Astragalus spp

Photo: Mostphotos.com

                    Photo: Mostphotos.com

Description

Astragalus is a plant belonging to the Leguminosae family. The roots of Astragalus membranaceous or mongholicus are most commonly used for medicinal purposes. Also known as milk vetch or huangqi, Astragalus is one of the most commonly used herbs in Traditional Chinese Medicine (TCM) for conditions where there is a deficiency of qi.  In the context of Western medicine it is claimed to have immune modulating effects, anticancer actions, and support quality of life for people with cancer.  

Efficacy

Astragalus is often used in combination with other herbs, however three meta-analyses and six randomized controlled trials have evaluated Astragalus as a single-herb for cancer outcomes.  Methodological quality of existing studies is a concern, and higher quality studies are needed.

Fatigue: IV infusion of Astragalus three times weekly during chemotherapy probably improves fatigue for people with advanced cancer

Quality of life: Concurrent use of Astragalus injections with chemotherapy or chemoradiotherapy in patients with advanced cancer likely improves performance status and Quality of Life 

Toxicities: Most, but not all studies found a reduction in chemotherapy side effects including haematological toxicities (leukopenia, thrombocytopenia, anaemia), gastrointestinal toxicities, and neurotoxicity.

Astragalus has mixed but generally positive effects on immune function, but more research is needed to better understand.

 Antitumour treatment: Astragalus injections probably improve objective response and 1-year survival in people with advanced NSCLC treated with platinum-based chemotherapy, and may improve outcomes for gastric cancer patients treated with FOLFOX. There is insufficient evidence for the impact of Astragalus on antitumor effects in colon cancer, head and neck cancer, or any other cancer type.

Safety

Astragalus is generally well tolerated and considered safe, but more research is needed particularly for possible herb-drug interactions.

Citation

Conte E, CAM Cancer Collaboration. Astragalus spp (A. membranaceus, A. mongholicus) [online document]Jun 22, 2020.

Document history

Substantial rewriting and update by Ellen Conte in June 2020.
Assessed as up to date in April 2016 by Barbara Wider.
Assessed as up to date in September 2013 by Barbara Wider.
Update in September 2012 by Klara Rombauts.
Summary first published in April 2011, authored by Klara Rombauts.

Description, background and characterisation of the medicinal plant

Astragalus is a plant belonging to the Leguminosae family. The  roots of Astragalus membranaceous or mongholicus are most commonly used for medicinal purposes. This herb is also know by its common names of milk vetch in the West, and Huangqi in China (Sinclair 1998; Guo 2019).

Astragalus originates from Shanxi Province of China, but now grows in several provinces in northern China (Sun 1983). Herbal medicine is an important aspect of Traditional Chinese Medicine (TCM), and Astragalus, one of the most commonly used herbs in Chinese Herbal Medicine (CHM), has been used for over 2000 years (Guo 2019). In the 1980s, Astragalus was popularized as an immunostimulant in the United States by the media (Natural Medicines Database 2020).

Ingredients and quality issues

Astragalus root contains several active constituents; the three most important bioactive compounds are polysaccharides, saponins, and isoflavonoids (Gou 2019; Alternative Medicine Review 2003; Ragupathi 2009. Well over 100 saponins (specifically triterpene saponins) have been isolated from Astragalus, most of them contain the term astragaloside in their name. Astragaloside IV has been increasing studied over the past several years. Over 60 flavonoids have been isolated from Astragalus, and approximately 30 Astragalus polysaccharides (Guo 2019).

The constituents of Astragalus may vary depending on the age, size and growing conditions of the root.

Application and dosage

Astragalus can be used as a single-herb, but is often administered in combination with other Chinese herbs chosen depending on the TCM diagnosis (Alternative Medicine Review 2012, Sinclair 1998). 

Astragalus can be administered as a decoction, aqueous injection (Guo 2012), alcohol extraction (tincture), dried or powdered root (Alternative Medicine Review 2003), or standardized extract (Liu 2016). Dosing varies depending on route of administration and condition.  Oral dosing of aqueous decoctions has varied from 3-6g of dried root per 350ml water (Sinclair 1998) to 60g daily (Tian 2016).  Extracts of 2.8g three times daily have been used for post-stroke fatigue (Liu 2016), and 4.5g-15g daily have been used in congestive heart failure (Yang 2011). Traditional dosing of dried root ranges from 2-4.8g (Hoffman 2003).

