Research Article

A Conceptual Hypothesis on the Traditional East Asian Medicine Pathogenesis of Steroid-Induced Sarcopenia:
A Zang–Fu and Pat-tern Identification 

Jeongheun Han¹, Sanghyun Ahn², Nayoung Jo¹ ,*

Abstract

Background/Objectives: Steroid-induced sarcopenia exhibits complex pathophysiological mechanisms involving muscle protein metabolism and sys-temic metabolic disturbances; however, a pathological model grounded in traditional East Asian medicine (TEAM) has not been explored. The objective of this study is to preliminarily propose a TEAM pattern identification model for steroid-induced sarcopenia based on Zang–Fu theory.

Methods: Through a narrative literature review, we searched biomedical and TEAM databases (PubMed, CNKI, KISS, and OASIS) for studies on the pathophysiology and clinical management of steroid-induced sarcopenia, TEAM-based sarcopenia mechanisms, and preclinical/network pharmacology studies of herbal medicine. Combined with manual reference screening, 16 studies were qualitatively synthesized.

Results: From a biomedical perspective, steroid-induced sarcopenia is characterized by glucocorticoid receptor–mediated inhibition of IGF-1/Akt/mTOR signaling, activation of FOXO-dependent atrogenes, increased myostatin expression, enhanced autophagy, mitochondrial dysfunction, and systemic insulin resistance.

Integrative analysis based on TEAM theory suggests a stage-wise pathological progression. Initial glucocorticoid exposure is conceptualized as excessive heat stimulation associated with spleen Qi deficiency and dampness–heat accumulation in the spleen and stomach, followed by progression to liver–kidney Yin deficiency with depletion of liver blood and kidney essence.

Preclinical and network pharmacology studies indicate that herbal medicines associated with these patterns modulate key sig-naling pathways—including PI3K/Akt/mTOR, FOXO, AMPK, NF-κB, and SIRT1/PGC-1α—in aging- and dexame-thasone-induced muscle atrophy models.

Conclusions: This study proposes a Traditional East Asian Medicine–based pathophysiological hypothesis that interprets steroid-induced sarcopenia as a progressive pattern involving spleen–stomach deficiency, dampness–heat accumulation, and liver–kidney Yin deficiency. Although not a definitive explanatory model, this preliminary conceptual framework provides a basis for future pattern-oriented preclinical and clinical research on steroid-induced sarcopenia.

Keywords

Steroid-induced sarcopenia, Glucocorticoids, Traditional East Asian Medicine, Zang–Fu organ theory, Pattern differentiation, Liver–kidney Yin deficiency

Introduction

Glucocorticoids are widely used across diverse clinical domains, including auto-immune diseases, inflammatory conditions, malignancies, and immunosuppressive therapy following organ transplantation [1]. However, prolonged glucocorticoid use is associated with adverse effects such as osteoporosis, metabolic abnormalities, and skeletal muscle atrophy with reduced muscle strength, collectively referred to as steroid-induced sarcopenia [2–4]. Steroid-induced sarcopenia is regarded as a form of secondary sarcopenia and is associated with increased risks of falls and fractures, higher rates of hospitalization, and reduced quality of life [5].

The condition arises from the complex interplay of multiple mechanisms, including suppressed muscle protein synthesis, enhanced protein degradation, endocrine dysregulation, insulin resistance, and mitochondrial dysfunction [6–9]. Glucocor-ticoid receptor–mediated disturbances in muscle protein metabolism are closely linked to systemic metabolic abnormalities involving adipose tissue and hepatic metabolism [1–3,6–10]. Despite this multifactorial nature, standardized preventive and therapeutic strategies remain limited, and current clinical management relies mainly on dose adjustment, exercise therapy, and nutritional support [5].

In contrast, studies that directly examine the etiology and pathogenesis of ster-oid-induced sarcopenia from a Traditional East Asian Medicine (TEAM) perspective remain scarce. Classical TEAM literature has primarily discussed muscle atrophy and weakness under the category of Wei syndrome (痿證), conceptualizing them not as isolated muscular disorders but as manifestations of systemic imbalance. [11]. Few studies have systematically treated glucocorticoid-induced sarcopenia as an independent pathological entity within a TEAM framework, particularly regarding its metabolic characteristics.

