[This corrects the article DOI: 10.1016/j.jgr.2020.08.005.].

Chronic metabolic inflammation in adipose tissue plays an important role in the development of obesity-associated diseases. Our previous study indicated that total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one main component of SPJ, could exert the anti-oxidative and anti-inflammatory effects. The present study aimed to investigate the in vivo and Ex vivo anti-inflammatory activities of another main component of SPJ, namely Chikusetsu saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis, and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA expression levels of inflammation-related genes and secretion of the chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages (ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced expression of NLRP3 inflammasome component genes and decreased IL-1β and Caspase-1 production in mice. Moreover, CS treatment also inhibited the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs). Meanwhile, CS treatment inhibited an NLRP3-induced ASC pyroptosome formation and lipopolysaccharide (LPS)-induced pyroptosis. Furthermore, CS treatment suppressed HFD-induced NF-κB signaling in vivo and LPS-induced NF-κB activation as reflected by the fact that their phosphorylated forms and the ratios of pNF-κB/NF-κB, pIKK/IKK, and pIκB/IκB were all decreased in EAT from HFD-fed mice treated with CS as compared with those of HFD mice. Taking together, this study has revealed that CS effectively inhibits HFD-induced inflammation in adipose tissue of mice through inhibiting both NLRP3 inflammasome activation and NF-κB signaling. Thus, CS can serve as a potential therapeutic drug in the prevention and treatment of inflammation-associated diseases.

Background Inflammation is a key factor contributing to aging-related morbidities. Inflammation is intimately linked to the iron metabolism in macrophages, and ferritin heavy chain (Fth) is the basis of iron metabolism in macrophages. Regulating Fth to control iron metabolism may help to reduce inflammation in macrophages, which can ultimately help to alleviate certain aging-related diseases. Methods The effects of total saponins from Panax Japonicus (TSPJs) in the intervention of aging-related obesity were explored. The in vitro and in vivo models were established using RAW264.7 macrophage cells and naturally aging rats and mice. The inflammation, iron content, and gene expressions of the models were analyzed. Senescence was induced in RAW264.7 cells with adriamycin (ADR), and Fth knockdown was introduced to the models to investigate related mechanisms. Results TSPJs reduced the iron content in the macrophages and prompted M2 polarization, which affected the JNK signaling pathway (p < 0.05) and reduced the expression of inflammatory cytokines in adipose tissue. Conclusion TSPJs mediate the iron metabolism of macrophages via Fth to reduce aging-related inflammation of the adipose tissue.

The escalating prevalence of type 2 diabetes (T2DM) has emerged as a global public health dilemma. This ailment is associated with insulin resistance and heightened blood glucose concentrations. Despite the rapid advancements in modern medicine, where a regimen of medications is employed to manage blood glucose effectively, certain treatments manifest significant adverse reactions. Recent studies have elucidated the pivotal role of gallotannins in mitigating inflammation and obesity, potentially reducing the prevalence of obesity-linked T2DM. Gallotannins, defined by their glycosidic cores and galloyl groups, are ubiquitously present in plants, playing diverse biological functions and constituting a significant segment of water-soluble polyphenolic compounds within the heterogeneous tannins group. The structural attributes of gallotannins are instrumental in dictating their myriad biological activities. Owing to their abundance of hydroxyl groups (-OH) and complex macromolecular structure, gallotannins exhibit an array of pro-physiological properties, including antioxidant, anti-inflammatory, antidiabetic, protein-precipitating, and antibacterial effects. Extensive research demonstrates that gallotannins specifically obstruct α-amylase and pancreatic lipase, enhance insulin sensitivity, modulate short-chain fatty acid production, alleviate oxidative stress, exhibit anti-inflammatory properties, and influence the gut microbiota, collectively contributing to their antidiabetic efficacy. This review aims to consolidate and scrutinize the extant literature on gallotannins to furnish essential insights for their potential application in diabetes management.

