A new study has found that the Chinese herbal medicine astragaloside IV (AS-IV) may benefit patients with pulmonary arterial hypertension (PAH) by increasing the expression of cysteine rich 61 (CCN1), which regulates proliferation, differentiation, apoptosis, angiogenesis, and fibrosis.

The study, published in the Journal of Cellular and Molecular Medicine, demonstrated reduced hemodynamic parameters, vascular wall area ratio, and vascular wall thickness ratio in an in vivo rat model of PAH.

“According to the research results of our laboratory and other laboratories, AS-IV has a protective effect against PAH,” the authors wrote. “However, the specific role of AS-IV and CCN1 and its associated ERK1/2 signaling pathway in PAH is unclear. Therefore, in this article we studied the effect of AS-IV against PAH by focusing on CCN1 and its related ERK1/2 signaling pathway.”

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AS-IV is a natural triterpene glycoside that can be extracted from the astragalus plant. The herbal compound is used as a treatment for cardiovascular disease, including myocardial hypertrophy and fibrosis. Based on previous research, AS-IV is suspected to have protective activity against PAH.

Read more about PAH therapies.

The research team injected male SD rats intraperitoneally with monocrotaline (MCT) or exposed them to hypoxia to create a model of PAH, and then treated them with 3 doses of AS-IV (20, 40, and 80 mg/kg/d), small interfering CCN1, and recombinant CCN1 protein.

Western blotting, immunohistochemistry, and immunofluorescence revealed increased expression of CCN1, particularly in the early stages of PAH, and activation of the ERK1/2 signaling pathway as a result of the treatments. These changes were accompanied by reduced apoptosis and improved hemodynamic parameters of PAH.

Other studies have shown controversial results in terms of the role of CCN1 in lung disease, with some showing increased cell proliferation and protection from apoptosis and others finding increased inflammation and pulmonary fibrosis. Therefore, the authors suggest caution when interpreting these results and conclude that further studies on the potentially protective effect of AS-IV in PAH are warranted.


Liu Y, Tang B, Lu M, et al. Astragaloside IV improves pulmonary arterial hypertension by increasing the expression of CCN1 and activating the ERK1/2 pathway. J Cell Mol Med. Published online February 10, 2023. doi:10.1111/jcmm.17681