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31 December 2025

Scutellaria baicalensis Georgi: A Promising Source of Bioactive Molecules for Kidney Disease Therapy

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Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China
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School of Medical Care, Sichuan Vocational and Technical College, No. 1 Xuefu North Road, Suining 629000, China
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School of Chemistry and Chemical Engineering, Xianyang Normal University, Xianyang 712000, China
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Authors to whom correspondence should be addressed.
Biomolecules2026, 16(1), 64;https://doi.org/10.3390/biom16010064 
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This article belongs to the Section Natural and Bio-derived Molecules
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Abstract

The incidence of kidney diseases has been increasing due to changes in modern lifestyles and the ecological environment. The progression of kidney disease is characterized by ongoing renal damage and a gradual decline in renal function, ultimately leading to end-stage renal disease. The limitations of present medications have brought many disadvantages to patients. Consequently, identifying bioactive molecules has emerged as a critical strategy in the development of novel therapies for kidney diseases, particularly those derived from natural medicinal resources. This review presents a comprehensive analysis of renoprotective effects and underlying mechanisms of the medicinal plant Scutellaria baicalensis Georgi based on evidence retrieved from multiple databases, including Web of Science, PubMed, and CNKI. Flavonoids from S. baicalensis have been demonstrated to have good renoprotective properties by mitigating inflammation and oxidative stress, inhibiting cell apoptosis, reducing renal fibrosis, etc. Baicalein, wogonin, baicalin, and wogonoside are considered as the main bioactive components of the renoprotective effect of S. baicalensis. Further research on candidate molecules derived from S. baicalensis represents a promising strategy for the development of novel therapeutic agents targeting kidney diseases.

1. Introduction

Kidney disease has emerged as a significant global public health challenge, clinically classified into two primary categories: acute kidney injury (AKI) and chronic kidney disease (CKD). According to the World Health Organization’s report, AKI exhibits an annual incidence exceeding 2000 cases per million population, with severe instances demonstrating mortality rates ranging from 50% to 80% [1]. Concurrently, CKD is characterized by a progressive decline in renal function and affects an estimated 850 million individuals worldwide, representing approximately 11% of the global population [2]. The epidemiological burden of renal pathologies is on the rise due to demographic aging, increasing prevalence of metabolic disorders—including diabetes mellitus and obesity—and escalating comorbidities associated with cardiovascular diseases. These converging health challenges highlight the urgency for enhanced preventive strategies and optimized disease management protocols.
The current clinical management of renal diseases primarily relies on pharmacotherapy, nutritional support therapy (e.g., low-protein diets and restricting salt, potassium, and phosphorus intake), renal replacement therapy, adjunctive treatment with traditional Chinese medicine, and lifestyle interventions [3,4,5,6,7]. Among these modalities, pharmacotherapy remains the cornerstone of treatment, which includes the use of renin–angiotensin–aldosterone system inhibitors to control hypertension and proteinuria, immunosuppressants for autoimmune nephropathies, and glucocorticoids to modulate immune responses. While these approaches demonstrate partial efficacy in slowing disease progression, they are accompanied by significant limitations and adverse effects. Firstly, a lack of specific targeted therapies results in supportive treatments being the primary strategy. Secondly, most interventions focus predominantly on delaying disease progression rather than reversing it. Thirdly, many treatments are associated with adverse reactions, such as hyperkalemia induced by renin–angiotensin system inhibitors, opportunistic infections related to immunosuppression, metabolic disorders, and hepatotoxicity and nephrotoxicity [8,9,10,11,12,13]. Consequently, there is an urgent need to develop novel renoprotective agents that integrate multi-pathway synergistic regulation while ensuring safety.
Long-term clinical practice and experimental studies have confirmed that bioactive molecules derived from medicinal plants, as well as their synthetic or semi-synthetic derivatives, serve as essential lead compounds in the design of target-specific therapeutics. Notable examples include the natural anticancer agents paclitaxel (from Taxus species), vincristine and vinblastine (from Catharanthus roseus), and camptothecin (from Camptotheca acuminata Decne) together with its semi-synthetic derivative irinotecan; the marine-derived antineoplastic trabectedin (from Ecteinascidia turbinata); and the antimalarial artemisinin (from Artemisia annua) [14,15,16,17,18]. These precedents underscore that medicinal plants constitute a critical reservoir for the development of therapeutics targeting kidney disorders. Radix scutellariaem, the dried root of the perennial herb Scutellaria baicalensis Georgi, is commonly used in traditional Chinese medicine in clinical practice and was first systematically documented in the “Shennong Bencao Jing”, where it is noted for its effects in “clearing heat and dampness, purging fire, and detoxifying” [19,20]. Numerous pharmacological studies have gradually elucidated that the renoprotective effects of S. baicalensis are closely associated with its abundant natural flavonoids, particularly baicalein, baicalin, wogonin, and wogonoside. These natural flavonoids possess unique chemical structures characterized by ortho-phenolic hydroxyl groups and C-ring unsaturated ketones, which can contribute to antioxidant properties and facilitate electron transfer capabilities. Consequently, they play a crucial role in regulating redox balance, inflammatory responses, and cell apoptosis [21,22,23,24]. This provides a scientific foundation for developing therapeutic strategies targeting kidney diseases based on the active components derived from S. baicalensis.
For this review, we systematically searched Web of Science, PubMed, and CNKI. After full-text screening, studies were excluded if they (i) lacked topical relevance, (ii) were outdated or redundant, or (iii) had flawed designs or incomplete datasets. We critically assessed the renoprotective potential of S. baicalensis, focusing on the bioactive constituents baicalein, wogonin, and baicalin, and elucidated their pharmacological mechanisms in renal protection, including antioxidant effects, anti-inflammatory pathways, apoptosis regulation, and fibrosis mitigation. The synthesized evidence provides mechanistic insights into S. baicalensis-mediated interventions for kidney disease while highlighting their therapeutic prospects. This work establishes a foundation for advancing translational research on therapeutics derived from S. baicalensis and supports the development of standardized phytopharmaceuticals for renal pathologies.

