**Chunmei Zhai 1,2, Jianping Zhao 2, Amar G. Chittiboyina 2, Yonghai Meng 1,2, Mei Wang <sup>3</sup> and Ikhlas A. Khan 1,2,4,\***


Academic Editors: Luisella Verotta and Derek J. McPhee

Received: 13 November 2020; Accepted: 8 December 2020; Published: 13 December 2020

**Abstract:** Thermally processed rhizomes of *Atractylodes macrocephala* (RAM) have a long history of use in traditional Chinese medicine (TCM) for treating various disorders, and have been an integral part of various traditional drugs and healthcare products. In TCM, herbal medicines are, in most cases, uniquely processed. Although it is thought that processing can alter the properties of herbal medicines so as to achieve desired functions, increase potency, and/or reduce side effects, the underlying chemical changes remain unclear for most thermally processed Chinese herbal medicines. In an attempt to shed some light on the scientific rationale behind the processes involved in traditional medicine, the RAM processed by stir-frying with wheat bran was investigated for the change of chemical composition. As a result, for the first time, five new chemical entities, along with ten known compounds, were isolated. Their chemical structures were determined by spectroscopic and spectrometric analyses. The possible synthetic pathway for the generation of such thermally-induced chemical entities was also proposed. Furthermore, biological activity evaluation showed that none of the compounds possessed cytotoxic effects against the tested mammalian cancer and noncancer cell lines. In addition, all compounds were ineffective at inhibiting the growth of the pathogenic microorganisms.

**Keywords:** *Atractylodes macrocephala*; wheat bran; processing; NMR; atractylon derivatives; isolation and identification
