Hydroxycitric Acid

• CAS: 6205-14-7
• Catalog Number: ACM6205147-1
• Category: Main Products
• Molecular Weight: 208.12
• Molecular Formula: C6H8O8
• Synonyms: TRIPOTASSIUM-2-HYDROXYCITRATE;Tripotassium-2-Hydroxycditracte;HAC;HYDROXYCITRICACIDANDITSTRISODIUMSALT;HYDROXYCITRIC ACID hplc;1,2-Dihydroxy-1,2,3-propanetricarboxylic acid;Hydroxycitric acid;Tripotassium-2-Hydroxycitrate(KHCA)
• IUPAC Name: 1,2-dihydroxypropane-1,2,3-tricarboxylic acid
• Canonical SMILES: C(C(=O)O)C(C(C(=O)O)O)(C(=O)O)O
• InChI: InChI=1S/C6H8O8/c7-2(8)1-6(14,5(12)13)3(9)4(10)11/h3,9,14H,1H2,(H,7,8)(H,10,11)(H,12,13)
• InChI Key: ZMJBYMUCKBYSCP-UHFFFAOYSA-N
• Boiling Point: 393.3ºC at 760 mmHg
• Flash Point: 205.8ºC
• Density: 1.947 g/cm³
• Appearance: Powder
• Exact Mass: 208.02200

Case Study

Hydroxycitric Acid for Cartilage Regeneration in Osteoarthritis Therapy

Mizushina Y, et al. Osteoarthritis and Cartilage Open, 2024, 100564.

Hydroxycitric acid (HCA) demonstrates a dual mechanism of action, enhancing cartilage matrix synthesis while modulating mitochondrial activity through metabolic reprogramming. These properties position HCA as a promising candidate for osteoarthritis treatment, addressing the critical unmet need for cartilage regeneration in degenerative joint diseases. This case study explores HCA's role in enhancing chondrogenesis and its application in osteoarthritis therapy.
Methodology: In vitro studies identified HCA as a potent enhancer of chondrogenic differentiation in mesenchymal stem cells (MSCs) derived from human-induced pluripotent stem cells. HCA inhibits ATP citrate lyase, leading to increased citrate and alpha-ketoglutarate (α-KG) levels while reducing cytosolic acetyl coenzyme A (Ac-CoA). Elevated α-KG levels promote collagen prolyl-4-hydroxylase activity, resulting in enhanced hydroxyproline production and extracellular matrix formation. Simultaneously, reduced Ac-CoA levels diminish the acetylation of β-catenin, alleviating its inhibitory effect on mitochondrial function and further supporting chondrogenesis.
In vivo, orally administered HCA was observed to accumulate in joint tissues of a mouse model of exercise-induced osteoarthritis. Histological analysis revealed significant cartilage regeneration in damaged areas, with newly synthesized cartilage tissues observed. Joint tissue extracts exhibited decreased Ac-CoA levels alongside increased citrate and α-KG concentrations, further supporting HCA's metabolic effects. A systemic increase in anabolic biomarkers was also detected, indicating overall cartilage repair.

Hydroxycitric Acid Inhibits Renal Interstitial Calcification and Apoptosis

Liu W-F, et al. Journal of Functional Foods, 2024, 119, 106317.

Hydroxycitric acid (CA) effectively inhibits ectopic calcification in renal interstitial fibroblasts by reducing apoptosis and calcium salt deposition. Its antioxidative and regulatory effects on calcification pathways position it as a promising alternative drug for preventing renal stone formation.
Mechanism of Action: HCA inhibits the calcification of renal interstitial fibroblasts by targeting cellular mechanisms involved in calcium salt deposition. Calcification-related proteins, significantly upregulated in animal and cell models, were effectively suppressed by HCA. The compound reduced oxidative stress and calcification-induced apoptosis in fibroblast cultures, demonstrating a dual protective role. Cellular transcriptomic analysis revealed HCA's ability to regulate gene expression altered by calcification, further emphasizing its therapeutic potential.
In Vivo Evidence: Animal studies corroborated HCA's efficacy, showing decreased calcium salt deposition and lower expression levels of calcification-related proteins in renal tissues. These findings highlight HCA's role in mitigating oxidative damage and cellular apoptosis, ultimately reducing the risk of renal stone formation.