2. Main Components of S. baicalensis for Renoprotective Effects

The kidney is an essential organ responsible for excreting waste in urine, playing a pivotal role in maintaining homeostasis and eliminating metabolic waste through the coordinated processes of glomerular filtration, tubular reabsorption, and endocrine secretion [25]. Kidney disease can be classified into two distinct forms, namely AKI and CKD, and each of them involves complex pathophysiological mechanisms (Figure 1). AKI is a clinical syndrome characterized by a rapid decline in renal function, which can be categorized into three types based on the different sites of etiological action: pre-renal, intrinsic renal, and post-renal [26,27,28]. Pre-renal AKI primarily results from renal hypoperfusion, commonly triggered by conditions such as hypovolemia (e.g., traumatic hemorrhage, surgical blood loss, severe diarrhea, or burns), reduced cardiac output (e.g., hemorrhagic shock), renal vasoconstriction, or mechanical obstruction of the renal artery [29,30,31]. Intrinsic renal AKI involves direct parenchymal damage frequently induced by nephrotoxic agents (e.g., contrast media or aminoglycosides), heavy metal exposure, or structural lesions affecting glomeruli or tubulointerstitial tissues [32,33]. Post-renal AKI typically arises from urinary tract obstruction with common causes including urolithiasis, neoplastic masses, and benign prostatic hyperplasia [34].
Figure 1. The forms and progression of kidney disease. As the primary organs responsible for urine production, the kidneys play a critical role in filtering blood to eliminate metabolic waste products and excess fluid, thus maintaining systemic fluid homeostasis and electrolyte balance. Renal injury can compromise kidney function and ultimately lead to the development of kidney disease. In clinical practice, kidney disease is broadly categorized into AKI and CKD. A variety of etiological factors can precipitate AKI, which, if unresolved or recurrent, may progress to CKD over time.
In contrast, the pathogenesis of CKD is predominantly associated with persistent metabolic dysregulation and systemic disorders. Major contributors to CKD include diabetic nephropathy, hypertensive nephropathy, autoimmune-mediated nephropathies (such as lupus nephritis), hyperuricemia (HUA), and drug-induced nephrotoxicity [35,36]. Furthermore, genetic anomalies such as polycystic kidney disease and Alport syndrome represent significant etiological factors in the development of CKD [37,38].
Epidemiological evidence illustrates a bidirectional interconversion between AKI and CKD. Prolonged AKI lasting beyond three months often progresses into CKD through maladaptive repair mechanisms. Conversely, patients with pre-existing CKD are susceptible to rapid deterioration of renal function due to acute triggers such as infection or hemorrhage, which can manifest as superimposed AKI—thereby accelerating progression to end-stage renal disease (ESRD) [39,40,41,42]. This reciprocal relationship establishes both conditions as critical determinants in the progression toward ESRD. Given the multidimensional pathological network characteristics inherent to kidney diseases, natural drugs exhibiting multi-target intervention features present unique advantages.
Renal diseases are orchestrated by a multidimensional pathological network that has traditionally been managed clinically with empirical combinations of renin–angiotensin–aldosterone system inhibitors, immunosuppressants, and corticosteroids to slow progression, while pre-clinical research has largely pursued “multi-target” interventions. These unspecific strategies often disrupt physiological homeostasis and exhibit poorly predictable dose–response relationships. Consequently, therapeutic development is transitioning toward precision paradigms that integrate (i) molecular-targeted modulation of critical signaling nodes, (ii) cell-type-restricted interventions, and (iii) spatiotemporal adjustment of targets according to disease stage. The emerging “component–target” specificity framework provides a new roadmap for complex disorders, coupling target deconvolution technologies, ligand optimization, targeted delivery systems, and individualized regimens to convert conventional multi-target approaches into precise, target-directed control. Medicinal plants, with their extensive chemodiversity, constitute an invaluable repository for identifying nephro-specific targets and are poised to accelerate the clinical translation of this precision strategy, offering patients more effective and safer therapeutic options.
