Natural plant compound berberine eased PF symptoms in mouse model

Studies have shown compound may aid pneumonia, lung infections, COPD

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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An oversized hand holds a mouse alongside a rack of filled vials.

Berberine, a naturally occurring plant compound, eased the signs and symptoms of pulmonary fibrosis (PF) in a mouse model where the disease was triggered by exposing animals to fine particulate matter found in air pollution.

The findings “offer novel insights into the mechanisms underlying the beneficial effects of [berberine] in alleviating pulmonary fibrosis,” the researchers wrote in “Berberine hydrochloride ameliorates PM2.5-induced pulmonary fibrosis in mice through inhibiting oxidative stress and inflammatory,” which was published in Chemico-Biological Interactions.

In PF, scarring, or fibrosis, of the lungs can cause symptoms such as shortness of breath and a dry, hacking cough. In most cases, the underlying cause of lung scarring isn’t known and here the form of the disease is referred to as idiopathic PF. Various autoimmune disorders, certain infections, or exposure to air pollution can also trigger the disease.

Fine particulate matter is a source of air pollution that contributes to lung disease, including PF. Such particulates are tiny, with a diameter equal to or smaller than 2.5 micrometers (PM2.5), which is about 30 times smaller than a strand of human hair. Sources of PM2.5 include smokestacks or fires, construction sites, and pollutants from power plants, industries, and automobiles.

Berberine is found in plants and has been shown to have anti-inflammatory, antioxidant, and anti-fibrotic properties. Studies suggest it may offer benefits for certain lung conditions, such as pneumonia, lung infections, and chronic obstructive pulmonary disease (COPD), leading researchers in China to investigate its mode of action and protective effects in a mouse model where PF was induced by exposing the animals to PM2.5.

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Triggering PF with PM2.5

Healthy mice were randomly assigned to pretreatment with berberine (50 mg/kg) via a feeding tube or water for 45 days. On day three, mice in the berberine and water, or control, groups started receiving a drip of PM2.5 suspension into the lungs once every three days for 15 times to trigger PF. Some animals were instead given a drip of saline solution as a control. Animal tissues were evaluated on day 45.

Compared with the unexposed, untreated control group, mice given PM2.5 had significantly heavier lungs and a higher ratio of lung weight to body weight. The berberine treatment significantly reversed these effects, suggesting “[berberine] pretreatment may improve PM2.5-induced pulmonary edema [swelling],” the researchers wrote.

A close examination of lung tissues revealed PM2.5 exposure caused the walls around the tiny air sacs in the lungs where gas exchanges take place, or alveoli, to thicken. This was accompanied by the loss of some alveoli. In comparison, lung tissues from unexposed control mice and those treated with berberine appeared normal. Treatment also decreased fibrosis and deposits of collagen, a protein compound of scar tissue.

Levels of inflammatory immune cells in blood and lung tissue were significantly higher in the PM2.5 group than the control group. With berberine, the number of these cells in the bloodstream and lung tissues dropped significantly. Likewise, elevated levels of lactate dehydrogenase, a marker of tissue damage, were reduced with berberine pretreatment.

Berberine’s effect on oxidative stress

Oxidative stress plays a major role in PF. It’s caused by an imbalance between the production of toxic reactive oxygen species (ROS) and the cells’ ability to neutralize them with antioxidants.

Mice in the PM2.5 group had lower levels of antioxidant molecules compared with unexposed mice. With berberine pre-treatment, the levels of these markers were similar to healthy controls.

“These experimental results indicate that PM2.5 exposure induces oxidative stress in the lung tissue of mice, while [berberine] pretreatment can counteract the oxidative stress induced by PM2.5,” the researchers wrote.

Berberine also ameliorated active inflammatory processes by reducing the levels of pro-inflammatory immune signaling proteins, including interleukin-6, interleukin 1-beta, and TNF-alpha. Markers of programmed cell death (apoptosis) and the levels of TGF-beta, a key pro-fibrotic molecule, were also reduced with berberine.

The researchers discovered berberine activated the PPAR-gamma pathway, which was suppressed by PM2.5 exposure. Activating PPAR-gamma mitigated oxidative stress and inflammatory-mediated lung injury, the researchers said.

“This study provides confirmation that exposure to PM2.5 leads to lung tissue fibrosis in mice, and [berberine] can activate PPAR-[gamma] to ameliorate PM2.5-induced pulmonary fibrosis,” wrote the researchers, who said the finding offers new paths for developing substances to prevent pulmonary fibrosis induced by PM2.5.