Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross is a perennial herb belonging to the Polygonaceae family, mainly distributed in southwestern China. Persicaria capitata is edible and boasts a high nutritional profile, and the entire plant serves medicinal purposes. According to the Guangxi Materia Medica, it has the functions of "relieving wind-dampness, enhancing blood circulation, and easing pain". Persicaria capitata is a major component of the traditional Chinese medicine formula, Re-Lin-Qing, which is widely used for treating urinary calculi (urolithiasis). However, its specific mechanisms of action remain unclear. In this study, we employed molecular biology, molecular dynamics, and cellular biology strategies to develop a rat experimental model of oxalate-induced urolithiasis and a cell model of oxalate-induced injury to study the active constituents and molecular mechanisms of Persicaria capitata in inhibiting oxalate stone formation both in vivo and in vitro. The results show that in vivo, Persicaria capitata significantly reduced the formation rate of oxalate stones in rats, decreased the levels of urinary oxalate, sodium, potassium, calcium, and magnesium, while increasing urine pH, urinary citrate levels, and urine excretion. Moreover, Persicaria capitata significantly lowered serum creatinine levels in oxalate stone model rats and mitigated kidney damage. In vitro, treatment with Persicaria capitata extract effectively alleviated oxalate-induced oxidative stress in HK-2 cells, reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing ATP levels and inhibiting oxalate-induced apoptosis. LC-MS analysis of Persicaria capitata components, in combination with transcriptomics, network pharmacology, and metabolomics sequencing, indicated that Myricetin might be one of its potential bioactive compounds. Both Persicaria capitata extract and its active compound, Myricetin, significantly reversed the oxalate-induced decrease in PI3K and ERK levels and inhibited the overexpression of oxidative stress-related proteins. Further analysis using cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) experiments revealed that Myricetin exhibits strong binding affinity to PIK3CA. Moreover, PI3K inhibitors reversed the protective effects of Persicaria capitata and Myricetin on oxalate-induced cell injury models. Persicaria capitata exerts its anti-urolithiasis effects by alleviating oxidative stress through a multi-component, multi-target synergistic mechanism. Additionally, Myricetin, one of the bioactive components of Persicaria capitata, directly binds to PIK3CA, promoting ERK expression, upregulating NRF2 levels, and subsequently reducing oxidative stress, thereby inhibiting oxalate stone formation and alleviating kidney injury.

The skin of the Chinese giant salamander (Andrias davidianus) is a rich source of collagen. However, current research indicates limited efficiency and activity in collagen protease hydrolysis from this source. Further enzymatic hydrolysis to produce small molecular weight active peptides and their antitumor potential remain underexplored. This study employed a two-step enzymatic hydrolysis method to prepare small molecular weight collagen peptides (SMWCPs), followed by ultrafiltration separation. The extraction process was optimized using single-factor and response surface methodology. The amino acid composition of SMWCPs was analyzed, and their antitumor activity was assessed in vitro through cell migration, cell cycle, and apoptosis assays. Results revealed a negative correlation between collagen peptide molecular weight and antitumor activity, with optimal antitumor activity observed for peptides with a molecular weight of 300–1 000 Da (neutral protease hydrolyzed Chinese giant salamander skin collagen peptides (NP-GSKCP)). Optimal extraction conditions were: enzyme dosage 8 000 U/g, enzymatic hydrolysis temperature 52.6 °C, enzymatic hydrolysis pH 7.1, and enzymatic hydrolysis time 4.3 h, yielding 87.82% NP-GSKCP-IV. Notably, NP-GSKCP-IV contained 55.31% hydrophobic amino acids. Treatment of A549 cells with 5 mg/mL NP-GSKCP-IV significantly altered cell morphology, inhibited migration, arrested the cell cycle at G0/G1 phase, and induced early apoptosis. This study contributes to the development of efficient extraction techniques for antitumor active ingredients from Chinese giant salamander skin and informs the potential development of medicinal functional foods.