In recent years, phytoestrogens, which are natural analogues of estrogen, have garnered extensive attention. These metabolites, extracted from plants, exhibit estrogen-like effects due to their structural similarity to endogenous steroid estrogens, enabling them to bind to estrogen receptors (Hsieh et al., 2018; Lóránd et al., 2010). Phytoestrogens exhibit bidirectional regulatory characteristics, can function as either estrogen agonists or antagonists, with their specific action depending on concentration and bioavailability (Rettberg et al., 2014). They can bind to estrogen receptors and exert weak estrogenic effects to compensate for the deficiency of estrogen. Alternatively, they can competitively bind to estrogen receptors with endogenous estrogen, exerting anti-estrogenic effects that inhibit the side effects of estrogen (Shelly et al., 2008). Phytoestrogens can influence the structural and functional integrity of various systems, presenting both positive and negative effects (Rietjens et al., 2017; Sirotkin and Harrath, 2014). Their beneficial effects include potential protective roles in the cardiovascular, skeletal, nervous, reproductive, and digestive systems, as well as in skin and breast health. They also show some effectiveness in pain relief (Ceccarelli et al., 2022). However, like estrogen, they may also increase the potential cancer risk in estrogen-sensitive tissues (Domínguez-López et al., 2020). Notably, phytoestrogens possess endocrine-disrupting properties, which may interfere with the hypothalamic-pituitary-thyroid axis and affect thyroid function, including the synthesis and secretion of thyroid hormones (Domínguez-López et al., 2020). However, concerns about adverse reactions mainly stem from data derived from in vitro, animal, or epidemiological studies, whereas clinical investigations generally report no significant adverse events (Rietjens et al., 2017). Nonetheless, when applying these findings, we focus on reviewing the known thyroid impacts and reproductive effects.

Although the chemical structure of phytoestrogens differs from that of endogenous estrogens, they can still bind to endogenous estrogen receptors and activate the associated signaling pathways to exert their various biological effects (Wang et al., 2008). ERs are classified into two intracellular subtypes: ERα and ERβ (Hilakivi-Clarke and de Assis, 2006). These receptors function similarly to nuclear transcription factors, regulating gene expression to elicit biological responses. Different phytoestrogens exhibit varying affinities for ERα and ERβ. For instance, isoflavones show approximately five times higher affinity for ERβ than for ERα (Vitale et al., 2013). Recent studies have also investigated artificially synthesized phytoestrogens, such as 4-(E)-{(4-hydroxyphenylimino)-methylbenzene,1,2-diol} (HPIMBD). HPIMBD enhances selectivity by using the stereochemical structure of its ortho-dihydroxy groups to precisely complement the ERβ binding cavity. This promotes the formation of additional hydrogen bonds, reduces binding energy, and selectively activates ERβ signaling. Unlike the first-generation phytoestrogen resveratrol, which forms only three hydrogen bonds and fails to bind effectively through its 3,5-hydroxy groups, HPIMBD offers greater stability and overcomes these limitations (Ronghe et al., 2014).

In addition to the genomic effects mediated by the intracellular α and β subtypes of estrogen receptors (ER), estradiol can also trigger rapid non-genomic signaling through the G protein-coupled estrogen receptor (GPER) (Levin, 2015; Prossnitz et al., 2008). Initially classified as an orphan receptor (Owman et al., 1996), GPER has been studied using computational simulations and molecular docking to analyze phytoestrogen binding modes. These studies show that phytoestrogens bind to GPER similarly to E2 (Ariyani et al., 2020; Luo and Liu, 2020). Typical phytoestrogens like resveratrol and quercetin have been confirmed to have high affinity for GPER, suggesting they may mediate rapid signaling through this receptor (Dong et al., 2013; Maggiolini et al., 2004).

