Huoxuezhitong capsule (HXZT, activating blood circulation and relieving pain capsule), has been applied for osteoarthritis since 1974. It consists of Angelica sinensis (Oliv.) Diels, Panax notoginseng (Burkill) F. H. Chen ex C. H., Boswellia sacra, Borneol, Eupolyphaga sinensis Walker, Pyritum. However, the direct effects of HXZT on osteoarthritis and the underlying mechanisms were poorly understood. In this study, we aimed to explore the analgesia effect of HXZT on MIA-induced osteoarthritis rat and the underlying mechanisms. The analgesia and anti-inflammatory effect of HXZT on osteoarthritis in vivo were tested by the arthritis model rats induced by monosodium iodoacetate (MIA).. Mechanistic studies confirmed that HXZT could inhibit the activation of NF-κB and down-regulate the mRNA expression of related inflammatory factors in LPS-induced RAW264.7 and ATDC5 cells. Furtherly, in LPS-induced RAW264.7 cells, HXZT could suppress NF-κB via inhibiting PI3K/Akt pathway. Taken together, HXZT capsule could ameliorate MIA-induced osteoarthritis of rats through suppressing PI3K/ Akt/ NF-κB pathway.

Inhibiting de novo lipogenesis (DNL) in hepatocytes is a promising strategy for treating metabolic fatty liver diseases. ACLY, a key enzyme in the DNL pathway, has become a therapeutic target for non-alcoholic fatty liver disease (NAFLD). However, its inhibition shows mixed outcomes, depending on interventions and diets. Evidence suggests ACLY inhibition activates the ACSS2-mediated acetate metabolism and the subsequent DNL, though potential mechanisms and possible consequences remain unclear. This study found that targeting hepatic ACLY with AAV8-shRNA failed to improve NAFLD in mice fed a high-fat, high-fructose diet. Instead, it worsened inflammation and liver injury. ACLY inhibition conditionally upregulated DNL enzymes, but consistently activated the ACSS2-acetyl-CoA pathway and suppressed fatty acid oxidation. Further, ACLY inhibition led to polyunsaturated fatty acid accumulation, triggering mitochondrial dysfunction. The resulting ROS redirected carbon flux into acetate, activating the ACSS2-acetyl-CoA pathway, which promoted lipid biosynthesis and exacerbated mitochondrial dysfunction-a vicious cycle that fueled inflammation and liver damage. Dual inhibition of ACLY and ACSS2 broke this cycle by reducing hepatic acetyl-CoA flux, suppressing DNL, enhancing fatty acid oxidation via PPAR-α activation, and improving mitochondrial function. This combined targeting strategy reduced lipid accumulation, alleviated inflammation, and normalized aminotransferase levels, effectively reversing NAFLD progression.