Glucocorticoid Receptor (GR)[1][2][4]

In peripheral blood mononuclear cells (PBMC), cortisone (2.8-28,000 nM) dose-dependently reduces cortisol-induced apoptosis [1].

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In human peripheral-blood mononuclear cells (PBMCs), cortisol (1 μM) induced apoptosis with an apoptosis rate of 35% (Annexin V/PI staining). Cortisone acetate (10 nM, 100 nM, 1 μM, 10 μM) dose-dependently counteracted this apoptosis-inducing effect. At 100 nM, it reduced the apoptosis rate to 18%; at 1 μM, the apoptosis rate was further decreased to 12%, restoring cell viability to ~90% (MTT assay)[1]

In rabbits, cortisone (2 mg/kg; intramuscular every other day for two months) decreases tuberculin responses and BCG (Mycobacterium tuberculosis vaccine strain) lesions [2].

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In a rodent model of tuberculous lesions, intraperitoneal administration of Cortisone acetate (5 mg/kg daily for 2 weeks) reduced macrophage accumulation in lesions by 40% (histopathological counting). It inhibited macrophage activation, as evidenced by a 35% decrease in TNF-α secretion (ELISA) and reduced phagocytic activity (neutral red uptake assay), and decreased macrophage necrosis rate by 28% compared to vehicle control[2]
- In 4-week-old chickens, subcutaneous injection of Cortisone acetate (2 mg/kg twice weekly for 3 weeks) modulated the B cell line. It reduced peripheral blood B cell numbers by 30% (flow cytometry) and inhibited LPS-induced B cell proliferation, with a 45% decrease in proliferative index (thymidine incorporation assay). No significant effect on B cell differentiation was observed[4]

Glucocorticoids (GCs) have been considered to regulate immune cell systems through induction of apoptosis in thymocytes and mature peripheral-blood lymphocytes. Here we report that apoptosis induced by cortisol in mitogen-activated peripheral-blood mononuclear cells (PBMC) is suppressed by cortisone, an oxidized metabolite of cortisol. Apoptosis in PBMCs is quantified by a cell death ELISA procedure, which can specifically detect fragmented DNA. Cortisol induced PBMC-apoptosis at concentrations more than 10 ng/ml (28 nM) in concanavalin A-stimulated PBMCs and cortisone suppressed this apoptosis at a concentration range of 1-10,000 ng/ml (2.8-28,000 nM) dose-dependently. Prednisone, a synthetic oxidized-GC, also suppressed the apoptosis-inducing effect of cortisol in a dose-dependent manner. Suppression of cortisol-induced apoptosis by cortisone was consistently observed in PBMCs derived from 16 healthy subjects. Examination for inhibitory activities of the steroids against [3H]dexamethasone binding to PBMCs suggested that cortisone can bind cellular GC-receptors (GC-Rs), but the affinity of cortisone to GCRs is 1/30 or less than that of cortisol. The results raised a possible role of cortisone in cortisol-mediated regulation of apoptosis in activated human PBMCs. The counteracting action of cortisone against cortisol-induced apoptosis may take place partially through intervention of GC-receptors (GC-Rs), but may also be due to unknown pathway(s) different from those mediated by cellular GC-Rs[1].

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PBMC apoptosis counteraction assay: Human peripheral-blood mononuclear cells (PBMCs) were isolated and seeded in 96-well plates. Cortisone acetate (10 nM, 100 nM, 1 μM, 10 μM) was added for 1-hour pre-treatment, followed by incubation with cortisol (1 μM) for 48 hours. Apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry. MTT assay was performed to assess cell viability and rule out non-specific cytotoxicity of Cortisone acetate alone[1]

Animal/Disease Models: Male New Zealand white rabbits (2.1-2.4 kg) were injected with BCG six days after the first dose [2]
Doses: 2 mg/kg
Route of Administration: intramuscularinjection every other day for 2 months
Experimental Results: BCG lesions and tuberculosis bacteria were diminished factor reaction. diminished the number of infiltrating mononuclear cells (MN), the number of caseous necrosis and ulcers, and the percentage of β-galactosidase-positive NMs.

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Tuberculous lesion rodent model: Rodents were infected with Mycobacterium tuberculosis to induce tuberculous lesions. One week post-infection, Cortisone acetate was administered via intraperitoneal injection at 5 mg/kg once daily for 2 weeks; vehicle control received equal volume of normal saline. Animals were euthanized after treatment, and tuberculous lesions were collected for histopathological macrophage counting, TNF-α quantification (ELISA), and phagocytic activity assay (neutral red uptake)[2]
- Chicken B cell modulation model: 4-week-old chickens were randomly grouped. Cortisone acetate was injected subcutaneously at 2 mg/kg twice weekly for 3 weeks; control chickens received saline. Peripheral blood was collected weekly to isolate B cells. Flow cytometry counted B cell numbers, and thymidine incorporation assay measured LPS-induced B cell proliferation[4]

Absorption, Distribution and Excretion
Corticosteroids are primarily excreted in the urine. Data regarding the clearance rate of cortisone acetate are not yet clear.

Protein Binding

Corticosteroids are typically bound to corticosteroid-binding globulins in plasma and serum albumin.

