Protective role and mechanism of flavonoids from Smilax glabra Roxb. against lead-induced neurotoxicity and hematotoxicity in Daniorerio.

Smilax glabra Roxb. (taxonomically verified via http://www.theplantlist.org, accessed December 17, 2025), commonly known as "Tu fuling" in China, is a well-recognized traditional Chinese herb extensively used for detoxification, dampness relief, and diuresis. Our previous research has demonstrated that Smilax glabra flavonoids extract (SGF) alleviate lead (Pb)-induced renal damage. However, the protective effects of SGF against Pb-induced neurotoxicity and hematotoxicity remain largely uninvestigated, and the underlying molecular mechanisms have not been fully elucidated. To reveal the potential protective effects and underlying molecular mechanisms of SGF against Pb-induced neurotoxicity and hematotoxicity, a lead poisoned zebrafish model was utilized. Zebrafish were randomly divided into four groups: (a) control group (no treatment); (b) Pb group (exposed to 80 μM lead acetate); (c) positive control group (Pb + DMSA group: first exposed to 80 μM lead acetate, then separately exposed to 15.6 μg/mL DMSA); (d) Pb + SGF groups (first exposed to 80 μM lead acetate, then separately exposed to SGF at 31.2, 62.5, or 125 μg/mL). All zebrafish were subjected to the respective sequential treatments for 4 consecutive days. Our results showed that SGF significantly reduced Pb content in zebrafish. SGF treatment markedly alleviated a series of adverse effects induced by Pb exposure in zebrafish, including trunk curvature, shortened body length, peripheral motor neuron damage, myelin and axonal injury, neuronal apoptosis, neurobehavioral impairment, and anemia. Moreover, SGF treatment led to a significant decrease in ROS levels in Pb-exposed zebrafish. Mechanistic experiments demonstrated that SGF significantly upregulated the mRNA expression levels of nerve protection-related genes (shha, gfap, mbp, and huc), memory-related genes (ache and gdnf), and antioxidant-related genes (nrf2 and cat). Conversely, SGF predominantly downregulated the mRNA expression levels of inflammation-related genes (il1β, il6, and tnfα) and apoptosis-related genes (caspase 3, bax, and p53). Meanwhile, SGF treatment significantly reduced the phospho-p65/p65 protein ratio. These results suggest that SGF may mitigate acute Pb-induced neurotoxicity and hematotoxicity, and these protective effects are associated with enhanced Pb excretion and the inhibition of Pb-induced oxidative stress, inflammation, and apoptosis. Moreover, the neuroprotective and memory-improving effects of SGF were observed in conjunction with the regulation of neurotrophic factors. Our findings highlight the potential pharmacological value of SGF in counteracting lead poisoning. However, given that the acute high-dose model does not fully recapitulate chronic low-dose human exposure, further validation in chronic models is essential before translational conclusions can be drawn.