For cancer, the most common route of administration is injectables of Astragalus or Astragalus polysaccharides at a dose of 250-500mg several times weekly to daily (Guo 2012; Huang 2019; Wang  2019; Chen 2012; Hsieh 2020).

Postulated indications

In Traditional Chinese Medicine (TCM), Astragalus is believed to have a “Qi tonifying” effect (Qi is vital energy, a concept closely linked to immunity). In TCM, Astragalus is used to treat conditions of Qi deficiency, and lung and spleen conditions (Gong 2018). Specifically, Astragalus has traditionally be used for a variety of conditions including anaemia, chronic fatigue, weakness, allergies, loss of appetite, uterine bleeding and prolapse (Guo 2019), shortness of breath, frequent colds, and oedema (Alternative Medicine Review 2003). In modern times, Astragalus has been used to treat chronic kidney disease, diabetes mellitus, congestive heart failure and heart disease, conditions of immune deficiency or imbalance, allergies, viral infections, and fatigue (Alternative Medicine Review 2003; Li 2014).

In cancer care, Astragalus has mainly been used to reduce the severity of chemotherapy side effects, such as nausea, vomiting, and fatigue as well as immune suppression.

Mechanism of action

Broadly, Astragalus has been proposed to have anti-inflammatory, immunostimulant, antioxidant, anti-cancer, anti-diabetic, cardioprotective, hepatoprotective, anti-oxidant, and antiviral properties (Gong 2018; Li 2014). In cancer care, Astragalus may exert multiple effects on cancer including inhibiting proliferation of cancer cells, inducing apoptosis, inhibiting invasion and migration of cancer cells, reducing drug resistance and enhancing immune function (Guo 2019). The three constituents which gain the most attention for the anti-cancer effects of Astragalus are formononetin (flavonoid), astragaloside IV (saponin), and Astragalus polysaccharides (APS) (Gong 2019).

Direct anti-cancer effects

Preclinical studies have demonstrated anticancer effects of astragalus against a variety of cancer cell lines including gastric (Ai 2008), colon (Tin 2007; Law 2012), hepatic (Huang 2016), and ovarian cancers (Zhang 2018). The mechanisms by which it exerts these effects are varied.  Formononetin, an important flavonoid found in Astragalus can inhibit proliferation, migration, and invasion of tumor cells and induce apoptosis in vitro (Guo 2019).  Astragalus saponins have been shown to induce apoptosis in vitro in human hepatocellular carcinoma cells, colon cancer cells, and human erythroleukaemia cells (Auyeung 2009), and inhibit cell proliferation in cells and animal models (Gong 2018). Saponins have demonstrated the ability in vitro to suppress VEGF, downregulate mTOR and p-AKT expression, and enhance immune response (Gong 2018). Additional targets of Astragalus saponins include NAG-1 (nonsteroidal anti-inflammatory drug (NSAID)-activated gene) (Auyeung 2010).  S phase and G2/M arrest, and suppression of p21 expression and inhibition of cyclin-dependant kinase activity (Tin 2007). Astragaloside IV in particular is one of the best studied saponins for its anticancer effects (Guo 2019). Astragalus polysaccharides may stimulate tumour cell apoptosis and exert effects of the immune system (Gong 2018).

Immune effects

Astragalus polysaccharides (APS) receive most of the attention for the immune effects of the herb, although astragalosides (saponins) and flavonoids also exert some effect (Guo 2019; Gong 2018).  APS stimulate all types of immune cells, including T cells, B cells, and NK cells (Wagner 1999), and enhance IgM antibody production (Gong 2018). Astragalosides have also demonstrated in vivo increase in monocytes, neutrophils, and lymphocytes, and flavonoids a stimulation in lymphocyte proliferation (Gong 2018). Lastly, it has also been demonstrated that Astragalus can prevent tumour-induced macrophage suppression (Cho 2007), allowing macrophages to infiltrate the tumour site to participate in inflammatory reactions leading to destruction of neoplasms (Clement 2008; Rittenhouse 1991).

Legal issues

Jinfukang, a liquid formulation extracted from 12 botanicals is approved by the State Drug Administration (SDA), the Chinese equivalent of the FDA in the US, for its use in the treatment of non-small-cell lung cancer.

Outside Asia, Astragalus is sold as a dietary supplement for oral use. This does not require any approval by the FDA (Food and Drug Administration) or EMA (European Medicines Agency) but no medicinal claims associated with milk vetch can be made. 