S. baicalensis, a natural medicinal plant, contains various kinds of bioactive components, including flavonoids, volatile oils, polysaccharides, alkaloids, terpenoids, and trace elements [43]. Numerous studies have demonstrated that flavonoids serve as the primary constituents of S. baicalensis to exert multiple pharmacological effects including renoprotection. A total of 125 flavonoids have been isolated from S. baicalensis, comprising 68 free flavonoid aglycones and 57 flavonoid glycosides [44,45,46,47,48]. The flavonoids present in S. baicalensis are responsible for the renoprotective activities, especially baicalein, wogonin, baicalin, and wogonoside. The fundamental characteristics of the four bioactive molecules are presented in Table 1.
Table 1. Main bioactive flavonoids in S. baicalensis that exert renoprotective effects.
For these flavonoids, aglycones such as baicalein and wogonin exhibit favorable lipophilicity, whereas their corresponding glycosides baicalin and wogonoside exhibit a certain degree of water solubility. Given that baicalein, wogonin, baicalin, and wogonoside all contain phenolic hydroxyl groups, they display weak acidic properties. As thus, for the extraction of these flavonoids from S. baicalensis, ethanol solutions of appropriate concentration can be employed, or alternatively, the alkali dissolution–acid precipitation method may be utilized. Yan et al. employed ultrasonic-assisted extraction to prepare flavonoids from the stems and leaves of S. baicalensis, finding that the total flavonoid content could reach 24.43 mg·g−1 under the optimized conditions: 55% ethanol concentration, a solid-to-liquid ratio of 1:50, an extraction duration of 60 min, and a temperature of 50 °C [49]. Jiang et al. investigated the application of the alkali dissolution–acid precipitation technique and demonstrated that both baicalin and baicalein can be effectively extracted from S. baicalensis. Subsequent acid hydrolysis enabled further purification, yielding baicalein with a purity of 99.35% [50].
Notably, the low solubility of flavonoids from S. baicalensis may result in suboptimal bioavailability. To address this issue, a solvent-evaporation method was employed to prepare a baicalein solid dispersion, achieving a 35.1-fold enhancement in apparent solubility compared to the raw drug, with excellent physicochemical stability maintained over 80 days [51]. In parallel, baicalein-β-cyclodextrin-grafted-chitosan nanoparticles with a narrow size distribution (mean diameter ≈ 424.5 nm) were prepared [52]. MIC determination against Staphylococcus aureus showed a 50% reduction in the minimum inhibitory concentration (12.5 µg·mL−1 versus 25 µg·mL−1 for free baicalein), and colony-count assays corroborated the superior bactericidal efficacy of the nanoparticulate formulation. Nanotechnology-based platforms have enabled the development of a series of baicalin nanoformulations, including nanoparticles, nanoliposomes, and nanoemulsions, which not only enhance the aqueous solubility of baicalin but confer size-dependent targeting capabilities [53,54,55]. In one study, a novel crystalline solid lipid nanoparticle system loaded with baicalin was prepared via coacervation using stearic acid alkaline salt as the lipid matrix [56]. These solid lipid nanoparticles significantly improved the oral bioavailability of baicalin, with the area under the concentration–time curve and maximum plasma concentration being 2.58-fold and 1.61-fold higher, respectively, than those of the free drug. This provides a novel strategy for addressing the poor aqueous solubility and low oral bioavailability of flavonoids.

