Hybrid adipocyte-derived exosome nano platform for potent chemo-phototherapy in targeted hepatocellular carcinoma.

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.

Material basis research for Echinacea purpurea (L.) Moench against hepatocellular carcinoma in a mouse model through integration of metabonomics and molecular docking.

BACKGROUND: Echinacea purpurea (L.) Moench (EP), a well-known "immunostimulant" in the West, is one of the most popular botanicals for patients with cancer. It has been proved to be effective against hepatocellular carcinoma (HCC), while the active ingredients remains unclear. PURPOSE: This study aimed to investigate the inhibitory effect and interpret the material basis of EP against HCC through metabolomics and molecular docking. METHODS: Tumor growth, biochemical analysis and pathological changes were detected in HCC-induced mice to evaluate the efficacy of EP. An integrative method combining molecular docking and LC-MS-based metabolomics was performed to evaluate the inhibitory role and screen the material basis of EP against HCC. RESULTS: EP significantly suppressed tumor growth and decreased the levels of AFP. Histological analysis showed that wide areas of necrosis in the EP-treated tumors that were almost absent in those in model group. Serum metabolomics results revealed EP could significantly improve 12 serum different metabolites induced by HCC, which were involved into phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism. Then, 5 related genes were selected out to be the key targets of EP against HCC based on Metscape. 22 identified compounds were docked through Sybyl-X. The herb-compound-gene-metabolic pathways network (HCGMN) was constructed to reveal the associations between EP and HCC. Finally, 19 compounds were screened as promising active ingredients of EP against HCC. CONCLUSION: The results showed that the approach integrating of metabonomics and molecular docking is a powerful strategy to obtain the active ingredients from plants.

Echinacea purpurea suppresses the cell survival and metastasis of hepatocellular carcinoma through regulating the PI3K/Akt pathway.

Echinacea purpurea (L.) Moench (Ep) is widely used as a kind of dietary supplements, and possesses various pharmacological activities, including immunomodulatory, anti-inflammatory, antitumor effects. However, the inhibitory effects of Ep on the growth and metastasis of hepatocellular carcinoma (HCC) is unclear. Here, the preventive effect and potential mechanism of Ep on HCC was elucidated by systems pharmacology and molecular docking. The results showed that Ep could significantly ameliorate HCC-induced tumor growth and migration in vivo and in vitro. System pharmacology results indicated that 180 genes associated with HCC were regarded as the potential therapeutic targets of Ep, mainly involved in metabolic pathways, cancer pathways, proteoglycans in cancer and PI3K/Akt signaling pathway, which might be a crucial pathway in HCC EMT. A herb-component-target-pathway network was constructed to reveal the interactions between Ep and HCC. Finally, predicted PI3K/Akt pathway was further validated by molecular docking and western blot experiment. This study showed that Ep ameliorates HCC-induced tumor cell survival and migration in mice via the regulation of the PI3K/Akt pathway. Thus, Ep might be a potential new strategy to prevent the growth and metastasis of HCC.

Echinacea in hepatopathy: A review of its phytochemistry, pharmacology, and safety.

BACKGROUND: Echinacea, one of the most popular herbs with double function of immunity and anti-inflammatory activity, has now attracted much interest for a possible alternative for the treatment of hepatopathy. This review is aimed at providing a comprehensive overview of Echinacea regarding its chemical composition, pharmacological action against various hepatopathy, and safety. METHODS: A comprehensive search of published articles was conducted to focus on original publications related to Echinacea and hepatopathy till the end of 2020 using various literature databases, including China National Knowledge Infrastructure, PubMed, and Web of Science database. RESULTS: Echinacea exhibited excellent activities in resisting a variety of hepatopathy induced by different causes in preclinical experiments and clinical trials by regulating cell proliferation and apoptosis, antioxidant defense mechanism, voltage-gated sodium channels, lipid metabolism, circadian rhythm, p38 MAPK signaling pathway, JNK signaling pathway, Nrf2/HO-1 signaling pathway, PI3K/AKT signaling pathway, and Akt/GSK3 beta signaling pathways. The high efficacy of Echinacea is related to its immunomodulatory and anti-inflammatory activities. The main ingredients of Echinacea include caffeic acid derivatives, alkylamides, and polysaccharides, which have been well established in preclinical studies of liver diseases. Studies on acute and subacute toxicity show that Echinacea preparations are well-tolerated herbal medicines. CONCLUSION: Echinacea may offer a novel potential strategy for clinical prevention and treatment of liver diseases and related diseases. Extensive studies are necessary to identify the underlying mechanisms and establish future therapeutic potentials of this herb. Well-designed clinical trials are still warranted to confirm the safety and effectiveness of Echinacea for hepatopathy.

