The Ethyl Acetate Extract of Phyllanthus emblica L. Alleviates Diabetic Nephropathy in a Murine Model of Diabetes.

Oil-Gan is the fruit of the genus Phyllanthus emblica L. The fruits have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN throughout the disease course. The primary aim of this study was to examine the protective effects (including analyses of urine and blood, and inflammatory cytokine levels) and mechanisms of the ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy; the secondary aim was to examine the expression levels of p- protein kinase Cα (PKCα)/t-PKCα in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-ß1 (TGF-ß1) by Western blot analyses. Eight db/m mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included a vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. The administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing 3 (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. A histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-ß1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.

Phytochemical Constituent Analysis of Phyllanthus emblica L. Fruit Nanoherbals by LC-HRMS and Their Antimutagenic Activity and Teratogenic Effects.

Pregnant women must be wary of using traditional medicines due to the possibility of their having oxytoxic effects. Indonesia is rich in plants containing antioxidants. One of these plants is Phyllanthus emblica L. This study aims to determine the phytochemical constituents of Phyllanthus emblica L. fruit nanoherbals by LC-HRMS analysis and their antimutagenic activity and teratogenic effects. The study commenced by producing nanoherbal extracts from P. emblica fruit. The phytochemical composition of these extracts was then analyzed using LC-HRMS. The nanoherbal extracts were also tested for their ability to prevent mutations, as indicated by a reduction in micronuclei observed in mouse femur bone marrow smear preparations. The teratogenicity test involved administering the P. emblica fruit nanoherbal at 100, 500, and 1000 mg/kg BW doses. The data were analyzed using SPSS. The phytochemical constituents of the P. emblica fruit nanoherbal include flavonoids, phenols, vitamins, and alkaloids. The P. emblica fruit nanoherbal exhibits antimutagenic activity, as evidenced by a statistical analysis that indicated a significant decrease in the quantity of micronuclei per 200 PCE compared to the negative control (p < 0.05). The administration of the P. emblica fruit nanoherbal at a dosage of 1000 mg/kg BW resulted in a teratogenic impact during the organogenesis stage, as shown by hemorrhage and anomalies in the sternum.

Effects of Ultra-High-Pressure Treatment on Chemical Composition and Biological Activities of Free, Esterified and Bound Phenolics from Phyllanthus emblica L. Fruits.

Phyllanthus emblica L. fruits (PEFs) were processed by ultra-pressure (UHP) treatment and then extracted by the ultrasonic-assisted extraction method. The influence of UHP on the phenolic composition, enzyme inhibitory activity and antioxidant activity of the free, esterified, and bound phenolic fractions from PEFs were compared. UHP pretreatment of PEFs significantly increased the total phenolic and flavonoid contents (p < 0.05). A total of 24 chemical compositions were characterized in normal and UHP-treated PEFs by UHPLC-ESI-HRMS/MS. Compared with normal PEFs, these three different phenolic fractions had stronger antioxidant activities and inhibitory effects on the intracellular reactive oxygen species (ROS) production in H2O2-induced HepG2 cells (p < 0.05). The ROS inhibition might be due to an up-regulation of the expressions of superoxide dismutase (SOD) and glutathione (GSH) activities. In addition, these three different phenolic fractions also significantly inhibited the activities of metabolic enzymes, including α-glucosidase, α-amylase and pancreatic lipase. This work may provide some insights into the potential economics and applications of PEFs in food and nutraceutical industries.

Characterization and metabolomic profiling of two pigment producing fungi from infected fruits of Indian Gooseberry.

Two pigment producing fungi, Talaromyces atroroseus and Penicillium choerospondiatis, were isolated and identified from infected fruits of Phyllanthus emblica L. based on amplification and sequencing of internal transcribed spacer region and beta-tubulin gene. This is the first occurrence report of these two fungi from fruits of P. emblica. Culture extract containing metabolites of T. atroroseus and P. choerospondiatis contained phenolics of 26.35 mg and 30.89 mg GAE/g dry extract respectively; whereas no significant amount of flavonoids and tannins were detected. P. choerospondiatis metabolites extract showed higher DPPH and ABTS activity with IC50 values of 21.94 mg/ml and 27.03 mg/ml respectively than T. atroroseus. LC-HRMS analysis of metabolites extract of T. atroroseus revealed presence of trimethyl-isopropyl-butanamide, perlolyrine, N-hexadecanoylpyrrolidine etc. whereas P. choerospondiatis displayed presence of tangeraxanthin, ugaxanthone, daphniphylline, etc. Therefore, fungal metabolites are rich natural sources of diversified compounds that can be utilized in dyeing industries, cosmetics and novel drug development.

