Acute kidney injury (AKI) is a clinical syndrome covering sudden loss of renal function due to retention of urea and other nitrogen-based compounds (Perazella, 2019; Zhou et al., 2023). Recently, the AKI has become one of the most critical public safety issues in the world with its high prevalence and mortality rates, which is also on the rise among elderly hospitalized cases. The AKI not only results in chronic kidney disease (CKD) or end-stage renal disease (ESRD) but also brings a long-term risk of cardiovascular disease, lung damage, or digestive disease (Gupta et al., 2020). Studies have shown that AKI, as a systemic disease that impairs the immune system and organ function, the clinical mechanism usually involves multiple complex biological actions such as inflammatory response, renal tubular injury, and microvascular damage, which cause a large number of complications (Perazella, 2018). Nowadays, renal replacement therapy (RRT) is the centerpiece of the AKI treatment, whose optimal mode of measurement has been accepted by experts (Bagshaw et al., 2017). Diuretics, acetylcysteine, sodium bicarbonate, and statins are frequently used to treat AKI in the clinical setting. However, there is no standard therapeutic agent for the AKI due to insufficient research evidence and inconsistent results.

Traditional Chinese Medicine (TCM) is widely used in China, Japan, Singapore and some countries in Southeast Asia to treat various diseases. In ancient China, although there was no accurate diagnosis of modern medicine, the overall dialectic treatment provides rich experience for AKI treatment. For example, the relationship between kidney and edema was firstly mentioned in Huangdi neijing, which believed that kidney was the master of water, and the insufficiency of kidney qi would lead to water and fluid metabolic disorders(Wang, 2010). According to Sheng Nong's herbal classic, Ganoderma lucidum (Leyss. ex Fr.) Karst (GL) is flat in nature, sweet in flavor, whose branch Amauroderma ruda (Berk.) Pat. entered the kidney meridian to “benefit waterways and kidney qi” (Lin, 2019). Ganoderma lucidum (Leyss. ex Fr.) Karst spore (GLS) is a mixture of tiny oval-shaped germ cells discharged from the cap of the Ganoderma lucidum fruiting body, which is widely used as a high-quality medicinal and food product (Liu et al., 2020), and its active ingredients are much higher than those of GL. It is effective in diabetic nephropathy, polycystic kidney and other diseases through anti-oxidative stress, alteration of metabolism and inhibition of DNA damage (Geng et al., 2020; Meng et al., 2020). Our team further investigated the effect of GLS on AKI.

Network pharmacology is a comprehensive discipline that combines omics and molecular bioinformatics. By constructing a TCM-COMPOUND-TARGETS network, the interactions between target molecules and drug-active molecules in vivo are investigated to identify specific signaling nodes. Using molecular docking to obtain patterns of protein-ligand (complex) interactions and potency (Yuan et al., 2021). The technique uses programs such as AutoDock Tool, PyRx, DS and PyMoL to accurately predict the binding mode of the target ligand. In addition, the surface enhanced raman spectroscopy (SERS) can be used to analyze biological tissues by generating images in the wavelength range of 190–4000 cm−1 using spectroscopy and spatial information technologies (Valsan et al., 2023). Disease information is obtained by detecting the characteristic wavenumbers of fats, proteins, and nucleic acids (Minaeva et al., 2021).

The occurrence of AKI has been extensively studied. The protective effect of GLS on the kidneys has been documented, but its therapeutic mechanism for AKI has not been identified. Therefore, the purpose of this study was to discover the protective pathway of GLS against AKI and further explore the mechanism of GLS in the treatment of AKI through molecular biology and network pharmacology.