Super Antibiotics, Part II. Hyperforin, Mass Spectroscopy (MS) and Gas Chromatography-Mass Spectrometry (GC-MS), Evidence of Permeability of the Blood-Testis Barrier (BTB) and the Blood-Brain Barrier (BBB) to Hyperforin
In the first article of this series, we presented some evidence of hyperforin as an antibiotic, antiprotozoal, antiviral, anticancer, and immunomodulatory substance. In the present article, evidence of the permeability of the blood-testis barrier (BTB) and blood-brain barrier (BBB) to hyperforin and its distribution in other organs of the domestic pig (Sus scrofa domesticus) are revealed. Seven-month-old male boars with a body mass of 100 kg were fed a diet containing hyperforin. Organs were surgically removed under anesthesia. Organs were suitable prepared and extracted, and then analyzed using gas chromatography-mass spectrometry with supersonic molecular beams (GC-MS with SMB). The presence of hyperforin was recorded in all organs and body fluids. Special attention was paid to the evaluation of the presence of hyperforin in the brain and testes of experimental animals. The presence of hyperforin in the brain and testes of experimental animals was established by GC-MS with SMB. The results are of interest because penicillin and numerous other antibiotics cannot pass through the BTB or BBB if healthy or non-inflamed, which limits their use in patients with meningitis and gonorrhea. The findings are also of interest in cases of penicillin- and multi-antibiotic-resistant bacterial infections.
References
[1]
Brondz, I. (2016) Super Antibiotics, Part I. Hyperforin. Voice of the Publisher, 2. (In Print)
[2]
Brondz, I. (1979) In: Antibiotikumet ”Hyperforin” og andre innholdsstoffer i drogen Hypricum perforatum L. Thesis (Cand. Pharm.), University of Oslo, Oslo. (In Norwegian)
[3]
Brondz, I. (1986) Lecture Entitled “The Influence of Hyperforin on Phagocytosis of E. coli by Human Polymorphonuclear Neutrophils in Vitro”. Symposium “Norlændskainfektionssjkdomar”, VårmØteti Sundsvall, 14-15 Maj 1986, Sweden.
https://www.researchgate.net/publication/233795016_The_influence_of_hyperforin_on_phagocytosis_of_Ecoli_by_human_polymorphonuclear_neutrophils_in_vitro
[4]
Brondz, I. (1987) Influence of Hyperforin upon Phagocytic Functions in Human Polymorphonuclear Leucocytes. 4th International Conference on Chemistry and Biotechnology of Biological Active Natural Products, Budapest, 10-14 August 1987, Abstr. B-15, 119.
[5]
Brondz, I. (2012) Enhancement of the Immunity in AIDS and Other Immunocompromised Patients by Hyperforin an Antibiotic from Hypericum perforatum L. 2nd ARIP European Conference on Antimicrobial Resistance & Infection Prevention, Vilnius, 4-5 October 2012, 12, 60. In: Oficialus Lietuvos Bendrosios Praktikos Gydytoju Kolegijos Leidinys, No. 7, 1392-3218.
[6]
Brondz, I. and Brondz, A. (2012) Recent Enhancement of the Immunity in AIDS and Other Immunocompromised Patients by Hyperforin an Antibiotic from Hypericum perforatum L. (in Vitro Model) Part I. Journal of Biophysical Chemistry, 3, 304-310.
https://doi.org/10.4236/jbpc.2012.34037
[7]
Volosovets, P.S. (1964) Microflora of suppurative wounds and the quantitative changes of the microflora due to the effect of treatment with amanine and novoimanine. Mikrobiologicheskii Zhurnal, 26, 60-65.
[8]
Volosovets, P.S. (1986) The Effect of Novoimanine on the Course of Experimental Staphylococcal Sepsis. Mikrobiologicheskii Zhurnal, 48, 60-64.
[9]
Derbentseva, N.A. Volosovets, P.S. and Garagulya, A.D. (1970) Distribution of Novoimanin in Albino Rats after Administration by Various Means. Antibiotiki (Moscow), 15, 716-718.
[10]
Donà, M., Dell’Aica, I., Pezzato, E., Sartor, L., Calabrese, F., Della Barbera, M., Donella-Deana, A., Appendino, G., Borsarini, A., Caniato, R. and Garbisa, S. (2004) Hyperforin Inhibits Cancer Invasion and Metastasis. Cancer Research, 64, 6225-6232.
https://doi.org/10.1158/0008-5472.CAN-04-0280
[11]
Sun, F., Liu, J.Y., He, F., Liu, Z., Wang, R., Wang, D.M., Wang, Y.F. and Yang, D.P. (2011) In-Vitro Antitumor Activity Evaluation of Hyperforin Derivatives. Journal of Asian Natural Products Research, 13, 688-699. https://doi.org/10.1080/10286020.2011.584532
[12]
Koeberle, A., Rossi, A., Bauer, J., Dehm, F., Luisella Verotta, L., Northoff, H., Sautebin, L. and Werz, O. (2011) Hyperforin, an Anti-Inflammatory Constituent from St. John’s Wort, Inhibits Microsomal Prostaglandin E2 Synthase-1 and Suppresses Prostaglandin E2 Formation in Vivo. Frontiers in Pharmacology, 2, 7. https://doi.org/10.3389/fphar.2011.00007
[13]
Verotta, L., Appendino, G., Bombardelli, E. and Brun, R. (2007) In Vitro Antimalarial Activity of Hyperforin, a Prenylated Acylphloroglucinol: A Structure-Activity Study. Bioorganic & Medicinal Chemistry Letters, 17, 1544-1548.
https://doi.org/10.1016/j.bmcl.2006.12.100
[14]
Mortensen, T.W. (2010) Hypericum perforatum as an Antimycobacterial Agent and Its Implications as an Additional Tuberculosis Medication. A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in Biological Engineering, Utah State University, Logan.
