Natural Bioactives: Back to the Future in the Fight against Human Papillomavirus? A Narrative Review

Massa, Silvia; Pagliarello, Riccardo; Paolini, Francesca; Venuti, Aldo

doi:10.3390/jcm11051465

Cited by 5 publications

(8 citation statements)

References 227 publications

(235 reference statements)

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“…The therapeutic approaches employed in the treatment of HPV-related cancers, such as surgery, chemo- and radiotherapy are considered insufficient [ 45 ]. Evidence from experimental studies elucidating the possible protective effects of ellagic acid are persuasive [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

The Use of Ellagic Acid and Annona Muricata Improves Semen Quality in Men with High-Risk Papillomavirus Infection

Vignera

Basile

Aversa

et al. 2022

JCM

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Background: Few data are currently available on the treatment of patients with HPV infection. In particular, there is no agreement on the use of antioxidants in these patients. Ellagic acid and annona muricata appear to improve HPV clearance in infected women. However, it is presently unknown whether they could enhance the clearance of HPV infection in infertile male patients. Aim: To evaluate the effects of a commercially available combined compound containing ellagic acid and annona muricata on semen quality in patients with documented papillomavirus (HPV) infection, and on the frequency of HPV DNA detection in seminal fluid after treatment. In addition, anti-sperm antibodies and the percentage of spermatozoa with fragmented DNA were evaluated. Materials and methods: This was a retrospective case-control study including patients attending our center for infertility. Fifty selected patients who were positive for high risk (HR)-HPV with available semen analysis results were consecutively enrolled. Patients were classified into two groups, according to the clinician’s decision to either administer ellagic acid 100 mg and annona muricata 100 mg (combined tablet formulation) for a period of three months (Group A; 25 patients), or to re-evaluate HPV DNA after a period of active surveillance only (protected sexual intercourse) (Group B; 25 patients). Results: Group A patients had a mean age of 31.0 ± 11.0 years, while Group B was 33.0 ± 8.0 years old (p > 0.05). After three months of treatment with ellagic acid and annona muricata, all conventional seminal parameters improved more significantly in Group A than in Group B patients: sperm concentration = 45 mil/mL vs. 20 mil/mL (p < 0.05); sperm progressive motility = 45% vs. 18% (p < 0.05); and normal sperm morphology = 18% vs. 6% (p < 0.05). After the treatment, the frequency of persistence of HPV DNA in the seminal fluid was significantly lower in Group A patients compared to those in Group B (12/25 = 48% vs. 22/25 = 88%; p < 0.05). Finally, after 3 months, Group A showed a significant reduction in anti-sperm antibodies and in the percentage of spermatozoa with fragmented DNA. Conclusion: The results of this study demonstrate, for the first time, the effects of a commercially available combined compound containing ellagic acid and annona muricata on semen quality in patients with HR-HPV infection, and that this therapy is also associated with a significant reduction in the persistence of HPV DNA in the seminal fluid.

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Section: Discussionmentioning

confidence: 99%

The Use of Ellagic Acid and Annona Muricata Improves Semen Quality in Men with High-Risk Papillomavirus Infection

Vignera

Basile

Aversa

et al. 2022

JCM

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“…In addition, flavonoids have the advantage of being less toxic and can be prescribed for an extended duration. Therefore, various plant-derived flavonoids use as drugs have been reported as a modulator for chronic inflammation caused by virus infection and other diseases, such as human papillomavirus [ 13 , 14 ], hepatitis virus [ 15 ], SARS-CoV-2 [ 16 , 17 ], autoimmune disease [ 18 , 19 ], type 2 diabetes [ 20 , 21 ], cardiovascular diseases [ 22 ], Alzheimer’s disease [ 23 ], Parkinson’s disease [ 24 ], and cancer [ 25 ]. The therapeutic effect of these flavonoids and polyphenols is to inhibit the function of the enzymes as ligands that attach to the specific sites of the enzymes.…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory, Antioxidative, and Nitric Oxide-Scavenging Activities of a Quercetin Nanosuspension with Polyethylene Glycol in LPS-Induced RAW 264.7 Macrophages

et al. 2022

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Quercetin (Qu) is a dietary antioxidant and a member of flavonoids in the plant polyphenol family. Qu has a high ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) molecules; hence, exhibiting beneficial effects in preventing obesity, diabetes, cancer, cardiovascular diseases, and inflammation. However, quercetin has low bioavailability due to poor water solubility, low absorption, and rapid excretion from the body. To address these issues, the usage of Qu nanosuspensions can improve physical stability, solubility, and pharmacokinetics. Therefore, we developed a Qu and polyethylene glycol nanosuspension (Qu-PEG NS) and confirmed its interaction by Fourier transform infrared analysis. Qu-PEG NS did not show cytotoxicity to HaCaT and RAW 264.7 cells. Furthermore, Qu-PEG NS effectively reduced the nitrogen oxide (NO) production in lipopolysaccharide (LPS)-induced inflammatory RAW 264.7 cells. Additionally, Qu-PEG NS effectively lowered the levels of COX-2, NF-κB p65, and IL-1β in the LPS-induced inflammatory RAW 264.7 cells. Specifically, Qu-PEG NS exhibited anti-inflammatory properties by scavenging the ROS and RNS and mediated the inhibition of NF-κB signaling pathways. In addition, Qu-PEG NS had a high antioxidant effect and antibacterial activity against Escherichia coli and Bacillus cereus. Therefore, the developed novel nanosuspension showed comparable antioxidant, anti-inflammatory, and antibacterial functions and may also improve solubility and physical stability compared to raw quercetin.

