Guanxin Danshen formula (GXDSF)

What It Is

Guanxin Danshen formula (abbreviated GXDSF) is a classical Chinese herbal prescription that is documented in the Chinese Pharmacopoeia (since at least the 1995 edition).

The formulation is composed of three main herbal parts:

1. Salviae miltiorrhizae Radix et Rhizoma (i.e. Danshen)
2. Notoginseng Radix et Rhizoma (i.e. Panax notoginseng, sometimes “sanqi”)
3. Dalbergiae odoriferae Lignum (i.e. the wood / volatile oil / aromatic heartwood of Dalbergia odorifera)

In traditional Chinese medicine (TCM) theory, GXDSF is used primarily for conditions involving "qi stagnation" and "blood stasis" (i.e. impaired circulation, pain, obstruction).

In modern research, much of the investigation around GXDSF centers on cardiovascular / cardiac protection, especially in the settings of ischemia-reperfusion injury, ventricular remodeling, and coronary heart disease. Frontiers

There is also emerging research into potential neuroprotective or antidepressant/anti-anxiety effects of GXDSF (or derivatives / “dripping pills” forms) in models of depression or anxiety comorbid with heart disease. atm.amegroups.org

In short: GXDSF is a TCM herbal formula combining Danshen, notoginseng, and Dalbergia odorifera components, traditionally aimed at improving circulation and resolving stagnation, and in modern research applied especially to cardiovascular protection and possibly mood / neural effects.

How It Works (Mechanisms of Action)

Because GXDSF is a multi-component herbal formula, its effects are thought to arise from a complex, multi-target set of actions. Below are the principal mechanisms supported (or proposed) by scientific / preclinical studies:

Cardioprotective / Anti-ischemia & reperfusion injury / Ventricular remodeling

• In a rat model of myocardial ischemia-reperfusion injury (MIRI) with subsequent ventricular remodeling, GXDSF was shown to improve cardiac functional indices (e.g. +dp/dt, LVSP), and raise ejection fraction (LVEF) and fractional shortening (LVFS) compared with untreated model groups. Frontiers
• GXDSF reduced biochemical markers of myocardial injury (AST, LDH, CK-MB) in treated animals versus controls. Frontiers
• Histologically, GXDSF reduced fibrosis markers (collagens I/III, α-SMA, fibrosis percentage) and altered the collagen III/I ratio (indicative of remodeling). Frontiers
• Through network pharmacology and experimental validation, a key proposed molecular target is estrogen receptor β (ERβ). GXDSF was found to upregulate ERβ in myocardial tissue, and blockade of ERβ with a selective antagonist (PHTPP) partially reversed the protective effects (on functional, biochemical, and fibrosis endpoints). This suggests the ERβ → PI3K / Akt signaling pathway is a critical axis in its effect. Frontiers
• In more recent mechanistic explorations, GXDSF is proposed to mitigate pyroptosis / inflammasome activation (e.g. NLRP3 inflammasome / caspase-1 / IL-1β) in myocardial cells under ischemia-reperfusion stress, thus reducing cell injury / death and improving outcomes. SciELO
• In a diabetic cardiomyopathy model (in db/db mice), GXDSF improved cardiac morphology and function, reduced apoptosis (TUNEL assays), and improved metabolic parameters (lipids, insulin sensitivity). The authors implicated modulation of apoptosis-associated gene/protein expression. Spandidos Publications

Circulation / Hemorheology / Anti-stasis / Microcirculation

• From the traditional TCM / pharmacological perspective, GXDSF is believed to “activate blood and remove stasis, regulate qi, relieve pain.” SpringerLink
• Some of its component herbs (especially Danshen, Panax notoginseng) are well studied in the cardiovascular literature:
• Danshen (Salvia miltiorrhiza) contains many bioactive molecules (e.g. tanshinones, salvianolic acids) known for antioxidant, anti-inflammatory, vasodilatory, anti-platelet, endothelial protective, and anti-fibrotic actions. ScienceDirect
• Panax notoginseng saponins (PNS) have been shown in various studies to improve endothelial function, reduce oxidative stress and inflammation, inhibit platelet aggregation, and support microcirculation. SpringerLink
• Dalbergia odorifera (volatile oil) is less intensively studied, but in TCM is classically attributed to improving qi flow, relieving pain, and potentially supporting circulation (especially in “stagnation” syndromes). SpringerLink

