**3.2 Scorpion venom: Traditional remedies**

636 Biomedical Science, Engineering and Technology

Position Amino acids High

A G V L I F Y W C S T D E N Q R H K M P

H1 0.07 0.10 0.02 0.01 0.02 0.01 0.01 0.15 0.15 0.05 0.03 0.14 0.05 0.06 0.04 0.08 0.04 H2 0.12 0.04 0.01 0.08 0.02 0.02 0.00 0.02 0.07 0.05 0.11 0.05 0.27 0.02 0.02 0.03 0.06 0.01 0.03 N H3 (C) 1.00 C H4 0.24 0.03 0.04 0.02 0.02 0.00 0.03 0.06 0.02 0.17 0.03 0.08 0.02 0.09 0.19 A H5 0.06 0.01 0.02 0.04 0.02 0.03 0.01 0.11 0.08 0.09 0.06 0.23 0.09 0.03 0.04 0.10 0.01 N H6 0.05 0.01 0.25 0.06 0.01 0.01 0.04 0.02 0.08 0.05 0.01 0.05 0.05 0.16 0.01 0.11 0.02 0.03 0.02 V H7 (C) 1.00 C H8 0.03 0.01 0.04 0.11 0.18 0.02 0.03 0.01 0.01 0.04 0.01 0.01 0.02 0.09 0.18 0.05 0.16 0.03 0.02 H9 0.06 0.02 0.01 0.01 0.01 0.01 0.09 0.21 0.02 0.07 0.19 0.11 0.08 0.01 0.10 0.01 0.02 T

S1 0.02 0.08 0.20 0.07 0.01 0.03 0.01 0.27 0.02 0.08 0.01 0.02 0.07 0.01 0.04 0.04 0.02 T L S2 (C) 1.00 C S3 0.01 0.04 0.07 0.02 0.02 0.02 0.01 0.05 0.03 0.05 0.34 0.01 0.04 0.08 0.04 0.11 0.07 0.01 E S4 0.06 0.02 0.07 0.05 0.03 0.18 0.10 0.04 0.07 0.08 0.02 0.13 0.03 0.12 0.01 S5 0.05 0.04 0.05 0.12 0.05 0.01 0.04 0.06 0.05 0.03 0.07 0.00 0.12 0.08 0.01 0.08 0.01 0.13

β21 0.05 0.35 0.05 0.01 0.02 0.01 0.01 0.01 0.11 0.03 0.08 0.02 0.05 0.01 0.05 0.14 0.05 G β22 (G) 1.00 G

β24 (C) 1.00 C β25 0.02 0.01 0.07 0.05 0.06 0.04 0.01 0.01 0.06 0.02 0.14 0.04 0.17 0.03 0.16 0.09 0.06 0.01 0.01

β31 0.05 0.02 0.02 0.07 0.02 0.02 0.04 0.05 0.01 0.02 0.04 0.06 0.30 0.04 0.23 0.05 K β32 (C) 1.00 C

β34 (C) 1.00 C β35 0.02 0.02 0.03 0.04 0.06 0.02 0.22 0.04 0.07 0.30 0.03 0.02 0.03 0.04 0.04 0.01 0.04 0.02 Y

Human beings have been using natural products containing CSαβ motif peptides for several hundreds years. The most well known natural products are sweet peptides of plants and scorpion venom. For their anti-microbial and pesticide abilities, in many cases, peptides with CSαβ motif are transfected into industrial crops to protect these transgenic plant from pathogens. In recent years, some of plant defensins are also screened and selected as antibiotics for therapeutic utilities. In this section, some peptides with therapeutic potential

Brazzein is isolated from *Pentadiplandra brazzeana*, a climbing plant plant of the West Africa. Berry fruits of *Pentadiplandra brazzeana* have sweetness and are traditional foods of African natives (Assadi-Porter et al., 2008;Yang & Lyu, 2008). For a long time, the sweetness of the berry fruits is a secret. Ding and Hellekant at University Wisconsin Madison isolated a small peptide with sweetness from *Pentadiplandra brazzeana* and named it as brazzein 1994 (Ming & Hellekant, 1994). Peptide sequence analysis shows that brazzein contains a set of (*i, i+4*) and (*j, j+1*) cysteine pattern. Its NMR structure is solved and confirms it as a CSαβ motif peptide 1998 (Caldwell et al., 1998). Brazzein is the smallest, most heat-stable and pH-stable protein known to have an intrinsic sweetness (Jin et al., 2006). Brazzein is 200 times sweeter than sugar and it can be used both in cold and hot drinks/foods without change its sweet

β23 0.04 0.02 0.05 0.01 0.01 0.05 0.06 0.18 0.07 0.05 0.06 0.07 0.03 0.11 0.06 0.17 0.01

β33 0.01 0.02 0.07 0.12 0.15 0.19 0.13 0.07 0.02 0.02 0.03 0.01 0.01 0.03 0.05 0.05 0.05

Table 3. The high frequent amino acids in the structural regions of plant defensin.

**3. Applications of CS**αβ **motif peptides** 

are selected and discussed.

**3.1 Sweet peptide: Brazzein** 

Strand 1

Helix

β2 strand

β3 strand

frequencya

Scorpion is therapeutically used in traditional Chinese medicine for hundreds of years. Figure 4 shows the therapeutic instruction of using scorpion described in the *Compendium of Materia Medica*, an ancient Chinese pharmacopoeia compiled in the 1500s AD. In traditional Chinese medicine, scorpion is recruited as one of the major treatments for stroke, rheumatism, epilepsy, hemiplegia, convulsions, cramps, twitchs, headaches, tetanus and scrofula. *Buthus martensii Karsch* is the most common species of scorpion that are processed as traditional Chinese medicine. Captured scorpions have to be preserved in salt. The preserved scorpions are usually boiled with herbs, such as licorice, to reduce toxicity after washing off the salt. Patients take the boiled extracts twice daily and the amount of scorpions should be controlled to under 10 grams for an adult daily. Most of proteins will be denatured and loss functions after being exposed to salt at a high concentration and water boiling temperature. The major effective composition of scorpion is scorpion venom. It has been demonstrated the venom can block cation channel of insects (Li et al., 2000;Wang et al., 2001). Several peptides containing CSαβ motif have been isolated from scorpion venom. The peptides can keep their structures and functions after be exposed to water boiling temperature and solvents of high salt concentration. BmK AEP, a peptide containing a CSαβ motif isolated from *Buthus martensii Karsch* venom, is the first anticonvulsant purified in the venom (Wang et al., 2001). BmK AEP has inhibitory effect to coriaria lactone-induced epilepsy model in rodents. It has a low toxicity to mice in doses up to 20 mg/animal (Rajendra et al., 2004). There is nearly no effect on heart rate, electroencephalogram, breathing rate and blood pressure (Rajendra et al., 2004;Wang et al., 2001). CII9, another peptide with a CSαβ motif isolated from *Centruroides limpidus Karsch*, can partially inhibit


Fig. 4. The therapeutic instruction of scorpion described in the ancient Chinese pharmacopoeia: *Compendium of Materia Medica.*

sodium ion currents from superior cervical ganglion neurons of rats (Dehesa-Davila et al., 1996;Possani et al., 1999). In the rat model, CII9 also exerts a depressant effect on the behavior and electroencephalographic activity and antagonizes the epileptiform activity induced by penicillin (Dehesa-Davila et al., 1996;Gazarian et al., 2005;Possani et al., 1999).
