Palmitoylethanolamide (PEA) is a natural compound with significant neuroprotective, anti-inflammatory, and analgesic properties, highlighting its potential therapeutic benefits in treating neurodegenerative diseases.

Source: Clayton P, Hill M, Bogoda N, Subah S, Venkatesh R. Palmitoylethanolamide: A Natural Compound for Health Management. Int J Mol Sci. 2021 May 18;22(10):5305. doi: 10.3390/ijms22105305. PMID: 34069940; PMCID: PMC8157570.

PEA exhibits significant neuroprotective effects by modulating inflammation and correcting endocannabinoid system dysregulation, offering promising therapeutic avenues for treating neurodegenerative diseases.

Source: Denora N, Laquintana V, Lopalco A, Cutrignelli A, Franco M. Palmitoylethanolamide and Its Biobased Analogs: From Mechanism of Action to Future Perspectives in Neuroprotection. Drug Sciences. 2022;3(4):58. doi:10.3390/drugsciences3040058.

PEA is investigated for its potential to alleviate COVID-19-related inflammation and oxidative stress by modulating neuroinflammatory pathways, highlighting its promise as a therapeutic agent against the complications of COVID-19.

Source: Natalello C, Fagiani F, Colombo E, Codazzi F, Pignataro M, Bassani S, et al. Palmitoylethanolamide as a Natural Ally in the Treatment of Redox Dysregulation and Neuroinflammation in COVID-19. Pharmaceuticals. 2022;15(2):253. doi:10.3390/ph15020253.

β-Caryophyllene (BCP) exhibits protective effects against chronic inflammation by reducing pro-inflammatory mediators and modulating cannabinoid receptors and PPARs, offering potential therapeutic benefits for metabolic and neurological disorders such as obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases.

Source: Scandiffio R, Geddo F, Cottone E, Querio G, Antoniotti S, Gallo MP, Maffei ME, Bovolin P. Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation. Molecules. 2020 Nov 19;25(22):5858. doi: 10.3390/molecules25225858.

β-Caryophyllene exhibits cardioprotective effects against myocardial injury by inhibiting the HSP-60/TLR/MyD88/NFκB signaling pathways, suggesting its potential as a therapeutic agent for myocardial infarction.

Source: Younis NS, Mohamed ME. β-Caryophyllene as a Potential Protective Agent Against Myocardial Injury: The Role of Toll-Like Receptors. Molecules. 2019 Jun 18;24(12):2278. doi: 10.3390/molecules24122278.

β-Caryophyllene (BCP), a selective CB2 receptor agonist, demonstrates significant immunomodulatory and anti-inflammatory effects that may alleviate neuroinflammation and endocannabinoid system dysregulation in depression and anxiety disorders, including those related to long-COVID, highlighting its potential as a therapeutic agent for emotional and cognitive disorders.

Source: Ricardi C, Barachini S, Consoli G, Marazziti D, Polini B, Chiellini G. Beta-Caryophyllene, a Cannabinoid Receptor Type 2 Selective Agonist, in Emotional and Cognitive Disorders. Int J Mol Sci. 2024 Mar 11;25(6):3203. doi: 10.3390/ijms25063203.

β-Caryophyllene decreases neuroinflammation and provides neuroprotection of dopaminergic neurons in a hemiparkinsonism model by inhibiting the NLRP3 inflammasome, highlighting its potential therapeutic role in Parkinson's disease.

Source: Brand-Rubalcava PA, Tejeda-Martínez AR, González-Reynoso O, Nápoles-Medina AY, Chaparro-Huerta V, Flores-Soto ME. β-Caryophyllene decreases neuroinflammation and exerts neuroprotection of dopaminergic neurons in a model of hemiparkinsonism through inhibition of the NLRP3 inflammasome. Parkinsonism Relat Disord. 2023 Dec;117:105906. doi: 10.1016/j.parkreldis.2023.105906.

β-Caryophyllene demonstrates wound-healing potential in rat skin wounds by promoting antioxidant, anti-inflammatory, and re-epithelialization activities, highlighting its effectiveness in accelerating skin repair.