Nevertheless, TEAM’s holistic understanding of disease—based on dynamic in-teractions among organ systems and the balance of Qi, Blood, Yin, and Yang—offers a potentially useful framework for interpreting this systemic disorder [12]. Moreover, accumulated TEAM pattern differentiation studies on age-related sarcopenia can serve as indirect reference material. Accordingly, this study sum-marizes the pathophysiology of steroid-induced sarcopenia through a litera-ture-based narrative review and interprets these findings within the framework of TEAM organ-based pattern differentiation theory. Given the paucity of direct TEAM research, this study proposes a tentative TEAM pattern progression hypothesis for steroid-induced sarcopenia based on prior studies of age-related sarcopenia and traditional TEAM interpretations of steroid-related pathology.

Materials & Methods

This study was conducted as a narrative literature review to examine the patho-physiology of steroid-induced sarcopenia and to explore its interpretation from the perspective of TEAM. The aim of this review was not to perform a systematic review or meta-analysis, but rather to provide a conceptual and pathophysiological inte-gration of existing evidence relevant to the research topic, rather than a compre-hensive quantitative synthesis of the literature.

Literature searches were performed using PubMed, CNKI (China National Knowledge Infrastructure), KISS (Korean Studies Information Service System) and OASIS (Oriental Medicine Advanced Searching Integrated System). The search terms included combinations of “sarcopenia,” “muscle atrophy,” “glucocorticoid,” “steroid,” and “dexamethasone,” using AND/OR Boolean operators. In addition to database searches, manual searches including reference list screening were con-ducted to identify relevant studies. The inclusion criteria encompassed: (1) studies addressing the muscular patho-physiology of steroid-induced sarcopenia and its associated systemic metabolic and endocrine alterations; (2) studies reporting the current clinical management of ster-oid-induced sarcopenia; (3) studies proposing pathogenic mechanisms or disease progression of sarcopenia from the perspective of TEAM; and (4) preclinical and network pharmacology studies investigating the mechanisms of action of herbal medicines or medicinal herbs in sarcopenia. Case reports, editorials, and grey liter-ature with low levels of evidence were excluded.

The selected studies were assessed through full-text review, focusing on their conceptual and pathophysiological relevance to the research objectives. Ultimately, 16 studies most relevant to the review objectives—particularly the biomedical pathophysiology of steroid-induced sarcopenia and its TEAM-based conceptual interpretation—were qualitatively synthesized (Fig. 1, Table 1). Because this was a narrative review, study selection prioritized conceptual and pathophysiological relevance rather than exhaustive quantitative synthesis.

Figure 1. Flow diagram of literature selection process for the narrative review

Table 1.

Results

Pathophysiological mechanisms of steroid-induced sarcopenia

Steroid-induced sarcopenia has been reported to result from glucocorticoid receptor (GR)–mediated signaling that suppresses muscle protein synthesis while promoting protein degradation [6,8,10]. Activation of GR inhibits the insulin-like growth factor 1/protein kinase B/mammalian target of rapamycin (IGF-1/Akt/mTOR) signaling pathway, thereby impairing translational initiation and ribosomal biogenesis. Con-currently, GR activation facilitates the nuclear translocation of Forkhead box O (FOXO) transcription factors, leading to increased expression of E3 ubiquitin ligases such as Atrogin-1 and muscle RING finger-1 (MuRF1), which activate protein degradation through the ubiquitin–proteasome system [6,10].

In particular, GR and FOXO1 have been shown to bind synergistically to the glucocorticoid response element (GRE) and FOXO binding element (FBE) within the MuRF1 promoter, thereby markedly enhancing MuRF1 transcription. Accordingly, the GR–FOXO1–MuRF1 axis has been proposed as a central molecular pathway underlying glucocorticoid-induced muscle atrophy [9].

Glucocorticoids have also been reported to promote muscle protein and organelle degradation by increasing myostatin expression, activating the autophagy–lysosome system, reducing mitochondrial membrane potential, and increasing oxidative stress [6,8]. These molecular alterations are closely associated with clinical myopathic features, including preferential atrophy of type II muscle fibers and proximal muscle weakness [8,10].

From an endocrine and metabolic perspective, GR activation has been shown to reduce the expression and phosphorylation of insulin receptor substrate (IRS) proteins in skeletal muscle and to impair intramuscular insulin signaling through modulation of regulators such as protein tyrosine phosphatase 1B (PTP1B) and p38 MAPK, thereby contributing to localized insulin resistance [7]. These alterations are not confined to skeletal muscle but are accompanied by increased lipolysis in adipose tissue, elevated circulating free fatty acids, adipokine imbalance, and enhanced hepatic gluconeogenesis, collectively aggravating systemic insulin resistance [7]. Consequently, glucose delivery to and utilization by skeletal muscle are reduced, leading to further disruption of intramuscular energy homeostasis and attenuation of insulin and IGF-1 signaling [7].

