Traditional Chinese medicine Largehead Atractylodes is the rhizome of Atractylodes, perennial herbaceous plant, Compositae, which is mainly produced in the following provinces, such as Zhejiang, Hubei, Hunan, Sichuan and Anhui.

Being a common traditional Chinese medicine, Largehead Atractylodes has a long history of cultivation and application in China. It likes cool environment but avoids heat and humidity. As it is more vulnerable to plant diseases and insect pests, which are easy to occur and spread quickly especially in places with poor drainage, it should pay attention to drainage during the process of planting. Furthermore, Largehead Atractylodes, a short-day plant, needs to be planted in the areas with the exposure to the rising sun but without the exposure to the setting sun and shadow ^{[1, 2]}. On the other hand, Largehead Atractylodes, a rhizome medicine, especially needs nitrogenous fertilizer and potassium fertilizer, followed by phosphorus fertilizer. Continuous cropping is also avoided to Largehead Atractylodes (Continuous cropping failure refers to the abnormal growth and development of crop caused by continuous cultivation of the same crop or close relatives on the same soil).

Largehead Atractylodes shows irregular incrassate masses with the length of 3-13cm and diameter of 1.5-7cm, whose surface, with the color of grayish yellow or grayish brown, has tuberculous protuberances and intermittent longitudinal wrinkles and furrow lines, fibrous root marks, and residual stem base and bud marks at the top. Its quality is hard and difficult to break. Its fracture surface is uneven, with the color of yellowish white to light brown, scattered with punctual oil chambers with the color of brownish yellow. Beside, its fracture surface after drying is keratoid with deeper color or fissures. It has fragrant odor, sweet and slightly pungent taste, and slightly sticky after chewing.

Baishu is one of common traditional Chinese medicines with long history of production, cultivation and application. Its primitive name is “Shu” while “Shu” also includes rhizoma atractylodis. “Shu” has been recorded in the ancient books such as Erya. The earliest medicinal application of Largehead Atractylodes was found in the Fifty-two Prescriptions for Diseases in the Warring States Period ^[3]. “Two medicines including Shu are boiled with 4 L water into the soup, which has therapeutic effects on scald injury with medicinal bath method”. Shen Nong Ben Cao Jing of the Han Dynasty contained “Shu” which was listed with top grade ^[4]. Largehead Atractylodes and rhizoma atractylodis had not yet been distinguished. In the middle of the Song Dynasty, many prescriptions, recorded in Prescriptions of Bureau of Taiping People’s Welfare Pharmacy, used Largehead Atractylodes and rhizoma atractylodis. For example, the prescription of Shengsanzi contained both Largehead Atractylodes and rhizoma atractylodis. In the Ming Dynasty, in Compendium of Materia Medica, Li Shizhen indicated that “Shu refers to Baishu”^[5]. During the Kangxi period in the Qing Dynasty, Largehead Atractylodes was introduced from Yu qian, Zhejiang to Jiangxi and then Hunan in the mid-18th century.

1. Essential oils

Largehead Atractylodes contains many volatile constituents, mainly sesquiterpenes. Nowadays, more than one hundred sesquiterpenoids have been identified from Largehead Atractylodes. The essential oils from Largehead Atractylodes have strong antioxidant effect in both  vivo and  vitro experiments, as well as  have anti-bacterial effect by damaging the cell membrane of both Gram-positive and Gram-negative bacteria.

Atractylenolides in the essential oils are the important components and also main active components isolated from Largehead Atractylodes, including atractylenolide I, atractylenolide II, atractylenolide III, atractylenolide IV, biatractylolide, 8, 9-epoxy- atractylenolide and 4, 15-epoxy-hydroxy atractylenolide, etc.

Both in vivo and in vitro experiments have shown that atractylenolide I  inhibited angiogenesis to alleviate and inhibit chronic inflammation by down-regulating the release of NO, TNF-α, inflammatory factors  (IL-1β and IL-6), vascular epithelial growth factor and placental growth factor ^[6]. In addition, atractylenolide I  also inhibited bladder cancer by inducing cell apoptosis ^[7]. A clinical randomized controlled trial on gastric cancer cachexia showed that atractylenolide I could alleviate the symptoms of gastric cancer by regulating inflammatory factors, improving the inflammatory state and inhibiting the hydrolysis of proteolytic inducers ^[8]. Atractylenolide II could inhibit the proliferation of melanoma by inhibiting key proteins in the cell cycle and resulting in cycle abnormalities ^[9]. Atractylenolide III showed  anti-cancer effect by inducing the apoptosis of lung cancer cells ^[10]. In addition, it can also play a protective role against gastric ulcers caused by alcohol ^[11].