[15]
Fialkov, A.B., Steiner, U., Jones, L. and Amirav, A. (2006) Sensitivity and Noise in GC-MS: Achieving Low Limits of Detection for Difficult Analytes. International Journal of Mass Spectrometry, 251, 47-58. https://doi.org/10.1016/j.ijms.2005.12.045
[16]
Amirav, A. (2008) US Patent US20080302959 A1, Pulsed Flow Modulation Gas Chromatography Mass Spectrometry with Supersonic Molecular Beams Method and Apparatus.
http://www.google.es/patents/US20080302959?hl=no
[17]
Brondz, I., Fialkov, A.B. and Amirav, A. (2009) Analysis of Quinocide in Unprocessed Primaquine Diphosphate and Primaquine Diphosphate Tablets Using Gas Chromatography-Mass Spectrometry with Supersonic Molecular Beams. Journal of Chromatography A, 1216, 824-829. https://doi.org/10.1016/j.chroma.2008.11.043
[18]
Fialkov, A.B., Gordin, A. and Amirav, A. (2003) Extending the Range of Compounds Amenable for Gas Chromatography-Mass Spectrometric Analysis. Journal of Chromatography A, 991, 217-240. https://doi.org/10.1016/S0021-9673(03)00247-4
[19]
Amirav, A., Gordin, A., Poliak, M. and Fialkov, A.B. (2008) Gas Chromatography-Mass Spectrometry with Supersonic Molecular Beams. Journal of Mass Spectrometry, 43, 141-163. https://doi.org/10.1002/jms.1380
[20]
štembírek, J., Kyllar, M., Putnová, I., Stehlík, L. and Buchtová, M. (2012) The Pig as an Experimental Model for Clinical Craniofacial Research. Laboratory Animals, 46, 269-279.
https://doi.org/10.1258/la.2012.012062
[21]
François Meurens, F., Summerfield, A., Nauwynck, H., Saif, L. and Gerdts, V. (2012) The Pig: A Model for Human Infectious Diseases. Trends in Microbiology, 20, 50-57.
https://doi.org/10.1016/j.tim.2011.11.002
[22]
Swindle, M.M., Makin, A., Herron, A.J., Clubb Jr., F.J. and Frazier, K.S. (2012) Swine as Models in Biomedical Research and Toxicology Testing. Veterinary Pathology, 49, 344-356.
http://vet.sagepub.com/content/49/2/344.full
https://doi.org/10.1177/0300985811402846
[23]
Tanaka, H. and Kobayashi, E. (2006) Education and Research Using Experimental Pigs in a Medical School. Journal of Artificial Organs, 9, 136-143.
https://doi.org/10.1007/s10047-006-0343-2
[24]
Sloley, B.D., Urichuk, L.J., Ling, L., Gu, L.-D., Coutts, R.T., Pang, P.K.T. and Shan, J.J. (2000) Chemical and Pharmacological Evaluation of Hypericum perforatum Extract. Acta Pharmacologica Sinica, 21, 1145-1152.
[25]
Fuzzati, N., Gabetta, B., Strepponi, I. and Villa, F. (2001) High-Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry and Multiple Mass Spectrometry Studies of Hyperforin Degradation Products. Journal of Chromatography A, 926, 187-198.
https://doi.org/10.1016/S0021-9673(01)01000-7
[26]
Piccinellia, A.L., Camponea, L., Piaza, F.D., Cuesta-Rubiob, O. and Rastrellia, L. (2009) Fragmentation Pathways of Polycyclic Polyisoprenylated Benzophenones and Degradation Profile of Nemorosone by Multiple-Stage Tandem Mass Spectrometry, Spectrometry. Journal of the American Society for Mass Spectrometry, 20, 1688-1698.
https://doi.org/10.1016/j.jasms.2009.05.004
[27]
Brondz, I., Klein, U., Karaliova, L., Vlachos, V., Oakley, P., Leideborg, R. and Mikhalitsyn, F. (2005) Nature of the Main Contaminant in the Drug Primaquine Di-Phosphate: Comparison of HPLC and SFC Methods. 29th International Symposium on High Performance Liquid Phase Separations and Related Techniques, Stockholm, 26-30 June 2005, 12-43.
[28]
Brondz, I., HØiland, K. and Lefler, J. (2007) Supercritical Fluid Chromatography of Secondary Metabolites and Multi-Analysis by Mass Spectrometry-Ultraviolet and Corona Charged Aerosol Detection. 12th Norwegian MS-Winter Meeting, Hafjell, 21-24 January 2007, 63.
[29]
Brondz, I. (2012) Editorial: Yesterday, Today and Tomorrow of Supercritical Fluid Extraction and Chromatography. American Journal of Analytical Chemistry, 3, 867-869.
https://doi.org/10.4236/ajac.2012.312A114
[30]
Brondz, I. and Brondz, A. (2014) Review: Isomer Separation, Chiral Resolution, and Structure Elucidation Analyses Are the Future of Analytical Supercritical Fluid Chromatography-Mass Spectrometry. International Journal of Analytical Mass Spectrometry and Chromatography, 2, 15-24. https://doi.org/10.4236/ijamsc.2014.21002