Many studies of Astragalus for cancer evaluate Astragalus-based herbal formulas. These studies do not allow conclusions to be drawn about the efficacy of Astragalus itself. This summary focuses on what is known about Astragalus as a single-herb. However, it would be remiss to not mention the importance of Astragalus as part of Chinese Herbal Medicine (CHM) treatments and protocols and acknowledge these studies of Astragalus-based herbal formulas. Hundreds of RCTs and dozens of meta-analyses have been published demonstrating the promise of such formulas as both decoctions and injections, a few are referenced here as examples (Cao 2019; Zhang 2017; Lin 2019; Duan 2002). To discuss these in detail is beyond the scope of this summary.

All studies evaluated below use Astragalus or Astragalus polysaccharides as an injection. Many of the studies reviewed had several outcomes, and thus they are referenced in multiple sections. Details of all meta-analyses and randomized controlled trials are found in the Evidence tables below

Supportive care

Astragalus injectables have been evaluated for its effect on fatigue, performance status, quality of life (QoL), chemotherapy toxicity, and immune function. Most studies used Astragalus injections, and the populations were generally people with advanced cancer receiving chemotherapy or chemoradiotherapy. In most studies, performance status was measured by Karnofsky Performance Status (KPS), and QoL measured by the European Organization of Research and Treatment of Cancer’s Quality of Life Questionnaire (EORTC QLQ-C30). Three RCTs evaluated IV Astragalus polysaccharides for cancer-related fatigue (CRF), two meta-analyses and four small RCTs evaluated Astragalus for quality of life outcomes or performance status, three meta-analyses, and three RCTs evaluated the effect of concurrent Astragalus on chemotherapy toxicities and side effects, and 1 meta-analysis, 1 RCT, and 2 open-label non-randomized trials evaluated the effect of Astragalus on the immune system. Methodological quality and selection bias, particularly from the meta-analyses, is generally a concern. Large, well-designed RCTs are needed to further elucidate the effect of Astragalus injections as a supportive care therapy.

Description of included studies

Fatigue

IV infusion of PG2 (Astragalus polysaccharides) has been evaluated for its impact on fatigue in three studies (Wang 2019; Chen 2012; Hsieh 2020). The results are promising with administration of 250mg-500mg 3x/week for up to 8 weeks. The first study to evaluate this was a phase II, double-blind RCT comparing IV saline to IV PG2 at 500mg 3 times weekly in patients with advanced cancer and cancer-related fatigue (CRF) (Chen 2012). There was a significantly greater fatigue response rate on the Brief Pain Inventory (BFI) in the PG2 group compared to placebo after week 1 (57% vs 32%, p = 0.043), but the results were not statistically significant after weeks 2-4 although they continued to favour the Astragalus group.  When the placebo group was then administered the PG2 in an open-label extension, there was a significant improvement in their fatigue scores, although the placebo-effect cannot be excluded. A phase IV double-blind multi-centre RCT compared the effect of 250mg versus 500mg PG2 administered 3x/week for 8 weeks in patients with advanced cancer with CRF (Wang 2019). They found that 65% of participants had a ≥10% improvement in BFI at 4 weeks (73% in high dose, 67% in low dose), there was no statistically significant different between high and low dose PG2, and patients with a higher performance status at baseline were significantly more likely to be responders (P<0.001). There was no placebo group, so although it was blinded all patients and clinicians knew patients were receiving PG2, just differing doses.  A small RCT of PG2 injection 3x/week during concurrent chemo-radiotherapy for people with advanced head and neck squamous cell carcinoma reported a trend toward decreased fatigue on the BFI, but no statistically significant changes although the study may have been underpowered (Hsieh 2020).

Quality of life and performance status

The meta-analysis discussed previously of Astragalus injection (AGI) in patients with advanced NSCLC found improvements in Karnofsky Performance Status (RR 2.28, 95% CI 1.63-3.18, P < 0.00001) with the combined use of AGI and platinum-based chemotherapy compared to chemotherapy alone (Cao 2019). An additional open-label RCT in lung cancer evaluated Astragalus polysaccharide injection (APS) administered to patients with advanced NSCLC on days 1-7 of vinorelbine and cisplatin treatment cycles (Guo 2012). The study, which enrolled 136 people, found significant improvements on the EORTC QLQ-C30 and LC13 for overall QoL (p = 0.003), and physical function (P = 0.01), fatigue (P< 0.001), nausea and vomiting (P < 0.001), pain (P = 0.007) and loss of appetite (P = 0.023) subscales with APS. In the meta-analysis of Chinese herbal medicine for gastric cancer, Astragalus polysaccharides combined with FOLFOX was evaluated in 3 RCTs, and was associated with improved performance status (OR 11.38, CI 4.62-30.17) compared to control groups (Zhang 2017). Caution is warranted given the small number of studies evaluated for gastric cancer, and for both gastric and lung cancer studies there are concerns of generally poor methodology. Thus more research is needed, but the data is encouraging.

