Jasmonates and Tetrahydrojasmonic Acid: A Novel Class of Anti-Aging Molecules

February 2016 | Volume 15 | Issue 2 | Original Article | 206 | Copyright © February 2016

Macrene Alexiades MD PhD

Dermatology and Laser Surgery Center, New York, NY

Jasmonates are plant-derived hormones from linoleic acid that were originally isolated from jasmine, and which are involved in plant stress regulation, wound repair and defense. They have been demonstrated through in vitro and in vivo studies to possess anti-neoplastic properties. Most recently, a novel jasmonate analog was developed, tetrahydrojasmonic acid (LR2412), which possesses favorable characteristics for cutaneous application and which induces improvements in epidermal hyaluronic acid and thickness. Clinical application of LR2412 to facial skin has been demonstrated to reduce the appearance of wrinkles and photoaging. In this issue, a clinical trial is published demonstrating the results of topical application of this agent for th cosmetic treatment of wrinkle appearance, poor texture and large pores.

J Drugs Dermatol. 2016;15(2):206-207.


Plant-derived ingredients have moved to the forefront of topical agents in the treatment of skin aging. A class of plant-derived anti-aging ingredients that have been developed for cutaneous use in recent years is the jasmonates, so-named due to the discovery of methyl jasmonate from jasmine oil derived from Jasminum grandiflorum.1 Jasmonic acid is a plant hormone derived from linoleic acid, which is involved in plant stress regulation, wound repair, and defense.2 Exposure to stress, such as wounding or pathogens, triggers expression of jasmonates in plants, which in turn induces a proteinase inhibitor.3

I. Jasmonates

Jasmonates including jasmonic acid, methyl jasmonate, and cis-jasmone have been studied in various systems.4-6

II. LR 2412

Chemical Properties in Skin
Recently, jasmonate analogs have been developed. Among these, tetrahydrojasmonic acid (LR2412) possesses characteristics favorable for use in topical therapy, including excellent safety profile and bioavailability.7 LR2412’s amphiphilic properties have conferred its ability to efficiently penetrate through the stratum corneum and into the superficial dermis, as demonstrated by X-ray diffraction studies.7 LR2412 has been shown to induce desquamation through potential disruption of corneodesmosomes. 7
In Vitro Data
The effect of a jasmonic acid derivative, LR2412 (1 μm and 10 μm), was investigated on an in vitro reconstructed skin model.8 Using real-time reverse transcription polymerase chain reaction studies, results showed an increase in hyaluronan synthase 2 and hyaluronan synthase 3 expression.8 Furthermore, increases in hyaluronic acid (HA) deposits in basal and suprabasal layers of the epidermis were observed. The percentages of positive Ki67 keratinocytes in the basal layer and epidermis thickness were also seen to increase.8 The jasmonate analog has also been shown to stimulate deposition of laminin-5, collagen IV, and fibrillin near the dermo-epidermal junction.7

Clinical Data

Prior Studies
Clinical studies of LR2412 application for the treatment of wrinkles and skin aging have been reported. In one randomized, split-design controlled study, 42 women were randomized to apply LR2412 to one side of the face and the vehicle to the contralateral side twice daily for up to 3 months.7 Silicone replicas were taken and computer-analyzed. The results demonstrated a statistically significant decrease in total wrinkle surface in the crow’s feet area after 1 and 3 month’s use.7
Recently, topical application of LR2412 combined with retinol was compared with topical tretinoin in a double-blind randomized clinical trial for the treatment of photoaging.9 In that randomized, parallel, double-blind, controlled clinical study, 120 women applied Retinol 0.2%/LR2412 2% or tretinoin 0.025% every evening for 3 months. Improvement in wrinkles, mottled pigmentation, pores, and global photodamage were observed in both treatment arms with no statistically significant difference between them. Retinol 0.2%/LR2412 2% cream was better tolerated than tretinoin 0.025% cream. Thus, LR2412 combined with retinol was determined to be equivalent to tretinoin.9