Plant-based echinacoside shown to ease signs of PAH in rat study
Naturally occurring compound may have therapeutic effects in people
Echinacoside (ECH), a naturally occurring compound derived from certain plants, particularly echinacea, was shown to ease the signs and symptoms of pulmonary arterial hypertension (PAH) in rats in a laboratory study.
The researchers found that ECH worked by normalizing calcium signaling in the muscle cells lining blood vessels, which are abnormally overgrown in PAH.
These findings suggest that the compound might have preventive and therapeutic effects in PAH, according to the team, who noted that ECH may have the “potential to mitigate PAH-associated inflammation.”
The study, “Echinacoside Improves Pulmonary Vascular Remodeling by Regulating the L- and T-Type Ca2+ Channels in the Prevention and Treatment of Pulmonary Hypertension,” was published in the journal Pulmonary Circulation.
In PAH, a type of pulmonary hypertension (PH), the narrowing of the pulmonary arteries — the blood vessels that pass through the lungs — drives up blood pressure and puts strain on the right side of the heart. Such narrowing is driven by excessive growth of cells lining blood vessels, particularly pulmonary artery smooth muscle cells, or PASMCs, a process known as vascular remodeling.
Researchers in China previously showed that ECH — discovered more than 60 years ago — slowed the abnormal growth of PASMCs under low-oxygen, or hypoxic, conditions. The plant-based compound also improved blood flow in the lungs of hypoxic rats, and lowered pulmonary blood pressure. Altogether, its use helped prevent strain and thickening of the right heart muscle.
Investigating the mechanisms underlying how echinacoside works
However, exactly how ECH works at the molecular level is not yet fully understood. Further, the previous studies solely examined rats with hypoxia-induced pulmonary hypertension (HPH), but not PAH. This research team, also from Qinghai Minzu University, sought to learn more.
To induce PAH, rats were exposed to a chemical called monocrotaline. ECH was administered directly into the stomach on the second day after the animals were given monocrotaline. The team assessed two indicators of PH: the mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index (RVHI), a measure of right heart wall thickening.
According to the researchers, treatment with ECH significantly lowered mPAP and RVHI in both PAH and HPH rats relative to untreated animals, with the greatest improvement seen at higher doses.
In a tissue assessment, animals with PAH showed thickened blood vessel walls, overgrowth of PASMCs, and inflammation. After ECH treatment, the lung structure improved significantly: The airways appeared normal, inflammation was mild, and the thickened lung blood vessels were greatly reduced, the team reported.
Inside PASMCs, a structure called the endoplasmic reticulum (ER), which helps store calcium and make proteins, was stressed and damaged in PAH. Treatment with ECH helped protect the ER, as indicated by an almost normal ER structure, reduced swelling and other changes, and the restoration of normal protein-making function, the researchers noted.
Further analysis found that two calcium channels in lung blood vessels, Cav1.2 and Cav3.2, were upregulated in rats with PAH and HPH, contributing to blood vessel thickening. Treatment with ECH significantly reduced the production of both calcium channels, limiting excess calcium entry into cells, which likely explained ECH’s therapeutic effects.
ECH treatment also significantly reduced the overactivation of the signaling pathway called PKC/MAPK in both PAH and HPH rat lungs. Active forms of proteins involved in this pathway were elevated in disease groups but decreased after ECH. In PASMCs, this effect was associated with reduced activity of the Cav1.2 and Cav3.2 calcium channels.
“Our study demonstrated that ECH effectively suppresses the activation of the PKC/MAPK signaling pathway by regulating the expression of Cav1.2 and Cav3.2,” the team wrote. The researchers added that “ECH improves pulmonary vascular remodeling … during PH development, thereby reducing mPAP and positively affecting the prevention and treatment of HPH and PAH.”
The team said further study is needed, and noted that future results “will also offer an important theoretical basis” for the compound’s use. “More effective and accurate PH prevention and treatment plans may be developed as studies progress,” the team concluded.
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