A sub-population from the 2019 study of Astragalus polysaccharide injection (PG2) for fatigue by (Wang 2019) evaluated PG2 for QoL and inflammatory markers (Huang 2018). This RCT evaluated the effect of 250mg PG2 and 500mg PG2 administered 3x/week on QoL and inflammatory cytokines in 23 advanced cancer patients. Global QoL on the EORTC-QLQ C30 was significantly improved in both high and low PG2 groups (p =0.01 and 0.02 respectively), a variety of inflammatory markers were decreased, and univariate and multivariate analyses revealed that IL-1β, IL-13 and GM-CSF are independent prognosticators of improved QoL. This is a small study and again had no placebo-group only a high and low dose PG2 group which are limitations. A small randomized, double-blind, placebo controlled trial evaluated PG2 injection 3x/week during concurrent chemo-radiotherapy for people with advanced head and neck squamous cell carcinoma (Hsieh 2020). The study only enrolled 17 people, thus the study found very few statistically significant results. However, there were encouraging trends toward stable QoL in the PG2 group on the EORTC. In an RCT 40mg daily of Astragalus injection alongside chemotherapy in patients with solid tumours for four cycles of treatment resulted in a significantly increased KPS compared to control group (Duan 2002).

Chemotherapy toxicity

All three meta-analyses discussed previously looked at chemotherapy toxicity. The meta-analysis of Astragalus injections for patients with NSCLC found significantly decreased leukopenia (RR 0.52, P < 0.00001), platelet toxicity (RR 0.62, P < 0.00001), and vomiting (RR 0.72, P = 0.0006) with the combined use of AGI and platinum-based chemotherapy compared to chemotherapy alone (Cao 2019). In the meta-analysis of Chinese herbal medicine for gastric cancer, Astragalus polysaccharides combined with FOLFOX was evaluated in 3 RCTs, and was associated with and decreased leukopenia OR 0.22 (0.060 – 0.74), and gastrointestinal toxicities OR 0.16 (CI 0.049-0.5) compared to control groups (Zhang 2017). A meta-analysis of Astragalus-based Chinese medicine for colon cancer included 5-studies that utilized Astragalus alone (no meta-analysis was conducted on this sub-set of studies) (Lin 2019). Risk of anaemia was reduced in one study (Zhu 2012) compared to control (RR 0.31, CI 0.13-0.74), but no study found a significant reduction in neutropenia or thrombocytopenia (Chen 2014, Rong 2011, Chen 2009). Neurotoxicity was significantly reduced in four studies: Luo 2012, RR 0.76  (CI 0.61-0.95), Chen 2014 RR 0.37 (CI 0.22-0.62), Chen 2009 RR 0.48 (CI 0.27-0.83), and Zhu 2012 RR 0.42 (CI 0.26-0.69), but no significant reduction in liver or renal dysfunction was found in the two studies which reported on them (Chen 2014, Rong 2011). Taken together, there are encouraging results for Astragalus injection reducing neurotoxicity alongside chemotherapy for colon cancer, and more research is needed to evaluate for haematological effects.

In an RCT 40mg daily of Astragalus injection alongside chemotherapy in patients with solid tumours for four cycles resulted in a significantly lesser decline in white blood cells (WBC) and platelet count (p < 0.05), and a lower CD8 (P < 0.05), increased CD4/CD8 ratio  (p< 0.01), and higher IgG and IgM levels  (p < 0.05) in the Astragalus arm (Duan 2002). Together, this indicates a protective effect on immune function and reduced risk of thrombocytopenia. An open-label RCT of Astragalus polysaccharide injection administered to patients with advanced NSCLC receiving vinorelbine and cisplatin chemotherapy found no significant difference in grade 3 and 4 toxicities between groups (Guo 2012). A small RCT of PG2 injection 3x/week during concurrent chemo-radiotherapy for people with advanced head and neck squamous cell carcinoma found there were generally fewer grade 3 and 4 toxicities in the PG2 group compared to control, but the results were not statistically significant (Hsieh 2020). However, it should be noted that the sample size was only 17 and thus the study was likely underpowered to detect statistically significant changes.