Collectively, abnormalities in muscle protein metabolism, endocrine dysregulation, increased insulin resistance, mitochondrial dysfunction, and overlapping systemic metabolic disturbances involving adipose tissue and the liver are considered to constitute the integrated pathophysiological basis of steroid-induced sarcopenia [1–3,6–10].

Current status of clinical management 

In current clinical practice, management of steroid-induced sarcopenia primarily focuses on minimizing glucocorticoid dosage and treatment duration whenever possible and avoiding risk factors such as high-dose or long-term administration, advanced age, pre-existing muscle disorders, and prolonged immobilization [8]. Compared with continuous daily administration, intermittent dosing at scheduled intervals has been reported to induce less muscle atrophy while being more favor-able for muscle regeneration; thus, adjustment of dosing frequency has been pro-posed as a potential risk-reduction strategy [13].

Exercise therapy is regarded as the non-pharmacological intervention with the most consistent evidence for steroid-induced muscle atrophy. Both aerobic and resistance exercise have been shown to partially restore muscle cross-sectional area and strength reduced by glucocorticoid treatment, increase phosphorylation of the mammalian target of rapamycin/p70 ribosomal protein S6 kinase (mTOR/p70S6K) pathway, and decrease expression of muscle RING finger-1 (MuRF1), thereby promoting favorable changes in muscle protein metabolism [14]. Consequently, regular exercise is widely recommended as a practical strategy to mitigate muscle loss in patients requiring long-term glucocorticoid therapy [8,14].

From a nutritional perspective, adequate protein intake and supplementation with branched-chain amino acids (BCAAs), particularly leucine and its metabolite β-hydroxy β-methylbutyrate (HMB have been suggested to attenuate steroid-induced muscle atrophy [15]. Preclinical studies have demonstrated that supplementation with BCAAs, leucine, or HMB can partially restore dexamethasone-induced reductions in muscle protein synthesis, muscle strength, and muscle mass, while suppressing protein degradation and autophagy-related activation, as reflected by reduced Atrogin-1 expression and decreased microtubule-associated protein 1 light chain 3-II (LC3-II) accumulation [15]. These findings support a potential role for nutritional supplementation as a conservative management strategy.

Pharmacological interventions remain largely investigational. Growth hormone, IGF-1, androgens (e.g., testosterone, DHEA), creatine supplementation, and myostatin inhibition have been explored as potential therapeutic options [8]. Other agents, including the farnesyltransferase inhibitor lonafarnib [16] and tauroursodeoxycholic acid (TUDCA) [17] have shown muscle-protective effects in dexamethasone-induced models by restoring mTOR signaling, modulating cellular stress responses, and suppressing E3 ubiquitin ligase expression. However, most approaches remain limited to preclinical or early-phase studies. To date, no pharmacological agent has been widely accepted as first-line therapy; therefore, optimization of glucocorticoid dosing combined with exercise and nutritional management remains the most feasible clinical strategy [8,13–17].

TEAM etiology and pathology of sarcopenia

Because direct TEAM studies on steroid-induced sarcopenia are scarce, this review incorporated manual reference screening and analyzed TEAM- and herb-al-medicine–related studies on age-related sarcopenia as complementary references [11–22]. Although age-related sarcopenia differs etiologically from steroid-induced sarcopenia, it has been more extensively examined in terms of pattern differentia-tion and herbal mechanisms; thus, these findings were used as indirect conceptual references.

Within TEAM, sarcopenia is generally discussed under the category of Wei syndrome (痿證). Patterns such as spleen–stomach deficiency, kidney Yang deficiency, kidney Yin deficiency, and liver–kidney deficiency have been closely associated with reductions in muscle mass and strength [11]. In particular, age-related decline in spleen–stomach transformative and transportive functions, progressive depletion of kidney essence, and deficiency of liver blood—leading to impaired nourishment of muscles and tendons—are regarded as key pathological features underlying sarcopenia. These patterns are often described as evolving over the disease course [11].