3. Effects and Mechanisms of S. baicalensis Against AKI

AKI is a multifactorial clinical syndrome characterized by complex pathological mechanisms that are intricately associated with the activation of inflammatory cascades, imbalances in oxidative stress, and various forms of cell death, including necrosis, apoptosis, autophagic cell death, and ferroptosis [57]. These pathological alterations ultimately lead to renal damage and an irreversible decline in renal function [34,58]. Recent studies have demonstrated that baicalin, baicalein, and wogonin intervene in the AKI process through a multi-target mechanism (Figure 2).
Figure 2. Mechanism of action of S. baicalensis against AKI. Baicalin, baicalein, and wogonin have been identified to inhibit AKI through multiple molecular pathways. Baicalin attenuates AKI by modulating oxidative stress via the miR-223-3p-TXNIP/NLRP3 pathway, suppressing TLR-induced inflammation, and activating the Nrf2/ARE, PI3K/Akt, and JAK2/STAT3 signaling cascades. Baicalein ameliorates AKI predominantly by inhibiting MAPK and NF-κB signaling, enhancing the Nrf2/HO-1-mediated antioxidant response, reducing reactive oxygen species (ROS) production, and modulating apoptosis via the Bcl-2/Bax and SIRT1 pathways. Wogonin exerts protective effects against AKI via dual-level regulation of the NF-κB and RIPK1 signaling axes.
Studies have elucidated that the renoprotective effects of baicalin are primarily manifested in the following pathways: (1) Antioxidant effects. Baicalin activates the Nrf2/HO-1 pathway and enhances the expression of miR-223-3p, which inhibits the TXNIP/NLRP3 pathway, resulting in reduced production of malondialdehyde (MDA) and myeloperoxidase while simultaneously increasing the activity of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione [59,60,61,62,63]. (2) Anti-inflammatory effects. Baicalin exerts anti-inflammatory effects via several pathways, including TLR2/4, Nrf2/ARE, PI3K/Akt, and JAK2/STAT3, by effectively reducing levels of inflammatory factors such as IL-1β and TNF-α while inhibiting NF-κB activation [64,65,66,67,68,69]. (3) Anti-apoptotic effects. Baicalin can regulate Klotho protein levels along with members of the caspase family (e.g., caspase-3 and caspase-11), thereby maintaining balance between Bcl-2/Bax proteins [64,70,71,72,73,74]. Additionally, baicalin intervenes in both the Ros/NLRP3/Caspase-1/Gsdmd and NLRP3/caspase-1 pathways [75], achieving dual inhibition of apoptosis and pyroptosis.
Researchers have also found that another flavonoid baicalein exhibits renoprotective effects in AKI through three mechanisms. Firstly, it alleviates inflammatory responses by inhibiting the production of pro-inflammatory mediators such as TNF-α and IL-1β; this process is regulated via the dual suppression of MAPK phosphorylation cascades and NF-κB nuclear translocation, alongside modulation of the Nrf2/HO-1 pathway [76,77,78,79,80]. Secondly, it mitigates oxidative stress damage by enhancing endogenous antioxidant defense systems, effectively decreasing ROS and reducing the generation of oxidative biomarkers such as advanced oxidative protein products and MDA [76,80,81]. Thirdly, baicalein modulates apoptotic pathways through coordinated regulation of the Bcl-2/Bax protein balance and SIRT1-mediated deacetylation of p53 [78,82]. Interestingly, emerging evidence reveals the anti-ferroptotic activity of baicalein by modulating arachidonate 12-lipoxygenase [83]. In contrast to baicalein’s multimodal mechanisms, wogonin mainly targets programmed necrosis through dual-level regulation of the NF-κB and RIPK1 signaling axis [84,85,86]. This mechanism involves concurrent transcriptional control and post-translational modifications to suppress inflammatory necrosis in renal cells. The differential targets exhibit preference between these two flavonoids. Baicalein mainly improves AKI via apoptosis/ferroptosis regulation, while wogonin treats AKI via necrotic pathways; this demonstrates their complementary therapeutic potential in managing AKI.

