HKU Bulletin February 2013 (Vol. 14 No. 2)

Research California, Berkeley looking into the mechanism action of HAS, and they are discussing ideas regarding how to make and study analogues of HAS that might produce stronger effects that are longer lasting. There is also a cosmetics company in Italy that may be interested. The company previously had started testing natural HAS as a means of reducing wrinkles. About 30 women were given a rather crude extract of Sichuan peppercorns to apply to their face and about half of them felt that it reduced their wrinkles. “It does something to the nerves that is not yet fully understood,” says Dr Toy, “but half the women in the study made the empirical observation that they felt there was a decrease in the wrinkles on their face.” However, at the same time, a lot of the women didn’t complete the study because the crude extract contained a mixture of compounds and it caused itchiness. “It made us think that if you have a pure compound it may not cause the itchiness, so further experiments on its efficacy at reducing wrinkles can be carried out,” says Dr Toy. The problem until now is that isolating HAS from the natural source – the peppercorn – has been very difficult. In a dried peppercorn it represents about one per cent by weight. There are also many similarly structured compounds and isolating the correct one is a very laborious process requiring time, equipment and materials. For example, the people at Berkeley started out with 50 grams of peppercorns and ended up with 50 milligrams of HAS – or just one one-thousandth of material that was pure enough to study in biological tests. “Even though the peppercorns are cheap,” says Dr Toy, “it’s impractical to extract HAS in its pure form, and without the pure form you get the bad side effects which may include itchiness and of course the bitter taste.” Pharmaceutical potential “So, while extracting it from the natural source is desirable, it is not practical. That’s what makes our method attractive. It has the potential for cosmetic usage and pharmaceutical usage.” There has been speculation that it may work on arthritis – if rubbed on joints. There is also the possibility of an anaesthetic pain-killer. For example, introducing it in candy form, so that patients could suck on one at the dentist, replacing the need for pain-killing injections. Since Dr Toy’s method of synthesising HAS is so simple, is it perhaps surprising no one has thought of it before? “I think that is because too often we don’t look at the simple things,” says Dr Toy. “This is what I tell my students. What is obvious to you isn’t necessarily obvious to everyone. And sometimes you just need a new viewpoint to make a discovery. In this case, people have been studying HAS for the past four or five years, but those people are biologists and neuro-scientists not chemists. It took chemists to work out how to find a viable alternative.” M Harnessing the ‘Pep’ in Sichuan Peppercorns A hotpot dinner inspired a group of chemists to synthesise the chemical that causes that tingling sensation. Its potential uses are numerous. We found a means to make hydroxyl alpha sanshool that doesn’t require a lot of fancy technology or equipment or skills... and it can be done on an industrial scale. “Look at the everyday things around you. Question what you see, hear, taste, smell – that is how discoveries are made,“ says Dr Patrick Toy, Associate Professor, Department of Chemistry in the Faculty of Science. It was this kind of thinking that led him and his team to find a way to synthesise hydroxyl alpha sanshool (HAS), a chemical found in Sichuan peppercorns (huajiao) – the chemical that causes your lips and tongue to tingle and go slightly numb. The discovery has potential applications in pharmaceutical and cosmetic fields. The idea of experimenting with peppercorns was born when Dr Toy and his research group were enjoying a Sichuan hotpot dinner and began discussing the tingling sensation you get when eating the hot peppercorns in the dish. “It’s not spicy, it’s bitter and it has a numbing, tingling sensation,” says Dr Toy. “As we enjoyed our hotpot we contemplated what caused that numbing sensation and how it could be usefully applied in research.” The next day, Dr Toy looked it up on that seemingly unlikely spot for scientific discovery – Wikipedia. He found that the compound which causes the numbness was discovered 20 years but it is only in the past four or five years that people have begun studying how it works in detail. In recent years, interest has risen because of the potential applications for HAS and it has suddenly become a hot area of research. Efficient production Dr Toy began working alongside Dr Bo Wu and Dr Kun Li and several research students on a way to synthesise HAS. “We found a means to make HAS that doesn’t require a lot of fancy technology or equipment or skills. It can be made very efficiently in a way that is relatively simple, cheap and practical and it can be done on an industrial scale.” The synthesised HAS has attracted much attention – the results of this research were published recently in the journal SYNLETT as well as in the local press. Dr Toy has been in contact with a leading researcher at the University of ¡ ¢ £ ¤ ¥ ¦ § ¨ © ª « ¬ ¤ ® ¯ ¨ « ° ¤ ¥ « « ± ² ¤ « § ³ ¡ ´ ¯ « ´ ¤ ² ¤ ¬ « « ¨ £ ¤ ¥ ± ¥ « ´ ¨ ± ± ¨ ¬ ´ ¨ µ ¶ ³ ¡ ¤ · ² ¤ ¯ « ¬ ´ ± © ¤ ¯ « ¬ « ¯ § § ¥ « ³ ¡ ´ ¯ « ² ¨ ² ² ¨ ¡ ¤ « ± 19 Feburary 2013