Myricanol improves metabolic profiles in dexamethasone induced lipid and protein metabolism disorders in mice.

Myricanol (MY) is one of the main active components from bark of Myrica Rubra. It is demonstrated that MY rescues dexamethasone (DEX)-induced muscle dysfunction via activating silent information regulator 1 (SIRT1) and increasing adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation. Since SIRT1 and AMPK are widely involved in the metabolism of nutrients, we speculated that MY may exert beneficial effects on DEX-induced metabolic disorders. This study for the first time applied widely targeted metabolomics to investigate the beneficial effects of MY on glucose, lipids, and protein metabolism in DEX-induced metabolic abnormality in mice. The results showed that MY significantly reversed DEX-induced soleus and gastrocnemius muscle weight loss, muscle fiber damage, and muscle strength loss. MY alleviated DEX-induced metabolic disorders by increasing SIRT1 and glucose transporter type 4 (GLUT4) expressions. Additionally, myricanol prevented muscle cell apoptosis and atrophy by inhibiting caspase 3 cleavages and muscle ring-finger protein-1 (MuRF1) expression. Metabolomics showed that MY treatment reversed the serum content of carnitine ph-C1, palmitoleic acid, PS (16:0_17:0), PC (14:0_20:5), PE (P-18:1_16:1), Cer (t18:2/38:1(2OH)), four amino acids and their metabolites, and 16 glycerolipids in DEX mice. Kyoto encyclopedia of genes and genomes (KEGG) and metabolic set enrichment analysis (MSEA) analysis revealed that MY mainly affected metabolic pathways, glycerolipid metabolism, lipolysis, fat digestion and absorption, lipid and atherosclerosis, and cholesterol metabolism pathways through regulation of metabolites involved in glutathione, butanoate, vitamin B6, glycine, serine and threonine, arachidonic acid, and riboflavin metabolism. Collectively, MY can be used as an attractive therapeutic agent for DEX-induced metabolic abnormalities.

Bidirectional effects and mechanisms of traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: The bidirectional property of traditional Chinese medicines (TCMs) was recorded in the classic work Medicine Origin (Yi Xue Qi Yuan) as early as the Jin and Yuan dynasties of ancient China. Since then, this imperative theory has been applied to guide the clinical application of TCMs. Studies have been performed to investigate this phenomenon only over the last three decades. A limited number of reviews on the bidirectional role of TCMs have been published, and almost all current studies are published in the Chinese language. AIM OF THE REVIEW: The aim of this review is to provide the first comprehensive evidence regarding the bidirectional effects and the underlying mechanisms of TCMs and their active compounds. MATERIALS AND METHODS: Information relevant to opposing pharmacological activities or opposing properties exerted by TCM prescriptions, herbal medicines, and their active compound, as well as their mechanisms was summarized by searching Chinese and English databases, including the Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data, Chinese Scientific Journal Database (VIP), Google Scholar, PubMed, Web of Science, Science Direct, and Wiley Online Library. RESULTS: Although the bidirectional regulation of TCMs has been applied in the clinic since ancient times in China, only limited reviews have been published in Chinese. The existing data showed that bidirectional effects can be found in TCM prescriptions, herbal medicines, and pure active compounds. Additionally, the bidirectional role of TCMs was primarily reported in the modulation of immune function, blood circulation and hemostasis, gastrointestinal motility, the central nervous system and blood pressure. This may because the therapeutic outcomes of these disorders are more obvious than those of other complicated diseases. Intriguingly, some herbal medicines have multiple bidirectional activities; for instance, Panax ginseng C. A. Meyer showed bidirectional regulation of immune function and the central nervous system; Astragalus membranaceus can bidirectionally regulate blood pressure and immune function; and Rheum officinale Baill exerts bidirectional effects on blood circulation and hemostasis, gastrointestinal motility and immune function. The mechanisms underlying the bidirectional effects of TCMs are largely attributed to the complexity of herbal constituents, dosage differences, the processing of herbal medicine, and compatibility of medicines, the physiological conditions of patients and adaptogenic effects. CONCLUSION: Uncovering the bidirectional effects and mechanisms of TCMs is of great importance for both scientific research and clinical applications. This review may help to facilitate the recognition of the bidirectional role of TCMs, to explain some seemingly-opposite phenomena in the pharmacological study of herbal medicines and to provide guidance for TCM practitioners.

Chitooligosaccharides-modified PLGA nanoparticles enhance the antitumor efficacy of AZD9291 (Osimertinib) by promoting apoptosis.

The nano drug delivery system (NDDS) has been extensively investigated for cancer treatment because of its ability to enhance drug efficacy. However, there are only a few studies attempting NDDS for AZD9291 (Osimertinib). Here, we encapsulated AZD9291 in chitooligosaccharides (COS)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles. COS, a cationic polymer, was used to develop positively charged nanoparticles with good biological affinity. The prepared AZD-PLGA-COS NPs exhibited a smaller particle size (176.6 ± 0.4 nm), a positively charged surface (+18.65 ± 0.38 mV), and an increased cellular uptake. The IC50 of H1975 cells was reduced by 45.90%, and the expression of p-EGFR, PARP, Bak, caspase-9, Bax, and Bcl-2 was regulated to promote cellular apoptosis. Furthermore, COS was found to inhibit the expression of immune checkpoint PD-L1. This study suggests that COS-modified PLGA nanoparticles with low toxicity and high encapsulation efficiency (EE) could potentially enhance drug efficacy.

Differentiation capacities of skeletal muscle satellite cells in Lantang and Landrace piglets.

We isolated and cultured satellite cells (SCs) from the longissimus dorsi muscles of 1-day-old male Landrace and Lantang piglets to compare the SC differentiation capacity in the two breeds. Lantang piglets yielded more (P < 0.05) SCs per gram of muscle than Landrace piglets (5.2 ± 0.9×104 vs. 2.4 ± 0.2×104). Transcription of the differentiation markers myogenin and myosin heavy chain I (MyHC I) in the longissimus dorsi muscle was higher in Lantang than Landrace piglets (P < 0.05). Protein levels of myogenin (P < 0.05), MyHC I (P < 0.05), and myogenic regulatory factor 4 (P = 0.07) were higher in Lantang than Landrace piglet SCs after 72 h of differentiation. Creatine kinase activity was higher in Lantang than Landrace piglet SCs after 24, 48, and 72 h of differentiation (P < 0.05), and there was a greater fusion index in Landrace piglet SCs after 72 h of differentiation. In addition, phosphorylation of Akt, mTOR, S6K1, S6, and 4EBP1 was lower in Lantang than Landrace piglet SCs (P < 0.05). Thus differentiation was more extensive in Lantang than Landrace piglet SCs, but expression of the mTOR signaling pathway was lower in Lantang piglet SCs, suggesting mTOR signaling may inhibit myogenic differentiation. These findings reveal that mTOR signaling is a factor in myogenesis and imply that mTOR could potentially serve as an activator of myoblast differentiation and muscle regeneration.