Microbial Fermentation Enhances the Effect of Black Tea on Hyperlipidemia by Mediating Bile Acid Metabolism and Remodeling Intestinal Microbes.

Black tea (BT), the most consumed tea worldwide, can alleviate hyperlipidemia which is a serious threat to human health. However, the quality of summer BT is poor. It was improved by microbial fermentation in a previous study, but whether it affects hypolipidemic activity is unknown. Therefore, we compared the hypolipidemic activity of BT and microbially fermented black tea (EFT). The results demonstrated that BT inhibited weight gain and improved lipid and total bile acid (TBA) levels, and microbial fermentation reinforced this activity. Mechanistically, both BT and EFT mediate bile acid circulation to relieve hyperlipidemia. In addition, BT and EFT improve dyslipidemia by modifying the gut microbiota. Specifically, the increase in Lactobacillus johnsonii by BT, and the increase in Mucispirillum and Colidextribacter by EFT may also be potential causes for alleviation of hyperlipidemia. In summary, we demonstrated that microbial fermentation strengthened the hypolipidemic activity of BT and increased the added value of BT.

Effects of fermentation duration on the flavour quality of large leaf black tea based on metabolomics.

Fermentation durations are crucial in determining the quality of black tea flavour. The mechanism underlying the degradation of black tea flavour caused by inappropriate fermentation duration remains unclear. In this study, the taste of black teas with different fermentation durations (BTFs) was analysed using sensory evaluation, electronic tongue, and metabolomics. The results revealed significant differences in 46 flavour profile components within the BTFs. Notably, metabolites such as gallocatechin gallate, gallocatechin, and epigallocatechin were found to be primarily reduced during fermentation, leading to a reduction in the astringency of black tea. Conversely, an increase in d-mandelic acid and guanine among others was observed to enhance the bitter flavour of black tea, while 3-Hydroxy-5-methylphenol nucleotides were found to contribute to sweetness. Furthermore, succinic acid and cyclic-3',5'-adenine nucleotides were associated with diminished freshness. This study offers a theoretical foundation for the regulation of flavour quality in large leaf black tea.

Lentinuses A-B, two alkaloids from the marine-derived fungus Lentinus sajor-caju with potent anti-pulmonary fibrosis activity.

By adding natural amino acids into the medium as sole nitrogen source, twenty-four compounds, including two new alkaloids lentinuses A-B (1-2) with a rare oxazinone core in marine natural products, one new natural product 3-acetamido-4-phenylfurazan (3), 9ß-ergosterol (22) were firstly discovered from a marine fungus, and twenty known compounds (4-21, 23-24) were isolated from the marine-derived fungus Lentinus sajor-caju. The chemical structures of all these compounds were elucidated by HRMS, NMR spectroscopy and X-ray diffraction. Compounds 1-24 were evaluated for their inhibitory activity against TGF-ß1-induced collagen accumulation in human fetal lung fibroblasts (HFL1). Compounds 2, 3, 12, 22, and 23 showed potent activity against TGF-ß1-induced collagen accumulation and low toxicity to HFL1 cells. The binding mode of lentinus B (2) with TGF-ß1 receptor was then performed by using Schrödinger software, and the result showed that lentinus B possesses a strong binding force such as hydrogen bonding and hydrophobic interactions to the protein, which may provide a theoretical basis to design more potent anti-fibrotic drugs in the future.

Nuanxinkang prevents the development of myocardial infarction-induced chronic heart failure by promoting PINK1/Parkin-mediated mitophagy.

BACKGROUND: Mitochondrial dysfunction is an important pathological feature of chronic heart failure (CHF). Regulation of mitophagy can effectively maintain mitochondrial homeostasis and energy metabolism, thereby inhibiting the development of CHF. Nuanxinkang (NXK), a Chinese herbal compound preparation, has significant cardioprotective effects on CHF; however, its underlying mechanism on mitophagy has not been completely clarified. This research intended to investigate the mechanism of NXK in treating myocardial infarction (MI)-induced CHF. METHODS: The left anterior descending coronary artery (LAD) ligation surgery was performed to establish an MI-induced CHF model in male C57BL/6 mice. From 1 day after surgery, mice were given NXK (0.41, 0.82 or 1.65 g/kg/d), Perindopril (PDPL, 0.607 mg/kg/d), or an equivalent amount of sterile water by gavage for 28 continuous days. Then, mice were examined for cardiac function, myocardial fibrosis, cardiomyocyte apoptosis, mitochondrial structure and mitophagy levels of cardiomyocytes, etc. In addition, a hypoxic injury model was created using HL-1 cardiomyocytes from wild-type (WT) mice. HL-1 cells were pretreated with or without NXK-containing serum. Mitochondrial function and mitophagy levels were examined in HL-1 cells. RESULTS: In MI-induced CHF mice, cardiac dysfunction, severe cardiac remodeling, elevated levels of oxidative stress, reduced ATP levels, and inhibition of PINK1/Parkin-mediated mitophagy were observed. High-dose NXK treatment (1.65 g/kg/d) significantly improved myocardial energy metabolism, inhibited cardiac remodeling, improved cardiac function, and restored cardiac PINK1/Parkin-mediated mitophagy levels to some extent in MI mice. In vitro, elevated levels of mitochondrial reactive oxygen species (ROS) with impaired mitochondrial membrane potential (ΔΨm) were observed in hypoxic HL-1 cells. While NXK treatment significantly protected cardiomyocytes from hypoxia-induced mitochondrial dysfunction, which is consistent with the in vivo results. Further studies showed that NXK could increase PINK1/Parkin-mediated mitophagy levels in cardiomyocytes, which could be blocked by the mitophagy inhibitor Mdivi-1. CONCLUSION: In conclusion, NXK could prevent cardiac mitochondrial dysfunction and improve cardiac function against MI-induced CHF by promoting Pink1/Parkin-mediated mitophagy, which represents a very prospective strategy for the treatment of CHF.

