Chinese Remedy XBCQ Improved Lung Function in COPD Mice
A Chinese remedy called Xuanbai Chengqi decoction, or XBCQ, used to treat chronic obstructive pulmonary disease (COPD), modulated immune cells, improved lung function, and reduced lung inflammation by potentially changing the gut microbiome of mice with the disease, a study suggested.
“XBCQ could alleviate COPD exacerbations by reshaping the gut microbiota and improving the [immune cell] balance, which aids in elucidating the mechanism through which XBCQ [works] as a therapy for COPD,” the researchers wrote.
The study, “Xuanbai Chengqi Decoction Ameliorates Pulmonary Inflammation via Reshaping Gut Microbiota and Rectifying Th17/Treg Imbalance in a Murine Model of Chronic Obstructive Pulmonary Disease,” by researchers in China, was published in the International Journal of Chronic Obstructive Pulmonary Disease.
COPD is a chronic inflammatory disease of the airways, which become blocked, causing cough with wheezing, mucus production, and shortness of breath.
Increasing evidence suggests that the balance between two types of immune cells — Th17 and T-regulatory (Treg) cells — plays vital roles in developing COPD.
Th17 cells are pro-inflammatory T-cells responsible for producing immune signaling proteins (cytokines) linked to inflammation. Treg cells, in contrast, are a type of regulatory T-cells that help maintain immune balance by releasing cytokines that suppress inflammatory responses.
People who smoke cigarettes — smoking is the leading cause of COPD — have fewer Treg cells and lower levels of anti-inflammatory cytokines. Further, the Th17/Treg imbalance worsens lung inflammation in COPD mouse models exposed to cigarette smoke extract.
In addition, an imbalance in gut microbes (microbiome) is thought to be connected with immune system impairment and an increased risk of infections. Recent studies suggest that the gut microbiome and resident metabolites of COPD patients are significantly different from those of healthy people.
Researchers at the Beijing University of Chinese Medicine, in China, have proposed that the interaction between the gut microbiome and Th17/Treg balance may further regulate the development and worsening of COPD.
XBCQ, a mixture of naturally occurring substances, has been used in China to treat various lung diseases, including COPD. The remedy consists of rhubarb, gypsum, apricot seed, and the rind of trichosanthes, a subtropical vine that belongs to the cucumber family.
A compound found in apricot seeds, called amygdalin, has suppressed COPD disease activity in mouse models. However, the underlying mechanism by which XBCQ suppresses lung inflammation remains poorly understood.
Now, the team of researchers conducted experiments to determine the effect of Th17/Treg balance in COPD patients, investigate the impact of XBCQ in a COPD mouse model, and understand the role of the gut microbiome and Th17/Treg balance.
First, the team measured the levels of Th17 and Treg cells in 15 COPD patients with an average age of 72.3 and a body mass index or BMI (a body fat measure) of 26.4. A normal BMI for adults is 18.5 to 24.9; those with a BMI of 25 to 29.9 — which would include these patients — are deemed overweight. Among the participants, 12 had a history of smoking.
The results were compared with those of 10 healthy individuals (controls) without a smoking history. These 10 people had an average age of 47.2 and a body mass index of 21.4, considered a healthy weight.
Compared with the healthy controls, the COPD patients had significantly higher levels of Th17 cells and a lower proportion of Treg cells. Overall, the Th17/Treg ratio was increased in the COPD group, which “suggested the important role of the Th17/Treg imbalance during the COPD exacerbations,” the team wrote.
Next, researchers induced COPD in mice by exposing animals to cigarette smoke extract (CSE) along with a pro-inflammatory molecule called LPS. Compared with unexposed control mice, CSE and LPS significantly and persistently lowered the animals’ body weight.
Treatment with a low- and medium-dose of XBCQ significantly reduced weight loss. No significant changes were observed with high doses of XBCQ.
The medium dose of XBCQ significantly improved the lung function of COPD mice compared with untreated mice. These findings were similar to mice treated with the anti-inflammatory corticosteroid medication dexamethasone. Additionally, lung tissue analysis showed XBCQ treatment reduced the levels of immune cells in the airways, mucus layers, and alveoli, which are tiny lung air sacs.
“These outcomes suggested that XBCQ treatments, especially [medium-dose] XBCQ, improved the lung function of CSE and LPS-induced COPD mice,” the researchers wrote.
The expression, or production, of pro-inflammatory biomarkers — TNF-alpha, interleukin-1-beta, and MMP-9 — were enhanced in the lung tissues of COPD mice, while XBCQ and dexamethasone treatments significantly suppressed these increases.
Cell analysis was then conducted to assess the distribution of Th17 and Treg cells in the lungs and colon of COPD mice. Th17 cells and related cytokines were significantly enriched in the lungs and colon of COPD mice, whereas Treg cells were markedly decreased. XBCQ treatments restored the balance of Th17 and Treg cells in COPD mice by suppressing the accumulation of Th17 cells and correcting Treg cells deficiency.
“These data suggested that [XBCQ] administration served as an effective damper on the Th17/Treg imbalance in the lung and colon of COPD mice,” the scientists wrote.
The team then examined the impact of XBCQ treatment on gut microbiota composition. The colon of COPD mice had less microbial diversity than controls, whereas XBCQ administration triggered an increasing trend in this diversity. Overall, there were differences in the gut microbe composition of the healthy control mice, the COPD mice, and the COPD mice treated with XBCQ.
Experiments to identify specific microbes found some bacteria were enriched, while others were less abundant in the colon of COPD mice than in the control group. Bacteria that were less abundant in COPD versus controls were significantly enriched with XBCQ treatment. However, XBCQ also suppressed the accumulation of some bacteria.
“These results showed an imbalanced state of the gut microbiota in COPD mice and the [XBCQ] administration had the potential to ameliorate this gut dysbiosis to a certain extent,” the investigators wrote. Of note, dysbiosis is a reduction in microbial diversity and a combination of the loss of beneficial bacteria.
Finally, researchers found significant correlations between gut microbiota and lung inflammatory responses, as well as the Th17/Treg ratio and pro-inflammatory cytokines in the lung. These findings suggested that “changes in the lung inflammatory status of COPD mice might be partly modulated by their intestinal microbiota.”
“Collectively, our investigation provides novel insights for elucidating the mechanism by which XBCQ [works] as a therapy for COPD in a microbiota-dependent manner via the gut-lung axis,” the scientists wrote.
“Future studies will focus on identifying the main active components in XBCQ decoction and uncover specific microbial biomarkers and their derived metabolites affecting the immune responses in the process of COPD,” they added.