A Serendipitous Finding, A New Scientific Innovation

Current research indicates that dynamic wrinkles—or expression lines—are not solely the result of structural skin aging but are closely associated with continuous neuro-muscular contraction. When neural signals are constantly transmitted to the muscles, repeated contractions and chronic skin folding eventually lead to the formation of permanent expression lines.

This neural dynamic process primarily involves three critical stages: 

Stage 1: Signal Conversion

Intracellular calcium ions (Ca²⁺) in neurons rise rapidly, converting electrical impulses into chemical signals and stimulating the fusion of synaptic vesicles with the presynaptic membrane. 

Stage 2: Neurotransmitter Release

Acetylcholine is released from the presynaptic membrane and captured by the postsynaptic membrane, effectively transmitting the contraction signal to the muscle. 

Stage 3: Physical Contraction

Myosin acts as the molecular motor to drive muscle contraction, resulting in repeated skin folding. To determine if PMSoothe® Kava97 could truly improve dynamic wrinkles, we investigated whether it acts on key regulatory nodes within this neuro-muscular signaling cascade. 

1. Can it attenuate neural excitation signals?

The initiation of neural signals is dependent on the rapid elevation of intracellular Ca²⁺. Ca²⁺ is not only a vital signaling molecule for neuronal excitation but also the primary "switch" for neurotransmitter release. Therefore, regulating Ca²⁺ levels may modulate neuro-muscular signal transmission from the very beginning of the pathway. 

We established a neuronal cell model using fluorescent probes to label intracellular Ca²⁺. By detecting changes in fluorescence intensity to reflect intracellular Ca²⁺ levels, we verified the regulatory capacity of PMSoothe® Kava97 on neural excitation signals. 

Results: Under 0.625% PMSoothe® Kava97, intracellular Ca²⁺ levels were downregulated by approximately 30%. This suggests that Kava97 may reduce neural excitation at the source, potentially modulating subsequent neurotransmitter release. 

However, reducing Ca²⁺ levels alone is insufficient to fully explain the observed instant anti-wrinkle performance. Consequently, we continued to investigate: is the transmission of neural signals to the muscle truly reduced?

Graph: Ca²⁺ Concentration Test Results

2. Can it inhibit the release of Acetylcholine?

Neural signals must be transmitted to the muscle via Acetylcholine to trigger contraction. This process relies on the SNARE complex mediating the fusion of synaptic vesicles with the presynaptic membrane, where VAMP2 is a critical regulatory protein. 

Using a neuronal cell model, we detected the expression of the synaptic vesicle membrane protein VAMP2 via immunofluorescence and ELISA. 

Results: At 0.625% concentration, VAMP2 expression was downregulated by 19.57%. To further confirm the impact on neurotransmitter release, we employed the human neuroblastoma SH-SY5Y cell model. By inducing chemical depolarization with KCl to construct a high-release neural excitation model, we detected Acetylcholine secretion in the supernatant via ELISA to directly simulate neuronal excitation and confirm if the active could truly reduce acetylcholine release. 

Results: The addition of 0.5% PMSoothe® Kava97 reduced Acetylcholine release by 7.54%.

This indicates that PMSoothe® Kava97 not only affects signal initiation but also reduces Acetylcholine release, further lowering neuro-muscular signal transmission efficiency.

PMSoothe® Kava97 Addresses Expression Lines Across the Entire Signaling Pathway

VAMP2 Test Results

Acetylcholine Release Inhibition Rate

3. Can it modulate muscle contraction?

Myosin is the "molecular motor" providing the power for muscle contraction. Based on a neuronal cell system, we utilized immunofluorescence to detect Myosin expression levels. This experiment aimed to verify if PMSoothe® Kava97 acts directly on the terminal endpoint of dynamic wrinkle formation, weakening the driving force from the effector stage. 

Results: At 0.625%, Myosin expression was downregulated by 53%. This implies that PMSoothe® Kava97 may reduce muscle contraction capacity in addition to neural signal generation and transmission. 

Together, these findings provide a mechanistic explanation for the initially observed rapid anti-wrinkle effect.

Diagram: Myosin Action Mechanism

Graph: Myosin Expression Results

Clinical Validation: Evidence from Real Skin

Mechanism studies are only the beginning. Truly valuable discoveries must be validated on human skin through rigorous clinical testing. 

We commissioned Intertek, the world's second-largest testing organization, to conduct a standardized In Vivo Efficacy Study. The test strictly followed industry standards for cosmetic efficacy evaluation and complied with ethical requirements for human trials; all subjects participated voluntarily after being fully informed.

A total of 44 candidates were screened, with 32 healthy Chinese women aged 30-50 successfully enrolled. All exhibited prominent facial expression lines and crow's feet. A randomized, split-face study was used: one side received a base moisturizing placebo cream, while the other side received a test sample containing 2% PMSoothe® Kava97. Subjects applied the products morning and night after cleansing. Efficacy was evaluated at Baseline, Day 7, and Day 14 through professional skin diagnostic instruments combined with subjective self-assessments.

Crow's Feet Improvement Case

 Data indicates that the anti-wrinkle efficacy of PMSoothe® Kava97 is clearly measurable: after only 7 days, the number of crow's feet decreased by 24.10%, with significant improvements in wrinkle depth, area, and length. After 14 days, the improvement was further enhanced: crow's feet count reduced by 27.45%, and wrinkle volume decreased by 15.36%, resulting in a shallower and smoother texture overall.

Anti-wrinkle Efficacy In Vivo (7 days & 14 days) 

Note: The lower the parameter value, the fewer wrinkles on the skin, the smaller their volume, the shallower their depth, the smaller their area, the shorter their length, and the smaller their proportion. 

Simultaneously, skin firmness and elasticity were improved. By Day 14, skin elasticity increased by 13.15%, with a firmer and plumper feel. In contrast, the side treated only with the base cream showed minimal improvement, highlighting a significant difference. 

Skin Firmness Efficacy In Vivo (7 days & 14 days) 

Note: The lower the F0 value for skin firmness, the firmer the skin. The higher the skin elasticity R2 value, the better the skin elasticity. 

Subjective feedback from volunteers highly correlated with the instrumental results: at Day 7, over 90% of subjects reported a visible reduction in wrinkles, and fading of crow's feet and nasolabial folds, with firmer and more elastic skin. 100% of subjects rated the product as mild and non-irritating. After 14 days, all subjects recognized the anti-wrinkle and firming effects, with overall product satisfaction reaching 100% and zero reports of irritation throughout the process.

Statistical results of self-report questionnaires from subjects after 7 days of continuous sample use

Statistical results of self-report questionnaires from subjects after 14 days of continuous sample use

From neuronal cell experiments to mechanism analysis and third-party In Vivo Efficacy Study, Plamed has established a robust body of evidence PMSoothe® Kava97 covering neural signal initiation, neurotransmitter release, and muscle contraction regulation. 

Plamed Philosophy

Innovation does not stem from serendipity itself, but from an attitude of continuous exploration and scientific validation toward every experimental observation.We believe that truly valuable innovation is a discovery built on the foundation of rigorous research and consistent validation.