Printer Friendly

Immunomodulatory, analgesic and antipyretic effects of violacein isolated from Chromobacterium violaceum.


Violacein was isolated from Chromobacterium violaceum, a soil Gram negative bacterium collected from the forest water body soil sample of Kolli Hills; Tamil Nadu, India. In the present study the immunomodulatory, analgesic and antipyretic activities of violacein were investigated in wistar rats and mice. Analgesic effect was evaluated by acetic acid- induced writhing, formalin induced paw licking and hotplate tests. Immunomodulatory effect was investigated by using ovalbumin- induced active paw anaphylaxis and sheep red blood cells (SRBC)-induced DTH tests. Antipyretic activity was evaluated by yeast- induced hyperpyrexia in rats. The anti- oedema effect was compared with indomethacin. Violacein inhibited 42.9% of ovalbumin- induced edema. Further we found that violacein (40mg/kg b.w.) reduced the edema induced by sheep red blood cells. Violacein also produced significant (p<0.05) analgesic activity in acetic acid induced writhing response, formalin induced paw licking response and hot plate analysis. Treatment with violacein showed a significant (p <0.05) dose-dependent reduction in pyrexia in rats. The results suggest that violacein possesses potent immunomodulatory, analgesic and antipyretic activities.

[C] 2009 Elsevier GmbH. All rights reserved.


Keywords: Analgesic Immunomodulatory Anti-pyretic Chromobacterium violaceum Violacein Writhing response


Chromobacterium violaceum is a Gram negative bacterium found in water body soils from tropical and subtropical regions of the world. Although rare, infections of humans and animals with this bacterium are characterized by rapid dissemination and high mortality (Martinez et al. 2003; Chattopadhyay et al. 2002). It produces a unique violet pigment called violacein.

The availability of the genome sequence of C. violaceum (Vasconcelos et al. 2003) provides important information concerning the potential applications of this opportunistic bacterium for biotechnological and pharmaceutical purposes. Previous studies showed that "constituents of C violaceum" possessed antibiotic and antichagasic (Duran and Menck 2001), antitumoral (Melo et al. 2000), antioxidant (Konzen et al. 2006), antileishma-nial (Leon et al. 2001) activities. Apoptotic induction capacities in colon cancer cells (Carvalho et al. 2006; Kodach et al. 2006) and leukemia cells (Melo et al. 2000; Ferreira et al. 2004) have also been reported. Violacein (Fig. 1) exhibited antimicrobial activity against Mycobacterium tuberculosis (De Souza et al. 1999), Trypanosoma cruzi (Caldas et al. 1978; Duran et al. 1989; Duran et al. 1994) and Leishmania sp. (Leon et al. 2001).


Violacein (with 10 percent of deoxyviolacein) showed activity against herpes and polioviruses (May et al. 1991). A patent has been registered (Duran 1998) for a formulation of cyclodextrin/ violacein for treating bacterial, viral, trypanocidal infections and for antitumoral activity (Melo et al. 2000; Duran and Menck 2001). Higher concentration of violacein showed a weak inhibition of viral replication in HSV-1, Poliovirus type 2 and Simian rotavirus SA11 (Andrighetti-Frohner et al. 2003). Violacein was biotransformed or decolorized by basidiomycetes and bacteria (Bromberg and Duran 2001). Violacein also showed anti-diar-rhoeal and ulcer-protective effects (Antonisamy et al. 2009).

In this study, we report for the first time the use of violacein as immunomodulatory, analgesic and antipyretic agent using animal models. Possible mechanisms of action are also examined.

Materials and methods

Adult wistar albino rats (200-220 g) and mice (24-28 g) of either sex were used for the experiments. Animals were maintained on 12 h light/dark cycle at approximately 25 [+ or -]1 [degrees]C, relative humidity 60-70% and they had access to diet and water ad libitum and were acclimatized at least 2 weeks before starting the experiments. All studies were carried out using six animals in each group. All the animal experiments were conducted according to the ethical norms approved by Ministry of Social Justice and Empowerment, Government of India and Institutional Animal Ethics Committee guidelines.

