Polygonum cuspidatum polysaccharide: A review of its extraction and purification, structure analysis, and biological activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum cuspidatum Sieb. et Zucc. is mainly distributed in Shanxi, Gansu, and Sichuan province of China. It is also found in Korea and Japan. Its dried roots and rhizomes are used as medicinal herbs and have been used to treat hyperglycemia and various inflammatory disorders. AIM OF THE REVIEW: This paper aims to provide an up-to-date review of the developments in the studies involving the extraction and purification, structure analysis, pharmacological effects, and potential applications of polysaccharides obtained from Polygonum cuspidatum. Additionally, the possible future research directions of this plant are discussed. MATERIALS AND METHODS: This article used "Polygonum cuspidatum polysaccharide (PCP)" and "Polygonum cuspidatum" as the keywords and gathered relevant data on Polygonum cuspidatum using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb. RESULTS: Excluding irrelevant and repetitive documents, 278 documents were finally included, of which 88 were in Chinese and 190 were in English. The CiteSpace software was used to visualize the trends and keywords in this research field. We concluded that the main extraction methods for Polygonum cuspidatum polysaccharide are water extraction and alcohol precipitation, microwave-assisted extraction, ultrasound-assisted extraction, and microjet extraction. High-performance liquid chromatography and column chromatography are also commonly used in the separation and purification of PCP. PCP has antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. This paper provides an updated and deeper understanding of PCP, serving as a theoretical foundation for the further optimization of polysaccharide structures and the development of PCP as a novel functional material for clinical application.

Three New 2,2'-Difurylketone Derivatives and Two New Chromones from the Rehmanniae Radix Praeparata.

Rehmanniae Radix Praeparata is the processed products of the root of Rehmannia glutinosa. It has been used as a Traditional Chinese Medicine for thousands of years, and it has been found to possess widely pharmacological activities. In this study, three new 2,2'-difurylketone derivatives (rehmanniaeketone A-C) and two new chromones [3,8-dihydroxy-2-(2-hydroxyethyl)chromone and 3,8-dihydroxy-2-[(2-O-α-D-galactopyranosyloxy)ethyl]chromone] were isolated from the Rehmanniae Radix Praeparata. Furthermore all of the compounds were subjected to cytotoxic testing against the human lung carcinoma A549 cells. The cytotoxic results showed that rehmanniaeketone B and rehmanniaeketone C exhibited more stronger inhibition effects on the cell activity of A549 cells with the IC50 5.23 µM and 2.05 µM than other compounds. And 3,8-dihydroxy-2-(2-hydroxyethyl)chromone exhibited moderately inhibitory activity with the IC50 61 µM. Rehmanniaeketone A and 3,8-dihydroxy-2-[(2-O-α-D-galactopyranosyloxy]chromone showed no inhibitory effects.

Structural characterization and immunomodulatory activities of two polysaccharides from Rehmanniae Radix Praeparata.

The structures and immunomodulatory activities of two polysaccharides (SDH-WA and SDH-0.2A) from Rehmanniae Radix Praeparata (RRP) were investigated. RRP crude polysaccharide was obtained by water extraction and purified. Ion chromatography, high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, methylation analysis, gas chromatography-mass spectrometry, and nuclear magnetic resonance were used to characterize the polysaccharides. The main chain of SDH-WA was →6)-α-D-Galp-(1→6)-α-D-Galp-(1→5)-α-L-Araf-(1→3,5)-α-L-Araf-(1→, terminal sugar residue α-L-Araf-(1→ linked to residue →3,5)-α-L-Araf-(1→ on the main chain by an O-3 bond. The other two terminal sugar residues α-D-Galp-(1→ and →6)-ß-D-Galp were linked to the end of the main chain. The main chain of SDH-0.2A was →2,4)-α-L-Rhap-(1→4)-α-D-GalpA-(1→. Three branched chains α-D-Galp-(1→6)-α-D-Galp-(1→5)-α-L-Araf-(1→3,5)-α-L-Araf-(1→, →3,6)-ß-D-Galp-(1→5)-α-L-Araf-(1→, and →4)-ß-D-Galp-(1→5)-α-L-Araf-(1→ were linked to the main chain residue →2,4)-α-L-Rhap-(1→ by an O-2 bond. Three terminal sugar residues α-D-Galp-(1→, α-L-Araf-(1→, and →6)-ß-D-Galp were linked to the end of the chain. Both polysaccharides showed no cytotoxic effects on and significantly promoted the phagocytic activity of RAW264.7 cells. They dose-dependently improved lysozyme activity and stimulated the production of TNF-α and IL-6 by RAW264.7 cells, but attenuated the secretion of lysozymes, TNF-α, IL-6, IL-1ß, and nitric oxide by lipopolysaccharide-induced RAW264.7 cells. The present studies suggest that PRR polysaccharide is a valuable source with immunomodulating.