Immune function

The meta-analysis of Astragalus injections for patients with NSCLC found improved immune function indicated by significantly increased percentages of CD3, CD4, NK cells, and decreased CD4/CD8 ratio (Cao 2019). In an RCT, 40mg daily of Astragalus injection alongside chemotherapy in patients with solid tumours for four cycles resulted in a significantly lesser decline in white blood cells (WBC) and a lower CD8 (P < 0.05), increased CD4/CD8 ratio  (p< 0.01), and higher IgG and IgM levels  (p < 0.05) compared to the control arm (Duan 2002). Together, these indicate a protective effect on immune function and reduced risk of thrombocytopenia.

A non-randomized trial of 30 patients with cervical cancer published in a Chinese journal (information retrieved from abstract only) found that Astragalus injections could regulate the imbalanced Th1/Th2 cell function found in cervical cancer patients (Hu 2010). Blood samples were taken before and after 1-week of daily 40mg Astragalus injections, and data was compared to 10 healthy volunteers.  This supports Astragalus as having an effect on immune function in people with cancer. An extract from milk vetch induced a restored immune reaction in 9 out of 10 patients with a significant increase in local graft versus host (GVH) reaction (P<0.01). This suggested that milk vetch contains potent immune stimulants. This was evaluated in 19 cancer patients and 15 normal healthy controls. Circulating mononuclear cells were isolated from heparinized peripheral venous blood, half of which were treated with milk vetch extract; the treated and untreated cells were then injected in partially immunosuppressed rats. Local GVH reaction was used as an outcome of a boosted immune reaction (Sun 1983).

Antitumor treatment

Description of included studies

A meta-analysis of RCTs for Astragalus injection (AGI) in patients with advanced NSCLC receiving platinum-based chemotherapy found improvements in 1-year survival and objective tumour response with the addition of AGI, however methodological quality of studies was low and risk of publication bias high (Cao 2019). The meta-analysis included 19-RCTs (n=135) and demonstrated for objective response rate a relative risk (RR) of 1.19 (95% CI 1.06-1.33, P = 0.002), and 1-year survival RR 1.4 (95% CI 1.16-1.70, P = 0.0005). High quality RCTs are needed to confirm these findings.  An open-label RCT not included in the aforementioned lung cancer meta-analysis evaluated Astragalus polysaccharide injection (APS, 250mg) for patients with advanced NSCLC (Guo 2012). APS was injected on days 1-7 of three, 28-day vinorelbine and cisplatin treatment cycles. The study enrolled 136 people, and evaluated tumour response and survival, quality of life (QoL), and chemotherapy toxicity.  This study found no significant differences in APS versus control arm for tumour response (42.64% vs 36.76%), median survival (10.7 and 10.2 months), or 1-year survival rate (35.3% and 32.4%).

In a meta-analysis of Chinese herbal medicine for gastric cancer, Astragalus polysaccharides combined with FOLFOX was deemed the most efficacious treatment when compared to FOLFOX alone or FOLFOX with other Chinese herbal medicines (Zhang 2017). In the meta-analysis, 3 of 81 RCTs studied Astragalus with FOLFOX chemotherapy, other studies used different herbal medicines. Astragalus combined with FOLFOX was associated with improved clinical efficacy (OR 3.06, CI 1.01 to 8.99) compared to control groups. Caution is warranted given the small number of studies and generally poor methodology of included trials. Thus more research is needed, but the data is encouraging. A meta-analysis of Astragalus-based Chinese medicine for colon cancer included mostly Astragalus-based combination formulas, which are excluded from this summary, however there were 5-studies that utilized Astragalus alone (Lin 2019). There was no meta-analysis done on the Astragalus-only studies, and full-text of these papers could not be obtained and are suspected to be Chinese-language only. Thus, only a brief summary can be provided based on the information in the meta-analysis.  All five studies evaluated Astragalus injection alongside chemotherapy for patients with stage II-IV colon cancer compared to chemotherapy alone, and sample sizes ranged from 40 to 124.  Two studies (Chen 2009, Luo 2012) looked at tumour response; one found no significant difference between control and Astragalus (Chen 2009), while the other demonstrated a significantly better response in the treatment versus control group (RR 1.86, CI 1.24-2.79) (Luo 2012).

