ABSTRACT
In traditional oral practice, the presystemic interactions with gut microbiota is an important mechanism underlying the holistic health benefits of Chinese herbal medicines (CHMs), making the study of CHMs distinct from the research of Western medicines of which the systemic exposure (level in blood) is the starting point and the core. Gut microbial metabolism complements host metabolism in maintaining metabolic homeostasis of many biologically important endogenous molecules and the disposition of numerous exogenous compounds. Among them, the widely distributed gut bacterial β-glucuronidases (BGUSs) coordinate with host UDP-glucuronosyltransferases (UGTs) to play a role in the occurrence and intervention of diseases by affecting the glucuronidation homeostasis and altering the intestinal local and/or systemic exposure of endogenous compounds and xenobiotics. On one hand, many ingredients of CHMs undergo enterohepatic circulation; On the other hand, CHMs can act on BGUSs directly or indirectly change the distribution and function of BGUSs through reprogramming gut microbiome. The multiple interactions between BGUSs and CHMs may play an important role in the overall therapeutic benefits of CHMs. This work firstly summarizes the latest research progress on BGUSs; then the physiological, pathological and pharmacological significance of BGUSs are exemplified with representative endogenous and exogenous compounds from the aspects of nutrient utilization, metabolic homeostasis, and therapeutic response based on the varied substrate spectra of BGUSs; finally, the scattered data in literature were integrated to summarize the multiple interactions between BGUSs and CHMs, highlighting the important role of BGUSs in the holistic actions of CHMs.
ABSTRACT
Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattern of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine (WM). On the basis of the combination of the advantages of integrated Chinese medicine (CM) and WM, with unified understanding of such diseases, the new concept of glucolipid metabolic disease (GLMD) is introduced. In this new concept, disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD. The key points of pathology included dysfunction of neuronal-endocrine-immune system, insulin resistance, oxidative stress, inflammation and intestinal flora imbalance. In the core pathogenic perspective of CM, it can be explained as "Gan (Liver) Shi Shu Xie" (dysfunction of Gan in metabolism and emotion regulation) that will lead to the occurence/production of endogenous dampness and phlegm, blood stasis and turbid. This leads to the new concept of "Liver-based regulatory system for metabolic homeostasis" to be introduced further. The comprehensive prevention and control strategy "Tiao Gan Qi Shu Hua Zhuo" (modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness). Its representative formula Fufang Zhenzhu Tiaozhi Capsule () is innovated under such rationales. Comment for some commonly-used CM GLMD therapeutic drugs was presented. High-level evidence-based and epidemiological and mechanism studies should be carried out to further interpret and explain of the scientific connotation of GLMD.
ABSTRACT
Post-translational modifications (PTMs) of transcription factors play a crucial role in regulating metabolic homeostasis. These modifications include phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, and O-GlcNAcylation. Recent studies have shed light on the importance of lysine acetylation at nonhistone proteins including transcription factors. Acetylation of transcription factors affects subcellular distribution, DNA affinity, stability, transcriptional activity, and current investigations are aiming to further expand our understanding of the role of lysine acetylation of transcription factors. In this review, we summarize recent studies that provide new insights into the role of protein lysine-acetylation in the transcriptional regulation of metabolic homeostasis.