Source: Gushiken LFS, Beserra FP, Hussni MF, Gonzaga MT, Ribeiro VP, de Souza PF, et al. Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin wound excision model. Oxid Med Cell Longev. 2022;2022:9004014. doi: 10.1155/2022/9004014.

β-Caryophyllene mitigates collagen antibody-induced arthritis in mice by modulating inflammation through cross-talk between CB2 and PPAR-γ receptors, highlighting its potential as an anti-arthritic agent.

Source: Irrera N, D’Ascola A, Pallio G, Bitto A, Mazzon E, Mannino F, et al. β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors. Biomolecules. 2019 Aug;9(8):326. doi: 10.3390/biom9080326.

Astaxanthin, a natural antioxidant carotenoid, modulates neuroinflammation by alleviating oxidative stress, suppressing inflammatory pathways, and maintaining blood-brain barrier integrity, highlighting its strong therapeutic potential for neurological and neurodegenerative diseases due to its good biosafety and bioavailability.

Source: Wang S, Qi X. The Putative Role of Astaxanthin in Neuroinflammation Modulation: Mechanisms and Therapeutic Potential. Front Pharmacol. 2022;13:916653. doi: 10.3389/fphar.2022.916653.

Astaxanthin exhibits significant benefits for skin health, repair, and disease by providing photoprotective, antioxidant, and anti-inflammatory effects, suggesting its potential clinical applications in dermatology.

Source: Davinelli S, Nielsen ME, Scapagnini G. Astaxanthin in Skin Health, Repair, and Disease: A Comprehensive Review. Nutrients. 2018 Apr;10(4):522. doi: 10.3390/nu10040522.

Astaxanthin supplementation for three months suppressed oxidative stress and improved cardiac contractility and exercise tolerance in heart failure patients with left ventricular systolic dysfunction, suggesting its therapeutic potential for improving cardiac function.

Source: Kato T, Kasai T, Sato A, Ishiwata S, Yatsu S, Matsumoto H, et al. Effects of 3-Month Astaxanthin Supplementation on Cardiac Function in Heart Failure Patients with Left Ventricular Systolic Dysfunction—A Pilot Study. Nutrients. 2020 Jun;12(6):1896. doi: 10.3390/nu12061896.

Astaxanthin, a potent antioxidant carotenoid, acts as a nutraceutical that promotes health and combats age-related conditions by reducing oxidative stress, supporting brain health, and maintaining skin homeostasis, emphasizing its potential clinical implications.

Source: Bjørklund G, Gasmi A, Lenchyk L, Shanaida M, Zafar S, Mujawdiya PK, et al. The Role of Astaxanthin as a Nutraceutical in Health and Age-Related Conditions. Molecules. 2022 Nov;27(21):7167. doi: 10.3390/molecules27217167.

Quercetin exhibits significant anti-allergic and anti-inflammatory properties by modulating the immune response through inhibition of histamine release, pro-inflammatory cytokines, and suppression of inflammatory mediators, highlighting its potential therapeutic use in allergic and inflammatory diseases.

Source: Mlcek J, Jurikova T, Skrovankova S, Sochor J. Quercetin and Its Anti-Allergic Immune Response. Molecules. 2016 May;21(5):623. doi: 10.3390/molecules21050623.

Quercetin, a flavonoid found in fruits and vegetables, exhibits significant antioxidant, antimicrobial, anti-inflammatory, antiviral, and anticancer properties, making it a promising candidate for preventing and treating chronic diseases, though further studies are needed to optimize its bioavailability and assess long-term safety.

Source: Aghababaei F, Hadidi M. Recent Advances in Potential Health Benefits of Quercetin. Pharmaceuticals (Basel). 2023 Jul;16(7):1020. doi: 10.3390/ph16071020.

Quercetin prevents osteoarthritis progression by regulating local and systemic inflammatory cascades, suggesting its potential as a therapeutic agent to prevent OA development in at-risk groups.

Source: Wang H, Yan Y, Pathak JL, Hong W, Zeng J, Qian D, et al. Quercetin prevents osteoarthritis progression possibly via regulation of local and systemic inflammatory cascades. J Cell Mol Med. 2023 Feb;27(4):515–528. doi: 10.1111/jcmm.17672.