A small randomized, double-blind, placebo controlled trial evaluated an Astragalus polysaccharide injectable, called PG2, injected 3x/week during concurrent chemo-radiotherapy for people with advanced head and neck squamous cell carcinoma (Hsieh 2020). The study only enrolled 17 people as it was stopped prematurely due to a new formulation of PG2 coming on the market. Thus, the study found very few statistically significant results. There was no difference in tumour response or survival at 59-month follow-up.

Prevention

No studies have evaluated Astragalus for cancer prevention.

Astragalus is generally considered to be safe when used orally or intravenously under proper medical supervision (Alternative Medicine Review 2003; Natural Medicines Database 2020). The LD50 of milk vetch in rats is 40g/kg, via intraperitoneal injection.

Studies of Astragalus in people with cancer have found either no difference in adverse events (AEs) between Astragalus and placebo groups (Guo 2012; Chen 2012) or decreased AEs and toxicity in the Astragalus group (Hsieh 2020). One study reported AE rates to be <9% in people with advanced cancer receiving palliative care only treated with 500mg or 250mg PG2 injections, and >80% were grade 1-2 (Wang 2019). Given the advanced population the safety is considered good.

Some Astragalus species produce the toxin swainsonine (Stegelmeier 1999; Sun 2009). Other species accumulate selenium what may cause selenium poisoning (Sors 2005). Therefore, it is very important to be cautious when buying Astragalus supplements.

Adverse events

Astragalus is generally well tolerated when used orally or intravenously. Adverse events are infrequent and generally mild. Reported AEs from clinical trials in patients with cancer include rash, eczema, pruritus, feeling cold, chills, and hypersensitivity (Wang 2019; Chen 2012). In many studies, reported AEs were the same or lower in the Astragalus arm compared to the placebo or control arm (Guo 2012; Hsieh 2020).

No adverse effects were reported in rats given Astragalus via gastric lavage for doses up to 100g/kg (Sinclair 1998). Animal and human studies have shown some extent of blood pressure and glucose lowering effects (Natural Medicines Database 2020). 

Contraindications

There are no known contraindications to Astragalus. Theoretically, given the immune modulating properties of Astragalus it may have the potential to exacerbate auto-immune conditions (Natural Medicines Database 2020) and thus should be used cautiously by anyone with an auto-immune conditions particularly if it is not well managed.

Interactions

There is insufficient data from published human studies on Astragalus-drug interactions.

Studies in cancer populations have used astragalus alongside a variety of chemotherapy agents including platinums (cisplatin, carboplatin, oxaliplatin), vinorelbine, tegafur-uracil, leucovorin, and 5-fluorouracil, and external beam radiation with generally beneficial outcomes. See table 1 for details

Several theoretical concerns exist based on mechanism of action or preclinical data, but human research is needed to confirm the clinical relevance.

  • Immunosuppressants: Due to the immune-modulating properties of Astragalus, it may decrease the effectiveness of immunosuppressant medications (Natural Medicines Database 2020; Sun 1983).
  • Diuretics: A small study in healthy volunteers found Astragalus had a diuretic effect (Ai 2008), and thus may potentiate the effect of diuretic medications.
  • Antihypertensive medications: Astragalus can lower systolic and diastolic blood pressure (Denzler 2016; Zhang 2014) and therefore, it may have additive effects on antihypertensive medications.
  • Gemcitabine: One study in rats found that pre-treatment with 3g/kg daily of Astragalus alerted the pharmacokinetics of gemcitabine but not pemetrexed (Chu 2019). Whether this is relevant clinically is not known.
  • CYP P450 enzymes: One preclinical study found that Astragalus injections and granules may upregulate cytochrome P450 (CYP) 3A1 activity and CYP3A4 reporter gene (Zhang 2013), however another preclinical pharmacokinetic study found that Astragalus caused CyP3A4 inhibition (Lau 2013). Thus, it is unclear if astragalus affects CYP P450 enzymes.

P-glycoprotein substrates: Astragalus may inhibit P-glycoprotein efflux pump (Tian 2012), which may decrease multidrug resistance but could theoretically increase toxicity of some drugs including doxorubicin, etoposide, and vincristine.

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