Antidiabetic and Immunoregulatory Activities of Extract of Phyllanthus emblica L. in NOD with Spontaneous and Cyclophosphamide-Accelerated Diabetic Mice.

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits are high in nutrients and display excellent health care functions and development values. The primary aim of this study was to investigate the activities of ethyl acetate extract from Phyllanthus emblica L. (EPE) on type 1 diabetes mellitus (T1D) and immunoregulatory activities in non-obese diabetes (NOD) mice with spontaneous and cyclophosphamide (Cyp)-accelerated diabetes. EPE was vehicle-administered to spontaneous NOD (S-NOD) mice or Cyp-accelerated NOD (Cyp-NOD) mice once daily at a dose of 400 mg/kg body weight for 15 or 4 weeks, respectively. At the end, blood samples were collected for biological analyses, organ tissues were dissected for analyses of histology and immunofluorescence (IF) staining (including expressions of Bcl and Bax), the expression levels of targeted genes by Western blotting and forkhead box P3 (Foxp3), and helper T lymphocyte 1 (Th1)/Th2/Th17/Treg regulatory T cell (Treg) cell distribution by flow cytometry. Our results showed that EPE-treated NOD mice or Cyp-accelerated NOD mice display a decrease in levels of blood glucose and HbA1c, but an increase in blood insulin levels. EPE treatment decreased blood levels of IFN-γ and tumor necrosis α (TNF-α) by Th1 cells, and reduced interleukin (IL)-1ß and IL-6 by Th17 cells, but increased IL-4, IL-10, and transforming growth factor-ß1 (TGF-ß1) by Th2 cells in both of the two mice models by enzyme-linked immunosorbent assay (ELISA) analysis. Flow cytometric data showed that EPE-treated Cyp-NOD mice had decreased the CD4+ subsets T cell distribution of CD4+IL-17 and CD4+ interferon gamma (IFN-γ), but increased the CD4+ subsets T cell distribution of CD4+IL-4 and CD4+Foxp3. Furthermore, EPE-treated Cyp-NOD mice had decreased the percentage per 10,000 cells of CD4+IL-17 and CD4+IFNγ, and increased CD4+IL-4 and CD4+Foxp3 compared with the Cyp-NOD Con group (p < 0.001, p < 0.05, p < 0.05, and p < 0.05, respectively). For target gene expression levels in the pancreas, EPE-treated mice had reduced expression levels of inflammatory cytokines, including IFN-γ and TNF-α by Th1 cells, but increased expression levels of IL-4, IL-10, and TGF-1ß by Th2 cells in both two mice models. Histological examination of the pancreas revealed that EPE-treated mice had not only increased pancreatic insulin-expressing ß cells (brown), and but also enhanced the percentage of Bcl-2 (green)/Bax (red) by IF staining analyses of islets compared with the S-NOD Con and the Cyp-NOD Con mice, implying that EPE displayed the protective effects of pancreas ß cells. EPE-treated mice showed an increase in the average immunoreactive system (IRS) score on insulin within the pancreas, and an enhancement in the numbers of the pancreatic islets. EPE displayed an improvement in the pancreas IRS scores and a decrease in proinflammatory cytokines. Moreover, EPE exerted blood-glucose-lowering effects by regulating IL-17 expressions. Collectively, these results implied that EPE inhibits the development of autoimmune diabetes by regulating cytokine expression. Our results demonstrated that EPE has a therapeutic potential in the preventive effects of T1D and immunoregulation as a supplementary.

Phyllanthi Tannin Loaded Solid Lipid Nanoparticles for Lung Cancer Therapy: Preparation, Characterization, Pharmacodynamics and Safety Evaluation.