Anti-fatigue effect of Lepidium meyenii Walp. (Maca) on preventing mitochondria-mediated muscle damage and oxidative stress in vivo and vitro.

Maca (Lepidium meyenii Walp.) has emerged as a popular functional plant food due to its various pharmacological properties, including anti-oxidation, anti-inflammation and anti-fatigue activity. In this study, we investigated the role of Maca aqueous extract (ME) on muscle during exercise-induced fatigue both in vivo and in vitro. As a result, ME significantly enhanced mouse leg grip-strength and increased exercise endurance in the rota-rod test. ME could clear the accumulation of metabolites - blood lactic acid (BLA), blood urea nitrogen (BUN) and reactive oxygen species (ROS) levels after weight-loaded forced swimming. Focusing on muscle, we found that the administration of ME strengthened mouse muscle structures so that exercise-induced metabolic stress was alleviated by upregulating NAD+/NADH. Furthermore, ME inhibited the reduction of the viability and accumulation of ROS by treatment with H2O2 in C2C12 skeletal muscle cells. ME-induced activation of energy metabolism in skeletal muscle might up-regulate mitochondrial biogenesis and function, thereby protecting against oxidative stress-induced damage. We concluded that the effects of Maca played a crucial role in the regulation of exercise-induced fatigue in mouse muscle, which could be expected to serve as a functional food supplement for improving exercise performance and alleviating physical fatigue.

Network pharmacology research of Astragali Radix in treating chronic atrophic gastritis rats based on mitochondrial metabonomics.

Astragali Radix (HuangQi), one important traditional Chinese herb, is used for treatment of chronic atrophic gastritis (CAG). To comprehensively evaluate its regulation on CAG, a mitochondria-specific metabonomics was applied to reveal its action on energy metabolism based on ultra high performance liquid chromatography coupled with quadrupole - Exactive mass spectrometry. 16 related metabolites from mitochondria samples were served as potential biomarkers of CAG. Nine out of them were significantly regulated by HuangQi. Combining with network pharmacology, three active components from HuangQi and 3 mitochondrial metabolites exerted better docking abilities with 56 predicted targeted proteins based on SystemsDock, which were involved into multiple biological abnormities including mitochondrion dysfunction. The results demonstrated that mitochondrial energy metabolism played crucial role contributing to HuangQi against CAG, which was one important mechanism of HuangQi.

Evaluations of the effect of HuangQi against heart failure based on comprehensive echocardiography index and metabonomics.

BACKGROUND: HuangQi (HQ) is a major medicinal herb commonly used as an ingredient of traditional Chinese medicine (TCM) formulas. It has been proved to be effective against heart failure (HF). However, its holistic therapeutic mechanism is not yet well explored. PURPOSE: The present study was designed to investigate the inhibitory effects and action mechanism of HQ in adriamycin (ADR)-induced HF rats. METHODS: An integrative approach combining comprehensive echocardiography index (CEI) and metabonomics was conducted to assess the integral efficacy of HQ against HF. CEI was constructed to comprehensively evaluate the protection of HQ through principal component analysis of eight echocardiography parameters. Meanwhile, NMR-based untargeted metabolomic studies were performed to investigate the regulative effects of HQ coupled with correlation analysis. RESULTS: HQ showed significant regulatory effects on four echocardiography parameters (left ventricular diastolic diameter, left ventricular systolic wall thickness, ejection fraction and fractional shortening). The effect on comprehensive CEI also demonstrated the efficacy of HQ against HF, especially on the first principal component (PC1). HQ could exert marked metabolic regulations on five key metabolites related to HF (NAG, 3-hydroxybutyrate, glutamine, succinate and acetoacetate), which were mainly involved into alterations of energy metabolism, oxidative stress, hypertrophy, as well as inflammatory. Their correlation analysis revealed the relationship between the metabolic profiles and cardiac function, which further authenticated the systemic regulation of HQ against HF. CONCLUSION: Current evidences revealed that HQ was effective in control of HF from cardiac dysfunction and metabolic alterations. This study provided a useful approach for evaluating the efficacy of TCMs against HF.

