Class 14 · Cosmetic & topical · expression-line + matrix-support peptide stack · topical cosmetic only · injectable blocked
Cosmetic Peptide StackArgireline · Matrixyl · Leuphasyl — a topical expression-line & collagen-support hub, not an injectable
These are three topical anti-aging skincare peptides that work in different ways. Argireline (Acetyl Hexapeptide-8) targets expression lines by interfering with the nerve-signal machinery behind facial-muscle contraction — often called "topical Botox," though it's far weaker and works only superficially. Matrixyl (Pal-KTTKS) is a collagen-fragment-inspired peptide meant to support the skin's matrix and improve photoaged skin. Leuphasyl (Pentapeptide-18) is an enkephalin-like peptide that softens expression lines. All three are topical cosmetics only.
This stack sits in a cosmetic-dermatology / aesthetic research lane for fine lines, early-to-moderate expression lines, photoaging texture, crow's feet, forehead and periorbital lines, roughness, hydration, and elasticity — not deep static folds, dermatochalasis, scarring, or neurologic spasm. Argireline and Leuphasyl are neurotransmitter-inhibiting peptides; Matrixyl is a matrikine signal peptide. The engine therefore splits endpoints: dynamic-wrinkle (Argireline + Leuphasyl) vs static/photoaging (Matrixyl).
Argireline (Ac-EEMQRR-NH₂) is a SNAP-25 N-terminal mimetic that competitively interferes with SNARE-complex assembly and Ca²⁺-dependent neurotransmitter exocytosis. Leuphasyl mimics enkephalin, inhibiting Ca²⁺ influx and reducing transmitter release, and enhances Argireline's effect ~1.5-fold. Matrixyl's KTTKS core is a matrikine from the procollagen-I C-terminal propeptide that signals fibroblasts to make collagen I/III, collagen IV, fibronectin, and GAGs; palmitoylation enables stratum-corneum penetration.
3 peptidesExpression-line + matrix stack
topicalCosmetic-only · OTC
dynamic + staticTwo endpoint lanes
BLOCKEDInjectable / oral / systemic
Status
Cosmetic topical only · concentration-reference engine · injectable blocked
COSMETIC TOPICAL ONLY · injectable & systemic output BLOCKED
These are topical cosmetic ingredients, not systemic peptides. Intrasigna blocks injectable, subcutaneous, intramuscular, oral, intranasal, ophthalmic, and mucosal protocols and makes no medical or botulinum-toxin-equivalence claims. The "dose" here is a topical concentration %, frequency, region, and endpoint — never a mg-to-mL injection. Verify supplier-solution % vs actual active-peptide % before reading any concentration.
01 · At a glance
Two mechanisms, one serum.
This is the foundation cosmetic-peptide page for the atlas. It pairs two neurotransmitter-inhibiting "expression-line" peptides (Argireline, Leuphasyl) with one matrikine "matrix-support" peptide (Matrixyl) into a rational topical stack — while keeping their evidence honestly separated. Matrixyl has the strongest human cosmetic data; Argireline has solid review/trial support; Leuphasyl is the weakest. The engine is a topical concentration + endpoint tracker, and every route except topical is blocked.
💉
Argireline
"Topical Botox"
A SNAP-25 mimetic that competitively blocks SNARE assembly to soften expression lines. Grade B/C.
🧵
Matrixyl
Collagen signal
A procollagen-I matrikine that signals fibroblasts to rebuild matrix. Strongest evidence — Grade B.
🔉
Leuphasyl
Expression support
An enkephalin-like peptide active at ≥2%; softens lines but inferior to Botox. Grade C/D.
🤝
Synergy
~1.5×
Leuphasyl enhances Argireline's wrinkle effect about 1.5-fold via a complementary mechanism. Grade C.
"10% Argireline solution" is not 10% pure peptide — the engine separates supplier vs active %. Admin rule.
⛔
Routes
Topical only
Injectable, oral, intranasal, ophthalmic, and mucosal use are blocked. Admin rule.