Flavonoids are natural small-molecule products consisting of two benzene rings (A and B) connected by a heterocyclic pyranone (C). They are present in a wide variety of plants (Sun et al., 2022). Flavonoid PE, one of the most common and extensively studied phytoestrogens, mainly comprises flavones and isoflavones, and serves as significant raw materials in the fields of nutrition, medicine, and cosmetics. Research demonstrates that baicalin can exert a renal protective effect through multiple mechanisms. With respect to apoptosis, baicalin can inhibit this process and mitigate kidney damage by down-regulating the expression of the pro-apoptotic protein BCL2-associated X protein (BAX) and up-regulating the expression of the anti-apoptotic protein b-cell cell lymphoma 2(BCL2) (Zhu et al., 2016). In terms of inhibiting inflammatory responses, baicalin can also enhance the expression of microRNA-223-3p (miR-223-3p) and suppress the activation of the thioredoxin-interacting protein (TXNIP)/nucleotide-binding domain, leucine-rich repeat containing pyrin domain containing 3(NLRP3) inflammatory signaling pathway, thus diminishing inflammatory reactions (Sun et al., 2020a). Moreover, baicalin can inhibit the EMT of podocytes by repressing the Notch1-Snail axis, markedly reducing adriamycin-induced glomerular damage in mice and lowering proteinuria levels (Dou et al., 2020). Additionally, studies have revealed that baicalin can inhibit the expression of inflammatory and fibrotic genes induced by TGF-β, while concurrently boosting fatty acid oxidation (FAO) levels by activating carnitine palmitoyl transferase 1A (CPT1A), thereby enhancing kidney energy metabolism and effectively alleviating renal fibrosis (Hu et al., 2024; Miguel et al., 2023). Diabetic nephropathy (DN) is one of the primary microvascular complications of diabetes and has emerged as the leading cause of CKD in China. Oxidative stress and inflammation are crucial factors in the onset and progression of DN. Research indicates that baicalin can significantly lower blood glucose levels in db/db mice and decrease urinary albumin excretion. This effect may be associated with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway and the inhibition of the mitogen-activated protein kinase (MAPK)-mediated inflammatory signaling pathway (Ma et al., 2021).

Puerarin is a hydroxyisoflavone with the molecular formula C21H20O9. This metabolite is found in various plants and botanical drugs, including Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (Fabaceae). It has been extensively studied for its estrogenic effects. Research indicates that puerarin exhibits significant kidney-protective properties. A study conducted by Wang et al., in 2021 demonstrated that in a renal fibrosis model induced by UUO, puerarin effectively inhibits the expression of inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), reduces ECM deposition, alleviates inflammatory and fibrotic reactions, and ultimately improves renal function by regulating the NF-κB p65/STAT3 and TGF-β1/Smads signaling pathways (Wang et al., 2021). Furthermore, in experiments involving intraperitoneal injection of puerarin (50 or 100 mg/kg) prior to renal ischemia-reperfusion in rats, it was observed that puerarin pretreatment reduced the expression of the renal fibrosis marker α-smooth muscle actin (α-SMA) in a dose-dependent manner. When HK-2 cells were subjected to hypoxia/reoxygenation, the expression of α-SMA significantly increased. Similarly, puerarin pretreatment (1 µM or 10 µM) also attenuated this increase in a dose-dependent manner. These findings indicate that puerarin possesses the ability to alleviate renal fibrosis in both in vivo and in vitro models. Puerarin has demonstrated significant antioxidant capacity in animal experiments (Jian et al., 2023). It upregulates the levels of antioxidant enzymes such as superoxide dismutase (SOD), glutathione, and catalase, while simultaneously reducing the levels of malondialdehyde. This action effectively mitigates oxidative stress-induced damage to the kidneys. Dyslipidemia is a common complication of chronic kidney disease and is closely associated with the deterioration of renal function. In animal model experiments, puerarin has been shown to regulate blood lipid levels, significantly reducing triglycerides, total cholesterol, and low-density lipoprotein cholesterol, thereby delaying the progression of chronic kidney disease (Xu et al., 2025). Podocyte injury is a primary pathological process in diabetic nephropathy. Studies indicate that puerarin may inhibit podocyte pyroptosis, reduce podocyte injury, and alleviate renal inflammatory damage by regulating the silent mating type information regulation 2 homolog 1 (SIRT1)/nucleotide-binding domain, leucine-rich repeat containing pyrin domain 3 (NLRP3)/cysteine-aspartic acid protease 1 (Caspase-1) pathway (Wang et al., 2025).

