Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application
Abstract
:1. Introduction
2. Natural Source of Papaverine
3. Chemistry of Papaverine
4. Biosynthesis of Papaverine
5. Mechanism of Action of Papaverine
6. Pharmacological Properties of Papaverine
6.1. Activity against Erectile Dysfunction (ED)
6.2. Activity against Pulmonary Vasoconstriction
6.3. Postoperative Vasospasm
6.4. Antiviral Properties
6.5. Cardiovascular Activity
6.6. Anti-Inflammatory Activity
6.7. Anticancer Activity
6.8. Neuroprotective Effect
6.9. Gestational Activity
6.10. Other Activities
7. Limitations of the Study
8. Discussion and Future Recommendations
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Molecule | Activity Against | Experimental Approaches | Key Result | Mechanism of Action | Reference |
---|---|---|---|---|---|
Papaverine hydrochloride | HIV | Determination of viral replication by liquid competition radioimmunoassay in H9 cell line and in peripheral blood mononuclear cell (PBMC) culture. |
|
| [58] |
Determination of viral replication in MT4 cell line and in peripheral blood mononuclear cell (PBMC) culture. Examination of T-cell lymphocytes. | Papaverine significantly inhibited HIV replication by more than 99% at doses of 30 μM with an CD50 and ED50 of 32 μM and 5.8 μM, respectively. | The drug might affect cellular DNA synthesis and reverse transcription, indirectly inhibiting HIV replication. | [61] | ||
Papaverine | Measles virus | Determination of viral replication in neural and non-neural cells. Analysis of mechanism for the inhibition of viral replication. | Suppression of virus growth was most prominent in neuroblastoma cells, followed by that in epidermoid carcinoma and glioblastoma cells. |
| [59] |
Papaverine | CMV | Assays for inhibition of infectious CMV yields on human embryo skin-muscle (SM) cells. Assays for the rate of cell DNA synthesis by measuring the incorporation of [methyl3H] thymidine into cell DNA. | Inhibition of the multiplication of CMV. Papaverine was the most potent of the three drugs (papaverine, verapamil and sodium nitroprusside); at a concentration of 30 μg/m (80 μM) the CMV yield was inhibited by 5.21 log10 at 120 hr postinfection (PI). |
| [60] |
Papaverine | Various strains of influenza virus as well as the paramyxoviruses parainfluenza virus 5 (PIV5), human parainfluenza virus 3 (HPIV3), and respiratory syncytial virus (RSV) | Determination of antiviral activity by plaque reduction neutralization test (PRNT). | Dose-dependent inhibition of influenza virus strains. |
| [63] |
Papaverine | SARS-CoV-2 | Cytopathicity assays. | Inhibit SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2, with IC50 value of 1.1 ± 0.39. | Additional studies required. | [64] |
Molecule | Cell Line | Cell Type | Significant Benefit Achieved | Reference |
---|---|---|---|---|
Papaverine | PC-3, DU145, and LNCaP | Prostate cancer | Induced morphologic change and also raised intracellular cyclic AMP levels in LNCaP cells. | [73] |
Papaverine combined with prostaglandin E2 (PGE2) | LNCaP | Prostate cancer | Decreased proliferation and malignancy of LNCaP cells and caused the suppression of the expression of oncogenes such as c-myc and Bcl-2 in differentiated LNCaP cells. | [74] |
Papaverine | PC-3 | Prostate cancer | Showed cytotoxic effects by inducing early and late apoptosis along with inducing sub-G1 cell cycle arrest, and caused the downregulation of Blc-2, Bax, and NF-kB proteins and PI3K and phospho-Akt expression. | [75] |
Papaverine | HT29, T47D, and HT1080 | Colorectal cancer, breast cancer, and fibrosarcoma cells | Showed cytotoxic effects by selective DNA damage and induction of apoptosis. | [76] |
Papaverine | MCF-7 and MDA-MB-231 | Breast cancer | Showed cytotoxic effects by arresting cell cycle in G0/G1 phase and inducing apoptosis. | [77] |
Papaverine | HepG-2 | Hepatocarcinoma | Induced antiproliferative activity by inhibiting telomerase through downregulation of hTERT gene. | [78] |
Papaverine combined with temozolomide | U87MG and T98G | Glioblastoma | Significantly inhibited the clonogenicity of the cell lines, delayed tumor growth, and increased the radiosensitivity of T98G cells. | [80,81] |
Papaverine–Au(III) complex | MCF-7 and HepG-2 | Breast cancer and hepatocellular carcinoma | Showed significant cytotoxic activity against the examined cell lines. Additionally, the Au complex showed anticancer activity against the breast cancer MCF-7 cells better than that of cisplatin. | [16] |
Papaverine | HCT15 (colon), A549 (lung), HeLa (cervical), K562 (Bcr-Abl positive CML), and RAW 264.7 | Colon, lung, cervical, and lymphoblast cancers | Induced ROS-mediated apoptosis and inhibited Bcr-Abl downstream signaling. | [84] |
Caroverine, derivative of papaverine | LT97 and SW480 | Colorectal cancer | Inhibition of expression of VEGF. | [82] |
6a,12a-diazadibenzo-[a,g]fluorenylium, derivative of papaverine | MCF-7 | Breast cancer | Inhibition of MCF-7 cell line by blocking G0/G1 phase of the cell cycle and telomerase activity. | [83] |
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Ashrafi, S.; Alam, S.; Sultana, A.; Raj, A.; Emon, N.U.; Richi, F.T.; Sharmin, T.; Moon, M.; Park, M.N.; Kim, B. Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application. Molecules 2023, 28, 3149. https://doi.org/10.3390/molecules28073149
Ashrafi S, Alam S, Sultana A, Raj A, Emon NU, Richi FT, Sharmin T, Moon M, Park MN, Kim B. Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application. Molecules. 2023; 28(7):3149. https://doi.org/10.3390/molecules28073149
Chicago/Turabian StyleAshrafi, Sania, Safaet Alam, Arifa Sultana, Asef Raj, Nazim Uddin Emon, Fahmida Tasnim Richi, Tasnuva Sharmin, Myunghan Moon, Moon Nyeo Park, and Bonglee Kim. 2023. "Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application" Molecules 28, no. 7: 3149. https://doi.org/10.3390/molecules28073149