☀️
Endpoint validity
Sunscreen + photos
Daily SPF and standardized photo tracking are needed to judge anti-aging endpoints. Grade C.
02 · Mechanism of action
Two ways to soften a wrinkle.
A wrinkle has two sources: repeated muscle movement (dynamic expression lines) and loss of dermal matrix (static photoaging lines). This stack addresses both. Argireline and Leuphasyl quiet the nerve-to-muscle signal that creases skin during expression; Matrixyl sends a "build collagen" signal to fibroblasts to support the matrix underneath. They are not one mechanism and should never be evaluated as one.
Grade B/C
💉
1 · Argireline — SNARE/SNAP-25 mimicry
It impersonates a piece of the docking machinery nerves use to fire.
Mechanism: Acetyl Hexapeptide-8 mimics the N-terminal of SNAP-25 and competitively interferes with assembly of the SNARE complex required for Ca²⁺-dependent vesicle fusion, the same complex botulinum toxin targets — reducing acetylcholine-driven contraction signaling at superficial expression-line zones.
Detail: The hexapeptide (Ac-EEMQRR-NH₂, SNAP-25 aa 12–17) takes SNAP-25's place, preventing it from binding partners such as syntaxin-1a and VAMP2; a deficient SNARE complex yields less transmitter release. Whether topically applied AH-8 truly reaches neuromuscular junctions through skin remains uncertain. A palmitoylated acetyl-hexapeptide-3 variant has also been studied for dampening nociceptor exocytosis (TRPV1/CGRP), an adjacent research direction.
Grade C
🔉
2 · Leuphasyl — enkephalin-like modulation
It calms the nerve from a different angle, by limiting calcium entry.
Mechanism: Pentapeptide-18 mimics endogenous enkephalins, decreasing neuronal excitation by inhibiting Ca²⁺ influx and thereby reducing Ca²⁺-dependent neurotransmitter release — a complementary route to Argireline's SNARE interference.
Detail: By acting upstream on calcium-dependent excitation rather than on SNARE assembly itself, Leuphasyl addresses a different node of the same contraction-signaling pathway, which is the mechanistic basis for combining the two.
Grade C
🤝
3 · The Argireline + Leuphasyl synergy
Together they hit two points in the same signal, amplifying the effect.
Mechanism: Using Leuphasyl together with Argireline has been reported to enhance Argireline's effect roughly 1.5-fold — because one peptide limits calcium-dependent excitation while the other blocks SNARE assembly downstream.
Detail: This is the rationale for the "expression-line neuropeptide duo." It is a mechanism-based formulation logic, not equivalence to botulinum toxin, and the combined effect remains modest and topical.
Grade B
🧵
4 · Matrixyl — matrikine collagen signal
It mimics a natural "make more collagen" message the skin already uses.
Mechanism: KTTKS is a matrikine fragment from the C-terminal propeptide of procollagen I; when collagen is processed, the released KTTKS signals fibroblasts to sustain synthesis. Matrixyl supplies this signal exogenously without requiring collagen breakdown to trigger it.
Detail: In fibroblast culture Pal-KTTKS stimulates procollagen I, with reported increases in collagen synthesis and fibronectin (+~117%) along a bell-shaped 1–10 ppm dose-response, and also regulates collagen IV and glycosaminoglycan/hyaluronic-acid synthesis.
Grade B
🚪
5 · Palmitoylation — skin delivery
A fatty tail lets the otherwise water-loving peptide cross the skin barrier.
Mechanism: The 16-carbon palmitoyl chain makes the hydrophilic KTTKS sequence lipophilic enough to partition into the stratum corneum and reach fibroblasts — the conjugation is the delivery mechanism, not branding.
Detail: Studies of dermal stability and skin permeation contrast KTTKS with pal-KTTKS, showing the palmitoylated form penetrates and persists better; formulation (oil-in-water emulsion, pH ~5–6.5) further governs delivery.
