Isolation and microbial transformation of tea sapogenin from seed pomace of Camellia oleifera with anti-inflammatory effects.

In the current study, tea saponin, identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel., was meticulously extracted and hydrolyzed to yield five known sapogenins: 16-O-tiglogycamelliagnin B (a), camelliagnin A (b), 16-O-angeloybarringtogenol C (c), theasapogenol E (d), theasapogenol F (e). Subsequent biotransformation of compound a facilitated the isolation of six novel metabolites (a1-a6). The anti-inflammatory potential of these compounds was assessed using pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns molecules (DAMPs)-mediated cellular inflammation models. Notably, compounds b and a2 demonstrated significant inhibitory effects on both lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1)-induced inflammation, surpassing the efficacy of the standard anti-inflammatory agent, carbenoxolone. Conversely, compounds d, a3, and a6 selectivity targeted endogenous HMGB1-induced inflammation, showcasing a pronounced specificity. These results underscore the therapeutic promise of C. oleifera seed pomace-derived compounds as potent agents for the management of inflammatory diseases triggered by infections and tissue damage.

The combined effect of a novel formula of herbal extracts on bacterial infection and immune response in Micropterus salmoides.

Herbal extracts have been considered as ideal alternative to antibiotics in aquaculture and application of combinatory effective extracts always can exhibit the enhanced bioactivity with high efficiency. In our study, a novel herbal extract combination GF-7, which is composed of Galla Chinensis, Mangosteen Shell extracts as well as the effective parts of Pomegranate peel and Scutellaria baicalensis Georgi extracts, was prepared and applied for the therapy of bacterial infection in aquaculture. The HPLC analysis of GF-7 was also investigated for quality control and chemical identification. In the bioassay, GF-7 had excellent antibacterial activity against various aquatic pathogenic bacteria in vitro, and the related MIC values were between 0.045 and 0.36 mg/mL. After feeding Micropterus salmoide with GF-7 (0.1, 0.3, and 0.6%, respectively) for 28 days, the activities of ACP, AKP, LZM, SOD, and CAT of the liver in each treatment group were significantly increased and the content of MDA was significantly decreased. Meanwhile, the hepatic expression of the immune regulators including IL-1ß, TNF-α, and Myd88 at different times was up-regulated in varying degrees. The challenge results exhibited a good dose-dependent protective effect on M. salmoides infected with A. hydrophila, which was further confirmed by liver histopathology. Our results imply that the novel combination GF-7 is a potential natural medicine for the prevention and treatment of numerous aquatic pathogenic infectious diseases in aquaculture.

Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives to reduce SREBPs expression for the treatment of hyperlipidemia.

Statins play an important role in the treatment of hyperlipidemia, but drug resistance and adverse effects greatly limits their application. To discover new lipid-lowering drugs, three different series of tetrahydroprotoberberine derivatives (THPBs) were designed and synthesized. These compounds were first tested for their effects on viability of HepG2 cells and 21 compounds with the percent of cell viability over 90% were further screened to evaluate their ability to reduce total cholesterol (TC) and triglyceride (TG) levels. Among these derivatives, two compounds displayed significant down-regulation both intracellular of TC and TG content, especially compound 49 exhibited the greatest efficacy. Mechanistically, compound 49 promoted proteasomal degradation of SREBPs. Importantly, compound 49 displayed superior bioavailability (F = 65.1%) and obvious efficacy in the treatment of high fat diet induced obesity in vivo. Therefore, compound 49 is a promising candidate to develop new treatment of hyperlipidemia.

Nandinine, a Derivative of Berberine, Inhibits Inflammation and Reduces Insulin Resistance in Adipocytes via Regulation of AMP-Kinase Activity.

Nandinine is a derivative of berberine that has high efficacy for treating cardiovascular diseases. This study investigated the effects of berberine and nandinine on the regulation of insulin sensitivity in adipocytes. Through treatment with macrophage-derived conditioned medium in 3T3-L1 adipocytes, dysregulation of adipokine production and activation of the IκB kinase ß/nuclear factor-kappa B pathway was induced. However, these phenomena were effectively reversed by berberine, nandinine, and salicylate pretreatments. Furthermore, both berberine and nandinine inhibited serine phosphorylation of insulin receptor substrate-1 induced by IκB kinase ß and increased tyrosine phosphorylation of insulin receptor substrate-1 to activate the PI3K/Akt pathway, which finally led to insulin-mediated glucose uptake. In addition, berberine and nandinine significantly increased AMP-activated protein kinase activity, thereby contributing to their anti-inflammatory effect by inhibiting IκB kinase ß activation. Finally, in vivo studies demonstrated that both berberine (100 or 200 mg/kg) and nandinine (100 or 200 mg/kg) effectively ameliorated glucose intolerance and induced the insulin sensitivity index in mice. In conclusion, berberine and nandinine attenuated insulin resistance in adipocytes by inhibiting inflammation in an AMP-activated protein kinase-dependent manner. Berberine and nandinine may be used as dietary supplements and nandinine is a new candidate for obesity treatment.

Tetrahydroberberrubine attenuates lipopolysaccharide-induced acute lung injury by down-regulating MAPK, AKT, and NF-κB signaling pathways.

Acute lung injury (ALI) is a life-threatening syndrome that is characterized by overwhelming lung inflammation and increased microvascular permeability, which causes a high mortality worldwide. Here, we studied the protective effect of tetrahydroberberrubine (THBru), a berberine derivative, on a mouse model of lipopolysaccharide (LPS)-induced acute lung injury that was established in our previous studies. The results showed that a single oral administration of THBru significantly decreased the lung wet to dry weight (W/D) ratio at doses of 2, 10 and 50mg/kg administered 1h prior to LPS challenge (30mg/kg, intravenous injection). Histopathological changes, such as pulmonary edema, infiltration of inflammatory cells and coagulation, were also attenuated by THBru. In addition, THBru markedly decreased the total cell counts, total protein and nitrate/nitrite content in bronchoalveolar lavage fluid (BALF), significantly decreased tumor necrosis factor-α (TNF-α) and nitrate/nitrite content in the plasma, and reduced the myeloperoxidase (MPO) activity in the lung tissues. Additionally, THBru (10µM) significantly decreased the content of TNF-α and nitric oxide (NO) in LPS-induced THP-1 cells in vitro. Moreover, THBru significantly suppressed the activation of the MAPKs JNK and p38, AKT, and the NF-κB subunit p65 in LPS-induced THP-1 cells. These findings confirm that THBru attenuates LPS-induced acute lung injury by inhibiting the release of inflammatory cytokines and suppressing the activation of MAPKs, AKT, and NF-κB signaling pathways, which implicates it as a potential therapeutic agent for ALI or sepsis.

Diversity synthesis of tetrahydroprotoberberines glycosides by combined chemical and microbial catalysis.

The present study was designed to construct the structurally diverse library of tetrahydroprotoberberines (THPBs) by combining the methods of chemical nonselective demethylation and microbial glycosylation. HPLC-MS/MS analyses tentatively identified 12 de-methylated and 9 glycosylated derivates of THPBs and 5 rarely oxidized glycosides of THPBs in the library. Through this effort, we achieved not only a variety of the THPBs and their glycosides but also tested the catalytic characteristics and capabilities of G. deliquescens NRRL 1086.