Evaluation of widely consumed botanicals as immunological adjuvants

• Published in: Vaccine 2008-09, Vol.26 (37), p.4860-4865
• Main Authors: Ragupathi, Govind, Yeung, K. Simon, Leung, Ping-Chung, Lee, Mavis, Lau, Clara Bik San, Vickers, Andrew, Hood, Chandra, Deng, Gary, Cheung, Nai-Kong, Cassileth, Barrie, Livingston, Philip
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - isolation & purification; Adjuvants, Immunologic - pharmacology; Allergy and Immunology; Animals; Antibodies, Neoplasm - blood; Applied microbiology; Astragalus; Biological and medical sciences; Botanicals; Cancer; Cancer vaccine; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Carbohydrates; Conjugate vaccine; Coriolus versicolor; Curcuma longa; Echinacea; Enzyme-Linked Immunosorbent Assay; Ethanol; Experiments; Female; Fundamental and applied biological sciences. Psychology; Fungi - chemistry; Gangliosides - immunology; Glycoproteins; Herbal medicine; Immunization; Immunization, Secondary; Immunological adjuvant; Injections, Subcutaneous; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Molecular weight; Plant Extracts - pharmacology; Plants, Medicinal - chemistry; PSK; Saponin; Tumors; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Conjugate - immunology; Yeast; Yeasts; β-Glucan
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.06.098

Abstract Background Many widely used botanical medicines are claimed to be immune enhancers. Clear evidence of augmentation of immune responses in vivo is lacking in most cases. To select botanicals for further study based on immune enhancing activity, we study them here mixed with antigen and injected subcutaneously (s.c.). Globo H and GD3 are cell surface carbohydrates expressed on glycolipids or glycoproteins on the cell surface of many cancers. When conjugated to keyhole limpet hemocyanin (KLH), mixed with an immunological adjuvant and administered s.c. the magnitude of the antibody responses against globo H, GD3 and KLH depend largely on the potency of the adjuvant. We describe here the results obtained using this s.c. immunization model with seven botanicals purported to have immune stimulant effects. Methods Groups of 5–10 mice were immunized with globo H–KLH or GD3–KLH mixed with botanical, saline or positive control immunological adjuvant, s.c. three times at 1 week intervals. Antibody responses were measured 1 and 2 weeks after the 3rd immunization. The following seven botanicals and fractions were tested: (1) H-48 (Honso USA Co.), (2) Coriolus versicolor raw water extract, purified polysaccharide-K (PSK) or purified polysaccharide-peptide (PSP) (Institute of Chinese Medicine (ICM)), (3) Maitake extract (Yukiguni Maitake Co. Ltd. and Tradeworks Group), (4) Echinacea lipophilic, neutral and acidic extracts (Gaia Herbs), (5) Astragalus water, 50% or 95% ethanol extracts (ICM), (6) Turmeric supercritical (SC) or hydro-ethanolic (HE) extracts (New Chapter) or 60% ethanol extract (ICM) and (7) yeast β-glucan (Biotec Pharmacon). Purified saponin extract QS-21 (Antigenics) and semisynthetic saponin GPI-0100 (Advanced BioTherapies) were used as positive control adjuvants. Sera were analyzed by ELISA against synthetic globo H ceramide or GD3 and KLH. Results Consistent significant adjuvant activity was observed after s.c. vaccination with the Coriolus extracts (especially PSK), a 95% ethanol extract of Astragalus and yeast β-glucan, and (to a lesser extent) Maitake. Antibodies against KLH in all cases and against globo H in most cases were induced by these botanicals. Little or no adjuvant activity was demonstrated with H-48 or Echinacea extracts or the Astragalus water extract. Experiments with GD3–KLH as immunogen confirmed the adjuvant activity of the Coriolus, yeast β-glucan and Astragalus extracts. While extraction with ethanol concentrated the activ