In this study, the chemical components of Panacis Japonici Rhizoma extract and absorbed components in rats were identified by ultra-high performance liquid chromatography-quadrupole exactive orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS). The separation was performed by gradient elution on Waters UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) with the mobile phase of water and acetonitrile containing 0.1% formic acid. High resolution multistage mass spectrometry data were collected by electrospray ionization in positive and negative ion modes. The chemical components of Panacis Japonici Rhizoma extract were identified by comparing with the retention time, high resolution precise molecular weight, and secondary fragment ions of reference substances and related literature. After intragastric administration of Panacis Japonici Rhizoma extract, blood was collected from the abdominal aorta of rats for separation of the serum, and the absorbed components were scanned and identified. The results showed that 43 chemical components were detected in the Panacis Japonici Rhizoma extract, including 22 saponins, 9 amino acids, 5 polysaccharides, 2 volatile oils, and 5 nucleosides. In the serum, 18 components were detected, including 10 prototype components, 6 metabolites, and 2 unknown components. This study analyzed the chemical components and absorbed components of Panacis Japonici Rhizoma extract, providing clues for clarifying the pharmacological basis of Panacis Japonici Rhizoma.

The decline of aging brain neurons is the main cause of various neurodegenerative disease. This study aimed to examine the impact of Balanophora polyandra polysaccharides (BPP) against aging related neuronal deterioration. C57BL/6 mice were fed with regular feed for 27 months to establish a natural aging mouse model. From 3 months of age, mice in the drug-treated group were respectively fed with feed containing 0.05 or 0.18% BPP until 27 months of age. The effects of BPP treatment on the pathological changes of neurons in mice brain were evaluated, as well as autophagy-related and signaling pathway proteins. BPP treatment had a notable positive impact on the pathological injury of cortical and hippocampal neurons, alleviated neuronal degeneration, and enhanced the staining of Nissl bodies in natural aging mice. Furthermore, BPP upregulated autophagy-related proteins LC3 II/I, Parkin, and PINK1 in the cortex and hippocampus of aging mice, and significantly decreased the expression of p62, PI3K, p-protein Kinase B (AKT), and p-mTOR. Immunofluorescence results showed a reduction in the brightness of LC3, which mainly coexpressed with NeuN in natural aging mice brain, and increased LC3-positive neurons were observed after BPP treatment. Collectively, BPP treatment enhanced neuronal autophagy to improve brain functional degradation through the PI3K/AKT/mTOR signaling in natural aging mice. These finding suggested that BPP has potential to mitigate or delay the neurodegeneration associated with aging and further investigation was needed to validate its efficacy in elderly populations.

Background:: Long non-coding RNA (LncRNA) is a type of non-coding RNA that plays an important role in the body and accounts for the majority of RNA, and this non-coding RNA can regulate disease onset and progression with its wide range of functions. LncRNA Xist, also known as the long non-coding RNA X inactive specific transcript, is a member of them. It can regulate the development of organismal diseases by acting downstream on specific target genes. In addition to this, it can also influence disease onset and progression by acting on apoptosis, migration, invasion, and other processes. It has been shown that XIST plays an important role in the development of inflammation. Objective:: To explore the role played by XIST in inflammation-related diseases and to explore its mechanism of action. Methods:: This paper summarizes and analyzes the role played by XIST in inflammation- related diseases by conducting a search in PubMed. Conclusion:: In this paper, we summarize the mechanism of action of XIST in different types of inflammation-related diseases and propose new protocols for the future clinical treatment of these diseases.

Adipocytic lipolysis is strongly related to the increase of visceral fat, decrease of exercise capacity, and various other metabolic syndromes during aging. It is significantly influenced by the paracrine relationship between adipocytes and the adipose tissue macrophages (ATMs), and the cytokines secreted by ATMs have endocrine effects on adjacent tissues. We previously reported that the total saponins from Panax japonicus (TSPJs) can enhance lipid metabolism. In this work, we for the first time proved that TSPJs promoted adipocytic lipolysis by preventing NLRP3 activation in ATMs to inhibit the expression of GDF3. The decrease of GDF3 by TSPJs restored the expression of the adipose triglyceride lipase (ATGL) and phosphorylated hormone-sensitive lipase (p-HSL), both of which are known to decrease with aging. Thus, the NLRP3 inflammasome/GDF3/ATGL axis may be a worthy target in developing future clinical solutions for aging-related obesity.