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“…Kerra TM comprises of nine medicinal plants, in which some of their phytochemicals have been studied to have anti-inflammatory and anticancer properties [11]. These phytochemicals affect various signaling pathways, including anti-inflammation, cell proliferation, and apoptosis [8,10,[37][38][39][40][41][42]. For example, the heartwood of P. santalinus L.f. contains various bioactive compounds, e.g., pterostilbene, which has been shown to be potent against cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Swingle such as limonoids, phenolic acids (gallic acid and ferulic acid), and flavones (hesperetin and naringenin) have been shown to be anti-cervical cancer agents through various pathways. [10,41,42]. Ferulic acid has been shown to inhibit HeLa and CaSki cell proliferation and invasion via under-expression of MMP-9 mRNA, induction of G0/G1 cell arrest, as well as the inhibition of autophagy [42].…”

Section: Discussionmentioning

confidence: 99%

“…[10,41,42]. Ferulic acid has been shown to inhibit HeLa and CaSki cell proliferation and invasion via under-expression of MMP-9 mRNA, induction of G0/G1 cell arrest, as well as the inhibition of autophagy [42]. For limonoids, though there is no evidence of anti-cervical cancer properties, it has been shown to inhibit colon, stomach, and breast cancers by inhibiting cell proliferation and caspase-mediated apoptosis [10,42].…”

Section: Discussionmentioning

confidence: 99%

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The Inhibitory Effect of KerraTM, KSTM, and MinozaTM on Human Papillomavirus Infection and Cervical Cancer

Choowongkomon,

Choengpanya,

Pientong

et al. 2023

Medicina

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Background and Objectives: Cervical cancer is one of the most common types of frequently found cancers in Thailand. One of the causative agents is the infection of the high-risk human papillomavirus (HPV) type 16 and 18. Traditional medicines are rich sources of bioactive compounds which are a valuable source for the development of novel cancer therapies. In this study, the therapeutic effects of 3 traditional medicines, KerraTM, KSTM, and MinozaTM, were studied on HeLa and CaSki cells. Materials and Methods: The effects of KerraTM, KSTM, and MinozaTM on cancer cells were evaluated through cytotoxicity and cell death assays. The infection assay using HPV-16 pseudovirus was also carried out. Results: All traditional medicines efficiently suppressed cell growths of HeLa and CaSki, with KerraTM being the most potent anticancer agent followed by KSTM and MinozaTM. KerraTM at 158 µg/mL and 261 µg/mL significantly increases the percentage inhibition of the HPV-16 pseudovirus infection in a pre-attachment step in a dose-dependent manner, while KSTM at 261 µg/mL efficiently inhibited viral infection in both pre-attachment and adsorption steps. However, KerraTM, KSTM, and MinozaTM at subtoxic concentrations could not reduce the viral E6 mRNA expressions of HPV-16 and HPV-18. Cell death assay by acridine orange/ethidium bromide showed that KerraTM increased population of dead cells in dose-dependent manner in both CaSki and HeLa. The percentage of secondary necrosis in KerraTM-treated CaSki was higher than that of HeLa cells, while the percentage of late apoptotic cells in HeLa was higher than that of CaSki, indicating that HeLa was more susceptible to KerraTM than CaSki. For KSTM and MinozaTM, these extracts at 250 µg/mL promoted autophagy over cell death. At 500 µg/mL, the percentage of dead cells in KerraTM was higher than that of KSTM and MinozaTM. Conclusions: KerraTM is a potent traditional medicine for promoting cancer cell death. KerraTM is possibly useful in the prevention and treatment of cervical cancer. Further investigation will be carried out to gain a better understanding of the biochemical mechanism and the pharmacological activity underlying this effect.

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Natural Bioactives: Back to the Future in the Fight against Human Papillomavirus? A Narrative Review

Cited by 5 publications

References 227 publications

The Use of Ellagic Acid and Annona Muricata Improves Semen Quality in Men with High-Risk Papillomavirus Infection

The Use of Ellagic Acid and Annona Muricata Improves Semen Quality in Men with High-Risk Papillomavirus Infection

Anti-Inflammatory, Antioxidative, and Nitric Oxide-Scavenging Activities of a Quercetin Nanosuspension with Polyethylene Glycol in LPS-Induced RAW 264.7 Macrophages

The Inhibitory Effect of KerraTM, KSTM, and MinozaTM on Human Papillomavirus Infection and Cervical Cancer

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