| Description: |
Telocinobufagin is a novel endogenous digitalis, it shows a reversible local anesthetic action, similar to BUPI, however, without cardiac toxicity in vitro. Telocinobufagin has antimicrobial, potential immune system regulatory effects, it could be developed as a novel immunotherapeutic agent to treat and other immune-mediated diseases, and it may become a new immunomodulatory agent in many regions. |
| In vitro: |
| Fundam Clin Pharmacol. 2009 Aug;23(4):457-64. | | The effects of telocinobufagin isolated from Chan Su on the activation and cytokine secretion of immunocytes in vitro.[Pubmed: 19709323] |
Many traditional Chinese medicines have been used as immunomodulators that act as either immunosuppressants or immunostimulators. Recently, our lab successfully isolated a monomer Telocinobufagin (TCB) from the chloroform extract of Chan Su (Venenum Bufonis). In the present paper, we evaluated the immunomodulatory effects of this compound in vitro.
METHODS AND RESULTS:
We found that TCB significantly stimulates splenocyte proliferation when administered alone or in combination with polyclonal T-cell mitogens concanavalin A (Con A) and lipopolysaccharide. Telocinobufagin markedly enhances natural killer cell and peritoneal macrophage activation. Telocinobufagin increases the percentage of CD4, CD8 positive cells within a population of splenocytes. Moreover, we found that the level of several Th1 cytokines, including interleukin-2 (IL-2), interleukin-12 (IL-12), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), are significantly increased after TCB treatment, while the level of the Th2 cytokine interleukin-4 (IL-4) is significantly decreased. As a result, the ratio of Th1/Th2 is significantly increased.
CONCLUSIONS:
Taken together, these results indicate that TCB has potential immune system regulatory effects and suggest that this compound could be developed as a novel immunotherapeutic agent to treat cancer and other immune-mediated diseases, and it may become a new immunomodulatory agent in many regions. | | Toxicon. 2005 May;45(6):777-82. | | Antimicrobial activity of the bufadienolides marinobufagin and telocinobufagin isolated as major components from skin secretion of the toad Bufo rubescens.[Pubmed: 15804527] | The increase in the emergence of antibiotic-resistant microorganisms and difficult to treat infections caused by these pathogens stimulate research aiming the identification of novel antimicrobials. Skin secretion of amphibian contains a large number of biologically active compounds, including compounds that performance defense mechanisms against microorganisms.
METHODS AND RESULTS:
In the present work, two antimicrobial bufadienolides, Telocinobufagin (402.1609 Da) and marinobufagin (400.1515 Da), were isolated from skin secretions of the Brazilian toad Bufo rubescens. The specimens were collected in Brasilia (Distrito Federal, Brazil), the skin secretions extracted by electric stimulation, and submitted to purification by RP-HPLC. The molecular structure and mass determination were done by (1)H and (13)C NMR and mass spectrometry data, respectively. The antimicrobial activity was performed by liquid growth inhibition against Staphylococcus aureus and Escherichia coli.
The minimum inhibitory concentrations of Telocinobufagin and marinobufagin were, respectively, 64.0 and 16.0 microg/mL for E. coli and both 128 microg/mL for S. aureus.
CONCLUSIONS:
Besides the antimicrobial activity both bufadienolides promoted an increase of the contraction force in isolated frog ventricle strips. | | Universidade Federal do Ceará, 2004.5.26. | | Pharmacological effects of telocinobufagin, a bufodienolide originated from the parotoid glands of Bufo paracnemis: comparative study with local anesthetic bupivacaine.[Reference: WebLink] | The pharmacological effects of Telocinobufagin (TCB), a bufadienolide extracted from Bufo paracnemis parotoid glands by HPLC, were compared to that induced by bupivacaine (BUPI).
METHODS AND RESULTS:
On guinea-pig isolated ileum, TCB (10-8 to 10-4 M) inhibited both, the electrical field stimulation (EFS)-induced contraction (with a value of 0.9 ± 0.9 % of the control response at 6x10-4 M), and the contractions elicited by ACh, in a concentration-dependent manner. BUPI (10-7 to 10-3 M) also inhibited both, the EFS- and the ACh-induced contractions on guinea-pig isolated ileum, in a concentration-dependent manner. On rat isolated sciatic nerve, TCB (1 mM) reduced the compound action potential (CAP) peak-to-peak amplitude (PPA) to 64.9±7.2 % and 12.9±4.4 % of the control amplitude after 15 min and 30 min, respectively; withdrawal of Telocinobufagin reversed to 83.2±17.5% after 45 min. TCB reduced the CAP conduction velocity (CV) to 15.0±15.0 % of the control after 30 min; wash reversed to 78.7±7.2 % of the control. BUPI (1 mM) inhibited the CAP PPA to 46.7±14,4 % and 11.8.±6.5 % of the control after 15 min and 30 min, respectively; it recovered partially to 29.7±8.3 % after 45 min of wash. BUPI inhibited the CAP CV to 17.4±11.2 % of the control after 30 min; it recovered partially to 44.8±14.5 % after 45 min of wash. On rat isolated atrium, TCB (10-6 to 10-4 M) did not alter the spontaneous inotropism, which was abolished by BUPI.
CONCLUSIONS:
Thus, TCB showed a reversible local anesthetic action, similar to BUPI, however, without cardiac toxicity in vitro. This study shows perspectives to research of new molecules for local anesthetic activity with therapeutic interest. |
|
| In vivo: |
| Int Immunopharmacol. 2015 Apr;25(2):353-62. | | Telocinobufagin enhances the Th1 immune response and protects against Salmonella typhimurium infection.[Pubmed: 25687199] | Ideal potential vaccine adjuvants to stimulate a Th1 immune response are urgently needed to control intracellular infections in clinical applications. Telocinobufagin (TBG), an active component of Venenum bufonis, exhibits immunomodulatory activity. Therefore, we investigated whether TBG enhances the Th1 immune response to ovalbumin (OVA) and formalin-inactivated Salmonella typhimurium (FIST) in mice.
METHODS AND RESULTS:
TBG augmented serum OVA- and FIST-specific IgG and IgG2a and the production of IFNγ by antigen-restimulated splenocytes. TBG also dramatically enhanced splenocyte proliferative responses to concanavalin A, lipopolysaccharide, and OVA and substantially increased T-bet mRNA levels and the CD3(+)/CD3(+)CD4(+)/CD3(+)CD8(+) phenotype in splenocytes from OVA-immunized mice. In in vivo protection studies, TBG significantly decreased the bacterial burdens in the spleen and prolonged the survival time of FIST-immunized mice challenged with live S. typhimurium. In vivo neutralization of IFNγ with anti-IFNγ mAbs led to a significant reduction in FIST-specific IgG2a and IFNγ levels and in anti-Salmonella effect in TBG/FIST-immunized mice.
CONCLUSIONS:
In conclusion, these results suggest that TBG enhances a Th1 immune response to control intracellular infections. |
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