Material basis research for Huangqi Jianzhong Tang against chronic atrophic gastritis rats through integration of urinary metabonomics and SystemsDock.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Jianzhong Tang (HQJZ), a celebrated traditional Chinese medicine (TCM), is commonly used for treatment of chronic atrophic gastritis (CAG) in China. AIM OF THE STUDY: We aimed to screen out the material basis of HQJZ against CAG. MATERIALS AND METHODS: CAG rat model was constructed by alternant administrations of ammonia solution and sodium deoxycholate, and the hunger disorder method. Body weight, biochemical indexes and histopathological exam were used to evaluate the efficacy of HQJZ. 1H NMR-based metabonomics was employed to analyze the urine metabolic features of HQJZ deviated from CAG rats. SystemsDock analysis was utilized to explore the active compounds involved into the efficacy of HQJZ against CAG based on the targeted metabolic biomarkers. RESULTS: The metabonomic results indicated that HQJZ could significantly improve 16 urinary perturbed metabolites in CAG rats, which were involved into the metabolism of energy and amino acids. And then 28 related proteins and genes were selected out to be the potential targets of HQJZ against CAG based on the six key metabolites closely correlating with biochemical indexes (α-ketoglutarate, valine, sarcosine, glycine, malonate and fumarate). 71 previous identified compounds were docked through systemsDock-aided molecular docking experiments. And the constructed herb-component-protein-metabolite interaction network (HCPMN) revealed the associations between the herbal formulae and CAG. At last, 51 compounds of them were screened as promising active constitutes for the inhibition of CAG, which could act on various targeted proteins. CONCLUSIONS: he results showed that the approach integrating of metabonomics and systemsDock is a powerful tool to obtain the material basis and regulatory mechanism of TCM formula.

Formation of crystalline Zn-Al layered double hydroxide precipitates on γ-alumina: the role of mineral dissolution.

To better understand the sequestration of toxic metals such as nickel (Ni), zinc (Zn), and cobalt (Co) as layered double hydroxide (LDH) phases in soils, we systematically examined the presence of Al and the role of mineral dissolution during Zn sorption/precipitation on γ-Al(2)O(3) (γ-alumina) at pH 7.5 using extended X-ray absorption fine structure spectroscopy (EXAFS), high-resolution transmission electron microscopy (HR-TEM), synchrotron-radiation powder X-ray diffraction (SR-XRD), and (27)Al solid-state NMR. The EXAFS analysis indicates the formation of Zn-Al LDH precipitates at Zn concentration ≥0.4 mM, and both HR-TEM and SR-XRD reveal that these precipitates are crystalline. These precipitates yield a small shoulder at δ(Al-27) = +12.5 ppm in the (27)Al solid-state NMR spectra, consistent with the mixed octahedral Al/Zn chemical environment in typical Zn-Al LDHs. The NMR analysis provides direct evidence for the existence of Al in the precipitates and the migration from the dissolution of γ-alumina substrate. To further address this issue, we compared the Zn sorption mechanism on a series of Al (hydr)oxides with similar chemical composition but differing dissolubility using EXAFS and TEM. These results suggest that, under the same experimental conditions, Zn-Al LDH precipitates formed on γ-alumina and corundum but not on less soluble minerals such as bayerite, boehmite, and gibbsite, which point outs that substrate mineral surface dissolution plays an important role in the formation of Zn-Al LDH precipitates.