Radix Astragali and Salvia miltiorrhiza Bunge: Therapeutic Insights and Future Research Directions in Acute Kidney Injury

TO THE EDITOR We read with great interest the article by He et al. (2025), titled “The Renoprotective Effects of Radix Astragali and Salvia miltiorrhiza Bunge on Short-Term Outcomes of Acute Kidney Injury: A Retrospective Study”. This study represents a meaningful contribution to the growing body of research investigating the role of traditional Chinese medicine (TCM) in the management of acute kidney injury (AKI), providing valuable clinical insights. AKI is a prevalent and serious condition associated with significant morbidity and mortality. Current therapeutic approaches are inadequate, possibly due to an incomplete understanding of its complex pathophysiology [Figure 1]. Therefore, identifying novel therapeutic targets and effective treatment strategies has become a key objective in nephrology research. In this context, TCM offers a potentially valuable therapeutic paradigm, characterized by its multi-component, multi-target, and system-level approach guided by holistic diagnostic principles. Recent studies have increasingly focused on the renoprotective effects of specific herbal agents, with proposed mechanisms such as anti-inflammatory and antioxidant activities,[1,2] regulation of immune responses, and improvement of microcirculation [Figure 2].[3,4] Notwithstanding these contributions, we would like to offer some considerations that may help guide future research.Figure 1.: Molecular underpinnings of AKI pathogenesis. Schematic overview summarizing the molecular and cellular events driving AKI initiation and progression. AKI, acute kidney injury; ER, endoplasmic reticulum.Figure 2.: Substances of phytochemicals of traditional Chinese medicine in treatment of AKI. Natural compounds in TCM may improve AKI through antioxidant, anti-inflammatory, reduced ferroptosis and anti-apoptosis effects. TCM, traditional Chinese medicine; AKI, acute kidney injury. AKT, Protein kinase B; AMPK, AMP-activated protein kinase; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; GPX4, Glutathione peroxidase 4; HO-1, Heme oxygenase-1; mTOR, Mechanistic target of rapamycin; MyD88, Myeloid differentiation primary response 88; NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, NLR family pyrin domain containing 3; NQO1, NAD(P)H quinone oxidoreductase 1; Nrf2, Nuclear factor erythroid 2-related factor 2; PI3K, Phosphoinositide 3-kinase; ROS, Reactive oxygen species; SIRT1, Sirtuin 1; TCM, Traditional Chinese Medicine; TLR4, Toll-like receptor 4.First, the use of a real-world retrospective cohort design provides clinically relevant insights into the therapeutic potential of Radix Astragali (RA) and Salvia miltiorrhiza Bunge (SM). The authors’ statistical adjustment for key confounders, such as baseline renal function and comorbidities, is commendable. However, several important covariates remain unaddressed. For instance, psychological stressors such as anxiety and depression have been linked to AKI prognosis through neuroendocrine and behavioral mechanisms, potentially influencing inflammatory processes, treatment adherence, and clinical outcomes.[5] In addition, dietary factors, particularly sodium and protein intake, play a critical role in renal hemodynamics, glomerular filtration, and tubular injury.[6-8] Excessive sodium intake may exacerbate fluid overload and glomerular hypertension, while inappropriate protein intake—whether excessive or deficient—can either increase renal overload or impair tissue repair, respectively. Future studies would benefit from including standardized dietary and psychological assessments. Moreover, advanced analytical approaches, such as propensity score matching, could further strengthen causal inference and reduce residual confounding. Second, the underlying mechanisms contributing to the synergistic renoprotective effects of RA and SM warrant further investigation. Both herbs have shown promise in modulating oxidative stress, inflammation, fibrosis, and endothelial dysfunction, but their combined pharmacodynamic interactions remain poorly understood. Future research should explore whether co-administration affects pharmacokinetics, including absorption, bioavailability, and tissue distribution, or whether their effects converge on common molecular targets, such as TGF-β/Smad, PI3K/AKT, or Nrf2/HO-1 pathways. Moreover, optimization of dosage ratios and formulation strategies may enhance clinical efficacy. The safety profile of this herbal combination also requires careful evaluation, particularly with respect to herb–drug interactions, hepatotoxicity, and immunogenicity. Well-designed randomized controlled trials (RCTs) and rigorous toxicological studies will be critical to translating these findings into clinical practice. Third, the study opens avenues for integrative therapeutic strategies combining herbal medicine with conventional AKI treatments. Future investigations could examine whether RA and SM potentiate the effects of diuretics, reduce the incidence of dialysis initiation, or mitigate ischemia–reperfusion injury in perioperative or intensive care unit (ICU) settings. Furthermore, mechanistic studies using animal models, organoid systems, and omics-based approaches (e.g., transcriptomics or metabolomics) may uncover new therapeutic targets and clarify the temporal dynamics of herbal intervention in AKI progression. Finally, from a public health standpoint, the clinical application of RA and SM may hold particular promise in resource-limited settings. If standardized and validated across multicenter and multiethnic populations, these herbal therapies could serve as cost-effective adjuncts or alternatives to conventional treatments, potentially improving access to care and patient outcomes among underserved populations.[9] However, widespread implementation will require not only efficacy data but also rigorous quality control of herbal preparations, consensus on diagnostic and staging criteria for AKI, and culturally sensitive patient education programs. In summary, this study contributes meaningfully to the expanding field of nephroprotective herbal medicine. It highlights the therapeutic potential of Radix Astragali and Salvia miltiorrhiza Bunge in AKI management while also underscoring the need for further mechanistic, prospective, and translational research. We commend the authors for their important contribution and hope these comments inspire further refinement and expansion of this promising line of inquiry. Financial support and sponsorship This work was supported by the National Natural Science Foundation of China (82374271), Guangdong Basic and Applied Basic Research Foundation (2023A1515012539), and the Fifth Batch of National Training Programs for Clinical Excellence in Traditional Chinese Medicine (National TCM Human Education Letter [2022] No. 1). Author contributions Wang R, Xie JR: Conceptualization, Writing—Original draft preparation, Writing—Reviewing and editing. Wang M: Conceptualization, Supervision, Project administration. All authors reviewed and approved the final manuscript. Ethics approval and consent to participate Not applicable. Conflict of Interest The authors declare no competing interests related to the present study. Use of large language models, AI and machine learning tools None declared. Data Availability Statement No additional data.