Ginsenoside - a promising natural active ingredient with steroidal hormone activity.

Ginsenosides are a class of natural products with hormone-like activity of triterpenoid saponins and have a variety of pharmacological activities such as anti-aging, immune regulation and cognitive improvement. With the great research interest in alternative medicine and natural products, they are gradually becoming research hotspots. Ginsenosides have a four-ring rigid steroid backbone similar to steroid hormones, and a series of experimental studies have shown that they can exhibit hormone-like activity by binding to nuclear receptors or affecting hormone levels, thereby affecting a wide range of inflammatory conditions, cancers, and menopause-related diseases. This review summarizes the mechanisms and potential health effects of ginsenosides exhibiting estrogen-like, glucocorticoid-like and androgen-like activities, providing an important reference for the exploration of safe phytohormone replacement therapy.

Analysis of Polyphenol Extract from Hazel Leaf and Ameliorative Efficacy and Mechanism against Hyperuricemia Zebrafish Model via Network Pharmacology and Molecular Docking.

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.

UPLC-MS/MS profiling, antioxidant and anti-inflammatory activities, and potential health benefits prediction of phenolic compounds in hazel leaf.

Hazel leaf, one of the by-products of hazelnut, which is widely used in traditional folk medicine around the world. In the present study, the profile of free, conjugated, and bound phenolic compounds from hazel leaf was detected and their antioxidant and anti-inflammatory activities were investigated. The potential health benefits of different phenolic compounds were also predicted. The results showed that the 35 phenolic substances of free, conjugated and bound forms were identified including phenolic acids, flavonoids and catechins. Most of the hazel leaf phenolics were presented in free form, followed by conjugated and bound form. All the fractions effectively inhibited the production of reactive oxygen species and malondialdehyde in TBHP-stimulated human umbilical vein endothelial cells by enhancing endogenous superoxide dismutase, and accordingly alleviated inflammatory cytokines (NO, IL-1ß, TNF-α, and IL-6) in LPS-stimulated RAW264.7 cells, showing obvious antioxidant and anti-inflammatory capacity. Moreover, combined with network pharmacology, the potential therapeutic effects and functional pathways of hazel leaf phenolics were predicted, which provided value basis for exploring their treatment on diseases and developing health products in the future.

Functional Mechanism of Ginsenoside Compound K on Tumor Growth and Metastasis.

Ginsenosides, as the most important constituents of ginseng, have been extensively investigated in cancer chemoprevention and therapeutics. Among the ginsenosides, Compound K (CK), a rare protopanaxadiol type of ginsenoside, has been most broadly used for cancer treatment due to its high anticancer bioactivity. However, the functional mechanism of CK in cancer is not well known. This review describes the structure, transformation and pharmacological activity of CK and discusses the functional mechanisms of CK and its metabolites, which regulate signaling pathways related to tumor growth and metastasis. CK inhibits tumor growth by inducing tumor apoptosis and tumor cell differentiation, regulates the tumor microenvironment by suppressing tumor angiogenesis-related proteins, and downregulates the roles of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). There is currently much research on the potential development of CK as a new strategy when administered alone or in combination with other compounds.

Effect of carbendazim on honey bee health: Assessment of survival, pollen consumption, and gut microbiome composition.

Gut microbiota and nutrition play major roles in honey bee health. Recent reports have shown that pesticides can disrupt the gut microbiota and cause malnutrition in honey bees. Carbendazim is the most commonly used fungicide in China, but it is not clear whether carbendazim negatively affects the gut microbes and nutrient intake levels in honey bees. To address this research gap, we assessed the effects of carbendazim on the survival, pollen consumption, and sequenced 16 S rRNA gene to determine the bacterial composition in the midgut and hindgut. Our results suggest that carbendazim exposure does not cause acute death in honey bees even at high concentrations (5000 mg/L), which are extremely unlikely to exist under field conditions. Carbendazim does not disturb the microbiome composition in the gut of young worker bees during gut microbial colonization and adult worker bees with established gut communities in the mid and hindgut. However, carbendazim exposure significantly decreases pollen consumption in honey bees. Thus, exposure of bees to carbendazim can perturb their beneficial nutrition homeostasis, potentially reducing honey bee immunity and increasing their susceptibility to infection by pathogens, which influence effectiveness as pollinators, even colony health.

Genus Suaeda: Advances in phytology, chemistry, pharmacology and clinical application (1895 - 2021).