The objective of the present study was to develop PTF-loaded solid lipid nanoparticles (PTF-SLNs) and investigate their efficacy in treating lung cancer. The PTF-SLNs were prepared by the thin film hydration method and verified by FTIR and TEM. Their physicochemical properties were characterized by particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), drug loading (DL), etc. Then, the pharmacodynamic studies of PTF-SLNs were performed on Lewis lung cancer cells and tumor-bearing mice. Finally, the safety studies were assessed by organ index, serum biochemical indicators, and histopathological changes. The PTF-SLNs were characterized by around 50 nm sphere nanoparticles, sustained ideal stability, and controlled drug release effects. The pharmacodynamic evaluation results showed that PTF-SLNs had stronger anti-tumor efficacy than PTF. An in vitro study revealed a more obvious cytotoxicity and apoptosis effect. The IC 50 values of PTF and PTF-SLNs were 67.43 µg/mL and 20.74 µg/mL, respectively. An in vivo study showed that the tumor inhibition rates of 2 g/kg PTF and 0.4 g/kg PTF-SLNs were 59.97% and 64.55%, respectively. The safety preliminary study indicated that PTF-SLNs improve the damage of PTF to normal organs to a certain extent. This study provides a nanoparticle delivery system with phenolic herbal extract to improve anti-tumor efficacy in lung cancer.

Functional nutrition as integrated approach in vitiligo management.

Vitiligo is a common disease of unknown cause that produces disfiguring white patches of depigmentation that can be treated using various new and experimental therapies, such as narrow-band ultraviolet B (NB-UVB) microphototherapy, NB-UVB excimer laser, and monochromatic excimer light. Medical treatments include topical corticosteroids and other topical treatments, such as antioxidants, tacrolimus and pimecrolimus, prostaglandin E, and vitamin D derivatives (Lotti, Berti, & Moretti, 2009). The goal of treating vitiligo is to make it less noticeable either by restoring lost pigment or by eliminating remaining pigment. Functional foods and healthy diet, with nutrients, form a variety of sources, could be considered an integral part, as well as helpful, of vitiligo's medical therapy.

Ultrasound-assisted extraction of phenolic compounds from Phyllanthus emblica L. and evaluation of antioxidant activities.

OBJECTIVE: The objective of this study was to optimize ultrasound-assisted extraction of phenolic compounds from Phyllanthus emblica. METHODS: Extracts obtained by UAE were evaluated for their antioxidant activities. Extraction experiments were carried out with three factors and three levels namely extraction time (varying from 15 to 60 min), ethanol concentration (varying from 50 to 90%) and frequency (varying from 28 to 56 kHz). RESULTS: The results showed that the UAE optimal conditions of extracting total phenol components were as follows: 15 min of extraction time, 60°C of extraction temperature, 70% of ethanol concentration, 56 kHz of ultrasonic frequency and a 1: 50 solid to solvent ratio. Under optimal conditions, the leaching-out rate of phenolic compounds was up to 55.34 mg g(-1) , and the yield of crude extract of P. emblica was up to 56.82%. The results reveal that the yield of phenolic compounds of UAE (56.82%) is higher than that of conventional solvent extraction (16.78%). Furthermore, the antioxidant activities of ethanol extracts obtained by UAE were evaluated in terms of activities of DPPH (1,1'-diphenyl-2-2'-picrylhydrazyl) radical scavenging activity, total antioxidant activity, metal chelating activity, and reducing power. P. emblica extracts obtained by UAE showed high antioxidant activity (26.00, 50.11 and 115.91 µg mL(-1) of IC50 values for DPPH radicals, total antioxidant ability and chelating ability of ferrous ion). CONCLUSION: The result of this study showed that UAE was a suitable method for the extraction of total phenolic compounds. Moreover, the author's main finding in this work is the fact that phenolic compounds from P. emblica show excellent antioxidant activity in multi-test systems.

Anti-inflammation mechanisms of a homogeneous polysaccharide from Phyllanthus emblica L. on DSS induced colitis mice via the gut microbiota and metabolites alteration.

Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation.

Tannins in Phyllanthus emblica L. improves cisplatin efficacy in lung cancer cells by boosting endoplasmic reticulum stress to trigger immunogenic cell death.

BACKGROUND: Lung cancer is one of the deadliest cancers world-wide and immunotherapy has been considered as a promising therapeutic strategy. Previously, our study found that tannins in Phyllanthus emblica L. (PTF) could inhibit the growth of tumor by activating the immune response in liver cancer, and also exhibited a cytotoxicity on human lung cancer cells A549, H460, H1703 in vitro. OBJECTIVE: To explore whether PTF inhibited the growth of lung cancer through its immune-regulating function and to clarify underlying mechanisms. METHODS: The induction of immunogenic cell death (ICD) were characterized by calreticulin exposure, extracellular ATP secretion, and High Mobility Group Box 1(HMGB1) release both in vivo using LLC-derived xenograft tumor model and in vitro using both mouse LLC and human A549 cancer cells. RESULTS: PTF inhibited lung cancer cells growth and tumorigenesis in vivo/vitro and promoted anti-tumor immune responses. We further found that PTF could induce ICD, which then activated Type I interferon responses and CXCL9/10-mediated chemotaxis. Mechanistically, PTF induced the formation of intracellular protein aggregates and following activation of PERK/ATF4/CHOP-dependent endoplasmic reticulum stress-related ICD. Moreover, PTF improved the antitumor efficacy of cisplatin by inducing ICD both in vitro and in vivo. Finally, we screened out 5 components from PTF, including gallocatechin, gallic acid, methyl gallate, ethyl gallate and ellagic acid, which could induce ICD in vitro and might be considered as the potential antitumor pharmacodynamic substances. CONCLUSION: In conclusion, PTF inhibits the growth of lung cancer by triggering ICD and remodeling the tumor microenvironment, suggesting that PTF may have promising prospects as an adjacent immunotherapy for cancers.

Extract of Phyllanthus emblica L. fruit stimulates basal glucose uptake and ameliorates palmitate-induced insulin resistance through AMPK activation in C2C12 myotubes.

BACKGROUND: The fruit of Phyllanthus emblica L., a traditional medicine in China and India, is used to treat diabetes mellitus. Its water extract (WEPE) has demonstrated hypoglycemic effects in diabetic rats, but its mechanisms on glucose utilization and insulin resistance in skeletal muscle remain unclear. Therefore, this study aims to investigate the effects and underlying mechanisms of WEPE on glucose utilization and insulin resistance using C2C12 myotubes. METHODS: Effects of WEPE on glucose uptake, GLUT4 translocation, and AMPK and AKT phosphorylation were investigated in C2C12 myotubes and palmitate-treated myotubes. An AMPK inhibitor and siRNA were used to explore the mechanisms of WEPE. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay, and protein expression and GLUT4 translocation were assessed via western blotting. RESULTS: In normal myotubes, WEPE significantly stimulated glucose uptake and GLUT4 translocation to the plasma membrane at concentrations of 125 and 250 µg/mL. This was accompanied by an increase in the phosphorylation of AMPK and its downstream targets. However, both compound C and AMPK siRNA blocked the WEPE-induced GLUT4 translocation and glucose uptake. Moreover, pretreatment with STO-609, a calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß) inhibitor, inhibited WEPE-induced AMPK phosphorylation and attenuated the WEPE-stimulated glucose uptake and GLUT4 translocation. In myotubes treated with palmitate, WEPE prevented palmitate-induced insulin resistance by enhancing insulin-mediated glucose uptake and AKT phosphorylation. It also restored the insulin-mediated translocation of GLUT4 from cytoplasm to membrane. However, these effects of WEPE on glucose uptake and GLUT4 translocation were blocked by pretreatment with compound C. CONCLUSIONS: WEPE significantly stimulated basal glucose uptake though CaMKKß/AMPK pathway and markedly ameliorated palmitate-induced insulin resistance by activating the AMPK pathway in C2C12 myotubes.

Phyllanthus emblica L. polysaccharides ameliorate colitis via microbiota modulation and dual inhibition of the RAGE/NF-κB and MAPKs signaling pathways in rats.

Pharmacological treatments for colitis have limited efficacy and side effects. Plant polysaccharides improve colitis by modulating the gut microbiota. However, the specific benefits of Phyllanthus emblica L. polysaccharides (PEPs) in colitis remain unclear. Therefore, this study aimed to assess the physical characteristics and health advantages of PEP in rats subjected to 2,4,6-trinitrobenzene sulfonic acid (TNBS) treatment. The results showed that PEP (1.226 × 103 kDa) was an α-acidic pyran heteropolysaccharide rich in galactose and galacturonic acid. Prefeeding rats with PEP significantly decreased the levels of NO, MDA, proinflammatory cytokines (IL-6, IL-1ß, TNF-α), apoptosis, and the activities of mucinase and ß-glucuronidase. These changes were accompanied by increases in the levels of anti-inflammatory cytokines (IL-4, IL-10) and antioxidant enzymes (SOD, catalase, GPx) in colitis rats. Mechanistically, PEP suppressed the abundance of inflammatory-related bacteria (Bacteroides, Intestinimonas, and Parabacteroides) while promoting the growth of short-chain fatty acid (SCFA)-producing bacteria (Romboutsia, Clostridium_sensu_stricto_1, and Lactobacillus), along with an increase in SCFA secretion. SCFAs may engage with the GPR43 receptor and inhibit downstream HDAC3, consequently downregulating the activation of the RAGE/NF-κB and MAPK pathways. In conclusion, PEP demonstrated preventive effects through its antioxidant, anti-inflammatory, and microbiota modulation properties, thereby ameliorating TNBS-induced colitis in rats.

Phyllanthus emblica L. fruit extract induces chromosomal instability and suppresses necrosis in human colon cancer cells.

Phyllanthus emblica L. (PE) is an edible fruit indigenous to Southeast Asia. It has been considered as a potent functional food due to its numerous pharmacological applications, such as anti-oxidant, antimicrobial, anti-diabetic and protection for multiple organs. The aim of this study was to evaluate the effects of a water extract of PE fruit on genomic damage and cell death in the human colon adenocarcinoma cell line COLO320 using the cytokinesis-block micronucleus cytome assay. Cells were exposed to RPMI-1640 medium containing 0, 20, 40, 80, or 160 µg/mL PE for 24, 48, 72, or 96 hours. The results showed that PE induced a significant decrease in necrosis (p < 0.001) and nuclear division index (NDI) (p < 0.001) in a dose- and time-dependent manner, and there was a highly significant correlation between the reduction of necrosis and NDI (r = 0.820, p < 0.001). Dose- and time-dependent increases (p < 0.001) in the frequency of chromosomal instability (CIN) were observed after PE exposure, and the frequency of CIN was negatively correlated with NDI (r = - 0.640, p < 0.001). PE also significantly increased apoptosis (p < 0.001), and there was a significant correlation of apoptosis with CIN (r = 0.566, p < 0.001). In conclusion, PE suppresses necrosis and delays mitotic progression, which results in massive CIN followed by apoptosis in COLO320 cells.

Antidiabetic and antihyperlipidemic activities of Phyllanthus emblica L. extract in vitro and the regulation of Akt phosphorylation, gluconeogenesis, and peroxisome proliferator-activated receptor α in streptozotocin-induced diabetic mice.