Neuro / Mood / Antidepressant-like effects

• In animal models of depression (chronic unpredictable mild stress, CUMS), GXDSF was found to produce antidepressant-like effects, likely via the CaMK II → CREB → BDNF signaling pathway, which is classically implicated in synaptic plasticity, neuronal survival, and mood regulation. atm.amegroups.org
• Given that GXDSF includes components (e.g. Panax notoginseng saponins) already known to affect neurotransmitter systems (5-HT, NE, dopamine) and neurotrophic signaling, the hypothesis is that the formula may modulate multiple neural pathways in addition to its cardiovascular effects. atm.amegroups.org
• In a human clinical trial in patients with coronary heart disease after percutaneous coronary intervention (PCI) who also had depression or anxiety, the “Guanxin Danshen Dripping Pills” (a formulation derived from GXDSF) significantly reduced PHQ-9 (depression) and GAD-7 (anxiety) scores vs. placebo over 12 weeks, improved angina symptoms (via Seattle Angina Questionnaire), improved quality of life (SF-12), and decreased inflammatory markers (e.g. high-sensitivity CRP) and endothelin levels. Importantly, no serious adverse events were reported. SpringerLink

Other possible pathways / network effects

• A review of GXDSF’s potential molecular mechanisms in ventricular remodeling lists about 20 candidate signaling pathways (beyond the ERβ / PI3K / Akt axis) that may participate, indicating a broad “network pharmacology” view (i.e. multiple synergistic targets). SpringerLink
• Because herbal formulas often act via multi-target, low-dose synergy, GXDSF’s efficacy might lie in the simultaneous modulation of oxidative stress, inflammation, fibrosis, apoptosis, endothelial function, and microvascular circulation.

Thus, GXDSF is thought to work by modulating multiple interlocking biological systems (cardiac cell survival, anti-inflammation, anti-fibrosis, microcirculation, neurotrophic signaling) with an emphasis on the ERβ / PI3K / Akt axis in cardiac protection, plus possible central nervous system effects in mood regulation.

Why It’s Important (Potential Benefits / Relevance)

Here are the reasons GXDSF is of interest from both traditional / clinical and research perspectives:

Addressing a major target: cardiovascular disease

• Coronary heart disease, myocardial infarction, ischemia/reperfusion injury, and resultant heart failure / remodeling are leading causes of morbidity and death globally.
• Conventional therapies help but often have limitations (e.g. incomplete protection against reperfusion injury, side effects, limited reverse remodeling). Research into adjunctive or complementary therapies is ongoing.
• GXDSF offers a TCM-based, multi-target therapeutic candidate that may help protect myocardium, reduce remodeling, and improve functional outcomes in ischemic / reperfusion injury settings. Frontiers

Bridge between traditional theory and modern biology

• GXDSF is a concrete example of a TCM formulation being re-examined with modern pharmacology / systems biology / network pharmacology approaches.
• ts mechanisms (ERβ, PI3K/Akt, inflammasome, apoptosis, neurotrophic signaling) provide mechanistic anchors that may help translate TCM concepts (e.g. qi / stasis) into biomedical terms.

Adjunctive / complementary potential in comorbid conditions

• Its observed beneficial effects on mood (anxiety / depression), quality of life, and microcirculation in CHD patients suggest a holistic action beyond purely cardiovascular endpoints. The ability to act on both heart and brain may be especially valuable in patients with overlapping cardiovascular and neuropsychiatric risk. SpringerLink
• In the study of “dripping pills” derived from GXDSF in CHD patients, few serious adverse events were seen, which suggests a favorable safety / tolerability profile in at least that context. SpringerLink

Potential in metabolic / diabetic cardiomyopathy settings

• The study in db/db mice (a type 2 diabetes model) suggests GXDSF might have beneficial effects in diabetic cardiomyopathy (improving cardiac structure / function, metabolism, reducing apoptosis) which broadens its potential therapeutic horizon. Spandidos Publications

Scientific and translational value

• Understanding GXDSF’s multi-target, synergistic mechanisms can advance the field of integrative medicine and provide models for how to study complex herbal formulas rigorously.
• Its inclusion in the Chinese Pharmacopoeia attests to its recognized status in TCM, which gives it a degree of standardization and credibility. SpringerLink

In sum, GXDSF is important because it is a historically rooted herbal formula with translational potential in cardiovascular disease and possibly neuropsychiatric comorbidity, offering a multi-mechanistic approach that complements conventional therapies.