4. Effects and Mechanism of S. baicalensis Against CKD

4.1. Diabetic Kidney Disease (DKD)

DKD is a leading cause of ESRD, and its pathology is intricately linked to structural and functional damage to the renal microvasculature resulting from disorders in glucose metabolism [87]. For patients with DKD, clear pathological changes can be observed in their kidneys, including thickening of the glomerular basement membrane, proliferation of the extracellular matrix (ECM), and impairment of microvascular function [88,89]. Recent studies have demonstrated that S. baicalensis extracts and their bioactive components such as baicalin and wogonin can mitigate the progression of DKD through a multi-target regulatory mechanism (Table 2).
Table 2. Bioactive components of S. baicalensis and their mechanisms of action against DKD.
Baicalin has been demonstrated to possess significant anti-inflammatory and antioxidant effects through targeting multiple pathways. At the molecular level, baicalin activates the Nrf2 signaling pathway, specifically involving Keap1/Nrf2/ARE regulation, to promote the expression of antioxidant enzymes. Concurrently, baicalin inhibits pro-inflammatory signaling pathways such as MAPK and SphK1/S1P/NF-κB to mitigate inflammatory responses [90,91]. Additionally, baicalin can suppress miR-141 expression to activate the Sirt1/Nrf2 signaling axis, thereby establishing a multi-pathway synergistic network [92]. As a result, the levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, as well as oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, can be significantly altered by baicalin. Additionally, baicalin can upregulate gene expression of CAT and Mn-SOD, along with promoting forkhead box O3a protein expression, which effectively ameliorates oxidative stress in damaged renal tissues [93]. Moreover, baicalin employs a dual inhibition strategy to intervene in the pathological processes associated with DKD. Baicalin can also decrease PKC activity alongside the expression of phosphorylated connexin 43, and reduce ECM production, TGF-β1 expression, and the production of advanced glycation end products and VEGF [94,95,96,97]. This multi-pathway coordination can effectively reverse DKD-related pathological damage via both metabolic modulation and vascular repair. Furthermore, baicalin can improve lipid metabolism disorders associated with DKD by specifically targeting FK506-binding protein 51 [98].
The molecular regulatory mechanisms of baicalein and wogonin in DKD has been further elucidated by some experimental studies. Baicalein was demonstrated to inhibit the activity of 12/15-lipoxygenase (12/15-LO) and AMPKα, thereby modulating glucose metabolism by suppressing anabolic processes while promoting catabolic pathways [99,100]. Additionally, it attenuates the hs-CRP/FC-γR signaling axis and significantly reduces the overexpression of inducible iNOS and TGF-β1 mediated by NF-κB, thus alleviating renal inflammatory responses [99,101]. Wogonin can synergistically regulate various signaling pathways including TLR/NF-κB, PI3K/Akt/NF-κB, and KLF4/NF-κB [102,103,104], which are critical for modulating inflammatory responses. It also inhibits the macrophage signaling cascade DKDM3OS/KLF4 while balancing Bcl-2-mediated apoptosis and autophagy [105,106,107], effectively safeguarding podocyte structure and function. Notably, wogonin’s inhibitory effects on the TLR4-JAK/STAT/AIM2 signaling axis and MRP8 expression present new therapeutic targets for mitigating pathological damage in DKD [106]. As another active component in S. baicalensis, wogonoside targets both the NF-κB p65-MMP28 and HNF4A-NRF2 signaling axes, and this dual action exerts good inhibitory effects on inflammatory responses as well as oxidative stress during the pathological progression of DKD [106,108].

