The known immunologically active components of Astragalus account for only a small proportion of the immunological adjuvant activity when combined with conjugate vaccines.
The 95 % ethanol extract of Astragalus has been demonstrated to have potent activity as an immunological adjuvant when administered with vaccines of various types. We endeavor here to identify the components of this extract that are responsible for this adjuvant activity. Mice were immunized with KLH conjugated to cancer carbohydrate antigens globo H and GD3 and cancer peptide antigen MUC1 combined with different Astragalus fractions or with commercially available Astragalus saponins and flavonoids. The antibody responses against cancer antigens and KLH were quantitated in ELISA assays, and toxicity was calculated by weight loss. Astragalosides II and IV were the most active components, but the toxicity of these two differed dramatically. Astragaloside II was the most toxic Astragalus component with 5-10 % weight loss at a dose of 500 µg while astragaloside IV showed no weight loss at all at this dose, suggesting that astragaloside IV might be utilized as an immunological adjuvant in future studies. Several flavonoids also had significant adjuvant activity. However, when the activities of these known immunologically active components of Astragalus (and of endotoxin) are calculated based on the extent of their presence in the 95 % ethanol extract, they provide only a small proportion of the immunological activity. This raises the possibility that additional uniquely active components of Astragalus may contribute to adjuvant activity, or that the adjuvant activity of Astragalus is greater than the activity of the sum of its parts.
Laboratory of Tumor Vaccinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Feng
F
Hong
Weilie
W
Xiao
Govind
G
Ragupathi
Clara B S
CB
Lau
Ping Chung
PC
Leung
K Simon
KS
Yeung
Constantine
C
George
Barrie
B
Cassileth
Edward
E
Kennelly
Philip O
PO
Livingston
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D027885:Astragalus propinquus / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D012503:Saponins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D014315:Triterpenes / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D018074:Vaccines, Conjugate / Q000276:immunology / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D005419:Flavonoids; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; D018074:Vaccines, Conjugate; C502358:globo H-KLH vaccine; C052064:astragaloside A