Neral is a plant-derived anti-inflammatory, antioxidant and anticancer agent. Neral inhibits the phosphorylation of ERK1/2, p38 MAPK and IκB in macrophages induced by LPS, suppresses the secretion of TNF-α and IL-6, as well as the expression of pro-IL-1β, iNOS and COX-2 in cells, and reduces the production of ROS in cells. Neral inhibits the activation of the NLRP3 inflammasome, and decreases the activation of caspase-1 and the secretion of IL-1β in mouse macrophages. Neral induces autophagy, and exhibits antiproliferative activity both in in vitro breast cancer cell models and mouse xenograft models. Neral regulates brassinosteroid, jasmonic acid and ethylene signaling pathways, and induces the expression of AP2/ERF-ERF and bHLH family genes in rice roots. Neral acts as a herbicide safener, alleviates the damage induced by Fenoxaprop-P-ethyl, and promotes the elongation of rice roots. Neral can be used in research related to breast cancer, inflammatory and immune system diseases, and herbicide safeners [1] [2] [3] [4].
In Vivo, Neral (40-80 mg/kg; i.v.; once daily on days 13, 16, 19, and 22 post-tumor implantation) inhibits the growth of 4T1 breast cancer xenografts by inducing autophagy[2][4].
In Vitro, Neral (6.6-66 μM; 24 h) promotes J774A.1 cell proliferation at the concentration of 66 μM[1]. Neral (0-100 μM; 30 min preincubation followed by 6 h LPS stimulation) dose-dependently inhibits LPS-induced secretion of TNF-α and IL-6, suppresses the expression of iNOS, COX-2 and NLRP-3, and significantly reduces the expression of pro-IL-1β[1] in J774A.1 mouse macrophages. Neral (6.6-66 μM; 30 min preincubation, followed by 5.5 h LPS stimulation and 30 min ATP stimulation) inhibits the activation of NLRP-3 inflammasome in J774A.1 mouse macrophages, and reduces the production of caspase-1 p10 and the secretion of IL-1β[1]. Neral (66 μM; 30 min preincubation followed by 10-60 min LPS stimulation) inhibits LPS-induced phosphorylation of p38 and IκB in J774A.1 murine macrophages, slightly reduces the level of phosphorylated ERK1/2, and exerts no effect on phosphorylated JNK1/3[1]. Neral (6.6-66 μM; 30 min preincubation with neral and CM-DCFH-DA, followed by 0-60 min LPS stimulation) inhibits LPS-induced intracellular ROS production in J774A.1 mouse macrophages[1]. Neral (9.9 μM, micelle-encapsulated) inhibits the proliferation of 4T1 breast cancer cells, with an IC50 of 9.9 μM[2]. Neral (20 mg/L; 72 h, co-applied with 0.35 mg/L fenoxaprop-p-ethyl) significantly promotes root elongation of 'Mianyou 838' rice, resulting in a root length 1.8 times that of plants treated with fenoxaprop-p-ethyl alone[3]. Neral (20 mg/L; 24 h) induces 895 uniquely up-regulated genes in the roots of 'Mianyou 838' rice, and these genes are significantly enriched in plant hormone synthesis and signaling pathways; it also up-regulates 93 transcription factor genes, mainly from the AP2/ERF-ERF and bHLH families[3].
References:
[1]. Zeng S, Kapur A, Patankar MS, Xiong MP. Formulation, Characterization, and Antitumor Properties of Trans- and Cis-Citral in the 4T1 Breast Cancer Xenograft Mouse Model. Pharm Res. 2015 Aug;32(8):2548-58.
[2]. Pei-Chun Liao, et al. Anti-inflammatory activity of neral and geranial isolated from fruits of Litsea cubeba Lour. Journal of Functional Foods Volume 19, Part A, December 2015, Pages 248-258
[3]. Silva GDSE, et al. Review of anticancer activity of monoterpenoids: Geraniol, nerol, geranial and neral. Chem Biol Interact. 2022;362:109994.
[4]. Sun L, et al. Protective mechanisms of neral as a plant-derived safener against fenoxaprop-p-ethyl injury in rice. Pest Manag Sci. 2024;80(3):1249-1257.
In Vivo, Neral (40-80 mg/kg; i.v.; once daily on days 13, 16, 19, and 22 post-tumor implantation) inhibits the growth of 4T1 breast cancer xenografts by inducing autophagy[2][4].
In Vitro, Neral (6.6-66 μM; 24 h) promotes J774A.1 cell proliferation at the concentration of 66 μM[1]. Neral (0-100 μM; 30 min preincubation followed by 6 h LPS stimulation) dose-dependently inhibits LPS-induced secretion of TNF-α and IL-6, suppresses the expression of iNOS, COX-2 and NLRP-3, and significantly reduces the expression of pro-IL-1β[1] in J774A.1 mouse macrophages. Neral (6.6-66 μM; 30 min preincubation, followed by 5.5 h LPS stimulation and 30 min ATP stimulation) inhibits the activation of NLRP-3 inflammasome in J774A.1 mouse macrophages, and reduces the production of caspase-1 p10 and the secretion of IL-1β[1]. Neral (66 μM; 30 min preincubation followed by 10-60 min LPS stimulation) inhibits LPS-induced phosphorylation of p38 and IκB in J774A.1 murine macrophages, slightly reduces the level of phosphorylated ERK1/2, and exerts no effect on phosphorylated JNK1/3[1]. Neral (6.6-66 μM; 30 min preincubation with neral and CM-DCFH-DA, followed by 0-60 min LPS stimulation) inhibits LPS-induced intracellular ROS production in J774A.1 mouse macrophages[1]. Neral (9.9 μM, micelle-encapsulated) inhibits the proliferation of 4T1 breast cancer cells, with an IC50 of 9.9 μM[2]. Neral (20 mg/L; 72 h, co-applied with 0.35 mg/L fenoxaprop-p-ethyl) significantly promotes root elongation of 'Mianyou 838' rice, resulting in a root length 1.8 times that of plants treated with fenoxaprop-p-ethyl alone[3]. Neral (20 mg/L; 24 h) induces 895 uniquely up-regulated genes in the roots of 'Mianyou 838' rice, and these genes are significantly enriched in plant hormone synthesis and signaling pathways; it also up-regulates 93 transcription factor genes, mainly from the AP2/ERF-ERF and bHLH families[3].
References:
[1]. Zeng S, Kapur A, Patankar MS, Xiong MP. Formulation, Characterization, and Antitumor Properties of Trans- and Cis-Citral in the 4T1 Breast Cancer Xenograft Mouse Model. Pharm Res. 2015 Aug;32(8):2548-58.
[2]. Pei-Chun Liao, et al. Anti-inflammatory activity of neral and geranial isolated from fruits of Litsea cubeba Lour. Journal of Functional Foods Volume 19, Part A, December 2015, Pages 248-258
[3]. Silva GDSE, et al. Review of anticancer activity of monoterpenoids: Geraniol, nerol, geranial and neral. Chem Biol Interact. 2022;362:109994.
[4]. Sun L, et al. Protective mechanisms of neral as a plant-derived safener against fenoxaprop-p-ethyl injury in rice. Pest Manag Sci. 2024;80(3):1249-1257.