Balanophora harlandii Hook (B. harlandii), a folk medicine, has been traditionally employed to treat traumatic bleeding, gastroenteritis, icteric hepatitis, hemorrhoids, and other conditions. In this work, polysaccharides with anti-inflammatory effects were extracted from B. harlandii and purified. The extraction conditions were optimized, and the properties of one purified neutral fraction, denoted as BHPs-W-S3, were analyzed. BHPs-W-S3 has a molecular weight of 14.1kDa, and its three main monosaccharides are glucose, galactose, and xylose, with a molar ratio of 6.4:1.7:1.1. Its main chain consists of →6)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →6)-β-D-Galp-(1→, →3,6)-β-D-Galp-(1→, and it has branch chains at the O-4 and/or O-3 positions. In addition, in vitro experiments showed that the polysaccharides from B. harlandi can decrease the phosphorylation level of p65 and IκBα in LPS-induced RAW264.7 cells to reduce the expression of the pro-inflammatory genes such as TNF-α, IL-6, and IL-1β.

Minor ginsenosides are a class of processed saponins with minor natural content, high bioavailability, and outstanding bio-logical activity, which are usually obtained by biological or chemical transformation of prototype saponins directly extracted from Panax plants. In recent years, with the clarification of the biosynthetic pathway of saponins and the development of synthetic biology, it has become possible to use synthetic metabolic engineering methods with microorganisms as hosts to produce saponins. Minor ginsenosides have received widespread attention because of their remarkable biological activities in enhancing the immune function of the body and antitumor property. At present, most of the reviews on minor ginsenosides focus on transformation preparation, process optimization, and pharmacological activity, but there are some deficiencies in industrial analysis. This study summarized structural types, pharmacological activities, sources of acquisition, and transformation pathways of minor ginsenosides based on the relevant literature in China and abroad, proposed problems in the preparation of existing minor ginsenosides, and discussed the future research and utilization prospects, to provide a theoretical basis for improving the basic research of minor ginsenosides and promoting their industrialization.

Aging and obesity are closely related. A key change in the adipose tissue during the aging process is the decline of lipolysis. The excitation of the sympathetic nerve system is a key pathway to promote lipolysis, but the underlying mechanism remains unclear. In this work, in vitro and in vivo aging models with and without tyrosine hydroxylase (TH) knockdown were treated with total saponins from Panax japonicus (TSPJs), and the expression of lipolysis-related proteins was examined. It was found that TSPJs could promote the expression of lipolysis-related genes and TH in adipocytes both in vitro and in vivo, and the expression of lipolysis-related genes was downregulated after TH knockdown. It was inferred that TSPJs could promote the excitation of sympathetic nerves by increasing the expression of TH in adipose tissue, which positively regulated the expression of lipases to revitalize lipolysis. The results suggested that TSPJs resisted aging-induced obesity and could be a potential medication for weight management.

Recent scientific studies have highlighted the importance of long-chain noncoding RNAs (lncRNAs) in a variety of metabolic diseases, but the specific functions and mechanisms of lncRNAs in aberrant lipid synthesis associated with aging are unknown. In this work, we inspected the effects of lncRNAs on the lipid metabolism in aging mice, as substantial evidence suggests that aging disturbs lipid metabolism. The results revealed that the expression of lncRNA Gm15232 was significantly elevated in the epididymal white adipose tissue of aging mice compared to adult mice. This upregulation of Gm15232 functioned as a competitive endogenous RNA by inhibiting the expression of miR-192-3p, and the ensuing downregulation of miR-192-3p increased the expression of the glucocorticoid receptor gene, which ultimately stimulated fat synthesis. The upregulation of Gm15232 thus increased lipogenesis through this mechanism. This study reveals a potential target for the treatment of age-related abnormalities of lipid metabolism.

