A traditional Japanese medicine used for obesity may do more than support weight loss. Researchers at the University of Osaka, working with Kobayashi Pharmaceutical Co., Ltd. investigated whether Bofutsushosan could protect aging tissues from fibrosis - the excessive buildup of scar-like tissue that can make organs stiff and less functional. The study was published in Phytomedicine.

Aging and obesity can promote chronic inflammation and fibrosis in fat tissue and organs such as the liver, heart, and kidneys. Although Bofutsushosan contains 18 crude-drug ingredients and is widely used in Japan for obesity, its effects on fibrosis associated with aging and obesity, and the contribution of each ingredient, remained unclear.

The team fed 63-week-old male mice a high-fat diet with or without 2% Bofutsushosan for eight weeks. Mice receiving Bofutsushosan weighed 14.8% less than untreated mice at the end of the study. They also ate less, had smaller fat deposits, showed less fat buildup in the liver, and had fewer fibrosis-related changes in fat tissue and the liver.

Because weight loss itself can improve fibrosis, the researchers also used cultured fat-cell precursors to investigate whether Bofutsushosan had a more direct effect. In these cells, Bofutsushosan reduced several fibrosis-related signals and partly suppressed the TGF-β/SMAD2/3 pathway, which helps drive the buildup of scar-like tissue.

The researchers then tested the 18 ingredients separately. Forsythiae Fructus, Zingiberis Rhizoma, Rhei Rhizoma, and Scutellariae Radix showed particularly strong anti-fibrotic activity in cultured cells. Some mineral ingredients, particularly Sal Mirabilis, showed the opposite effect under the same cell-culture conditions.

The researchers caution that this finding does not show that Sal Mirabilis promotes fibrosis in the body or during clinical use. The effect may be specific to the cell-culture environment.　Increasing the amounts of the four candidate anti-fibrotic ingredients, with or without removing Sal Mirabilis, produced stronger suppression of some fibrosis-related markers in cultured cells. The modified formulas have not yet been tested in animals or people.

The findings suggest that Bofutsushosan may have benefits beyond weight control and provide a scientific basis for studying how the ingredients in multi-component Kampo medicines work together.

The results are preclinical and do not support changing the approved formula or altering treatment without medical advice. Further animal and human studies will be needed to determine whether this approach could eventually contribute to treatments for fibrosis associated with obesity and aging.

"Bofutsushosan is best known for its effects on obesity," said lead author Ayano Onishi. "Our findings suggest that it may also act on fibrosis associated with aging and obesity. Understanding the role of each ingredient could help guide future research into Kampo medicines, but human studies will be needed before the findings can be applied to treatment."

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