A systematic review of observational studies in older adults with sarcopenia reported recurrent identification of liver–kidney deficiency, spleen–stomach deficiency, and spleen–stomach dampness–heat, with relatively high pooled prevalences [18]. This review included TEAM-based observational studies involving adults aged 60 years or older and selected five studies using a mutually exclusive diagnostic approach for me-ta-analysis [18]. The pooled prevalence of liver–kidney deficiency was 39% (95% confidence interval [CI], 31–47%; four studies), spleen–stomach deficiency was 32% (95% CI, 27–37%; three studies), and spleen–stomach dampness–heat was 34% (95% CI, 29–39%; two studies) [18]. These distributions were reported to reflect diverse clinical manifestations of sarcopenia, including muscle weakness, weight loss, fatigue, digestive dysfunction, and sleep disturbances, and were interpreted as indicating distinct pathological characteristics among different patterns [18].

TEAM-based interventions, including herbal medicine, have been suggested to improve muscle strength and physical function in patients with sarcopenia [19]. Nevertheless, studies specifically addressing the etiology and pathology of steroid-induced sarcopenia from a TEAM perspective remain limited, underscoring the need for further investigation.

Preclinical and network pharmacology studies on TEAM-based treatments

The pathophysiological mechanisms of herbal medicines and medicinal herbs in sarcopenia have been primarily investigated through preclinical experiments and network pharmacology analyses, which have reported associations with the regula-tion of muscle protein metabolism, inflammation and oxidative stress, mitochondrial function, and energy metabolism [11,20–22].

Polysaccharides derived from Astragalus membranaceus have been reported to activate the PI3K/Akt/mTOR/p70S6K signaling pathway in dexamethasone- and hydrogen peroxide–induced C2C12 myotube atrophy models while suppressing FOXO3a and FOXO1 activity and reducing MuRF1 and atrogin-1 expression, thereby promoting protein synthesis and inhibiting protein degradation [22]. In addition, antioxidant and anti-apoptotic effects have been observed, including reduced reactive oxygen species (ROS) production, increased superoxide dismutase (SOD) and catalase (CAT) activity, regulation of the Bax/Bcl-2 ratio and caspase-3 activity, and preservation of mitochondrial membrane potential [22]. Astragaloside IV (ASIV), a major constituent of Astragalus membranaceus, has further been shown to suppress TGF-β1/Smad signaling in sepsis-induced C2C12 myotube atrophy, leading to decreased MuRF1 and atrogin-1 expression and attenuation of muscle atrophy progression [11].

In dexamethasone-induced animal models, Panax ginseng and mountain ginseng have been associated with improvements in muscle mass and fibrosis-related indices, alongside suppression of FOXO3a signaling and modulation of MuRF1 and atrogin-1 expression [11]. Long-term administration has also been associated with increased muscle mass and strength, as well as delayed transition from fast-twitch to slow-twitch fibers [11].

Codonopsis pilosula has been reported to activate mTORC1 signaling, reduce MuRF1 and atrogin-1 expression, and modulate mitochondrial functional indices associated with the SIRT1/PGC-1α pathway [11]. Network pharmacology analyses have identified Angelica sinensis, Rehmannia glutinosa, and Eucommia ulmoides as highly connected to targets related to PI3K/Akt, IGF-1, AMPK, and inflammatory mediators such as NF-κB, IL-6, and TNF-α [20]. Corresponding preclinical studies have reported antioxidant and anti-inflammatory effects, regulation of myocyte differentiation and satellite cell activity, and improvements in mitochondrial-related indices [11, 20–21].

Mechanistic studies have associated Lycium barbarum (Fructus Lycii) with activation of SIRT1 and modulation of the AMPK/SIRT1/PGC-1α axis [11]. Moreover, nanovesicles derived from Lycium barbarum have been shown to regulate muscle atrophy–related indices in dexamethasone-induced models through activation of the same pathway [11]. Schisandra chinensis has been reported to reduce caspase-3 and poly(ADP-ribose) polymerase (PARP) expression in dexamethasone-induced models, suggesting modulation of apoptosis-related signaling involved in cellular stress and muscle damage regulation [11].

Magnesium lithospermate B (MLB), a major component of Salvia miltiorrhiza, has demonstrated reductions in TNF-α, IL-6, and TNFRI levels and suppression of NF-κB activity in high-fat diet–fed mouse models [11]. In addition, tanshinone IIA has been reported to modulate excessive mitochondrial mitophagy and mitigate mitochondrial ROS accumulation under inflammatory conditions [11].