Coumarin metabolites, characterized by their aromatic odors, are a class of natural products widely distributed throughout the plant kingdom, found in families including Umbelliferae, Rutaceae, Asteraceae, Leguminosae, and Orchidaceae (Lončar et al., 2020; Tang et al., 2024). In recent years, traditional Chinese medicines and proprietary Chinese medicines containing coumarin metabolites have been increasingly utilized in clinical treatments. Coumarin PE, an aromatic chemical with a benzopyranone structure, has angelicin and psoralen as typical representatives of this metabolite class. Despite their structural similarities, their mechanisms of action differ significantly. Angelicin has been shown to activate the NF-κB pathway, which contributes to its anti-inflammatory effects in various diseases (Mahendra et al., 2020). The NF-κB pathway is also crucial in the context of chronic kidney diseases, positioning angelicin as a potential phytoestrogen in TCM. However, research on its effects on kidney diseases remains limited, necessitating future investigations to enhance our understanding of its role in kidney health. In contrast, psoralen exerts anti-inflammatory effects by inhibiting the production of nitric oxide (NO) (Y. J. Kim et al., 2016).

In traditional medicine, psoralen has been widely used for treating a range of conditions, including inflammatory and fibrosis-related diseases (Ren et al., 2020). The inflammatory response is a critical pathological mechanism in the progression of chronic kidney disease, which can activate the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3(NLRP3) inflammasome, leading to renal tissue damage and fibrosis. Research findings indicate that psoralen can not only reduce the activation of the NLRP3 inflammasome in UUO mice and decrease the expression of downstream cytokines, but it can also inhibit the TGF-β1/Smad pathway. This inhibition subsequently leads to a reduction in the expression level of the fibrotic marker α-smooth muscle actin (α-SMA) and alleviates renal fibrosis induced by UUO (Lee et al., 2023). Psoralen is the primary metabolite of the seed extract from Cullen corylifolium (L.) Medik. (formerly Psoralea corylifolia L.). After administering psoralen extract (500 mg/kg/day) orally for 8 weeks to streptozotocin -induced diabetic mice, notable decreases were observed in creatinine clearance, urine volume, urinary microalbumin, and mesangial expansion, alongside a significant reduction in renal tissue fibrosis in diabetic mice. In vitro experiments demonstrated that both the psoraleae corylifoliae semen (PCS) extract and its main metabolite, psoralen, significantly enhanced the viability of high-glucose-treated glomerular mesangial cells and reduced the expression of apoptosis-related proteins and fibrosis-related genes [such as TGF-β1, FN, and plasminogen activator inhibitor-1(PAI-1)]. Moreover, the expression of anti-apoptotic proteins (including Bcl-2 and phosphorylated Bad) was also increased (Seo et al., 2017). These studies suggest that, following appropriate clinical trials, this traditional Chinese botanical drug phytoestrogen has the potential for widespread application in the treatment of chronic kidney disease.

Cnidium monnieri (L.) Cusson (Apiaceae), known in Chinese as She Chuang Zi, is an important botanical drug that has been used in China for centuries to treat chronic kidney disease, female genital issues, male impotence, and frigidity (Sun et al., 2020b). Its biological activity is mainly attributed to osthole, a coumarin-based TCM metabolite. Researchers established a type 2 diabetes rat model induced by streptozotocin combined with a high-fat and high-sugar diet, using metformin as a positive control, to explore the therapeutic effects of osthole on diabetic nephropathy. After 8 weeks of intervention treatment, the study found that Cnidium monnieri can reduce the increase of ROS in high glucose-induced glomerular mesangial cells and downregulate the expression of the TGF-β1/Smads signaling pathway and related proteins, thus exerting a preventive and therapeutic effect on diabetic nephropathy (Li et al., 2024c). In research on a mouse renal fibrosis model, osthole demonstrated significant anti-fibrosis effects through multiple mechanisms. On one hand, it effectively inhibits the renal fibrosis process by blocking the TGF-β/Smad signaling pathway; on the other hand, osthole can also directly act on the interleukin-11 (IL-11)/extracellular signal–regulated kinase 1/2 (ERK1/2) signaling pathway to inhibit the translation of fibrotic proteins, thereby improving renal fibrosis (Wu et al., 2021). In vitro experiments have further confirmed the effects of osthole on rat renal interstitial fibroblasts normal rat kidney fibroblast cell line (NRK-49F). Osthole can inhibit the activation of NRK-49F cells and significantly reduce the expression of α-SMA, FN, and collagen I, thereby decreasing the production of extracellular matrix. Additionally, osthole can inhibit the proliferation of NRK-49F cells, contributing to the improvement of renal fibrosis from multiple aspects (Zhang et al., 2018). Research has identified that a significant characteristic of diabetic nephropathy is the massive accumulation of advanced glycation end products (AGEs) in renal tissue. AGEs bind to receptors receptor for advanced glycation end products (RAGEs), activating multiple intracellular signaling pathways that trigger oxidative stress responses, leading to tubular interstitial hypertrophy and fibrosis. Furthermore, studies have shown that osthole can inhibit the activation of the AGE/RAGE-induced janus kinase 2 (JAK2)- signal transducer and activator of transcription 1/3(STAT1/3) signaling pathway by inducing the expression of Klotho protein, reducing the expression of p21Waf1/Cip1, collagen IV, and RAGE protein, effectively inhibiting AGE-induced tubular hypertrophy and protecting the kidneys (Kan et al., 2019). The expression level of Klotho is closely related to the progression of CKD (Liu J. et al., 2024). Osthole may treat chronic kidney disease by regulating Klotho expression, although its mechanism of action requires further investigation.