4.2. Hyperuricemia

HUA is a metabolic disorder primarily characterized by dysfunction in purine metabolism, leading to an imbalance between the overproduction of uric acid and its impaired excretion [109]. Notably, approximately 90% of clinical cases are attributed to compromised uric acid excretion function [110]. In this pathological state, supersaturated serum uric acid can crystallize into sodium urate crystals, which precipitate and deposit in the kidneys, thereby inducing severe renal inflammation [111,112].
Baicalin exhibits a multi-target anti-HUA mechanism. Firstly, baicalin regulates the Panx-1/P2X7 purinergic signaling pathway and the NLRP3 inflammasome-mediated classical pyroptosis pathway to effectively inhibit signal transduction in renal tubular epithelial cells activated by sodium urate crystals and thereby reduce the level of pyroptosis in kidney cells [113]. Secondly, baicalin competitively binds to the active site of xanthine oxidase to obstruct substrate binding of hypoxanthine/xanthine and significantly inhibit uric acid biosynthesis [114]. Thirdly, by downregulating the secretion of lactate dehydrogenase, nitric oxide, and pro-inflammatory factors such as TNF-α and IL-1β, baicalin synergistically modulates oxidative stress (resulting in reduced ROS levels) and apoptosis pathways, thus alleviating damage to renal tubular epithelial cells induced by sodium urate crystals [114]. Furthermore, baicalin can regulate the PI3K/Akt/NF-κB signaling axis to achieve an integrated effect that combines xanthine oxidase inhibition with inflammation relief and apoptosis blockade through cross-regulation of the TLR/NLRP3/NF-κB and MAPK pathways [115,116].
Baicalein was demonstrated to have a renoprotective effect through a dual mechanism. Firstly, it directly inhibits the activity of xanthine oxidoreductase, thereby reducing uric acid production. Secondly, it was found to enhance the excretion of uric acid in a hyperuricemic model mice [117,118]. This combined action ultimately alters serum uric acid levels and improves renal function.

