Limonene – Terpenes and Cannabinoid Research

Summary of Limonene Effects

Anticancer activity, may protect against breast and skin cancers (via inhibition of inflammation, oxidative stress, Ras-signaling, induction of pro-apoptotic state of tumor initiation, growth, and angiogenesis and the induction of cancer cells apoptosis by multiple pathways including: increase Bax expression, release cytochrome c, activate the caspase pathway, increase the expression of p53, and reduction in tumor cyclin D1 expression, decrease the activity of Ras/Raf/MEK/ERK and PI3K/Akt pathways, decrease the expression of VEGF and increase the activities of the Man-6-P / IGF2R and TGF-βIIR receptors)

Anti-inflammatory, antioxidant, and anti-asthmatic (bronchial asthma), also gastroprotective of intestinal epithelial cells in induced colitis mice models. Also may normalize peristalsis in cases of heartburn and GERD (via binding to both A2A and A2B receptors, reducing IL-5 and IL-6 levels, reducing cytokines, inhibition of TNFα, and TNFα-induced NF-κB translocation)

Potentially anti-osteoarthritic and anti-catabolic in chondrocytes, may slow down cartilage destruction and osteoarthritis progression that warrants further investigation (via antiinflammatory activity, inhibiting IL-1β-induced nitric oxide production, decreasing IL-1β-induced NF-κB, JNK and p38 activation and the expression of inflammatory (iNOS) and catabolic (MMP-1 and MMP-13) genes, increasing the expression of anti-catabolic gene TIMP-1, increase expression of collagen I induced by IL-1β)

Antidepressant effects in preclinical studies and small scale human study (via normalizing neuroendocrine hormone levels and immune function, reducing serum and brain nitrite levels and reduces the expression of IL-1β, TNF-α, and nitrite in the hippocampus, boosts serotonin and dopamine)

Anxiolytic and sedative effects (via A2A receptor-mediated regulation of dopaminergic and GABAergic activity, possible action on benzodiazepine-type receptors)

May reduce obesity and promote weight loss. Obese-preventive effects in high-fat diet-fed mice, decreased the size of white and brown adipocytes, lowered serum triglyceride (TG) and fasting blood glucose levels, and prevented liver lipid accumulations. In obese mice, d-limonene reduced serum TG, low-density lipoprotein cholesterol (LDL-c) and fasting blood glucose levels and glucose tolerance, and increased serum high-density lipoprotein cholesterol (HDL-c) (via peroxisome proliferator-activated receptor (PPAR)-α signaling and inhibiting liver X receptor (LXR)-β signaling)

Antihyperlipidemic, may help with cholesterol-based gallbladder stones (via solubilizing gallstones and lowering TG levels)

Antifungal in metabolite form, perillyl alcohol (via inhibiting glyoxylate cycle in C. albicans)

Antibacterial and anti-acne effects. Anti-biofilm effects in models of P. aeruginosa and S. aureus. May be synergistic with gentamicin in cases of MRSA (via superoxide anion radical-scavenging activity, affecting expression of different levels of biofilm-forming gene, slow toxicity against S. epidermidis and P. acnes, and reducing P. acnes-induced secretion of interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) in THP-1 cells)

Last reviewed by Dr. Abraham Benavides M.D., 05-09-2022