Immunomodulatory effect of Cannabis root extract on inflammatory cascades via endocannabinoid system regulation

“Cannabis roots have been widely used in traditional medicine, with documented references in classical texts describing their use for the treatment of various inflammatory diseases and pain. Despite their longstanding ethnopharmacological significance, the bioactive compounds responsible for these effects and their underlying mechanisms remain unexplored. The present study was conducted to evaluate the unique anti-inflammatory mechanisms of Cannabis sativa root fractions, and moreover, to investigate its mechanism related with the endocannabinoid system (ECS).

Methods

Antioxidant activities and phenol contents of various Cannabis root fractions were determined by chemical assays. The effects of cannabis root fractions on inflammatory markers and endocannabinoid receptor (CB1, CB2) levels were evaluated in LPS-stimulated RAW 264.7 cells. Intracellular 2-arachidonoylglycerol (2-AG) levels were measured using LC-MS/MS. The fraction with the highest potential was further investigated to elucidate its mechanism using endocannabinoid receptor antagonists.

Results

Among the fractions, ethyl acetate fraction (CSREA) demonstrated the highest potential in both antioxidant and anti-inflammatory effects. However, its effect was not attributed to the inhibition of NF-κB signaling pathways. LC-MS/MS analysis showed that CSREA affected intracellular 2-AG levels, supporting its potential via the ECS. CSREA also effectively suppressed ERK phosphorylation, a critical inflammatory signaling pathway modulated by ECS. However, CSREA activity was reduced by co-treatment with a CB1 antagonist.

Conclusion

This study demonstrates that CSREA suppresses inflammatory responses and restores cellular homeostasis primarily by regulating the endocannabinoid system. However, its exclusive use of an acute in vitro inflammation model represents a limitation, and the effects of CSREA in chronic and in vivo settings require further investigation.”

https://link.springer.com/article/10.1186/s12906-026-05317-2

Structural characterization, physicochemical properties and hypolipidemic activity of hemp (Cannabis sativa L.) protein hydrolysates prepared via enzyme-microbial synergy

“This study aims to prepare hemp protein hydrolysate (HPH) with hypolipidemic activity using an enzyme-bacterial synergistic approach and to investigate its mechanism of action.

We found that enzymatic hydrolysis and fermentation altered the secondary and tertiary structures of hemp protein (HP). Particularly, the reduction of the α-helical structure and the increase of β-sheet endow HPH with better functional properties.

In vitro experiments demonstrated that HPH exhibited potent inhibitory activity against pancreatic lipase and cholesterol esterase, with IC₅₀ values of 1.999 ± 0.142 mg/mL and 3.046 ± 0.102 mg/mL, respectively. In free fatty acid-induced HepG2 cells, high concentrations of HPH reduced total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels by 39.71%, 30.84%, and 21.94%, respectively, while increasing high-density lipoprotein cholesterol levels by 1.4-fold. Additionally, WB results demonstrated that HPH activated the AMPK signaling pathway and regulated the SREBP1/PPARα/HMGCR/PCSK9-LDLR metabolic pathway, ultimately improving intracellular lipid accumulation.

These results demonstrated that HP may be a promising natural source candidate drug for the prevention and treatment of hyperlipidemia.”

https://pubmed.ncbi.nlm.nih.gov/41763749

“Hemp Protein is an excellent source for the development of hypolipidemic peptides.”

https://www.sciencedirect.com/science/article/abs/pii/S0963996926000293?via%3Dihub

“Hyperlipidemia is a common condition characterized by high levels of lipids (cholesterol and triglycerides) in the blood, often causing no symptoms but significantly increasing risks of stroke, heart attack, and cardiovascular disease.”