Grade B/C
🧪
6 · Matrix output — beyond marketing
It changes real fibroblast behavior, not just surface appearance.
Mechanism: Pal-KTTKS at 0.1 µM reduced α-smooth-muscle-actin and fibroblast-to-myofibroblast transdifferentiation dose-dependently, showing it influences fibroblast biology beyond a cosmetic claim.
Detail: The original KTTKS was identified as "a pentapeptide from type I procollagen that promotes extracellular-matrix production"; Matrixyl translates that biology into a topical cosmetic with a recognizable human photoaging trial behind it.
L3 · two parallel pathways
Dynamic-line vs matrix-support routes
😐 Expression lane
Argireline + Leuphasyl
→
🔇 ↓ contraction signal
SNARE · Ca²⁺
→
🙂 dynamic lines ↓
crow's feet · forehead
‖
🧵 Matrix lane
Matrixyl (Pal-KTTKS)
→
🧬 ECM support
collagen · fibronectin
L2 · peptide-class map
Three peptides, two classes
Anti-aging topical-peptide reviews group these as neurotransmitter-inhibiting peptides (Argireline, Leuphasyl) versus signal/matrikine peptides (Matrixyl).
Peptide
Class
Endpoint lane
Argireline
Neurotransmitter inhibitor
Dynamic expression
Leuphasyl
Neurotransmitter inhibitor (enkephalin-like)
Dynamic expression (support)
Matrixyl
Matrikine / signal peptide
Static / photoaging
L3 · Matrixyl fibroblast output
Reported ECM effects (in-vitro)
Target
Effect
Note
Procollagen I / collagen I
↑ synthesis
Bell-shaped 1–10 ppm
Collagen III / IV
↑ expression
Matrix structure
Fibronectin
↑ (~117%)
ECM organization
GAG / hyaluronic acid
Regulated
Limits excess aged-skin GAG
α-SMA / myofibroblast
↓ (0.1 µM)
Fibroblast behavior
03 · Formulation engine & protocol lanes
A topical concentration engine — not an injection calculator.
These peptides never feed an injection calculator. The "dose" is a concentration %, application frequency, skin region, formulation type, duration, and endpoint — gated by route and skin condition. The lanes below match the peptide to the wrinkle type: dynamic expression lines (Argireline + Leuphasyl), static/photoaging texture (Matrixyl), the full triad, a sensitive-skin routine, and the explicitly blocked routes. The engine always separates supplier-solution % from actual active-peptide %, and outputs cosmetic concentration references only — never injectable, oral, or medical instructions.
Engine mode · topical cosmetic concentration reference
The calculator is route-gated (topical only), product-type-gated (no sterile/injectable/oral/nasal/ophthalmic forms), and concentration-basis-gated. If the active-peptide % is unknown, it returns "formulation review required," because supplier-solution % and pure active % must be separated.
Honest claim strength
Individual peptide claims can be stronger than stack claims. Matrixyl has the firmest human cosmetic trial; Argireline has supportive review/trial evidence; Leuphasyl is weakest. The triad is mechanism-rational, not proven superior as a standalone clinical stack.
Matrixyl is generally well tolerated (the key trial reported good tolerability), making it a gentle starting point.
Pause with dermatitis/rosacea flare; patch test; avoid broken skin and the eye/lash margin.
Sensitive · sequencing
Introduce gradually
Step
Action
Watch
Start
Matrixyl alone
Tolerance
Add
Low Argireline
Irritation
Separate
Acids/retinoids to alternate nights
Barrier
Blocked routes & outputs
Topical only
Blocked
Injectable / SC / IM / IV
Blocked — these are cosmetic topical ingredients, not sterile injectables.
Oral / intranasal
Blocked — no ingestion or nasal use.
Ophthalmic / mucosal
Blocked — never apply to the eye surface, lash margin, mucosa, or broken skin.
Medical claims
Blocked — no disease-treatment or botulinum-toxin-equivalence claims.
Sterile compounding
Blocked — no sterile/injection preparation guidance.
