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Neuroactive cosmetics? Psychodermatology? Plants in skincare advertising.

No, you didn’t miss the birth of new scientific branches: those words are just advertising by the skin care industry, where, unfortunately, most of the creativity happens in the advertising department (not in the formulation lab).

The “neuroactive cosmetic” in this case is Zanthoxylum alatum fruit extract (tumbru. timut pepper, Sichuan pepper). Timut pepper grows as shrubs in the southern edge of the Himalayas, but also grows in Pakistan, Japan, Korea and further in South West Asia. The fruits are sun-dried after harvesting and they are used as a spice for traditional dishes.The fruits of timut pepper are also used as traditional remedy for toothache  and other ailments. 

Figure. Zanthoxylum alatum Curtis’s Botanical Magazine, London., vol. 144, 1918.

At Skin Actives, we take plants and their secondary metabolites, very seriously. Unless you are a believer in the fundamental love of Mother Earth for her humans (I am not), you will know that plants and animals have lots of chemicals that are dangerous, even lethal, to us. Many plant chemicals are beneficial, but the burden of proof is heavy, just like it should be; safety is most important and timut pepper probably is:  an ingredient of the Chinese ‘five spice’ mixture; its use as a spice indicates that it’s probably safe used at small concentrations.

Why call this spice “neuroactive”? It seems to relieve “depression-like” symptoms in lab rats, hence the “jump” that it can do so in humans when used topically.That’s quite a jump.

In our bathrooms we have examples of neuroactive plant chemicals, like menthol, a chemical that triggers the cold-sensitive TRPM8 receptors in the skin and gives us a cooling sensation . There is also a long list of plant chemicals that have profound effects of the human brain, some are well understood. We know of the long-term effects of plant chemicals that can bind to neural receptors. Caveat emptor (buyer beware!).

Secondary metabolites, the plant chemicals  that are not directly involved in the growth, development or reproduction of the plant (like chlorophyll, cellulose or Rubisco) are present in all higher plants.  More than 100 years ago Ernst Stahl, a pioneer of ecophysiology, showed that secondary metabolites serve as defense compounds against snails and other herbivores. At the time, other botanists preferred the simpler explanation that secondary metabolites were waste products of primary metabolism but today, adaptive explanations are preferred to explain the existence and diversity of secondary metabolites.

Plants cannot run away when they are attacked by snails, insects or vertebrate herbivores, and they don’t have an immune system to protect them when attacked by bacteria, fungi or viruses. Herbivores and microbes were already there as plants had to evolve survival strategies. Like other immobile or slow moving organisms (like amphibians, marine sponges, corals) plants have evolved defense chemicals to defend from or kill their enemies.  Many alkaloids represent adaptations that has appeared during evolution by natural selection in order to protect against viruses, bacteria, fungi, competing plants and herbivores.

Sometimes, chemicals have dual functions, both attractive and defensive activities: anthocyanins or monoterpenes can be insect attractants in flowers requiring pollination, but are insecticidal and antimicrobial at the same time. In addition, some secondary metabolites also carry out physiological functions, for example alkaloids and peptides (lectins, protease inhibitors) can serve as mobile and toxic nitrogen transport and storage compounds. Phenolics like flavonoids, can function as UV-protectants or antioxidants.

Many specific interactions of secondary metabolites with proteins like enzymes, receptors, ion-channels, structural proteins and other cellular components have been studied . Structures of these defense chemicals have been shaped during evolution in a way that they can mimic the structures of endogenous substrates, hormones, neurotransmitters or other ligands. This process has been called ‘‘evolutionary molecular modelling’’ (like that done by modern pharmacologists in their labs). For example, under physiological conditions several alkaloids adopt a configuration in space that looks like neurotransmitters; many alkaloids are analogs or antagonists of neurotransmitters and neuroreceptors . These defense chemicals are useful for plants against most vertebrates, not just humans, because the basics of neuronal signalling pathways are similar in animals. These inhibitors have the advantage that corresponding molecular targets are not present in the plant producing these compounds so they don’t interfere with the plant itself. Other examples of specific interactions are cardiac glycosides (inhibit Na+, K+-ATPase), cyanogenic glycosides (they block cytochrome oxidase in respiratory chain), or salicylates (inhibit cyclooxygenase and prostaglandin formation).

What’s the take home message? That Mother Nature is not necessary benevolent to humans. Human, defend yourself: use only plant chemicals or extracts that have been shown through millennia to be safe. Trust chemicals once the mechanism of action is/are well understood; check on the long-term effect of those chemicals on the human body.

You can use the plant derived ingredients (hundreds of them) used by Skin Actives for safety and effectiveness. As for Zanthoxylum alatum, you can go all the way to the Himalayas and pick up the fruits, buy a neuroactive cosmetic or purchase the spice in your local store (look for Sichuan pepper). I don’t think the cosmetic will alleviate depression, but cooking is good for you and the spice will make for a nice dinner.


Prakash B, Singh P, Mishra PK, Dubey NK. (2012) Safety assessment of Zanthoxylum alatum Roxb. essential oil, its antifungal, antiaflatoxin, antioxidant activity and efficacy as antimicrobial in preservation of Piper nigrum L. fruits. Int J Food Microbiol. 2012 153:183-91. doi: 10.1016/j.ijfoodmicro.2011.11.007. Epub 2011 Nov 15. PMID: 22137251.

Barua CC, Haloi P, Saikia B, Sulakhiya K, Pathak DC, Tamuli S, Rizavi H, Ren X. (2018)  Zanthoxylum alatum abrogates lipopolysaccharide-induced depression-like behaviours in mice by modulating neuroinflammation and monoamine neurotransmitters in the hippocampus. Pharm Biol. 56:245-252. doi: 10.1080/13880209.2017.1391298. PMID: 29569964; PMCID: PMC6130615.

Tang D, Liang Q, Zhang M, Li M, Zhang Q, Zhang S, Ai L, Wu C. (2022) Anti-depression effectiveness of essential oil from the fruits of Zanthoxylum bungeanum maxim. on chronic unpredictable mild stress-induced depression behavior in mice. Front Pharmacol. 13:999962. doi: 10.3389/fphar.2022.999962. PMID: 36204228; PMCID: PMC9530639.
Wink, M. (2003). Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective. Phytochemistry, 64: 3–19. doi:10.1016/s0031-9422(03)00300-5