2. Polysaccharides

Polysaccharides obtained from Largehead Atractylodes were mainly atractylodes macrocephalaon polysaccharide PSAM-1, composed of galactose (Ga1), rhamnose (Rha), arabinose (Ara) and mannose (Man), and PSAM-2 composed of xylose (xy1), arabinose (Ara) and galactose (Ga1). Atractylodes macrocephalaon polysaccharides could regulate the intestinal immune system by regulating lymphoid aggregation cells ^[12]. In vivo experiments showed that the acidic polysaccharides in Largehead Atractylodes could play a good protective effect on mice infected with Candida, which reflected anti-bacterial effect ^[13]. Furthermore, atractylodes macrocephalaon polysaccharides  promoted the metabolism of reducing sugars in intestine and regulated the disorder of intestinal flora. Therefore, atractylodes macrocephalaon polysaccharides were likely to be the oral regulator of intestinal flora ^[14]. In addition, atractylodes macrocephalaon polysaccharides  played an anti-cancer effect by inhibiting the proliferation of esophageal cancer ^[15]. In the rat model of renal failure caused by adenine, it was proved that atractylodes macrocephalaon polysaccharides had a good protective effect on renal failure in rats ^[16].

3. Others

Largehead Atractylodes also contains some coumarins and phytosterols. In addition, it contains a variety of amino acids and trace elements. Among 17 amino acids identified from Largehead Atractylodes, 7 amino acids are essential amino acids for human body. Largehead Atractylodes is also rich in trace elements, such as calcium, magnesium and iron, which could  maintain human health ^[17].

In winter, when the lower leaves are yellow and the upper leaves become brittle, Largehead Atractylodes can be collected and dug, the sediment is removed, the fibrous roots are removed after drying in the sun or over the fire, and then the thick slices are cut for either raw usage, fried with soil or fried with bran.

Raw atractylodes: Remove the impurities from Largehead Atractylodes obtained, wash and moisten them thoroughly, cut into thick slices, and then dry in the sun or over the fire before direct use.

Atractylodes fried with soil: Fry the soil in the bottom center of the oven in the wok to loose and flexible state, then put the slices of atractylodes in and stir fry them until the surface is evenly hung with soil powder, sieve to remove the soil powder, and let the slices cool.

Atractylodes fried with bran: Heat the wok over medium fire, sprinkle the wheat bran into the wok, and put the slices of atractylodes in until the smoke comes out. Stir fry them continuously until the slices are with the color of caramel, remove the slices after the burnt fragrance is escaped, sieve to remove the wheat bran, and let the slices cool.

Largehead Atractylodes obtained after different preparation and processing have different efficacy. For example, raw atractylodes has the advantages such as reinforcing spleen, promoting diuresis and relieving constipation, Atractylodes fried with soil has stronger effects on reinforcing spleen and anti-diarrhea, while Atractylodes fried with bran has stronger effect on anti-diarrhea.

Largehead Atractylodes is one of Traditional Chinese medicine applied in health food, announced by National Health Commission of the People’s Republic of China. According to the normative technical documents of Ministry of Public Health, China, the results have shown that, for the safety studies including acute toxicity, cytotoxicity and mutagenicity, Largehead Atractylodes is actually non-toxic or non-toxic Chinese medicine ^[18]. Nowadays, the toxicity of Largehead Atractylodes has not been reported in Europe, America, Japan and South Korea.

The clinical studies on Largehead Atractylodes are mainly associated with anti-tumor efficacy. In a randomized controlled clinical study, it has been shown that atractylenolide I can effectively improve weight loss and appetite loss caused by gastric cancer, increase mid-arm muscle circumference and improve cachexia ^[19].

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10. Kang TH, Bang JY, Kim MH, Kang IC, Kim HM, Jeong HJ. Atractylenolide III, a sesquiterpenoid, induces apoptosis in human lung carcinoma A549 cells via mitochondria-mediated death pathway. Food and Chemical Toxicology. 2011 Feb 1;49(2):514-9.

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14. Wang R, Zhou G, Wang M, Peng Y, Li X. The metabolism of polysaccharide from Atractylodes macrocephala Koidz and its effect on intestinal microflora. Evidence-based Complementary and Alternative Medicine. 2014 Jan 1;2014.

15. Feng YY, Ji HY, Dong XD, Liu AJ. An alcohol-soluble polysaccharide from Atractylodes macrocephala Koidz induces apoptosis of Eca-109 cells. Carbohydrate polymers. 2019 Dec 15;226:115136.

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19. Liu Y, Jia Z, Dong L, Wang R, Qiu G. A randomized pilot study of atractylenolide I on gastric cancer cachexia patients. Evid Based Complement Alternat Med. 2008 Sep; 5(3):337-44.