Effects of Shenling Baizhu powder on intestinal microflora metabolites and liver mitochondrial energy metabolism in nonalcoholic fatty liver mice.

Background & purpose: Non-alcoholic fatty liver disease (NAFLD) is characterised by the excessive accumulation of triglycerides in the liver. Shenling Baizhu powder (SLBZP) is formulated from various natural medicinal plants that protect the liver and are used to treat intestinal diseases. SLBZP improves the symptoms of NAFLD. However, its mechanism of action remains unclear. Herein, we investigated the ameliorative effect of SLBZP on model mice with high-fat-diet (HFD)-induced NAFLD. Additionally, we evaluated the impact of SLBZP on the intestinal flora and its metabolites and mitochondrial energy metabolism in NAFLD. Methods: We used HFD to establish a mouse model of NAFLD. Different drug interventions were administered. We measured serum biochemical indices. Liver sections were visualised with hematoxylin-eosin and oil red O staining. 16S rDNA amplicon sequencing technology was used to analyse the diversity and abundance of the intestinal flora. Short-chain fatty acids (SCFAs) in the intestinal contents were detected using GC-MS. Liver tissue was sampled to detect mitochondrial membrane functional indices. Western blotting was used to determine the levels of mitochondrial pathway-related proteins, namely, uncoupling protein 2 (UCP2), adenosine monophosphate-activated protein kinase (AMPK) and inhibitory factor 1 (IF1) of F1Fo ATP synthesis/hydrolase, in the liver. Results: The spleen-invigorating classic recipe of SLBZP reduced liver lipid deposition in mice with HFD-induced NAFLD. Additionally, SCFAs produced by intestinal flora metabolism regulated the UCP2/AMPK/IF1 signalling pathway involved in liver mitochondrial energy metabolism to improve the liver mitochondrial membrane permeability, respiratory state and oxidative phosphorylation efficiency of mice with NAFLD. Finally, SLBZP increased the liver ATP level. Conclusion: Our results suggest that the therapeutic effect of SLBZP on NAFLD is related to the regulation of hepatic mitochondrial energy metabolism by intestinal flora and its metabolites and is possibly associated with the UCP2/AMPK/IF1 signalling pathway.

A multifunctional nanocomposite coated with a BSA membrane for cascaded nitric oxide therapy.

Gas therapy based on nitric oxide (NO) has emerged as a potential therapeutic approach for cancer, and in conjunction with multi-mode combination therapy, offers new possibilities for achieving significant hyperadditive effects. In this study, an integrated AI-MPDA@BSA nanocomposite for diagnosis and treatment was constructed for PDA based photoacoustic imaging (PAI) and cascade NO release. Natural NO donor L-arginine (L-Arg) and photosensitizer (PS) IR780 were loaded into mesoporous polydopamine (MPDA). Bovine serum albumin (BSA) was conjugated to the MPDA to increase the dispersibility and biocompatibility of the nanoparticles, as well as to serve as a gatekeeper controlling IR780 release from the MPDA pores. The AI-MPDA@BSA produced singlet oxygen (1O2) and converted it into NO through a chain reaction based on L-Arg, enabling a combination of photodynamic therapy and gas therapy. Moreover, due to the photothermal properties of MPDA, the AI-MPDA@BSA performed good photothermal conversion, which allowed photoacoustic imaging. As expected, both in vitro and in vivo studies have confirmed that the AI-MPDA@BSA nanoplatform has a significant inhibitory effect on cancer cells and tumors, and no apparent systemic toxicity or side effects were detected during the treatment period.

[Advances in traditional Chinese medicine treatment of non-alcoholic fatty liver disease via farnesoid X receptor].

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.

[Prevention and treatment of non-alcoholic fatty liver disease by regulation of mitochondrial function with Chinese medicine].