Indomethacin, Sheep Red Blood Cells (SRBC), Formalin, Naloxone, Morphine, Dexamethasone and dimethyl sulfoxide (DMSO) were obtained from Sigma-Aldrich (USA). CMC (Carbox-ymethylcellulose), and Ovalbumin were obtained from Himedia (India).

The violet pigmented C. violaceum ESBV 4400 was isolated from forest water body soil samples from Kolli Hills of Tamil Nadu, India at latitude 11[degrees] 10' to 11[degrees] 30' N and longitude 78[degrees] 15' to 78[degrees] 30' E. It was identified using standard biochemical methods (Cappuccino and Sherman 2004) and confirmed by 16S rRNA gene identification (Hao et al. 2007).

Animals were sensitised by injecting 0.25 [micro]g of ovalbumin adsorbed on 6 mg of aluminium hydroxide gel on the back of the mice s.c. on day 0. Violacein in doses of 10, 20 and 40mg/kg b.w. was fed from day 1 to day 11. On the 11th day, animals were challenged with 10 [micro]g of (0.5 ml of 200 [micro]g/ml) ovalbumin in normal saline s.c. in the planter region of the hind paw. The contralateral paw received an equal volume of saline. The paw thickness was measured by a digital vernier caliper at 24 h after the challenge. The difference in paw thickness reflected the edema due to the antigen-antibody reaction (Hunskaar and Hole 1987; Adzu et al. 2003). 5 mg/kg b.w. of DSCG (disodium chromoglycate) was used as the reference drug for comparison (Teotino et al. 1963).

The effect of violacein on the antigen specific cellular immune response in experimental animals was measured by determining the degree of DTH response using the foot paw swelling test (Benencia et al. 2000). Rats were injected intraperitoneally with a suspension containing 1 x [10.sup.6] SRBC in 0.2 ml of phosphate buffered saline (PBS) on day zero sensitization. Seven days later (day +7), the same animals were injected subcutaneously with 1 x [10.sup.6] SRBC suspended in 50 [micro]1 of PBS into the right hind foot pad for elicitation of the DTH reaction. The left hind foot pad was injected with 50 [micro]1 of PBS as control. Foot pad swelling was measured on day +8 with a digital vernier caliper. The difference between the means of right and left hind foot pad thickness gave a degree of foot pad swelling which was used for group comparisons. To establish the effect of violacein and dexamethasone on this immune response, a daily dose of violacein (10, 20 and 40 mg/ kg b.w.) and dexamethasone (10 mg/kg b.w.) was administered orally at the induction phase (+4 to +7 days). Simultaneously, another group of animals (control) was inoculated with 0.5 ml of 0.5% CMC under the same condition.

Mice weighing 24-28 g were used and divided into nine groups of six animals. The study was carried out by a modified method (Mungantiwar et al. 1999). Each mouse was given an injection of 0.75% acetic acid aqueous solution in a volume of 0.1 ml/10 g b.w. into the peritoneal cavity and the animals were then placed in a transparent plastic box. The number of writhes was counted for 15min beginning from 5 min after the acetic acid injection. Test drugs violacein (10, 20 and 40 mg/kg p.o.), indomethacin (10 mg/ kg p.o.), morphine (05 mg/kg s.c), morphine+naloxone ((05 mg/kg s.c+02 mg/kg i.p.), violacein+naloxone (40 mg/kg p.o.+02 mg/kg i.p.), indomethacin+naloxone (10mg/kg p.o.+02 mg/kg i.p.) and control vehicle (0.5 ml of 0.5% CMC p.o.) were administered 1 h before the acetic acid injection.