In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERß-STAT3 Pathway.

Lung cancer is the most leading cause of cancer mortality throughout the world, of which about 85% cases comprise the non-small cell lung cancer (NSCLC). Estrogen and estrogen receptors are known to be involved in the pathogenesis and development of lung cancer. Dioscorea oppositifolia L. is a traditional Chinese medicine and a nutritious food, and can be an excellent candidate as an anti-cancer agent owing to its estrogen-like effects. However, the stems and leaves of D. oppositifolia L. are piled up in the field as a waste, causing environmental pollution and waste of resources. In the present study, a new diphenylethane (D1) was isolated from the stems and leaves of D. oppositifolia L. It was observed that D1 reduced the cell viability, migration, energy metabolism, and induced apoptosis in the A549 cells. Mechanistic studies showed that D1 reduced the STAT3 nuclear localization and downregulated the expression of the STAT3 target genes like Mcl-1, Bcl-xL and MMP-2 that are involved in the cell survival and mobility. Moreover, our results indicated that D1 exhibited estrogenic activities mediated by ERß, and antagonising ERß decreased the cytotoxic effect of D1 in A549 cells. In addition, inhibition of the nuclear translocation of STAT3 did not interfere with the binding of D1 and ERß. However, after antagonizing ERß, the nuclear translocation of STAT3 increased, thereby demonstrating that STAT3 was the downstream signaling molecule of ERß. In conclusion, the D1 mediated anti-NSCLC in vitro effects or at least in part can be attributed to the ERß-STAT3 signaling. Our findings suggest the role of D1 in treating NSCLC on a molecular level, and can help to improve the comprehensive utilization rate of D. oppositifolia L.

Arbutin attenuates LPS-induced acute kidney injury by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway.

BACKGROUND: Arbutin (Ar) has anti-oxidative and anti-inflammatory activities. However, the effects of Ar on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) are not clear. PURPOSE: This study aimed to investigate the effects of Ar on LPS-induced AKI in rats. METHODS: The possible data regarding the effects of Ar on AKI were collected by network pharmacology research. Histological changes in the kidney and the levels of blood urea nitrogen, serum creatinine, and kidney injury molecule 1 were measured to assess the effects of Ar on renal function in LPS-induced AKI. The levels of inflammatory were detected by live small-animal imaging, cytometric bead array and enzyme linked immunosorbent assay. The levels of reactive oxygen species and apoptosis of primary kidney cells were detected by flow cytometry. The oxidative stress-related markers were detected by the cuvette assay. The TLR4/NF-κB and PI3K/Akt/Nrf2 levels and apoptosis were detected by Western blot analysis. The effects of GDC-0068 (GDC, Akt inhibitor) on Ar interposed on LPS-induced NRK-52e cell apoptosis were investigated by flow cytometry. RESULTS: The data collected by network pharmacology suggested that Ar might inhibit AKI by exerting an anti-inflammatory effect and regulating the Akt signaling pathway. The experimental results showed that Ar markedly improved renal function, and attenuated inflammation and cell apoptosis via regulating PI3K/Akt/Nrf2 pathway following LPS challenge in vivo, which blocked by GDC effectively in vitro. CONCLUSION: In a word, this study demonstrated that Ar attenuated LPS-induced AKI by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway.