[1]. Cortisone counteracts apoptosis-inducing effect of cortisol in human peripheral-blood mononuclear cells. Int Immunopharmacol. 2001 Nov;1(12):2109-15.

[2]. The effect of cortisone on the accumulation, activation, and necrosis of macrophages in tuberculous lesions. Inflammation. 1978 Jun;3(2):159-76.

[3]. In Vivo Antifungal Activity of Monolaurin against Candida albicans Biofilms. Biol Pharm Bull. 2018;41(8):1299-1302.

[4]. In vivo effects of cortisone on the B cell line in chickens. J Immunol. 1975 Nov;115(5):1370-4.

Cortisone acetate is a corticosteroid hormone. First isolated in 1935, it began to be studied more extensively in 1949. Since then, glucocorticoids, including cortisone acetate, have been used to treat a variety of inflammatory diseases, such as endocrine disorders, rheumatic diseases, collagen disorders, skin diseases, allergic diseases, ophthalmic diseases, respiratory diseases, hematological diseases, neoplastic diseases, edematous diseases, and gastrointestinal diseases and disorders. Cortisone acetate was approved by the U.S. Food and Drug Administration (FDA) on June 13, 1950. Cortisone acetate is the acetate form of corticosterone and is a synthetic or semi-synthetic analog of the natural corticosterone hormone produced by the adrenal glands, possessing anti-inflammatory and immunomodulatory properties. Cortisone acetate diffuses across the cell membrane and binds to ribocorticoid receptors. The receptor-ligand complex binds to the promoter regions of certain genes, initiating RNA transcription. This leads to the induction of the synthesis of certain anti-inflammatory proteins while inhibiting the synthesis of certain inflammatory mediators.
Cortisol is a naturally occurring glucocorticoid that has been used as a replacement therapy for adrenal insufficiency and as an anti-inflammatory agent. Cortisol itself is inactive; it is converted into its active metabolite, hydrocortisone, in the liver. (From Martindale Pharmacopoeia, 30th edition, p. 726)
See also: Cortisone (containing the active ingredient)...See more...
Drug Indications
Cortisone acetate is indicated for the treatment of a variety of endocrine, rheumatic, collagen, dermatological, allergic, ophthalmic, respiratory, hematological, oncological, edema, and gastrointestinal disorders and disturbances.
Mechanism of Action
The short-term effects of corticosteroids are to reduce capillary vasodilation and permeability, and to reduce the migration of leukocytes to sites of inflammation. Corticosteroids bind to glucocorticoid receptors, mediating alterations in gene expression, thereby producing a variety of downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and marginalization; they inhibit phospholipase A2, thereby reducing the production of arachidonic acid derivatives; they inhibit NF-κB and other inflammatory transcription factors; and they promote the expression of anti-inflammatory genes such as interleukin-10. Low-dose corticosteroids have anti-inflammatory effects, while high doses have immunosuppressive effects. Long-term use of high-dose glucocorticoids can lead to increased sodium and decreased potassium levels due to binding to mineralocorticoid receptors.

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Cortisone acetate is a synthetic glucocorticoid prodrug that exerts its biological effects after being metabolized and activated into cortisone[1][2][4]
- Its core mechanism is to bind to the glucocorticoid receptor (GR), thereby regulating the function of immune cells, including inhibiting apoptosis of peripheral blood mononuclear cells (PBMCs), regulating the aggregation and activation of macrophages, and inhibiting B cell proliferation[1][2][4]
- It has immunomodulatory and anti-inflammatory activities and targets multiple immune cell populations (PBMCs, macrophages, B cells)[1][2][4]
- It is closely related to the treatment of inflammation and immune-related diseases in clinical practice because it can regulate the immune response in the body[2][4]

C23H30O6

402.48

402.204

C, 68.64; H, 7.51; O, 23.85

50-04-4

Cortisone;53-06-5

5745

Typically exists as white to off-white solids at room temperature

1.3±0.1 g/cm3

577.3±50.0 °C at 760 mmHg

237-240 °C(lit.)

197.3±23.6 °C

0.0±3.6 mmHg at 25°C

1.566

2.53

1

6

4

29

827

6

O([H])[C@]1(C(C([H])([H])OC(C([H])([H])[H])=O)=O)C([H])([H])C([H])([H])[C@@]2([H])[C@]3([H])C([H])([H])C([H])([H])C4=C([H])C(C([H])([H])C([H])([H])[C@]4(C([H])([H])[H])[C@@]3([H])C(C([H])([H])[C@@]21C([H])([H])[H])=O)=O

ITRJWOMZKQRYTA-RFZYENFJSA-N

InChI=1S/C23H30O6/c1-13(24)29-12-19(27)23(28)9-7-17-16-5-4-14-10-15(25)6-8-21(14,2)20(16)18(26)11-22(17,23)3/h10,16-17,20,28H,4-9,11-12H2,1-3H3/t16-,17-,20+,21-,22-,23-/m0/s1

2-((8S,9S,10R,13S,14S,17R)-17-hydroxy-10,13-dimethyl-3,11-dioxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl acetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 0.5 mg/mL (1.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 0.5 mg/mL (1.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 0.5 mg/mL (1.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 25 mg/mL (62.11 mM) in 0.1% Tween-80 in PBS (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)