Output is limited to topical concentration references, frequency, region guidance, duration, endpoint tracking, and irritation warnings.
Route · status
Output rules by route
Route
Status
Output
Topical cosmetic
Allowed
Concentration reference
Injectable / SC / IM / IV
Blocked
None
Oral / intranasal
Blocked
None
Ophthalmic / mucosal
Blocked
None
L2 · Topical cosmetic concentration reference · no injection math
Concentration-Reference Engine
These are topical cosmetic peptides. This engine does not output injectable, oral, intranasal, or ophthalmic doses, sterile compounding, or medical/Botox-equivalence claims. It shows a topical concentration reference, frequency, and endpoint lane. Concentration percentages are formula-reference ranges — always verify the actual active-peptide % versus the supplier-solution %. Selecting any non-topical route returns BLOCKED. This is cosmetic research context, not medical advice.
Concentration (formula-reference)
—
Concentration basis
—
Frequency
—
Endpoint lane
—
Route / output
—
04 · Stacking & ingredient interactions
Building the routine around the peptides.
Unlike systemic peptides, the relevant "stacks" here are skincare-ingredient interactions — how these peptides sit alongside retinoids, acids, vitamin C, copper peptides, and sunscreen — plus the three defined peptide stack groups. Peptides are generally compatible with most actives, but barrier irritation from strong acids or retinoids can blunt tolerance, and sunscreen is non-negotiable for any anti-aging endpoint to be valid.
Expression-line duo
Stack group 1
ArgirelineLeuphasyl
Mechanism-rational dynamic-line duo — Leuphasyl enhances Argireline ~1.5×. Topical only; not equivalent to botulinum toxin; avoid mucosa/eyes. Grade C.
Endpoint
Target
Note
Crow's feet / forehead / glabella
Dynamic lines
Argireline stronger
Matrix-support (Matrixyl)
Stack group 2
Matrixyl
The best-evidenced lane — a human cosmetic study plus ECM mechanism. Topical cosmetic only; patch test; no wound-treatment claims. Grade B.
Endpoint
Target
Note
Roughness / static lines / firmness
Photoaging
Strongest evidence
Full cosmetic triad
Stack group 3
ArgirelineMatrixylLeuphasyl
Dynamic + static wrinkle appearance support in one serum. Combination-rational; direct triple-stack evidence limited. Cosmetic claims only. Grade C/D.
Endpoint
Target
Note
Wrinkle score / elasticity / hydration
Mixed lines
Formula stability review
+ Retinoids
Allow · tolerance caution
PeptidesRetinoid
Complementary anti-aging actives, but overlapping irritation can reduce tolerance — alternate nights if irritated. Allow with caution. Grade C.
Combo
Rule
Watch
Retinoid
Alternate if irritated
Barrier
+ AHA / BHA acids
Caution
PeptidesAHA/BHA
Exfoliating acids can compromise the barrier and reduce peptide tolerance; separate in the routine if irritation-prone. Caution. Grade C.
Combo
Rule
Watch
AHA/BHA
Separate if reactive
Irritation
+ Vitamin C / copper peptides
Formula-dependent
PeptidesVit C / GHK-Cu
Usually formula-dependent: avoid unstable low-pH conflicts with vitamin C; copper peptides may have formula-interaction/oxidation considerations — often best separated. Grade C.
Combo
Rule
Watch
Vit C / GHK-Cu
Separate / formula check
pH · oxidation
+ Sunscreen (daily)
Strongly recommended
PeptidesSPF
Daily sunscreen is strongly recommended — without UV protection, anti-aging endpoints are confounded and the routine's validity drops. Grade B.
Combo
Rule
Why
SPF
Daily AM
Endpoint validity
+ Botox / fillers
Adjunct, not replacement
PeptidesNeuromodulator/filler
Do not claim these peptides replace botulinum toxin or fillers; they can be a cosmetic adjunct after procedure recovery. Benzoyl peroxide is best avoided in the same routine if irritation-prone. Grade C.