More than 100 species of annual herb genus Suaeda widely distribute (Asia, North America, northern Africa and Europe), are rich in resources (about hundreds of millions of tons/Y) and have a long historical application. Most of them are mainly used for traditional food, feed and medicine. Recently, they have been employed to repair saline-alkali land and beautify the environment. So far, only 27 species have been reported on the bioactivity diversity, broad spectrum and effectiveness in clinical practice. Therefore, the in-depth and extensive research of Suaeda has become a research hotspot around the world. However, only one review summarized the nutritional, chemical and biological values of Suaeda. By searching the international authoritative databases (ACS Publications, ScienceDirect, PubMed, Springer, web of Science and Bing International etc.) and collecting 103 literatures closely related to Suaeda (1895-2021), herewith a comprehensive and systematic review was conducted on the phytology, chemistry, pharmacology and clinical application, enveloping the classification evolution between Amaranthaceae and Chenopodiaceae, distribution and common botanical characteristics; involving 9 chemical categories of 163 derivatives covering 14 new and 6 first-isolated ones, and appraising the content determination of 6 categories of components; mainly including the pharmacology of 13 species in vivo and vitro; estimating the clinical application of 16 species cured the related diseases of eight human physiological system except for the motor system. It is expected that this paper will provide forward-looking scientific ideas and literature support for the further modern research, development and utilization of the genus.

Investigating the Mechanism of Shengmaiyin (Codonopsis pilosula) in the Treatment of Heart Failure Based on Network Pharmacology.

BACKGROUND AND OBJECTIVE: To explore the molecular mechanism by which Shengmaiyin (Codonopsis pilosula) (SMY) improves isoproterenol (ISO)-induced heart failure (HF) in rats via a traditional Chinese medicine (TCM) integrated pharmacology research platform, The Chinese Medicine Integrated Pharmacology Platform (TCMIP V2.0). METHOD: The chemical constituents and drug targets of SMY medicines were identified through TCMIP, and HF disease target information was collected. A prescription Chinese medicinecomponent- core target network was constructed through the TCM network mining module, and biological process and pathway enrichment analyses of core targets were conducted. In vivo experiments in rats were performed to verify the pathway targets. Hematoxylin and eosin staining was used to observe myocardial tissue morphology. ELISA kits were used to detect cAMP content, and Western blotting was used to detect the expression levels of signaling pathway-related proteins. RESULTS: The TCMIP analysis indicated that SMY treatment of HF activates the GS-ß-adrenergic receptor (ßAR)-cAMP-protein kinase A (PKA) signaling pathway. The in vivo experimental results confirmed this finding. High-dose SMY significantly improved the morphology of ISO-injured myocardium. The levels of G-protein-coupled receptor (GPCR), adenylate cyclase (AC), ßAR, and PKA proteins in myocardial tissue were significantly increased in the SMY group. In addition, the content of cAMP in myocardial tissue was increased, and the content of cAMP in serum was decreased. CONCLUSION: Based on the analysis of TCMIP, SMY treatment of HF may activate the GS-ßARcAMP- PKA signaling pathway. The findings provide a theoretical basis for further research on the anti-HF mechanism of SMY.

Quercus salicina Blume: Research Progress in Chemistry and Pharmacodynamics (1959-2021).

The crude extracts of different parts (leaves and shoots) of Quercus salicina Blume (QS) have shown considerable effect in urolithiasis. QS has been widely used in clinical practice and has attracted great research interest The relevant published literature, however, reveals only partial education of its chemical components and bio-active mechanisms, and only two review articles have summarized the QS research progress. In this review, a comprehensive and systematic review of chemistry and pharmacodynamics of QS was carried out using the international authoritative databases (1959-2021), focusing on phenols and flavonoids, and their effect such as urinary stone dissolution, anti-inflammatory, anti-diabetes, anti-bacterial, antioxidant, and anti-allergy activities as well as toxic effects. The aim of review is to provide the most recent and effective literature support for further basic research and application development.

Incompatible effects of Panax ginseng and Veratrum nigrum on estrogen decline in rats using metabolomics and gut microbiota.

Panax ginseng (PG) and Veratrum nigrum (VN) are the most representative incompatibility herb pair in traditional Chinese medicine (TCM). This theory is derived from long-term clinical practice and has been applied for thousands of years. However, its mechanism has not yet been clearly investigated. The purpose of this work is to examine the incompatible effects of PG and VN on estrogen decline in rats to better understand the adverse effects of inappropriate herbal combinations using metabolomics and gut microbiota. The ovariectomized rats were administered with PG, VN and their combination decoction decoction intragastrically. After the combination of PG and VN, the improvement of depression-like behavior, neurotransmitter of brain, serum estrogen levels on ovariectomized rats was decreased; the regulation of PG on eight metabolic biomarkers and four intestinal bacteria was reduced by metabolomic and gut microbiota analysis. In addition, the correlation analysis revealed that the above four gut flora showed a relative trend with the significant metabolites of Pantothenic acid, 4, 6-Dihydroxyquinoline, Chenodeoxycholic acid and Caprylic acid. They were involved in tryptophan metabolism, pantothenic acid and coenzyme A biosynthesis, fatty acid biosynthesis and primary bile acid biosynthesis. These results provide further insight into the pathway by which PG and VN combine to reduce the therapeutic effects of estrogen decline. It is helpful to comprehend the incompatible mechanisms of PG and VN.

