Fungus Used in Chinese Medicine Eased PAH Damage in Rat Model

Treatment with a fungus called Ophiocordyceps sinensis eased disease signs and improved survival in a rat model of pulmonary arterial hypertension (PAH), suggesting a potential to treat patients.

The findings were in the study “Substantial involvement of TRPM7 inhibition in the therapeutic effect of Ophiocordyceps sinensis on pulmonary hypertension,” published in Translational Research.

Ophiocordyceps sinensis, abbreviated OCS, is an entomopathogenic fungus — a type of fungus that can cause disease in certain kinds of arthropods (e.g., insects and crustaceans). OCS is used in traditional Chinese medicine to treat conditions including liver inflammation, high blood pressure, and cancer. Recent research has shown that OCS can lessen fibrosis (scarring) and inflammation in various animal models of disease.

A team led by researchers in Japan tested OCS as a treatment in a rat model of PAH, in which symptoms are induced by a chemical called monocrotaline. OCS was administered orally every day, starting 11 days after monocrotaline injection.

Imaging of the heart (echocardiography) showed that OCS treatment lessened the extent of PAH-like damage that was induced by monocrotaline. For example, certain parts of the heart in this model become scarred, and the tissue grows thicker; this was eased by OCS treatment. Notably, the use of OCS in the absence of PAH-inducing monocrotaline did not substantially affect heart health.

Rats with PAH-mimicking symptoms treated with OCS also, on average, lived significantly longer.

“The present study demonstrated, for the first time, that OCS, a traditional Chinese medicine, ameliorated the pathological [disease-related] findings of experimental pulmonary hypertension and significantly improved the survival of [monocrotaline-induced pulmonary hypertension],” the researchers wrote.

Prior research had suggested that OCS might work by acting on a protein called TRPM7. Experiments using cells in dishes confirmed that OCS treatment lessened the activity of TRPM7, as well as downstream molecular signaling pathways in cells.

In the rats, monocrotaline’s use increased TRPM7 levels, and this effect was lessened by OCS.

To further study the relevance of this protein, the researchers experimented on rats that had been engineered to lack TRPM7. Compared to wild-type (normal) rats, TRPM7 deficiency countered the increase in right ventricular systolic pressure (RVSP) — a measure of the pressure inside the artery that supplies blood to the lungs. OCS did not affect RVSP regardless of monocrotaline use.

These findings, “strongly suggest a crucial role of TRPM7 in the development of experimental pulmonary hypertension,” the team wrote.

Finally, the scientists examined samples of pulmonary artery smooth muscle cells (PASMCs) collected from people with and without PAH. These cells surround blood vessels in the lungs. Abnormal smooth muscle contractility has been implicated in the development of PAH.

The team found that PASMCs from PAH patients had significantly higher TRPM7 expression, and proliferated (divided) more rapidly than PASMCs from people without PAH.

When PASMCs from PAH patients were treated with OCS, cell division slowed. OCS treatment also induced relaxation of these muscle cells.

“These observations obtained with clinical specimens suggest the potential of the administration of OCS as a new therapeutic strategy for the treatment of PAH,” the researchers concluded.

The precise mechanism by which OCS exerts its effects — such as the active compounds made by the fungus — remain to be worked out, the researchers added. They broadly noted a need for further research into the mechanisms by which PAH develops, as well as strategies to treat it.