Hydrogen Sulfide: A Versatile Molecule and Therapeutic Target in Health and Diseases

Abstract

In recent years, research has unveiled the significant role of hydrogen sulfide (H₂S) in many physiological and pathological processes. The role of endogenous H₂S, H₂S donors, and inhibitors has been the subject of studies that have aimed to investigate this intriguing molecule. The mechanisms by which H₂S contributes to different diseases, including inflammatory conditions, cardiovascular disease, viral infections, and neurological disorders, are complex. Despite noteworthy progress, several questions remain unanswered. H₂S donors and inhibitors have shown significant therapeutic potential for various diseases. This review summarizes our current understanding of H₂S-based therapeutics in inflammatory conditions, cardiovascular diseases, viral infections, and neurological disorders.

Keywords: H2S donors; H2S inhibitors; cardiovascular diseases; hydrogen sulfide; inflammatory conditions; molecular pathways; neurological disorders; therapeutic applications; viral infections.

Figure 1

An overview of H₂S biosynthesis. This pathway shows the biosynthesis of H₂S. Pyridoxal 5’-phosphate (PLP) acts as a co-factor for Cystathionine β-synthase (CBS) and Cystathionine γ-lyase (CSE) dependent H₂S synthesis.

Figure 2

Endogenous and exogenous H₂S and effects on cells.

Figure 3

Mechanisms of action of H₂S donors in inflammatory diseases. GYY4137 and DADS inhibit NF-κB pathways and activate the Nrf2/ARE pathway, which inhibits pro-inflammatory cytokines and activates antioxidant pathways, respectively. NaHS activates NF-κB and SRF pathways and activates pro-inflammatory mediators. NaHS also activates antioxidant pathways. FW1256 and ACS-15 also suppress the NF-κB pathway and show anti-inflammatory effects.

Figure 4

Role of H₂S donors in CVD. SPRC promotes angiogenesis and decreases myocardial apoptosis in HF and MI. SG1002 maintains vascular hemostasis and decreases oxidative stress in HF and cardiac hypertrophy. GYY4137 decreases oxidative stress, inflammation, myocardial fibrosis, and infarct size in MI. NaHS opens up K_ATP channels and reduces myocardial infarct size and ischemic injury. AP39 attenuates oxidative stress, apoptosis, and mitochondrial damage in cardiotoxicity.

Figure 5

Role of H₂S in viral infections. Controlled production of H₂S provides protection against pulmonary viral infections. Decreased H₂S production exacerbates infection.

Figure 6

Role of H₂S in neurological disorders. Controlled H₂S production helps in the maintenance of mitochondrial function and provides anti-inflammatory effects, whereas increased H₂S production results in mitochondrial dysfunction and damages cellular proteins.