ArticlePublisher preview availableLiterature Review

Pharmacotherapeutic Strategies for Fine Particulate Matter-Induced Lung and Cardiovascular Damage: Marketed Drugs, Traditional Chinese Medicine, and Biological Agents

Authors:
Shuiqing Qu
Shuiqing Qu
Shuiqing Qu
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Yan Liang
Yan Liang
Yan Liang
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Shuoqiu Deng
Shuoqiu Deng
Shuoqiu Deng
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Yu Li
Yu Li
Yu Li
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Show all 8 authorsHide
Read publisher preview
Download citation
To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

Fine particulate matter (PM2.5), defined as airborne particles with a diameter of ≤ 2.5 μm, represents a major constituent of air pollution and has been globally implicated in exacerbating public health burdens by elevating morbidity and mortality rates associated with respiratory and cardiovascular diseases (CVDs). Adverse health effects of PM2.5 exposure manifest across diverse susceptibility profiles and durations of exposure, spanning both acute and chronic timelines. While prior reviews have predominantly focused on elucidating the toxicological mechanisms underlying PM2.5-induced pathologies, there remains a paucity of comprehensive summaries addressing therapeutic interventions for cardiopulmonary damage. This review systematically synthesizes pharmacological agents with potential therapeutic efficacy against PM2.5-induced pulmonary and cardiovascular injury. By integrating mechanistic insights with translational perspectives, this work aims to provide a foundational framework for advancing research into novel therapeutic strategies targeting PM2.5-associated cardiopulmonary disorders. Graphical Abstract
Figures - available from: Cardiovascular Toxicology
This content is subject to copyright. Terms and conditions apply.
A preview of this full-text is provided by Springer Nature.
Learn more
Content available from Cardiovascular Toxicology
This content is subject to copyright. Terms and conditions apply.
Vol:.(1234567890)
Cardiovascular Toxicology (2025) 25:666–691
https://doi.org/10.1007/s12012-025-09985-3
REVIEW
Pharmacotherapeutic Strategies forFine Particulate Matter‑Induced
Lung andCardiovascular Damage: Marketed Drugs, Traditional
Chinese Medicine, andBiological Agents
ShuiqingQu1,3· YanLiang1· ShuoqiuDeng1· YuLi1· YuanminYang1· TuoLiu1,2· LinaChen1,2· YujieLi1
Received: 27 January 2025 / Accepted: 10 March 2025 / Published online: 20 March 2025
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025
Abstract
Fine particulate matter (PM2.5), defined as airborne particles with a diameter of ≤ 2.5μm, represents a major constituent of
air pollution and has been globally implicated in exacerbating public health burdens by elevating morbidity and mortality
rates associated with respiratory and cardiovascular diseases (CVDs). Adverse health effects of PM2.5 exposure manifest
across diverse susceptibility profiles and durations of exposure, spanning both acute and chronic timelines. While prior
reviews have predominantly focused on elucidating the toxicological mechanisms underlying PM2.5-induced pathologies,
there remains a paucity of comprehensive summaries addressing therapeutic interventions for cardiopulmonary damage.
This review systematically synthesizes pharmacological agents with potential therapeutic efficacy against PM2.5-induced
pulmonary and cardiovascular injury. By integrating mechanistic insights with translational perspectives, this work aims
to provide a foundational framework for advancing research into novel therapeutic strategies targeting PM2.5-associated
cardiopulmonary disorders.
Graphical Abstract
Keywords Air pollution· Fine particulate matter· Pulmonary injury· Cardiovascular injury· Medical therapy
Abbreviations
BEAS-2B Human alveolar epithelial cells
CVD Cardiovascular disease
COPD Chronic obstructive pulmonary disease
DEP Diesel exhaust particle
Shuiqing Qu and Yan Liang contributed equally to this work.
Extended author information available on the last page of the article
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Amygdalin prevents multidrug-resistant Staphylococcus aureus-induced lung epithelial cell injury by regulating inflammation and oxidative stress
Article
Full-text available
Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that can cause severe bacterial pneumonia. Amygdalin is the main active pharmaceutical ingredient of bitter almond, which has broad-spectrum antibacterial, anti-inflammatory, anti-oxidation and immunomodulatory effects. It is also the main ingredient of Yinhua Pinggan granule, which is commonly used to moisten the lung and relieve cough. However, little is known about the effects of amygdalin on MRSA. In this study, we found that amygdalin exhibited good antimicrobial activity in vitro against MRSA. Amygdalin has a protective effect on MRSA infected cells, and the effect is better when combined with levofloxacin. It also can reduce the adhesion and invasion of MRSA to cells. Amygdalin has anti-inflammatory and antioxidant effects, which can significantly reduce the increase of inflammatory factors and the production of ROS caused by infection. The protective mechanism of amygdalin on cells may be related to inhibiting the expression of NLRP3, ASC and IL-1β pyroptosis pathways. Taken together, our study suggests that amygdalin exerts antibacterial effects by affecting biofilm formation, the expression of virulence factors, and drug resistance genes. Amygdalin combined with levofloxacin has a protective effect on A549 cells infected with MRSA, and the mechanism may be related to the inhibition of inflammatory response, oxidative damage and pyroptosis.