Impact of TCM on Tumor-Infiltrating Myeloid Precursors in the Tumor Microenvironment.

The tumor microenvironment (TME) is composed of tumor cells, blood/lymphatic vessels, the tumor stroma, and tumor-infiltrating myeloid precursors (TIMPs) as a sophisticated pathological system to provide the survival environment for tumor cells and facilitate tumor metastasis. In TME, TIMPs, mainly including tumor-associated macrophage (TAM), tumor-associated dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs), play important roles in repressing the antitumor activity of T cell or other immune cells. Therefore, targeting those cells would be one novel efficient method to retard cancer progression. Numerous studies have shown that traditional Chinese medicine (TCM) has made extensive research in tumor immunotherapy. In the review, we demonstrate that Chinese herbal medicine (CHM) and its components induce tumor cell apoptosis, directly inhibiting tumor growth and invasion. Further, we discuss that TCM regulates TME to promote effective antitumor immune response, downregulates the numbers and function of TAMs/MDSCs, and enhances the antigen presentation ability of mature DCs. We also review the therapeutic effects of TCM herbs and their ingredients on TIMPs in TME and systemically analyze the regulatory mechanisms of TCM on those cells to have a deeper understanding of TCM in tumor immunotherapy. Those investigations on TCM may provide novel ideas for cancer treatment.

Screening and Isolation of Natural Antioxidants from Acer Ginnala Max by TLC-MS/MS Guided Bioautographic Method.

A rapid and simple method has been developed for the screening and identification of natural antioxidants from the leaves of Acer ginnala Maxim (AG). The process is that upon reaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH), the white yellow spots of compounds with potential antioxidant effects will be significantly observed on the thin-layer chromatography (TLC), and possible structures will be presumed by the ESI/MS technique. Using the improved approach, 6 compounds in the AG extract were found to possess a potential antioxidant activity. They were speculated as quercetin-3-O-α-L-(3"-galloyl)-rhamnoside (1), quercetin-3-O-α-L-(2"-galloyl)-rhamnoside (2), quercetin-3-O-α-L-(2"-galloyl)-arabinopyranoside (3), acertannin (4), gallic acid (5), and methyl gallate (6). In addition, we were still found that compounds 2, 3, and 5 had favorable antioxidant activity from the scannogram of the DPPH reaction plate. As a result, the isolated 6 compounds structures were in accordance with the presumed structures. Furthermore, the free radical scavenging capacities of the available identified compounds were also investigated. Compounds 2, 3, and 5 showed significant DPPH.Scavenging capacities, with IC50 values of 2.83 µg/mL, 2.34 µg/mL, and 1.86µg/mL, respectively. The results indicated that this newly improved method could be widely applied for rapid screening and identification of natural antioxidants from Chinese herbal medicines.

Esterified Derivatives of Panaxadiol and Their Inhibitory Effect on HL-60, THP-1, and PC-3 Cell Lines.

Panaxadiol is a dammarane-type ginsenoside having high ginseng content. The 3-hydroxy group of panaxadiol (PD) was modified by fatty acids and diacids. The modified panax glycol had enhanced anticancer activity. Twelve PD derivatives were evaluated and purified by chemical synthesis, column chromatography, co-synthesis, and identification. The human leukemia cells THP-1, HL-60, and human prostate cancer cell lines PC-3 were evaluated; PD derivatives were tested and evaluated in vitro by MTT assay. The results showed that the antitumor activities of some derivatives on three tumor cell lines were better than those of PD.

Preventive effects of cedrol against alopecia in cyclophosphamide-treated mice.

Although numerous hypotheses have been proposed to prevent chemotherapy-induced alopecia (CIA), effective pharmaceuticals have yet to be developed. In our study, the back hairs of C57BL/6 mice were factitiously removed. These mice were then treated with cedrol or minoxidil daily. Mice with early-stage anagen VI hair follicles were treated with cyclophosphamide (CYP, 125mg/kg) to induce alopecia. The CYP-damaged hair follicles were observed and quantified by using a digital photomicrograph. The results demonstrated that the minoxidil-treated mice suffered from complete alopecia similar to the model 6days after CYP administration. Simultaneously, the cedrol-treated (200mg/kg) mice manifested mild alopecia with 40% suppression. Histological observation revealed that anagen hair follicles of the cedrol-pretreated mice (82.5%) likely provided from damage compared with the sparse and dystrophic hair follicles of the model mice (37.0%). Therefore, the use of topical cedrol can prevent hair follicle dystrophy and provide local protection against CIA.