Lignan phytoestrogens are widely present in various diets, including cereal bran, beans, flaxseed, sesame, and unrefined grains (Rizzolo-Brime et al., 2022). Schisandrin A (SchA) and Schisandrin B(SchB), both essential active metabolites of S. chinensis (Turcz.) Baill. (Schisandraceae), belong to lignan metabolites. Data indicate that Schisandra chinensis is considered a natural dietary supplement for protecting kidney function. In an experimental model of cisplatin-induced acute kidney injury in mice, the Schisandra chinensis stem extract (SCE), primarily composed of lignan metabolites, demonstrated significant multi-target renal protection. Firstly, SCE effectively improved renal function indicators by significantly reducing serum creatinine and blood urea nitrogen levels. Regarding apoptotic regulation, SCE significantly inhibited the expression of the pro-apoptotic protein Bax while simultaneously upregulating the expression of the anti-apoptotic protein Bcl-2, thereby bidirectionally regulating the expression of apoptotic-related proteins and effectively reducing the apoptosis of renal tubular epithelial cells. In terms of antioxidant and anti-inflammatory effects, SCE reduced the generation of lipid peroxidation products (such as Malondialdehyde) and increased the content of antioxidants (such as Glutathione) to alleviate oxidative damage to renal cells. Additionally, it inhibited the expression of inflammatory mediators’ inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the activation of the NF-κB signaling pathway, thereby reducing kidney damage caused by inflammatory reactions (Li et al., 2018). Molecular docking and cellular thermal shift analysis show that SchA directly binds to the PKCβ protein and inhibits its activity. This inhibition subsequently reduces the levels of fibrotic markers, such as FN, collagen I, vimentin, and α-smooth muscle actin. Additionally, SchA inhibits the proliferation and differentiation of fibroblasts, thereby mitigating the progression of renal fibrosis (Liu H. L. et al., 2024). SchB has also been shown to ameliorate renal damage induced by mercury and arsenic (Chiu et al., 2008; Stacchiotti et al., 2011). The lignan active metabolites, SchA and SchB, found in S. chinensis, exhibit significant protective potential against CKD through the synergistic action of multiple targets and pathways.

