TABLE 1.
Recent studies on inosine effects across various diseases.
| Disease | Subject | Intervention | Effect | Mechanism | References |
|---|---|---|---|---|---|
| Cancers | |||||
| Cervical cancer | HPV-positive patients after cervical conization | Inosine pranobex | Reduce relapse of HSIL and high-risk HPV infection | Clear cervical HPV infection | Kovachev, (2020) |
| Colon cancer, bladder cancer, and melanoma | Mice with xenograft or chemical-induced tumor | Inosine | Augment immune checkpoint inhibitor efficacy | Promote Th1 immunity through activating adenosine 2A receptor | Mager et al. (2020) |
| Liver cancer | HepG2 cells | Inosine pranobex | Cytotoxic effect | Mitochodrial damage | Tobólska et al. (2018) |
| Melanoma | Mice with xenograft tumor | Inosine | Enhance immunotherapy efficacy | Support proliferation and function of effector T cells | Wang et al. (2020) |
| Cardiovascular diseases | |||||
| Atherosclerosis | Rats with hypercholesterolemic diet | Inosine | Alleviate atherogenic index and platelet aggregation | Activate eNOS and inhibit the NF-κB pathway | Lima et al. (2020) |
| Mitochondrial disease | Mt-cardiomyopathy and mt-diabetes patients | Inosine plus febuxostat | Decrease BNP and increase insulinogenic index | Enhance cellular ATP levels | Kamatani et al. (2019) |
| Infectious diseases | |||||
| Acute respiratory viral infection | Laboratory-confirmed viral infection patients with ILI | Insoine pranobex | Reduce time to symptom resolution | Control viral infection | Beran et al. (2016) |
| COVID-19 | SARS-CoV-2-positive patients | Inosine pranobex | Reduce case-fatality rate | Control viral infection | Beran et al. (2020) |
| Influenza | Influenza A (H3N2)-infected mice | Inosine pranobex | Extend survival time with oseltamivir and ellagic acid | Protect from damaging superoxide radicals | Pavlova et al. (2018) |
| NTM pulmonary disease | NTM-infected mice | Inosine | Decrease bacterial loads in lungs | Enhance IFN-γ-related responses | Kim et al. (2022) |
| Inflammatory disease | |||||
| Acute hepatic injury | LPS-injected mice | Inosine | Suppress inflammatory cytokines and conserve liver function | Alter the microflora composition and attenuate the TLR4 pathway | Guo et al. (2021) |
| Alcoholic liver disease | Mice with alcohol-induced liver injury | Inosine plus LGG | Improve the liver structure and function | Suppress oxidative stress and attenuate inflammatory cytokine expression | Zhu et al. (2022) |
| IPEX syndrome | Scurfy mouse | Inosine | Prolong lifespan and reduce multiorgan inflammation | Inhibit Th1 and Th2 cell differentiation through adenosine A2 receptor | He et al. (2017) |
| NSAID-induced enteropathy | Mice with indomethacin-induced enteropathy | Inosinic acid plus pottasium oxonate | Conserve intestinal structure | Remove ROS through serum uric acid accumulation | Yasutake et al. (2017) |
| Sepsis | LPS-injected mice | Inosine monophosphate | Decrease TNF-α and increase IL-10 | Augment inosine produced by ecto-5′-nucleotidase | Lovászi et al. (2021) |
| Systemic lupus erythematosus | LPS-treated human monocytes | Inosine | Inhibit autophagy and IFN-β release | Increase phosphorylated S6 and decrease phosphorylated IRF3 | Wu et al. (2022) |
| Ulcerative colitis | Mice with DSS-induced colitis | Inosine | Protect intestinal function | Activate adenosine A2 receptor/PPAR-γ axis | Li et al. (2021b) |
| Neuropsychological disease | |||||
| Alzheimer’s disease | Rats with streptozotocin-induced Alzheimer’s disease | Inosine | Prevent memory deficits and weight loss | Increase BDNF and anti-inflammatory cytokines | Teixeira et al. (2022a) |