Hydroxycitric Acid Suppresses Adipogenesis via RPS6KA1/FoxO1 Signaling Pathway in Obesity Management

Lee H-W, et al. Phytomedicine, 2024, 128, 155551.

Hydroxycitric acid (HCA) inhibits adipogenesis by targeting the RPS6KA1/FoxO1 signaling axis, arresting preadipocyte proliferation during MCE. These findings underscore HCA's role as a promising therapeutic agent for obesity, offering a molecular framework for its application in metabolic health interventions.
Mechanism of Action: HCA effectively arrests the cell cycle of 3T3-L1 preadipocytes at the G0/G1 phase, thereby inhibiting MCE, a crucial process in adipogenesis. The compound suppresses the phosphorylation of Forkhead Box O1 (FoxO1), facilitating the nuclear retention of FoxO1 and upregulating cyclin-dependent kinase inhibitor 1B (CDKN1B). Concurrently, HCA reduces the expression of cell proliferation markers, including cyclin-dependent kinase 2, cyclin E1, and proliferating cell nuclear antigen (PCNA), while attenuating retinoblastoma protein phosphorylation. Ribosomal protein S6 kinase A1 (RPS6KA1) was identified as a key regulator in the HCA-mediated inactivation of FoxO1, providing a molecular basis for its anti-adipogenic effects.
In Vivo Evidence: In a 12-week study on HFD-fed mice, HCA significantly reduced body weight gain and decreased epididymal and mesenteric white adipose tissue mass. Histological analysis revealed a reduction in adipocyte numbers, consistent with the suppression of RPS6KA1/FoxO1 signaling and its downstream targets in vivo.

Hydroxycitric Acid for Inhibition of Renal Calcium Oxalate Deposition and Oxalate Nephropathy

Zhang Y-H, et al. Journal of Functional Foods, 2023, 105, 105561.

This case study explores HCA's inhibitory effects on calcium oxalate (CaOx) deposition, oxidative damage, and nephrotoxicity through molecular and cellular mechanisms.
Mechanism of Action: Hydroxycitric acid (HCA) effectively prevents CaOx crystal deposition by reducing crystal adhesion and oxidative stress. Transcriptomic and in vitro analyses revealed that HCA stabilizes its binding with peroxisome proliferator-activated receptor α (PPARα), enhancing the expression of downstream oxidative stress-regulating molecules. This modulation reduces calcium ion release, mitigates mitochondrial dysfunction, and decreases oxalate-induced lipid peroxidation damage.
In Vivo Evidence: In an oxalate-induced rat model, HCA significantly inhibited renal CaOx deposition, reduced oxidative stress markers, and alleviated nephrotoxicity. The compound's dual action on lipid metabolism regulation and CaOx formation inhibition underscores its therapeutic efficacy in reducing renal damage and improving kidney function.
Conclusion: Hydroxycitric acid demonstrates significant potential in treating oxalate nephropathy by targeting oxidative stress pathways and mitigating calcium oxalate deposition. Its ability to modulate PPARα activity highlights its promising role as a therapeutic option for managing renal stone disease and associated nephropathies.

Hydroxycitric Acid in Phytoformulation Therapy for Obesity-Associated Cardiomyopathy

Uddandrao VVS, et al. Journal of Traditional and Complementary Medicine, 2024, 14(2), 162-172.

Hydroxycitric acid (HCA) in phytoformulation therapy offers a novel approach to managing obesity-related cardiomyopathy. By regulating fatty acid metabolism and suppressing inflammation, HCA demonstrates significant potential in protecting cardiac function and addressing metabolic disorders linked to obesity.
The phytoformulation suppressed fatty acid synthesis and uptake by downregulating genes such as sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and fatty acid binding protein 1 (FABP1). Concurrently, it enhanced fatty acid catabolism by upregulating lysosomal acid lipase (LAL), hormone-sensitive lipase (HSL), and lipoprotein lipase (LPL). Anti-inflammatory and anti-apoptotic effects were mediated through the downregulation of the NF-kB/TLR4/BAX/caspase-3 pathway, reducing cytokine levels and cellular apoptosis in cardiac tissue.
In HFD-fed Sprague-Dawley rats, the phytoformulation significantly reduced hyperglycemia, dyslipidemia, and myocardial lipid accumulation. Histological analysis confirmed alleviation of cardiac inflammation and apoptosis. Moreover, markers of improved insulin sensitivity and reduced myocardial damage were observed.