Quercetin, a bioactive compound found in fruits and vegetables and their wastes, imparts cardiovascular and neuroprotective benefits, suggesting its potential as a therapeutic agent for treating cardiovascular and neurological diseases while aligning with circular economy concepts.

Source: Bhat IUH, Bhat R. Quercetin: A Bioactive Compound Imparting Cardiovascular and Neuroprotective Benefits: Scope for Exploring Fresh Produce, Their Wastes, and By-Products. Biology (Basel). 2021 Jul;10(7):586. doi: 10.3390/biology10070586.

This systematic review found that omega-3 polyunsaturated fatty acids improve learning, memory, cognitive well-being, and cerebral blood flow, highlighting their potential benefits for brain function and supporting the promotion of dietary omega-3 intake.

Source: Dighriri IM, Alsubaie AM, Hakami FM, Hamithi DM, Alshekh MM, Khobrani FA, et al. Effects of Omega-3 Polyunsaturated Fatty Acids on Brain Functions: A Systematic Review. Cureus. 2022 Oct;14(10):e30091. doi: 10.7759/cureus.30091.

This systematic review and meta-analysis found that omega-3 fatty acids may reduce certain inflammatory biomarkers and triglyceride levels among diabetic and cardiovascular disease patients, but may also increase fasting blood glucose and LDL cholesterol, indicating mixed effects on lipid profiles and inflammatory markers.

Source: Natto ZS, Yaghmoor W, Alshaeri HK, Van Dyke TE. Omega-3 Fatty Acids Effects on Inflammatory Biomarkers and Lipid Profiles among Diabetic and Cardiovascular Disease Patients: A Systematic Review and Meta-Analysis. Sci Rep. 2019 Dec;9(1):18867. doi: 10.1038/s41598-019-54535-x.

Omega-3 fatty acids may modulate disease activity in rheumatoid arthritis by exerting immunomodulatory effects that limit or modulate inflammatory responses, potentially reducing the number of swollen and tender joints.

Source: Kostoglou-Athanassiou I, Athanassiou L, Athanassiou P. The Effect of Omega-3 Fatty Acids on Rheumatoid Arthritis. Mediterr J Rheumatol. 2020 Jun;31(2):190–194. doi: 10.31138/mjr.31.2.190.

Omega-3 fatty acids may modulate disease activity in rheumatoid arthritis by exerting immunomodulatory effects that limit or modulate inflammatory responses, potentially reducing the number of swollen and tender joints.

Source: Kostoglou-Athanassiou I, Athanassiou L, Athanassiou P. The Effect of Omega-3 Fatty Acids on Rheumatoid Arthritis. Mediterr J Rheumatol. 2020 Jun;31(2):190–194. doi: 10.31138/mjr.31.2.190.

Lactobacillus acidophilus enhances the intestinal epithelial tight junction barrier via a Toll-like receptor 2–dependent mechanism, protecting against intestinal inflammation by preventing increased intestinal permeability and colitis, highlighting its potential therapeutic role in inflammatory bowel disease.

Source: Al-Sadi R, Nighot P, Nighot M, Haque M, Rawat M, Ma TY. Lactobacillus acidophilus Induces a Strain-specific and Toll-Like Receptor 2–Dependent Enhancement of Intestinal Epithelial Tight Junction Barrier and Protection Against Intestinal Inflammation. Am J Pathol. 2021 May;191(5):1109-1124. doi: 10.1016/j.ajpath.2021.01.013.

This review highlights the potential of Lactobacillus strains in reducing oxidative stress and preventing diseases such as inflammatory bowel disease, cancer, and liver diseases through their antioxidant, anti-inflammatory, and immunomodulatory effects, emphasizing the need for further mechanistic studies and clinical trials.

Source: Zhao T, Wang H, Liu Z, Liu Y, DeJi, Li B, Huang X. Recent Perspective of Lactobacillus in Reducing Oxidative Stress to Prevent Disease. Antioxidants (Basel). 2023 Mar;12(3):769. doi: 10.3390/antiox12030769.

Lactobacillus plays a beneficial role in alleviating inflammatory bowel disease and related conditions by strengthening intestinal barriers and modulating the gut-brain and gut-liver axes, highlighting its therapeutic potential and underlying mechanisms.

