Resolve+ — Advanced Support for Healthy Inflammatory Balance and Cellular Recovery

Chronic low-grade inflammation is not a single pathway problem. Resolve+ was not built as a single pathway solution.*

Most inflammatory balance supplements target one mechanism — typically COX-2 inhibition through curcumin or Boswellia. Resolve+ was designed around the understanding that persistent, age-related inflammatory signaling operates through multiple simultaneous pathways: the endocannabinoid system, NF-κB transcription, COX and LOX enzyme cascades, oxidative stress signaling, gut-immune inflammatory tone, and cellular antioxidant defense.

Six clinically studied ingredients. Six complementary mechanisms. One formula designed to support inflammatory balance across the full biological spectrum — for joint comfort, muscle recovery, cellular resilience, and systemic vitality.*

KEY SUPPORTED BENEFITS

Resolve+ is formulated to support:*

• Healthy inflammatory response balance — multi-pathway support*
• Joint comfort, flexibility, and healthy mobility*
• Muscle recovery and reduced exercise-associated discomfort*
• Endocannabinoid tone and healthy CB2 receptor signaling*
• NF-κB pathway modulation and healthy cytokine balance*
• COX and LOX enzyme balance — healthy eicosanoid signaling*
• Cellular antioxidant defense and oxidative stress resilience*
• Gut and immune inflammatory balance*
• Vascular and tissue health through antioxidant and polyphenol activity*
• Respiratory comfort and healthy histamine response*

THE SIX-PATHWAY INFLAMMATORY BALANCE SYSTEM

• Endocannabinoid Modulation → Acmella oleracea (spilanthol — CB2 agonist, FAAH inhibitor)
• NF-κB & Cytokine Balance → Theracurmin Super® 85X + CurcuPrime® (dual curcuminoid system)
• COX/LOX & 5-Lipoxygenase → Casperome® Boswellia Phytosome (AKBA — 5-LOX inhibition)
• Broad Polyphenol Defense → Quercetin Phytosome® (20x bioavailability · antioxidant · immune)
• Multi-Pathway Comfort → Perilla frutescens (luteolin, apigenin, rosmarinic acid)
• Bioavailability Foundation → AstraGin® (nutrient transporter upregulation)

THE FORMULA

Acmella oleracea (Jambu Extract, standardized for Spilanthol)

Role: Endocannabinoid System Modulation — CB2 Receptor Agonism & FAAH Inhibition Sustainably sourced from Sardinia, Italy

Acmella oleracea — known as jambu or the "toothache plant" — is one of the most pharmacologically interesting ingredients in the Resolve+ formula, and the one most likely to be unfamiliar to practitioners. Its primary bioactive compound, spilanthol, works through a mechanism that is distinct from every other ingredient in the formula: direct engagement with the endocannabinoid system.*

The endocannabinoid system is one of the body's most important regulatory networks for inflammatory balance, comfort signaling, stress response, and immune tone. It operates through two primary receptor types — CB1 (primarily CNS) and CB2 (primarily peripheral tissues and immune cells) — and is modulated by endogenous cannabinoids including anandamide and 2-arachidonoylglycerol (2-AG).*

Spilanthol engages this system through two complementary mechanisms:

CB2 Receptor Agonism: Spilanthol has been shown to directly activate human CB2 receptors — the peripheral cannabinoid receptors expressed on immune cells, joints, and connective tissues — where CB2 activation supports healthy inflammatory tone and comfort without the psychoactive effects associated with CB1 stimulation.* A published receptor pharmacology study confirmed that Acmella oleracea extract and pure spilanthol exerted significant CB2 activation in human cell-based assays, with CB2-receptor-specific effects confirmed on mock cell lines.*

FAAH Inhibition: Spilanthol inhibits fatty acid amide hydrolase (FAAH) — the enzyme responsible for breaking down anandamide and other endogenous cannabinoids. By slowing FAAH activity, spilanthol supports higher endogenous levels of anandamide, extending its comfort-supporting and anti-inflammatory signaling activity.*

Additional published mechanisms:*

• NF-κB pathway modulation: spilanthol inhibits LPS-induced NF-κB activation in macrophages, reducing downstream inflammatory mediator production including iNOS, COX-2, IL-1β, IL-6, and TNF-α in preclinical models*
• Sodium channel modulation: local anesthetic-like activity supporting tissue comfort*
• Blood-brain barrier permeability: pharmacokinetic research confirms spilanthol crosses the blood-brain barrier with a high unidirectional influx rate — delivering central as well as peripheral effects*