Stilbene, a polyphenolic organic metabolite of plant origin with the chemical formula C₁₄H₁₂ (Dubrovina and Kiselev, 2017), has a carbon skeleton of 1,2-diphenylethylene (C6–C2–C6), formed by connecting two benzene rings via an ethylene bridge. Grapes, peanuts, berries, and certain botanical drugs are the main sources of stilbene (Al-Khayri et al., 2023). Among stilbene metabolites, resveratrol has been the subject of extensive research, particularly for its anti-inflammatory properties. Yu Qinzhou (Zhou et al., 2024) and colleagues found that resveratrol can improve glomerular atrophy and tubular structure, reduce renal fibrosis and inflammation, and ultimately alleviate hyperuricemia and associated renal injury. This is achieved by inhibiting liver xanthine oxidase activity and decreasing the expression of renal inflammatory factors such as IL-6 and TNF-α. Resveratrol is abundant in Reynoutria japonica Houtt. (Polygonaceae), a commonly used nephrology medication for treating acute and chronic renal failure. Meta-analyses have provided definitive evidence of resveratrol’s renal protective effect in adults (Abdollahi et al., 2023). The protective mechanism primarily involves activating the SIRT1 (silent information regulator 1) pathway, enhancing mitochondrial function, and reducing ROS production (Guarente, 2011; Kitada et al., 2013). Additionally, it effectively inhibits the mechanistic target of rapamycin (mTOR) pathway associated with renal injury in mammals (Inoki et al., 2011; Liu et al., 2010; Sakaguchi et al., 2006). In addition, resveratrol can protect renal mitochondria from glucose-induced oxidative stress damage by maintaining mitochondrial complex III activity (Xu et al., 2012), inhibiting c-Jun N-terminal kinase (JNK) and NF-κB activation (Zhang et al., 2012), and down-regulating plasminogen activator inhibitor-1 expression (Xu et al., 2014). Although cell and animal experiments have shown that resveratrol has various potential benefits, its effects in humans need further research verification, and it should be used with caution in practical applications.

End-stage renal disease represents a more advanced and challenging stage of chronic kidney disease. The primary pathological features include progressive glomerular sclerosis and renal interstitial fibrosis (Xie et al., 2023). The main active metabolite in R. multiflora (Thunb.) Moldenke (Polygonaceae), 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), exhibits significant renal protective effects. In the study investigating the mechanism of glomerular sclerosis improvement, mice were continuously treated with oral gavage of TSG at doses of 2.5 and 10 mg/kg for 24 days, while a single intravenous dose of adriamycin (AD, 10 mg/kg) was administered on the third day. The experimental results indicate that TSG can maintain the expression level of podocin, a podocyte marker, mitigate AD-induced podocyte damage, and ultimately reduce the occurrence of proteinuria and the formation of glomerular sclerosis. In terms of renal fibrosis improvement, TSG significantly diminishes oxidative stress levels by activating the nuclear factor erythroid 2-related factor 2- Kelch-like ECH-associated protein 1(Nrf2-Keap1) antioxidant pathway. This mechanism of action results in decreased mRNA and protein expression levels of fibrosis markers in the kidneys, thereby effectively alleviating the renal fibrosis process induced by AD and providing renal protection in the AD-induced Focal segmental glomerulosclerosis mouse model (Lin et al., 2018). In many regions, diabetes is the leading cause of ESRD (Reutens and Atkins, 2011). Between 25% and 50% of diabetic patients may develop CKD, commonly referred to as DN (Li et al., 2016; Plantinga et al., 2010). In Streptozotocin induced diabetic models, TSG can inhibit the expression of downstream profibrotic and proinflammatory factors (such as TGF-β, CTGF, MCP-1, etc.) by blocking the activation of the RAS and reducing the accumulation of angiotensin II. Furthermore, TSG can restore the expression of key structural proteins of the glomerular filtration barrier, thereby reducing proteinuria and tubulointerstitial fibrosis (Chen G. T. et al., 2016). As a botanical drug with various clinical pharmacological benefits, Reynoutria multiflora holds potential for preventing the progression of CKD and has significant clinical application value.

Terpenoids are a class of organic metabolites that are widely present in nature. They are composed of isoprene units and exhibit diverse biological activities (Chen et al., 2011). Among the extensive family of terpenoids, certain members with specific structures have been identified to possess estrogenic activity and regulate estrogen receptors (Hsu et al., 2011). Panax ginseng C.A. Mey. (Araliaceae), a staple in Eastern medicine, is notable for its high content of triterpene saponins and other active metabolites, which confer pharmacological effects such as enhanced immunity and prevention of chronic diseases (Osbourn et al., 2011; Ratan et al., 2021). Given the substantial evidence supporting its efficacy, P. ginseng and its extracts have transitioned from traditional Eastern remedies to natural medicines that are increasingly acknowledged within the Western medical system (Li Z. et al., 2023).

The primary active metabolites in P. ginseng, including ginsenoside Re, Rg1, Rg3, Rh1, and Rb1, all belong to the triterpenoid class and exhibit estrogen-like activity (Li et al., 2024a). In the context of treating kidney diseases, G-Rh1 has been shown to significantly reduce the expression of Bax and cleaved caspase 3 and caspase 9 in the renal tissue of DN mice. Concurrently, it upregulates the expression of Bcl-2 and Bcl-XL, indicating its anti-apoptotic effects. Histological analysis via H&E staining revealed a reduction in pathological damage to the renal tissue of DN mice, including thickening of the glomerular basement membrane and glomerular atrophy. These findings collectively suggest the protective effect of G-Rh1 on the kidneys (Su et al., 2021). Furthermore, in terms of antioxidant and anti-inflammatory effects, ginsenosides can significantly enhance the expression levels of antioxidant enzymes by activating the Nrf2/ARE signaling pathway, thereby effectively mitigating oxidative damage. They also alleviate renal inflammatory responses by inhibiting the activation of the NF-κB signaling pathway and reducing the expression of inflammatory factors. More importantly, ginsenosides can also regulate the TGF-β1/Smad signaling pathway, inhibit excessive deposition of extracellular matrix, and block the progression of renal fibrosis. Thus, they play a protective role in glomerular filtration function and tubular reabsorption function (Fan et al., 2023). Vascular calcification (VC), a strong prognostic marker for cardiovascular disease mortality, is commonly observed in CKD. Studies have shown that CKD patients are prone to VC even in the early stages, with a prevalence of 25% in stage 3 and 35% in stage 4. Once CKD patients begin dialysis, the prevalence of VC rises rapidly, exceeding 50% (Russo et al., 2004; Sigrist et al., 2007). G-Rb1 can not only alleviate the progression of early CKD by regulating oxidative stress and inflammation (Xu et al., 2017), but it can also improve CKD-related VC by activating peroxisome proliferator-activated receptor-γ (PPAR-γ) to inhibit the Wnt/β-catenin pathway (Zhou et al., 2019). These comprehensive effects demonstrate that ginseng exhibits significant protective effects in various kidney disease models.

Dioscin, a natural steroidal saponin metabolite primarily found in Dioscorea panthaica Prain & Burkill (Dioscoreaceae), belongs to a class of phytoestrogens that perform various functions, including endocrine regulation and anti-inflammatory effects (Tang et al., 2015; Yang et al., 2019). Recent research has demonstrated that dioscin possesses significant antioxidant activity and lipid-lowering effects (Mao et al., 2023). In the context of CKD, although research is relatively limited, experimental evidence suggests that dioscin can function as a phytoestrogen and exert renal protective effects through multiple mechanisms. Notably, dioscin reduces the expression level of microRNA-145-5p (miR-145-5p), thereby inhibiting miR-145-5p-mediated oxidative damage. Concurrently, it decreases the levels of the oxidative stress product malondialdehyde (MDA) while increasing the levels of glutathione (reduced form) (GSH) and glutathione peroxidase (GSH-Px), which collectively improve methionine-induced liver and kidney injury (Li et al., 2021a). Furthermore, it has been reported that dioscin can inhibit renal cell apoptosis by enhancing the quality and quantity of mitochondria, thus reducing renal injury in diabetic nephropathy models (Zhong et al., 2022). In chronic kidney disease, both apoptosis and necrosis of renal cells are critical factors contributing to the decline of renal function. Animal studies further confirm that dioscin treatment can significantly enhance renal function indicators, such as blood creatinine and urea nitrogen levels (Wang et al., 2024). Proteinuria is a significant marker of chronic kidney disease, and its production is closely associated with damage to the glomerular filtration barrier. Massive proteinuria can further impair glomerular filtration function, creating a vicious cycle between the two (Makhammajanov et al., 2024). Podocytes, which are highly differentiated epithelial cells, surround the glomerular capillaries. Alterations in their foot process structure, such as fusion or disappearance, are critical factors leading to proteinuria. Therefore, safeguarding podocyte function is crucial for preventing and mitigating proteinuria (Nagata, 2016). Dioscin has been shown to protect podocytes from damage and reduce proteinuria by regulating SIRT6 and diminishing lipid accumulation (Wang et al., 2022). These findings provide a scientific basis for considering dioscin as a potential therapeutic agent for chronic kidney disease (Figure 1).