ABSTRACT
Yunüjian （Jing Yue's Collected Works）， composed of Gypsum Fibrosum， Rehmanniae Radix Praeparata， Anemarrhenae Rhizoma， Ophiopogonis Radix， and Achyranthis Bidentatae Radix， is used for the treatment of "headache， toothache， consumptive thirst， and other diseases caused by heat and Yin deficiency in the stomach". In modern clinical settings， it has definite hypoglycemic efficacy， as it improves insulin resistance， inhibits oxidative stress and inflammatory response， and down-regulates estrogen level. It is often directly used， modified before use， combined with other formulae （Liuwei Dihuangtang， Shashen Maidongtang， Shenqi Sanjingtang， Huangqi Guizhi Wuwutang， Zengyetang， Zengye Baihutang， etc.）， or used together with western medicine （insulin， metformin， pioglitazone， glurenorm， etc.）. Modified Yunüjian can be applied for the treatment of type 2 diabetes mellitus， gestational diabetes， polycystic ovary syndrome with insulin resistance， pruritus induced by diabetes mellitus， diabetic peripheral neuropathy， diabetic nephropathy， diabetic ketoacidosis， diabetic retinopathy， and diabetic periodontitis. According to previous experiment， the protection for pancreatic islet β-cells is an important way of Yunüjian to improve diabetes mellitus. The formula can remove damaged proteins and organelles by increasing the expression of autophagy-related 2B （Atg2B）， ubiquitin-like-conjugating enzyme （Atg3）， γ-aminobutyric acid type A receptor-associated protein （GABARAP）， selective autophagy receptor （p62/SQSTM1）， etc. Moreover， it plays an active role in islet cell proliferation and apoptosis by regulating the expression of mammalian target of rapamycin （mTOR） and reducing the expression of islet β-cell autophagy gene （Beclin）. These are pivotal for maintaining the quantitative structure and functions of islet cells. The modulatory effect of Yunüjian on growth hormone-releasing peptide （ghrelin）， gastrin， and growth hormone secretagogue receptor （GHSR） mRNA expression is also the underlying mechanism for the formula to protect pancreatic β-cells. In this study， we summarized the clinical and experimental studies on the therapeutic effect of this formula on diabetes mellitus， discussed the mechanisms， and proposed suggestions on the problems， hoping to provide a reference for the clinical application and further development of Yunüjian. This study is of practical significance for the scientific interpretation of the modern connotation of Yunüjian and the expansion of its clinical application.