[DuzhongButiansu Capsules improve adenine-induced reproductive dysfunction in male rats].

OBJECTIVE: To study the effect of DuzhongButiansu Capsules (DBC) on adenine-induced reproductive dysfunction (RD) in male rats. METHODS: Eighty male SD rats were randomly divided into six groups, blank control (n = 8), solvent control (n = 8), RD model control (n = 16), Shengjing Capsules (SJC) (n = 16), low-dose DBC (n = 16) and high-dose DBC (n = 16). The RD model was made by intragastric administration of adenine at 200 mg/kg/d for 5 successive weeks in the latter four groups of animals, and in the meantime the rats in the latter three groups were treated intragastrically with SJC at 0.560 mg/kg/d and DBC at 0.242 and 0.968 mg/kg/d, respectively. At the end of the fourth week, all the rats were mated with female ones in a 1:1 ratio for 7 days. Then the male rats were killed and the right epididymides collected for detection of sperm concentration and motility, and the female ones sacrificed after fed for another 2 weeks and the numbers of pregnancies and fetal rats were recorded. The heart, liver, spleen, lung, kidney, thymus, testis, epididymis and seminal vesicle were harvested for obtainment of the visceral coefficients and semen parameters, observation of the histopathological changes in the testis, epididymis and kidneys by HE staining, measurement of the levels of serum T, E2, FSH and LH by ELISA, detection of the contents of serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA) and creatinine (Scr), blood urea nitrogen (BUN), and determination of the expressions of Bax, Bcl-2, Caspase-3 and Caspase-9 proteins in the renal tissue by immunohistochemistry. RESULTS: No statistically significant difference was observed between the blank control and solvent control groups in any of the indexes obtained (P > 0.05).Compared with the blank controls, the rats in the RD model control group showed significantly decreased sperm concentration (ï¼»40.67 ± 7.37ï¼½vs ï¼»27.10 ± 2.72ï¼½ ×106/ml, P < 0.01), sperm motility (ï¼»54.75 ± 3.92ï¼½%vs ï¼»25.60 ± 4.83ï¼½%, P < 0.01) and pregnancy rate (85.7% vs 43.8%, P < 0.01). The rats in thelow- and high-dose DBCgroups exhibited remarkable increases in sperm concentration (ï¼»53.00 ± 4.55ï¼½% and ï¼»65.63 ± 12.47ï¼½% ×106/ml, P < 0.01) and sperm motility (ï¼»53.50 ± 8.83ï¼½% and ï¼»54.33 ± 7.92ï¼½ %, P < 0.01), and so did those in the high-dose DBC group in pregnancy rate (54.5%, P < 0.01).After medication, the animals showed markedly increased body weight and visceral coefficients of the testis, epididymis and seminal vesicle (P < 0.05 or P < 0.01), recovered morphology of the testis, epididymis and kidneys, reduced levels of Scr, BUN, FSH, LH and MDA in the serum (P < 0.05 or P < 0.01), increased contents of T, SOD and GSH-PX (P < 0.05 or P < 0.01), down-regulated expressions of Bax, Caspase-3 and Caspase-9 and up-regulated expression of Bcl-2 in the renal tissue (P < 0.05 or P < 0.01). CONCLUSIONS: DBC can improve adenine-induced reproductive dysfunction in male rats, which may be attributed to its effects of inhibiting the apoptosis of proteins, improving oxidative stress and elevating the levels of reproductive hormones.

Raw and salt-processed Achyranthes bidentata attenuate LPS-induced acute kidney injury by inhibiting ROS and apoptosis via an estrogen-like pathway.

