Calebin A

Calebin A is a PI3K/Akt/mTOR, MAPK, and NF-κB inhibitor with oral effectiveness. Calebin A can block the autophagy-repressive, inhibiting apoptosis. Calebin A has anti-tumor activity by epigenetic regulation. Calebin A suppresses adipogenesis, modulates thermogenesis, and enriches gut probiotics. Calebin A can be used in research on osteoarthritis, Alzheimer's disease, type 2 diabetes, malignant peripheral nerve sheath tumors, and colorectal cancer ^{[1] [2] [3] [4] [5]}.

In Vivo, Calebin A (100 mg/kg/d; p.o.; daily; 90 days) is safe when administered orally to female and male Wistar rats for 90 days, with no observed toxicity^[2]. Calebin A (500 mg/kg; oral; single dose ) exhibits pharmacokinetic properties including ~0.5% bioavailability, 1-3 hour serum half-life, and primarily non-renal excretion in male Sprague-Dawley rats^[2]. Calebin A (100 mg/kg; i.p.; three times a week; 15 days) significantly reduces xenograft tumor size in a mouse MPNST model^[3]. Calebin A (0.1-0.5%; dietary supplementation; daily; 12 weeks) exhibits dose-dependent anti-obesity effects in high-fat diet-induced obese mice by reducing body weight and blood glucose, restoring liver weight, enhancing adaptive thermogenesis, and modulating gut microbiota composition^[4].

In Vitro, Calebin A (5 μM) suppresses apoptosis and promotes autophagic Beclin-1 expression in primary canine chondrocytes cultured in an osteoarthritis environment^[1]. Calebin A (5 μM) upregulates ECM and autophagy markers, downregulates inflammation, degradation, apoptosis, and mTOR/PI3K/Akt signaling in primary canine chondrocytes cultured in an osteoarthritis environment, with effects dependent on intact autophagy^[1]. Calebin A inhibits colonosphere formation, proliferation, invasion/migration, and enhances apoptosis in HCT116, RKO, and SW480 colorectal cancer cells via modulation of TNF-β/NF-κB signaling and associated biomarkers^[2]. Calebin A overcomes vincristine resistance, induces G2/M-phase arrest and apoptosis in SGC7901 gastric cancer cells via modulation of MAPK signaling and P-glycoprotein^[2]. Calebin A reduces growth and viability of Sup-T1 lymphoma cells and modulates epigenetic enzymes (HAT, HDAC, PCAF)^[2]. Calebin A down-regulates inflammation in canine tenocytes via NF-κB/Scleraxis signaling^[2]. Calebin A (20 μM) suppresses adipogenesis and induces lipolysis in adipocytes, with lipolysis induced at 20 μM^[2]. Calebin A (25 μM; 24 h) induces G2/M phase decrease and G1 phase increase in STS26T, S462-TY, ST8814, and T265 MPNST cells, arresting cell cycle progression^[3]. Calebin A (12.5-25 μM) downregulates phosphorylated AKT, phosphorylated ERK1/2, survivin, hTERT, and acetylated histone H3 in MPNST cells^[3].

References:
[1]. Oliveira AL, et al. Calebin A: Analytical Development for Pharmacokinetics Study, Elucidation of Pharmacological Activities and Content Analysis of Natural Health Products. J Pharm Pharm Sci. 2015;18(4):494-514.
[2]. Brockmueller A, et al. Calebin A modulates inflammatory and autophagy signals for the prevention and treatment of osteoarthritis. Front Immunol. 2024;15:1363947. Published 2024 Mar 4.
[3]. Brockmueller A, et al. Multifunctionality of Calebin A in inflammation, chronic diseases and cancer. Front Oncol. 2022;12:962066. Published 2022 Sep 16.
[4]. Lee MJ, et al. Calebin-A induced death of malignant peripheral nerve sheath tumor cells by activation of histone acetyltransferase. Phytomedicine. 2019;57:377-384.
[5]. Lee PS, et al. Calebin-A prevents HFD-induced obesity in mice by promoting thermogenesis and modulating gut microbiota. J Tradit Complement Med. 2022;13(2):119-127. Published 2022 Jan 5.
[6]. Buhrmann C, et al. Multitargeting Effects of Calebin A on Malignancy of CRC Cells in Multicellular Tumor Microenvironment. Front Oncol. 2021;11:650603. Published 2021 Sep 29.