Combo
Rule
Watch
Botox/filler
Adjunct after recovery
No replacement claim
Stack safety note — These peptides are topical cosmetic ingredients and should not be used for injectable, sterile, oral, intranasal, or ophthalmic protocols. The expression-line duo and triad are cosmetic appearance stacks, not botulinum-toxin replacements; introduce alongside acids/retinoids gradually and pause with active irritation.
05 · Safety & tolerance
A cosmetic, topical-only safety model.
These peptides have a generally favorable topical-tolerability profile and don't require lab biomarkers — they need skin baseline assessment and tolerance monitoring. The real safety work is route gating (topical only), region gating (never eyes/mucosa/broken skin), and timing around barrier-disrupting procedures, plus honest claim boundaries: cosmetic appearance, not medical treatment.
⛔ Topical cosmetic only — These are cosmetic ingredients; injectable, sterile, oral, intranasal, and ophthalmic protocols are blocked, and no medical or botulinum-toxin-equivalence claims are made. Avoid the eye surface, lash margin, mucosa, and broken skin, and pause with active dermatitis.
Standardized facial-expression photos, crow's-feet score, forehead and glabellar line scores — for the Argireline + Leuphasyl lane. Judge over 4–12 weeks of consistent use, with controlled lighting and positioning.
Static / matrix endpoints
Wrinkle depth, texture/roughness score, elasticity, firmness, and hydration for the Matrixyl lane, assessed over 8–12+ weeks. Smartphone imaging can help if baseline normalization and controlled imaging are used.
Tolerance & validity
Log irritation, redness, dryness, or stinging and adjust frequency. Maintain daily sunscreen so that any anti-aging change reflects the peptides rather than uncontrolled photodamage. Cosmetic appearance endpoints only — no medical outcomes.
Safety gates & claim boundaries
Condition / request
Concern
Action · grade
Injectable / subcutaneous / IM / IV use
Topical-only ingredients
Blocked
Oral / intranasal use
No ingestion/nasal basis
Blocked
Ophthalmic / eye-margin / mucosa
Irritation / unsafe site
Blocked
Open skin / wounds
Barrier compromised
Block application
Sterile compounding request
Not a sterile product
Blocked
Medical / disease-treatment claim
Cosmetic appearance only
Blocked
Botox/filler-equivalence claim
Not equivalent
Blocked
Active dermatitis / eczema / rosacea flare
Irritation risk
Pause / patch test
Recent peel / laser / microneedling
Barrier recovery
Pause until recovered
Severe rosacea / reactive skin
Tolerance
Caution / patch test
Known ingredient allergy
Hypersensitivity
Block product
Pregnancy / breastfeeding
Conservative caution
Cosmetic review only
Pediatric anti-aging use
Not appropriate
Block
Active skin infection
Treat first
Block cosmetic protocol
Unknown active-peptide %
Supplier ≠ active %
Formulation review
Irritation-prone + multiple strong actives
Barrier load
Sequence / alternate
No daily sunscreen
Endpoint validity
Add SPF
Perioral / lip-margin application
Mucosa proximity
Keep off vermilion/mucosa
Benzoyl peroxide in same routine
Irritation / peptide stability
Separate if reactive
Vitamin C low-pH layering
Formula incompatibility
Separate / formula check
Photosensitivity-risk regimen
UV exposure
Strict daily SPF
GRADE summary — Identities and mechanisms are well characterized (Argireline SNARE-mimetic B; Matrixyl matrikine B; Leuphasyl enkephalin-like C). Human cosmetic evidence is strongest for Matrixyl (B, photoaged-skin trial), supportive for Argireline (B/C, multiple wrinkle studies), and weakest for Leuphasyl (C/D). Stacks are mechanism-rational (C–C/D) rather than directly trial-proven. The decisive levers are route gating (topical only), region/timing gates (no eyes/mucosa/broken skin; pause around barrier procedures), the active-vs-supplier % distinction, and honest claim boundaries — cosmetic appearance, never medical treatment or Botox equivalence.