View
Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021
Article
Full-text available
  • May 2024
  • LANCET
Background Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. Funding Bill & Melinda Gates Foundation.
View
Protective Effect of Lonicera japonica on PM2.5-Induced Pulmonary Damage in BALB/c Mice via the TGF-β and NF-κB Pathway
Article
Full-text available
  • Apr 2023
This study aimed to assess the protective effect of an extract of Lonicera japonica against particulate-matter (PM)2.5-induced pulmonary inflammation and fibrosis. The compounds with physiological activity were identified as shanzhiside, secologanoside, loganic acid, chlorogenic acid, secologanic acid, secoxyloganin, quercetin pentoside, and dicaffeoyl quinic acids (DCQA), including 3,4-DCQA, 3,5-DCQA, 4,5-DCQA, and 1,4-DCQA using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). The extract of Lonicera japonica reduced cell death, reactive oxygen species (ROS) production, and inflammation in A549 cells. The extract of Lonicera japonica decreased serum T cells, including CD4⁺ T cells, CD8⁺ T cells, and total T helper 2 (Th2) cells, and immunoglobulins, including immunoglobulin G (IgG) and immunoglobulin E (IgE), in PM2.5-induced BALB/c mice. The extract of Lonicera japonica protected the pulmonary antioxidant system by regulating superoxide dismutase (SOD) activity, reduced glutathione (GSH) contents, and malondialdehyde (MDA) levels. In addition, it ameliorated mitochondrial function by regulating the production of ROS, mitochondrial membrane potential (MMP), and ATP contents. Moreover, the extract of Lonicera japonica exhibited a protective activity of apoptosis, fibrosis, and matrix metalloproteinases (MMPs) via TGF-β and NF-κB signaling pathways in lung tissues. This study suggests that the extract of Lonicera japonica might be a potential material to improve PM2.5-induced pulmonary inflammation, apoptosis, and fibrosis.
View
View
View
View
Ephedrae herba: A comprehensive review of its traditional uses, phytochemistry, pharmacology, and toxicology
Article
  • Jan 2023
  • J ETHNOPHARMACOL
Ethnopharmacological relevance: Ephedrae herba (called Mahuang in China) is the dried herbaceous stem of Ephedra sinica Stapf, Ephedra intermedia Schrenk et C. A. Mey., and Ephedra equisetina Bge. Ephedrae herba has a long history of use as an herb, and it was originally recorded in Sheng Nong's herbal classic. Ephedrae herba has also been widely used as both medicine and food. In the clinic, Ephedrae herba is commonly used for treating colds, bronchial asthma, nasal congestion, and other diseases. Aim of review: This review aims to provide a systematic summary on the traditional use, chemical constituents, pharmacological effects, clinical applications, quality control, toxicology, and pharmacokinetics of Ephedrae herba to provide a theoretical basis for further reasonable development of Ephedrae herba in clinical practice and creation of new drugs. Materials and methods: Information on Ephedrae herba was gathered from various sources, including the scientific databases including CNKI, PubMed, SciFinder and ScienceDirect, classical books on traditional Chinese herbal medicine, Ph.D. and M.Sc. dissertations; Baidu Scholar; and from different professional websites. Results: Ephedrae herba is distributed in regions of China and other areas. Ephedra and its compound preparations can be used for colds, bronchial asthma, nasal congestion and other diseases. Approximately 281 chemical constituents have been isolated from Ephedrae herba, including alkaloids, flavonoids, tannins, polysaccharides, volatile oils, organic acids, and other compounds. Among these constituents, alkaloids and volatile oils are the most abundant and represent the major bioactive constituents. Ephedrae herba possesses multiple pharmacological activities, including diuretic effect, anti-allergic effect, blood pressure regulatory, anti-inflammatory effect, anti-oxidation effect and anti-viral effects. Ephedrine hydrochloride and pseudoephedrine hydrochloride are generally selected as indicators for the quantitative determination of Ephedrae herba. The maximum dosage of Ephedrae herba should not exceed 10 grams. If overused, adverse reactions such as palpitations, sweating, irritability and insomnia will occur. Conclusions: Ephedrae herba is an ancient herbal medicine with a broad spectrum of pharmacological activities that has been used for thousands of years in China. It is one of the most commonly used herbal components of the TCM formulas. Hydrochloride and pseudoephedrine are the major bioactive constituents. However, there is a need to further understand the mechanisms of active components of Ephedrae herba. Future studies should perform an in-depth analyses of the pharmacokinetics and mechanisms of toxicity of Ephedrae herba. Quality standards should be developed to correspond to the various application methods to ensure the efficacy of drugs in actual treatment.
