Chinese Herbs and Repurposing Old Drugs as Therapeutic Agents in the Regulation of Oxidative Stress and Inflammation in Pulmonary Diseases

Abstract

Several pro-inflammatory factors and proteins have been characterized that are involved in the pathogenesis of inflammatory diseases, including acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma, induced by oxidative stress, cytokines, bacterial toxins, and viruses. Reactive oxygen species (ROS) act as secondary messengers and are products of normal cellular metabolism. Under physiological conditions, ROS protect cells against oxidative stress through the maintenance of cellular redox homeostasis, which is important for proliferation, viability, cell activation, and organ function. However, overproduction of ROS is most frequently due to excessive stimulation of either the mitochondrial electron transport chain and xanthine oxidase or reduced nicotinamide adenine dinucleotide phosphate (NADPH) by pro-inflammatory cytokines, such as interleukin-1β and tumor necrosis factor α. NADPH oxidase activation and ROS overproduction could further induce numerous inflammatory target proteins that are potentially mediated via Nox/ROS-related transcription factors triggered by various intracellular signaling pathways. Thus, oxidative stress is considered important in pulmonary inflammatory processes. Previous studies have demonstrated that redox signals can induce pulmonary inflammatory diseases. Thus, therapeutic strategies directly targeting oxidative stress may be effective for pulmonary inflammatory diseases. Therefore, drugs with anti-inflammatory and anti-oxidative properties may be beneficial to these diseases. Recent studies have suggested that traditional Chinese medicines, statins, and peroxisome proliferation-activated receptor agonists could modulate inflammation-related signaling processes and may be beneficial for pulmonary inflammatory diseases. In particular, several herbal medicines have attracted attention for the management of pulmonary inflammatory diseases. Therefore, we reviewed the pharmacological effects of these drugs to dissect how they induce host defense mechanisms against oxidative injury to combat pulmonary inflammation. Moreover, the cytotoxicity of oxidative stress and apoptotic cell death can be protected via the induction of HO-1 by these drugs. The main objective of this review is to focus on Chinese herbs and old drugs to develop anti-inflammatory drugs able to induce HO-1 expression for the management of pulmonary inflammatory diseases.

Keywords:

• inflammatory mediators
• tracheal smooth muscle cells
• pulmonary alveolar epithelial cells
• ROS
• Nrf2
• HO-1

Abbreviations

AA, asiatic acid; AFC, alveolar fluid clearance; ALI, acute lung injury; AOR, adjusted odds ratio; AP-1, activator protein 1; APCs, antigen-presenting cells; ARDS, acute respiratory distress syndrome; AREs, antioxidant response elements; CAT, catalase; CDDO, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid; CDDO-Me, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester; CI, confidence interval; CO, carbon monoxide; COPD, chronic obstructive pulmonary disease; COX-2, cyclooxygenase-2; cPLA₂, cytosolic phospholipase A₂; CTGF, connective tissue growth factor; CVD, cardiovascular disease; 15d-PGJ₂, 15-deoxy-D12,14-prostaglandin J₂; ENaC, epithelial sodium channel; EndMT, endothelial-to-mesenchymal transition; E3RSIκB, E3 ubiquitin-ligases; ERKs, extracellular signal-regulated kinases; FBS, fetal bovine serum; fMLP, N-formyl methionyl-leucylphenylalanine; G-CSF, granulocyte colony-stimulating factor; GSH, glutathione; GSTs, glutathione S-transferases; HDM, house dust mite; HO, heme oxygenase; ICAM-1, intercellular adhesion molecule-1; IHD, ischaemic heart disease; IκB, inhibitory κB; IL-1β, interleukin-1β; NLRP3, Nod-like receptor with pyrin domain containing 3; NQO1, NAD(P)H: quinone oxidoreductase 1; JNKs, c-Jun NH2-terminal kinases; Keap1, Kelch-like ECH associated protein 1; KPF, kaempferol; LPS, lipopolysaccharide; LTA, lipotechoic acid; LTB4, leukotriene B4; MAPKs, mitogen-activated protein kinases; MCP-1, monocyte chemoattractant protein-1; MDA, malondialdehyde; MMP, matrix metalloproteinase; NF-κB, nuclear factor-kappaB; NO, nitric oxide; Nox, NADPH oxidase; Nrf2, NF-E2-related factor 2; OA, oleanolic acid; OVA, ovalbumin; PARP, poly(ADP-ribose) polymerase; PPARs, peroxisome proliferator-activated receptors; PKC, protein kinase C; Pris, pristimerin; ROS, reactive oxygen species; Sal, salvianolic acid; SGK1, serum and glucocorticoid-induced kinase-1; SOD, superoxide dismutase; Ssa, saikosaponin A; TAK1, TGF-β-activated kinase 1; TGF, transforming growth factor; TNF-α, tumor necrosis factor-α; TSMCs, tracheal smooth muscle cells; TLR, Toll-like receptor; TZDs, Thiazolidinediones; VCAM-1, vascular cell adhesion molecule-1.

Author contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by the Ministry of Science and Technology, Taiwan [Grant numbers: MOST108-2320-B-039-061, MOST109-2320-B-039-061, MOST109-2813-C-039-029-B, and MOST108-2320-B-182-014]; China Medical University, Taiwan [Grant number: CMU109-MF-09]; Chang Gung Medical Research Foundation, Taiwan [Grant numbers: CMRPG5F0203, CMRPG5J0142, and CMRPG5J0143].

Disclosure

The authors report no conflicts of interest in this work.