| Alzheimer’s disease | Rats with streptozotocin-induced Alzheimer’s disease | Inosine | Attenuate memory loss | Modulate the ion pump activities and clear the oxidative stress | Teixeira et al. (2020) |
| Alzheimer’s disease | Rats with scopolamine-induced cognitive impairment | Inosine | Protect from memory consolidation impairment | Modulate the ion pump and AchE activities and reduce the oxidative stress | Teixeira et al. (2022b) |
| Bipolar disorder | Rats with ketamine-induce mania | Inosine | Prevent hyperlocomotion behavior | Need to elucidate, not associated with adenosine receptor | Camerini et al. (2020) |
| CNS injury | Rat with unilateral CST transection | Contralateral inosine minipump | Stimulate axon collateral growths | Induce axon sprouting and crossing | Benowitz et al. (1999) |
| CNS injury | Rat with spinal cord compression | Inosine | Improve recovery of motor and urinary function | Increase axonal ramification | Kuricova et al. (2014) |
| Cognitive dysfunction | Aged female rats | Inosine | Elevate learning and memory function | Conserve hippocampal CA1 region with anti-inflammatory and antioxidant effect | Ruhal and Dhingra, (2018) |
| Diabetic peripheral neuropathy | Rats with streptozotocin and nicotinamide induced diabetes | Inosine | Recover the structure and function of the sciatic nerve | Reduce blood glucose level and oxidative stress | Abdelkader et al. (2022) |
| Huntington’s disease | Rats with 3-NP-induced neurotoxicity | Inosine | Mitigate the disease symptoms | Activate adenosine A2 receptor/BDNF/ERK axis | El-Shamarka et al. (2022) |
| Methamphetamine withdrawal syndrome | Methamphetamine-treated mice | Inosine | Restore the anxiety and depression-like behavior | Potential neuroprotective function | Yang et al. (2022) |
| Multiple system atrophy | Multiple system atrophy patients | Inosine monophosphate | Improve cognitive function | Increase serum uric acid | Jung Lee et al. (2021) |
| Parkinson’s disease | Early Parkinson’s disease patients | Inosine | Mitigate the disease progression | Increase cerebrospinal fluid urate | Schwarzschild et al. (2014) |
| Parkinson’s disease | Parkinson’s disease patients | Inosine plus febuxostat | Improve disease symptoms | Increase blood hypoxanthine and xanthine but decrease uric acid | Watanabe et al. (2020) |
| Parkinson’s disease | Early Parkinson’s disease patients | Inosine | No significant difference in the disease progression | — | Schwarzschild et al. (2021) |
| PNS injury | Mice with sciatic nerve crush | Inosine | Accelerate axonal regeneration and functional recovery | Reduce the number of macrophages and myelin ovoids | Soares Dos Santos Cardoso et al. (2019) |
Abbreviation: 3-NP, 3-nitropropionic acid; AChE, acetylcholinesterase; ATP, adenosine triphosphate; BDNF, brain-derived neurotrophic factor; BNP, brain natriuretic peptide; CNS, central nervous system; CST, corticospinal tract; DSS, dextran sulfate sodium; eNOS, endothelial nitric oxide synthase; ERK, extracellular signal-regulated kinase; HSIL, high-grade squamous intraepithelial lesion; HPV, human papilloma virus; IFN, interferon; IL, interleukin; ILI, influenza-like illnesses; IPEX syndrome, immune dysregulation, polyendocrinopathy, and enteropathy, with X-linked inheritance; IRF3, interferon regulatory factor 3; LGG, Lactobacillus rhamnosus GG; LPS, lipopolysaccharide; Mt, mitochondria; NF-κB, nuclear factor-κB; NSAID, nonsteroidal anti-inflammatory drug; NTM, nontuberculous mycobacteria; PNS, peripheral nervous system; PPAR, peroxisome proliferator-acitvated receptor; ROS, reactive oxygen species; TLR4, toll-like receptor 4; TNF, tumor necrosis factor.