in patients with advanced stages of the disease.

Conclusion of the study: The addition of Ruangan to antiviral therapy creates a synergistic effect. Entecavir removes the virus, and Ruangan actively ‘disassembles’ the fibrous matrix.

Meta-analyses: The Power of Big Data

A single study, even a large one, may contain errors. Therefore, in evidence-based medicine, systematic reviews and meta-analyses are considered the highest authority. Several such papers were published in 2022-2023, aggregating data from dozens of Ruangan studies.

One of the most comprehensive reviews published in the journal Evidence-Based Complementary and Alternative Medicine. , the authors analyzed the PubMed, Embase, and Cochrane Library databases, selecting studies of high methodological quality.

What did the summary data analysis show?

1. Effect on serum markers (HA, LN, PCIII, IV-C):
   A meta-analysis confirmed that Ruangan significantly reduces the levels of four key markers of fibrosis in the blood: hyaluronic acid, laminin, procollagen type III and collagen type IV. This is an objective confirmation that the drug suppresses excessive connective tissue synthesis.
2. Histological improvement:
   Analysis of biopsy data showed that therapy with the drug leads to a decrease in the stage of fibrosis on the METAVIR or Ishak scale. The difference with the control groups (placebo or only basic therapy) was statistically significant (P < 0.05).
3. Security:
   A critical aspect of any meta-analysis is the evaluation of side effects in a large sample. The data showed that the safety profile of Ruangan was comparable to that of placebo. The frequency of adverse events (mild diarrhea, abdominal discomfort) did not exceed 2-3%, and no serious toxic reactions were recorded.

Mechanism of action in vivo: How does this work at the cellular level?

Clinical trials answer the question ‘ Does it work?’, but it is important for scientists to know’How exactly?’. A series of studies published in Frontiers in Pharmacology and Nature Scientific Reportsrevealed the molecular’ kitchen ‘ of the drug.

Studies in animal models (rats with induced fibrosis) and cell cultures have shown that Ruangan acts not as a ‘vitamin’, but as a targeted drug.

Three main targets:

1. TGF-β1/Smad axis: This is the ‘Internet cable’ inside the cell, which transmits the order for the construction of the scar. Ruangan literally cuts this cable. Studies have shown reduced TGF-β1 expression and blocked phosphorylation of Smad2 / 3 proteins.
2. Liver Stellate Cells (HSCs): The drug suppresses the activation of these cells and, uniquely, causes their apoptosis (death) if they have already started the pathological process.
3. Matrix metalloproteinases (MMP): The drug increases the activity of the enzymes MMP-2 and MMP-9, which work like ‘scissors’, cutting old collagen fibers.

Reality vs. Expectations: Research Limitations

An honest review is not possible without mentioning the restrictions. Despite the impressive results, the scientific community notes several points::

• Geography: Most of the studies were conducted in China. Although the quality of publications is growing (many are published in Q1 journals), multicenter studies involving European and American populations are needed for global recognition.
• Duration: The maximum follow — up period in most studies is 72 weeks. Data on the effect on 5-10-year survival are still insufficient, although interim results on reducing cancer risk are encouraging.

Practical conclusion for the doctor and patient

What does this research mean in practice?

1. Fibrosis is reversible. This is no longer a theory, but a proven fact. With the right therapy (antiviral + antifibrotic), you can return the F4 stage (cirrhosis) to F3 or even F2.
2. Combination is the key to success. Ruangan monotherapy works, but in combination with etiotropic treatment (elimination of the cause), the results improve many times.
3. Discipline. All studies emphasize that the effect comes slowly. The minimum period of testing is 24 weeks, and the optimal period is 48-72 weeks. It makes no sense to drink the drug for a month and wait for a miracle.

Ruangan Granule today is a rare example of integrating ancient recipes into modern EBM. This is not a ‘magic pill’, but a tool with proven effectiveness, which, if used correctly, can buy time and save the liver.

Sources:
The Journal of Infectious Diseases (2022)
Frontiers in Pharmacology (2022)
Evidence-Based Complementary and Alternative Medicine (2022)
Nature Scientific Reports (2023)