BACKGROUND: Traditional Chinese medicine suggests that Radix Achyranthis Bidentatae nourishes and protects the kidneys, the effect of which is enhanced following a salt treatment. Raw and salt-processed Achyranthes bidentata are produced via different processing techniques from the same crude Achyranthes root. The anti-inflammatory and immunomodulatory properties of this plant have been verified earlier. However, there is a scarcity of experimental evidence for the renal-protective effects. AIM: The purpose of present study is to compare the protective effects of raw and salt-processed Achyranthes on lipopolysaccharide (LPS) - induced acute kidney injury in mice and chemically characterize their extracts. METHOD: The monomer components of raw and salt-processed Achyranthes extracts were analyzed using high performance liquid chromatography (HPLC). The aggregation and distribution of 2-Deoxy-D-glucose (2-DG) near infrared fluorescence probe in mice was examined with a small animal imaging systems. The pathological and morphological changes of kidneys were observed by H&E staining, and the serum urea nitrogen (BUN) and serum creatinine (Scr) levels were used to evaluate the renal function. The levels of cytokines in serum were detected by cytometric bead array. Flow cytometry assay was performed to assess the apoptosis and reactive oxygen species (ROS) in the kidney cells, and cell surface marker expression including CD45+, F4/80+, and Ly-6G+. The estrogenic activities of the raw and salt-processed Achyranthes were observed by uterine weight gain test in sexually immature mice. Western blot was used to detect the protein expression levels in the kidney. RESULTS: Chemical analysis showed that the salt-processed Achyranthes contained more ginsenoside Ro and chikusetsusaponin Ⅳa than the raw Achyranthes, but there was no difference in the contents of ß-ecdysterone, 25R-inokosterone, and 25S-inokosterone.in vivo near-infrared fluorescence imaging showed a significant reduced inflammation in the AKI mice. Histological studies showed that the raw and salt-processed Achyranthes markedly decreased the inflammatory infiltration, swelling and vacuolar degeneration in renal tissues and the Scr and BUN. Importantly, the raw and salt-processed Achyranthes extracts demonstrated different degrees of inhibition on the LPS-induced AKI, with salt-processed Achyranthes showing better inhibition. Results of flow cytometry showed a significant inhibition of IFN-γ, TNF-α, and IL-2, and promoted IL-10, along with reduced macrophages (CD45 + F4/80+), neutrophils (CD45+ Ly-6G+) and phagocytes. Furthermore, the extracts reduced the accumulation of ROS and apoptosis in the kidney, and also regulated the expression of apoptosis marker proteins TLR4, Bcl-2, Bax, cleaved caspase 3 and cleaved caspase 9 levels. Notably, they increased ERα, ERß, and GPR30 in the renal tissues of AKI mice and LPS non-treated mice. In the subsequent experiments, it was found that the raw and salt-processed Achyranthes extracts increased the uterine coefficient in sexually immature mice, improved the LPS-induced decrease in NRK52e cell viability, and reduced the apoptosis, which could be antagonized by ICI182, 780 (estrogen receptor-unspecific antagonist, Faslodex). CONCLUSIONS: The renal-protective effect of raw and salt-processed Achyranthes was exhibited through antiapoptotic and antioxidant mechanisms via an estrogen-like pathway, along with a modulation of the inflammatory response by regulating immune cells. Ginsenoside Ro and Chikusetsu saponin IVa were found to be the key factors to enhance the protective effect of salt-processed Achyranthes.

Protopine Protects Mice against LPS-Induced Acute Kidney Injury by Inhibiting Apoptosis and Inflammation via the TLR4 Signaling Pathway.

Corydalis humosa Migo is a traditional Chinese medicine that clears away damp heat, relieves sore. Protopine (PRO) is an alkaloid component isolated from C. humosa Migo. However, the role of protopine in acute kidney injury (AKI) has not yet been reported. This study aims to investigate the effect and mechanism of protopine isolated from C. humosa Migo on lipopolysaccharide (LPS)-induced AKI in mice. Inflammation accumulation was assessed by small animal living imaging. The blood urea nitrogen (BUN), and serum creatinine (Scr) were measured to assess the effects of protopine on renal function in LPS-induced AKI. The levels of tumor necrosis factor (TNF), interleukin-2 (IL-2), interferon-γ (IFN-γ), and (interleukin-10) IL-10 in serum were detected by cytometric bead array. Flow cytometry was used to detect the levels of reactive oxygen species (ROS) in primary kidney cells. The proportions of granulocytes, neutrophils, and macrophages in peripheral blood were examined to evaluate the effect of protopine on immune cells in mice with AKI. Toll-like receptor (TLR4) and apoptotic signaling pathway were detected by Western blot analysis. The results showed that protopine markedly improved the renal function, relieve inflammation, reversed inflammatory cytokines, transformed apoptosis markers, and regulated the TLR4 signaling pathway in mice with AKI induced by LPS. The protopine isolated from C. humosa Migo protected mice against LPS-induced AKI by inhibiting apoptosis and inflammation via the TLR4 signaling pathway, thus providing a molecular basis for a novel medical treatment of AKI.

Adenosine Attenuates LPS-Induced Cardiac Dysfunction by Inhibition of Mitochondrial Function via the ER Pathway.

Sepsis is a life-threatening organ dysfunction syndrome with a high rate of mortality. It is caused by an abnormal immune response to infection, and the occurrence of sepsis-induced cardiomyopathy is the primary cause of death. The present study was designed to examine the effects of adenosine on lipopolysaccharide- (LPS-) induced cardiac anomalies and the underlying mechanisms involved. Adenosine (25, 50, and 100 mg/kg, i.g., 2 times/day) was administered for three days, followed by the induction of sepsis by intraperitoneal injection of LPS (10 mg/kg/2h). The effects of adenosine on inflammatory factors, LVEF, LVFS, and MAPK in septic rats (half male and half female) were observed. Subsequently, the effect of adenosine (10 µM) on the mitochondrial function of H9c2 cells stimulated with LPS (20 µg/mL, 24 h) was observed in the presence and absence of the estrogen receptor-specific antagonist ICI182,780. The results show that medium to high doses of adenosine can significantly promote cardiac function (LVEF and LVFS) and reduce the levels of inflammatory factors (TNF-α, IL-6, PCT, and cTnI) and p-JNK in septic rats, with a significant difference seen between male and female rats. The results of flow cytometry show that adenosine significantly inhibited increases in ROS levels, mitochondrial membrane potential, and the swelling degree of mitochondria in H9c2 cells stimulated with LPS, but this effect could be blocked by ICI182,780, indicating that adenosine attenuated LPS-induced cardiac dysfunction by inhibiting mitochondrial function via the ER pathway.

A new compound from Lygodium japonicum (Thunb.) Sw.

A new ecdysteroside was isolated from the roots of Lygodium japonicum (Thunb.) Sw. The structure was identified as 2beta,3beta,14alpha,20R,22R-pentahydroxy-24R-methyl-5beta-cholest-7-en-6-one-3-O-beta-D-glucopyranoside by spectral and chemical methods.

A new ecdysteroside from Lygodium japonicum (Thunb.) Sw.

A new ecdysteroside, named lygodiumsteroside A, as well as a known ecdysteroside, were isolated from the roots of Lygodium japonicum (Thunb.) Sw. Their structures were identified by spectral and chemical methods.

A new arylbenzofuran from the aerial parts of alfalfa.

A new arylbenzofuran, 4-hydroxy-2-(4'-hydroxy-2'-methoxyphenyl)-6-methoxybenzofu-ran-3-carbaldehyde (1), was isolated from the aerial parts of alfalfa (Medicago sativa L.), together with three known compounds. The structure of the new compound (1) was determined by spectroscopic methods.