4.3. Renal Fibrosis (RF)

RF represents the primary pathological feature of CKD as it progresses to its end stage. This condition is characterized by the loss of functional nephrons, abnormal proliferation of fibroblasts, and excessive deposition of ECM. These changes lead to glomerulosclerosis, tubular atrophy, and interstitial fibrosis, ultimately culminating in irreversible renal failure [119,120,121]. Recent pharmacological studies have demonstrated that the active components derived from S. baicalensis exhibit significant advantages in multi-target therapy for combating organ fibrosis. The methanol extract of S. baicalensis has been shown to exert anti-fibrotic effects by modulating TGF-β1-mediated activation of renal fibroblasts and intervening in oxidative stress pathways [122]. Furthermore, the total aglycone extract can downregulate the expression of ECM-related genes, thereby preventing the progression of renal interstitial fibrosis [123].
In-depth mechanistic studies have elucidated that flavonoids such as baicalein, baicalin, and wogonin can modulate the progression of RF through synergistic effects across multiple pathways (Figure 3). Specifically, baicalein exhibits a good inhibitory effect on RF. Baicalein was demonstrated to inhibit fibroblast proliferation and ECM deposition via several signaling axes, including TGF-β/Smad, PI3K/Akt, and MAPK [124,125,126]. Furthermore, it counteracts renal ferroptosis by upregulating the expression of ferroptosis-related proteins such as SLC7A11, GPX4, and FTH [127]. Additionally, baicalein can enhance the survival of renal tubular epithelial cells while mitigating interstitial fibrosis by regulating the balance of endoplasmic reticulum stress-related factors including caspase-3/9 and Bax/Bcl-2 [128].
Figure 3. Mechanism of action of S. baicalensis against RF. Baicalein, baicalin, and wogonin were found to modulate the progression of RF through synergistic effects across multiple pathways. Baicalein can inhibit fibroblast proliferation and ECM deposition via TGF-β/Smad, PI3K/Akt, and MAPK. Baicalin suppresses RF by regulating TGF-β-mediated Smad and Notch1, microRNA-124/TLR4/NF-κB and Galectin-3/Akt/GSK-3β/Snail signaling pathways. Wogonin and its glycoside derivatives exhibit a potent inhibitory effect on RF via the inhibition of the TGF-β-associated p38MAPK and Smad branches as well as the NF-κB axes.
According to some studies, another flavonoid, namely baicalin, also has obvious therapeutic effects on RF. Baicalin has been found to suppress RF at the molecular level by targeting multiple key nodes of the TGF-β signaling pathway. It downregulates Smad3 and upregulates Smad7 expression through modulation of the TGF-β/Smad signaling axis [129,130,131]. Additionally, baicalin indirectly regulates TGF-β1 levels via the Notch1 signaling pathway or by reducing plasma Angiotensin II content [132,133]. Moreover, baicalin inhibits renal tubular epithelial cell trans-differentiation and ECM deposition [124], thereby delaying the progression of renal tubular fibrosis through regulation of the microRNA-124/TLR4/NF-κB signaling pathway and enhancement of CPT1α-mediated fatty acid oxidation [134,135,136]. For glomerular fibrosis, baicalin reduces α-smooth muscle actin (α-SMA) levels by inhibiting TGF-β1 expression while also decreasing advanced glycation end products and connective tissue growth factor expression. This action contributes to improvements in diabetic nephropathy-related glomerular lesions [95,96,137,138]. Furthermore, baicalin demonstrates multi-target characteristics in overall kidney protection by regulating the Galectin-3/Akt/GSK-3β/Snail signaling pathway [139]; reversing inhibitory effect of DNA hypermethylation on the Klotho gene [140]; and significantly alleviating glomerular, tubular, and interstitial fibrosis in CKD model rats. The mechanism for improving mitochondrial function involves enhancing CPT1α-mediated fatty acid oxidation [135]. Additionally, it was found to attenuate renal interstitial fibrosis by inhibiting NF-κB nuclear translocation as well as STAT3 phosphorylation processes [141].
In addition, wogonin and its glycoside derivatives exhibit a potent inhibitory effect on RF through a multi-target synergistic mechanism. The primary mechanisms involve the modulation of inflammation-related signaling pathways and the regulation of pro-fibrogenic factors. Research has demonstrated that these compounds significantly inhibit the TGF-β1 signaling pathway, including both the p38MAPK and Smad3 branches as well as the NF-κB signaling pathway and the TLR4/MAPK axis, thereby establishing a coordinated regulatory network across multiple inflammatory pathways [138,142,143,144]. At the molecular level, they effectively downregulate the expression of fibrogenic markers such as fibronectin, α-SMA, collagen I, E-cadherin, and TGF-β1 while concurrently modulating oxidative stress-related enzymes such as CAT and SOD to mitigate oxidative damage [145]. Furthermore, these components inhibit the release of pro-inflammatory cytokines including TNF-α and IL-1β and alleviate endoplasmic reticulum stress, thereby delaying apoptosis in renal tubular epithelial cells [145]. This multifaceted mechanism not only reduces inflammatory infiltration but inhibits abnormal ECM deposition. In all, these regulatory effects can contribute to ameliorating glomerulosclerosis and renal tubulointerstitial fibrosis and ultimately preserve renal parenchymal structure.

4.4. Renal Cell Carcinoma

Renal cell carcinoma (RCC), a malignant neoplasm originating from the renal tubular epithelium, accounts for approximately 90% of all renal malignancies and is recognized as one of the most aggressive tumor types within the urinary system. Contemporary pharmacological research has demonstrated that substances from S. baicalensis exhibit significant anti-tumor activity. Ethanol extract of S. baicalensis demonstrated tumor proliferation by inducing G2/M phase arrest in the human renal cancer cell line Caki-1. Network pharmacology analyses indicate that the core components in S. baicalensis exert anti-RCC effects through multiple signaling pathways, including PI3K-Akt, Ras, MAPK, p53, VEGF, and JAK-STAT [146]. Some investigations have elucidated that flavonoids repress RCC in various ways, specifically wogonin. Wogonin was demonstrated to inhibit tumor growth by interfering with cell cycle progression, inducing DNA damage stress responses, and activating apoptosis pathways [147]. Additionally, wogonin selectively induces programmed cell death in RCC cells by targeting the CDK4-RB signaling pathway [148]. These findings provide compelling experimental evidence supporting the potential application of S. baicalensis and its active components in the treatment of renal cancer.