Background: The fruits of Phyllanthus emblica L. are high in nutrients and have excellent health care function and developmental value. There are many management strategies available for diabetes and hyperlipidemia. Nevertheless, there is a lack of an effective and nontoxic drug. Objective: The present study was designed to first screen four extracts of P. emblica L. on insulin signaling target gene expression levels, including glucose transporter 4 (GLUT4) and p-Akt/t-Akt. The ethyl acetate extract of P. emblica L. (EPE) exhibited the most efficient activity among the four extracts and was thus chosen to explore the antidiabetic and antihyperlipidemic activities in streptozotocin (STZ)-induced type 1 diabetic mice. Design: All mice (in addition to one control (CON) group) were administered STZ injections (intraperitoneal) for 5 consecutive days, and then STZ-induced mice were administered EPE (at 100, 200, or 400 mg/kg body weight), fenofibrate (Feno) (at 250 mg/kg body weight), glibenclamide (Glib) (at 10 mg/kg body weight), or vehicle by oral gavage once daily for 4 weeks. Finally, histological examination, blood biochemical parameters, and target gene mRNA expression levels were measured, and liver tissue was analyzed for the levels of malondialdehyde (MDA), a maker of lipid peroxidation. Results: EPE treatment resulted in decreased levels of blood glucose, HbA1C, triglycerides (TGs), and total cholesterol and increased levels of insulin compared with the vehicle-treated STZ group. EPE treatment decreased blood levels of HbA1C and MDA but increased glutathione levels in liver tissue, implying that EPE exerts antioxidant activity and could prevent oxidative stress and diabetes. The EPE-treated STZ mice displayed an improvement in the sizes and numbers of insulin-expressing ß cells. EPE treatment increased the membrane expression levels of skeletal muscular GLUT4, and also reduced hepatic mRNA levels of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase thereby inhibiting hepatic gluconeogenesis. This resulted in a net glucose lowering effect in EPE-treated STZ mice. Furthermore, EPE increased the expression levels of p-AMPK/t-AMPK in both the skeletal muscle and liver tissue compared with vehicle-treated STZ mice. EPE-treated STZ mice showed enhanced expression levels of fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα), but reduced expression levels of lipogenic genes including fatty acid synthase, as well as decreased mRNA levels of sterol regulatory element binding protein 1c (SREBP1c), apolipoprotein-CIII (apo-CIII), and diacylglycerol acyltransferase-2 (DGAT2). This resulted in a reduction in plasma TG levels. EPE-treated STZ mice also showed reduced expression levels of PPAR γ. This resulted in decreased adipogenesis, fatty acid synthesis, and lipid accumulation within liver tissue, and consequently, lower TG levels in liver tissue and blood. Furthermore, EPE treatment not only displayed an increase in the Akt activation in liver tissue, but also in C2C12 myotube in the absence of insulin. These results implied that EPE acts as an activator of AMPK and /or as a regulator of the insulin (Akt) pathway. Conclusions: Taken together, EPE treatment exhibited amelioration of the diabetic and hyperlipidemic state in STZ-induced diabetic mice.

Dextran-Sulfate-Sodium-Induced Colitis-Ameliorating Effect of Aqueous Phyllanthus emblica L. Extract through Regulating Colonic Cell Gene Expression and Gut Microbiomes.

The anti-inflammation effect of aqueous Phyllanthus emblica L. extract (APE) and its possible underlying mechanism in dextran sulfate sodium (DSS)-induced mice chronic colonic inflammation were studied. APE treatment significantly improved the colitic symptoms, including ameliorating the shortening of the colon, increasing the DSS-induced body weight loss, reducing the disease activity index, and reversing the condition of colon tissue damage of mucus lost and goblet cell reduction. Overproduction of serum pro-inflammatory cytokines were suppressed by the treatment of APE. Gut microbiome analysis showed that APE remodeled the structure of gut bacteria in phylum and genus levels, upregulating the abundance of phylum Bacteroidetes, family Muribaculaceae, and genus Bacteroides and downregulating the abundance of phylum Firmicutes. The reshaped gut microbiome caused metabolic functions and pathway change with enhanced queuosine biosynthesis and reduced polyamine synthesis pathway. Colon tissue transcriptome analysis further elucidated APE-inhibited mitogen-activated protein kinase (MAPK), cytokine-cytokine receptor interaction, and tumor necrosis factor (TNF) signaling pathways and the expressions of the genes that promote the progress of colorectal cancer. It turned out that APE reshaped the gut microbiome and inhibited MAPK, cytokine-cytokine receptor interaction, and TNF signaling pathways as well as the colorectal-cancer-related genes to exert its colitis protective effect.

Thermal treatment enhances the resisting exercise fatigue effect of Phyllanthus emblica L.: novel evidence from tannin conversion in vitro, metabolomics, and gut microbiota community analysis.

Polyphenols are the main component of Phyllanthus emblica (PE). However, polyphenols are so easy to transform that it is unknown that how drying methods driven by heating affect the anti-fatigue effect of PE. This manuscript investigated the effects of five drying methods on the chemical composition transformation and anti-fatigue of PE, and discussed the action mechanism. The results suggested that the anti-fatigue effect of PE with hot-air-dried at 100 °C was the best, which was as 1.63 times as that with freeze-drying. Ellagic acid (EA) may be a key component of PE in anti-fatigue, and its mechanism of action may be related to regulating intestinal microbiota, protecting mitochondria, and regulating energy metabolism. This study first revealed the thermal transformation of polyphenols in PE, found the most effective strategy for enhancing the anti-fatigue function, and explores its action mechanism.

