Pharmacological Properties of Atractylodes macrocephala Koidz.: A Comprehensive Review

Jiang-Bao Wang^{²^,^†}, Lu Wang^{³^,^†}, Song-Hong Yang^¹()

1School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China

2School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China

3Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Sciences, Ourense 32004, Spain

^†These authors contribute equally to this work.

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Highlights

(1) AMK, as a traditional qi-invigorating medicine, has extremely high value of both medicine and food, and its pharmacological research is very important.

(2) In this review, botanical characteristics, phytochemistry, pharmacology, pharmacokinetics of AMK were comprehensively analyzed and summarized.

(3) By consolidating current research, this review seeks to offer a thorough reference for the practical application, development and utilization of AMK as a food with homology of medicine and food.

Graphical Abstract

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Major active components, pharmacological activities and traditional records of AMK. Major active component of the figure contain Triterpenoids Sesquiterpenoids, Coumarins, Phenylpropanoids and Polyacetylenes. Pharmacological activities contain Neuroprotection, Anti-Inflammation and Gastrointestinal Function.

Abstract

Atractylodes macrocephala Koidz. (AMK), commonly known as Baizhu, is a medicinal and edible plant. Researchers have identified over 77 metabolites in AMK. Many studies have demonstrated the diverse pharmacological activities of AMK, including enhancing gastrointestinal function; modulating immune responses; regulating hormonal secretion; and exerting antitumor, anti-inflammatory, antiaging, antioxidant, antiosteoporotic, antibacterial, and neuroprotective effects.

Keywords

Atractylodes macrocephala Koidz.pharmacological activities active ingredients

References

[1]

Editorial Committee of the Flora of China, Chinese Academy of Sciences. Flora of China. Beijing: Science Press, 1993.

[2]

Liu, B., Kou, Z., Chen, B. Effects and mechanisms of traditional Chinese medicines on functional dyspepsia: A review. Chinese herbal medicines, 2023, 15: 516–525. https:// https://doi.org/10.1016/j.chmed.2023.06.001