5. Conclusions and Future Perspectives

S. baicalensis, a natural medicinal plant with abundant therapeutic properties, has a variety of bioactive compounds, such as flavonoids, terpenoids, and polysaccharides. Notably, flavonoids such as baicalein and wogonin, along with their glycosides, have been demonstrated to exert significant renoprotective effects. For AKI, S. baicalensis exerts robust renoprotective actions through multi-target synergistic mechanisms that include the inhibition of MAPKs/NF-κB inflammatory signaling pathways, activation of the antioxidant defense system, regulation of the Bcl-2/Bax-SIRT1/p53 apoptosis pathway, and suppression of ferroptosis mediated by 12-lipoxygenase. Among these mechanisms, the modulation of ferroptosis represents a novel therapeutic avenue for AKI treatment. In CKD, the active components derived from S. baicalensis can enhance renal function by delaying the progression of fibrosis through the inhibition of the TGF-β/Smad signaling pathway and cell injury induced by oxidative stress. Nevertheless, current evidence primarily originates from animal studies; therefore, further clinical validation is essential to confirm their translational potential for therapeutic applications.
Despite these promising findings, several significant challenges persist within the current research landscape.
First, current studies predominantly concentrate on flavonoids as the bioactive ingredients from S. baicalensis for the treatment of kidney disease, with insufficient exploration of other structurally diverse components such as terpenoids and polysaccharides. Second, there is a substantial body of research focusing on the inhibitory effects on renal tubular injury, but there is a lack of investigations concerning glomerular injury. Thirdly, the intricate regulatory network underlying the synergistic nephroprotective effects of multiple components necessitate further elucidation through systems biology approaches. Fourth, the strategy for clinical evaluation of the active components of S. baicalensis has yet to be established.
To address these challenges, future research is necessary to systematically explore the renoprotective effects and underlying mechanisms. Firstly, the renoprotective effects of other types of compounds in S. baicalensis, such as terpenoids and polysaccharides, should be further explored. Secondly, the integration of multi-omics technologies, including spatial transcriptomics and protein–protein interaction network analysis, can be employed to facilitate a comprehensive mechanistic understanding of the “component–target–pathway” regulatory network. Thirdly, advanced models such as organoids and organ-on-a-chip platforms should be used to enhance the translational value in new drug development. Furthermore, special attention should be directed towards creating novel nano-drug delivery systems to increase the therapeutic effects of molecules from S. baicalensis to overcome its bioavailability limitations through formulation innovations. These systematic and multidisciplinary approaches will effectively promote the application of S. baicalensis in treating kidney disease.

Author Contributions

Conceptualization, H.C., Y.F. and K.J.; methodology, H.C., X.Y., F.D. and L.H.; formal analysis, H.C., X.Y. and F.D.; data curation, Y.X., J.C., Y.C. and R.W.; resources, H.C. and X.Y.; writing—original draft preparation, X.Y. and F.D.; writing—review and editing, H.C., Y.F. and K.J.; supervision, H.C. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by National Natural Science Foundation of China (No. 82460731, 82003836), Key R&D Plan Project of Ningxia (No. 2024BEG01006, 2021BEB04080), and Research Project of Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Ningxia Medical University (No. KFKT202313).

Institutional Review Board Statement

Not applicable.

Data Availability Statement

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.

Acknowledgments

During the preparation of this manuscript, the authors used ERNIE-4.5 and DeepSeek-R1 (Open AI) in the writing process to improve readability. The authors have reviewed and edited the output and take full responsibility for the content of this publication.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

The following abbreviations are used in this manuscript:
AKIAcute kidney injury
ALOX12Arachidonate 12-lipoxygenase
CATCatalase
CKDChronic kidney disease
DKDDiabetic kidney disease
DMDiabetes mellitus
ECMExtracellular matrix
ESRDEnd-stage renal disease
HUAHyperuricemia
12/15-LO12/15-Lipoxygenase
MDAMalondialdehyde
RCCRenal cell carcinoma
RFRenal fibrosis
S. baicalensisScutellaria baicalensis
SODSuperoxide dismutase
VEGFVascular endothelial growth factor
α-SMAα-Smooth muscle actin

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