06 · Evidence base & studies
Honest evidence, peptide by peptide.
The credibility of a cosmetic-peptide page rests on not flattening the evidence. Matrixyl has the most-replicated human cosmetic data; Argireline has a foundational mechanism paper plus several wrinkle studies; Leuphasyl is mechanistically interesting but thinly studied. The stack is a rational formulation, not a proven clinical superior. Below, each claim is tied to its own source and grade.
Review of 302F/10M; wrinkle decreases, no significant AEs. Dermatology review.
Leuphasyl · 2014
≥2% lane
Botox-like at ≥2%, inferior to BoNT, expressivity preserved. Cosmetic study.
BArgireline · mechanism
A synthetic hexapeptide with antiwrinkle activity
The foundational paper rationally designed Ac-EEMQRR-NH₂ from the SNAP-25 N-terminus and showed it inhibits neurotransmitter release by interfering with SNARE-complex formation/stability, without oral toxicity or primary irritation at high doses — positioning Argireline as a biosafe topical alternative to botulinum toxin in cosmetics.
Topical 30-day use of a cream containing 10% Argireline was reported to reduce the depth of mimic wrinkles by around 30% versus placebo — an often-cited efficacy figure, though formulations and delivery vary widely between products.
A clinical study evaluated Argireline for periorbital wrinkles with safety/efficacy outcomes, and a 2023 study of an Argireline-containing serum found a slight decrease in wrinkle score by four weeks with no significant adverse events, allergic reactions, or irritation — modest, well-tolerated cosmetic effects.
A 2025 review summarized ten studies (302 females, 10 males); all reported decreases in wrinkle or scar prominence, though statistical significance varied, with no significant adverse effects, while noting uncertainty over whether AH-8 reaches neuromuscular junctions through the skin.
The KTTKS pentapeptide is a fragment of the procollagen-I C-terminal propeptide originally shown to promote extracellular-matrix production (Katayama 1993); Sederma's Pal-KTTKS adds a 16-carbon palmitoyl chain so the hydrophilic sequence can penetrate the stratum corneum.
A 12-week, double-blind, placebo-controlled, split-face study in 93 women (35–55) compared a moisturizer vs the same product with 3 ppm pal-KTTKS; pal-KTTKS was well tolerated and significantly improved wrinkles/fine lines by both quantitative and expert image analysis — the key human Matrixyl record.
In fibroblast culture, Pal-KTTKS stimulates procollagen-I with reported large increases in collagen synthesis and fibronectin (+~117%) along a bell-shaped 1–10 ppm dose-response, and at 0.1 µM reduced α-SMA and myofibroblast transdifferentiation dose-dependently — real fibroblast effects beyond marketing.
Dermal stability & skin permeation of KTTKS vs pal-KTTKS
A study of dermal stability and in-vitro skin permeation of the collagen pentapeptides KTTKS and palmitoyl-KTTKS demonstrated the role of palmitoylation in penetration and persistence — the delivery rationale that makes Matrixyl topically useful where bare KTTKS is not.
A 2014 cosmetics study concluded Leuphasyl has Botox-like wrinkle-softening action at a minimum 2% concentration but is clearly inferior to botulinum-toxin injections while preserving facial expressivity, and a 2025 review describes Pentapeptide-18 as promising but less studied than other neurotransmitter-inhibiting peptides.
Combining Leuphasyl with Argireline has been reported to enhance Argireline's wrinkle-reducing effect roughly 1.5-fold, because Leuphasyl limits Ca²⁺-dependent excitation while Argireline blocks SNARE assembly downstream — the rationale for the expression-line duo, which remains non-equivalent to botulinum toxin.
Pal-KTTKS stimulates collagen I/III and collagen IV and regulates glycosaminoglycan/hyaluronic-acid synthesis, including limiting the excess GAG accumulation seen in aged and photodamaged skin — a broader matrix-support profile than a single-collagen claim.