Tested substance	Model	Tissue	Dose	Time	Results	Reference
Anti-inflammatory effects
Atractylenolide I	Freund’s complete adjuvant-induced air pouch mice model	Blood; fluid from air pouches; granuloma tissues	5, 10, 20 mg/kg; i.p.	11 days	↓NO, TNF-α, IL-1β, IL-6, VEGF, PlGF	[42]
Atractylenolide I	Aortic ring cocultured with peritoneal macrophages (mouse model)	/	1, 5, 10 μg/ml	12 h	↓NO, TNF-α, IL-1β, IL-6, VEGF, PlGF	[42]
Atractylenolide I	LPS-treated inflammatory RAW264.7 cells	/	20, 40, 60 μM	24 h	↓IL-6, IL-1β	[43]
Supercritical CO₂ fluid extracts of AMKatractylenolide I14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol	Acetic acid-induced vascular permeability mouse mode	Pigment in the abdominal cavity	125, 250, 500 mg/kg (extracts), p.o.;30, 100, 300 mg/kg; p.o.	30 min	↓increased vascular permeability	[44]
	Carrageenan-induced paw edema mouse model	Paw volume	100, 200, 400 mg/kg; i.p.	3 days	↑inhibition of edema
	Cotton-pellet granuloma mouse model	Granuloma tissues	30, 100, 300 mg/kg; p.o.	7 days	↑the percentage of inhibition of inflammation
Atractylenolide I	LPS-treated inflammatory RAW264.7 cells	/	1-100 µM	24 h	↓IL-6, TNF-α, activity of nuclear NF-κB and phosphorylation of ERK1/2 and p38, MD-2, CD14, SR-A, TLR4, MyD88	[45]
Immunomodulatory effects
Polysaccharide extracts of AMK	Immune responses to foot-and-mouth vaccine (FMDV) (mouse model)	Blood, spleen tissue	0, 0.025, 0.05, 0.1, 0.25 g; oral	7 weeks	↑IgG titers, IgG subclasses, IFN-γ, IL-5 and splenocyte proliferation stimulated by concanavalin A, lipopolysaccharide, and FMDV	[48]
Polysaccharide extracts of AMK	FMDV mouse model	Blood, intestinal mucosa	0.05 g; oral	1 week and 2 weeks	↑total sIgA, TGF-β, IL-6, TNF-α, IgA⁺ cells, intestinal intraepithelial lymphocytes in duodenum	[50]
Water extracts of AMK	FMDV mouse model	Serum, spleen tissue	0, 0.0625, 0.125, 0.25, 0.5 g; oral	7 weeks	↑IgG titers, IgG subclasses, IL-5, IFN-γ	[51]
Pure AMK polysaccharidesCrude AMK polysaccharides	Piglets	Blood, contents from ileum, cecum and colon	0.3%; oral	14 days	↑peripheral blood lymphocyte transformation rates and mRNA abundances of interleukin-6, TNF-α, IFN-γ, and nuclear factor of activated T cells transcription factor	[52]
AMK powder	Piglets	Blood, spleen tissue	1 g/kg; oral	30 days	↑IgG, IgA, IL-1, IL-2	[53]
Polysaccharide extracts of AMK	Heat stress chicken model	Spleen tissue	200 mg/kg; oral	6 weeks	↑IL-2, IFN-γ, CAT activity, T-AOC, -OH inhibition, activities of mitochondrial complexes I, II and V, Mg²⁺-ATPase, Na⁺-K⁺-ATPase, Ca²⁺-ATPase, Drp1, Mfn1, Mfn2, Mff, Opa1, Bcl-xl↓IL-1β, TNF-α, Cyt-c, p53, Bak, Bax	[54]
Antitumor effects
Ethanol extracts of AMK	Head and neck cancer KB cell line	/	1, 2, 3, 4 mg/mL	24 h	↑Bax/Bcl-2, LC3II, ATG5↓PARP1, p-AKT/AKT, mTOR	[59]
Methanol extracts of AMK	Human lymphoma Jurkat T cells, leukemia U937 and HL-60 cells	/	75, 100, 125 µg/mL	24 h	↑apoptosis, ROS	[60]
Atractylenolide I	Human K562 CML, U937 AML and Jurkat T leukemia cells	/	3.13-100 µg/mL	12-72 h	↑apoptosis↓caspase-3, caspase-9, CD14, CD68	[61]
Polysaccharide extracts of AMK	Glioma C6 cells	/	10, 50, 100, 250, 500, 1,000 g/mL	24, 48, and 72 h	↑PARP, caspase-3, caspase-9, cytosol↓mitochondria	[62]
Atractylenolide II	MCF 10A cells	/	1-1,000 μM	24, 48, and 72 h	↑Nrf2, GSH/GSSG ratio↓IL-6, IL-1β, MDA, 8-OHdG	[63]
Atractylenolide II	N-nitroso-N-methylurea-induced breast cancer rat model	Mammary glands	100, 200 mg/kg; i.p.	3, 5, 9 weeks	↑GSH/GSSG ratio, Nrf2, Ho-1, Nqo1, p-JNK/JNK, p-Erk1/2/Erk1/2↓IL-6, TNF-α, 8-OHdG, MDA, TNF-α, IL-6	[63]
Regulator effects on energy metabolism
Water extracts of AMK	3T3-L1 cells	/	1, 5, 10, 25 g/mL	8 days	↓adipogenesis, adipocyte differentiation, p-AKT/AKT	[64]
Water extracts of AMK	High fat diet-fed rats	Plasma	0.5 g/kg; oral	6 weeks	↓final body weight, triglyceride	[64]
Water extracts of AMK	C2C12 cells	/	0.2, 0.5, 1.0 mg/mL	25 h	↑PGC1α, NRF1, TFAM, total ATP, UCP3, p-AMK/AMK, p-ACC/ACC, SIRT1, GLUT-4, glucose uptake, CPT-1β↓FFA	[65]