Non-alcoholic fatty liver disease(NAFLD), as a metabolic stress liver injury disease, is one of the most common chronic liver diseases, which seriously threatens people's health. The pathogenesis of NAFLD is very complex. A large number of studies show that the hepatic mitochondrial dysfunction leads to the disorder of hepatic glucose and lipid metabolism, oxidative stress, and inflammation, thus inducing hepatocyte apoptosis, which plays an important role in the progression of NAFLD. In recent years, researchers have begun to focus on developing drugs that slowed the progression of NAFLD by regulating the hepatic mitochondrial function. Chinese medicine has a good curative effect on the treatment of NAFLD, with the advantages of high safety and few side effects. Various studies have shown that Chinese medicine prevented and treated NAFLD by regulating the mitochondrial function. Therefore, this paper summarized the relationship between NAFLD and mitochondria, and the mechanism of Chinese medicine(single Chinese medicine, Chinese medicine monomer, and Chinese medicine compound prescription) in the prevention and treatment of NAFLD by regulating mitochondrial function. This paper is expected to provide references for clinical application of traditional Chinese medicine in the treatment of NAFLD by regulating mitochondrial function.

Literature Review on the Use of Herbal Extracts in the Treatment of Non- Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease is a common chronic liver injury disease, and its incidence is rapidly increasing across the globe, thus becoming a serious threat to human health. So far, the clinical prevention and treatment of non-alcoholic fatty liver disease mainly include single-targeted drug therapy, surgical treatment and lifestyle changes. However, these treatments cannot completely address the complex pathogenesis of non-alcoholic fatty liver disease and have various side effects. Recent studies reveal that many herbal extracts are found to have potential anti-non-alcoholic fatty liver disease activities. OBJECTIVE: This paper presents a review on herbal extracts used for the treatment of non-alcoholic fatty liver disease in experimental studies to provide a theoretical basis for their clinical application in the treatment of non-alcoholic fatty liver disease and for new drug development. METHODS: Scientific papers were retrieved by searching the PubMed database up to Feb 2021 using the following keywords: 'non-alcoholic fatty liver disease', 'herbal extracts' ('flavonoids', 'saponins', 'quinones', 'phenolic compounds', 'alkaloids', 'polysaccharides', 'ginkgolide B', 'schizandrin B', 'ursolic acid') and 'mechanism'. RESULTS: The pharmacological effects and mechanisms of many herbal extracts can reverse the adverse health effects of non-alcoholic fatty liver disease. CONCLUSION: In vitro and in vivo experimental studies indicated that herbal extracts can improve the symptoms of non-alcoholic fatty liver disease by inhibiting inflammation, antioxidant stress, improvement of lipid metabolism and insulin sensitivity and regulating intestinal bacteria flora. However, there needs to be sufficient data from human clinical trials to prove their efficacy and safety.

Nanoparticles prepared from pterostilbene reduce blood glucose and improve diabetes complications.

BACKGROUND: Diabetes complications are the leading cause of mortality in diabetic patients. The common complications are decline in antioxidant capacity and the onset of micro-inflammation syndrome. At present, glucose-responsive nanoparticles are widely used, as they can release insulin-loaded ultrafine particles intelligently and effectively reduce blood sugar. However, the toxicology of this method has not been fully elucidated. The plant extracts of pterostilbene (PTE) have a wide range of biological applications, such as antioxidation and inflammatory response improvement. Therefore, we have proposed new ideas for the cross application of plant extracts and biomaterials, especially as part of a hypoglycaemic nano-drug delivery system. RESULTS: Based on the PTE, we successfully synthesised poly(3-acrylamidophenyl boric acid-b-pterostilbene) (p[AAPBA-b-PTE]) nanoparticles (NPs). The NPs were round in shape and ranged between 150 and 250 nm in size. The NPs possessed good pH and glucose sensitivity. The entrapment efficiency (EE) of insulin-loaded NPs was approximately 56%, and the drug loading (LC) capacity was approximately 13%. The highest release of insulin was 70%, and the highest release of PTE was 85%. Meanwhile, the insulin could undergo self-regulation according to changes in the glucose concentration, thus achieving an effective, sustained release. Both in vivo and in vitro experiments showed that the NPs were safe and nontoxic. Under normal physiological conditions, NPs were completely degraded within 40 days. Fourteen days after mice were injected with p(AAPBA-b-PTE) NPs, there were no obvious abnormalities in the heart, liver, spleen, lung, or kidney. Moreover, NPs effectively reduced blood glucose, improved antioxidant capacity and reversed micro-inflammation in mice. CONCLUSIONS: p(AAPBA-b-PTE) NPs were successfully prepared using PTE as raw material and effectively reduced blood glucose, improved antioxidant capacity and reduced the inflammatory response. This novel preparation can enable new combinations of plant extracts and biomaterials to adiministered through NPs or other dosage forms in order to regulate and treat diseases.