The test was performed according to the method (Reisine and Pasternack, 1996). Mice weighing 24-28 g were used and divided into two sets of nine groups of six animals. Test drugs violacein (10, 20 and 40 mg/kg p.o.), indomethacin (10 mg/kg p.o.), morphine (05 mg/kg s.c), morphine+naloxone ((05 mg/kg s.c+02 mg/kg i.p.), violacein+naloxone (40 mg/kg p.o.+02 mg/kg i.p.), indomethacin+naloxone (10 mg/kg p.o.+02 mg/kg i.p.) and control vehicle (0.5 ml of 0.5% CMC p.o.) were administered 1 h prior to formalin injection to animals in the first set (for early phase) and 40 min prior to formalin injection to animals in the second set (for late phase), respectively. Mice were injected subcutaneously with 50 [micro]1 of 1% formalin in normal saline solution into the right dorsal hind paw. The time animals spent in licking of injected paw was determined during 0-5 min (the first set of mice for early phase) and during 20-30 min (the second set of mice for late phase) after the injection of formalin.

Experiments were carried out according to previously described method (Parkhouse and Pleuvry 1979). Mice weighing 24-28 g were used and divided into seven groups of six animals. For testing, mice were placed on hot plate maintained at 55 [+ or -] 5 [degrees]C. The time that elapsed until occurrence of either a hind paw licking or a jump off from the surface was recorded as the hot plate latency. Before treatment, the reaction time of each mouse (licking of the forepaws or jumping response) was done at 0 and 10 min interval. The average of the two readings was obtained as the initial reaction time. Mice with baseline latencies of < 5s or > 30s were eliminated from the study. The initial reaction time following the administration of violacein (10, 20 and 40 mg/kg p.o.), morphine (05 mg/kg s.c), naloxone+morphine (02 mg/kg i.p.+05 mg/kg s.c), naloxone+violacein (02 mg/kg i.p.+40 mg/kg p.o.) and vehicle (0.5 ml of 0.5% CMC p.o.) was measured at 30 min.

Hyperthermia was induced in rats by the method (Vogel and Vogel 1997). Rats were given 10 ml/kg of 20% aqueous suspension of brewer's yeast subcutaneously. Initial rectal temperature was recorded. After 18 h animals that showed an increase of 0.3-0.5 [degrees]C in rectal temperature were selected. The thermometer was inserted about 3 cm into the rectum of each rat. Violacein (10, 20, 40 mg/kg b.w.) was administered to three groups. Control group received 0.5ml of vehicle. Paracetamol (150mg/kg b.w.) was used as reference drug. Rectal temperature was determined at 30, 60, 90 and 120 min after drugs administration.

Data were statistically analysed by analysis of variance (ANOVA) followed by Student's t-test, and a probability level lower than 0.05 was considered statistically significant (Tallarida and Murria 1987).


In the case of the edema induced by SRBC in mice, violacein (40 mg/kg b.w.) clearly and significantly reduced edema by 45.3% on 8th day. This reduction was higher than the edema reduced by dexamethasone (43.7%) (Table 1).
Table 1
Effects of violacein on the SRBC- induced delayed- type
hypersensitivity and ovalbumin- induced active paw anaphylaxis tests.

SRBC induced DTH

Test samples            Dose (mg/kg b.w.)     Paw thickness (mm)

Control                        -           6.95 [+ or -] 0.53
Dexamethasone                 10           3.91 [+ or -] 0.30(43.7) *
Violacein                     10           5.73 [+ or -] 0.44(17.5)
                              20           5.21 [+ or -] 0.40(25.0) *
                              40           3.80 [+ or -] 0.29 (45.3) *

Active paw anaphylaxis

Test samples            Dose (mg/kg b.w.)      Paw thickness (mm)
Control                         -          7.61 [+ or -] 0.58
DSCG                           05          4.29 [+ or -] 0.33 (43.6) *
Violacein                      10          7.10 [+ or -] 0.54 (6.7)
                               20          5.26 [+ or -] 0.40 (30.8) *
                               40          4.34 [+ or -] 0.33 (42.9) *

Data represent mean[+ or -]S.D. (standard deviation) (n = 6).
Values in the parenthesis indicate paw edema inhibition percentage.

Note: SRBC (sheep red blood cells); DTH (delayed-type
hypersensitivity); DSCG (disodium chromoglycate).

