Japanese herbal medicine shows promise against age-related tissue scarring in mice

Researchers at the University of Osaka have found that Bofutsushosan, a traditional Japanese herbal remedy long prescribed for weight management, appears to offer protection against a different problem altogether: the scarring and stiffening of tissues that comes with age. The discovery emerged from a study published in Phytomedicine, conducted in partnership with Kobayashi Pharmaceutical Co., Ltd., and it suggests that this 18-ingredient formula may work on multiple fronts to preserve tissue health as the body ages.

The problem the researchers were investigating is real and consequential. As people grow older and carry excess weight, chronic inflammation takes hold in fat tissue and vital organs—the liver, heart, kidneys. This inflammation triggers fibrosis, a process in which tissues accumulate scar-like material, becoming stiff and less able to function. Bofutsushosan has been used in Japan for decades to help with obesity, but whether it could also slow or prevent this age-related scarring remained unknown.

To find out, the team gave 63-week-old male mice a high-fat diet, with some animals receiving 2% Bofutsushosan mixed into their food for eight weeks. The results were striking. Mice that received the herbal medicine weighed 14.8% less than their untreated counterparts by the study's end. They consumed less food overall, accumulated smaller fat deposits, showed reduced fat buildup in the liver, and most importantly, displayed fewer of the cellular changes associated with fibrosis in both fat tissue and liver.

But weight loss alone can improve fibrosis, so the researchers needed to know whether Bofutsushosan was doing something more direct. They grew fat-cell precursors in laboratory dishes and exposed them to the herbal extract. The formula reduced several signals that drive fibrosis and partially blocked a specific cellular pathway—the TGF-β/SMAD2/3 pathway—that normally promotes the buildup of scar-like tissue. This suggested the medicine was acting on the problem at a molecular level, independent of weight reduction.

The next step was to identify which of the 18 ingredients were responsible. When tested individually in cultured cells, four stood out: Forsythiae Fructus, Zingiberis Rhizoma, Rhei Rhizoma, and Scutellariae Radix all showed particularly strong anti-fibrotic activity. Interestingly, some mineral ingredients, especially Sal Mirabilis, appeared to work in the opposite direction under these laboratory conditions—though the researchers emphasized that this does not mean the mineral promotes fibrosis in living organisms or in actual clinical use. The effect may be an artifact of the cell-culture environment.

When the researchers tested modified formulas that increased the amounts of the four promising ingredients, they saw stronger suppression of fibrosis-related markers in the cultured cells. These revised recipes have not yet been tested in animals or people. The lead researcher, Ayano Onishi, noted that while Bofutsushosan is known primarily for its weight-loss effects, the new findings suggest it may also combat fibrosis linked to aging and obesity. Understanding how each ingredient contributes could guide future research into how multi-component Kampo medicines work together.

The researchers were careful to note that these are early findings. The results are preclinical, meaning they come from laboratory and animal work, not human trials. No one should alter their treatment based on this research, and the approved formula should not be changed without medical guidance. What comes next is clear: animal studies of the modified formulas, followed eventually by human trials to determine whether this approach could lead to new treatments for the fibrosis that accompanies obesity and aging.