Hydroxycitric acid

Hydroxycitric acid is an orally active, multi-target, multi-bioactive organic acid. activates Nrf2 and its downstream molecule GPX4, increases glutathione levels, and thereby inhibits ferroptosis. Hydroxycitric acid activates the Nrf2/Keap1 and ACLY/NF-κB signaling pathways, upregulates the activities of antioxidant enzymes such as superoxide dismutase, reduces MDA content, thereby alleviating oxidative stress and renal tubular epithelial cell apoptosis, and improves pulmonary vascular and right ventricular remodeling. Hydroxycitric acid activates both the AMPK and mTORC1/S6K pathways, triggers the unfolded protein response, arrests the cancer cell cycle, and induces DNA fragmentation^[1][2][3][4]. In Vitro:Hydroxycitric acid (1-100 mM; 72 h) potently inhibits the proliferation of K562, MEG-01, CML-T1, KYO-1 and SKH-1 chronic myeloid leukemia (CML) cell lines, with IC₅₀ values ranging from 3.73 to 11.34 mM; in contrast, it exerts no effect on normal mouse embryonic fibroblasts even at concentrations as high as 100 mM^[1].
Hydroxycitric acid (0.5-5 mM) induces DNA fragmentation in K562 chronic myeloid leukemia (CML) cells^[1].
Hydroxycitric acid (0.5-10 mM; 48-72 h) induces G₂/M cell cycle arrest in K562 chronic myeloid leukemia (CML) cells, with significant effects observed at the concentration of 10 mM after 48 h, as well as at concentrations of 5 mM and 10 mM after 72 h^[1].
Hydroxycitric acid (0.5-5 mM, 24-48 h) activates AMPK by increasing the phosphorylation level of T172 in K562, MEG-01, KYO-1 and SKH-1 chronic myeloid leukemia (CML) cells, without altering the total protein level of AMPK^[1].
Hydroxycitric acid (0.5-1 mM; 24-48 h) activates both the AMPK and mTORC1 pathways, and triggers the unfolded protein response in K562 chronic myeloid leukemia (CML) cells by upregulating the phosphorylation level of eIF2α and the expression level of ATF4^[1].
Hydroxycitric acid (5-10 mM) significantly inhibits hypoxia-induced proliferation of human pulmonary artery smooth muscle cells at concentrations of 5 mM and 10 mM^[3].
Hydroxycitric acid (matched to hypoxic/normoxic exposure conditions) inhibits the proliferation of human pulmonary artery smooth muscle cells under both normoxic and hypoxic conditions, with a stronger inhibitory effect on cells in a hypoxic environment^[3].
Hydroxycitric acid (24 h) significantly inhibits hypoxia-induced migration of human pulmonary artery smooth muscle cells^[3].
Hydroxycitric acid (overnight) significantly reduces hypoxia-induced reactive oxygen species production in human pulmonary artery smooth muscle cells^[3].
Hydroxycitric acid (combined with hypoxic exposure) significantly reduces the expression of hypoxia-inducible factor-1 (HIF-1) mRNA in hypoxia-induced human pulmonary artery smooth muscle cells^[3]. In Vivo:Hydroxycitric acid (3 mg/kg; p.o.; daily; 25 days) reduces the final tumor volume to 1/3 of the original level and significantly decreases tumor weight in a chronic myeloid leukemia xenograft mouse model^[1].
Hydroxycitric acid (250 mg/kg; i.p.; administered daily for 4 consecutive weeks) significantly reduces monocrotaline-induced pulmonary arterial hypertension in rats, decreases RVSP by 28.97% via anti-inflammatory and anti-fibrotic effects, and ameliorates right ventricular and pulmonary vascular remodeling^[3].
hydroxycitrate (250 mg/kg; i.p.; administered daily for 4 consecutive weeks) significantly alleviates hypoxia-induced pulmonary arterial hypertension in rats, reduces RVSP by 17.5% via anti-inflammatory and antioxidant effects, and improves right ventricular and pulmonary vascular remodeling^[3].