The original Matrixyl led Sederma to develop later matrikine systems such as Matrixyl 3000 (Palmitoyl Tripeptide-1 + Palmitoyl Tetrapeptide-7), adding anti-inflammatory activity to the collagen-stimulating effect — natural future expansions of this hub's matrix-support lane.
Anti-aging topical-peptide reviews classify cosmetic peptides into neurotransmitter-inhibiting peptides (Argireline, Leuphasyl) and signal/matrikine peptides (Matrixyl) — which is exactly why this engine splits dynamic-expression endpoints from static/photoaging endpoints rather than treating the stack as one mechanism.
A palmitoylated acetyl-hexapeptide-3 variant has been explored for dampening exocytosis in nociceptive neurons — reducing recruitment of TRPV1 channels and release of CGRP in laboratory models — an adjacent research direction that underscores the peptide's exocytosis-modulating mechanism (not a cosmetic claim).
Many cosmetic peptide raw materials are sold as diluted solutions, so a "10% Argireline solution" is not necessarily 10% pure peptide; the engine requires both an ingredient-supplier-solution % and an actual-active-peptide % so concentration lanes aren't misread.
Intrasigna publishes these as cosmetic topical peptides — injectable, subcutaneous, intramuscular, intravenous, oral, intranasal, ophthalmic, and mucosal protocols are blocked, sterile compounding is blocked, and no medical or botulinum-toxin-equivalence claims are made, with daily SPF and standardized imaging required for valid anti-aging endpoints.
The most important comparison is the one this page refuses to overstate: topical neurotransmitter-inhibiting peptides are not botulinum toxin. They are non-invasive, work superficially with repeated use, and produce modest appearance changes. Among themselves, the three split into two classes — and this hub is the template for the rest of the cosmetic-peptide family.
L1 · Consumer — Argireline, Matrixyl, and Leuphasyl are topical anti-aging skincare peptides. Argireline and Leuphasyl gently soften expression lines (forehead, crow's feet) by calming the nerve signal behind muscle movement; Matrixyl supports collagen for smoother, firmer skin. They're applied to the skin, not injected, and they're much milder than Botox. Give them 8–12 weeks, wear daily sunscreen, keep them away from your eyes and any broken skin, and treat results as cosmetic — these aren't medical treatments.
L2 · Aesthetic — A cosmetic-dermatology stack pairing two neurotransmitter-inhibiting peptides (Argireline, Leuphasyl; dynamic expression lines) with a matrikine (Matrixyl; static/photoaging texture and matrix support). Matrixyl has the strongest human cosmetic evidence; Argireline is supportive; Leuphasyl is weakest but synergizes ~1.5× with Argireline. Dosing is a topical concentration reference (verify active vs supplier %), not injection math; route is topical-only; endpoints run 8–12 weeks with standardized photos and daily SPF.
L3 · Research — Argireline (Ac-EEMQRR-NH₂) is a SNAP-25 (aa12–17) mimetic competing in SNARE assembly to reduce Ca²⁺-dependent exocytosis; Leuphasyl (Pentapeptide-18) is an enkephalin-mimetic limiting Ca²⁺ influx, enhancing Argireline ~1.5×. Matrixyl (Pal-KTTKS) is a procollagen-I C-terminal-propeptide matrikine driving fibroblast collagen I/III/IV, fibronectin, and GAG synthesis (bell-shaped 1–10 ppm), delivered via palmitoylation across the stratum corneum. Human evidence: Robinson 2005 (Matrixyl) strongest; Argireline multiple wrinkle studies; Leuphasyl thin. Topical-only, cosmetic-claims-only; no botulinum-toxin equivalence.
08 · References & evidence
Source register.
Evidence grades reflect the strength of support for the specific claim cited, not the prestige of the journal. Matrixyl's photoaging trial and matrikine mechanism are the firmest cosmetic records; Argireline's mechanism and wrinkle studies are supportive; Leuphasyl's evidence is thinnest. Formulation and admin sources anchor the active-vs-supplier-% rule and the topical-only gating.