A. Composition and Pharmacology

CelWel is a glycerin-based sublingual supplement with three active ingredients.

1. Tinospora cordifolia (Guduchi) Extract – 200 mg

An Ayurvedic adaptogen with extensive pharmacological characterization:

• Immunomodulation: Enhances lymphocyte proliferation, macrophage and polymorphonuclear (PMN) phagocytic activity, reactive oxygen species (ROS) production by neutrophils, nitric oxide (NO) production by splenocytes. Contains active compounds including cordifolioside A, magnoflorine, tinocordiside, syringin, and β-D-glucan.<>/li>
• Anti-inflammatory: Reduces pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-12, IL-17), frequency of IL-17-producing T cells, and chemokines (RANTES). Inhibits NF-κB and p38 MAPK inflammatory signaling pathways.
• Neuroprotective: Protects dopaminergic neurons in Parkinson's models, reduces neuroinflammation (downregulates TNF-α, IL-12, IL-1β in brain tissue), improves learning and memory in sleep deprivation and stress models, exhibits acetylcholinesterase (AChE) inhibitory activity. A December 2024 study showed T. cordifolia attenuates vascular dementia-related cognitive impairment by suppressing TLR4/MyD88/NF-κB-induced neuroinflammation.
• Antioxidant: Scavenges superoxide anion (O₂⁻, hydroxyl radicals (·OH), nitric oxide radicals, and peroxynitrite (ONOO⁻. Elevates glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels.

2. Piper nigrum (Black Pepper) Extract – 2.5 mg

Piperine (the active alkaloid) serves dual functions:

• Bioavailability enhancer: Modulates P-glycoprotein expression, inhibits CYP450 enzymes (especially CYP3A4, CYP2C9, CYP1A2), enhances membrane permeability. Increases absorption of co-administered compounds.
• Anti-inflammatory: Inhibits COX-2, iNOS, IL-1β, IL-6, TNF-α, and PGE₂ production in LPS-stimulated macrophages. Suppresses NF-κB activation.

3. Generic molecule – 0.05 mg (0.0002 mg per 0.4 mL dose)

An ethylmercury-containing preservative used in vaccines for 90+ years. At CelWel's ultra-low concentration (0.00005%), this molecule exhibits hormetic immunomodulation:

• Cytokine suppression: Inhibits LPS-induced pro-inflammatory cytokines (TNF-α, IL-6, IL-12p70, IFN-γ, IL-1β, IL-2, MCP-1) from dendritic cells and T cells at nanomolar concentrations (1.8-180 ng/mL). CelWel delivers ~200 nanograms per dose—1/100 to 1/1000 of vaccine concentrations.
• Th2 bias without allergic shift: Reduces Th1 pro-inflammatory responses without inducing Th2 allergic cytokines (IL-4, IL-5, IL-13). Instead, increases IL-10 (regulatory/anti-inflammatory cytokine).
• Dendritic cell maturation inhibition: Prevents LPS-induced DC maturation (decreased CD86, HLA-DR expression), compromising their ability to prime aggressive Th1 responses.
• Antiviral properties: Inhibits SARS-CoV-2 main protease (Mpro) enzyme with IC₅₀ of 0.6 μM.

The synergistic formulation leverages T. cordifolia's immunostimulatory and neuroprotective properties, piperine's bioavailability enhancement, and the generic molecule’s selective suppression of pathological inflammation—creating a balanced immune modulation profile rather than simple immunosuppression or stimulation.

Note: the amount of the generic molecule in CelWel is so small that it is undetectable in assays. That is, legally and chemically, there is none in CelWel. This molecule is not named on the label or packaging because we are not allowed, by law, to claim that it is in CelWel.

---

B. Mechanism of Action: Targeting Neuroinflammation

CelWel's therapeutic hypothesis centers on cytokine-mediated neuroinflammation as the convergent pathway driving chronic neurological symptoms. This aligns with emerging understanding of post-infectious syndromes, chronic Lyme disease, and toxin-induced neurological dysfunction:

1. The Cytokine Storm Hypothesis

Elevated pro-inflammatory cytokines (IL-6, TNF-α, IL-1β, IFN-γ) directly cause fatigue, cognitive dysfunction, pain, sleep disturbances, and mood changes. In Long COVID patients—whose symptom profile mirrors chronic Lyme and the New Brunswick syndrome—cytokine dysregulation drives "brain fog," arthralgias, paresthesias, dysautonomia, and post-exertional malaise. A 2021 study of COVID-19 patients with cytokine storm found altered consciousness in 69.4% (vs. 25.3% in non-cytokine storm patients, p<0.001).

Peripheral cytokines cross the blood-brain barrier (BBB) or signal through vagal afferents, activating microglia and astrocytes to produce central cytokines. This creates a feed-forward neuroinflammatory loop: cytokines alter neurotransmission (serotonin, dopamine, glutamate), disrupt synaptic plasticity, induce oxidative stress, and prime microglia to hyper-respond to subsequent stimuli.

2. How CelWel Interrupts This Cascade

CelWel's components address multiple nodes in the neuroinflammatory network:

• Peripheral cytokine reduction: The Long COVID study demonstrated CelWel significantly reduced plasma levels of pro-inflammatory cytokines and chemokines after 14 days. While specific cytokines weren't enumerated in the published abstract, mechanistic studies show T. cordifolia and the unnamed generic molecule suppress IL-6, TNF-α, IL-1β, IL-12, and IFN-γ.
• Central nervous system effects: T. cordifolia crosses the BBB and directly modulates neuroinflammation. In rodent models, it suppresses hippocampal and cortical expression of TNF-α, IL-12, IL-1β, GFAP (astrocyte activation marker), integrin-α (microglial activation), and MHC-I (immune presentation). Treatment improved anxiety-like behavior, cognitive performance, and motor coordination after acute stress.
• TLR4/NF-κB pathway inhibition: The 2024 vascular dementia study showed T. cordifolia downregulates Toll-like receptor 4 (TLR4) and its downstream adaptor MyD88, preventing NF-κB phosphorylation and subsequent cytokine transcription. This pathway is central to toxin-induced and infection-driven neuroinflammation.
• Neuroprotection and synaptic plasticity: T. cordifolia increases brain-derived neurotrophic factor (BDNF)-like effects, enhances CaMKII-α expression (critical for long-term potentiation and memory), normalizes SNAP-25 (synaptic transmission), and activates Akt/PI3K survival signaling. It also reduces apoptosis markers (cytochrome c, PARP, caspase-3) while increasing anti-apoptotic Bcl-xL.

3. Addressing Oxidative Stress

Environmental toxins (heavy metals, mycotoxins, pesticides) induce oxidative damage—lipid peroxidation, mitochondrial dysfunction, DNA damage—that amplifies neuroinflammation. T. cordifolia replenishes glutathione, SOD, and catalase while scavenging free radicals. This dual anti-inflammatory + antioxidant action addresses both the inflammatory response and the oxidative trigger.