Female ICR mice were used. *P. acnes* (ATCC 6919, 1×10⁷ CFU in 20 μL PBS) was intradermally injected into the left ear; the right ear received PBS as a control. For intradermal treatment, Lauric acid (2 μg in 20 μL of 5% DMSO in PBS) was injected immediately after bacterial injection at the same site. For epicutaneous treatment, lauric acid (150 μg in 5% acetone mixed with 15 mg Vaseline) was applied to the ear surface immediately after bacterial injection. Control groups received vehicle (5% DMSO in PBS for intradermal; 5% acetone in Vaseline for epicutaneous). Ear thickness was measured with a micro caliper before and 24 hours after bacterial injection. To quantify bacterial CFUs, ear tissue was punched (8 mm biopsy punch), homogenized in PBS, and serial dilutions were plated on Brucella agar. Plates were incubated anaerobically at 37°C for 72 hours. For histology, ear sections were stained with hematoxylin and eosin. TUNEL assays were performed on ear sections to detect apoptosis, with keratin 10 (K10) co-staining to identify differentiated keratinocytes. [1]

Absorption, Distribution and Excretion
Fatty acids derived from adipose tissue storage either bind to serum albumin or exist in the blood as free fatty acids. Oleic acid, palmitic acid, myristic acid, and stearic acid are primarily transported via the lymphatic system, while lauric acid is transported via both the lymphatic system and the portal venous system (in the form of free fatty acids). The mechanisms of fatty acid absorption in different tissues include passive diffusion, facilitated diffusion, or a combination of both. Absorbed fatty acids can be stored as triglycerides (98% of which are found in adipose tissue) or oxidized for energy through catabolic pathways such as β-oxidation and the tricarboxylic acid cycle. Metabolism/Metabolites The induction of microsomal drug-metabolizing enzymes by various lipid-lowering drugs varies. Clofibrate, clofibrate, fenofibrate, and dulofibrate, which primarily lower triglycerides, increased cytochrome P450 levels (77-185% higher than the control group), especially cytochrome P452-dependent laurate 12-hydroxylation (5.6-8.4-fold increase). Bilirubin glucuronidation was enhanced by 2.1-2.8-fold; epoxide hydrolase (benzo[a]pyrene oxide) activity was only slightly increased. In contrast, F1379, which only lowers plasma cholesterol, did not alter cytochrome P450 levels and had minimal effect on laurate 12-hydroxylation. It significantly enhanced epoxide hydrolase activity (7.6-fold) and increased glucuronidation of group I planar substrates (4-nitrophenol, 4-methylumbelliferone, 1-naphthol) by 200%. These effects were accompanied by strong positive staining for gamma-glutamyl transferase in the liver, characterized by numerous strongly stained foci in the periportal and perilobular regions. This typical feature of enzyme induction remained unchanged after three weeks of treatment with F1379 in rats. This sustained effect may reveal some biochemical changes of significant toxicological importance in hepatocytes. Treatment of rats with both metabolites of F1379 resulted in decreased induction potency for epoxide hydrolases and UDP-glucuronyl transferases compared to the parent compound; in contrast, cytochrome P450 levels increased.
Fatty acid ω-oxidation was assessed in rats. Aspirin increased the content of free fatty acids in the liver and enhanced ω-oxidation capacity by 3 to 7 times. ω-oxidation of long-chain substrates was more stimulated than that of medium-chain substrates and was observed within one day of treatment, at which time serum aspirin concentrations were below the therapeutic range in humans. The apparent Km value for lauric acid was 0.9 mM, and for palmitic acid, it was 12 mM. Of the total recovered lauric acid ω-oxidation activity, 97% was found in microsomes, while 32% of palmitic acid ω-oxidation activity was found in the cytosol. Aspirin is a potent stimulator of ω-oxidation. ω-oxidation may involve multiple enzymes, and there is overlap in substrate specificity. CYP6A8 was expressed in Saccharomyces cerevisiae, and its catalytic activity was enzymatically characterized after reconstruction with Drosophila P450 reductase and NADPH. Although some saturated or unsaturated fatty acids cannot be metabolized by CYP6A8, the short-chain unsaturated fatty acid lauric acid (C12:0) can be oxidized by CYP6A8 to 11-hydroxylauric acid, with an apparent maximum reaction rate (V_max) of 25 nmol/min/nmol P450. This is the first report of a member of the CYP6 family catalyzing the hydroxylation of lauric acid. Known metabolites of lauric acid include 12-hydroxylauric acid.

Interactions
This study investigated the effect of lauric acid on the transdermal absorption of benzodiazepines in vivo. Results showed that lauric acid treatment increased the maximum anticonvulsant effect of benzodiazepines in the transdermal therapy system by 3 times compared to the control group. Pharmacokinetic studies of the benzodiazepine transdermal therapy system showed higher bioavailability in the presence of lauric acid (f=0.9). This study used a Franz diffusion cell to investigate the effects of two fatty acids—oleic acid and lauric acid (dordecanoic acid)—on the transport of the cationic drugs naphthazoline, neutral caffeine, and anionic sodium salicylate through isolated human skin. Both acids increased the in vitro skin permeability of all permeates. Oil-water partition data and rotating diffusion cell measurements in the presence of fatty acids suggested that the increased flux of cationic naphthazoline was likely due to the formation of ion pairs with the carboxyl anions of fatty acids, thereby increasing its lipophilicity. Neutral caffeine and sodium salicylate failed to form ion pairs; therefore, the increased skin permeability was also due to stratum corneum disruption. Increased transepidermal water loss and increased in vivo skin permeability of the nonionic compound methyl nicotinate in fatty acid-treated skin sites further support this conclusion. The transdermal absorption of bupranol was studied in vitro using model membranes and human skin samples; the effects of oleic acid and lauryl acid (lauric acid) on bupranol absorption were also assessed. Bupranol rapidly diffused across skin samples. Transmembrane transport of bupranol across the model membrane was enhanced in the presence of oleic acid and lauryl acid. However, they did not significantly enhance transmembrane transport across human skin samples. Cytochrome P450 IVA1 and IVA3 shared 72% amino acid sequence similarity and were expressed in the liver of rats treated with the lipid-lowering drug clofibrate. The catalytic activities of IVA1 and IVA3 were detected by directed cDNA expression using vaccinia virus. The relative molecular weights of IVA1 and IVA3 expressed by cDNA were 51,500 and 52,000, respectively, in SDS-polyacrylamide gel electrophoresis. Both enzymes exhibited reduced CO-binding absorption spectra with a maximum absorption wavelength of 452.5 nm. IVA1 and IVA3 hydroxylated laurate at the ω and ω-1 positions, with an ω/ω-1 ratio of approximately 12.5. The substrate turnover rate of IVA1 was 21/min, approximately four times that of IVA3. These P450 enzymes also catalyzed the ω and ω-1 hydroxylation of palmitic acid, with total turnover rates of 45/min for IVA1 and 18/min for IVA3, respectively. The ω/ω-1 oxidation ratio of palmitic acid by IVA1 was 1.25, almost four times that of IVA3. These enzymes also catalyzed the ω oxidation of physiologically important eicosic acid compounds prostaglandins E1 and F2α, with turnover rates approximately one-tenth that of fatty acid oxidation. No ω-1 hydroxyl metabolites were detected. These studies indicate that the P450 enzymes IVA1 and IVA3 can catalyze the oxidation of fatty acids and prostaglandins. This study investigated the effects of ciprofibrate, a potent oxoisobutyric acid derivative, on various liver enzyme parameters in five rat strains after a 14-day treatment regimen. Hepatomegaly was observed in all rat strains at both dose levels (2 and 20 mg/kg). The treatment groups showed a 10- to 15-fold increase in laurate 12-hydroxylation activity and a 1.5- to 5-fold increase in 11-hydroxylation activity, though the increases were relatively small. A dose-dependent increase in fatty acid hydroxylase activity was associated with a maximum 10-fold increase in the specific content of the cytochrome P-450 IVA1 isoenzyme apolipoprotein, as determined by ELISA immunochemistry. Following treatment, the activities of the cytochrome P-450 I (IA1 and IA2) and II (IIB1 and IIB2) families were determined by ethoxyhalothrin-O-deethylase and amphetamine-N-demethylase activities, respectively, showing decreased activity. At higher dose levels, mitochondrial monoamine oxidase activity was significantly reduced, while α-glycerophosphate dehydrogenase activity was increased. In all tested strains, total carnitine acetyltransferase activity (mitochondrial and peroxisome) and peroxisome β-oxidation activity were significantly increased at both dose levels. Cytoplasmic glutathione peroxidase activity, measured using tert-butyl hydroperoxide and hydrogen peroxide as substrates, decreased to approximately 50% of the control group after treatment. In the treated animals, mRNA levels encoding cytochrome P-450 IVA1 and fatty acid β-oxidation helical peroxisome bifunctional proteins were significantly increased. However, contrary to the aforementioned decrease in glutathione peroxidase activity, mRNA levels encoding glutathione peroxidase appeared to remain unchanged after ciprofibrate administration. In summary, our results further confirm the close association between the induction of rat liver microsomal cytochrome P-450 IVA1, peroxisome β-oxidation, and total carnitine acetyltransferase activity, and provide a conceptual basis for rationalizing the chronic toxicity of peroxisome proliferators in this species.

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Non-human toxicity values
Mouse intravenous LD50: 131 mg/kg
Rat oral LD50: 12,000 mg/kg

[1]. Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. J Invest Dermatol. 2009 Oct;129(10):2480-8.

