Tag Archives: TNF-alpha

Standardized Curcuma longa-Cannabis sativa extract derived from a traditional Thai formulation for psoriasis: anti-inflammatory activity, keratinocyte modulation, and skin-targeted delivery

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A new study tested a standardized combination of Curcuma longa (turmeric) and Cannabis sativa derived from a traditional Thai topical formulation for psoriasis. The combined extract contained curcuminoids, ar-turmerone and cannabidiol, including 35.47 mg/g CBD, and was evaluated for anti-inflammatory activity, effects on psoriasis-related keratinocytes and its ability to remain concentrated in the skin.

At 12.5 µg/mL, the combined extract reduced nitric oxide production by 48.97% and PGE₂ production by 91.15%. It also altered psoriasis-associated gene expression in TNF-α/IL-17A-stimulated keratinocytes, showing activity against several biological processes involved in psoriasis.

The skin-delivery experiments found strong deposition of the extract’s markers in the skin, with none detected in the receptor compartment during the 24-hour test. The authors concluded that the standardized turmeric–cannabis combination showed anti-inflammatory, psoriasis-relevant and skin-targeted activity supporting further development as a localized phytotherapeutic approach for psoriasis.

“Ethnopharmacological relevance: Curcuma longa rhizomes and Cannabis sativa leaves are traditionally combined in Thai topical remedies using cottonseed oil. However, the pharmacological basis and dermal delivery of this combination remain unclear.

Aim of the study: This study evaluated a standardized Thai CL-CS combined extract (CLCS) by integrating phytochemical characterization, psoriasis-relevant biological activities, and ex vivo skin deposition and permeation, with comparison to the single extracts.

Materials and methods: CLCS was standardized by validated HPLC using curcuminoids, ar-turmerone, and cannabidiol as markers. Anti-inflammatory activity was evaluated in RAW264.7 macrophages, while psoriasis-relevant activity was assessed in TNF-α/IL-17A-stimulated HaCaT keratinocytes. Skin deposition and permeation were evaluated using porcine ear skin and Franz diffusion cells.

Results: CLCS contained bisdemethoxycurcumin (18.79 ± 1.54 mg/g), demethoxycurcumin (12.89 ± 1.02 mg/g), curcumin (22.12 ± 1.62 mg/g), ar-turmerone (75.35 ± 3.94 mg/g), and cannabidiol (35.47 ± 2.39 mg/g). IC50 values were 41.22 ± 1.70 and 22.91 ± 0.51 μg/mL in HaCaT and RAW264.7 cells, respectively. At 12.5 μg/mL, CLCS inhibited NO and PGE2 production by 48.97 ± 0.88% and 91.15 ± 3.66%, respectively, and modulated psoriasis-associated genes. Cottonseed oil containing 20% DG achieved the highest skin deposition of BCM, DCM, and CM, with no detectable markers in the receptor compartment over 24 h.

Conclusions: Standardized CLCS exhibited anti-inflammatory and psoriasis-relevant activities and preferential skin deposition, supporting its potential as a localized phytotherapeutic approach for psoriasis.”

https://pubmed.ncbi.nlm.nih.gov/42772617

“The present study provides an integrated chemical, biological, and skin-targeted delivery evaluation of a standardized CLCS co-extract derived from a traditional Thai topical formulation. The extract was successfully standardized by its characteristic bioactive constituents derived from both botanical components. CLCS demonstrated anti-inflammatory and psoriasis-relevant biological activities”

https://www.sciencedirect.com/science/article/abs/pii/S0378874126012833?via%3Dihub

Δ9-Tetrahydrocannabinol treatment impairs CD8+ T cell differentiation into interferon gamma-competent CD45RO+ cells

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New research published in The Journal of Pharmacology and Experimental Therapeutics shows that Δ9-tetrahydrocannabinol (THC) can alter the development of CD8+ T cells involved in inflammatory immune responses. Researchers found that THC reduced secretion of interferon gamma (IFNγ), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNFα), three signaling molecules involved in immune activation and inflammation.

Rather than simply preventing cells from producing IFNγ, THC appeared to change how the T cells developed. THC reduced the differentiation of CD8+ T cells into mature CD45RO+ cells capable of secreting IFNγ. A selective CB2 receptor agonist produced similar effects, suggesting that activation of the cannabinoid CB2 receptor may play an important role in THC’s immune-modulating activity.

The researchers examined these effects partly because IFNγ-producing CD8+ T cells contribute to persistent neuroinflammation associated with HIV-associated neurocognitive disorders. They concluded that reducing CD8+ T-cell-derived IFNγ in the central nervous system may potentially improve cognitive outcomes during HIV infection, while noting that the findings may also have relevance to other inflammatory diseases involving IFNγ-producing CD8+ T cells.

“Chronic human immunodeficiency virus (HIV) infection results in a persistent state of neuroinflammation, even with combined antiretroviral therapy. Neuroinflammation contributes to pathology termed HIV-associated neurocognitive disorder, which is exacerbated by interferon gamma (IFNγ)-producing CD8+ T cells in the central nervous system.

Many people living with HIV self-report using Cannabis sativa to mitigate symptoms of chronic infection and side effects of treatment. C. sativa is composed of various phytocannabinoids, including Δ9-tetrahydrocannbinol (THC), which possesses immune-modulating properties.

This study aims to determine whether C. sativa use by people living with HIV, and specifically THC, affects IFNγ secretion by CD8+ T cells.

We found that HIV status does not influence T cell IFNγ responses, and C sativa use modestly reduces the average secretion of IFNγ by CD8+ T cells from HIV+ donors. Treatment of CD8+ T cells with THC and the selective cannabinoid receptor 2 agonist, JWH-015, reduced T-cell cytokine secretion, with THC eliciting greater suppression than cannabidiol.

These results suggest that THC treatment does not directly impair IFNγ gene expression or protein production, as determined by polymerase chain reaction and flow cytometry. However, THC treatment impaired CD8+ T cell differentiation into IFNγ-competent CD45RO+ cells.

These studies are of clinical relevance because reduction of CD8+ T-cell-derived IFNγ in the central nervous system may improve cognitive outcomes during HIV infection. Furthermore, these findings may be generalizable to other inflammatory diseases in which IFNγ-producing CD8+ T cells have been implicated.

SIGNIFICANCE STATEMENT: Δ9-Tetrahydrocannbinol (THC) treatment reduces CD8+ T cell interferon gamma (IFNγ) secretion isolated from HIV- and HIV+ individuals. THC and the selective cannabinoid receptor 2 agonist, JWH-015, both reduced CD8+ T cell secretion of IFNγ, interleukin 2, and tumor necrosis factor α, suggesting the involvement of cannabinoid receptor 2. Although THC treatment does not suppress IFNγ mRNA or protein levels, it reduces the number of IFNγ-secreting cells by impairing CD8+ T-cell differentiation into IFNγ-competent CD45RO+ cells.”

https://pubmed.ncbi.nlm.nih.gov/42748512

https://jpet.aspetjournals.org/article/S0022-3565(26)01210-3/abstract

Need this THC study explained? thcXplained.com