Berberine, a principal alkaloid of Coptis chinensis, has been shown to regulate mitochondrial-related factors—including PGC-1α, NRF1, TFAM, and SIRT1—in association with AMPK activation, indicating links to metabolic regulatory pathways [11]. Baicalin, a flavonoid from Scutellaria baicalensis, has been reported to attenuate muscle atrophy–related pathology by reducing ROS production, activating the Nrf2/HO-1 pathway, suppressing NF-κB and MAPK signaling, regulating PGC-1α–mediated mitochondrial biogenesis, activating Akt/mTOR signaling, and decreasing MuRF1 and atrogin-1 expression [21].

Other flavonoids—including quercetin, luteolin, catechin, hesperidin, and naringin—have shown comparable effects, such as ROS reduction, activation of the Nrf2/HO-1 pathway, suppression of NF-κB and MAPK signaling, regulation of mitochondrial biogenesis, and activation of Akt/mTOR signaling with concomitant reductions in MuRF1 and atrogin-1 expression [21]. In particular, naringin has been reported to activate the Sp1–ERRγ transcriptional axis, thereby increasing oxidative muscle fiber composition and enhancing aerobic metabolism [11].

Overall, these preclinical studies indicate that multiple herbal medicines can modulate key signaling pathways—including PI3K/Akt/mTOR, FOXO, AMPK, and NF-κB—in both aging-related and steroid-induced muscle atrophy models [11,20–22]. However, substantial heterogeneity exists across experimental models (e.g., dexamethasone-induced, aging-related, or disuse models), herbal medicines or active compounds, and treatment conditions. Moreover, studies directly targeting steroid-induced sarcopenia using glucocorticoids are often intermixed with those examining general sarcopenia models; therefore, careful distinction is required when interpreting the applicability of these findings to steroid-induced sarcopenia versus their relevance as general references for sarcopenia-related pathology [11,22].

Discussions

Steroid-induced sarcopenia is recognized as a complex pathological condition characterized by dysregulation of muscle protein metabolism, endocrine signaling, and systemic metabolic homeostasis, making it difficult to interpret or manage through a single mechanistic framework [1–3,6–10]. This condition is fundamentally characterized by simultaneous suppression of muscle protein synthesis and acceleration of protein degradation. At the molecular level, activation of GR suppresses IGF-1/Akt/mTOR signaling, while the GR–FOXO–MuRF1/Atrogin-1 axis is activated, leading to enhanced proteolysis. In parallel, myostatin expression is increased, autophagy is upregulated, and mitochondrial dysfunction ensues [6,8–10].

In addition to these muscle-specific mechanisms, glucocorticoids suppress IRS/PI3K–Akt insulin signaling in skeletal muscle, increase lipolysis and circulating free fatty acids in adipose tissue, and enhance hepatic gluconeogenesis, thereby inducing dyslipidemia and exacerbating systemic insulin resistance [1–3,7]. These processes contribute not only to muscle atrophy but also to the worsening of metabolic abnormalities such as hyperglycemia, dyslipidemia, weight gain, and hypertension. Consequently, steroid-induced sarcopenia represents a vicious cycle involving skeletal muscle, liver, and adipose tissue, and should therefore be understood as a systemic metabolic disorder rather than an isolated muscle disease [7].

In contrast, TEAM literature addressing the pathological interpretation of steroid-induced sarcopenia remains extremely limited. Accordingly, the present study sought to examine TEAM perspectives on muscle physiology, integrate pattern differentiation frameworks for age-related sarcopenia, and incorporate TEAM interpretations of steroid-related pathology to propose a preliminary stage-wise pathogenic hypothesis for steroid-induced sarcopenia.

In TEAM theory, skeletal muscle is interpreted in relation to the liver, spleen, and kidney Zang organs. According to classical texts such as the Huangdi Neijing, the liver stores blood and nourishes the muscles and tendons, enabling contraction and relaxation through the regulation of liver Qi and liver blood [28]. The spleen governs transformation and transportation of nutrients derived from food and distributes Qi and Blood to the muscles, limbs, and entire body [29]. The kidney stores essence, governs the bones, and is responsible for growth, development, regeneration, and repair [30].