* p<0.05 significant from the control.

In active paw anaphylaxis test animals treated with violacein and DSCG showed significant reduction in paw edema when compared with control (p<0.05). Animals treated with violacein (40mg/kg b.w.) showed less reduction of paw edema (42.9%) when compared with animals treatd with DSCG (43.6%) (Table 1).

Evidence of analgesic activities in the violacein was detected in the three different models for nociception used to investigate the anti-nociceptive effect.

Violacein significantly reduced writhings and stretchings induced by acetic acid (Table 2). The protective effect of violacein was dose dependent with 81.2% (p<0.05) reduction observed in 40 mg/kg b.w. Indomethacin (10 mg/kg b.w.) inhibited 78.0% (p<0.05) and morphine (a centrally acting analgesic) inhibited 93.9% (p<0.05). Naloxone partially blocked the protective actions of violacein. On the other hand naloxone completely arrested morphine activity. Effect was exerted by violacein on the first phase (0-5 min) as well as in the second phase (20-30 min) of formalin test. These phases corresponded to neurogenic and inflammatory pains respectively. The dose 40 mg/ kg b.w. inhibited 88.0% (p<0.05) in the first phase and 90.0% (p<0.05) in the second phase. Indomethacin was significantly active (73.4%, p<0.05) on the second phase whereas morphine acted in both the phases, (Table 2). The opioid antagonist naloxone inhibited the action of morphine at both the phases, but the action of naloxone on violacein was partial. In both tests (acetic acid induced writhing and formalin induced paw licking) the activity of indomethacin was not disrupted by naloxone.
Table 2

Effects of violacein, indomethacin, morphine and naloxone on acetic
acid- induced writhing response and formalin- induced paw licking in

Test samples                Dose      Acetic acid (a) Number of writhes
                        (mg/kg b.w.)
Control                       _         57.83 [+ or -] 4.75
Indomethacin                 10         12.67 [+ or -] 1.37 (78.0) *
Violacein                    10         50.50 [+ or -] 3.83 (12.6)
                             20         29.67 [+ or -] 2.25 (48.6) *
                             40         10.83 [+ or -] 0.75 (81.2) *
Morphine                     05          3.50 [+ or -] 0.55 (93.9) *
Morphine+Naloxone            05+02      56.83 [+ or -] 4.31 (1.72)
Violacein+Naloxone           40+02      40.67 [+ or -] 3.14 (29.6) *@
Indomethacin+Naloxone        10+02      12.83 [+ or -] 1.17 (77.8) *@

Test samples           Formalin test (b) Early phase Licking time (s)

Control                          36.17 [+ or -] 2.23
Indomethacin                     27.50 [+ or -] 2.07 (23.9) *
Violacein                        25.33 [+ or -] 1.97 (29.9) *
                                 12.83 [+ or -] 1.17 (64.5) *
                                  4.33 [+ or -] 0.82 (88.0) *
Morphine                          2.83 [+ or -] 0.41 (92.1) *
Morphine+Naloxone                37.00 [+ or -] 2.83 (-2.29)
Violacein+Naloxone               25.50 [+ or -] 2.51 (29.4) *@
Indomethacin+Naloxone            26.67 [+ or -] 1.51 (26.26) *@

Test samples           Late phase Licking time (s)

Control                  37.00 [+ or -] 3.29
Indomethacin              9.83 [+ or -] 0.75 (73.4)*
Violacein                22.00 [+ or -] 1.90 (40.5)*
                          9.33 [+ or -] 0.82 (74.7)*
                          3.67 [+ or -] 0.52 (90.0)*
Morphine                  2.50 [+ or -] 0.55 (93.2)*
Morphine+Naloxone        37.00 [+ or -] 3.16 (00)
Violacein+Naloxone       28.83 [+ or -] 2.04 (22.0)*@
Indomethacin+Naloxone     9.64 [+ or -] 0.73 (73.9)*@

Data represent mean [+ or -] S.D. (standard deviation) (n = 6).
Comparison made between:* Control with all the groups; @
Morphine+Naloxone with Violacein+Naloxone and Indomethacin+Naloxone.
*@p< 0.05 significant from the control.