Water extracts of AMK	High fat diet-fed mice	Serum and liver, brown adipose tissue, pancreas, gastrocnemius muscle tissue	100, 300 mg/kg	16 weeks	↑PGC1α, UCP1, p-AMPK/AMPK, HO-1, CAT, NRF1, TFAM↓body weight, fasting serum glucose, serum insulin levels, glucose intolerance, serum total cholesterol	[66]
Regulatory effects on gastrointestinal function
Polysaccharide extracts of AMK	Intestinal flora rat model	Feces	0.035, 0.105 g/kg; oral	10 days	↑body weights, Shannon’s diversity index↓ecological balance of intestinal flora, flora species	[33]
Methanol extracts of AMK	IEC-6 cell injury model	/	50, 100, 200 µg/mL	24 h	↑polyamine content, membrane hyperpolarization, elevation of [Ca²⁺]cyt, acceleration of cell migration, Kv1.1	[67]
Ethanol extracts of AMK	IEC-6 cell injury model	/	50, 100, 200 mg/L	12 h	↑cellular polyamine content, RhoA, nonmuscle myosin II, formation of nonmuscle myosin II stress fibers, acceleration of cell migration, Rac1 ↓CDC42	[68]
Water extracts of raw AMK, bran-roasted AMK and charred AMK	Alcohol-induced gastric ulcer mouse model	Stomach tissue	1.5 g/kg; oral	5 days	↓Percentage of ulcer area, ulcer index	[69]
Charred AMK nanocomponents	Alcohol-induced gastric ulcer mouse model	Blood, stomach tissue	0.4, 1.3, 5.1 g/kg	5 days	↑IL-10, PGE2, MUC5AC↓Percentage of ulcer area, ulcer index, IL-6, MDA, H⁺, K⁺ ATPase, Pepsin, IL-1β, TNF-α	[69]
Neuroprotective effects
Ethanol extracts of AMK	Excitotoxicity induced by glutamate in cortical neurons	Cortical neurons	120-240 µg/mL	24 h	↑cell viability↓apoptosis, DNA laddering	[73]
Biatractylolide	PC12 and SH-SY5Y Cells	/	10, 15, 20 μM	24 h	↑p-Akt↓GSK3 β, apoptosis, LDH release, ROS	[74]
Atractylenolide III	Learning and memory impairment rat model	Hippocampus	0.6, 1.2, 2.4 mg/kg; oral	6 weeks	↑p-PKC↓ROS, Casp-3	[76]
Atractylenolide III	Glutamate-induced neuronal apoptosis model	Cortical neurons	10, 20, 40 μM	24 h	↓apoptosis, DNA laddering, Casp-3	[77]
Polysaccharide extracts of AMK	Neuronal apoptosis induced by hypoxia	Cortical neurons	0.025, 0.05, 0.10, 0.25, 0.50, 1.0, 2.0, 4.0 g/L	48 h	↑Bcl-2, Bcl-2/Bax↓apoptosis, Casp-3, Bax	[78]
Regulatory effects on sex hormones and anti-uterine contraction effects
Ethanol extracts of AMK	Hyperandrogenic rat model of PCOS	Blood, uterus and ovaries	0.1, 0.3, 0.9 g/kg; oral	8 weeks	↑follicle stimulating hormone, follicle stimulating hormone receptor, aquaporin-9↓total testosterone, free androgen index, androstenedione, luteinizing hormone/follicle stimulating hormone, antimüllerian hormone	[80]
Soluble AMK extract (powder)	IL-6-stimulated human pregnant myometrial smooth muscle cell model	Human pregnant myometrial smooth muscle cells	1, 2, 4 mg/mL	/	↑BK_ca	[81]
Ethanol extracts of AMK	Bilaterally ovariectomized rat model	Serum	0.3 g/kg; oral	8 weeks	↑E2, osteocalcin↓FSH, IL-6	[82]
Antioxidant and antiaging effects
Polysaccharide extracts of AMK	Ischemia‒reperfusion injury rat model	Liver	0.4 g/kg; oral	7 days	↑↓ALT, AST, TBIL, DBIL, MDA, NF-κB, IL-1β	[83]
Polysaccharide extracts of AMK	D-galactose-treated rat model	Blood, brain	100, 200 mg/kg; oral	6 weeks	↑GSH-Px, CAT, T-AOC, SOD↓MDA, MAO, Lipo	[84]
Antiosteoporotic effects
Ethanol extracts of AMK	RANKL-induced bone loss mouse model	Bone marrow-derived macrophages	10-200 µg/mL	48 h	↓c-Fos, NFATc1, p-ERK/ERK, p-JNK/JNK, p-P38/P38	[85]
Ethanol extracts of AMK	RANKL-induced bone loss mouse model	Right femur	0.25, 0.75 g/kg; oral	5 days	↓bone loss	[85]
Atractylenolide I, atractylenolide Ⅲ	Mesenchymal stem cells	/	1-300 µg/mL	7 days	↑collagen II, aggrecan, SOX9, Shh, Gli-1	[86]
Antibiotic effects
Ethanol extracts of AMK	Staphylococcus aureus,Escherichia coli, Bacillus,subtilis, Shigella flexneri	/	5-40 mg/mL	24 h	↑inhibited growth	[88]
Water extracts of AMK	Staphylococcus aureus,Escherichia coli	/		24 h	↑inhibited growth	[89]