View
Modelling patient specific cardiopulmonary interactions
Article
  • Oct 2022
  • COMPUT BIOL MED
Mechanical ventilation is well known for having detrimental effects on the cardiovascular system, particularly when using high positive end-expiratory pressure. High positive end-expiratory pressure levels cause a decrease in stroke volume, which, under normal conditions, usually bring about a decrease in stressed blood volume. Stressed blood volume, defined as the total pressure generating volume of the cardiovascular system, has been shown to be a potential index of fluid responsiveness, making it a potentially important diagnostic tool. Generally, respiratory and haemodynamic care are provided independently of one another. However, that positive end-expiratory pressure alters both stroke volume and stressed blood volume suggests both the pulmonary and cardiovascular state should be conjointly optimised and used to guide positive end-expiratory pressure. However, the complex and patient-specific nature of cardiopulmonary interactions which occur during mechanical ventilation presents a challenge for accurate modelling of respiratory and cardiovascular interactions required to better optimise care. Previous models attempting to incorporate cardiopulmonary interactions have suffered from poor reliability at higher PEEP levels, largely due to an exaggerated effect of intrathoracic pressure on the cardiovascular system. A new parameter, alpha, is added to a previously validated cardiopulmonary model, to modulate the percentage of intrathoracic pressure applied to the vena cava and left ventricle. The new parameter aims to increase reliability under high PEEP conditions as well as provide a patient specific solution to modelling cardiopulmonary interactions. The results from the identified optimal alpha are compared to the original model to investigate how this new parameter may be used to create a more patient-specific cardiopulmonary model, which would be better suited for guidance of care in the ICU.
View
Long-term exposure to PM2.5 aggravates pulmonary fibrosis and acute lung injury by disrupting Nrf2-mediated antioxidant function
Article
  • Aug 2022
  • ENVIRON POLLUT
Epidemiological studies have indicated that exposure to ambient air-borne fine particulate matter (PM2.5) is associated with many cardiopulmonary diseases; however, the underlying pathological mechanisms of PM2.5-induced lung injury remain unknown. In this study, we aimed to assess the impact of acute or prolonged exposure to water-insoluble fractions of PM2.5 (PM2.5 particulate) on lung injury and its molecular mechanisms. Balb/c mice were randomly exposed to PM2.5 once (acute exposure) or once every three days for a total of 6 times (prolonged exposure). Lung, BALF and blood samples were collected, and pulmonary pathophysiological alterations were analyzed. Nrf2 knockout mice were adapted to assess the involvement of Nrf2 in lung injury, and transcriptomic analysis was performed to delineate the mechanisms. Through transcriptomic analysis and validation of Nrf2 knockout mice, we found that acute exposure to PM2.5 insoluble particulates induced neutrophil infiltration-mediated airway inflammation, whereas prolonged exposure to PM2.5 insoluble particulate triggered lung fibrosis by decreasing the transcriptional activity of Nrf2, which resulted in the downregulated expression of antioxidant-related genes. In response to secondary LPS exposure, prolonged PM2.5 exposure induced more severe lung injury, indicating that prolonged PM2.5 exposure induced Nrf2 inhibition weakened its antioxidative defense capacity against oxidative stress injury, leading to the formation of pulmonary fibrosis and increasing its susceptibility to secondary bacterial infection.
View
Estimates, trends, and drivers of the global burden of type 2 diabetes attributable to PM 2·5 air pollution, 1990-2019: an analysis of data from the Global Burden of Disease Study 2019
Article
  • Jul 2022
Background: Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2·5 originating from ambient and household air pollution. Methods: We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2·5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure-response curve from the extracted relative risk estimates using the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2·5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2·5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals. Findings: In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2·5 exposure, with an estimated 3·78 (95% uncertainty interval 2·68-4·83) deaths per 100 000 population and 167 (117-223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13·4% (9·49-17·5) of deaths and 13·6% (9·73-17·9) of DALYs due to type 2 diabetes were contributed by ambient PM2·5, and 6·50% (4·22-9·53) of deaths and 5·92% (3·81-8·64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2·5. Interpretation: Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2·5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes.
View