(a),(b) Values in the parenthesis indicate writhing and paw licking
inhibition percentage.

In the hot plate test, violacein showed significant results in a dose dependent manner. The maximum latent time (36.3) was observed at the dose of 40 mg/kg b.w. Naloxone partialy inhibited the action of violacein. Morphine sulphate at 0.5 mg/kg b.w. manifested its maximum latent time of 34.6 (p<0.05). Action of morphine was completely arrested by naloxone (2 mg/kg b.w.) (Table 3).
Table 3
Effect of the violacein, morphine and naloxone on pain threshold of
mice in the hot plate test.

Test samples         Dose           Mean latent time (sec.)

                                 Initial           After 30 min.

Control            -       10.83 [+ or -] 0.75   11.00 [+ or -] 0.89

Morphine           05      11.00 [+ or -]  0.89  34.67 [+ or -] 2.73 *

Violacein          10      10.17 [+ or -] 0.75   12.83 [+ or -] 1.17

                   20      10.00 [+ or -]0.89    27.67 [+ or -] 2.25 *

                   40      10.67 [+ or -] 0.52   36.33 [+ or -] 2.80 *

Morphine+Naloxone  05+02   10.33 [+ or -] 0.52   10.67 [+ or -] 0.52

Violaein+Naloxone  40+02   10.84 [+ or -] 0.75   18.83 [+ or -] 1.47 *@

Data represent mean[+ or -]S.D. (standard deviation) (n = 6).
Comparison made between:* Control with alll the groups; @
with Violacein+Naloxone.

*@ p < 0.05 significant from the control.

The results of the antipyretic effect of the violacein are presented in Table 4. Administration of brewer's yeast to rats produced a significant increase in rectal temperature 18 h after yeast injection (p<0.05). The results of the antipyretic study showed that oral administration of violacein at 20 and 40 mg/kg b.w. caused a significant (p<0.05) inhibition of pyrexia induced by yeast. The antipyretic effect of 40 mg/kg b.w. of violacein was highly effective when compared with paracetamol (150 mg/kg b.w.).
Table 4
Effect of the violacein and paracetamol in yeast- induced hyperthermia
test in rats.

Test              Dose               Rectal temperature (*C)
samples      (mg/kg b.w.)

                               Before yeast      18 hr after yeast

Control            _       37.14 [+ or -] 2.83  39.29 [+ or -] 2.99

Paracetamol       150      37.28 [+ or -] 2.84  39.22 [+ or -] 2.99

Violacein          10      37.19 [+ or -] 2.83  39.38 [+ or -] 3.00

                   20      37.13 [+ or -] 2.83  39.43 [+ or -] 3.00

                   40      37.15 [+ or -] 2.83  39.40 [+ or -] 3.00

Test samples             Time after treatment (min)

                       30                          60

Control       39.38 [+ or -] 3.00         39.25 [+ or -] 2.99

Paracetamol   38.30 [+ or -] 2.92 *       37.73 [+ or -] 2.87 *

Violacein     39.22 [+ or -] 2.99         39.12 [+ or -] 2.98

              38.65 [+ or -] 2.94         38.32 [+ or -] 2.92 *

              37.85 [+ or -] 2.88 *       37.53 [+ or -] 2.86 *

Test samples            Time after treatment (min)

                       90                   120

Control       39.41 [+ or -] 3.00    39.00 [+ or -] 2.99

Paracetamol   37.55 [+ or -] 2.86 *  37.32 [+ or -] 2.84 *

Violacein     38.95 [+ or -] 2.97    38.73 [+ or -] 2.95

              38.13 [+ or -] 2.90 *  37.85 [+ or -] 2.88 *

              37.42 [+ or -] 2.85 *  37.23 [+ or -] 2.83 *

Data represent mean[+ or -]S.D. (standard deviation) (n = 6). * p <
0.05 significant from the control.