Our prophase studies have manifested that the sweet triterpenoid glycoside from the leaves of Cyclocarya paliurus (CPST) effectively improved the disorders of glucolipid metabolism in vitro and in patients. The current purpose was to further detect its mechanisms involved. The results demonstrated that CPST could ameliorate high-fat diet (HFD)-induced insulin resistance (IR), which was linked to reducing HFD-induced mice's body weight, serum glucose (GLUO), triglyceride (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C), lowering the area under the oral glucose tolerance curve and insulin tolerance, elevating the percentage of brown adipose, high-density lipoprotein cholesterol (HDL-C), reducing fat droplets of adipocytes in interscapular brown adipose tissue (iBAT) and cross-sectional area of adipocytes. Further studies manifested that CPST obviously downregulated TLR4, MyD88, NLRP3, ASC, caspase-1, cleased-caspase-1, IL-18, IL-1β, TXNIP, and GSDMD protein expressions and p-NF-кB/NF-кB ratio in iBAT. These aforementioned findings demonstrated that CPST ameliorated HFD induced IR by regulating TLR4/NF-κB/NLRP3 signaling pathway, which in turn enhancing insulin sensitivity and glucose metabolism.

Ethnopharmacological relevance: Wuzi Yanzong Prescription (WZ), a classic traditional Chinese medicine formula, has the properties of kidney nourishing and essence strengthening, and it is widely used to treat male infertility with a long history. Sertoli cells are injured with aging, resulting in testicular dysfunction, and WZ effectively rejuvenates the age-related decline of testicular function. However, whether the therapeutic effects of WZ on aging-related testicular dysfunction are dependent on the restoration of Sertoli cell function remains unclear.Aim of the study: In a mouse model of natural aging, we explored the protective effects of WZ and its potential mechanisms.Materials and methods: Fifteen-month-old C57BL/6 mice were randomized to receive either standard diet or WZ (2 and 8 g/kg) for 3 months. Meanwhile, 10 1-month-old mice were considered the adult control group and received standard diet for 3 months. The testis and epididymis were rapidly collected, and the sperm quality, testicular histology, Sertoli cell numbers, tight junction (TJ) ultrastructure, and blood-testis barrier-associated protein expression and localization were assessed. Results: WZ significantly increased sperm concentration and sperm viability, improved the degenerative histo-morphology and elevated the seminiferous epithelium height. Furthermore, WZ increased the number of Sertoli cells, restored the ultrastructure of the Sertoli cell TJ, and upregulated the expression of TJ-associated proteins (zonula occludens-1 and Claudin11), ectoplasm specialized-associated proteins (N-Cadherin, E-Cadherin and 8-Catenin), and gap junction-associated protein (connexin 43), but did not affect the expression of Occludin and cytoskeletal protein (Vimentin). In addition, WZ did not change the localization of zonula occludens-1 and 8-Catenin in aged testis. Moreover, WZ increased the expression of autophagy-associated proteins (light chain 3 beta and autophagy related 5) and decreased the expression of p62, phosphorylated mammalian target of rapamycin, and phosphorylated AKT in Sertoli cells. Finally, we found that WZ attenuated mTOR complex 1 (mTORC1) activity and upregulated mTORC2 activity, as evidenced by inhibition of the expression of the regulatory-associated protein of mTOR, phosphorylated p70 S6K, and phosphorylated ribosomal protein s6 and enhancement of the expression of Rictor in the Sertoli cells of aging mice.Conclusions: WZ improves the injury of Sertoli cells by restoring AKT/mTOR-mediated autophagy and the mTORC1-mTROC2 balance in Sertoli cells during aging. Our findings provide a new mechanism of WZ in the treatment of aging-induced testicular dysfunction.

ABSTRACTBalanophora harlandiiHook (B. harlandii), a folk medicine, has been traditionally employed to treat traumatic bleeding, gastroenteritis, icteric hepatitis, hemorrhoids, and other conditions. In this work, polysaccharides with anti-inflammatory effects were extracted and purified fromB. harlandii.The extraction conditions were optimized, and the properties of one purified neutral fraction, denoted as BHPs-W-S3, were analyzed. Gel permeation chromatography (GPC) was carried out to measure the molecular weight. The structure of BHPs-W-S3 was assessed based on monosaccharide composition analysis, Fourier transform infrared (FT-IR) spectroscopy, methylation analysis, and nuclear magnetic resonance (NMR) spectroscopy. BHPs-W-S3 has a molecular weight of 14.1 kDa, and its three main monosaccharides are glucose, galactose, and mannose with a molar ratio of 6.4:1.7:1.1. Its main chain consists of →6)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →6)-β-D-Galp-(1→, →3,6)-β-D-Galp-(1→, and it has branch chains at the O-4 and/or O-3 positions. In addition,in vitroexperiments show that the polysaccharides fromB. harlandican decrease the phosphorylation level of p65 and IKB-α in LPS-induced RAW264.7 cells to reduce the expression of the pro-inflammatory genes such as TNF-α, IL-6, and IL-1β.Abstract Figure

Balanophora harlandii Hook ( B. harlandii) , a folk medicine, has been traditionally employed to treat traumatic bleeding, gastroenteritis, icteric hepatitis, hemorrhoids, and other conditions. In this work, polysaccharides with anti-inflammatory effects were extracted and purified from B. harlandii. The extraction conditions were optimized, and the properties of one purified neutral fraction, denoted as BHPs-W-S3, were analyzed. Gel permeation chromatography (GPC) was carried out to measure the molecular weight. The structure of BHPs-W-S3 was assessed based on monosaccharide composition analysis, Fourier transform infrared (FT-IR) spectroscopy, methylation analysis, and nuclear magnetic resonance (NMR) spectroscopy. BHPs-W-S3 has a molecular weight of 14.1 kDa, and its three main monosaccharides are glucose, galactose, and mannose with a molar ratio of 6.4:1.7:1.1. Its main chain consists of →6)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →6)-β-D-Galp-(1→, →3,6)-β-D-Galp-(1→, and it has branch chains at the O-4 and/or O-3 positions. In addition, in vitro experiments show that the polysaccharides from B. harlandi can decrease the phosphorylation level of p65 and IKB-α in LPS-induced RAW264.7 cells to reduce the expression of the pro-inflammatory genes such as TNF-α, IL-6, and IL-1β. ![Figure][1] * ### Abbreviations Ara : arabinose B. harlandii : Balanophora harlandii Hook BHPs : B. harlandii polysaccharides BHPs-W-S3 : a neutral polysaccharide of B. harlandii polysaccharides BSA : bovine serum albumin DEX : Dexamethasone Fru : Fructose Fuc : Fucose FT-IR : Fourier transform infrared spectroscopy GalA : Galacturonic acid GC-MS : gas chromatography-mass spectrometry GlcN : Gal galactose GlcN : Glucosamine hydrochloride GlcA : Glucuronic acid GlcNC : N-Acetyl-D glucosamine Glc : glucose GulA : Gullochuronic acid GPC : gel permeation chromatography IκBα : inhibitor of kappa Bα LPS : lipopolysaccharide ManA : Mannuronic acid Man : mannose NMR : nuclear magnetic resonance NFκB : Nuclear factor kappa-B PI : polydispersity index PVDF : polyvinylidene difluoride PBS : phosphate-buffered saline p-IκBα : phospho-inhibitor of kappa Bα Rha : Rhamnose Rib : Ribose SD : standard deviation SAR : structure-activity relationship TBS-Tween : Tris-buffered saline-Tween TFA : trifluoroacetic acid TBS-Tween : Tris-buffered saline-Tween UV : ultraviolet Xyl : Xylose [1]: pending:yes

Background: The rising incidence of metabolic diseases due to chronic inflammation in the adipose tissue has been attributed to factors such as high fat diet (HFD). Previous studies have demonstrated that the total saponins from Panax japonicus (TSPJ) can reduce HFD-induced adipocyte inflammation, but the underlying mechanism remains unclear. In this work, we explored the molecular mechanism by which TSPJ reduces inflammation response in adipocytes. Methods: We first established C57BL/6 mouse and 3T3-L1 adipocyte models. Lentiviruses packaged with the plasmids were injected into mice through the tail vein or into adipocytes to generate the in vivo and in vitro models with miR155 knockdown and overexpression. The mice were fed with HFD to trigger inflammation and administered TSPJ (25 mg/kg center dot d and 75 mg/kg center dot d) by gavage. The adipocytes were treated with palmitic acid (PA) to trigger inflammation response, then treated with TSPJ (25 mu g/ml and 50 mu g/ml). Finally, the expression of miR155, inflammatory factors, SOCS1, and NFKB pathway-related proteins was explored. Results: TSPJ significantly inhibited the expression of inflammation-related genes and the miR155 expression in adipocytes both in vitro and in vivo. The dual luciferase reporter gene assay revealed that miR155 mediated the downregulation of SOCS1. TSPJ significantly inhibited and upregulated the phosphorylation of the NFKB protein and the SOCS1 proteins, respectively. Conclusion: TSPJ inhibits miR155 to upregulate the SOCS1 expression, which subsequently inhibits the NFKB signaling pathway, thereby mitigating the inflammatory response in the adipocytes of HFD mice.

Selenium-enriched polysaccharides from Pyracantha fortuneana (SePFP) has many beneficial physiological activities, but how it improves the aging associated abnormal lipid metabolism is still unclear. Therefore, we explored the mechanisms of the regulatory role of SePFP on liver lipid accumulation in aging mice. Methods: 60 naturally aged C57BL/6J male mice were divided into 6 groups: adult group, aging group (21-month-old mice), aging mice treated with low-, medium- and high-doses of SePFP (SePFP-L, SePFP-M, SePFP-H), and aging mice treated with resveratrol (RSV). SePFP and RSV were administrated daily via oral gavage from 16 to 21 months old. The parameters of energy metabolism were measured in all mice before sacrifice, and liver tissues were collected to determine the levels of metabolism-related enzymes by real-time PCR and Western blot. Results: We found that SePFP significantly reduced the body weight, liver to bodyweight ratio, and white fat to body weight ratio in aging mice. SePFP also down-regulated the triglycerides and cholesterol levels in liver and serum, and decreased respiratory quotient in aging mice. The mechanism of SePFP regulating lipid metabolism was mainly through promoting fatty acid transportation to mitochondria and enhancing mitochondrial β-oxidation and ketone body production. Conclusion: SePFP attenuates liver lipid deposition in aging mice by enhancing hepatic mitochondrial β-oxidation.

Cyclocarya paliurus (Batalin) Iljinskaja (C. paliurus) is a single species of Cyclocarya paliurus in Juglandaceae. It is a unique rare medicinal plant resource in China that is mainly distributed in the south of China. The leaves of C. paliurus, as a new food ingredient, are processed into tea products in daily life. Triterpenoids are the main active ingredient in C. paliurus. So far, 164 triterpenoid compounds have been isolated and identified from C. paliurus, which are included 3,4-seco-dammaranes, dammaranes, oleanane, ursane, lupinanes, taraxeranes, and norceanothanes. Modern pharmacological studies manifested that these ingredients have a wide range of pharmacological activities both in vitro and in vivo, such as reducing blood sugar, lowering blood lipids, and anti-tumor, anti-inflammatory, anti-oxidant, and other activities. In addition, current results indicate that the pharmacological mechanisms of triterpenoids were closely related to their chemical structure, molecular signaling pathways, and the expression of related proteins. In order to further study C. paliurus based on the current research situation, this review summarizes the prospect and systematic summary of the triterpenes of C. paliurus from the aspects of structural characteristics, quality control, biological activity, and the structure-activity relationship, which provide a reference for further research and application of the triterpenoids from C. paliurus in the field of functional food and medicine.