Herbal Gel Formulation Developed for Anti-Human Immunodeficiency Virus (HIV)-1 Activity Also Inhibits In Vitro HSV-2 Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plant Materials
2.2. Preparation of Plants 50% Aqueous Ethanolic Extracts
2.3. Preparation of Gel Formulation
2.4. High Performance Liquid Chromatography Analysis
2.5. Cells and Viruses
2.6. Cytotoxicity Assay
2.7. Anti-viral Activity of the Gel Formulation
2.7.1. Anti-HIV-1 Activity of the Gel Formulation
2.7.2. Anti-HSV-2 Activity of the Gel Formulation
HSV-2 Virucidal Assay
HSV-2 Attachment and Penetration Assay
Post-infection anti-HSV-2 Activity of Gel Formulation
2.8. Safety Studies of Gel Formulation
2.8.1. Cytotoxicity of Gel Formulation on Lactobacilli
2.8.2. Epithelial Layer Integrity Resistance Assay
2.8.3. Pro-inflammatory Cytokines Assay
2.8.4. Mutagenic Effect of the Gel Formulation
2.9. Statistical Analysis
3. Results
3.1. Gel Formulation Has Potent anti-HIV-1 and HSV-2 Activities
Direct HSV-2 Virucidal Activity of 3 Additional Different Batches of Gel Formulation
3.2. Efficacy of the Gel Formulation on HSV-2 Attachment and Penetration to the Vero Cells
3.3. Gel Formulation was Less Effective as Compared to Acyclovir in Reducing HSV-2 Replication in Post-Infection Assay
3.4. Gel Formulation Has No Adverse Effect on the Survival of Vaginal Lactobacilli and Integrity of Epithelial Monolayer
3.5. Gel Formulation Does Not Lead to Any Significant Increase in the Secretion of Pro-inflammatory Cytokines
3.6. Gel Formulation Does not Show any Significant Increase in Mutagenic Index
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Extracts/Formulation | Cytotoxicity Using Vero Cells a CC50 ± SEM (μg/mL) b | HSV-2 Virucidal Activity a IC50 ± SEM (μg/mL) c |
---|---|---|
Phyllanthus emblica (Fruit) | 307.63 ± 20.10 | 2.48 ± 0.86 |
Terminalia chebula (Fruit) | 409.71 ± 47.70 | 0.01 ± 0.0002 |
Acacea catechu (Heart wood) | 395.35 ± 66.85 | 0.02 ± 0.001 |
Lagerstroemia speciosa (Leaf) | 1269.10 ± 47.78 | 0.44 ± 0.17 |
Gel Formulation | 3179.20 ± 116.60 | 27.26 ± 4.87 |
Gel Base | 13512.00 ± 231.28 | NS d |
Acyclovir | 449.03 ± 148.03 | 124.50 ± 6.05 |
Formulation Batches | Virucidal Activity of Gel Formulations IC50 ± SEM (μg/mL) a | |
---|---|---|
Anti-HSV-2 | Anti-HIV-1 | |
Gel Formulation (I batch) | 30.68 ± 5.5 (p = 0.15) b | 58.37 ± 4.9 (p = 0.78) b |
Gel Formulation (II batch) | 25.72 ± 5.2 (p = 0.64) c | 59.93 ± 2.7 (p = 0.56) c |
Gel Formulation (III batch) | 24.49 ± 4.0 (p = 0.09) d | 56.92 ± 4.6 (p = 0.80) d |
Cytokines | Concentration of Cytokines (pg/mL) Secreted by Vk2/E6E7 Cells Treated with | ||
---|---|---|---|
Gel Formulation a (1 mg/mL) | Gel Base a (1 mg/mL) | Cell Control a | |
Human IL-1β | 12.06 ± 0.5 | 7.28 ± 0.5 | 7.33 ± 0.5 |
Human IL-6 | 574.74 ± 26.7 (p = 0.02) c | 534.36 ± 19.3 | 754.43 ± 1.9 |
Human IL-8 | 318.70 ± 11.0 (p = 0.004) c | 451.68 ± 12.1 | 559.63 ± 11.1 |
Human IL-10 | 0.30 ± 0.1 | ND b | 0.10 ± 0.1 |
Human IL-12p70 | 0.26 ± 0.3 | ND b | 0.26 ± 0.3 |
Human TNF | 15.12 ± 1.8 | 5.80 ± 2.5 | 11.23 ± 1.1 |
Treatment | Dose (μg/mL) | TA-100 (Number of Revertants/Plate) | TA-98 (Number of Revertants/Plate) | Mutagenic Index a | |
---|---|---|---|---|---|
TA-100 | TA-98 | ||||
Gel Formulation | 1000 | 137 ± 4.2 | 79 ± 2.0 | 0.98 | 1.16 |
Gel Base | 1000 | 142.67 ± 8.7 | 68 ± 0.0 | 1.02 | 1.00 |
Cell control | Only medium | 139.33 ± 8.6 | 68 ± 2.0 | - | - |
Sodium azide | 5 μg/plate | 426 ± 30.8 (p = 0.0008) b | - | 3.06 | - |
4-nitro-o-phenylenediamine | 5 μg/plate | - | 182 ± 26 (p = 0.04) b | - | 2.67 |
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Mishra, N.N.; Kesharwani, A.; Agarwal, A.; Polachira, S.K.; Nair, R.; Gupta, S.K. Herbal Gel Formulation Developed for Anti-Human Immunodeficiency Virus (HIV)-1 Activity Also Inhibits In Vitro HSV-2 Infection. Viruses 2018, 10, 580. https://doi.org/10.3390/v10110580
Mishra NN, Kesharwani A, Agarwal A, Polachira SK, Nair R, Gupta SK. Herbal Gel Formulation Developed for Anti-Human Immunodeficiency Virus (HIV)-1 Activity Also Inhibits In Vitro HSV-2 Infection. Viruses. 2018; 10(11):580. https://doi.org/10.3390/v10110580
Chicago/Turabian StyleMishra, Nripendra Nath, Ajay Kesharwani, Aakanksha Agarwal, Suja Kizhiyedath Polachira, Reshmi Nair, and Satish Kumar Gupta. 2018. "Herbal Gel Formulation Developed for Anti-Human Immunodeficiency Virus (HIV)-1 Activity Also Inhibits In Vitro HSV-2 Infection" Viruses 10, no. 11: 580. https://doi.org/10.3390/v10110580