In the present study we evaluated the immunomodulatory, analgesic and anti-pyretic effects of violacein employing various experimental test models.

In the DTH model, sensitized animals when challenged with the same allergen, produced a significant increase in paw edema when compared with right paw (receiving SRBC) and left paw (receiving PBS as control) establishing the validity of the model. The interaction of sensitized T cells with presented antigen is known to be associated with the release of mediators such as histamine, products of arachidonic acid metabolism and eventually interferon-[gamma] leading to DTH (Mungantiwar et al. 1999). Therefore the inhibitory action could be due to an influence of violacein on the biological mediators. Thus, violacein has immunomodulatory (immunosuppression) principles, specially affecting inflammatory responses.

The active paw anaphylaxis mice model, i.e. type-I IgE-mediated anaphylactic reaction using ovalbumin as an antigen, significantly increased the edema when compared with the control hind paw which received normal saline. Animals treated with DSCG showed significant reduction in paw edema when compared with control, re-establishing the role of DSCG as mast cell stabilizer and its use as a standard preparation for treating the IgE-mediated anaphylactic reaction. Violacein may have a potential antiallergic/regulating activity with respect to type-I IgE-mediated anaphylactic reaction.

The present results indicated that violacein exhibited central and peripheral antinociceptive activities. Opioid agents exert their analgesic effects via supraspinal ([[micro].sub.1], [[kappa].sub.3], [[delta].sub.1], [[sigma].sub.2]) and spinal ([[micro].sub.1], [[kappa].sub.1], [[delta].sub.1]) receptors (Reisine and Pasternack 1996). Violacein showed antinociceptive activity in all the tests (Acetic acid induced writhing response, formalin induced paw licking response and hot plate test) and this effect was partially inhibited by naloxone (opioid antagonist). The formalin test possesses two distinctive phases which reflect different types of pain. The earlier phase reflects direct effect of formalin on nocciceptors (non-inflammatory pain), whereas the late phase reflects pain from inflammation (Hunskaar and Hole 1987). Violacein showed analgesic activity on both phases of the formalin test, suggesting that both direct effect on the nocciceptor and an inhibition of inflammatory pain implying its effect on the synthesis and/or release of PGs and/or other pain mediators. The hot plate test is a specific central antinociceptive test (Parkhouse and Pleuvry 1979). It is possible that violacein exerted its effect through central opioid receptors or promoted release of endogenous opiopeptides. Antinociceptive activity of opioid agonist, opioid partial agonist and non-steroidal anti-inflammatory agents can be determined by the writhing test (Vogel and Vogel 1997). As the antinociceptive activity of violacein was partially inhibited by naloxone, violacein probably acts on spinal opioid receptors such as [[micro].sub.2], [[kappa].sub.1] and [[delta].sub.2] receptors, although, other mechanism of action such as inhibition of cyclooxygenase is also possible.

Antipyretic activity is commonly mentioned as a characteristic of drugs or compounds which have an inhibitory effect on prostaglandin-biosynthesis (Vane 1987). The yeast- induced hyperthermia in rats was employed to investigate the antipyretic activity of violacein. It was found that violacein caused a significant decrease in rectal temperature similar to paracetamol. This result seems to support the view that violacein has some influence on prostaglandin-biosynthesis, because prostaglandin is believed to be a regulator of body temperature (Milton 1982).


The results of the present study have empirically indicated that violacein is effective in the treatment of inflammatory diseases. Violacein shows potent in vivo immunomodulatory, analgesic and antipyretic effect. Inhibition of the synthesis and/or release of inflammatory mediators may be the main mechanism(s) of action of violacein. Due to the remarkable biological activity of violacein it will be appropriate to conduct further researches in order to develop it into a medicine.


We are grateful to Dr. P. Kannan, Entomology Research Institute for his help in providing violacein.


Adzu, B., Amos, S., Kapu, S.D., Gamaniel, K.S., 2003. Anti-inflammatory and antinociceptive effects of Sphaeranthus senegalensis. J. Ethnopharmacol. 84, 169-173.

