2,3,4-Trihydroxy-benzaldehyde, C7H6O4, crystallizes with two independent mol-ecules in the asymmetric unit. In both mol-ecules, the 2-hydr-oxy group is bound via intra-molecular hydrogen bonds to the aldehyde group. The mol-ecules inter-act through O—H?O hydrogen bonds to form a three-dimensional network structure; each hydr-oxy group serves as a donor to only one acceptor atom. 2,3,4-Trihydroxybenzaldehyde condenses with primary amines to afford Schiff bases. The crystal structures of only few such Schiff bases have been reported. The 2-fluoroaniline derivative exists as a zwitterion as the hydrogen atom of the 2-hydroxy substituent is transferred to the imino nitrogen atom. On the other hand, the antipyrine derivative has the expected neutral structure. Although there are several structural studies on hydroxy-substituted benzaldehydes, the structure of 2,3,4-trihydroxybenzaldehyde has not been reported.

Synthesis of 2,3,4-Trihydroxy-benzaldehyde

Add 150 ml of 30% sulfuric acid solution, keep warm at 40°C for 1 h, cool to room temperature, separate the layers, extract the aqueous layer with toluene three times, combine the organic phases, concentrate to dryness, dissolve the solid in 5% methanol water at 90-100°C and stir for 1 h, cool and crystallize to obtain 30.1 g of light brown solid, with a yield of 90.7% (based on the first step intermediate).[1]

2,3,4-trihydroxybenzaldehyde as a potential anti-obesity treatment

2,3,4-trihydroxybenzaldehyde has been shown to decrease human colon cancer cell viability by regulating pro-oncogenic signals. It has also been reported that THB significantly reduced blood glucose and inhibited α-glucosidase, suggesting that THB might be useful for treating diabetes. However, there have been no published studies on the effects of 2,3,4-trihydroxybenzaldehyde on adipocyte differentiation or the effects of THB on fat accumulation in animal models of obesity. Therefore, in the present study, we evaluated these effects of THB in murine 3T3-L1 cells and in mice fed a high-fat diet (HFD).[2]

The effect of 2,3,4-trihydroxybenzaldehyde on cell viability of 3T3-L1 cells was evaluated by performing the MTT assay. THB did not influence the cell viability of 3T3-L1 cells at 50 and 100 μM. Therefore, these concentrations were used in all subsequent experiments in 3T3-L1 cells. In order to investigate whether 2,3,4-trihydroxybenzaldehyde inhibited MDI-induced lipid accumulation during differentiation in 3T3-L1 cells, we performed Oil Red O staining. Microscopic observations of the morphology of cells stained with Oil Red O, a lipid stain, and the OD values measured after isopropanol elution of Oil Red O showed decreased cellular lipid content with increased 2,3,4-trihydroxybenzaldehyde concentration. Lipid accumulation related to adipogenic differentiation is accompanied by the induction of key adipogenic transcription factors, including PPARγ, C/EBPα, FAS and SREBP-1c, and we examined the levels of these transcription factors by Western blot. THB treatment significant decreased the protein expression of PPARγ, C/EBPα, FAS and SREBP-1c compared to the expression seen in MDI-induced cells without THB treatment. We found that feeding mice a HFD and treating with 2,3,4-trihydroxybenzaldehyde for 13 weeks resulted in markedly decreased hepatic accumulation of lipid droplets in THB-treated mice compared to the HFD only group. These results suggest that 2,3,4-trihydroxybenzaldehyde might improve non-alcoholic fatty liver disease. In addition, histological analysis of the epididymal white adipose tissue revealed smaller adipocytes in THB-treated group compared with those in HFD group, demonstrating that the reduced body weight gain was due to decreased fat accumulation in adipocytes.

In conclusion, we have shown that 2,3,4-trihydroxybenzaldehyde inhibits adipogenesis that is likely mediated by down-regulation of the adipocyte-specific transcriptional regulators PPARγ, C/EBPα, and SREBP-1c. In addition, 2,3,4-trihydroxybenzaldehyde prevented HFD-induced increases in body weight, fat deposition in the liver, adipose cell size, and total cholesterol, triglyceride, and glucose levels in plasma. These results suggested that 2,3,4-trihydroxybenzaldehyde might be beneficial for the prevention and/or treatment of obesity and related metabolic disorders.[3]

References

[1]QINGDAO XUNTIAN TECH - CN117820100, 2024, A

[2]Sancheti, S., Sancheti, S., Bafna, M., & Seo, S.-Y. (2010). 2,4,6-Trihydroxybenzaldehyde as a potent antidiabetic agent alleviates postprandial hyperglycemia in normal and diabetic rats. Medicinal Chemistry Research, 20, 1181-1187.

[3]Kim KN, Kang MC, Kang N, Kim SY, Hyun CG, Roh SW, Ko EY, Cho K, Jung WK, Ahn G, Jeon YJ, Kim D. 2,4,6-Trihydroxybenzaldehyde, a potential anti-obesity treatment, suppressed adipocyte differentiation in 3T3-L1 cells and fat accumulation induced by high-fat diet in C57BL/6 mice. Environ Toxicol Pharmacol. 2015 Mar;39(2):962-8. ;