1.Professor LIU Minru's Medication Rule in Treatment of Polycystic Ovary Syndrome (Intracellular Lipid Membrane Congestion Syndrome)
Xinbo HE ; Xiang HU ; Minru LIU ; Fuzhu LI ; Yuhuan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):169-176
ObjectiveTo analyze and sum up the medication rule and the core prescription of Professor LIU Minru in the treatment of polycystic ovary syndrome (intracellular lipid membrane congestion syndrome)and explore the effect mechanism underlying the medication. MethodTwo platforms were used to carry out data mining to analyze the characteristics and rules of Professor LIU's prescriptions for the treatment of this disease. Network pharmacology was used to further clarify active ingredients in the core prescription,and a traditional Chinese medicine-active ingredient-target network was constructed,with the potential mechanism of action analyzed. ResultA total of 321 prescriptions were included in the medical records,involving 178 Chinese medicinals and 28 kinds of formula granules.The Chinese medicinals mainly act on the liver and kidney meridians, whose main tastes were sweetness,pungency,and bitterness and properties were mainly warm,mild,and slightly cold.Commonly used medicine pairs include Dioscoreae Rhizoma-Rehmanniae Radix Praeparata,Chuanxiong Rhizoma-Angelicae Sinensis Radix,Bupleuri Radix-Aurantii Fructus,and Gleditsiae Spina-Curcumae Rhizoma.The commonly used formulas are Xuefu Zhuyutang,Siwugang,Yangjing Zhongyutang,etc. The core prescription is composed of 12 Chinese medicinals such as angelica,white peony,saponaria thorn,and epimedium,containing 74 active ingredients,including quercetin,luteolin,kaempferol,fisetin,and β-sitosterol.A total of 37 key targets were found,involving phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt),mitogen-activated protein kinase (MAPK),Janus protein tyrosine kinase (JAK)/signal transduction and activator of transcription (STAT),and other signaling pathways. ConclusionThe pathogenesis of this disease is complex.Professor LIU adheres to the pathogenesis of "kidney deficiency as the root cause,and phlegm retention as the symptom". Under the guidance of the academic ideology of "kidney Qi as the root,and protecting Yin as the foundation" and "nurturing Yin to support Yang",she takes into account Yin and Yang in kidney tonic,replenishes and consolidates the essence and blood,and relieves manifestations by dissipating mass, activating blood, and regulating Qi. She has a rigorous thinking in formulating prescriptions. The core prescription has the characteristics of comprehensive regulation by multiple components at multiple targets in multiple pathways.
2.Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications.
Ling ZOU ; Minru LIAO ; Yongqi ZHEN ; Shiou ZHU ; Xiya CHEN ; Jin ZHANG ; Yue HAO ; Bo LIU
Acta Pharmaceutica Sinica B 2022;12(10):3743-3782
UNC-51-like kinase 1 (ULK1), as a serine/threonine kinase, is an autophagic initiator in mammals and a homologous protein of autophagy related protein (Atg) 1 in yeast and of UNC-51 in Caenorhabditis elegans. ULK1 is well-known for autophagy activation, which is evolutionarily conserved in protein transport and indispensable to maintain cell homeostasis. As the direct target of energy and nutrition-sensing kinase, ULK1 may contribute to the distribution and utilization of cellular resources in response to metabolism and is closely associated with multiple pathophysiological processes. Moreover, ULK1 has been widely reported to play a crucial role in human diseases, including cancer, neurodegenerative diseases, cardiovascular disease, and infections, and subsequently targeted small-molecule inhibitors or activators are also demonstrated. Interestingly, the non-autophagy function of ULK1 has been emerging, indicating that non-autophagy-relevant ULK1 signaling network is also linked with diseases under some specific contexts. Therefore, in this review, we summarized the structure and functions of ULK1 as an autophagic initiator, with a focus on some new approaches, and further elucidated the key roles of ULK1 in autophagy and non-autophagy. Additionally, we also discussed the relationships between ULK1 and human diseases, as well as illustrated a rapid progress for better understanding of the discovery of more candidate small-molecule drugs targeting ULK1, which will provide a clue on novel ULK1-targeted therapeutics in the future.