Andrighetti-Frohner, C.R., Antonio, R.V., Creczynski-Pasa, T.B., Barardi, C.R.M., Simoes, C.M.O., 2003. Cytotoxicity and potential antiviral evaluation of violacein produced by Chromobacterium violaceum. Mem. Inst. Oswaldo Cruz Rio de Janeiro 98, 843-848.

Antonisamy, P., Kannan, P., Ignacimuthu, S., 2009. Anti-diarrhoeal and ulcer protective effects of violacein isolated from Chromobacterium violaceum in wistar rats. Fund. & Clin. Pharmacol. (in press).

Benencia, Fabian, Courreges, Maria Cecilia, Coulombie, Felix Carlos, 2000. In vivo and in vitro immunomodulatory activities of Trichilia glabra aqueous leaf extracts. J. Ethanopharmacol. 69, 199-205.

Bromberg, N., Duran, N., 2001. Violacein transformation by peroxidases and oxidases: implications on its biological properties. J. Mol. Catal. B: Enzyme 11, 463-467.

Caldas, L.R., Leitao, A.A.C., Santos, S.M., Tyrrell, R.M.,1978. Preliminary experiments on the photobiological properties of violacein. In: Tyrrell, R.M. (Ed.), Proceedings of the International Symposium on Current Topics in Radiology and Photobiology. Academia Brasileira de Ciencias, Rio de Janeiro, pp. 121-126.

Cappuccino, J.G., Sherman, N., 2004. Microbiology: A Laboratory Manual. Pearson Education. Singapore Pte. Ltd., pp. 137-185.

Carvalho, D.D., Costa, F.T.M., Duran, N., Haun, M., 2006. Cytotoxic activity of violacein in human colon cancer cells. Toxicol. In vitro 20, 1514-1521.

Chattopadhyay, A., Kumar, V., Bhat, N., Rao, P., 2002. Chromobacterium violaceum infection: a rare but frequently fatal disease. J. Pediatr. Surg. 37, 108-110.

De Souza, A.O., Aily, D.C.G., Sato, D.N., Duran, N., 1999. Atividade da violaceina in vitro sobre o Mycobacterium turbeculosis H37RA. Rev. Inst. Adolfo Lutz 58, 59-62.

Duran, N., 1998. Formulation of cyclodextrin/violacein based medicine-comprises enhancement of violacein solubility, with increase in versatility. BR PI 9801307-A.

Duran, N., Antonio, R.V., Haun, M., Pilli, R.A., 1994. Biosynthesis of a trypanocide by Chromobacterium violaceum. World J. Microbiol. Biotechnol. 10, 686-690.

Duran, N., Campos, V., Riveros, R., Joyas, A., Pereira, M.F., Haun, M., 1989. Bacterial chemistry: III. Preliminary studies on the trypanosomal activities of Chromobacterium violaceum products. An Acad. Bras. Cienc. 61, 31-36.

Duran, N., Menck, C.F.M., 2001. Chromobacterium violaceum: a review of pharmacological and industrial perspective. Crit. Rev. Microbiol. 27, 201-222.

Ferreira, C.V., Bos, C.L., Versteeg, H.H., Justo, G.Z., Duran, N., Peppelenbosch, M.P., 2004. Molecular mechanism of violacein-mediated human leukemia cell death. Blood 104,1459-1464.

Hao, C, Zhang, H., Has, R., Bai, Z., Zhang, B., 2007. A novel community of acidophiles in an acid mine drainage sediment. World J. Microbiol. Biotechnol. 23,15-21.

Hunskaar, S., Hole, K., 1987. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 30,103-114.

Kodach, L.L., Bos, C.L, Duran, N., Peppelenbosch, M.P., Ferreira, C.V., Hardwick, J.C.H., 2006. Violacein Synergistically Increases 5-Fluorouracil Cytotoxicity, Induces Apoptosis and Inhibits Akt-Mediated Signal Transduction in Human Colorectal Cancer Cells. Oxford University Press.