A 2024 observational study found that Acmella oleracea combined with Boswellia supported comfort and mobility outcomes in subjects with musculoskeletal concerns — the same two ingredients that anchor Resolve+'s joint comfort positioning.*

A 2025 systematic review of the Acmella genus for musculoskeletal disorders found consistent anti-inflammatory, analgesic, and anti-arthritic properties across clinical and preclinical evidence.*

Acmella oleracea provides a genuinely novel mechanism that no other ingredient in the inflammatory balance supplement category addresses — making it one of the most differentiating clinical reasons to choose Resolve+ over standard curcumin or Boswellia formulas.*

Theracurmin Super® 85X (Amorphous Curcumin, 36% Curcumin)

Role: NF-κB Pathway Support, Cytokine Balance & Systemic Antioxidant Defense — 85x Bioavailability

Curcumin is one of the most studied natural anti-inflammatory compounds in existence — with thousands of peer-reviewed publications documenting its activity across NF-κB, COX-2, iNOS, and cytokine pathways. The limitation of standard curcumin has always been its bioavailability: crystalline curcumin is highly lipophilic, poorly water-soluble, and poorly absorbed, with oral bioavailability as low as 1% in some studies.*

Theracurmin Super® 85X solves this through Amorphous Conversion Technology — converting crystalline curcumin into an amorphous nano-particle state with dramatically improved water solubility and dispersion. Unlike crystalline curcumin which resists dissolution in aqueous environments, amorphous curcumin disperses readily in the gut environment, supporting dramatically enhanced absorption.*

Clinical Bioavailability Evidence:*

• Randomized crossover pharmacokinetic study (NCT04028739): Theracurmin demonstrated 18.4–20.5-fold higher maximum plasma concentration (Cmax) and 35.9–42.6-fold higher AUC versus unformulated curcumin powder*
• Earlier Theracurmin research demonstrated 27-fold higher AUC versus commercially available curcumin*
• Theracurmin Super® further improves on the original Theracurmin: 1.54-fold higher Cmax and comparable AUC versus CR-033P at half the dose — representing the highest bioavailability curcumin formulation in the Theracurmin series*
• 2024 randomized double-blind, placebo-controlled parallel trial: Theracurmin Super® significantly affected oxidative stress index (OSI) values in healthy adults following exercise-induced oxidative stress*
• 12-month double-blind placebo-controlled trial: Theracurmin showed chondroprotective effects in patients following knee surgery, with anti-inflammatory markers significantly improved versus placebo*

At effective absorbed doses, curcumin's anti-inflammatory mechanisms include:*

• NF-κB pathway inhibition — reducing the transcription of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8)*
• COX-2 and iNOS downregulation*
• Nrf2 pathway activation — upregulating endogenous antioxidant defense*
• Direct antioxidant and free radical scavenging activity*

CurcuPrime® (Tetrahydrocurcumin)

Role: Direct Antioxidant Defense, Phase II Detoxification & Curcuminoid Metabolic Delivery

CurcuPrime® delivers tetrahydrocurcumin (THC) — the primary active metabolite that curcumin is converted to in the body, delivered directly for consistent and predictable bioavailability.

Tetrahydrocurcumin provides:*

• More potent direct antioxidant activity than curcumin itself — greater DPPH radical scavenging capacity due to its reduced double bonds*
• Superior metabolic stability: unlike curcumin which undergoes rapid phase II metabolism, tetrahydrocurcumin is inherently stable and maintains circulating activity longer*
• Phase II detoxification enzyme induction through Nrf2 pathway activation*
• Complementary anti-inflammatory activity through NF-κB and cytokine pathway modulation*
• White color and neutral flavor — no staining, no taste impact*

Together, Theracurmin Super® 85X and CurcuPrime® provide complementary curcuminoid coverage: Theracurmin Super® delivers rapidly absorbed, highly bioavailable parent curcumin for immediate activity; CurcuPrime® delivers the active metabolite for sustained antioxidant and anti-inflammatory support — addressing both the acute and the sustained dimensions of curcuminoid activity.*

Casperome® (Boswellia serrata Resin Extract, standardized to AKBA)

Role: 5-LOX Inhibition, Joint Comfort & Leukocyte Migration Support

Casperome® is Indena's clinically studied Phytosome® formulation of Boswellia serrata resin — standardized to boswellic acids including AKBA (acetyl-11-keto-β-boswellic acid), the most pharmacologically active boswellic acid.*