These three Zang organs are interconnected according to Zang–Fu theory. After food intake, the spleen generates Qi, Blood, and body fluids from nutrients, which are stored in the liver; the liver disperses these substances to regulate systemic metabolism, while the kidney stores essence as the fundamental source of vitality [12]. Therefore, from a TEAM perspective, functional impairment or pathological changes in any one of these organs inevitably affect the others.

Pattern differentiation frameworks for age-related sarcopenia have been relatively well described in TEAM literature. Systematic reviews have classified age-related sarcopenia within the categories of Wei syndrome and Consumptive disease, with spleen–stomach deficiency, spleen–stomach dampness–heat, liver–kidney Yin deficiency, Qi–Blood deficiency, and combined Yin–Yang deficiency frequently reported as major patterns [11,18,23]. Kwon et al. further investigated the prevalence of pattern differentiation among patients diagnosed with age-related sarcopenia and reported liver–kidney deficiency, spleen–stomach deficiency, and spleen–stomach dampness–heat as the most prevalent patterns, demonstrating consistency between previously proposed theoretical patterns and clinical distribution [18].

Although no consensus has been established regarding TEAM interpretations of steroid medications, several scholars have proposed conceptual frameworks. Tian et al. interpreted steroid-induced pathology based on the theory of junior fire and sthenic fire, describing steroids as agents with a purely Yang nature. According to this theory, steroids initially act as junior fire, augmenting Yang Qi and suppressing inflammatory pathology; however, prolonged or high-dose exposure transforms this effect into sthenic fire, in which excessive heat consumes body fluids and essence [25]. Fan et al. similarly interpreted steroids as heat-natured agents that initially generate heat, subsequently progressing to dampness–heat and Yin deficiency, and ultimately leading to spleen deficiency with Qi stagnation and combined Yin–Yang deficiency [26].

Persistent heat stimulation is considered to impair the transformative and transportive functions of the spleen and stomach, preventing proper distribution of nutrients and leading to internal retention of dampness and turbidity, thereby forming a spleen–stomach dampness–heat pattern. As dampness–heat persists, spleen function further deteriorates, while heat continuously consumes body fluids, aggravating Yin deficiency. As a result, insufficient Qi and Blood are generated in the spleen and stomach, liver blood fails to adequately nourish the muscles, and kidney essence becomes progressively depleted, leading to a transition from spleen–stomach dampness–heat to liver–kidney Yin deficiency [25,27,30]. Applying this pathological sequence to steroid-induced sarcopenia, prolonged glucocorticoid exposure may be conceptualized as a form of excessive heat stimulation that is hypothesized to disturb the spleen, liver, and kidney concurrently, gradually consuming body fluids and weakening the generation of Qi and Blood [25]. From a biomedical perspective, glucocorticoid administration induces muscle protein degradation, suppresses protein synthesis, and initiates impairment of intramuscular insulin signaling [6–10]. With continued exposure, TEAM pathology progresses from spleen–stomach dampness–heat to exacerbated liver–kidney Yin deficiency, accompanied by depletion of essence. In this stage, the liver fails to nourish the muscles, and the kidney is unable to support regeneration of muscle and bone, resulting in declines in muscle strength, muscle mass, and bone mineral density [27,28,30]. Concurrently, increased insulin resistance in muscle and liver promotes fatty liver, dyslipidemia, and central obesity, pathological features that overlap with spleen–stomach dampness–heat [24], thereby further aggravating sarcopenia. Accordingly, steroid-induced sarcopenia may be interpreted as a systemic pathological condition characterized by spleen–stomach dampness–heat, impaired Qi and Blood generation, and progressive liver–kidney Yin deficiency induced by excessive heat stimulation.

Preclinical and network pharmacology studies provide partial conceptual correspondence between these TEAM interpretations and molecular mechanisms. In this review, herbal medicines associated with the spleen, liver, and kidney were examined, and several were found to exert biological effects in aging- and dexamethasone-induced sarcopenia models.

Herbal medicines that tonify the spleen and support Qi and Blood generation include Astragalus membranaceus, Panax ginseng, and Codonopsis pilosula. Polysaccharides derived from Astragalus membranaceus activated PI3K/Akt/mTOR signaling in dexamethasone- and oxidative stress–induced C2C12 myotube atrophy models, promoted protein synthesis, and suppressed protein degradation through reductions in MuRF1 and Atrogin-1 expression [22]. Astragaloside IV further inhibited TGF-β1/Smad signaling and attenuated muscle atrophy [11]. Mountain ginseng was reported to suppress FOXO3a signaling and regulate MuRF1 and Atrogin-1 expression in dexamethasone-induced muscle atrophy models [11]. In TEAM theory, Qi and Blood are generated through nutrient absorption and distribution by the spleen and stomach [30]; thus, the protein anabolic and anti-catabolic effects of these herbs may be conceptually associated with spleen-tonifying actions.