Konzen, M., De Marco, D., Cordova, C.A.S., Vieira, TO., Antonio, R.V., Creczynski-Pasa, T.B., 2006. Antioxidant properties of violacein: possible relation on its biological function. Bioorg. Med. Chem. 14. 8307-8313.

Leon, L.L, Miranda, C.C., De Souza, A.O., Duran, N., 2001. Antileishmanial activity of the violacein extracted from Chromobacterium violaceum. J. Antimicrob. Agents Chemother. 48, 449-450.

Martinez, L, Rorvik, L.M., Brox, V., Lassen, J., Seppola, M., Gram, L, Vogel, F., 2003. Genetic variability among isolates of Listeria monocytogenes from food products, clinical samples and processing environments, estimated by RAPD typing. Int. J. Food Microbiol. 84, 285-297.

May, G., Brummer, B., Ott, H., 1991. Treatment of prophylaxis of polio and herpes virus infections--comprises admin, of 3- (1, 2-dihydro-5-(5-hydroxy-1Hindol-3-yl)-2-oxo-3Hpyrrole- 3-ylidene)-l,3-dihydro-2H-indol-2-one. Ger Offen DE 3935066.

Melo, P.S., Maria, S.S., Vidal, B.C., Haun, M., Duran, N., 2000. Violacein cytotoxicity and induction of apoptosis in V79 cells. In vitro Cell Dev. Biol. Anim. 36, 539-543.

Milton, A.S., 1982. Prostaglandins and fever. Trends Pharmacol. Sci. 40, 490-492.

Mungantiwar, A.A., Nair, A.M., Shinde, U.A., Dikshit, V.J., Saraf, M.N., Thakur, VS., Sainis, *., 1999. Studies on the Immunomodulatory effects of Boerhaavia diffusa alkaloidal fraction. J. Ethanopharmacol. 65, 125-131.

Parkhouse, J., Pleuvry, B.J., 1979. Analgesic Drug. Blackwell. Oxford, pp. 1-5.

Reisine, T., Pasternack, G., 1996. Opioid analgesics and antagonists. In: Hardman, J.G., Limbird, L.E. (Eds.), Goodman and Gilman's, the Pharmacological Basis of Therapeutics 9th ed McGraw-Hill, New York, pp. 521-526.

Tallarida, R.J., Murria, R.B., 1987. Manual of pharmacologic calculations with computer programs, second ed Springer-Verlag, New York, pp. 110-134.

Teotino, U.M., Friz, LP., Ganduni, A, Bella, D.D., 1963. Thio derivatives of 2, 3-dihydro-4H-l, 3-benzoazin-4-one, synthesis and pharmacological properties. J. Med. Chem. 6, 248-250.

Vane, J.R., 1987. The evolution of non-steroidal anti-inflammatory drugs and their mechanisms of action. Drugs 33,18-27.

Vasconcelos, A.T.R., et al., 2003. The complete genome sequence of Chromobacterium violaceum reveals remarkable and exploitable bacterial adaptability. Brazilian Nat. Genome Proj. Consortium 100,11660-11665.

Vogel, H.G., Vogel, W.H., 1997. Drug Discovery and Evaluation, Pharmacological Assays. Springer, Berlin, pp. 402-403.

P. Antonisamy, S. Ignacimuthu *

Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai-600 034, Tamil Nadu, India

* Corresponding author. Tel.: +044 28178348; fax: +04428174644. E-mail address: (S. Ignacimuthu).

0944-7113/$-see front matter[C] 2009 Elsevier GmbH. All rights reserved.

COPYRIGHT 2010 Urban & Fischer Verlag
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2010 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Short Communication
Author:Antonisamy, P.; Ignacimuthu, S.
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Article Type:Report
Geographic Code:9INDI
Date:Mar 1, 2010
Previous Article:The effect of mastic gum on Helicobacter pylori: a randomized pilot study.
Next Article:Wormwood (Artemisia absinthium) suppresses tumour necrosis factor alpha and accelerates healing in patients with Crohn's Disease - a controlled...

Terms of use | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters