Topical application of Zanthoxylum piperitum extract improves lateral canthal rhytides by inhibiting muscle contractions

Abstract

Facial wrinkles are the predominant phenotypes of skin aging. To date, one of the most effective ways to improve wrinkles is botulinum toxin type A (BoNT/A) injection, which inhibits muscle contractions by reducing acetylcholine release from neurons. However, since BoNT/A is a hazardous neurotoxin, the injection can only be performed by medical doctors and the procedure is only possible through invasive injection, causing inconveniences such as pain. To overcome these inconveniences, we tried to find a way to reduce wrinkles non-invasively via mechanisms similar to BoNT/A. We first designed in vitro assays to test BoNT/A-like muscle contraction inhibition in two different model systems. By using the assays, we identified Zanthoxylum piperitum (Z. piperitum) fruit extract as a BoNT-like reagent (27.7% decrease of muscle contraction rates by 1000 ppm of Z. piperitum extract treatment). Next, we determined mechanisms of how Z. piperitum extract decreases muscle contraction rates and found that the extract treatment inhibits electrical signal transduction in neurons. We also showed that among known components of Z. piperitum extract, quercitrin is responsible for muscle contraction inhibition. We further identified that Z. piperitum extract has synergistic effects with acetyl hexapeptide-8 and BoNT/A light chain, which are well-known BoNT-like peptides. Finally, we showed that topical treatment of the Z. piperitum extract indeed decreases facial wrinkles and treatment of Z. piperitum extract with acetyl hexapeptide-8 has a tendency to improve wrinkles synergistically (14.5% improvement on average). The synergistic effect of the combination is expected to improve wrinkles effectively by implementing the BoNT/A mechanisms in a non-invasive way.

Clinical evidence of the efficacy and safety of a new multi‐peptide anti‐aging topical eye serum

“…Besides, the anti-wrinkle effect of plant extracts has recently attracted extremely interest. [33][34][35] Most aim to slow skin Independently, positive responses to the product-evaluation questionnaire administered at the end of the study confirmed consumer acceptance.…”

“…Previously published studies 30–32 have primarily focused on the combination of peptides with antioxidants for the topical treatment of aging (with enhanced performance compared to antioxidants alone). Besides, the anti‐wrinkle effect of plant extracts has recently attracted extremely interest 33–35 . Most aim to slow skin aging by repairing the disruption and fragmentation of the ECM and preventing the loss of collagen and elastin.…”

Hydroxy-β-sanshool isolated from Zanthoxylum piperitum (Japanese pepper) shortens the period of the circadian clock

“…1 Many other components and physiological functions of Sanshō have been identified and added to the traditional body of knowledge. For example, quercitrin can inhibit muscle contraction 2 and it is also a tyrosinase inhibitor, 3 ( E )-β-caryophyllene protects against chronic inflammation, 4 and flavonol glycosides from Z. piperitum have anti-viral activity against influenza. 5 Eleven compounds including lignans, flavonoids and phenolics with peroxyl radical-scavenging activities have been isolated from Z. piperitum roots, and they seem to have important roles in the anti-oxidative activity of this plant.…”

Zanthoxylum Species: A Review of Traditional Uses, Phytochemistry and Pharmacology in Relation to Cancer, Infectious Diseases and Sickle Cell Anemia

“…Z. piperitum Benn.) is widely used as a food condiment because of its perceived health benefits Hwang et al (2008) and as cosmetics for maintaining skin quality ( Hwang et al, 2020 ). In Chinese medicine, Z. bungeanum is used as spices and for treating infection and bone diseases ( Lee and Lim 2008 ; Kim et al, 2017 ).…”