Spore Loads May Not be Used Alone as a Direct Indicator of the Severity of Nosema ceranae Infection in Honey Bees Apis mellifera (Hymenoptera:Apidae).

Nosema ceranae Fries et al., 1996, a microsporidian parasite recently transferred from Asian honey bees Apis cerana F., 1793, to European honey bees Apis mellifera L., 1758, has been suspected as one of the major culprits of the worldwide honey bee colony losses. Spore load is a commonly used criterion to describe the intensity of Nosema infection. In this study, by providing Nosema-infected bees with sterilized pollen, we confirmed that pollen feeding increased the spore loads of honey bees by several times either in the presence or absence of a queen. By changing the amount of pollen consumed by bees in cages, we showed that spore loads increased with an increase in pollen consumption. Nosema infections decrease honey bee longevity and transcription of vitellogenin, either with or without pollen feeding. However, the reduction of pollen consumption had a greater impact on honey bee longevity and vitellogenin level than the increase of spore counts caused by pollen feeding. These results indicate that spore loads may not be used alone as a direct indicator of the severity of N. ceranae infection in honey bees.

[Splitted fractions and unoverlapping analysis of chemical constituents of Poria cocos].

With the combined applications of steam distillation, water extraction and alcohol precipitation, liquid-liquid extraction and column chromatography over macroporous resin, a splitted-fractions method of the chemical constituents of Poria cocos was established. The unoverlapping property of the fractions of P. cocos was qualitatively analysed by using principal component analysis and cluster analysis. With angle cosine, squared euclidean distance and the overlapping analysis of peak area of crude herbs, the unoverlapping property of the fractions of P. cocos was half-quantitatively analysed. The chemical components of P. cocos was divided into the fractions of polysaccharide, petroleum ether, ethyl acetate, alcohol eluate from macroporous resin and water eluate from macroporous resin. Non similarity degree among each chemical fraction was above 80% and main chemical components were identified. The established method for splitting fractions of P. cocos has good stability and repeatability and all chemical components in P. cocos could be completely divided into six fractions. It is the first time that the author half-quantitatively analyse the unoverlapping property of the chemical fractions of P. cocos.

[Antioxidant activity constituents from root of Rubus crataegifolius].

OBJECTIVE: To study the antioxidant constituents from the root of Rubus crataegifolius. METHOD: The constituents isolation and purification from the root of R. crataegifolius was carried by reported column chromatography including silica gel, toyopearl, and their structures were elucidated on the basis of spectral compounds. DPPH method was used to evaluate the free radical scavenging activity of the isolated compounds. RESULT: Nine compounds were isolated from the root of R. crataegifolius, and their structures were identified as follow: euscaphic acid (1), kaempferol-3-O-beta-D-galactopyranoside (2), tormentic acid (3), 2alpha, 19alpha, 24-trihydroxyurs-12-ene-3-oxo-28-acid (4) , 2alpha-hydroxy-oleanolic acid (5), ursolic acid (6), daucosterol (7), beta-sitosterol (8) and polydatin (9). By experiment of antioxidant activity, the result showed compounds 2 and 9 revealed DPPH free radical scavenging rates were 95.60% and 75.23% at the concentration of 50 mg x L(-1). CONCLUSION: Compounds 1-8 were isolated from this plant for the first time, and compounds 2 and 9 showed the significant antioxidant activity.

[Effects of pilose antler and antler glue on osteoporosis of ovariectomized rats].

OBJECTIVE: To observe the effects of pilose antler and antler glue on osteoporosis of ovariectomized rats. METHODS: 60 6-month-old female rats were divided randomly into sham-operated group, model group, the positive group, pilose antler high-dose group, pilose antler low-dose group and antler glue group. We extracted bilateral ovaries to establish osteoporosis model and treated at two weeks postoperationally for consecutively 13 weeks, then observed the effects of pilose antler and antler glue on rat bone mineral density, bone mineral content, serum biochemical indicators, bone tissue morphology and other indicators. RESULTS: After 13 weeks, the high-dose group and antler glue group could significantly improve the BMD and bone mineral content of the ovariectomized rats, reduce BGP and ALP content, and remarkably increase the width of trabecula bone and bone trabecula area percentage, increase osteoblasts significantly, and decrease osteoclast cells significantly. Pilose antler low-dose also had the phenomenon above, but the result was not so good as high-dose group. CONCLUSION: Pilose antler and antler glue can antagonize osteoporosis of the ovariectomized rats.