Herbal medicines related to spleen–stomach dampness–heat include berberine and baicalin. Berberine has been reported to activate AMPK and regulate mitochondrial-related factors such as PGC-1α, NRF1, TFAM, and SIRT1 [11], while baicalin suppressed NF-κB and MAPK signaling and activated the Nrf2/HO-1 pathway, thereby reducing inflammation and oxidative stress [21]. In TEAM, dampness–heat is commonly associated with chronic inflammation, fatty liver, and central obesity [24,26]. Although these pharmacological effects may be conceptually related to dampness–heat pathology, they cannot be directly equated with specific TEAM treatment principles.

Herbal medicines associated with liver–kidney Yin deficiency, including Lycium barbarum, Schisandra chinensis, Rehmannia glutinosa, Angelica sinensis, and Eucommia ulmoides, have been reported to modulate SIRT1 and the AMPK/PGC-1α axis, exert antioxidant effects, and inhibit apoptosis [11,20–21]. Nanovesicles derived from Lycium barbarum activated AMPK/SIRT1/PGC-1α signaling in dexamethasone-induced muscle atrophy models [11], while Schisandra chinensis reduced caspase-3 and PARP expression [11]. Liver–kidney Yin deficiency is conceptualized as depletion of liver blood and kidney essence, resulting in impaired nourishment and regeneration of muscle and bone [28,30]. Regulation of mitochondrial function and energy metabolism through SIRT1 and PGC-1α may therefore be conceptually linked to kidney-related functions in TEAM theory.

Nevertheless, correspondences between molecular mechanisms and TEAM pattern differentiation remain conceptual rather than deterministic. These correspondences should therefore be interpreted as heuristic rather than causal. TEAM pattern differentiation is based on clinical manifestations, tongue diagnosis, and pulse patterns, whereas molecular biology operates within a distinct explanatory paradigm. Accordingly, the proposed stage-wise pattern model and pharmacological mechanisms should be applied complementarily, not interchangeably, when interpreting steroid-induced sarcopenia. Future preclinical and clinical studies are required to clarify which molecular mechanisms are influenced by specific herbal medicines in steroid-induced sarcopenia and to validate their effects in patient populations characterized by distinct patterns.

Conclusions

This narrative review summarized the pathophysiological mechanisms of steroid-induced sarcopenia and proposed a TEAM-based pathological interpretation. Glucocorticoids induce a complex pathological state characterized by GR-mediated suppression of muscle protein synthesis, acceleration of protein degradation, increased insulin resistance, and metabolic abnormalities involving adipose tissue and the liver, collectively forming a systemic metabolic disorder driven by interactions among muscle, liver, and adipose tissue [1–3,6–10].

In TEAM, muscle physiology is understood in relation to the liver, spleen, and kidney, and age-related sarcopenia has been interpreted within pattern differentiation frameworks including spleen–stomach deficiency, spleen–stomach dampness–heat, and liver–kidney Yin deficiency [11,18]. By integrating these established frameworks with TEAM interpretations of steroid-related pathology, this study proposed a preliminary TEAM stage-wise pathological model for steroid-induced sarcopenia. Prolonged glucocorticoid exposure was interpreted as excessive heat stimulation, leading to impairment of spleen–stomach function, progression to spleen–stomach dampness–heat, and subsequent depletion of liver blood and kidney essence, summarized as a spleen–stomach dampness–heat to liver–kidney Yin deficiency progression model. This model frames conceptualizes steroid-induced sarcopenia as a systemic condition involving sequential dysfunction of multiple organ systems rather than a localized muscle disorder.

Furthermore, preclinical and network pharmacology studies were reviewed to summarize the reported effects of herbal medicines on muscle protein metabolism, inflammation, oxidative stress, and mitochondrial function [11,20–22]. Attempts were made to conceptually associate these pharmacological effects with TEAM pattern differentiation, and partial conceptual correspondences were identified. However, direct one-to-one mapping between molecular mechanisms and specific patterns was not established, reflecting the fundamentally different theoretical paradigms of TEAM and molecular biology.

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