Source: Li C, Peng K, Xiao S, Long Y, Yu Q. The role of Lactobacillus in inflammatory bowel disease: from actualities to prospects. Cell Death Discov. 2023;9:361. doi: 10.1038/s41420-023-01666-w.

Lactobacillus acidophilus mitigates osteoarthritis-associated pain, cartilage disintegration, and gut microbiota dysbiosis in an experimental murine OA model, suggesting its potential as a safe osteoarthritis disease-modifying drug.

Source: O-Sullivan I, Anbazhagan AN, Singh G, Ma K, Green SJ, Singhal M, et al. Lactobacillus acidophilus Mitigates Osteoarthritis-Associated Pain, Cartilage Disintegration and Gut Microbiota Dysbiosis in an Experimental Murine OA Model. Biomedicines. 2022 Jun;10(6):1298. doi: 10.3390/biomedicines10061298.

Palmitoylethanolamide combined with other phytochemicals as add-on therapy reduced chronic pain and improved functional abilities and quality of life in elderly patients, suggesting that phytochemicals may be effective adjuncts to conventional analgesics.

Source: Gianni W, Di Carlo M, Colangelo L, Della Grotta G, Sonato C, Cilli M, Toto A, Minisola S. Short-term efficacy of a fixed association of Palmitoylethanolamide and other phytochemicals as add-on therapy in the management of chronic pain in elderly patients: a real-world retrospective study. Geriatric Care. 2018 May 2;4(1):7177. doi: 10.4081/gc.2018.7177.

Astaxanthin and omega-3 fatty acids (DHA and EPA), individually and in combination at low concentrations, protect against oxidative stress by activating the Nrf2-ARE pathway, demonstrating synergistic antioxidant effects.

Source: Saw CLL, Yang AY, Guo Y, Kong AN. Astaxanthin and omega-3 fatty acids individually and in combination protect against oxidative stress via the Nrf2-ARE pathway. Food Chem Toxicol. 2013 Dec;62:869–875. doi: 10.1016/j.fct.2013.10.023.

Maternal supplementation with astaxanthin and DHA during gestation and lactation ameliorated cognitive impairments and synaptic plasticity deficits in offspring induced by perinatal undernutrition, highlighting the critical role of nutraceuticals in reversing maternal undernutrition-induced cognitive impairment.

Source: Agni MB, Hegde PS, Rai P, Sadananda M, Gowda KMD. Astaxanthin and DHA Supplementation Modulates the Maternal Undernutrition-induced Impairment of Cognitive Behavior and Synaptic Plasticity in Adult Life of Offspring's—Exploring the Molecular Mechanism. Mol Neurobiol. 2024 Apr 5. doi: 10.1007/s12035-024-04147-y.

Quercetin potentiates docosahexaenoic acid (DHA) to more effectively suppress lipopolysaccharide-induced oxidative and inflammatory responses in microglial cells at lower concentrations, enhancing Nrf2-mediated antioxidant pathways and suggesting their combined potential as nutraceuticals for improving health.

Source: Sun GY, Li R, Yang B, Fritsche KL, Beversdorf DQ, Lubahn DB, et al. Quercetin Potentiates Docosahexaenoic Acid to Suppress Lipopolysaccharide-induced Oxidative/Inflammatory Responses, Alter Lipid Peroxidation Products, and Enhance the Adaptive Stress Pathways in BV-2 Microglial Cells. Int J Mol Sci. 2019 Feb;20(4):932. doi: 10.3390/ijms20040932.

Docosahexaenoic acid (DHA) and quercetin used in combination exhibit enhanced anti-inflammatory effects in lipopolysaccharide-induced RAW264.7 macrophages by synergistically inhibiting NF-κB and MAPK activation, suggesting their potential as potent anti-inflammatory compounds for preventing or alleviating obesity, atherosclerosis, and cardiovascular diseases.

Source: Si T-L, Liu Q, Ren Y-F, Li H, Xu X-Y, Li E-H, et al. Enhanced anti-inflammatory effects of DHA and quercetin in lipopolysaccharide-induced RAW264.7 macrophages by inhibiting NF-κB and MAPK activation. Mol Med Rep. 2016 Jul;14(1):499–508. doi: 10.3892/mmr.2016.5259.