Huang-Qi San ameliorates hyperlipidemia with obesity rats via activating brown adipocytes and converting white adipocytes into brown-like adipocytes.

BACKGROUND: Brown adipose tissue (BAT) activation is a promising therapeutic target to treat hyperlipidemia with obesity. Huang-Qi San (HQS), an traditional Chinese medicine, can ameliorate hyperlipidemia with obesity, but its mechanism of action (MOA) is not understood. PURPOSE: To articulate the MOA for HQS with animal models. METHODS: The main chemical constituents of HQS were identified by high-performance liquid chromatography (HPLC) based assay. Hyperlipidemia with obesity rat models induced by high-fat diet were employed in the study. The levels of the fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were measured to evaluate the ability of HQS to ameliorate hyperlipidemia with obesity. Pathological analyses of organs were conducted with Oil Red O staining, hematoxylin-eosin (H&E) staining and transmission electron microscopy. The expression of mRNAs related to thermogenic genes, fatty acid oxidation-related genes and mitochondria biogenic genes were examined by quantitative real-time PCR. The protein expressions of uncoupling protein 1 (UCP1) were investigated by immunohistochemistry and western blot. Simultaneously, the protein expression of PR domain containing 16 (PRDM16), ATP synthase F1 subunit alpha (ATP5A) was detected by western blot. RESULTS: HQS ameliorates metabolic disorder, lipid ectopic deposition, obesity and maintained glucose homeostasis in hyperlipidemia with obesity rats. HQS can significantly increase the number of mitochondria and reduced the size of the intracellular lipid droplets in BAT, and increase the expression of BAT activation-related genes (UCP1, PGC1α, PGC1ß, Prdm16, CD137, TBX1, CPT1a, PPARα, Tfam, NRF1 and NRF2) in vivo. Furthermore, UCP1, PRDM16 and ATP5A proteins of BAT were increased. CONCLUSION: HQS can activate BAT and browning of S-WAT (subcutaneous white adipose tissue) through activating the PRDM16/PGC1α/UCP1 pathway, augmenting mitochondrial biogenesis and fatty acid oxidation to increase thermogenesis and energy expenditure, resulting in a significant amelioration of hyperlipidemia with obesity. Therefore, HQS is an effective therapeutic medicine for the treatment of hyperlipidemia with obesity.

[Effect of Huangqi San on AMPK/ACC/CPT1 pathway in hyperlipidemia rats].

To investigate the mechanism of the treatment of hyperlipidemia rats induced by Huangqi San. The 40 male SD rats were randomly divided into normal group, model group, Huangqi San low and high dose group (1, 2 g·kg⁻¹), and positive lipitor group (2 mg·kg⁻¹). The normal group feeds on base feed, and other groups feed on high-fat feed. After 8 weeks, the hyperlipidemia model was successful. After intervention by drugs for 13 weeks, fasting blood glucose, total cholesterol, triglycerides and LDL cholesterol content of all rats were measured. The pathological changes of liver and skeletal muscle of rats were observed in rats. Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of AMPK signaling pathway in the liver and skeletal muscles (AMPK, ACC, CPT1A, SREBP2, HMGCR). The degree of FPG, TC, TG and LDL-C were the highest in the model group, and the liver and skeletal muscle pathology were the most obvious. After intervention by Huangqi San and lipitor, a significant reduction in the blood sugar blood fat, liver, and skeletal muscle injury has improved significantly, except SREBF2 and HMGCR mRNA and protein expression of this enzyme is reduced, other AMPK pathway related mRNA and protein expression increased significantly. Huangqi San effect is superior to lipitor. Huangqi San may improve hyperlipidemia by regulating the AMPK signaling pathway, increasing the oxidation of fatty acids and inhibiting cholesterol synthesis.

The design and synthesis of a novel compound of berberine and baicalein that inhibits the efficacy of lipid accumulation in 3T3-L1 adipocytes.

The combination of berberine and baicalein may have a better therapeutic effect against disease. To explore the combined effect of baicalein and berberine in the treatment of obesity, we designed and synthesized a hybrid compound, and its biological activities were evaluated in 3T3-L1 adipocytes. The structures of the berberine-baicalein (BBS) compounds were confirmed by 1H NMR, 13C NMR, ultraviolet spectroscopy and high resolution mass spectrometry (HRMS). The present study showed that the IC50 values of the inhibitory effects of baicalein, berberine and BBS against 3T3-L1 cells were 29.81±0.90, 21.84±1.67 and 9.42±0.60µM, respectively. The expression of mRNAs related to lipolysis and lipogenesis were examined by quantitative real-time PCR. The results showed that BBS could up-regulate the expression of the Atgl gene and down-regulate the mRNA expression of Srebp-1c, Fasn, Scd1, and Acc in 3T3-L1 adipocytes. These results indicate that BBS may have a stronger effect than baicalein and berberine on the viability of 3T3-L1 preadipocytes. In addition, BBS may have therapeutic effects and pharmacological activities against obesity. This "medicine couple" may be beneficial for studies of traditional Chinese medicine.