Phyllanthi Fructus: A modal medicinal and food homologous item in quality evaluation.

Phyllanthi Fructus is a highly unique medicine and food homologous item, which exhibits distinctive flavor, notable nutritional value, and abundant pharmacological activity. It has enormous potential in the creation of health products and pharmaceuticals. However, due to the unique laws of quality formation and transfer of Phyllanthi Fructus, its appearance, shape, chemical compositions, nutrients, and sensory flavors are frequently greatly influenced by botanical resources, the processing and storage conditions. As a result, the current quality evaluation model is difficult to meet the needs of Phyllanthi Fructus as a medicine and food homologous item in the development of diversified products. This paper constructs the hierarchical utilization mode of Phyllanthi Fructus based on its unique quality formation and transmission laws, explores the quality evaluation model for food-oriented use and medicinal-oriented use, respectively, and systematically describes the quality evaluation idea under diversified application scenarios. This paper aims to serve as a reference for the construction of a quality evaluation model suitable for the medicine and food homologous item of Phyllanthi Fructus.

Two pyrrole acids isolated from Phyllanthus emblica L. and their bioactivities.

An undescribed pyrrole acid, 1-(4'-methoxy-4'-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid (1) and one known pyrrole acid (2) were isolated from the fruits of Phyllanthus emblica. The structures of these compounds were elucidated via the comprehensive analyses of IR, HRESIMS, 1D and 2D spectroscopic data. A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide (NO), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor-α (TNF-α) by reducing the phosphorylation of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. Additionally, compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages.

Purification of polyphenols from Phyllanthus emblica L. pomace using macroporous resins: Antioxidant activity and potential anti-Alzheimer's effects.

Phyllanthus emblica L. pomace is a waste residue obtained following juicing that contains many polyphenols. In this study, NKA-II resin was selected as the optimal macroporous resin for separation and employed to separate the crude polyphenol extract of P. emblica pomace. The separation conditions were optimized, and the polyphenol content, polyphenol components, antioxidant activity, and potential anti-Alzheimer's effects of the extract were measured before and after purification. Results showed that the polyphenol content of the purified extract was 656.85 mg/g, which was 2.1 times higher than that of the nonpurified form. Further, the polyphenol components of the pomace, which was like that of the fruit, did not vary after purification. The antioxidant activity of the purified extract was also significantly improved. Moreover, purified extract significantly reduced the paralysis rate of the transgenic Caenorhabditis elegans model of Alzheimer's disease, and the mechanism was related to maintenance of redox homeostasis. PRACTICAL APPLICATION: The polyphenol content and antioxidant activity of purified polyphenol from Phyllanthus emblica L. pomace extracts were significantly improved using optimal separation methods with NKA-II macroporous resin and 70% aqueous ethanol as the eluent in this study. Moreover, purified polyphenols showed potential effects in alleviating Alzheimer's disease. These results suggest that polyphenols separated from P. emblica pomace are valuable for further research and development, and the utilization rate of P. emblica fruit is improved due to the further development of P. emblica pomace.

Aqueous Extract of Phyllanthus emblica L. Alleviates Functional Dyspepsia through Regulating Gastrointestinal Hormones and Gut Microbiome In Vivo.

Phyllanthus emblica L. fruits were extracted by a hot water assistant with ultrasonication to obtain aqueous Phyllanthus emblica L. extract (APE). The ameliorating functional dyspepsia (FD) effect of a low dose (150 mg/kg) and a high dose (300 mg/kg) of APE was exhibited by determining the gastrointestinal motility, gastrointestinal hormones, and gut microbiome shifts in reserpine induced FD male balb/c mice. APE increased the gastrointestinal motility including the gastric emptying (GE) rate and small intestinal transit (SIT) rate. The level of serum gastrointestinal hormones such as motilin (MTL) and gastrin (GAS) increased, and the vasoactive intestinal peptide (VIP) level decreased after the administration of APE. Furthermore, the gut microbiome analysis demonstrated that APE could regulate the microbiome structure and restore homeostasis by elevating useful bacterial abundance, while simultaneously decreasing harmful bacterial abundance. This study demonstrated the ameliorating FD effect of APE and its potential efficacy in curing functional gastrointestinal disorders and maintaining a healthy digestive tract.