Boswellia's primary mechanism is distinct from curcumin's NF-κB focus: AKBA specifically inhibits 5-lipoxygenase (5-LOX) — the enzyme that converts arachidonic acid into leukotrienes, a class of pro-inflammatory lipid mediators particularly involved in joint tissue inflammation, respiratory inflammation, and vascular inflammatory tone.* This LOX pathway inhibition is complementary and non-redundant to curcumin's primarily COX-pathway activity — together they address both major arachidonic acid inflammatory cascades simultaneously.*

AKBA also supports healthy leukocyte elastase activity and modulates LFA-1 binding — limiting leukocyte migration to sites of tissue stress and supporting joint tissue health.*

The challenge with standard Boswellia extracts: boswellic acids are poorly water-soluble and have limited oral bioavailability in conventional supplement forms. Casperome® uses Indena's Phytosome® technology to complex Boswellia with phospholipids at the molecular level — significantly improving oral absorption and consistent delivery of active boswellic acid fractions.*

Clinical Evidence — Casperome®:*

• Multiple randomized, controlled human trials demonstrating support for joint comfort, mobility, and physical function scores in adults with joint health concerns*
• 2024 observational study: Acmella oleracea combined with Boswellia (the two lead endocannabinoid-modulating and LOX-inhibiting ingredients in Resolve+) supported comfort and mobility outcomes in adults with musculoskeletal concerns — validating the specific combination used in this formula*
• Casperome® Phytosome absorption significantly higher than standard Boswellia extract in comparative bioavailability studies*

Quercetin Phytosome® (Quercefit™)

Role: Cellular Antioxidant Defense, Immune Modulation & Broad Inflammatory Signaling Support

Quercetin Phytosome® (Quercefit™) delivers quercetin complexed with lecithin phospholipids through Indena's Phytosome® technology — achieving up to 20-fold higher bioavailability versus standard quercetin aglycone, confirmed by a 2024 systematic review and meta-analysis of 31 human intervention studies.*

Quercetin's anti-inflammatory and antioxidant mechanisms span multiple pathways:*

• Inhibition of pro-inflammatory kinases and transcription factors including NF-κB and AP-1*
• Mast cell stabilization and healthy histamine response support*
• Antioxidant activity across both lipophilic and hydrophilic cellular compartments*
• Immune modulation — supporting regulatory T-cell activity and balanced cytokine profiles*
• Vascular integrity and endothelial health support*
• Healthy uric acid metabolism — 2025 published human study*

In Resolve+, Quercetin Phytosome® provides a broad-spectrum antioxidant and immune-modulating layer that complements Theracurmin Super®'s NF-κB focus and Casperome®'s 5-LOX focus — catching the inflammatory pathways that neither curcumin nor Boswellia specifically addresses.*

Perilla frutescens Seed Extract

Role: Rosmarinic Acid, Luteolin & Apigenin — Respiratory Comfort, Histamine Balance & Antioxidant Support

Perilla frutescens seed extract provides a natural complex of three synergistic bioactives:

Rosmarinic acid: a caffeic acid ester with well-documented activity in supporting healthy histamine response, DAO enzyme function, and balanced immune signaling in respiratory and mucosal tissues.* Rosmarinic acid also inhibits complement activation and supports healthy mast cell activity.*

Luteolin: a flavone with broad NF-κB inhibitory activity, antioxidant properties, and support for healthy inflammatory enzyme balance — complementing curcumin's anti-inflammatory activity through flavone-mediated pathways.*

Apigenin: supports NAD+ homeostasis through CD38 modulation and provides independent antioxidant and anti-inflammatory activity — shared with the anti-aging properties of apigenin featured in Prime Time+ and Rejuvenate.*

Together, Perilla frutescens adds a respiratory and histamine balance dimension to Resolve+'s inflammatory support profile — making the formula relevant not only for joint and muscle concerns but for patients where systemic inflammatory tone, respiratory comfort, and seasonal immune challenges are concurrent clinical priorities.*

AstraGin® (Astragalus membranaceus + Panax notoginseng Root Extracts)

Dose: 50 mg Role: Nutrient Absorption, Bioavailability Enhancement & Gut Integrity

AstraGin® upregulates intestinal nutrient transporter proteins — supporting the absorption and bioavailability of Resolve+'s active polyphenol compounds. In a formula where bioavailability is already dramatically enhanced through three separate phytosome and amorphous conversion technologies, AstraGin® provides an additional intestinal absorption advantage — ensuring consistent delivery regardless of individual GI variation.*

AstraGin® also supports gut barrier integrity and healthy inflammatory tone in the intestinal environment — contributing directly to the gut-immune inflammatory balance dimension of Resolve+'s clinical positioning.*

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† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.