[2]. Lauric acid alleviates insulin resistance by improving mitochondrial biogenesis in THP-1 macrophages. Mol Biol Rep. 2020 Dec;47(12):9595-9607.

[3]. Acute Treatment with Lauric Acid Reduces Blood Pressure and Oxidative Stress in Spontaneously Hypertensive Rats. Basic Clin Pharmacol Toxicol. 2017 Apr;120(4):348-353.

Therapeutic Uses
Gly-Arg-Gly-Asp-Ser (GRGDS) was modified by coupling with lauric acid (LA) to facilitate its incorporation into polycarbonate-urea-carbamate (PCU) matrices for vascular bypass grafting. GRGDS and LA-GRGDS were chemically synthesized using solid-phase Fmoc and characterized by high-performance liquid chromatography and Fourier transform infrared spectroscopy. LA-GRGDS was passively coated and incorporated into PCU films in the form of nanoparticle dispersions. The biocompatibility of the modified surfaces was investigated. Endothelial cells seeded on LA-GRGDS-coated and incorporated PCU showed significantly increased metabolism at 48 and 72 hours compared to unmodified PCU (p < 0.05). Platelet adhesion and hemolysis studies indicated that the modification of PCU had no adverse effects. In summary, LA-conjugated RGD derivatives, such as LA-GRGDS, are soluble in solvents used in solvent casting, thus showing broad application prospects in polymer development for coronary artery, vascular, and dialysis bypass grafts, as well as scaffolds for tissue regeneration and tissue engineering. This study aimed to investigate the in vitro activity of lauric acid and myristicin in combination with six antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA). The combined effects of lipids and antimicrobial agents were assessed using a checkerboard method to obtain partial inhibitory concentration (FIC) indices. Among the 12 combinations, the combinations of lauric acid + gentamicin (GM) and lauric acid + imipenem (IPM) both showed synergistic effects against clinical isolates. Antagonism was observed only in the myristicin + GM combination. We investigated the antimicrobial activity of the two synergistic combinations in detail. The addition of GM and IPM did not enhance the cytotoxicity of lauric acid. In time-based sterilization experiments, lauric acid + GM and lauric acid + IPM combinations at concentrations one-eighth of the minimum inhibitory concentration (MIC) both exhibited antibacterial activity. Staphylococcus aureus can cause various human infections, including toxic shock syndrome, osteomyelitis, and mastitis. Mastitis is a common disease in dairy cows, and Staphylococcus aureus has been confirmed as the leading cause of mastitis. This study aimed to determine which fatty acids and their esterified forms can inhibit the growth of Staphylococcus aureus. This study tested the inhibitory effects of fatty acids and their monoacylglycerols, diacylglycerols, and triacylglycerols on a human toxic shock syndrome clinical isolate (MN8) and two Staphylococcus aureus clinical isolates of bovine mastitis (305 and Novel). Minimum inhibitory concentration (MIC) analysis revealed that the seven most potent inhibitors among all tested strains included lauric acid, glyceryl monolaurate, capric acid, myristic acid, linoleic acid, cis-9, trans-11 conjugated linoleic acid, and trans-10, cis-12 conjugated linoleic acid. Selected lipids were used to analyze the 48-hour growth curves of Staphylococcus aureus isolate Novel at concentrations of 0, 20, 50, and 100 μg/mL. Myristic acid was tested at concentrations of 0, 50, 100, and 200 μg/mL. Saturated fatty acids (lauric acid, capric acid, and myristic acid) and glyceryl monolaurate showed similar effects, both inhibiting overall bacterial growth. Conversely, polyunsaturated fatty acids (linoleic acid and cis-9, trans-11 conjugated linoleic acid) delayed the onset of bacterial exponential growth in a dose-dependent manner. These results suggest that lipids may play an important role in controlling Staphylococcus aureus infection.

C12H24O2

200.322

200.177

143-07-7

Lauric acid-d23;59154-43-7;Lauric acid-d3;79050-22-9;Lauric acid-13C;93639-08-8;Lauric acid-d2;64118-39-4;Lauric acid-13C-1;287100-78-1;Lauric acid-d5;1219804-38-2

3893

White to off-white solid powder

0.9±0.1 g/cm3

296.1±3.0 °C at 760 mmHg

44-46 °C(lit.)

134.1±11.9 °C

0.0±0.7 mmHg at 25°C

1.448

5.03

1

2

10

14

132

0

O([H])C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O

POULHZVOKOAJMA-UHFFFAOYSA-N

InChI=1S/C12H24O2/c1-2-3-4-5-6-7-8-9-10-11-12(13)14/h2-11H2,1H3,(H,13,14)

dodecanoic acid

Vulvic acid Lauric acid Dodecanoic Acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

DMSO : ~100 mg/mL (~499.20 mM)
0.1 M NaOH : ~10 mg/mL (~49.92 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (10.38 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 20.8 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 2: ≥ 2.08 mg/mL (10.38 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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