Considerations (Risks, Limitations, Knowledge Gaps)

While GXDSF (and derivative preparations) shows promise, it is essential to adopt a cautious, critical stance. Here are the key considerations:

Evidence base is still limited / mostly preclinical

• Many of the mechanistic and efficacy studies are in animals or in vitro models (rats, mice, cardiomyocyte cell lines) rather than large-scale human clinical trials. SciELO
• The human clinical trial (GLAD study) on GXDSF-derived “dripping pills” in CHD + depression/anxiety is relatively small (≈200 patients) and relatively short duration (12 weeks). SpringerLink
• Long-term safety, efficacy for “hard” endpoints (e.g. mortality, major cardiac events), and comparative studies against standard-of-care drugs remain very sparse.

Standardization, quality, consistency

• Herbal formulas can suffer from variability in herb sourcing, harvesting, processing, and preparation (e.g. concentration, purity of active components).
• Ensuring consistent ratios, purity, absence of contaminants (e.g. heavy metals, pesticides, adulterants) is critical but challenging.
• The precise chemical fingerprint of GXDSF (e.g. concentrations of tanshinones, salvianolic acid, ginsenosides, notoginsenosides, volatile oils) may vary across batches / manufacturers. Some studies have quantified component percentages (e.g. notoginsenoside R1, ginsenoside Rg1, salvianolic acids, tanshinone IIA) for characterization. Spandidos Publications

Safety / adverse effects / herb-drug interactions

• As a complex herbal formula, GXDSF (or its derivatives) carries the potential for adverse effects, allergic reactions, or interactions with conventional cardiovascular drugs (e.g. anti-platelet agents, anticoagulants, statins, ACE inhibitors).
• In the human trial cited, no serious adverse events were reported, but sample size and duration were limited. SpringerLink
• Because some components (e.g. Danshen) have anticoagulant or blood-thinning properties, there is a plausible risk of bleeding when combined with other antithrombotic medications.
• Herbal components may affect cytochrome P450 enzymes, transporters, or other drug-metabolizing pathways, which can lead to altered pharmacokinetics of coadministered drugs.
• For patients with compromised liver or kidney function, caution is required as herbal metabolites may exert stress on detoxification systems.

Patient selection / contraindications

• The TCM principle of GXDSF is for “qi stagnation and blood stasis” presentations; it may not be appropriate (or may be less effective) in TCM syndromes with other dominant patterns (e.g. deficiency, cold, etc.).
• In patients with active bleeding, coagulation disorders, peptic ulcers, hemorrhagic stroke risk, or on strong anticoagulant regimens, caution is warranted.
• Pregnant or breastfeeding women, or pediatric populations, would require special scrutiny due to lack of safety data.

Dose, formulation, pharmacokinetics / biodistribution

• The optimal dose, formulation (herbal decoction, extract, “dripping pills,” capsules, etc.), timing (pre- versus post-injury), and delivery method (oral, intravenous, etc.) are not well standardized or fully studied.
• The absorption, metabolism, distribution, and elimination (ADME) of each active component in the context of the full formula (with possible interactions) are not fully elucidated.
• The bioavailability of many herbal constituents is often low, and achieving effective concentrations in target tissues (e.g. myocardium, brain) may be challenging.

Regulatory, legal, and translational hurdles

• erbal formulas often face stricter regulatory scrutiny (in many jurisdictions) due to complexity, variability, and safety concerns.
• Translating preclinical efficacy into approved therapeutic indications would require well-designed, large randomized controlled trials (RCTs) with robust endpoints, which are expensive and time-consuming.
• Intellectual property / standardization challenges (e.g. patenting a formula, ensuring batch consistency) may limit commercial incentives for rigorous development.

Synergistic vs antagonistic effects / complexity risk

• Because multiple constituents may act synergistically, antagonistically, or independently, it is difficult to pinpoint which components are essential and which may cause side effects.
• In some cases, the presence of many bioactive compounds increases the risk of unpredictable interactions (within the formula or with external drugs).